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| 1 | History of the infantile hepatic hemangioma:From imaging to generating a differential diagnosis显示文摘We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions. | Maria Gnarra Gerald Behr Alison Kitajewski June K Wu Sudha A Anupindi Carrie J Shawber Nick Zavras Dimitrios Schizas Chris Salakos Konstantinos P Economopoulos | 2016 | World Journal of Clinical Pediatrics2016，5，3： | 27 |
| 2 | Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date显示文摘The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cause of complications in diabetes and within this,heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom.There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops.This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility.T2D is associated with inefficient substrate utilisation,an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling,glucotoxicity,lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure.The review also gives a concise update on developments within clinical imaging,specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D.A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction. | Lavanya Athithan Gaurav S Gulsin Gerald P McCann Eylem Levelt | 2019 | World Journal of Diabetes2019，10，10： | 15 |
| 3 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 4 | RANKL/RANK control Brca1 mutation-driven mammary tumors显示文摘 | Verena Sig Kwadwo Owusu-Boaitey Puma A Joshi Anoop Kavirayani Gerald Wimsberger Maria Novatchkova Ivona Kozieradzki Daniel Schramek Nnamdi Edokobi Jerome Hersl Aishia Sampson Ashley Odai-Afotey Conxi Lazaro Eva Gonzalez-Suarez Miguel A Pujaaa for CIMBA Holger Heyn Enrique Vidal Jennifer Cru. ickshank Hal Berman Renu Sarao Melita Tieevic Iris Uribesalgo Luigi Tortola Shuan Rao Yen Tan Georg Pfeiler Eva YHP Lee Zsuzsanna Bago-Horvath Lukas Kenner Helmuth Popper Christian Singer Rama Khokha LaundeRe P Jones Josef M Penninger | 2016 | Cell Research2016，26，7： | 3 |
| 5 | 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 |
| 6 | Bovine immunoglobulin protein isolates for the nutritional management of enteropathy显示文摘The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus(HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome(IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function(e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management ofenteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasmaor serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy. | Bryon W Petschow Anthony T Blikslager Eric M Weaver Joy M Campbell Javier Polo Audrey L Shaw Bruce P Burnett Gerald L Klein J Marc Rhoads | 2014 | World Journal of Gastroenterology2014，20，33： | 2 |
| 7 | Global myocardial strain assessment by different imaging modalities to predict outcomes after ST-elevation myocardial infarction:A systematic review显示文摘AIM: To conduct a systematic review relating myocardial strain assessed by different imaging modalities for prognostication following ST-elevation myocardial infarction(STEMI).METHODS: An online literature search was performed in Pub Med and OVID® electronic databases to identify any studies that assessed global myocardial strain parameters using speckle-tracking echocardiography(STE) and/or cardiac magnetic resonance imaging(CMR) techniques [either myocardial tagging or feature tracking(FT) software] in an acute STEMI cohort(days 0-14 post-event) to predict prognosis [either development of major adverse cardiac events(MACE)] or adverse left ventricular(LV) remodelling at follow-up(≥ 6 mo for MACE,≥ 3 mo for remodelling). Search was restricted to studies within the last 20 years. All studies that matched the pre-defined search criteria were reviewed and their results interpreted. Due to considerable heterogeneity between studies,metaanalysis was not performed.RESULTS: A total of seven studies(n = 7) were identified that matched the search criteria. All studies used STE to evaluate strain parameters- five(n = 5) assessed global longitudinal strain(GLS)(n = 5),one assessed GLS rate(GLS-R)(n = 1) and one assessed both(n = 1). Three studies showed that GLS independently predicted the development of adverse LV remodelling by multivariate analysis- odds ratio between 1.19(CI: 1.04-1.37,P < 0.05) and 10(CI: 6.7-14,P < 0.001) depending on the study. Four studies showed that GLS predicted the development of MACE- hazard ratio(HR) between 1.1(CI: 1-1.1,P = 0.006) and 2.34(1.10-4.97,P < 0.05). One paper found that GLS-R could significantly predict MACEHR 18(10-35,P < 0.001)- whilst another showed it did not. GLS <-10.85% had sensitivity/specificity of 89.7%/91% respectively for predicting the development of remodelling whilst GLS <-13% could predict the development of MACE with sensitivity/specificity of 100%/89% respectively. No suitable studies were identified that assessed global strain by CMR tagging or FT techniques.CONCLUSION: GLS measured acutely post-STEMI by STE is a predictor of poor prognosis. Further research is needed to show that this is true for CMR-based techniques. | Abhishek Shetye Sheraz A Nazir Iain B Squire Gerald P McCann | 2015 | World Journal of Cardiology2015，7，12： | 2 |
| 8 | Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life. | Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant | 2022 | World Journal of Diabetes2022，13，3： | 2 |
| 9 | Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials显示文摘 | Peter M Rothwell F Gerald R Fowkes Jill FF Belch Hisao Ogawa Charles P Warlow Tom W Meade | 2011 | The Lancet2011，，9759： | 2 |
| 10 | Activation of PKC-delta and SHP-1 by hyperglycemia causes vaseular cell apop- tosis and diabetic retinopathy 显示文摘 | Geraldes P Hiraoka-Yamamoto J Matsumoto M | 2009 | Nat Med2009，15，11： | 1 |
| 11 | Activation of PKC- 8 and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy显示文摘 | Geraldes P Hiraoka Yamamoto J Matsumoto M | 2009 | Nat Med2009，15，11： | 1 |
| 12 | The Swiss lithoclast:a new device for endoscopic stone disintegration显示文摘 | Harald S Gerald H Marco P | 1993 | J urol1993，149，3： | 1 |
| 13 | NonParametric tests for trends in wa- ter quality 显示文摘 | Gerald V B James P H | 2001 | Water Resources Research2001，37，4： | 1 |
| 14 | Hot-cor- rosion Resistance of Ni-Cr-A1-Y and Ni-18 % Si SI- loys in Sulfate Eutectic and Sulfate Plus Vanadate Melts at 973 K 显示文摘 | BRUCE M W FRED S P GERALD H M | 2002 | Oxidation of Metals2002，58，56： | 1 |
| 15 | Apractical guide to ass- essment of ventricular diastolic function using Doppler echocar- diography显示文摘 | Gerald I C Joseph F P James D T | 1996 | JACC1996，27，7： | 1 |
| 16 | Oxidation rids diesel fuel of sulfur and so does this ultrasonic oxidationmethod显示文摘 | Gerald P | 2001 | Chemical Engineering2001，108，4： | 1 |
| 17 | Mutual Fund Persistence and Market Capitalization显示文摘 | Madden Gerald P Kenneth P.Nunn Jr Alan Wiemann | | 0，，： | 1 |
| 18 | Estrogen regulation of endothelial and smooth muscle cellmigration and proliferation: role of p38 and p42/44 mitogenactivated protein kinase显示文摘 | Geraldes P Sirois MG Bematchez PN | 2002 | A rterioscler Thromb Vasc Boil2002，22，： | 1 |
| 19 | Higher differentiation among subspecies of the house mouse(Mus muscu/us )in genomic regions with low recombination显示文摘 | GERALDES A BASSET P SMITH K L | 2011 | Molecular Ecology2011，20，22： | 1 |
| 20 | XAFS characterization of mercury captured from combustion gases on sorbents at low temperatures显示文摘 | Frank E H Nora Y Gerald P H | | 0，，02： | 1 |
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