bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia
Authors: Gómez-Chacón Beatriz , Gámiz Fernando , Foster Thomas C. , Gallo Milagros
Published: December 2015

Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.
Research on Thermal-Field and Sound-Field Coupling Properties of Different Grid Forms
Authors: Zhang Enlai , Hou Liang , Cai Huikun , Shen Chao , Zhang Yaxiang
Published: December 2015

The inlet grid and exhaust grid are widely used in engineering machinery products. The process that airflow goes through grids is a complex turbulent flow and directly related to the heat dispersion and aerodynamic noise. The theoretical analysis result shows that the jet noise generated by airflow has a connection with the grid structure form, fluid flowing situation, and heat conduction. In addition, the influences of different grid structure forms (included the round hole, long hole, and square hole) and porosity on the heat dissipation and aerodynamic noise were analyzed and presented based on the verified computational fluid dynamics (CFD) model. Results show that the heat dispersion and aerodynamic noise of the round hole are most effective under the same porosity; as the porosity increases, the disturbance degree decreases and the noise reduction effect gets better. Finally, the research result provides the scientific basis for improving grid structure and achieving energy saving and noise reduction.
Endothelium‐Independent Hypoxic Contraction Is Prevented Specifically by Nitroglycerin via Inhibition of Akt Kinase in Porcine Coronary Artery
Authors: Liu Huixia , Li Yanjing , An Yuanming , He Peixin , Wu Liling , Gao Yuansheng , Dou Dou
Published: December 2015

Objective. Hypoxia‐induced sustained contraction of porcine coronary artery is endothelium‐independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia‐induced endothelium‐independent contraction and the underlying mechanism. Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8‐Br‐cGMP, which can be reversed by ODQ, and Rp‐8‐Br‐PET‐cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt‐p at Ser‐473 by NTG, DETA NONOate, and 8‐Br‐cGMP was significantly inhibited by ODQ, PKG‐I. The decrease in Akt‐p level by NTG and 8‐Br‐cGMP was prevented by calyculin A but not by okadaic acid. Conclusions. These results demonstrated that the endothelium‐independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved.
Analysis of Residual Dependencies of Independent Components Extracted from fMRI Data
Authors: Vanello N. , Ricciardi E. , Landini L.
Published: December 2015

Independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data can be employed as an exploratory method. The lack in the ICA model of strong a priori assumptions about the signal or about the noise leads to difficult interpretations of the results. Moreover, the statistical independence of the components is only approximated. Residual dependencies among the components can reveal informative structure in the data. A major problem is related to model order selection, that is, the number of components to be extracted. Specifically, overestimation may lead to component splitting. In this work, a method based on hierarchical clustering of ICA applied to fMRI datasets is investigated. The clustering algorithm uses a metric based on the mutual information between the ICs. To estimate the similarity measure, a histogram-based technique and one based on kernel density estimation are tested on simulated datasets. Simulations results indicate that the method could be used to cluster components related to the same task and resulting from a splitting process occurring at different model orders. Different performances of the similarity measures were found and discussed. Preliminary results on real data are reported and show that the method can group task related and transiently task related components.
Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells
Authors: Barati Michelle T. , Gould James C. , Salyer Sarah A. , Isaacs Susan , Wilkey Daniel W. , Merchant Michael L.
Published: December 2015

The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG) growth conditions as compared to isoosmotic/normal glucose control (NG⁎) conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1) proteins involved in cell survival/cell signaling and (2) proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB), supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase), suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis.
Engineering Tendon: Scaffolds, Bioreactors, and Models of Regeneration
Authors: Youngstrom Daniel W. , Barrett Jennifer G.
Published: December 2015

Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force‐sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell‐matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems.
Blockade of Toll-Like Receptors (TLR2, TLR4) Attenuates Pain and Potentiates Buprenorphine Analgesia in a Rat Neuropathic Pain Model
Authors: Jurga Agnieszka M. , Rojewska Ewelina , Piotrowska Anna , Makuch Wioletta , Pilat Dominika , Przewlocka Barbara , Mika Joanna
Published: December 2015

Accumulating evidence indicates that microglial TLR2 and TLR4 play a significant role in nociception. Experiments were conducted to evaluate the contribution of TLR2 and TLR4 and their adaptor molecules to neuropathy and their ability to amplify opioid effectiveness. Behavioral tests (von Frey’s and cold plate) and biochemical (Western blot and qRT-PCR) analysis of spinal cord and DRG tissue were conducted after chronic constriction injury (CCI) to the sciatic nerve. Repeated intrathecal administration ofLPS-RS(TLR2 and TLR4 antagonist) andLPS-RS Ultrapure(TLR4 antagonist) attenuated allodynia and hyperalgesia. Biochemical analysis revealed time-dependent upregulation of mRNA and/or protein levels of TLR2 and TLR4 and MyD88 and TRIF adaptor molecules, which was paralleled by an increase in IBA-1/CD40-positive cells under neuropathy.LPS-RSandLPS-RS Ultrapuresimilarly influenced opioid analgesia by enhancing the effectiveness of buprenorphine but not morphine. Summing up, in light of their upregulation over the course of pain, both TLR2 and TLR4 may indeed play a significant role in neuropathy, which could be linked to the observed activation of IBA-1/CD40-positive cells. Blockade of TLR2 and TLR4 produced analgesia and enhanced buprenorphine’s effectiveness, which suggests that they may be a putative target for future pharmacological pain relief tools, especially for opioid rotation, when the effect of morphine is tolerated.
Comparison of Clinical Trajectories before Initiation of Renal Replacement Therapy between Diabetic Nephropathy and Nephrosclerosis on the KDIGO Guidelines Heat Map
Authors: Abe Masanori , Okada Kazuyoshi , Maruyama Noriaki , Takashima Hiroyuki , Oikawa Osamu , Soma Masayoshi
Published: December 2015

This study investigated differences between the clinical trajectories of diabetic nephropathy and nephrosclerosis using the Kidney Disease: Improving Global Outcomes (KDIGO) heat map and the clinical characteristics between the two diseases at RRT initiation. This single-center, retrospective study enrolled 100 patients whose estimated glomerular filtration rate (eGFR) was ≥45 mL/min/1.73 m2at their first visit and who were initiated on RRT. Fifty consecutive patients were assigned to each of the diabetic nephropathy and nephrosclerosis groups. All data for simultaneously measured eGFR and urinary albumin to creatinine ratio (UACR) were collected from first visit to RRT initiation and were plotted on the KDIGO heat map. Diabetic nephropathy was characterized by higher blood pressure and UACR and lower age, eGFR, and serum albumin levels compared with nephrosclerosis at RRT initiation. The vast majority of patients with diabetic nephropathy and eGFR < 60 mL/min/1.73 m2had concomitant macroalbuminuria, whereas for patients with nephrosclerosis, even when eGFR was <45 mL/min/1.73 m2, many still had normoalbuminuria or microalbuminuria. The rate of decline of eGFR was significantly faster in the diabetic nephropathy group than that in the nephrosclerosis group. The clinical trajectories of diabetic nephropathy and nephrosclerosis differed markedly on the KDIGO heat map.
Comparison of Signaling Pathways Gene Expression in CD34− Umbilical Cord Blood and Bone Marrow Stem Cells
Authors: Stojko Rafał , Bojdys-Szyndlar Monika , Drosdzol-Cop Agnieszka , Madej Andrzej , Wilk Krzysztof
Published: December 2015

The aim of the study was to compare the biological activity of the total pool of genes in CD34− umbilical cord blood and bone marrow stem cells and to search for the differences in signaling pathway gene expression responsible for the biological processes. The introductory analysis revealed a big similarity of gene expression among stem cells. When analyzing GO terms for biological processes, we observed an increased activity of JAK‐STAT signaling pathway, calcium‐mediated, cytokine‐mediated, integrin‐mediated signaling pathway, and MAPK in a cluster of upregulating genes in CD34− umbilical cord blood stem cells. At the same time, we observed a decreased activity of BMP signaling pathways, TGF‐beta pathway, and VEGF receptor signaling pathway in a cluster of downregulating genes in CD34− umbilical cord blood stem cells. In accordance with KEGG classification, the cytokine‐cytokine receptor interaction, toll‐like receptor signaling pathway, and JAK‐STAT signaling pathway are overrepresented in CD34− umbilical cord blood stem cells. A similar gene expression in both CD34− UCB and BM stem cells was characteristic for such biological processes as cell division, cell cycle gene expression, mitosis, telomere maintenance with telomerase, RNA and DNA treatment processes during cell division, and similar genes activity of Notch and Wnt signaling pathways.
Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms
Authors: Li Fengyuan , Duan Kangmin , Wang Cuiling , McClain Craig , Feng Wenke
Published: December 2015

Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.
Correlation between Histological Activity and Endoscopic, Clinical, and Serologic Activities in Patients with Ulcerative Colitis
Authors: Kim Dae Bum , Lee Kang-Moon , Lee Ji Min , Chung Yoon Yung , Sung Hea Jung , Paik Chang Nyol , Chung Woo Chul , Jung Ji-Han , Choi Hyun Joo
Published: December 2015

Objectives. Recent studies suggest that histological healing is a treatment goal in ulcerative colitis (UC). We aimed to evaluate the correlation between histological activity and clinical, endoscopic, and serologic activities in patients with UC.Methods. We retrospectively reviewed medical records from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsies. The Mayo endoscopic subscore was used to assess endoscopic activity. Biopsy specimens were reviewed by two blinded pathologists and scored using the Geboes scoring system.Results. We analyzed 154 biopsy specimens from 82 patients with UC. Histological scores exhibited strong correlation with endoscopic subscores (Spearman’s rank correlation coefficientr=0.774,p<0.001) and moderate correlation with C-reactive protein levels (r=0.422,p<0.001) and partial Mayo scores (r=0.403,p<0.001). Active histological inflammation (Geboes score ≥ 3.1) was observed in 6% (2 of 33) of the endoscopically normal mucosa samples, 66% (19 of 29) of mild disease samples, and 98% (90 of 92) of moderate-to-severe disease samples.Conclusions. Histological activity was closely correlated with the endoscopic, clinical, and serologic UC activities. However, several patients with mild or normal endoscopic findings exhibited histological evidence of inflammation. Therefore, histological assessment may be helpful in evaluating treatment outcomes and determining follow-up strategies.
Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p72 Syk
Authors: Pantaleo Antonella , Ferru Emanuela , Pau Maria Carmina , Khadjavi Amina , Mandili Giorgia , Mattè Alessandro , Spano Alessandra , De Franceschi Lucia , Pippia Proto , Turrini Francesco
Published: December 2015

In erythrocytes, the regulation of the redox sensitive Tyr phosphorylation of band 3 and its functions are still partially defined. A role of band 3 oxidation in regulating its own phosphorylation has been previously suggested. The current study provides evidences to support this hypothesis: (i) in intact erythrocytes, at 2 mM concentration of GSH, band 3 oxidation, and phosphorylation, Syk translocation to the membrane and Syk phosphorylation responded to the same micromolar concentrations of oxidants showing identical temporal variations; (ii) the Cys residues located in the band 3 cytoplasmic domain are 20‐fold more reactive than GSH; (iii) disulfide linked band 3 cytoplasmic domain docks Syk kinase; (iv) protein Tyr phosphatases are poorly inhibited at oxidant concentrations leading to massive band 3 oxidation and phosphorylation. We also observed that hemichromes binding to band 3 determined its irreversible oxidation and phosphorylation, progressive hemolysis, and serine hyperphosphorylation of different cytoskeleton proteins. Syk inhibitor suppressed the phosphorylation of band 3 also preventing serine phosphorylation changes and hemolysis. Our data suggest that band 3 acts as redox sensor regulating its own phosphorylation and that hemichromes leading to the protracted phosphorylation of band 3 may trigger a cascade of events finally leading to hemolysis.
Energy Conservation Analysis and Control of Hybrid Active Semiactive Suspension with Three Regulating Damping Levels
Authors: Chen Long , Shi Dehua , Wang Ruochen , Zhou Huawei
Published: December 2015

Active suspension has not been popularized for high energy consumption. To address this issue, this paper introduces the concept of a new kind of suspension. The linear motor is considered to be integrated into an adjustable shock absorber to form the hybrid active semiactive suspension (HASAS). To realize the superiority of HASAS, its energy consumption and regeneration mechanisms are revealed. And the system controller which is composed of linear quadratic regulator (LQR) controller, mode decision and switch controller, and the sliding mode control based thrust controller is developed. LQR controller is designed to maintain the suspension control objectives, while mode decision and switch controller decides the optimal damping level to tune motor thrust. The thrust controller ensures motor thrust tracking. An adjustable shock absorber with three regulating levels to be used in HASAS is trial produced and tested to obtain its working characteristics. Finally, simulation analysis is made with the experimental three damping characteristics. The impacts of adjustable damping on the motor force and energy consumption are investigated. Simulation results demonstrate the advantages of HASAS in energy conservation with various suspension control objectives. Even self-powered active control and energy regenerated to the power source can be realized.
Nonlinear Seismic Behavior of Different Boundary Conditions of Transmission Line Systems under Earthquake Loading
Authors: Tian Li , Gai Xia
Published: December 2015

Nonlinear seismic behaviors of different boundary conditions of transmission line system under earthquake loading are investigated in this paper. The transmission lines are modeled by cable element accounting for the nonlinearity of the cable. For the suspension type, three towers and two span lines with spring model (Model 1) and three towers and four span lines’ model (Model 2) are established, respectively. For the tension type, three towers and two span lines’ model (Model 3) and three towers and four span lines’ model (Model 4) are created, respectively. The frequencies of the transmission towers and transmission lines of the suspension type and tension type are calculated, respectively. The responses of the suspension type and tension type are investigated using nonlinear time history analysis method, respectively. The results show that the responses of the transmission tower and transmission line of the two models of the suspension type are slightly different. However, the responses of transmission tower and transmission line of the two models of the tension type are significantly different. Therefore, in order to obtain accurate results, a reasonable model should be considered. The results could provide a reference for the seismic analysis of the transmission tower-line system.
Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1
Authors: Jung Joo Young , Ryu Min-Hee , Ryoo Baek-Yeol , Han Boram , Cho Ji Woong , Lim Man Sup , Lim Hyun , Kang Ho Suk , Kim Min-Jeong , Ha Hong Il , Song Hunho , Kim Jung Han , Kim Hyeong Su , Kang Yoon-Koo , Zang Dae Young
Published: December 2015

Background.This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS).Patients and Methods.We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011.Results.A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%).Conclusion.FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.
The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars
Authors: Seo Bommie Florence , Jung Sung-No
Published: December 2015

Excessive scars, including keloids and hypertrophic scars, result from aberrations in the process of physiologic wound healing. An exaggerated inflammatory process is one of the main pathophysiological contributors. Scars may cause pain, and pruritis, limit joint mobility, and cause a range of cosmetic deformities that affect the patient’s quality of life. Extensive research has been done on hypertrophic scar and keloid formation that has resulted in the plethora of treatment and prevention methods practiced today. Mesenchymal stem cells, among their multifunctional roles, are known regulators of inflammation and have been receiving attention as a major candidate for cell therapy to treat or prevent excessive scars. This paper extensively reviews the body of research examining the mechanism and potential of stem cell therapy in the treatment of excessive scars.
Comparison of Three Statistical Downscaling Methods and Ensemble Downscaling Method Based on Bayesian Model Averaging in Upper Hanjiang River Basin, China
Authors: Liu Jiaming , Yuan Di , Zhang Liping , Zou Xia , Song Xingyuan
Published: December 2015

Many downscaling techniques have been developed in the past few years for projection of station-scale hydrological variables from large-scale atmospheric variables to assess the hydrological impacts of climate change. To improve the simulation accuracy of downscaling methods, the Bayesian Model Averaging (BMA) method combined with three statistical downscaling methods, which are support vector machine (SVM), BCC/RCG-Weather Generators (BCC/RCG-WG), and Statistics Downscaling Model (SDSM), is proposed in this study, based on the statistical relationship between the larger scale climate predictors and observed precipitation in upper Hanjiang River Basin (HRB). The statistical analysis of three performance criteria (the Nash-Sutcliffe coefficient of efficiency, the coefficient of correlation, and the relative error) shows that the performance of ensemble downscaling method based on BMA for rainfall is better than that of each single statistical downscaling method. Moreover, the performance for the runoff modelled by the SWAT rainfall-runoff model using the downscaled daily rainfall by four methods is also compared, and the ensemble downscaling method has better simulation accuracy. The ensemble downscaling technology based on BMA can provide scientific basis for the study of runoff response to climate change.
Nanosensors for a Monitoring System in Intelligent and Active Packaging
Authors: Fuertes Guillermo , Soto Ismael , Vargas Manuel , Valencia Alvaro , Sabattin Jorge , Carrasco Raúl
Published: December 2015

A theoretical wireless nanosensor network (WNSN) system that gives information about the food packaging condition is proposed. The protection effectiveness is estimated by measuring many factors, such as the existence of microorganisms, bacteria, gases, and contaminants. This study is focused on the detection of an antimicrobial agent (AA) attached on a polymer forming an active integrated package. All monitoring technologies for food conservation are analyzed. Nanobiosensor nanomachine (NM), which converts biological or chemical signals into electrical signals, is used. A mathematical model, which describes the constituent’s emigration from the package to food, is programmed in MatLab software. The results show three nanobiosensors forming a WNSN. The nanobiosensors are able to carry out the average concentration for different spots in the package. This monitoring system shows reading percentages in three degrees and different colors: excellent (green), good (cyan), and lacking (red). To confirm the utility of the model, different simulations are performed. Using the WNSNs, results of AA existing in food package (FP) through time were successfully obtained.
Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia
Authors: Drazilova Sylvia , Janicko Martin , Kristian Pavol , Schreter Ivan , Kucinsky Branislav , Kozlej Marek , Hockickova Ivana , Jarcuska Peter
Published: December 2015

Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia.Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment.Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control groupp=0.0009. There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority,p=0.003). We also did not find significant difference at the rate of HBsAg loss.Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response.
Gastric Mucinous Cancer Histology: Clinicopathological Characteristics and Prognostic Value
Authors: Jian-Hui Chen , Shi-Rong Cai , Hui Wu , Jian-bo Xu , Kai-Ming Wu , Si-le Chen , He Yu-Long
Published: December 2015

MC tended toward worse tumor biological behavior and long-term survival outcome compared to WMDC. Moreover, MC also showed worse clinicopathological features and survival outcome in some selected patients. For these reasons, MC should be deemed as a special histological type of gastric cancer with worse clinicopathological features and survival outcome.
Endogenous Sulfur Dioxide: A New Member of Gasotransmitter Family in the Cardiovascular System
Authors: Huang Yaqian , Tang Chaoshu , Du Junbao , Jin Hongfang
Published: December 2015

Sulfur dioxide (SO2) was previously regarded as a toxic gas in atmospheric pollutants. But it has been found to be endogenously generated from metabolism of sulfur‐containing amino acids in mammals through transamination by aspartate aminotransferase (AAT). SO2 could be produced in cardiovascular tissues catalyzed by its synthase AAT. In recent years, studies revealed that SO2 had physiological effects on the cardiovascular system, including vasorelaxation and cardiac function regulation. In addition, the pathophysiological effects of SO2 were also determined. For example, SO2 ameliorated systemic hypertension and pulmonary hypertension, prevented the development of atherosclerosis, and protected against myocardial ischemia‐reperfusion (I/R) injury and isoproterenol‐induced myocardial injury. These findings suggested that endogenous SO2 was a novel gasotransmitter in the cardiovascular system and provided a new therapy target for cardiovascular diseases.
Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis
Authors: Bianchessi Marta , Chen Yuwen , Durgam Sushmitha , Pondenis Holly , Stewart Matthew
Published: December 2015

Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF‐2) on SF‐CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF‐2 would stimulate SF‐CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony‐forming unit (CFU) assays were performed during primary cultures. At first passage, SF‐cells were seeded at low density, with or without FGF‐2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF‐2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF‐2 did not alter the immunophenotype of SF‐CPs during monolayer expansion, nor did FGF‐2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF‐2 groups. FGF‐2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF‐2 significantly accelerates in vitro SF‐CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity.
Blocking HSP90 Addiction Inhibits Tumor Cell Proliferation, Metastasis Development, and Synergistically Acts with Zoledronic Acid to Delay Osteosarcoma Progression
Authors: Ory Benjamin , Baud'huin Marc , Verrecchia Franck , Royer Bénédicte Brounais-Le , Quillard Thibaut , Amiaud Jérôme , Battaglia Séverine , Heymann Dominique , Redini Francoise , Lamoureux Francois
Published: December 2015

Purpose: Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants the development of new strategies to improve overall patient survival. Among them, HSP90 is a molecular chaperone involved in the maturation and stability of various oncogenic proteins leading to tumor cells survival and disease progression. We assessed the antitumor properties of a synthetic HSP90 inhibitor, PF4942847, alone or in combination with zoledronic acid in osteosarcoma.

Experimental Design: The effects of PF4942847 were evaluated on human osteosarcoma cells growth and apoptosis. Signaling pathways were analyzed by Western blotting. The consequence of HSP90 therapy combined or not with zoledronic acid was evaluated in mice bearing HOS-MNNG xenografts on tumor growth, associated bone lesions, and pulmonary metastasis. The effect of PF4942847 on osteoclastogenesis was assessed on human CD14+ monocytes.

Results: In osteosarcoma cell lines, PF4942847 inhibited cell growth in a dose-dependent manner (IC50 ±50 nmol/L) and induced apoptosis with an increase of sub-G1 fraction and cleaved PARP. These biologic events were accompanied by decreased expression of Akt, p-ERK, c-Met, and c-RAF1. When administered orally to mice bearing osteosarcoma tumors, PF4942847 significantly inhibited tumor growth by 80%, prolonged survival compared with controls, and inhibited pulmonary metastases by blocking c-Met, FAK, and MMP9 signaling. In contrast to 17-allylamino-17-demethoxygeldanamycin (17-AAG), PF4942847 did not induce osteoclast differentiation, and synergistically acted with zoledronic acid to delay osteosarcoma progression and prevent bone lesions.

Conclusions: All these data provide a strong rationale for clinical evaluation of PF4942847 alone or in combination with zoledronic acid in osteosarcoma. Clin Cancer Res; 22(10); 2520–33. ©2015 AACR.
Surgical Guidance in Prostate Cancer: “From Molecule to Man” Translations
Authors: van Leeuwen Fijs W.B. , van der Poel Henk G.
Published: December 2015

Given the frequency of the disease and the difficulty of tumor resections, image-guided surgery technologies may aid the surgical management of prostate cancer patients. The “from molecule to man” translation of such approaches is, however, complex and depends on many different features, both from a technical and a practical perspective. Clin Cancer Res; 22(6); 1304–6. ©2015 AACR.

See related article by Sonn et al., p. 1403
The Doylestown Algorithm: A Test to Improve the Performance of AFP in the Detection of Hepatocellular Carcinoma
Authors: Wang Mengjun , Devarajan Karthik , Singal Amit G. , Marrero Jorge A. , Dai Jianliang , Feng Ziding , Rinaudo Jo Ann S. , Srivastava Sudhir , Evans Alison , Hann Hie-Won , Lai Yinzhi , Yang Hushan , Block Timothy M. , Mehta Anand
Published: December 2015

Biomarkers for the early diagnosis of hepatocellular carcinoma (HCC) are needed to decrease mortality from this cancer. However, as new biomarkers have been slow to be brought to clinical practice, we have developed a diagnostic algorithm that utilizes commonly used clinical measurements in those at risk of developing HCC. Briefly, as α-fetoprotein (AFP) is routinely used, an algorithm that incorporated AFP values along with four other clinical factors was developed. Discovery analysis was performed on electronic data from patients who had liver disease (cirrhosis) alone or HCC in the background of cirrhosis. The discovery set consisted of 360 patients from two independent locations. A logistic regression algorithm was developed that incorporated log-transformed AFP values with age, gender, alkaline phosphatase, and alanine aminotransferase levels. We define this as the Doylestown algorithm. In the discovery set, the Doylestown algorithm improved the overall performance of AFP by 10%. In subsequent external validation in over 2,700 patients from three independent sites, the Doylestown algorithm improved detection of HCC as compared with AFP alone by 4% to 20%. In addition, at a fixed specificity of 95%, the Doylestown algorithm improved the detection of HCC as compared with AFP alone by 2% to 20%. In conclusion, the Doylestown algorithm consolidates clinical laboratory values, with age and gender, which are each individually associated with HCC risk, into a single value that can be used for HCC risk assessment. As such, it should be applicable and useful to the medical community that manages those at risk for developing HCC. Cancer Prev Res; 9(2); 172–9. ©2015 AACR.
Patient-Specific Quantitation of Mitral Valve Strain by Computer Analysis of Three-Dimensional Echocardiography
Authors: Ben Zekry Sagit , Freeman Jeff , Jajoo Aarti , He Jiwen , Little Stephen H. , Lawrie Gerald M. , Azencott Robert , Zoghbi William A.
Published: December 2015

Background—

A paucity of data exists on mitral valve (MV) deformation during the cardiac cycle in man. Real-time 3-dimensional (3D) echocardiography now allows dynamic volumetric imaging of the MV, thus enabling computerized modeling of MV function directly in health and disease.

Methods and Results—

MV imaging using 3D transesophageal echocardiography was performed in 10 normal subjects and 10 patients with moderate-to-severe or severe organic mitral regurgitation. Using proprietary 3D software, patient-specific models of the mitral annulus and leaflets were computed at mid- and end-systole. Strain analysis of leaflet deformation was derived from these models. In normals, mean strain intensity averaged 0.11±0.02 and was higher in the posterior leaflet than in the anterior leaflet (0.13±0.03 versus 0.10±0.02;
P
<0.05). Mean strain intensity was higher in patients with mitral regurgitation (0.15±0.03) than in normals (0.11±0.02;
P
=0.05). Higher mean strain intensity was noted for the posterior leaflet in both normal and organic valves. Regional valve analysis revealed that both anterior and posterior leaflets have the highest strain concentration in the commissural zone, and the boundary zone near the annulus and at the coaptation line, with reduced strain concentration in the central leaflet zone.

Conclusions—

In normals, MV strain is higher in the posterior leaflet, with the highest strain at the commissures, annulus, and coaptation zones. Patients with organic mitral regurgitation have higher strain than normals. Three-dimensional echocardiography allows noninvasive and patient-specific quantitation of strain intensities because of MV deformations and has the potential to improve noninvasive characterization and follow-up of MV disease.
Targeted Transthoracic Acoustic Activation of Systemically Administered Nanodroplets to Detect Myocardial Perfusion Abnormalities
Authors: Porter Thomas R. , Arena Christopher , Sayyed Samer , Lof John , High Robin R. , Xie Feng , Dayton Paul A.
Published: December 2015

Background—

Liquid core nanodroplets containing condensed gaseous fluorocarbons can be vaporized at clinically relevant acoustic energies and have been hypothesized as an alternative ultrasound contrast agent instead of gas-core agents. The potential for targeted activation and imaging of these agents was tested with droplets formulated from liquid octafluoropropane (C3) and 1:1 mixtures of C3 with liquid decafluorobutane (C3C4).

Methods and Results—

In 8 pigs with recent myocardial infarction and variable degrees of reperfusion, transthoracic acoustic activation was attempted using 1.3 to 1.7 MHz low (0.2 mechanical index [MI]) or high MI (1.2 MI) imaging in real time (32–64 Hertz) or triggered 1:1 at end systole during a 20% C3 or C3C4 droplet infusion. Any perfusion defects observed were measured and correlated with delayed enhancement magnetic resonance imaging and postmortem staining. No myocardial contrast was produced with any imaging setting when using C3C4 droplets or C3 droplets during low MI real-time imaging. However, myocardial contrast was observed in all 8 pigs with C3 droplets when using triggered high MI imaging and in 5 of 6 pigs that had 1.7 MHz real time-high MI imaging. Although quantitative myocardial contrast was lower with real-time high MI imaging than 1:1 triggering, the correlation between real-time resting defect size and infarct size was good (
r
=0.97;
P
<0.001), as was the correlation with number of transmural infarcted segments by delayed enhancement imaging.

Conclusions—

Targeted transthoracic acoustic activation of infused intravenous C3 nanodroplets is effective, resulting in echogenic and persistent microbubbles which provide real-time high MI visualization of perfusion defects.
Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia
Authors: van Rijn Bas B. , Bruinse Hein W. , Veerbeek Jan H. , Post Uiterweer Emiel D. , Koenen Steven V. , van der Bom Johanna G. , Rijkers Ger T. , Roest Mark , Franx Arie
Published: December 2015

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (
P
=0.04). Preeclampsia was associated with higher IL-1β (
P
<0.05) and IL-8 (
P
<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common
TLR4
gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers.
Socioeconomic Position, But Not African Genomic Ancestry, Is Associated With Blood Pressure in the Bambui-Epigen (Brazil) Cohort Study of Aging
Authors: Lima-Costa M. Fernanda , Mambrini Juliana Vaz de Mello , Leite Maria Lea Corrêa , Peixoto Sérgio Viana , Firmo Josélia Oliveira Araújo , Loyola Filho Antônio Ignácio de , Gouveia Mateus H. , Leal Thiago P. , Pereira Alexandre Costa , Macinko James , Tarazona-Santos Eduardo
Published: December 2015

The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use. We used 370 539 single-nucleotide polymorphisms to estimate each individual’s African, European, and Native American trihybrid ancestry proportions. Median African, European, and Native American ancestry were 9.6%, 84.0%, and 5.3%, respectively. Among those with African ancestry, 59.4% came from East and 40.6% from West Africa. Baseline systolic and diastolic blood pressure, controlled hypertension, and their respective trajectories, were not significantly (
P
>0.05) associated with level (in quintiles) of African genomic ancestry. Similar results were found for West and East African subcontinental origins. Lower schooling level (<4 years versus higher) showed a significant and positive association with systolic blood pressure (Adjusted β=2.92; 95% confidence interval, 0.85–4.99). Lower monthly household income per capita (<USD 180.00 versus higher) showed an inverse association with hypertension control (β=−0.35; 95% confidence interval, −0.63 to −0.08, respectively). Our results support the view that favors social and environmental factors as determinants of blood pressure and hypertension control.
Validation of The Bureau of Meteorology’s Global, Diffuse, and Direct Solar Exposure Forecasts Using the ACCESS Numerical Weather Prediction Systems
Authors: Gregory Paul A. , Rikus Lawrie J.
Published: December 2015

Forecast solar exposure fields produced by the Australian Bureau of Meteorology’s updated numerical weather prediction systems were validated against multiple sites for the 2012 calendar year. The updated systems are denoted as the Australian Community Climate and Earth-System Simulator (ACCESS) model and became operational in August 2010. The systems are based on the Met Office’s Unified Model and feature improved assimilation methods and radiation parameterizations that were expected to greatly improve forecasts of solar exposure several days in advance. In this study forecasts of global, direct, and diffuse exposure from the mesoscale model ACCESS-A were validated. Statistics were generated for all-sky and clear-sky conditions. Additionally, evaluation of the model’s forecast exposure through single-layer low clouds was conducted. Results show an improvement in global forecasts relative to the older operational model; however, forecasts of diffuse and direct exposure still suffer from large biases. These can be attributed to the choices of the asymmetry factor used in the two-stream approximation for incoming radiation, which determines scattering of the direct beam through clouds.