bluuebunny/crossref_metadata_2025_split huggingface dataset:
A common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: A meta‐analysis
Authors: Zain Shamsul Mohd , Mohamed Zahurin , Mohamed Rosmawati 
Published: August 2014

AbstractBackground and AimAlthough studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta‐analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD.MethodsWe searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined.ResultsThis meta‐analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14–1.36, P < 0.00001). Analysis also revealed significant associations with different alternative genetic models for the inheritance: dominant, recessive, and homozygote (OR 1.40, 95%CI 1.23–1.61, P < 0.00001; OR 0.79, 95% CI 0.68–0.91, P = 0.001, and; (OR 1.27, 95% CI 1.10–1.47, P = 0.001, respectively), but not the heterozygote model. Population subgroup analysis demonstrated similar effect size in both Asians and non‐Asians (OR 1.27, 95%CI 1.12–1.45, P = 0.0003 and OR 1.22, 95%CI 1.10–1.37, P = 0.0003, respectively).ConclusionsOur meta‐analysis provides evidence of significant association between GCKR rs780094 and risk of NAFLD. Similar effect size was demonstrated in both Asian and non‐Asian populations.
Long‐term lamivudine treatment achieves regression of advanced liver fibrosis/cirrhosis in patients with chronic hepatitis B
Authors: Xu Bei , Lin Lanyi , Xu Guoguang , Zhuang Yan , Guo Qing , Liu Yunye , Wang Hui , Zhou Xiaqiu , Wu Shanming , Bao Shisan , Cai Wei , Xie Qing 
Published: August 2014

AbstractBackground and AimAntiviral therapy is important in advanced liver fibrosis/cirrhosis with chronic hepatitis B (AdLF‐CHB) patients, but complete regression of cirrhosis remains to be the challenge. We aimed to investigate whether up to 10 years lamivudine treatment achieves liver fibrosis/cirrhosis regression in AdLF‐CHB patients.MethodsImprovement of hepatic fibrosis/cirrhosis, virological response and disease progression were evaluated in 28 AdLF‐CHB patients with up to 10 years lamivudine treatment. Liver biopsy was performed in all of the 28 patients at baseline, but only 19 patients had second biopsy at year 10.ResultsThere were 24 hepatitis B e antigen (HBeAg)‐positive and 4 HBeAg‐negative patients within the original 28 AdLF‐CHB patients. At the end of 10 years lamivudine treatment, 20 of the 24 HBeAg‐positive patients had HBeAg loss. HBeAg seroconversion was detected in 10 of these 20 HBeAg loss patients. HBsAg loss was observed in 4 of the original 28 patients. Among these four HBsAg loss patients, three had HBsAg seroconversion. All patients achieved hepatitis B virus DNA (HBV DNA) undetectable. Histopathology was evaluated between paired original and final liver biopsies among 19 patients as follows: 4/19 achieved complete liver fibrosis/cirrhosis regression; 9/19 improved in Ishak fibrosis score; whereas 6/19 showed no fibrosis improvement. About 75% patients achieved inflammatory/fibrotic improvement. No significant disease progression was observed in 24/28 patients. Furthermore, no significant difference in histopathology improvement, cirrhosis regression, disease progression between non‐resistance and rescue for resistance was observed.ConclusionLong‐term lamivudine therapy achieves regression of fibrosis/cirrhosis and improvement of histological and disease progression in AdLF‐CHB patients.
Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox
Authors: Sobbe Amy , Bridle Kim R , Jaskowski Lesley , de Guzman C Erika , Santrampurwala Nishreen , Clouston Andrew D , Campbell Catherine M , Subramaniam V Nathan , Crawford Darrell H G 
Published: August 2014

AbstractBackground and AimDevelopment of effective antifibrotic treatments that can be translated to clinical practice is an important challenge in contemporary hepatology. A recent report on β‐thalassemia patients demonstrated that deferasirox treatment reversed or stabilized liver fibrosis independent of its iron‐chelating properties. In this study, we investigated deferasirox in cell and animal models to better understand its potential antifibrotic effects.MethodsThe LX‐2 stellate cell line was treated with 5 μM or 50 μM deferasirox (Exjade, Novartis Pharmaceuticals Australia, North Ryde, NSW, Australia) for up to 120 h. Three‐week‐old multidrug resistance 2 null (Mdr2–/–) mice received oral deferasirox or vehicle for 4 weeks (30 mg/kg/day). Cells and liver tissue were collected for assessment of fibrosis and fibrogenic gene expression.ResultsIn LX‐2 cells treated with 50 μM deferasirox for 12 h, α1(I)procollagen expression was decreased by 25%, with maximal reductions (10‐fold) seen following 24–120 h of treatment. Similarly, α‐smooth muscle actin (αSMA) expression was significantly lower. Alterations in matrix remodeling genes, specifically decreased expression of matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐2, were observed. There was no significant difference in hepatic hydroxyproline content in Mdr2–/– mice following deferasirox administration (vehicle: 395 ± 27 μg/g vs deferasirox: 421 ± 33 μg/g). Similarly, no changes in the expression of fibrogenic genes were observed.ConclusionDespite reductions in α1(I)procollagen and αSMA expression and alterations in matrix degradation genes in LX‐2 cells, deferasirox did not exhibit antifibrotic activity in Mdr2–/– mice. Given the positive outcomes seen in human trials, it may be appropriate to study deferasirox in other animal models of fibrosis and/or for a longer duration of therapy.
Association of downregulation of WWOX with poor prognosis in patients with intrahepatic cholangiocarcinoma after curative resection
Authors: Huang Changjun , Tian Yuan , Peng Rui , Zhang Changhe , Wang Dong , Han Sheng , Jiao Chenyu , Wang Xing , Zhang Hai , Wang Yun , Li Xiangcheng 
Published: August 2014

AbstractBackground and AimDownregulation of the WW domain containing oxidoreductase (WWOX) has been reported to be involved in tumorigenesis in several neoplasms. This study sought to investigate the expression and role of WWOX in intrahepatic cholangiocarcinoma (ICC).MethodsWWOX expression was measured by quantitative real‐time polymerase chain reaction (PCR), immunoblot, immunofluorescence, and immunohistochemistry. The prognostic significance was assessed by Kaplan–Meier and Cox regression analyses. The role of WWOX in proliferation, anchorage‐independent growth, gene expression regulation, and tumorigenesis was assessed by WWOX re‐expression using lentivirus. Methylation‐specific PCR was performed to evaluate the methylation status of the WWOX gene regulatory region. A DNA methyltransferase inhibitor, 5‐aza‐2′‐deoxycytidine (AZA), was used to activate the endogenous WWOX gene in ICC cells both in vitro and in vivo.ResultsThe expression of WWOX in ICC tissues was much lower than that in nontumorous samples and showed reverse correlation with proliferative status. Restoration of WWOX expression resulted in suppression of the growth of WWOX‐deficient ICC cells through activation of the intrinsic apoptotic signaling pathway, but did not affect growth of WWOX‐sufficient human intrahepatic biliary epithelial derived non‐cancer cells. Multivariate analyses revealed that downregulation of WWOX was an unfavorable predictor for overall survival and cumulative recurrence rates. The WWOX gene regulatory region was frequently methylated in ICC tissues and cell lines, and intratumoral WWOX restoration, through AZA injection, suppressed tumor growth in nude mice.ConclusionDownregulation of WWOX may occur as a result of hypermethylation and implies a poor prognosis in ICC; WWOX re‐expression may be a potential molecular therapeutic target for ICC.
Small intestinal contrast ultrasonography for the detection of small bowel complications in Crohn's disease: Correlation with intraoperative findings and magnetic resonance enterography
Authors: Kumar Shankar , Hakim Aishah , Alexakis Christopher , Chhaya Vivek , Tzias Demitrios , Pilcher James , Vlahos Johnny , Pollok Richard 
Published: August 2014

AbstractBackground and AimsIn evaluating small bowel Crohn's disease (CD), small intestine contrast‐enhanced ultrasonography (SICUS) is emerging as an alternative to magnetic resonance enterography (MRE). This retrospective study compared the diagnostic accuracy of SICUS and MRE with surgical findings, and their level of agreement.MethodsWe identified a cohort of CD patients investigated by either SICUS and/or MRE that subsequently required resective bowel surgery within 6 months. The accuracy and agreement of SICUS and MRE to detect small bowel complications were compared with intraoperative findings using kappa coefficient (κ). Agreement between SICUS and MRE in those undergoing both modalities was also assessed.ResultsA total of 67 patients were evaluated; 25 underwent SICUS and 17 underwent MRE prior to surgery. Another 25 patients underwent both SICUS and MRE. When compared with intraoperative findings, the sensitivity of SICUS and MRE was 87.5% and 100%, respectively, in detecting strictures, 87.7% and 66.7% for fistulae, 100% for both in identifying abscesses, 100% and 66.7% for bowel dilatation, and 94.7% and 81.8% in defining bowel wall thickening. When correlating SICUS and MRE with surgery, there was a high level of agreement in localizing strictures (κ = 0.75, 0.88, respectively), fistulae (κ = 0.82, 0.79) and abscesses (κ = 0.87, 0.77). Concordance between SICUS and MRE was substantial or almost complete in identifying stricturing disease (κ = 0.84), their number and location (κ = 0.85), fistulae (κ = 0.65), and mucosal thickening (κ = 0.61).ConclusionSICUS accurately identified small bowel complications and correlated well with MRE and intraoperative findings. SICUS offers an alternative in the preoperative assessment of CD.
Long‐term clinical outcome of patients with cirrhosis and refractory ascites treated with transjugular intrahepatic portosystemic shunt insertion
Authors: Tan Hiang Keat , James Paul Damien , Sniderman Kenneth Wilfred , Wong Florence 
Published: August 2014

AbstractBackground and AimTransjugular intrahepatic portosystemic shunt (TIPS) is indicated for the treatment of refractory ascites in cirrhosis. The long‐term outcome of TIPS for refractory ascites is unknown. The aim of this study is to describe the natural history of patients with refractory ascites post‐TIPS, and compare between polytetrafluoroethylene (PTFE)‐covered versus bare stents.MethodsA retrospective chart review of patients who had TIPS for refractory ascites was conducted. Prospectively collected data include demographics, angiographic data, blood work, and urinary sodium excretion.ResultsThere were 136 patients who received TIPS (bare = 104, covered = 32) for over 22 years. Patients with PTFE stents had lower international normalized ratio and model for end‐stage liver disease score. More patients with bare stents developed shunt dysfunction (74.0% vs 24.1%, P < 0.0001) and required more TIPS revisions (1.6 ± 0.2/patient vs 0.2 ± 0.1, P < 0.0001). Urinary sodium excretion increased significantly from first month and progressed to 98 ± 9 mmol/day at 12th month post‐TIPS (P < 0.001 vs baseline), concurrent with improved renal function. Most patients (77.6%) completely cleared the ascites without diuretics, but many achieved this beyond 2 years. Number of TIPS revision was predictive of complete response at 12 months (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5–0.9, P < 0.05). Age (hazard ratio [HR] = 1.05 [95% CI 1.02–1.08], P < 0.01), complete response (HR = 0.22 [95% CI 0.12–0.40], P < 0.0001) and polytetrafluoroethylene stents (HR = 0.23 [95% CI 0.05–0.97], P < 0.05) were predictive of survival.ConclusionTIPS is an effective treatment for cirrhotic refractory ascites. Ascites clearance is dependent on number of TIPS revision, whereas survival is predicted by younger age, complete response, and covered stent use, although era effect likely contributed to improved survival with covered stent use.
Use of non‐invasive serum glycan markers to distinguish non‐alcoholic steatohepatitis from simple steatosis
Authors: Yamasaki Yasushi , Nouso Kazuhiro , Miyahara Koji , Wada Nozomu , Dohi Chihiro , Morimoto Yuki , Kinugasa Hideaki , Takeuchi Yasuto , Yasunaka Tetsuya , Kuwaki Kenji , Onishi Hideki , Ikeda Fusao , Miyake Yasuhiro , Nakamura Shinichiro , Shiraha Hidenori , Takaki Akinobu , Iwasaki Yoshiaki , Amano Maho , Nishimura Shin‐Ichiro , Yamamoto Kazuhide 
Published: August 2014

AbstractBackground and AimsSerum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non‐alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non‐alcoholic steatohepatitis (NASH) from simple steatosis (SS).MethodsWe collected sera from 42 histologically proven NASH and 15 SS patients prior to treatment. Serum glycan profiles were measured by comprehensive, quantitative, high‐throughput glycome analysis, and diagnostic values of serum glycans for NASH prediction were examined.ResultsAmong the 41 serum glycans examined, the expression levels of 8 glycans in NASH were significantly higher than those of SS. Out of these eight glycans, three glycans (m/z 1955, 2032, and 2584) showed high areas under the receiver operating characteristic curve (0.833, 0.863, and 0.866, respectively) for distinguishing NASH from SS. In multivariate analyses with clinical parameters and serum glycans, these three glycans were significant predictive factors for distinguishing NASH from SS. The odds ratio of m/z 1955, 2032, and 2584 were 48.5, 6.46, and 11.8, respectively. These glycans also correlated significantly with lobular inflammation, ballooning, and fibrosis, but not with steatosis.ConclusionWe clearly demonstrated whole‐serum glycan profiles in NASH patients, and the feasibility of serum glycans (m/z 1955, 2032, and 2584) as new noninvasive biomarkers for distinguishing NASH from SS.
Safety and efficacy of entecavir in adefovir‐experienced patients
Authors: Nguyen Nghia H , Trinh Huy N , Nguyen Thuan T , Do Son T , Tran Phuong , Nguyen Huy A , Nguyen Khanh K , Garcia Ruel T , Lutchman Glen A , Nguyen Mindie H 
Published: August 2014

AbstractBackground and AimSuboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B. Few studies have evaluated the efficacy of entecavir (ETV) in ADV‐experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV‐experienced patients.MethodsADV‐experienced patients switched to ETV were enrolled from six US clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV‐DNA at switch) or complete responders (undetectable HBV‐DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV‐DNA < 60 IU/mL) and biochemical response (BR, alanine aminotransferase [ALT] < 40 U/L), respectively.ResultsA total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive, hepatitis B e antigen status before ADV and higher HBV‐DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV resistance, seven achieved CVS after 24 months of ETV, and all achieved BR.ConclusionIn ADV‐experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.
Congenital toxoplasmosis from a mother with type 2 diabetes mellitus: A case report
Authors: Sato Shimpei , Nishida Masakazu , Nasu Kaei , Narahara Hisashi , Norose Kazumi , Aosai Fumie 
Published: August 2014

AbstractA 33‐year‐old woman with type 2 diabetes mellitus (DM) was suspected of being primarily infected with Toxoplasma gondii at 12 weeks of gestation (GW). Although acetylspiramycin was started at 17 GW, the T. gondii DNA gene was detected in the amniotic fluid at 18 GW. Chemotherapy was changed to pyrimethamine plus sulfadiazine from 20 GW, but was changed back to acetylspiramycin after 2 weeks because of vomiting. Acetylspiramycin was continued until her delivery. DM was controlled well during the pregnancy. An asymptomatic male baby was born by cesarean section at 37 GW, and was treated with acetylspiramycin for 4 weeks because the polymerase chain reaction results of umbilical cord blood were positive. He has developed normally until the present, that is, 6 months of age. Herein, we describe a case report in which symptomatic congenital toxoplasmosis was avoided in a pregnant woman with an immunosuppressive risk due to prompt chemotherapy.
Fatal case of multiple recurrences of endometrial stromal sarcoma after fertility‐sparing management
Authors: Morimoto Atsushi , Tsubamoto Hiroshi , Inoue Kayo , Ikeda Yuuki , Hirota Seiichi 
Published: August 2014

AbstractSeveral cases of the uterus being preserved after diagnosis of endometrial stromal sarcoma (ESS) have been reported. Most of these patients were alive and did not experience relapse, but this might have reflected the short follow‐up period, given the indolent recurrence of ESS. We report the first fatal case of ESS 10 years after fertility‐sparing management. A specimen obtained from the last operation showed loss of estrogen receptor status and expression of c‐kit without c‐kit or PDGFR‐α gene mutations.
Days of Labour: Topographies of Power in Modern Peripheral Capitalism. The Case of The Industrial City ofŁódź
Authors: Marzec Wiktor , Zysiak Agata 
Published: August 2014

AbstractThe article investigates the city ofŁódź as an exceptional case of a settlement constitutive of different kinds and techniques of power typical of nineteenth century industrial capitalism. We considerFoucault's disciplinary power/biopower through the convergence of the paternalistic gaze of the factory owner, and theTsarist rule in theScheibler andGrohman industrial establishment and the nearby workers housing estate. The aim of this article is to investigate a specificlocusof peripheral capitalism and the relations accompanying it through theFoucauldian analysis of power. We argue that unique and unstable patterns of correlation of power techniques emerged here. Power is no longer strictly related to the temporal matrix or the functional demands of capitalist production, and only temporarily ossified in contingent configurations. WhileFoucault's canonical theoretical premises and concepts are of explanatory value, the very relations between them become problematic when confronted with the particular entanglement inŁódź. Therefore we opt for the new paradigm of power analysis throughS.J.Collier's “topological analysis”.
Elevation in 5‐FU‐induced apoptosis in Head and Neck Cancer Stem Cells by a combination of CDHP and GSK3β inhibitors
Authors: Shigeishi Hideo , Biddle Adrian , Gammon Luke , Rodini Camila O. , Yamasaki Miho , Seino Sayaka , Sugiyama Masaru , Takechi Masaaki , Mackenzie Ian C. 
Published: August 2014

BackgroundCancer stem cells (CSCs) are involved in both tumourigenesis and in tumour recurrence after therapy. In head and neck squamous cell carcinoma (HNSCC), there are two biologically different CSC phenotypes both of which express high levels of CD44 but differ in their expression levels of epithelial‐specific antigen (ESA). One phenotype is CD44high/ESAhigh and has epithelial features (Epi‐CSCs), while the other is CD44high/ESAlow, has undergone epithelial to mesenchymal transition (EMT‐CSCs), has mesenchymal features and is migratory (Biddle et al., 2011). CSCs are resistant to therapeutically induced apoptosis but the molecular mechanisms by which they develop apoptotic resistance remains unclear. However, glycogen synthase kinase 3β (GSK3β) contributes to regulation of both the self‐renewal and switching of these two CSC phenotypes (Shigeishi et al., 2013).MethodsCD44high/ESAlow, CD44high/ESAhigh and CD44low cells were FACS sorted from the HNSCC cell line LUC4, and 5‐FU‐induced apoptosis was analysed by Annexin V staining followed by flow cytometry analysis.ResultsCD44high/ESAlow cells exhibited marked resistance to 5‐FU‐induced apoptosis and had high expression of dihydropyrimidine dehydrogenase (DPD). The DPD inhibitor, 5‐chloro‐2, 4‐dihydroxypyridine (CDHP) significantly enhanced 5‐FU‐induced apoptosis of CD44high/ESAlow cells. Inhibition of GSK3β induced CD44high/ESAlow cells to undergo mesenchymal‐to‐epithelial transition (MET) to CD44high/ESAhigh cells and pre‐existing CD44high/ESAhigh cells to differentiate. Apoptosis induced by 5‐FU was thus facilitated. Combination of both CDHP and GSK3β inhibitors markedly enhanced 5‐FU‐induced apoptosis of CD44high/ESAlow cells.ConclusionsOur results suggest potentially new approaches for the elimination of the therapy resistant HNSCC CSC population.
Gene–environment interaction and susceptibility in head and neck cancer patients and in their first‐degree relatives: a study of Northeast Indian population
Authors: Choudhury Javed Hussain , Ghosh Sankar Kumar 
Published: August 2014

BackgroundThe environmental and genetic factors are known to be associated with head and neck squamous cell carcinoma (HNSCC). Here, we investigated the GSTM1 and GSTT1 polymorphisms and tobacco uses in patients and in their first‐degree relatives to evaluate susceptibility toward HNSCC. Further, we explored high‐risk interaction between genetic and environmental risk factors.Subjects and methodsGenotyping of GSTM1 and GSTT1 was performed in 170 patients, 300 first‐degree relatives of patients and 300 controls using multiplex PCR. Multifactor dimensionality reduction (MDR) and logistic regression approach were applied for statistical analysis.ResultsAnalysis revealed that GSTM1 and GSTT1 null genotype frequencies were significantly higher in patients (adjusted odds ratio (OR) = 2.18; P < 0.001 and OR = 1.61; P = 0.031, respectively). Also, the GSTM1 and GSTT1 null genotype frequencies were significantly higher in first‐degree relatives of patients compared with controls (P = 0.004 and P = 0.041, respectively). In MDR analysis, the best model for HNSCC risk was four‐factors model of tobacco, betel quid chewing, smoking and GSTM1 null genotypes (cross‐validation consistency = 10/10 and P < 0.0001), whereas in interaction entropy graphs, tobacco chewing and GSTM1 null genotype further showed strongest synergistic interaction.ConclusionGSTM1 and GSTT1 null genotypes may act as markers to determine the genetic susceptibility in HNSCC patients and in their first‐degree relatives. Furthermore, tobacco chewing and GSTM1 null genotype interaction identified as the strongest gene‐environment model to predict HNSCC.