bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between GH/IGF-1 Axis, Graft Recovery, and Early Survival in Patients Undergoing Liver Transplantation
Authors: Salso Angela , Tisone Giuseppe , Tariciotti Laura , Lenci Ilaria , Manzia Tommaso Maria , Baiocchi Leonardo
Published: April 2014

Background. High levels of IGF-1 have been reported in patients with initial poor function of the graft after liver transplantation (LT). Correlation with other clinical variables or early survival has not been extensively investigated.Aim. To evaluate the GH/IGF-1 profile as a function of liver recovery and patients’ early survival after LT.Methods. 30 transplanted patients (23 survivors and 7 nonsurvivors), were retrospectively enrolled in the study. GH and IGF-1 serum levels were assessed at baseline, graft reperfusion, and 1, 7, 15, 30 , 90, and 360 days after LT. Individual biochemical variables were also recorded.Results. After grafting, IGF-1 in blood linearly correlated with cholesterol(r=0.6,  P=0.001). IGF-1 levels from day 15 after surgery were statistically higher in survivors as compared to nonsurvivors. ROC curves analysis identified an IGF-1 cut-off >90 μg/L, from day 15 after surgery, as a good predictor of survival (sensitivity 86%, specificity 95%, andP<0.001).Conclusions. After LT, GH levels correlate with the extent of cytolysis, while IGF-1 is an indicator of liver synthetic function recovery. IGF-1 levels >90 μg/L (day 15–30) seem to be an indicator of short-term survival.
Microstructure and Mechanical Properties of MWCNTs Reinforced A356 Aluminum Alloys Cast Nanocomposites Fabricated by Using a Combination of Rheocasting and Squeeze Casting Techniques
Authors: Elshalakany Abou Bakr , Osman T. A. , Khattab A. , Azzam B. , Zaki M.
Published: April 2014

A356 hypoeutectic aluminum‐silicon alloys matrix composites reinforced by different contents of multiwalled carbon nanotubes (MWCNTs) were fabricated using a combination of rheocasting and squeeze casting techniques. A novel approach by adding MWCNTs into A356 aluminum alloy matrix with CNTs has been performed. This method is significant in debundling and preventing flotation of the CNTs within the molten alloy. The microstructures of nanocomposites and the interface between the aluminum alloy matrix and the MWCNTs were examined by using an optical microscopy (OM) and scanning electron microscopy (SEM) equipped with an energy dispersive X‐ray analysis (EDX). This method remarkably facilitated a uniform dispersion of nanotubes within A356 aluminum alloy matrix as well as a refinement of grain size. In addition, the effects of weight fraction (0.5, 1.0, 1.5, 2.0, and 2.5 wt%) of the CNT‐blended matrix on mechanical properties were evaluated. The results have indicated that a significant improvement in ultimate tensile strength and elongation percentage of nanocomposite occurred at the optimal amount of 1.5 wt% MWCNTs which represents an increase in their values by a ratio of about 50% and 280%, respectively, compared to their corresponding values of monolithic alloy. Hardness of the samples was also significantly increased by the addition of CNTs.
Weak Solutions for a Sixth Order Cahn-Hilliard Type Equation with Degenerate Mobility
Authors: Liu Aibo , Liu Changchun
Published: April 2014

We study an initial-boundary problem for a sixth order Cahn-Hilliard type equation, which arises in oil-water-surfactant mixtures. An existence result for the problem with a concentration dependent diffusional mobility in three space dimensions is presented.
Nonmotor Symptoms in a Malaysian Parkinson’s Disease Population
Authors: Azmin Shahrul , Khairul Anuar Abdul Manaf , Tan Hui Jan , Nafisah Wan Yahya , Raymond Azman Ali , Hanita Othman , Shah Shamsul Azhar , Norlinah Mohamed Ibrahim
Published: April 2014

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson’s disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson’s disease.Methods. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS).Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (rs: 0.727,P<0.001).Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson’s disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study.
Outcomes after Trifocal Femoral Fractures
Authors: Griffin Michelle , Dick Alastair G. , Umarji Shamim
Published: April 2014

Trifocal femur fractures are those of the femoral neck, diaphysis, and distal femur. These high-energy injuries predominantly occur in young people with the potential for long-term complications and disability. We present the cases of two men who were treated with proximal dynamic hip screws and distal periarticular locking plates to effectively manage trifocal femur fractures. Our cases have shown union at 2 years with good functional outcomes without the need for reintervention. We provide evidence for a successful surgical treatment option for these rare and complex injuries.
OntoTrader: An Ontological Web Trading Agent Approach for Environmental Information Retrieval
Authors: Iribarne Luis , Padilla Nicolás , Ayala Rosa , Asensio José A. , Criado Javier
Published: April 2014

ModernWeb-based Information Systems(WIS) are becoming increasingly necessary to provide support for users who are in different places with different types of information, by facilitating their access to the information, decision making, workgroups, and so forth. Design of these systems requires the use of standardized methods and techniques that enable a common vocabulary to be defined to represent the underlying knowledge. Thus, mediation elements such astradersenrich the interoperability of web components in open distributed systems. These traders must operate with otherthird-partytraders and/or agents in the system, which must also use a common vocabulary for communication between them. This paper presents theOntoTraderarchitecture, anOntological Web Tradingagent based on the OMG ODP trading standard. It also presents the ontology needed by some system agents to communicate with the trading agent and the behavioral framework for the SOLERESOntoTraderagent, anEnvironmental Management Information System(EMIS). This framework implements a “Query-Searching/Recovering-Response” information retrieval model using a trading service, SPARQL notation, and the JADE platform. The paper also presents reflection, delegation and, federation mediation models and describes formalization, an experimental testing environment in three scenarios, and a tool which allows our proposal to be evaluated and validated.
C-Reactive Protein in Human Atherogenesis: Facts and Fiction
Authors: Zimmermann Oliver , Li Kefei , Zaczkiewicz Myron , Graf Matthias , Liu Zhongmin , Torzewski Jan
Published: April 2014

The role of C-reactive protein (CRP) in atherosclerosis is controversially discussed. Whereas initial experimental studies suggested a pathogenic role for CRP in atherogenesis, more recent genetic data from Mendelian randomization trials failed to provide evidence for a causative role of CRP in cardiovascular disease. Also, experimental results from laboratories all over the world were indeed contradictory, partly because of species differences in CRP biology and partly because data were not accurately evaluated. Here we summarize the published data from experimental work with mainly human material in order to avoid confusion based on species differences in CRP biology. Experimental work needs to be reevaluated after reconsideration of some traditional rules in research: (1) in order to understand a molecule’s role in disease it may be helpful to be aware of its role in physiology; (2) it is necessary to define the disease entity that experimental CRP research deals with; (3) the scientific consensus is as follows: do not try to prove your hypothesis. Specific CRP inhibition followed by use of CRP inhibitors in controlled clinical trials may be the only way to prove or disprove a causative role for CRP in cardiovascular disease.
On 10-Centralizer Groups of Odd Order
Authors: Foruzanfar Z. , Mostaghim Z.
Published: April 2014

Let G be a group, and let Cent(G) denote the number of distinct centralizers of its elements. A group G is called n-centralizer if Cent(G)=n. In this paper, we investigate the structure of finite groups of odd order with Cent(G)=10 and prove that there is no finite nonabelian group of odd order with Cent(G)=10.
Serum Activins and Follistatin during the Treatment of Chronic Hepatitis C Genotypes 1 and 4 and Their Correlations with Viral Load and Liver Enzymes: A Preliminary Report
Authors: Refaat Bassem , El-Shemi Adel Galal , Ashshi Ahmed Mohamed , AlZanbagi Adnan
Published: April 2014

Aims. To measure the effect of pegylated interferon-αtherapy on serum activin-A, activin-B, and follistatin and their correlation with viral load and liver fibrosis in chronic hepatitis C (CHC).Methods. This study was cross-sectional and sera were collected from 165 participants classified into 7 groups: 40 healthy negative control, 33 treatment naïve patients as positive control, 19 patients at week 4, 22 at week 12, and 19 at week 24 of treatment initiation and 21 responders and 11 nonresponders at the end of 48-week treatment protocol. Serum candidate proteins were measured using ELISA and liver fibrosis was assessed by AST platelet ratio index (APRI).Results. CHC significantly increased activins and decreased follistatin compared to negative control(P<0.05). Activin-A and follistatin levels returned to the levels of negative control group at weeks 4, 12, and 24 following treatment initiation and were significantly different from positive control(P<0.05). Both proteins were significantly different between responders and nonresponders. Activin-A correlated positively and significantly with the viral load and APRI.Conclusion. CHC modulates serum activin-A and follistatin and they appear to be influenced by pegylated interferon-αtherapy. Further studies are needed to explore the role of activins in CHC.
A Reconciliation of Packed Column Permeability Data: Column Permeability as a Function of Particle Porosity
Authors: Quinn Hubert M.
Published: April 2014

In his textbook teaching of packed bed permeability, Georges Guiochon uses mobile phase velocity as the fluid velocity term in his elaboration of the Darcy permeability equation. Although this velocity frame makes a lot of sense from a thermodynamic point of view, it is valid only with respect to permeability at a single theoretical boundary condition. In his more recent writings, however, Guiochon has departed from his long-standing mode of discussing permeability in terms of the Darcy equation and has embraced the well-known Kozeny-Blake equation. In this paper, his teaching pertaining to the constant in the Kozeny-Blake equation is examined and, as a result, a new correlation coefficient is identified and defined herein based on the velocity frame used in his teaching. This coefficient correlates pressure drop and fluid velocity as a function of particle porosity. We show that in their experimental protocols, Guiochon et al. have not adhered to a strict material balance of permeability which creates a mismatch of particle porosity and leads to erroneous conclusions regarding the value of the permeability coefficient in the Kozeny-Blake equation. By correcting the experimental data to properly reflect particle porosity we reconcile the experimental results of Guiochon and Giddings, resulting in a permeability reference chart which is presented here for the first time. This reference chart demonstrates that Guiochon’s experimental data, when properly normalized for particle porosity and other related discrepancies, corroborates the value of 267 for the constant in the Kozeny-Blake equation which was derived by Giddings in 1965.
Explorations of Unilateral Diaphragmatic Paralysis
Authors: Quesnel Alexandre , Beuret Blanquart Françoise , Marie Jean Paul , Verin Eric
Published: April 2014

Objective. The aim of the present study was to evaluate sniff test, maximal inspiratory pressure, and presence of paradoxical inspiratory diaphragmatic movements and their diagnostic value in patients referred for suspicion of diaphragmatic dysfunction.Methods. Twenty-two patients (8 men and 14 women,58±13years) with suspected diaphragmatic dysfunction were included. Pulmonary function test was evaluated by spirometry. Diaphragm dysfunction was diagnosed with unilateral phrenic nerve stimulation. Esophageal pressure was recorded during sniff test and maximal static inspiratory movements. Detection of paradoxical diaphragmatic movement was performed with anteroposterior projection of chest X-ray fluoroscopic video.Results.Phrenic nerve stimulationenabled diagnosis of diaphragmatic paralysis in 15 of the 22 patients. The remaining 7 patients had normal explorations. Lung volumes were significantly lower in patients with diaphragmatic paralysis than in control subjects, as maximal inspiratory pressure. No patient with normal diaphragmatic exploration had paradoxical inspiratory movement. The combined diagnostic value of reduced esophageal pressure during sniff test, reduced esophageal pressure during maximal static inspiratory movements, and presence of paradoxical inspiratory movement had a sensitivity of 87% and a specificity of 71%.Conclusion. Our results suggest that, in most cases, a combination of sniff test, maximal inspiratory pressure, and paradoxical inspiratory movement could help to diagnose diaphragmatic dysfunction. Nevertheless, phrenic nerve stimulation remains the best test for assessing diaphragmatic dysfunction.
Fault Detection for Network Control Systems with Multiple Communication Delays and Stochastic Missing Measurements
Authors: Zhang Jie , Lyu Ming , Karimi Hamid Reza , Zuo Jian , Bo Yuming
Published: April 2014

This paper is concerned with fault detection problem for a class of network control systems (NCSs) with multiple communication delays and stochastic missing measurements. The missing measurement phenomenon occurs in a random way and the occurrence probability for each measurement output is governed by an individual random variable. Besides, the multiple communication delay phenomenon reflects that networked control systems have different communication delays when the signals are transferred via different channels. We aim to design a fault detection filter so that the overall fault detection dynamics is exponentially stable in the mean square. By constructing proper Lyapunov‐Krasovskii functional, we acquire sufficient conditions to guarantee the stability of the fault detection filter for the discrete systems, and the filter parameters are also derived by solving linear matrix inequality. Finally, an illustrative example is provided to show the usefulness and effectiveness of the proposed design method.
Object Classification Using Substance Based Neural Network
Authors: Sengottuvelan P. , Arulmurugan R.
Published: April 2014

Object recognition has shown tremendous increase in the field of image analysis. The required set of image objects is identified and retrieved on the basis of object recognition. In this paper, we propose a novel classification technique called substance based image classification (SIC) using a wavelet neural network. The foremost task of SIC is to remove the surrounding regions from an image to reduce the misclassified portion and to effectively reflect the shape of an object. At first, the image to be extracted is performed with SIC system through the segmentation of the image. Next, in order to attain more accurate information, with the extracted set of regions, the wavelet transform is applied for extracting the configured set of features. Finally, using the neural network classifier model, misclassification over the given natural images and further background images are removed from the given natural image using the LSEG segmentation. Moreover, to increase the accuracy of object classification, SIC system involves the removal of the regions in the surrounding image. Performance evaluation reveals that the proposed SIC system reduces the occurrence of misclassification and reflects the exact shape of an object to approximately 10–15%.
How Can the Modified Dispersion Relation Affect Friedmann Equations?
Authors: Sefiedgar A. S.
Published: April 2014

The appearance of the quantum gravitational effects in a very high energy regime necessitates some corrections to the thermodynamics of Friedmann-Robertson-Walker (FRW) universe. The modified dispersion relation (MDR) as a phenomenological approach to investigate the high energy physics provides a perturbation framework upon which the FRW universe thermodynamics can be corrected. In this letter, we obtain the corrected entropy-area relation of the apparent horizon of FRW universe by utilizing the extra dimensional form of MDR, leading to the modification of Friedmann equations. The influence of MDR on the Friedmann equations provides a good insight into the understanding of the FRW universe dynamics in the final quantum gravity theory.
A Class of Transformation Matrices and Its Applications
Authors: Liu Wenhui , Deng Feiqi , Liang Jiarong , Liu Haijun
Published: April 2014

This paper studies a class of transformation matrices and its applications. Firstly, we introduce a class of transformation matrices between two different vector operators and give some important properties of it. Secondly, we consider its two applications. The first one is to improve Qian Jiling's formula. And the second one is to deal with the observability of discrete-time stochastic linear systems with Markovian jump and multiplicative noises. A new necessary and sufficient condition for the weak observability will be given in the second application.
Improving Training Condition Assessment in Endurance Cyclists: Effects of Ganoderma lucidum and Ophiocordyceps sinensis Dietary Supplementation
Authors: Rossi Paola , Buonocore Daniela , Altobelli Elisa , Brandalise Federico , Cesaroni Valentina , Iozzi Davide , Savino Elena , Marzatico Fulvio
Published: April 2014

The main reasons for taking daily dietary supplements are to maintain good health, to improve homeostasis, and to create conditions for reducing the risk of disease. Due to growing market demand, the search for effective, nontoxic, natural compounds with antioxidant and ergogenic properties has increasingly become a matter of interest. This paper describes how a specific combination of fungal supplements can help improve the performance of endurance athletes. We report the effects of a brief 3‐month trial of two fungal supplements, Ganoderma lucidum and Cordyceps sinensis (3 capsules of O. sinensis and 2 capsules of G. lucidum per day), in 7 healthy male volunteers, aged between 30 and 40 years, who are all amateur cyclists that participate in “Gran Fondo” cycling races. This trial investigated the effects of fungal supplements on the level of physical fitness of the athletes by monitoring and comparing the following biomarkers just before and after physical exertion: the testosterone/cortisol ratio in the saliva and oxidative stress (DPPH free radical scavenging activity). A decrease of more than 30% in the testosterone/cortisol ratio after race compared to before race was considered as a risk factor for nonfunctional overreaching (NFO) or the overtraining syndrome (OTS). The results show that, after 3 months of supplementation, the testosterone/cortisol ratio changed in a statistically significant manner, thereby protecting the athletes from NFO and OTS. Antioxidant activity was measured by quantifying the scavenging ability of the human serum on the synthetic free radical DPPH. After 3 months of fungal supplementation, the data demonstrate an increased scavenger capacity of free radicals in the athletes’ serum after the race, thereby protecting the athletes from oxidative stress.
Endothelial Cell-Secreted EGF Induces Epithelial to Mesenchymal Transition and Endows Head and Neck Cancer Cells with Stem-like Phenotype
Authors: Zhang Zhaocheng , Dong Zhihong , Lauxen Isabel S. , Filho Manoel Sant'Ana , Nör Jacques E.
Published: April 2014

Emerging evidence suggests that endothelial cell-secreted factors contribute to the pathobiology of squamous cell carcinoma (SCC) by enhancing invasive migration and resistance to anoikis. Here, we report that SCC cells within the perivascular niche have undergone epithelial to mesenchymal transition (EMT) in a primary human SCC of a patient that developed distant metastases. Endothelial cell–secreted EGF induced EMT of human SCC cells in vitro and also induced acquisition of a stem-like phenotype. In vivo, tumor xenografts vascularized with EGF-silenced endothelial cells exhibited a smaller fraction of cancer stem-like cells (ALDH+CD44+) and were less invasive than tumors vascularized with control endothelial cells. Collectively, these results demonstrated that endothelial cell-EGF induces EMT and acquisition of stem-like properties by head and neck tumor cells. On this basis, we suggest that vascular endothelial cells contribute to tumor dissemination by secreting factors that endow carcinoma cells with enhanced motility and stemness. Cancer Res; 74(10); 2869–81. ©2014 AACR.
LEO1 Is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myelogenous Leukemia
Authors: Chong Phyllis S.Y. , Zhou Jianbiao , Cheong Lip-Lee , Liu Shaw-Cheng , Qian Jingru , Guo Tiannan , Sze Siu Kwan , Zeng Qi , Chng Wee Joo
Published: April 2014

PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myelogenous leukemia (AML) and associated with poor survival. We found that stable expression of PRL-3 confers cytokine independence and growth advantage of AML cells. However, how PRL-3 mediates these functions in AML is not known. To comprehensively screen for PRL3-regulated proteins in AML, we performed SILAC-based quantitative proteomics analysis and discovered 398 significantly perturbed proteins after PRL-3 overexpression. We show that Leo1, a component of RNA polymerase II–associated factor (PAF) complex, is a novel and important mediator of PRL-3 oncogenic activities in AML. We described a novel mechanism where elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1 promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene expression. Furthermore, PRL-3 and Leo1 levels were positively associated in AML patient samples (N = 24; P < 0.01). On the other hand, inhibition of Leo1 reverses PRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of the PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid transformation. In conclusion, we identify an important and novel mechanism by which PRL-3 mediates its oncogenic function in AML. Cancer Res; 74(11); 3043–53. ©2014 AACR.
Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone MicroenvironmentIn Vivo
Authors: Ottewell Penelope D. , Wang Ning , Brown Hannah K. , Reeves Kimberly J. , Fowles C. Anne , Croucher Peter I. , Eaton Colby L. , Holen Ingunn
Published: April 2014

Purpose: Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings.

Experimental design: Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 μg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy.

Results: OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups.

Conclusions: This is the first demonstration that tumor growth is driven by osteoclast-mediated mechanisms in models that mimic post- but not premenopausal bone, providing a biologic rationale for the differential antitumor effects of ZOL reported in these settings. Clin Cancer Res; 20(11); 2922–32. ©2014 AACR.
Treatment Response Evaluation Using 18F-FDOPA PET in Patients with Recurrent Malignant Glioma on Bevacizumab Therapy
Authors: Schwarzenberg Johannes , Czernin Johannes , Cloughesy Timothy F. , Ellingson Benjamin M. , Pope Whitney B. , Grogan Tristan , Elashoff David , Geist Cheri , Silverman Daniel H.S. , Phelps Michael E. , Chen Wei
Published: April 2014

Purpose: This study compares the value of 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA) positron emission tomography (PET) and MRI in assessing outcome during antiangiogenic treatment in patients with recurrent high-grade gliomas.

Experimental Design: Thirty patients were prospectively studied with 18F-FDOPA PET scans immediately before, and two and six weeks after start of bevacizumab therapy. 18F-FDOPA metabolic tumor volumes (MTV) as well as max and mean standardized uptake values (SUV) within this MTV were obtained. MRI treatment response was assessed at six weeks. The predictive ability of 18F-FDOPA PET and MRI response assessment were evaluated with regard to progression-free survival (PFS) and overall survival (OS).

Results: A total of 30, 28, and 24 18F-FDOPA PET scans at baseline, two weeks, and six weeks, were available for analysis, respectively. 18F-FDOPA PET SUVs as well as their changes through therapy were not predictive of outcome. However, MTV parameters such as MTV changes were highly prognostic. Interestingly, absolute MTV at the first follow up scan provides the most significant prediction for increased OS (P < 0.0001) as well as PFS (P = 0.001). This surprising result was scrutinized with cross-validation and simulation analysis. Responders based on 18F-FDOPA PET data survived 3.5 times longer (12.1 months vs. 3.5 months, median OS, P < 0.001) than nonresponders (17 patients vs. 11 patients, respectively). In comparison, responders based on MRI data lived 1.5 times longer (11.4 months vs 7.7 months, P = 0.03) than nonresponders (22 patients vs. 7 patients, respectively).

Conclusions: 18F-FDOPA PET identifies treatment responders to antiangiogenic therapy as early as two weeks after treatment initiation. Clin Cancer Res; 20(13); 3550–9. ©2014 AACR.
KRAS Mutation Status Is Associated with Enhanced Dependency on Folate Metabolism Pathways in Non–Small Cell Lung Cancer Cells
Authors: Moran Diarmuid M. , Trusk Patricia B. , Pry Karen , Paz Keren , Sidransky David , Bacus Sarah S.
Published: April 2014

KRAS gene mutation is linked to poor prognosis and resistance to therapeutics in non–small cell lung cancer (NSCLC). In this study, we have explored the possibility of exploiting inherent differences in KRAS-mutant cell metabolism for treatment. This study identified a greater dependency on folate metabolism pathways in KRAS mutant compared with KRAS wild-type NSCLC cell lines. Microarray gene expression and biologic pathway analysis identified higher expression of folate metabolism– and purine synthesis–related pathways in KRAS-mutant NSCLC cells compared with wild-type counterparts. Moreover, pathway analysis and knockdown studies suggest a role for MYC transcriptional activity in the expression of these pathways in KRAS-mutant NSCLC cells. Furthermore, KRAS knockdown and overexpression studies demonstrated the ability of KRAS to regulate expression of genes that comprise folate metabolism pathways. Proliferation studies demonstrated higher responsiveness to methotrexate, pemetrexed, and other antifolates in KRAS-mutant NSCLC cells. Surprisingly, KRAS gene expression is downregulated in KRAS wild-type and KRAS-mutant cells by antifolates, which may also contribute to higher efficacy of antifolates in KRAS-mutant NSCLC cells. In vivo analysis of multiple tumorgraft models in nude mice identified a KRAS-mutant tumor among the pemetrexed-responsive tumors and also demonstrated an association between expression of the folate pathway gene, methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), and antifolate activity. Collectively, we identify altered regulation of folate metabolism in KRAS-mutant NSCLC cells that may account for higher antifolate activity in this subtype of NSCLC. Mol Cancer Ther; 13(6); 1611–24. ©2014 AACR.
Computed Tomographic Colonography Is Valuable for Post-Treatment Evaluation and Screening of Hidden Colorectal Cancer in Patients with Cryptogenic Pyogenic Liver Abscess
Authors: Jang Dong Kee , Jeong Sook-Hyang , Lee Sang Hyub , Lee Minjong , Jang Eun Sun , Kim Jin-Wook , Hwang Jin-Hyeok , Ryu Ji Kon , Kim Yong-Tae , Lee Yoon Jin , Lee Kyoung Ho , Kim Young Hoon
Published: April 2014

Background/Aims: It has been demonstrated that cryptogenic pyogenic liver abscess (PLA) is associated with colonic mucosal defect, especially colorectal cancer (CRC). Therefore, the screening of CRC in patients with cryptogenic PLA is important. This study was to investigate whether computed tomographic colonography (CTC) has value as a follow-up modality as well as CRC screening tool in patients with PLA. Methods: A retrospective evaluation of 109 patients with cryptogenic PLA who underwent CTC or colonoscopy for CRC screening between July 2005 and July 2012 was performed. The patients were divided into a CTC group (n = 68) and colonoscopy group (n = 41) after treatment of liver abscess, and compared concerning the detection rate of advanced neoplasia, consisting of advanced adenomas and invasive carcinomas. Patients with advanced polyps in CTC surveillance underwent subsequent colonoscopy. Results: Advanced colonic neoplasia was detected in 9 of the 68 patients (13.2%) in the CTC group and 8 of the 41 patients (19.5%) in the conventional colonoscopy group (p = 0.42). The treatment response of all abscess lesions was clearly visualized on CTC, with complete resolution in 17.6% (12/68) of patients. After adjustment for sex and pathogens, old age (≥65 years) was significantly associated with advanced neoplasia (OR 5.481; 95% CI 1.757-17.100; p = 0.03). Conclusion: CTC has a valuable dual role as a follow-up modality and in the screening of CRC in patients with cryptogenic PLA, particularly in elderly patients over 65 years of age.
Epigenetic Regulation of Telomere Maintenance
Authors: Fojtová Miloslava , Fajkus Jiří
Published: April 2014

As chromatin structures, telomeres undergo epigenetic regulation of their maintenance and function. In plants, these processes are likely of a higher complexity than in animals or yeasts, as exemplified by methylation of cytosines in plant telomeric DNA or reversible developmental regulation of plant telomerase. We highlight the dual role of telomeres from the epigenetic point of view: (i) as chromatin structures that are the subject of epigenetic regulation (e.g. DNA and histone modifications), and (ii) as chromosome domains acting themselves as epigenetic regulatory elements (e.g. in the telomere position effect). Possibly, some molecular tools (e.g. telomeric transcripts) are common to both these aspects of telomere epigenetics. We further discuss the justification for the classical textbook view of telomeres as heterochromatic structures.
A Case of Membranous Glomerulonephropathy Associated with Takayasu's Arteritis
Authors: Koda Ryo , Yoshino Atsunori , Imanishi Yuji , Kawamoto Shinya , Ueda Yoshihiko , Kazama Junichiro James , Narita Ichiei , Takeda Tetsuro
Published: April 2014

Glomerulonephropathy is a rare complication of Takayasu's arteritis (TA). To date, most glomerulonephropathies associated with TA show the histological feature of mesangial proliferation. Membranous glomerulonephropathy (MG) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with TA is extremely rare. A 54-year-old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria. Five years previously, he underwent percutaneous angioplasty for left subclavian artery stenosis. Kidney biopsy revealed stage II MG. General examination including enhanced CT scan confirmed the presence of TA. He started oral prednisolone therapy at a dose of 40 mg daily. The C-reactive protein level normalized 7 days after the prednisolone therapy. Three months later, proteinuria had remitted. Though the true relationship between MG and TA was not revealed in present case, considering the fact that complete remission of nephrotic syndrome occurred following the improvement of C-reactive protein level in response to steroid therapy, TA might be the secondary cause of MG. To our best knowledge, only two case reports described the association of MG and TA previously. Those two patients, however, also demonstrated the feature of systemic lupus erythematosus in addition to TA. This is the first case report that describes a patient who presented as MG associated with TA, but not complicated by systemic lupus erythematosus.
Glutathione S-Transferase T1 and M1 Polymorphisms Are Associated with Lung Cancer Risk in a Gender-Specific Manner
Authors: Pan Chunguo , Zhu Genhua , Yan Zhihong , Zhou Yi , Liu Zhihua
Published: April 2014

Background: Glutathione S-transferase (GST) T1 and M1 are detoxification enzymes which neutralize various carcinogenic compounds. Polymorphisms of the GSTT1 and GSTM1 genes which encode the enzymes could be associated with cancer risk. Patients and Methods: We investigated the association of GSTT1 and GSTM1 null polymorphisms with lung cancer risk in a tightly matched, considerably large sample in China. Genotyping was performed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing, and associations were measured by using logistic regression analysis. Results: We found that the null genotypes of both polymorphisms resulted in an increased lung cancer risk, with an odds ratio (OR) of 1.57 (95% confidence interval (CI) 1.23-2.00) for GSTT1 and OR 1.87 (95% CI 1.46-2.39) for GSTM1 (p < 0.01). Significant associations remained after stratification by histopathology (p < 0.01) and smoking status (p < 0.05). When gender-stratified association was performed, we found that the GSTT1 null genotype resulted in an increased risk among males (adjusted OR 2.95, 95% CI 2.07-4.20; p < 0.01) but not females (p > 0.05), while the GSTM1 null genotype resulted in an increased risk among females (adjusted OR 2.18, 95% CI 1.54-3.10; p < 0.01) but not males (p < 0.05). Conclusion: Polymorphisms in GSTT1 and GSTM1 are associated with the risk of lung cancer in a gender-specific manner.
Short-Term Disruption of Diurnal Rhythms After Murine Myocardial Infarction Adversely Affects Long-Term Myocardial Structure and Function
Authors: Alibhai Faisal J. , Tsimakouridze Elena V. , Chinnappareddy Nirmala , Wright David C. , Billia Filio , O’Sullivan M. Lynne , Pyle W. Glen , Sole Michael J. , Martino Tami A.
Published: April 2014

Rationale:

Patients in intensive care units are disconnected from their natural environment. Synchrony between environmental diurnal rhythms and intracellular circadian rhythms is essential for normal organ biology; disruption causes pathology. Whether disturbing rhythms after myocardial infarction (MI) exacerbates long-term myocardial dysfunction is not known.

Objective:

Short-term diurnal rhythm disruption immediately after MI impairs remodeling and adversely affects long-term cardiac structure and function in a murine model.

Methods and Results:

Mice were infarcted by left anterior descending coronary artery ligation (MI model) within a 3-hour time window, randomized to either a normal diurnal or disrupted environment for 5 days, and then maintained under normal diurnal conditions. Initial infarct size was identical. Short-term diurnal disruption adversely affected body metabolism and altered early innate immune responses. In the first 5 days, crucial for scar formation, there were significant differences in cardiac myeloperoxidase, cytokines, neutrophil, and macrophage infiltration. Homozygous clock mutant mice exhibited altered infiltration after MI, consistent with circadian mechanisms underlying innate immune responses crucial for scar formation. In the proliferative phase, 1 week after MI, this led to significantly less blood vessel formation in the infarct region of disrupted mice; by day 14, echocardiography showed increased left ventricular dilation and infarct expansion. These differences continued to evolve with worse cardiac structure and function by 8 weeks after MI.

Conclusions:

Diurnal rhythm disruption immediately after MI impaired healing and exacerbated maladaptive cardiac remodeling. These preclinical findings suggest that disrupted diurnal rhythms such as found in modern intensive care unit environments may adversely affect long-term patient outcome.
Associations of Birth Weight and Postnatal Weight Gain With Cardiometabolic Risk Parameters at 5 Years of Age
Authors: Lurbe Empar , Garcia-Vicent Consuelo , Torro Maria Isabel , Aguilar Francisco , Redon Josep
Published: April 2014

The present prospective study assessed the impact of birth weight (BW) and postnatal weight gain on blood pressure and metabolic profile during the first 5 years of life. One hundred thirty-nine newborns (63 women) born at term after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second day of life, infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters and blood pressure were measured at each visit and metabolic assessment was performed at 5 years of age. Among the BW groups, mothers did not differ in terms of age, smoking, and weight gain during pregnancy. BW was a positive determinant of systolic blood pressure at birth. Afterward, current weight was the strongest determinant, becoming significant at 2 years of age and progressively increasing in influence. At 5 years insulin, the homeostasis model assessment index and triglycerides were dependent on BW, current weight, and postnatal weight gain. In addition, BW was positively associated with high-density lipoprotein-cholesterol and inversely so to uric acid. A positive relationship among insulin, blood pressure values, and uric acid was observed even early in life. In conclusion, the acceleration of early infant weight gain may aggravate the effects of low BW. Multiple interactions between hemodynamic and metabolic parameters foreshadow the clustering of cardiometabolic risk factors later in life.
Husserl and the Question of Animality
Authors: Di Martino Carmine
Published: April 2014

Abstract

Is it possible to speak of a Husserlian phenomenology of the animal? In his phenomenological analyses, Husserl thematizes animals as a case of “abnormality” in order to investigate the subjectivity that constitutes the human world as a normal world. With respect to other perspectives—such as the Heideggerian one—which imply a drastic separation from animality, Husserl’s standpoint has the advantage of keeping a path of communication open between the phenomenological and the scientific investigation of the problem, in the multifarious forms taken on today by the latter. However, what is the original contribution of phenomenology on this issue, in comparison with that of the empirical sciences? Phenomenology addresses the experience of lifeworld as its own field of activity and as the implicit ground for every scientific observation and reconstruction. Phenomenology, thus, provides a new approach to animal life, avoiding naive ontological assumptions about it.
Minderheiten in Armenien: Anmerkungen zum Problem ihrer Dokumentation
Authors: Schulze Ilona
Published: April 2014

The article addresses both theoretical and methodological issues related to the documentation of ethnic minorities in present-day Armenia. Normally, Armenia is regarded as a prototypical example for a statehood that is marked for a homogenous ethnic composition. In fact, social groups typically referred to as ‘minorities’ constitute only some 2% of the total population. The minority map of Armenia includes fourteen groups two of which (Tats and Udis) represent migrants and refugees from Azerbaijan having arrived in Armenia as late as 1990. The documentation of the minorities in Armenia calls for a reconsideration of parameters of ethnicity and for the corresponding adjustment of methodology and descriptive patterns reflecting the peculiarities of ethnicity in Armenia. Most importantly, we cannot apply a unified, mono-dimensional perspective starting, e.g., from a parameter, such as ‘language’. Rather, we have to set up a weighted network of parameters that include both sociocultural and sociolinguistic features. The paper briefly illustrates this point with the help of preliminary data stemming from fieldwork related to the project “Minorities of Armenia: A Sociocultural and Sociolinguistic Survey”. It will be argued that the social construction of collective identity and ethnicity is controlled by both tendencies of growing self-awareness and likewise trends toward transcultural processes present especially in the diatopic and diastratic periphery of the given minorities.
Tawus Protogonos: Parallels between the Yezidi Theology and Some Ancient Greek Cosmogonies
Authors: Rodziewicz Artur
Published: April 2014

The paper concerns some crucial issues of theology and cosmogony of the Yezidis, which have distinct parallels in the writings of the ancient Greeks. A startling coincidence of certain topics and the manner of approach can lead to the conclusion that the Yezidi theology and mythology seem to have a distant genetic relationship with the Greek theology, or―which is also possible―we are dealing with distinct independent inscriptions of the same ideas, meaning here the highest factors governing the world. The paper also contains references to similar topics in the literature of Early Christianity and Gnosticism.
Armenian čandari ‘plane tree’
Authors: Martirosyan Hrach
Published: April 2014

The Armenian word čandar-i appears in two basic meanings: ‘plane tree’ and ‘poplar, aspen’. It is attested in a Commentary on Genesis hesitantly attributed to Eɫišē. The other two attestations of the word come from authors originating from eastern parts of Armenia: Kirakos Ganjakec‘i (13th century) and Zak‘aria Sarkawag K‘anak‘eṙc‘i (17th century). Particularly important is the testimony from Chapter 21 of Ganjakec‘i who mentions čandari, the local equivalent of sawsi ‘plane tree’. The Iranian origin of čandar-i is obvious, though the etymological details are unclear. Łarabaɫ tənǰərí/ɛ́, which refers to both ‘plane tree’ and ‘poplar’ and is found in a late mediaeval Armenian dictionary, Baṙgirk‘ hayoc‘, derives from čandari through metathesis: čandari > *čəndərí > tənǰərí/ɛ́. The combined evidence from Ganjakec‘i, Baṙgirk‘ hayoc‘ and the Łarabaɫ dialect testifies to the existence and unbroken development of the word in the territory of Łarabaɫ and surroundings and shows that the metathesis (čandari > tənǰərí/ɛ́) took place at some stage between the 13th and 16-17th centuries.
Paradiplomacy of Regional Governments in International Relations: The Foreign Relations of the Kurdistan Regional Government (2003 – 2010)
Authors: Mohammed Herish Khali , Owtram Francis
Published: April 2014

Until now there has been relatively little systematic analysis of the foreign relations of the Kurdistan Regional Government (KRG). Based on interviews with senior officials of the KRG, this article places this activity within the conceptual framework of paradiplomacy. It argues that, in the framework of regional geopolitics and economic benefits for the Kurdistan Region from its place in Iraq, the practice of this paradiplomacy does not indicate an intention to secede from Iraq.
A new species of Microprosthema Stimpson, 1860 (Crustacea: Decapoda: Stenopodidea: Spongicolidae) from the South China Sea
Authors: JIANG QIWU , LI XINZHENG
Published: April 2014

A new species of the spongicolid genus Microprosthema Stimpson, 1860 is described based on two specimens collected from Shi Island, Xisha Islands, South China Sea. The type specimens were collected within a sponge, representing an unusual habitat for the genus. M. personatum sp. nov. is easily distinguished from its closest congeners, M. takedai and M. fujitai, by its convex supraocular eaves and the number of teeth on the scaphocerite. A key to the Indo-West Pacific species of Microprosthema is given.
A new species of the genus Nothrholaspis Berlese (Acari: Macrochelidae) from Iran
Authors: BABAEIAN ESMAEIL , JOHARCHI OMID , JAMSHIDIAN MARYAM KESHAVARZ
Published: April 2014

A new mite species of the genus Nothrholaspis Berlese, Nothrholaspis saboorii Babaeian & Joharchi sp. nov., is described and illustrated from specimens collected from soil in the Karaj region of Iran. An identification key for the known species of Nothrholaspis is presented.
Low-Frequency SST and Upper-Ocean Heat Content Variability in the North Atlantic
Authors: Buckley Martha W. , Ponte Rui M. , Forget Gaël , Heimbach Patrick
Published: April 2014

A recent state estimate covering the period 1992–2010 from the Estimating the Circulation and Climate of the Ocean (ECCO) project is utilized to quantify the upper-ocean heat budget in the North Atlantic on monthly to interannual time scales (seasonal cycle removed). Three novel techniques are introduced: 1) the heat budget is integrated over the maximum climatological mixed layer depth (integral denoted as H), which gives results that are relevant for explaining SST while avoiding strong contributions from vertical diffusion and entrainment; 2) advective convergences are separated into Ekman and geostrophic parts, a technique that is successful away from ocean boundaries; and 3) air–sea heat fluxes and Ekman advection are combined into one local forcing term. The central results of our analysis are as follows: 1) In the interior of subtropical gyre, local forcing explains the majority of H variance on all time scales resolved by the ECCO estimate. 2) In the Gulf Stream region, low-frequency H anomalies are forced by geostrophic convergences and damped by air–sea heat fluxes. 3) In the interior of the subpolar gyre, diffusion and bolus transports play a leading order role in H variability, and these transports are correlated with low-frequency variability in wintertime mixed layer depths.