bluuebunny/crossref_metadata_2025 huggingface dataset:
Size‐Controlled Synthesis of CoFe2O4 Nanoparticles Potential Contrast Agent for MRI and Investigation on Their Size‐Dependent Magnetic Properties
Authors: Liu Fujun , Laurent Sophie , Roch Alain , Vander Elst Luce , Muller Robert N.
Published: November 2013

Cobalt ferrite nanoparticles (CoFe2O4 NPs) were synthesized by coprecipitation followed by treatments with diluted nitric acid and sodium citrate. Transmission electron microscope (TEM) and photon correlation spectroscopy (PCS) characterization showed that the size distributions of these nanoparticles were monodisperse and that no aggregation occurred. This colloid showed a long‐term stability. Through adjustment of the concentrations of reactants and reaction temperature, the size of the NPs can be tuned from 6 to 80 nm. The size‐control mechanism is explained by a nucleation‐growth model, where the local concentration of monomers is assumed to decide the size of nuclei, and reaction temperatures influence the growth of nuclei. Magnetization and relaxivity r1,2 measurements showed that the NPs revealed size‐dependent magnetization and relaxivity properties, which are explained via a “dead magnetic layer” theory where reductions of saturation magnetization (Ms) and r1,2 are assumed to be caused by the demagnetization of surface spins.
Abatement of Azo Dye from Wastewater Using Bimetal‐Chitosan
Authors: Asgari Ghorban , Ramavandi Bahman , Farjadfard Sima
Published: November 2013

We introduce a new adsorbent, bimetallic chitosan particle (BCP) that is successfully synthesized and applied to remove the orange II dye from wastewater. The effects of pH, BCP quantity, and contact time are initially verified on the basis of the percentage of orange II removed from the wastewater. Experimental data reveal that the Cu/Mg bimetal and chitosan have a synergistic effect on the adsorption process of the adsorbate, where the dye adsorption by Cu/Mg bimetal, chitosan alone, and bimetal‐chitosan is 10, 49, and 99.5%, respectively. The time required for the complete decolorization of orange II by 1 mg/L of BCP is 10 min. The Langmuir model is the best fit for the experimental data, which attains a maximum adsorption capacity of 384.6 mg/g. The consideration of the kinetic behavior indicates that the adsorption of orange II onto the BCP fits best with the pseudo‐second‐order and Elovich models. Further, the simulated azo dye wastewater can be effectively treated using a relatively low quantity of the adsorbent, 1 mg/L, within a short reaction time of 20 min. Overall, the use of BCP can be considered a promising method for eliminating the azo dye from wastewater effectively.
Hyperstability of the Fréchet Equation and a Characterization of Inner Product Spaces
Authors: Bahyrycz Anna , Brzdęk Janusz , Piszczek Magdalena , Sikorska Justyna
Published: November 2013

We prove some stability and hyperstability results for the well-known Fréchet equation stemming from one of the characterizations of the inner product spaces. As the main tool, we use a fixed point theorem for the function spaces. We finish the paper with some new inequalities characterizing the inner product spaces.
Electrical Capacitance Probe Characterization in Vertical Annular Two-Phase Flow
Authors: Monni Grazia , De Salve Mario , Panella Bruno , Randaccio Carlo
Published: November 2013

The paper presents the experimental analysis and the characterization of an electrical capacitance probe (ECP) that has been developed at the SIET Italian Company, for the measurement of two-phase flow parameters during the experimental simulation of nuclear accidents, as LOCA. The ECP is used to investigate a vertical air/water flow, characterized by void fraction higher than 95%, with mass flow rates ranging from 0.094 to 0.15 kg/s for air and from 0.002 to 0.021 kg/s for water, corresponding to an annular flow pattern. From the ECP signals, the electrode shape functions (i.e., the signals as a function of electrode distances) in single- and two-phase flows are obtained. The dependence of the signal on the void fraction is derived and the liquid film thickness and the phase’s velocity are evaluated by means of rather simple models. The experimental analysis allows one to characterize the ECP, showing the advantages and the drawbacks of this technique for the two-phase flow characterization at high void fraction.
A Game-Theoretic Analysis of Multiple Protocol Data Flows in Hierarchical M2M Communication Networks
Authors: Wang Gang , Leng Jie , Bai Lin
Published: November 2013

A hierarchical machine-to-machine (M2M) communication network, where multiple heterogeneous devices compete for transmission on congested links, is considered. In such a network, the cluster headers gather the network coding and routing messages from multiple M2M devices and forward them to the cellular network. We propose a novel discriminatory user-based utility mechanism for network coding users and routing users. The price of anarchy (PoA), which is used to characterize the worst-case efficiency bounds, is analyzed. The simulation results show that network coding could promote the efficiency to a certain extent.
Cubic Composite Sensor with Photodiodes for Tracking Solar Orientation
Authors: Chang Yong-Nong
Published: November 2013

A cubic composite solar sensor with photo diode is proposed for tracking the relative solar orientation. The proposed solar sensor composes of five photodiode detectors which are placed on the front, rear, left, right, and horizontal facets in a cubic body, respectively. The solar detectors placed on five facets can detect solar power of different facets. Based on the geometric coordinate transformation principle, the relationship equations of solar light orientation between measured powers with respect to various facets can be conducted. As a result, the solar orientation can be precisely achieved without needing any assistance of electronic compass and extra orientation angle corrector. Eventually, the relative solar light orientation, the elevation angle, and azimuth angle of the solar light can be measured precisely.
Improving Delay-Range-Dependent Stability Condition for Systems with Interval Time-Varying Delay
Authors: Qian Wei , Li Tao , Liu Juan
Published: November 2013

This paper discusses the delay-range-dependent stability for systems with interval time-varying delay. Through defining the new Lyapunov-Krasovskii functional and estimating the derivative of the LKF by introducing new vectors, using free matrices and reciprocally convex approach, the new delay-range-dependent stability conditions are obtained. Two well-known examples are given to illustrate the less conservatism of the proposed theoretical results.
Mast Cells Positive to Tryptase and c-Kit Receptor Expressing Cells Correlates with Angiogenesis in Gastric Cancer Patients Surgically Treated
Authors: Ammendola Michele , Sacco Rosario , Sammarco Giuseppe , Donato Giuseppe , Zuccalà Valeria , Romano Roberto , Luposella Maria , Patruno Rosa , Vallicelli Carlo , Verdecchia Giorgio Maria , Cavaliere Davide , Montemurro Severino , Ranieri Girolamo
Published: November 2013

Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation.Method. In a series of 25 gastric cancer patients with stage T3N2-3M0(by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD).Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r=0.64,P=0.001;r=0.66,P=0.041, resp.).Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.
Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue of Type 2 Diabeticdb/dbMice
Authors: Park Chan Hum , Noh Jeong Sook , Park Jong Cheol , Yokozawa Takako
Published: November 2013

Traditional medicines are being focused on as possible treatments for diabetes and its complications because of their negligible toxic and/or side effects. In line with this, our group has reported that Corni Fructus, a traditional medicine considered exhibiting beneficial effects on liver and kidney functions, possessed an antidiabetic effectviaameliorating glucose-mediated metabolic disorders. To add to these findings, we screened the iridoid glycoside fraction containing morroniside and loganin, and low molecular weight polyphenol fraction containing 7-O-galloyl-d-sedoheptulose (GS) from Corni Fructus. To our knowledge, GS is a compound only detected in Corni Fructus, and its biological activity has been poorly understood until now. For these reasons, we examined whether GS has an ameliorative effect on diabetic changes using type 2 diabeticdb/dbmice. Our findings suggest that GS has a beneficial effect on the pathological state of the serum, kidney, and adipose tissue related to diabetic damage.
Influence of Temperature Gradient on the Stability of a Viscoelastic Film with Gradually Fading Memory over a Topography with Ridges and Furrows
Authors: Sadiq Iqbal Mohammed Rizwan
Published: November 2013

A long-wave evolution equation is derived using an asymptotic analysis, and the linear stability of a viscoelastic film flowing along the direction of parallel grooves over a uniformly heated topography is studied. A numerical approach adopting spectral collocation technique is used to demarcate the stable and unstable flow regimes. The combined influence of thermocapillarity and viscoelasticity on the films stability is analyzed. By accounting the bottom topography comprising longitudinal gutters, the possibilities of regulating the film dynamics under iso- and nonisothermal conditions and/or optimizing design structure of an apparatus for desirable flow outcomes have been focussed.
Study of a New Chaotic Dynamical System and Its Usage in a Novel Pseudorandom Bit Generator
Authors: Dăscălescu Ana-Cristina , Boriga Radu Eugen , Diaconu Adrian-Viorel
Published: November 2013

A new chaotic discrete dynamical system, built on trigonometric functions, is proposed. With intent to use this system within cryptographic applications, we proved with the aid of specific tools from chaos theory (e.g., Lyapunov exponent, attractor’s fractal dimension, and Kolmogorov-Smirnov test) and statistics (e.g., NIST suite of tests) that the newly proposed dynamical system has a chaotic behavior, for a large parameter’s value space, and very good statistical properties, respectively. Further, the proposed chaotic dynamical system is used, in conjunction with a binary operation, in the designing of a new pseudorandom bit generator (PRBG) model. The PRBG is subjected, by turns, to an assessment of statistical properties. Theoretical and practical arguments, rounded by good statistical results, confirm viability of the proposed chaotic dynamical system and newly designed PRBG, recommending them for usage within cryptographic applications.
Three-Dimensional Reconstruction of Coronary Arteries and Its Application in Localization of Coronary Artery Segments Corresponding to Myocardial Segments Identified by Transthoracic Echocardiography
Authors: Zhong Chunyan , Guo Yanli , Huang Haiyun , Tan Liwen , Wu Yi , Wang Wenting
Published: November 2013

Objectives.To establish 3D models of coronary arteries (CA) and study their application in localization of CA segments identified by Transthoracic Echocardiography (TTE).Methods.Sectional images of the heart collected from the first CVH dataset and contrast CT data were used to establish 3D models of the CA. Virtual dissection was performed on the 3D models to simulate the conventional sections of TTE. Then, we used 2D ultrasound, speckle tracking imaging (STI), and 2D ultrasound plus 3D CA models to diagnose 170 patients and compare the results to coronary angiography (CAG).Results.3D models of CA distinctly displayed both 3D structure and 2D sections of CA. This simulated TTE imaging in any plane and showed the CA segments that corresponded to 17 myocardial segments identified by TTE. The localization accuracy showed a significant difference between 2D ultrasound and 2D ultrasound plus 3D CA model in the severe stenosis group (P<0.05) and in the mild-to-moderate stenosis group (P<0.05).Conclusions.These innovative modeling techniques help clinicians identify the CA segments that correspond to myocardial segments typically shown in TTE sectional images, thereby increasing the accuracy of the TTE-based diagnosis of CHD.
Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis
Authors: Qi Guo-Yan , Liu Peng , Gao Bu-Lang
Published: November 2013

Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy.Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system.Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P<0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P<0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P<0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group.Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy.

Erratum to “Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis”
An Obstacle Avoidance Method for Action Support 7-DOF Manipulators Using Impedance Control
Authors: Hamaguchi Masafumi , Taniguchi Takao
Published: November 2013

An obstacle avoidance method of action support 7-DOF manipulators is proposed in this paper. The manipulators are controlled with impedance control to follow user's motions. 7-DOF manipulators are able to avoid obstacles without changing the orbit of the end-effector because they have kinematic redundancy. A joint rate vector is used to change angular velocity of an arbitrary joint with kinematic redundancy. The priority of avoidance is introduced into the proposed method, so that avoidance motions precede follow motions when obstacles are close to the manipulators. The usefulness of the proposed method is demonstrated through obstacle avoidance simulations and experiments.
Passive Synchronization Based Energy-Efficient MAC Protocol over M2M Wireless Networks
Authors: Sthapit Pranesh , Pyun Jae-Young
Published: November 2013

Providing diverse quality-of-service (QoS) with ultra-low power consumption and mobility support is the most important and challenging issue in machine-to-machine (M2M) networks. In a typical beacon-enabled network, nodes need to wake up for receiving periodic beacon in order to maintain synchronization. Here, we present a new MAC protocol called passive-synchronization-based energy-efficient MAC (PSMAC) that synchronizes nodes in their sleep state by using interrupt generated from the proposed radio-triggered hardware. In order to activate the radio-triggered hardware, the synchronization frame is broadcast, but in a separate channel called synchronization channel, so that interrupts are not generated during data transmission. This synchronization frame is also used for providing the fast and energy-efficient association. Network information is embedded into the synchronization frame so that mobile nodes can learn about their neighbors just by scanning the synchronization channel. Furthermore, by positioning the beacon period after the contention access period, PSMAC provides fast and preemptive slot allocation that can handle diverse QoS requirements. We compare PSMAC with IEEE 802.15.4 and show that PSMAC has much better performance in node association time, energy efficiency, and faster data delivery at the cost of additional radio-triggered hardware and a dedicated channel.
A Gradient Boosting Algorithm for Survival Analysis via Direct Optimization of Concordance Index
Authors: Chen Yifei , Jia Zhenyu , Mercola Dan , Xie Xiaohui
Published: November 2013

Survival analysis focuses on modeling and predicting the time to an event of interest. Many statistical models have been proposed for survival analysis. They often impose strong assumptions on hazard functions, which describe how the risk of an event changes over time depending on covariates associated with each individual. In particular, the prevalent proportional hazards model assumes that covariates are multiplicatively related to the hazard. Here we propose a nonparametric model for survival analysis that does not explicitly assume particular forms of hazard functions. Our nonparametric model utilizes an ensemble of regression trees to determine how the hazard function varies according to the associated covariates. The ensemble model is trained using a gradient boosting method to optimize a smoothed approximation of the concordance index, which is one of the most widely used metrics in survival model performance evaluation. We implemented our model in a software package called GBMCI (gradient boosting machine for concordance index) and benchmarked the performance of our model against other popular survival models with a large-scale breast cancer prognosis dataset. Our experiment shows that GBMCI consistently outperforms other methods based on a number of covariate settings. GBMCI is implemented in R and is freely available online.
A Dynamic and Energy-Efficient Clustering Algorithm in Large-Scale Mobile Sensor Networks
Authors: Ma Changlin , Liu Nian , Ruan Yuan
Published: November 2013

Random mobility and energy constraint are two main factors affecting system performance in mobile sensor networks, which cause many difficulties to system design. It is necessary to develop high-efficiency algorithms and protocols for mobile sensor networks to adapt to dynamic network environment and energy limitation. In this paper, a new clustering algorithm based on residual energy difference ratio is presented to improve system performance. Firstly, it is an energy-efficient algorithm. The residual energy of sensor nodes and average residual energy of system are considered in the residual energy difference ratio, which effectively avoid the nodes with low residual energy being selected as cluster heads. An energy-optimal scheme is used in cluster formation phase to minimize energy consumption. Secondly, it is a dynamic algorithm. The system dynamically clusters the sensor nodes according to the data transmission delays. It makes the whole system adapt to the random mobility of sensor nodes. The NS2 software is used to simulate the new clustering algorithm. The simulation experiments can verify the validity of the proposed theory.
Reversal of Myoblast Aging by Tocotrienol Rich Fraction Posttreatment
Authors: Lim Jing Jye , Wan Ngah Wan Zurinah , Mouly Vincent , Abdul Karim Norwahidah
Published: November 2013

Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associatedβ-galactosidase (SA-β-galactosidase), and cell proliferation were determined. 50 μg/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA-β-galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA-β-galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA-β-galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed.
Circadian Regulation of mTOR by the Ubiquitin Pathway in Renal Cell Carcinoma
Authors: Okazaki Hiroyuki , Matsunaga Naoya , Fujioka Takashi , Okazaki Fumiyasu , Akagawa Yui , Tsurudome Yuuya , Ono Mayumi , Kuwano Michihiko , Koyanagi Satoru , Ohdo Shigehiro
Published: November 2013

Circadian clock systems regulate many biologic functions, including cell division and hormone secretion in mammals. In this study, we explored the effects of circadian control on the pivot cell growth regulatory mTOR, the activity of which is deregulated in tumor cells compared with normal cells. Specifically, we investigated whether the antitumor effect of an mTOR inhibitor could be improved by changing its dosing schedule in RenCa tumor-bearing mice. Active, phosphorylated mTOR displayed a 24-hour rhythm, and levels of total mTOR protein (but not mRNA) also showed a circadian rhythm in RenCa tumor masses. Through investigations of the oscillation mechanism for mTOR expression, we identified the ubiquitination factor Fbxw7 as an mTOR regulator that oscillated in its expression in a manner opposite from mTOR. Fbxw7 transcription was regulated by the circadian regulator D-site–binding protein. Notably, administration of the mTOR inhibitor everolimus during periods of elevated mTOR improved survival in tumor-bearing mice. Our findings demonstrate that the circadian oscillation of mTOR activity is regulated by circadian clock systems, which influence the antitumor effect of mTOR inhibitors. Cancer Res; 74(2); 543–51. ©2013 AACR.
Prognostic Impact of Cigarette Smoking on the Survival of Patients with Established Nasopharyngeal Carcinoma
Authors: OuYang Pu-Yun , Su Zhen , Mao Yan-Ping , Liang Xue-Xia , Liu Qing , Deng Wuguo , Xie Fang-Yun
Published: November 2013

Background: Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown.

Methods: We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model.

Results: The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58–4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03–3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89–3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses.

Conclusions: Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years.

Impact: It is clear that cigarette smoking not only promotes carcinogenesis in the normal nasopharyngeal epithelium, but also affects the survival of patients with nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev; 22(12); 2285–94. ©2013 AACR.
Cognitive Factors Associated with Adherence to Oral Antiestrogen Therapy: Results from the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) Study
Authors: Klepin Heidi D. , Geiger Ann M. , Bandos Hanna , Costantino Joseph P. , Rapp Stephen R. , Sink Kaycee M. , Lawrence Julia A. , Atkinson Hal H. , Espeland Mark A.
Published: November 2013

Little is known about the cognitive factors associated with adherence to antiestrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral antiestrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled nondemented participants ≥65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ≥80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2 ± 4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were nonadherent. In adjusted analyses, the odds of nonadherence were lower for those with better scores on verbal memory [OR (95% confidence interval): 0.75 (0.62–0.92)]. Larger relative deficits in verbal memory compared with verbal fluency were also associated with nonadherence [1.28 (1.08–1.51)]. Among nondemented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence. Cancer Prev Res; 7(1); 161–8. ©2013 AACR.
A Novel Molecular Pathway for Snail-Dependent, SPARC-Mediated Invasion in Non–Small Cell Lung Cancer Pathogenesis
Authors: Grant Jeanette L. , Fishbein Michael C. , Hong Long-Sheng , Krysan Kostyantyn , Minna John D. , Shay Jerry W. , Walser Tonya C. , Dubinett Steven M.
Published: November 2013

Definition of the molecular pathogenesis of lung cancer allows investigators an enhanced understanding of the natural history of the disease, thus fostering development of new prevention strategies. In addition to regulating epithelial-to-mesenchymal transition (EMT), the transcription factor Snail exerts global effects on gene expression. Our recent studies reveal that Snail is upregulated in non–small cell lung cancer (NSCLC), is associated with poor prognosis, and promotes tumor progression in vivo. Herein, we demonstrate that overexpression of Snail leads to the upregulation of secreted protein, acidic and rich in cysteine (SPARC) in models of premalignancy and established disease, as well as in lung carcinoma tissues in situ. Snail overexpression leads to increased SPARC-dependent invasion in vitro, indicating that SPARC may play a role in lung cancer progression. Bioinformatic analysis implicates transforming growth factor beta (TGF-β), extracellular signal–regulated kinase (ERK)1/2, and miR-29b as potential intermediaries in Snail-mediated upregulation of SPARC. Both the TGF-β1 ligand and TGF-β receptor 2 (TGF-βR2) are upregulated following Snail overexpression. Treatment of human bronchial epithelial cell (HBEC) lines with TGF-β1 and inhibition of TGF-β1 mRNA expression modulates SPARC expression. Inhibition of MAP–ERK kinase (MEK) phosphorylation downregulates SPARC. MiR-29b is downregulated in Snail-overexpressing cell lines, whereas overexpression of miR-29b inhibits SPARC expression. In addition, miR-29b is upregulated following ERK inhibition, suggesting a Snail-dependent pathway by which Snail activation of TGF-β and ERK signaling results in downregulation of miR-29b and subsequent upregulation of SPARC. Our discovery of pathways responsible for Snail-induced SPARC expression contributes to the definition of NSCLC pathogenesis. Cancer Prev Res; 7(1); 150–60. ©2013 AACR.
Temporal and Spatial Evolution of Somatic Chromosomal Alterations: A Case-Cohort Study of Barrett's Esophagus
Authors: Li Xiaohong , Galipeau Patricia C. , Paulson Thomas G. , Sanchez Carissa A. , Arnaudo Jessica , Liu Karen , Sather Cassandra L. , Kostadinov Rumen L. , Odze Robert D. , Kuhner Mary K. , Maley Carlo C. , Self Steven G. , Vaughan Thomas L. , Blount Patricia L. , Reid Brian J.
Published: November 2013

All cancers are believed to arise by dynamic, stochastic somatic genomic evolution with genome instability, generation of diversity, and selection of genomic alterations that underlie multistage progression to cancer. Advanced esophageal adenocarcinomas have high levels of somatic copy number alterations. Barrett's esophagus is a risk factor for developing esophageal adenocarcinoma, and somatic chromosomal alterations (SCA) are known to occur in Barrett's esophagus. The vast majority (∼95%) of individuals with Barrett's esophagus do not progress to esophageal adenocarcinoma during their lifetimes, but a small subset develop esophageal adenocarcinoma, many of which arise rapidly even in carefully monitored patients without visible endoscopic abnormalities at the index endoscopy. Using a well-designed, longitudinal case-cohort study, we characterized SCA as assessed by single-nucleotide polymorphism arrays over space and time in 79 “progressors” with Barrett's esophagus as they approach the diagnosis of cancer and 169 “nonprogressors” with Barrett's esophagus who did not progress to esophageal adenocarcinoma over more than 20,425 person-months of follow-up. The genomes of nonprogressors typically had small localized deletions involving fragile sites and 9p loss/copy neutral LOH that generate little genetic diversity and remained relatively stable over prolonged follow-up. As progressors approach the diagnosis of cancer, their genomes developed chromosome instability with initial gains and losses, genomic diversity, and selection of SCAs followed by catastrophic genome doublings. Our results support a model of differential disease dynamics in which nonprogressor genomes largely remain stable over prolonged periods, whereas progressor genomes evolve significantly increased SCA and diversity within four years of esophageal adenocarcinoma diagnosis, suggesting a window of opportunity for early detection. Cancer Prev Res; 7(1); 114–27. ©2013 AACR.
Ventricular Strain in Fetuses with Aortic Stenosis and Evolving Hypoplastic Left Heart Syndrome before and after Prenatal Aortic Valvuloplasty
Authors: Ishii Tetsuko , McElhinney Doff B. , Harrild David M. , Marcus Edward N. , Sahn David J. , Truong Uyen , Tworetzky Wayne
Published: November 2013

Objective: The impact of prenatal intervention on fetal cardiac function has not been well defined. We assessed standard ventricular function parameters and strain in fetuses with evolving hypoplastic left heart syndrome (HLHS) treated with fetal aortic valvuloplasty (fAVP). Methods: Fetuses with valvar aortic stenosis that underwent fAVP were studied. Echocardiographic images prior to intervention (Pre), within 1 week after fAVP (Post), and at the last prenatal follow-up examination (FU) were analyzed. Left ventricular (LV) circumferential (LVCS) and longitudinal strain (LVLS), right ventricular (RV) longitudinal strain (RVLS), and LV end-diastolic dimension Z-scores (LVIDD-Z) were documented and compared according to postnatal outcome. Results: Among 57 fetuses studied, the postnatal outcome was biventricular in 23 and univentricular in 34. Prior to fAVP, strain was <4 in most cases, regardless of outcome. Biventricular fetuses had higher LVCS and LVLS segmental strain than univentricular fetuses. Among fetuses with a biventricular outcome, LVCS and LVLS increased as LVIDD-Z decreased in late gestation, whereas LVCS and LVLS remained <4 in univentricular fetuses, although the LVIDD-Z decreased to <0 in all cases. Septal RVLS increased after fAVP in the biventricular but not the univentricular outcome group. Conclusion: In utero aortic valve dilation appears to have a beneficial effect on both LV and RV function in some fetuses with evolving HLHS.
Effectiveness of Collaborative Stepped Care for Anxiety Disorders in Primary Care: A Pragmatic Cluster Randomised Controlled Trial
Authors: Muntingh Anna , van der Feltz-Cornelis Christina , van Marwijk Harm , Spinhoven Philip , Assendelft Willem , de Waal Margot , Adèr Herman , van Balkom Anton
Published: November 2013

Background: Collaborative stepped care (CSC) may be an appropriate model to provide evidence-based treatment for anxiety disorders in primary care. Methods: In a cluster randomised controlled trial, the effectiveness of CSC compared to care as usual (CAU) for adults with panic disorder (PD) or generalised anxiety disorder (GAD) in primary care was evaluated. Thirty-one psychiatric nurses who provided their services to 43 primary care practices in the Netherlands were randomised to deliver CSC (16 psychiatric nurses, 23 practices) or CAU (15 psychiatric nurses, 20 practices). CSC was provided by the psychiatric nurses (care managers) in collaboration with the general practitioner and a consultant psychiatrist. The intervention consisted of 3 steps, namely guided self-help, cognitive behavioural therapy and antidepressants. Anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) at baseline and after 3, 6, 9 and 12 months. Results: We recruited 180 patients with a DSM-IV diagnosis of PD or GAD, of whom 114 received CSC and 66 received usual primary care. On the BAI, CSC was superior to CAU [difference in gain scores from baseline to 3 months: -5.11, 95% confidence interval (CI) -8.28 to -1.94; 6 months: -4.65, 95% CI -7.93 to -1.38; 9 months: -5.67, 95% CI -8.97 to -2.36; 12 months: -6.84, 95% CI -10.13 to -3.55]. Conclusions: CSC, with guided self-help as a first step, was more effective than CAU for primary care patients with PD or GAD.
The Effectiveness of Cognitive Remediation Therapy in Patients with a Severe or Enduring Eating Disorder: A Randomized Controlled Trial
Authors: Dingemans Alexandra E. , Danner Unna N. , Donker Judith M. , Aardoom Jiska J. , van Meer Floor , Tobias Karin , van Elburg Annemarie A. , van Furth Eric F.
Published: November 2013

Background: Individuals with eating disorders show deficits in neuropsychological functioning which might preexist and underlie the etiology of the eating disorders and influence relapse. Deficits in cognitive flexibility, i.e. set-shifting and central coherence, might perpetuate the symptoms. Cognitive remediation therapy (CRT) was developed to improve cognitive flexibility, thereby increasing the likelihood of improved outcome. The focus of CRT is on how patients think, rather than on what patients think. The present study investigated the effectiveness of CRT for patients with a severe or enduring eating disorder by means of a randomized controlled trial comparing intensive treatment as usual (TAU) to CRT plus TAU. Methods: Eighty-two patients were randomly assigned to CRT plus TAU (n = 41) or TAU alone (n = 41). Outcome measures were set-shifting, central coherence, eating disorder and general psychopathology, motivation, quality of life and self-esteem. Assessments were performed at baseline (n = 82) and after 6 weeks (T1; n = 75) and 6 months (T2; n = 67). Data were analyzed by means of linear mixed model analyses. Results: Patients who received CRT in addition to TAU improved significantly more with regard to eating disorder-related quality of life at the end of treatment (T1) and eating disorder psychopathology at follow-up (T2), compared to those who received TAU only. Moreover, moderator analyses revealed that patients with poor baseline set-shifting abilities benefited more from CRT than patients with no deficits in set-shifting abilities at baseline; the quality of life of the former group was higher than that of the latter at follow-up. Conclusions: CRT seems to be promising in enhancing the effectiveness of concurrent treatment.
Beyond the Randomized Clinical Trial: Citrate for Continuous Renal Replacement Therapy in Clinical Practice
Authors: Tovey L. , Dickie H. , Gangi S. , Terblanche M. , McKenzie C. , Beale R. , Treacher D. , Ostermann M.
Published: November 2013

Background: Premature circuit clotting is a major problem during continuous renal replacement therapy (CRRT). Six randomized controlled trials confirmed that regional anticoagulation with citrate is superior to heparin. Our objective was to compare circuit patency with citrate, heparin and epoprostenol in routine clinical practice. Methods: We retrospectively analysed data on circuit patency of all circuits used in a single centre between September 2008 and August 2009. We differentiated between premature filter clotting, elective discontinuation and waste. Results: 309 patients were treated with CRRT (n = 2,059 circuits). The mean age was 65.7; 63.8% were male. The methods to maintain circuit patency were unfractionated heparin (42.3%), epoprostenol (23.0%), citrate (14.7%), combinations of different anticoagulants (14.6%) and no anticoagulation (4.7%). Premature clotting was the most common reason for circuit discontinuation among circuits anticoagulated with heparin, epoprostenol or combinations of different anticoagulants (59-62%). Among circuits anticoagulated with citrate the main reason for discontinuation was elective (61%). Hazard regression analysis confirmed significantly better circuit survival with citrate. Changing from heparin to citrate decreased the risk of premature circuit clotting by 75.8%. Conclusion: In routine clinical practice, regional anticoagulation with citrate is associated with significantly better circuit patency than heparin or epoprostenol.
Components of the Metabolic Syndrome in Early Childhood in Very-Low-Birth-Weight Infants
Authors: de Jong Miranda , Lafeber Harrie N. , Cranendonk Anneke , van Weissenbruch Mirjam M.
Published: November 2013

Background/Aims: Term small-for-gestational-age and preterm born infants have an increased prevalence of metabolic syndrome components already in childhood. Data in very-low-birth-weight (VLBW) children are limited. We investigated the prevalence of metabolic syndrome components in VLBW infants at 2 years of corrected age. Methods: We included 38 children, participating in the Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial, a randomized controlled trial of early insulin therapy in VLBW infants. Metabolic syndrome components were defined as: body mass index SDS >2; blood pressure (systolic and/or diastolic) ≥90th percentile; triglycerides ≥0.98 mmol/l; high-density lipoprotein (HDL) cholesterol ≤1.03 mmol/l; glucose ≥5.6 mmol/l. Results: Two children (5%) had three metabolic syndrome components, 13 children (34%) had two components, and 11 children (29%) one component. 63% had raised blood pressure (prevalence higher in boys), 32% low HDL, and 30% high triglycerides (prevalence lower in early insulin group). In children with body mass index SDS <0, insulin-treated children had higher HDL than children with standard care. Systolic blood pressure was correlated with growth between term and 2 years of corrected age. Conclusions: VLBW infants already have a high prevalence of metabolic syndrome components at 2 years of corrected age. Early insulin treatment could have long-term benefits for some of these components.
Arginase-1: A Highly Specific Marker Separating Pancreatic Adenocarcinoma from Hepatocellular Carcinoma
Authors: Fatima Nazneen , Cohen Cynthia , Siddiqui Momin T.
Published: November 2013

Background: Arginase-1 and HepPar-1 are effective immunohistochemical (IHC) markers for hepatocellular carcinoma (HCC). In this study, we explored the possible efficacy of these stains in diagnosing pancreatic adenocarcinoma (PAD). Study Design: Arginase-1 and HepPar-1 IHC was performed on formalin-fixed, paraffin-embedded fine needle aspiration (FNA) cell blocks (CB) of PAD (n = 46), tissue microarray (TMA) of PAD (n = 33), FNA CB of HCC (n = 44) and TMA of HCC (n = 85). Negative controls without carcinoma were also applied (pancreas CB, n = 7; pancreas TMA, n = 3). Results: PAD CB demonstrated arginase-1 positivity in 0 of 46 cases and HepPar-1 positivity in 7 of 46 cases (15%). PAD TMA demonstrated arginase-1 positivity in 0 of 33 cases and HepPar-1 positivity in 4 of 33 cases (12%). HCC CB demonstrated arginase-1 positivity in 37 of 44 cases (84%) and HepPar-1 positivity in 32 of 44 cases (72%). HCC TMA demonstrated arginase-1 positivity in 75 of 85 cases (88%) and HepPar-1 positivity in 80 of 85 cases (94%). Conclusion: Both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Arginase-1 demonstrates superior sensitivity and specificity compared with HepPar-1 in the diagnosis of HCC. However, both arginase-1 and HepPar-1 have a low sensitivity and a very high specificity for PAD.
Giant Cell Tumors of the Skull Base: Case Series and Current Concepts
Authors: Prasad Sampath Chandra , Piccirillo Enrico , Nuseir Amjad , Sequino Giuliano , De Donato Giuseppe , Paties Carlo Terenzio , Sanna Mario
Published: November 2013

Objective: To study the clinical features, tumor characteristics and outcomes of giant cell tumors (GCTs) in the skull base based on long-term follow-up. We also report the largest series of GCTs in the temporal bone and the lateral skull base. Materials and Methods: A retrospective study was conducted of all GCTs managed at the Gruppo Otologico, a quaternary referral skull base institute, in Italy from 1993 to 2013. The clinical features, investigations, surgical management and follow-up were recorded. The surgical approaches used were infratemporal fossa approach (ITFA) type B and D and middle cranial fossa (MCF) approaches. Results and Observations: A total of 7 patients with GCTs of the skull base were treated at our institution. The principal complaints were hearing loss reported in 6 (85.71%) patients, tinnitus in 5 (71.43%) and swelling in 3 (42.9%). Pure-tone audiometry showed conductive hearing loss in 5 (71.43%) patients. High-resolution CT scan and MRI with gadolinium enhancement were done in all patients. Radiology showed involvement of the ITF and middle ear in 6 (85.71%) patients each, temporomandibular joint in 4 (57.14%) patients, invasions of the squamous part of the temporal bone, mastoid, MCF and greater wing of sphenoid in 3 (42.9%) patients each and the petrous bone in 2 (28.6%) patients. ITFA type B was applied as an approach for tumor removal in 5 (71.43%) patients, including a case where an additional MCF approach was employed, and ITFA type D and the transmastoid approach were applied in 1 (14.3%) patient each. Total tumor removal and successful cure was achieved in 6 (85.71%) patients. Subtotal removal leading to recurrence and eventual mortality was the result in 1 (14.3%) patient. Conclusions: A thorough knowledge of the anatomy of the skull base and the various skull base approaches is necessary to tackle GCTs. ITFA type B and D combined with MCF approaches provide good exposure of the tumor with minimal postoperative sequelae and good locoregional control. Recurrence due to either subtotal removal or suboptimal treatment may have disastrous consequences for the patient.
Suboptimal Initiation of Home Hemodialysis: Determinants and Clinical Outcomes
Authors: Nadeau-Fredette Annie-Claire , Tennankore Karthik K. , Kim S. Joseph , Chan Christopher T.
Published: November 2013

Background/Aims: Suboptimal initiation of conventional hemodialysis is associated with poor clinical outcomes. In this study, we aimed to ascertain the determinants and adverse events associated with suboptimal starts in home hemodialysis (HHD). Methods: We conducted a retrospective cohort study including consecutive incident HHD patients from January 1996 to December 2011. All patients had HHD as their first renal replacement therapy or returned to HHD after kidney transplantation. A suboptimal start was defined by dialysis initiation as an inpatient or with a central venous catheter. The primary outcome was time to first hospitalization, technique failure or death. Secondary outcomes included hospitalization rate, hospital days and determinants of suboptimal starts. Suboptimal starts were further categorized as unavoidable as adjudicated by two independent observers with prespecified criteria. Results: Among 95 incident HHD patients, 44 (46%) and 51 (54%) had optimal and suboptimal starts, respectively. A suboptimal start was associated with a shorter time to the primary outcome (log-rank p < 0.001). In a multivariable Cox proportional hazards model, the hazard ratio for the composite outcome (comparing suboptimal to optimal starts) was 2.94 (95% confidence interval, CI, 1.49-5.78, p = 0.002). Transplantation clinic follow-up (OR 3.18, 95% CI 1.15-8.79) and the Charlson comorbidity index (OR 1.47, 95% CI 1.09-1.97) were associated with higher odds of suboptimal start. Conclusion: Suboptimal initiation of HHD is associated with adverse clinical events including early hospitalization. Given the high proportion of suboptimal starts in patients returning from transplantation, better incorporation of dialysis planning and renal replacement therapy education is warranted.
Impact of Growth Hormone on Cystatin C
Authors: Sze Lisa , Bernays René L. , Zwimpfer Cornelia , Wiesli Peter , Brändle Michael , Schmid Christoph
Published: November 2013

Background: Cystatin C (CysC) is an alternative marker to creatinine for estimation of the glomerular filtration rate (GFR). Hormones such as thyroid hormones and glucocorticoids are known to have an impact on CysC. In this study, we examined the effect of growth hormone (GH) on CysC in patients with acromegaly undergoing transsphenoidal surgery. Methods: Creatinine, CysC, GH and insulin-like growth factor-1 (IGF-1) were determined in 24 patients with acromegaly before and following transsphenoidal surgery. Estimated GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Results: In all patients, surgical debulking resulted in decreased clinical disease activity and declining GH/IGF-1 levels. Postoperatively, biochemical cure was documented in 20 out of 24 patients. Creatinine levels (mean ± SEM) increased from 72 ± 3 to 80 ± 3 µmol/l (p = 0.0004) and concurrently, estimated GFR decreased from 99 ± 3 to 91 ± 3 ml/min (p = 0.0008). In contrast to creatinine, CysC levels decreased from 0.72 ± 0.02 to 0.68 ± 0.02 mg/l (p = 0.0008). Conclusions: Our study provides strong evidence for discordant effects of GH on creatinine and CysC in patients with acromegaly undergoing transsphenoidal surgery, thus identifying another hormone that influences CysC independent of renal function.