bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B – a prospective cohort study with paired transient elastography examinations
Authors: Wong G. L.‐H. , Chan H. L.‐Y. , Yu Z. , Chan A. W.‐H. , Choi P. C.‐L. , Chim A. M.‐L. , Chan H.‐Y. , Tse C.‐H. , Wong V. W.‐S. 
Published: February 2014

SummaryBackgroundMetabolic syndrome is a known risk factor of cirrhosis in chronic hepatitis B (CHB).AimTo investigate the effects of coincidental metabolic syndrome on liver fibrosis progression in treatment‐naïve CHB patients.MethodsA total of 1466 CHB patients underwent liver stiffness measurement (LSM) by transient elastography in 2006–2008; 663 patients remained treatment‐naïve and had second LSM in 2010–2012. Liver fibrosis progression was defined as an increase in LSM ≥30% at the second assessment. The impact of coincidental metabolic syndrome and its factors on liver fibrosis progression were evaluated after adjustment for viral load and hepatitis activity.ResultsAt baseline, the mean age was 43 ± 12 years, 55% were males, serum alanine aminotransferase (ALT) was 44 ± 40 IU/L, HBV DNA was 4.0 ± 2.0 log IU/mL and LSM was 6.3 ± 3.6 kPa. Metabolic syndrome was diagnosed in 80 (12%) and 142 (21%) patients at baseline and follow‐up visit, respectively; 84 (13%) and 22 (3%) patients had coincidental and resolved metabolic syndrome respectively. After an interval of 44 ± 7 months, 107 (16%) patients developed liver fibrosis progression. Coincidental metabolic syndrome [adjusted odds ratio (aOR) 2.0, 95% confidence interval (CI) 1.1–3.5, P = 0.015], central obesity (aOR 2.0, 95% CI 1.0–4.1, P = 0.05) and low level of high‐density lipoprotein cholesterol (aOR 1.9, 95% CI 1.0–3.7, P = 0.04) were associated with liver fibrosis progression independent of change in viral load and ALT level. The effects of coincidental metabolic syndrome were most apparent in the immune‐tolerant phase.ConclusionCoincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B infection, independent of viral load and hepatitis activity.
Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis
Authors: Rupp C. , Friedrich K. , Folseraas T. , Wannhoff A. , Bode K. A. , Weiss K.‐H. , Schirmacher P. , Sauer P. , Stremmel W. , Gotthardt D. N. 
Published: February 2014

SummaryBackgroundA recent genome‐wide association study identified the FUT2 secretor status and genotype defined by the single‐nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis (PSC), which significantly influences biliary bacterial composition.AimTo determine the impact of the rs601338‐FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver‐transplantation‐free survival in patients with PSC.MethodsCohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338‐FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews.ResultsFor the rs601338‐FUT2 genotype, 69 patients (32.1%) were found to be wildtype (GG), 97 (45.1%) patients were heterozygous (AG) and 49 patients (22.8%) were homozygous‐mutated (AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections (P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis (P = 0.0025), development of dominant stenosis (P < 0.002) and a reduced actuarial transplantation‐free survival (P = 0.044). Levels of biliary Ca19‐9 were significantly elevated in the homozygous‐mutated patients.ConclusionsThe rs601338‐FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host‐microbial diversity and disease progression in PSC.
Good clinical outcomes following transjugular intrahepatic portosystemic stent‐shunts in Budd–Chiari syndrome
Authors: Tripathi D. , MacNicholas R. , Kothari C. , Sunderraj L. , Al‐Hilou H. , Rangarajan B. , Chen F. , Mangat K. , Elias E. , Olliff S. 
Published: February 2014

SummaryBackgroundThere have been encouraging reports on transjugular intrahepatic portosystemic stent‐shunt (TIPSS) for Budd–Chiari syndrome (BCS). Long‐term data are lacking.AimTo assess long‐term outcomes and validate prognostic scores following TIPSS for BCS.MethodsA single centre retrospective study. Patients underwent TIPSS using bare or polytertrafluoroethane (PTFE)‐covered stents.ResultsSixty‐seven patients received successful TIPSS between 1996 and 2012 using covered (n = 40) or bare (n = 27) stents. Patients included had a Male: Female ratio of 21:46, and were characterised (mean ± s.d.) by age 39.9 ± 14.3 years, Model of end stage liver disease (MELD) 16.1 ± 7.0 and Child's score 8.8 ± 2.0. Seventy‐eight percent had haematological risk factors. Presenting symptoms were ascites (n = 61) and variceal bleeding (n = 6). Nine patients underwent hepatic vein dilatation or stenting prior to TIPSS. Mean follow‐up was 82 months (range 0.5–184 months). Fifteen percent had post‐TIPSS encephalopathy. Two have been transplanted. Primary patency rates (76% vs. 27%, P < 0.001) and shunt re‐interventions (22% vs. 100%, P < 0.001) significantly favoured covered stents. Secondary patency was 99%. Six‐, 12‐, 24‐, 60‐ and 120‐month survival was 97%, 92%, 87%, 80% and 72% respectively. Six patients had liver related deaths. Two patients developed hepatocellular carcinoma. The BCS TIPS PI independently predicted mortality in the whole cohort, but no prognostic score was a significant predictor of mortality after subgroup validation.ConclusionsLong‐term outcomes following TIPSS for Budd–Chiari syndrome are very good. PTFE‐covered stents have significantly better primary patency. The value of prognostic scores is controversial. TIPSS should be considered as first line therapy in symptomatic patients in whom hepatic vein patency cannot be restored.
Review article: the endocannabinoid system in liver disease, a potential therapeutic target
Authors: Basu P. P. , Aloysius M. M. , Shah N. J. , Brown Jr R. S. 
Published: February 2014

SummaryBackgroundEndocannabinoids are a family of potent lipid‐soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver.AimsTo review the current understanding of the role of the endocannabinoid system in liver disease‐associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease.MethodsOriginal articles and reviews were used to summarise the relevant pre‐clinical and clinical research findings relating to this topic.ResultsThe endocannabinoid system as a whole plays an important role in liver diseases (i.e. non‐alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre‐clinical stage of development.ConclusionsThe endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood–brain barrier.
Suitability and limitations of native species for seed mixtures to re‐vegetate degraded areas
Authors: Oliveira Graça , Clemente Adelaide , Nunes Alice , Correia Otília 
Published: February 2014

AbstractQuestionsHow do native species perform when included in seed mixtures to re‐vegetate degraded areas? Is their germination and establishment affected by seeding density?LocationLimestone quarry spoil, SW Portugal.MethodsA glasshouse experiment simulating usual hydroseeding procedures (substrate, time of the year, slurry composition, seed mixture) was performed to evaluate the suitability of six native species (Origanum vulgare, Piptatherum miliaceum, Phagnalon saxatile, Sedum album, S. sediforme, Thymus mastichina) to re‐vegetate a Mediterranean quarry. Other native species were added to create the seed mixtures. Three treatments were assayed for each target species sown: (1) alone (T), (2) in a low‐density seed mixture (ca. 15 g·m−2), and (3) in a high‐density seed mixture (ca. 30 g·m−2). Plants were monitored for 8 months.ResultsThe target species were able to germinate, establish and grow when sown alone, but their performance was drastically impaired when included in seed mixtures. This was related to plant morphologies, as some co‐seeded species rapidly developed large leaves, which presumably reduced resource availability for the small‐leaved seedlings of most target species. Almost no seedlings of the latter survived in the mixture treatments. Low‐ and high‐seeding densities yielded similar plant covers and heights.ConclusionsEven when apparently suitable to restore a given site, candidate native species cannot simply be included in current re‐vegetation ‘recipes’, because their success largely depends on the density and seedling characteristics of the co‐seeded species (even if these are also native). The early performance and morphology of the latter must be taken into account in the design of seed mixtures used in restoration actions.
Application of High‐Content Analysis in Clinical Cytology for Translational Safety Biomarkers of Drug‐Induced Toxicity for Lymphoma Chemotherapy
Authors: Domingos Margarida Canelas , Davies Anthony M. , O'Brien Peter J. 
Published: February 2014

AbstractDrug cytotoxicity detected by high‐content analysis (HCA) of live, cultured, human hepatocytes concurs with human toxic potential. We assessed HCA effectiveness in vivo using human, lymphoma line (HuT‐78) and blood cells from healthy dogs and lymphomatous dogs treated with anticancer drugs: cytarabine, arsenic trioxide (AT), doxorubicin and mitoxantrone. DNA was stained with Hoechst‐33342, calcium with fluo‐4, mitochondria with TMRM and cell permeability with toto‐3. HuT‐78 and canine blood lymphocytes were treated 24 hr with 10 times increasing drug concentrations to determine concentration–response relationships to test agents. These showed hormesis (biphasic response) for TMRM and nuclear area. Fluorescence intensity was decreased with AT and mitoantrone but increased with cytarabine for TMRM, decreased from cell injury or anthracycline interaction for Hoechst‐33342 and decreased with AT and interfered with by doxorubicin for fluo‐4. Nuclear area increased with anthracyclines and AT. Mitochondria, calcium and nuclear area were affected in peripheral blood lymphocytes of lymphomatous dogs receiving chemotherapy: mitochondria were inhibited by acute treatment, but increased 2 weeks after treatment, as were ionized calcium, nuclear area and DNA. We conclude (i) concentration–response relationships are determinable in vitro for human and canine lymphocytes by HCA, (ii) cytotoxicity is detectable in vivo during and after anticancer drug treatment using canine blood lymphocytes: mitochondria are most affected, with smaller changes in calcium and nuclei and (iii) blood cell viability may be a biomarker for anticancer drug toxicity.
Semi‐Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents
Authors: Yun Hwi‐yeol , Kang Wonku , Lee Byung‐yo , Park Sunkyung , Yoon Young‐Ran , Yeul Ma Jin , Kwon Kwang‐il 
Published: February 2014

AbstractAntiplatelet agents are a class of pharmaceuticals that decrease platelet aggregation and thus inhibit thrombus formation. We examined the relationships between plasma concentrations of antiplatelet agents (triflusal, clopidogrel and cilostazol) and the platelet aggregation inhibitory effect after dosing. We used triflusal, cilostazol and clopidogrel for the development of a semi‐mechanistic PK/PD model. The drugs chosen are used widely and reflect various mechanisms of antiplatelet agents. Time courses of plasma concentrations of the antiplatelet agents and their platelet aggregation effects were analysed using ADPAT V. Pharmacokinetic profiles were fitted to an extended parent–metabolite pharmacokinetic model, based on a two‐compartment model, and the pharmacodynamic effects of the agents were fitted to a platelet aggregation effect model that consisted of the following parameters: Ks, the active‐form platelet synthesis rate constant; K, the apparent reaction rate constant of the agent and active‐form platelets; Kel‐PRP, the apparent rate constant of platelets; and ε, an intrinsic activity parameter. This semi‐mechanistic PK/PD model described well the relationship between plasma concentrations of antiplatelet agents and platelet aggregation effects. In addition, the estimated parameters were suitable for the explanation of the agents and also have a good correlation with platelet characteristics, such as platelet half‐life and platelet aggregation baseline effects. Specifically, we discovered the strong correlations between estimated K parameter and in vitro drug activity. We conclude that this semi‐mechanistic PK/PD model explained drug PK/PD characteristics well and will be useful for accurate predictions of antiplatelet effect in the clinical situations.
Bayesian hidden Markov models to identify RNA–protein interaction sites in PAR‐CLIP
Authors: Yun Jonghyun , Wang Tao , Xiao Guanghua 
Published: February 2014

SummaryThe photoactivatable ribonucleoside enhanced cross‐linking immunoprecipitation (PAR‐CLIP) has been increasingly used for the global mapping of RNA–protein interaction sites. There are two key features of the PAR‐CLIP experiments: The sequence read tags are likely to form an enriched peak around each RNA–protein interaction site; and the cross‐linking procedure is likely to introduce a specific mutation in each sequence read tag at the interaction site. Several ad hoc methods have been developed to identify the RNA–protein interaction sites using either sequence read counts or mutation counts alone; however, rigorous statistical methods for analyzing PAR‐CLIP are still lacking. In this article, we propose an integrative model to establish a joint distribution of observed read and mutation counts. To pinpoint the interaction sites at single base‐pair resolution, we developed a novel modeling approach that adopts non‐homogeneous hidden Markov models to incorporate the nucleotide sequence at each genomic location. Both simulation studies and data application showed that our method outperforms the ad hoc methods, and provides reliable inferences for the RNA–protein binding sites from PAR‐CLIP data.
Test the reliability of doubly robust estimation with missing response data
Authors: Chen Baojiang , Qin Jing 
Published: February 2014

SummaryIn statistical inference, one has to make sure that the underlying regression model is correctly specified otherwise the resulting estimation may be biased. Model checking is an important method to detect any departure of the regression model from the true one. Missing data are a ubiquitous problem in social and medical studies. If the underlying regression model is correctly specified, recent researches show great popularity of the doubly robust (DR) estimates method for handling missing data because of its robustness to the misspecification of either the missing data model or the conditional mean model, that is, the model for the conditional expectation of true regression model conditioning on the observed quantities. However, little work has been devoted to the goodness of fit test for DR estimates method. In this article, we propose a testing method to assess the reliability of the estimator derived from the DR estimating equation with possibly missing response and always observed auxiliary variables. Numerical studies demonstrate that the proposed test can control type I errors well. Furthermore the proposed method can detect departures from model assumptions in the marginal mean model of interest powerfully. A real dementia data set is used to illustrate the method for the diagnosis of model misspecification in the problem of missing response with an always observed auxiliary variable for cross‐sectional data.
A Bayesian localized conditional autoregressive model for estimating the health effects of air pollution
Authors: Lee Duncan , Rushworth Alastair , Sahu Sujit K. 
Published: February 2014

SummaryEstimation of the long‐term health effects of air pollution is a challenging task, especially when modeling spatial small‐area disease incidence data in an ecological study design. The challenge comes from the unobserved underlying spatial autocorrelation structure in these data, which is accounted for using random effects modeled by a globally smooth conditional autoregressive model. These smooth random effects confound the effects of air pollution, which are also globally smooth. To avoid this collinearity a Bayesian localized conditional autoregressive model is developed for the random effects. This localized model is flexible spatially, in the sense that it is not only able to model areas of spatial smoothness, but also it is able to capture step changes in the random effects surface. This methodological development allows us to improve the estimation performance of the covariate effects, compared to using traditional conditional auto‐regressive models. These results are established using a simulation study, and are then illustrated with our motivating study on air pollution and respiratory ill health in Greater Glasgow, Scotland in 2011. The model shows substantial health effects of particulate matter air pollution and nitrogen dioxide, whose effects have been consistently attenuated by the currently available globally smooth models.
Relapse kinetics in acute myeloid leukaemias with MLL translocations or partial tandem duplications within the MLL gene
Authors: Ommen Hans B. , Hokland Peter , Haferlach Torsten , Abildgaard Lotte , Alpermann Tamara , Haferlach Claudia , Kern Wolfgang , Schnittger Susanne 
Published: February 2014

SummaryCorrect action upon re‐emergence of minimal residual disease in acute myeloid leukaemia (AML) patients has not yet been established. The applicability of demethylating agents and use of allogeneic stem cell transplantation will be dependent on pre‐relapse AML growth rates. We here delineate molecular growth kinetics of AML harbouring MLL partial tandem duplication (MLL‐PTD; 37 cases) compared to those harbouring MLL translocations (43 cases). The kinetics of MLL‐PTD relapses was both significantly slower than those of MLL translocation positive ones (median doubling time: MLL‐PTD: 24 d, MLL‐translocations: 12 d, P = 0·015, Wilcoxon rank sum test), and displayed greater variation depending on additional mutations. Thus, MLL‐PTD+ cases with additional RUNX1 mutations or FLT3‐internal tandem duplication relapsed significantly faster than cases without one of those two mutations (Wilcoxon rank sum test, P = 0·042). As rapid relapses occurred in all MLL subgroups, frequent sampling are necessary to obtain acceptable relapse detection rates and times from molecular relapse to haematological relapse (blood sampling every second month: MLL‐PTD: 75%/50 d; MLL translocations: 85%/25 d). In conclusion, in this cohort relapse kinetics is heavily dependent on AML subtype as well as additional genetic aberrations, with possibly great consequences for the rational choice of pre‐emptive therapies.
Effect of partial bladder outlet obstruction and reversal on rabbit bladder physiology and biochemistry: duration of recovery period and severity of function
Authors: Jock Marley , Leggett Robert E. , Schuler Catherine , Callaghan Connor , Levin Robert M. 
Published: February 2014

ObjectivesTo use a rabbit model of partial bladder outlet obstruction (BOO) to investigate the point at which obstructive bladder dysfunction becomes irreversible.MethodsPartial BOO was induced in New Zealand White rabbits. It was then reversed and the rabbits were allowed to recover for 4, 8 or 12 weeks. Both at the time of reversal and at the end of the study, the rabbits were grouped according to bladder decompensation level (mild, intermediate or severe) based on bladder mass (weight).ResultsA strong correlation was observed between the production and distribution of collagen and the reduction of smooth muscle contractile function. We found that only in the bladders that were severely decompensated at the time of reversal did collagen levels not decrease.ConclusionThe data show that recovery of function after reversal of partial BOO is directly related primarily to collagen levels at the time of reversal.
Novel method of full‐thickness bladder closure with an endoscopic suturing machine: a survival study in a porcine model
Authors: Oliveira Carlos , Autorino Riccardo , Ferreira Carlos , Cicione Antonio , Damiano Rocco , De Sio Marco , Correia‐Pinto Jorge , Lima Estevao 
Published: February 2014

ObjectiveTo assess the feasibility of a pure endoscopic closure method for vesical perforations using fully absorbable material.Materials and MethodsA pilot experimental study was performed in eight anaesthetized female pigs. Four 10‐mm and four 20‐mm endoscopic full thickness cystotomies were created. An endoscopic suturing machine (RD‐180®; LSI Solutions, Victor, NY, USA) was deployed through the working channel of a cystoscope and used to close the incisions with absorbable sutures. Immediate assessment of the quality of the closure was obtained by distending the bladder with saline solution stained with methylene blue under laparoscopic control. After 3 weeks of follow‐up, a necropsy examination was performed to check for signs of peritonitis and wound dehiscence and to assess the quality of healing.ResultsThe experiment was completed in all eight pigs without complications. The median procedure time was 10 ± 4.3 min. The immediate bladder distention test did not show any methylene blue leakage. The postoperative period was uneventful. The post mortem examination after 3 weeks revealed complete healing of the bladder wall incisions with no signs of infection, wound dehiscence or adhesions in the peritoneal cavity of any of the pigs.ConclusionThis study describes a successful novel method for endoscopic closure of bladder perforations. The technique was easy, reproducible and safe. Nevertheless, further experimental investigation should be carried out before clinical application of this method.