bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-24 Modulates Aflatoxin B1-Related Hepatocellular Carcinoma Prognosis and Tumorigenesis
Authors: Liu Yi-Xiao , Long Xi-Dai , Xi Zhi-Feng , Ma Yun , Huang Xiao-Ying , Yao Jin-Guang , Wang Chao , Xing Tian-Yu , Xia Qiang
Published: April 2014

MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66–8.47) and overall survival (HR=3.58, 95% CI = 2.34–5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.
Food Safety Challenges towards Safe, Healthy, and Nutritious Street Foods in Bangladesh
Authors: Khairuzzaman Md. , Chowdhury Fatema Moni , Zaman Sharmin , Al Mamun Arafat , Bari Md. Latiful
Published: April 2014

The street foods play an important socioeconomic role in meeting food and nutritional requirements of city consumers at affordable prices to the lower and middle income people. The number of food poisoning notifications rose steadily worldwide since the inception ofE. coliO157:H7 outbreak in the 1980s to date. This may be partly attributed to improved surveillance, increased global trade and travel, changes in modern food production, the impact of modern lifestyles, changes in food consumption, and the emergence of new pathogens. Consumer’s knowledge and attitude may influence food safety behavior and practice. For the sake of public health, it is important to understand the epidemiology of foodborne illnesses that help in prevention and control efforts, appropriately allocating resources to control foodborne illness, monitoring and evaluation of food safety measures, development of new food safety standards, and assessment of the cost-effectiveness of interventions. This review paper described the sociodemographic characteristics, common hazards, and occupational hazards of street food vendors, microbial risk associated with street food, food safety interventions and control measures, regulatory aspects and legal requirements, financial constraints, and attitudes.
Evaluation of Two Different Analytical Methods for Circulating Tumor Cell Detection in Peripheral Blood of Patients with Primary Breast Cancer
Authors: Jaeger B. A. S. , Jueckstock J. , Andergassen U. , Salmen J. , Schochter F. , Fink V. , Alunni-Fabbroni M. , Rezai M. , Beck Th. , Beckmann M. W. , Friese K. , Friedl T. W. P. , Janni W. , Rack B.
Published: April 2014

Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare.Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC.Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P=0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P<0.001).Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
Some Relations between Certain Complex Equations and Nonnormalized Meromorphic Functions
Authors: Irmak Hüseyin
Published: April 2014

The purpose of this investigation is first to reveal some relations between certain complex (differential) equations and nonnormalized meromorphic functions and then to point some of their useful consequences out.
Measurement of Cephalic Indices in Older Children and Adolescents of a Nigerian Population
Authors: Akinbami Babatunde Olayemi
Published: April 2014

Background. A study on the cephalic index was carried out on subjects from school students in Ogbia tribe of Bayelsa state in the Niger Delta region of Nigeria. This study determined the cephalic indices among the school students. In the present study, seven hundred subjects were randomly selected from secondary schools comprising 350 males and 350 females, respectively, with age range from 11–20 years, with both parents and grandparents of Ogbia tribe. The length and breadth of the head were measured using a spreading caliper from standard bony landmarks. The measurable point for head length was measured between the glabella and inions while the head breadth was the widest biparietal diameter. The cephalic index was head breadth divided by the head length and multiplied by 100. The result showed that the mean cephalic index was 76.56. Males had a cephalic index of 77.21, while females had a cephalic index of 76.50. Based on this study, 78.68% of individuals were mesocephalic, 11.4% dolichocephalic, 9.0% Brachycephalic, and 0.43% hyperbrachycephalic. This research showed that the school students have mesocephalic phenotype. The data from this research will be useful in anthropology, genetics, forensic medicine, and clinical practice.
An Efficient Method for Synthesis of N-tert-Butyl Amides Using Oxalic Acid Dihydrate in Solvent-Free Condition
Authors: Mokhtary Masoud , Nasernezhad Seyedeh Khadijeh
Published: April 2014

An efficient method for the synthesis of N-tert-butyl amides by reaction of nitriles with tert-butyl acetate or tert-butanol is described using oxalic acid dihydrate in solvent-free condition. The result showed that tert-butyl acetate served as a relatively better source of tert-butyl carbocation than tert-butanol.
Angular Velocity Affects Trunk Muscle Strength and EMG Activation during Isokinetic Axial Rotation
Authors: Fan Jian-Zhong , Liu Xia , Ni Guo-Xin
Published: April 2014

Objective. To evaluate trunk muscle strength and EMG activation during isokinetic axial rotation at different angular velocities.Method. Twenty-four healthy young men performed isokinetic axial rotation in right and left directions at 30, 60, and 120 degrees per second angular velocity. Simultaneously, surface EMG was recorded on external oblique (EO), internal oblique (IO), and latissimus dorsi (LD) bilaterally.Results. In each direction, with the increase of angular velocity, peak torque decreased, whereas peak power increased. During isokinetic axial rotation, contralateral EO as well as ipsilateral IO and LD acted as primary agonists, whereas, ipsilateral EO as well as contralateral IO and LD acted as primary antagonistic muscles. For each primary agonist, the root mean square values decreased with the increase of angular velocity. Antagonist coactiviation was observed at each velocity; however, it appears to be higher with the increase of angular velocity.Conclusion. Our results suggest that velocity of rotation has great impact on the axial rotation torque and EMG activity. An inverse relationship of angular velocity was suggested with the axial rotation torque as well as root mean square value of individual trunk muscle. In addition, higher velocity is associated with higher coactivation of antagonist, leading to a decrease in torque with the increase of velocity.
Early Preinvasive Lesions in Ovarian Cancer
Authors: Chene Gautier , Lamblin Gery , Le Bail-Carval Karine , Chabert Philippe , Bakrin Naoual , Mellier Georges
Published: April 2014

Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins.
Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases
Authors: Dixit Anshuman , Verkhivker Gennady M.
Published: April 2014

A central goal of cancer research is to discover and characterize the functional effects of mutated genes that contribute to tumorigenesis. In this study, we provide a detailed structural classification and analysis of functional dynamics for members of protein kinase families that are known to harbor cancer mutations. We also present a systematic computational analysis that combines sequence and structure-based prediction models to characterize the effect of cancer mutations in protein kinases. We focus on the differential effects of activating point mutations that increase protein kinase activity and kinase-inactivating mutations that decrease activity. Mapping of cancer mutations onto the conformational mobility profiles of known crystal structures demonstrated that activating mutations could reduce a steric barrier for the movement from the basal “low” activity state to the “active” state. According to our analysis, the mechanism of activating mutations reflects a combined effect of partial destabilization of the kinase in its inactive state and a concomitant stabilization of its active-like form, which is likely to drive tumorigenesis at some level. Ultimately, the analysis of the evolutionary and structural features of the major cancer-causing mutational hotspot in kinases can also aid in the correlation of kinase mutation effects with clinical outcomes.
Patterns in the Parathyroid Response to Sodium Bicarbonate Infusion Test in Healthy Volunteers
Authors: Papavramidis Theodossis S. , Anastasiou Olympia E. , Pliakos Ioannis , Michalopoulos Nick , Polyzonis Mike , Triantafyllopoulou Konstantina , Kokaraki Georgia , Papavramidis Spiros
Published: April 2014

Background. The sodium bicarbonate infusion test evaluates the function of the parathyroid glands. The present study aims to evaluate the range of parathyroid response in healthy individuals and the potential influence of various factors.Methods. Fifty healthy volunteers were subjected to the test. Levels of vitamin D, calcium, albumin, and PTH were measured before infusion. PTH was measured at 3, 5, 10, 30, and 60 minutes after infusion.Results. A curve describing the response of parathyroids to the test was drawn. Twenty percent of the subjects had blunted PTH response. No significant difference was observed between normal and blunted responders concerning age, BMI, baseline PTH, or calcium levels. Nonetheless, there was a significant difference in vitamin D levels (P=0.024).Interpretation. The test is easy to perform and may be used for everyday screening. It has to be clarified whether our observations are, at least partly, produced due to the presence of individuals with a constitutively blunted response or if low levels of vitamin D decrease the ability of the parathyroids to respond. Whichever the case, PTH response of normal individuals to sodium bicarbonate infusion test is more varied than previously thought and vitamin D levels influence it.
On Some Fuzzy Filters in Pseudo-BCIAlgebras
Authors: Zhang Xiaohong
Published: April 2014

Some new properties of fuzzy associative filters (also known as fuzzy associative pseudo-filters), fuzzyp-filter (also known as fuzzy pseudo-p-filters), and fuzzya-filter (also known as fuzzy pseudo-a-filters) in pseudo-BCIalgebras are investigated. By these properties, the following important results are proved: (1) a fuzzy filter (also known as fuzzy pseudo-filters) of a pseudo-BCIalgebra is a fuzzy associative filter if and only if it is a fuzzya-filter; (2) a filter (also known as pseudo-filter) of a pseudo-BCIalgebra is associative if and only if it is ana-filter (also call it pseudo-afilter); (3) a fuzzy filter of a pseudo-BCIalgebra is fuzzya-filter if and only if it is both a fuzzyp-filter and a fuzzyq-filter.
Two Hybrid Methods for Solving Two-Dimensional Linear Time-Fractional Partial Differential Equations
Authors: Jacobs B. A. , Harley C.
Published: April 2014

A computationally efficient hybridization of the Laplace transform with two spatial discretization techniques is investigated for numerical solutions of time-fractional linear partial differential equations in two space variables. The Chebyshev collocation method is compared with the standard finite difference spatial discretization and the absolute error is obtained for several test problems. Accurate numerical solutions are achieved in the Chebyshev collocation method subject to both Dirichlet and Neumann boundary conditions. The solution obtained by these hybrid methods allows for the evaluation at any point in time without the need for time-marching to a particular point in time.
High Conductivity of Mg-Doped Al0.3Ga0.7N with Al0.4Ga0.6N/AlN Superlattice Structure
Authors: Li Zhiming , Li Jinping , Jiang Haiying , Han Yanbin , Xia Yingjie , Huang Yimei , Yin Jianqin , Hu Shigang
Published: April 2014

The highly conductance of Mg-doped Al0.3Ga0.7N layer using low-pressure metal organic chemical vapour deposition (MOCVD) on Al0.4Ga0.6N/AlN superlattice structure was reported. The rapid thermal annealing (RTA) has been employed for the effective activation and generation of holes, and a minimum p-type resistivity of 3 Ω·cm for p-type Al0.3Ga0.7N was achieved. The RTA annealing impacted on electrical, doping profile and morphological properties of Mg-doped Al0.3Ga0.7N with Al0.4Ga0.6N/AlN superlattice structure have been also discussed. The quality of Mg-doped Al0.3Ga0.7N with Al0.4Ga0.6N/AlN superlattice structure degraded after annealing from HRXRD. At appropriate annealing temperature and time, surface morphology of Mg-doped Al0.3Ga0.7N can be improved. A step-like distribution of [Mg] and [H] in p-type Al0.3Ga0.7N was observed, and thermal diffusion direction of [Mg] and [H] was also discussed.
Investigation Performance and Mechanisms of Inverted Polymer Solar Cells by Pentacene Doped P3HT : PCBM
Authors: Lee Hsin-Ying , Huang Hung-Lin
Published: April 2014

The inverted polymer solar cells (PSCs) with pentacene-doped P3HT : PCBM absorption layers were fabricated. It was demonstrated that the pentacene doping modulated the electron mobility and the hole mobility in the resulting absorption layer. Furthermore, by varying the doping content, the optimal carrier mobility balance could be obtained. In addition, the pentacene doping led to an improvement in the crystallinity of the resulting films and made an enhancement in the light absorption, which was partly responsible for the performance improvement of the solar cells. Using the space-charge-limited current (SCLC) method, it was determined that the balanced carrier mobility (μh/μe=1.000) was nearly achieved when a pentacene doping ratio of 0.065 by weight was doped into the P3HT : PCBM : pentacene absorption layer. Compared with the inverted PSCs without the pentacene doping, the short circuit current density and the power conversion efficiency of the inverted PSCs with the pentacene doping ratio of 0.065 were increased from 9.73 mA/cm2to 11.26 mA/cm2and from 3.39% to 4.31%, respectively.
Realization of Negative Group Delay Network Using Defected Microstrip Structure
Authors: Chaudhary Girdhari , Jeong Yongchae , Lim Jongsik
Published: April 2014

A design of negative group delay (NGD) networks using a U-shaped defected microstrip structure (DMS) and lumped elements is presented in this paper. The signal attenuation characteristics of DMS were utilized to get NGD time. The group delay (GD) time and signal attenuation of the proposed networks are controlled by an external resistor connected across the DMS slot. For experimental validation, a single-stage and cascaded two-stage NGD networks were designed and fabricated. From experimental results, the GD of-8.24±1.1 ns with the maximum insertion loss of 37.84 dB was obtained over bandwidth of 40 MHz.
“Negotiating, Navigating, and Networking”: Three Strategies Used by Nursing Leaders to Shape the Adoption and Incorporation of Simulation into Nursing Curricula—A Grounded Theory Study
Authors: Taplay Karyn , Jack Susan M. , Baxter Pamela , Eva Kevin , Martin Lynn
Published: April 2014

Background. Implementing simulation requires a substantial commitment of human and financial resources. Despite this, little is known about the strategies used by academic nursing leaders to facilitate the implementation of a simulation program in nursing curricula. Methods. A constructivist grounded theory study was conducted within 13 nursing programs in Ontario, Canada. Perspectives of key stakeholders (n=27) including nursing administrators (n=6), simulation leaders (n=9), and nursing faculty (n=12) were analyzed using the constant comparison method. Results. Nursing leaders, specifically nursing administrators and simulation leaders who successfully led the adoption and incorporation of simulation into nursing curricula, worked together and utilized negotiating, navigating, and networking strategies that impacted the adoption and incorporation of simulation into nursing curricula. Conclusions. Strategies that were found to be useful when planning and executing the adoption and incorporation of an innovation, specifically simulation, into nursing curricula provide practical approaches that may be helpful to nurse leaders when embarking upon an organizational change.
An Improved Kernel Based Extreme Learning Machine for Robot Execution Failures
Authors: Li Bin , Rong Xuewen , Li Yibin
Published: April 2014

Robot execution failures prediction (classification) in the robot tasks is a difficult learning problem due to partially corrupted or incomplete measurements of data and unsuitable prediction techniques for this prediction problem with little learning samples. Therefore, how to predict the robot execution failures problem with little (incomplete) or erroneous data deserves more attention in the robot field. For improving the prediction accuracy of robot execution failures, this paper proposes a novel KELM learning algorithm using the particle swarm optimization approach to optimize the parameters of kernel functions of neural networks, which is called the AKELM learning algorithm. The simulation results with the robot execution failures datasets show that, by optimizing the kernel parameters, the proposed algorithm has good generalization performance and outperforms KELM and the other approaches in terms of classification accuracy. Other benchmark problems simulation results also show the efficiency and effectiveness of the proposed algorithm.
Models of Relative Nearness Incidence Based on Standard Distance Entropy
Authors: Wu Liusan , Tan Qingmei , Zhang Yuehui
Published: April 2014

The model of grey nearness incidence cannot reflect the nearness degree of sequences correctly. Therefore, the model of relative nearness incidence of sequences, curves, and surfaces is suggested based on standard distance entropy to remove the current bottlenecks and its properties are studied. At last, three cases are exemplified to demonstrate the validity and practicability of relative nearness incidence. The proposed models have enriched the theory of grey nearness incidence, filled the defects of grey nearness incidence.
Inhibition of Age-Related Cytokines Production by ATGL: A Mechanism Linked to the Anti-Inflammatory Effect of Resveratrol
Authors: Lettieri Barbato Daniele , Tatulli Giuseppe , Aquilano Katia , Ciriolo Maria R.
Published: April 2014

Ageing is characterized by the expansion and the decreased vascularization of visceral adipose tissue (vAT), disruption of metabolic activities, and decline of the function of the immune system, leading to chronic inflammatory states. We previously demonstrated that, in vAT of mice at early state of ageing, adipocytes mount a stress resistance response consisting in the upregulation of ATGL, which is functional in restraining the production of inflammatory cytokines. Here, we found that, in the late phase of ageing, such an adaptive response is impaired. In particular, 24-months-old mice and aged 3T3-L1 adipocytes display affected expression of ATGL and its downstream PPARα-mediated lipid signalling pathway, leading to upregulation of TNFαand IL-6 production. We show that the natural polyphenol compound resveratrol (RSV) efficiently suppresses the expression of TNFαand IL-6 in an ATGL/PPARαdependent manner. Actually, adipocytes downregulating ATGL do not show a restored PPARαexpression and display elevated cytokines production. Overall the results obtained highlight a crucial function of ATGL in inhibiting age-related inflammation and reinforce the idea that RSV could represent a valid natural compound to limit the onset and/or the exacerbation of the age-related inflammatory states.
miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM
Authors: Song Qiancheng , Xu Yuanfei , Yang Cuilan , Chen Zhenguo , Jia Chunhong , Chen Juan , Zhang Yue , Lai Pinglin , Fan Xiaorong , Zhou Xuan , Lin Jun , Li Ming , Ma Wenli , Luo Shenqiu , Bai Xiaochun
Published: April 2014

The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial–mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/β-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with β-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical β-catenin–activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM. Cancer Res; 74(11); 3031–42. ©2014 AACR.
Thrombin Drives Tumorigenesis in Colitis-Associated Colon Cancer
Authors: Turpin Brian , Miller Whitney , Rosenfeldt Leah , Kombrinck Keith , Flick Matthew J. , Steinbrecher Kris A. , Harmel-Laws Eleana , Mullins Eric S. , Shaw Maureen , Witte David P. , Revenko Alexey , Monia Brett , Palumbo Joseph S.
Published: April 2014

The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/− mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacologic inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC was temporally associated with the antecedent inflammatory colitis. However, direct studies of the antecedent colitis showed that mice carrying half-normal prothrombin levels were comparable to control mice in mucosal damage, inflammatory cell infiltration, and associated local cytokine levels. These results suggest that thrombin supports early events coupled to inflammation-mediated tumorigenesis in CAC that are distinct from overall inflammation-induced tissue damage and inflammatory cell trafficking. That prothrombin is linked to early events in CAC was strongly inferred by the observation that prothrombin deficiency dramatically reduced the formation of very early, precancerous aberrant crypt foci. Given the importance of inflammation in the development of colon cancer, these studies suggest that therapeutic interventions at the level of hemostatic factors may be an effective means to prevent and/or impede colitis-associated colon cancer progression. Cancer Res; 74(11); 3020–30. ©2014 AACR.
A Case of IgG4-Related Retroperitoneal Fibrosis from the Renal Pelvis Mimicking Bilateral Hydronephrosis
Authors: Inoue Seiya , Takahashi Chihiro , Hikita Katsuya
Published: April 2014

We describe a 49-year-old woman who presented with continuous bilateral lumbago. As the patient's ultrasonography manifestations were very similar to those of bilateral hydronephrosis, we performed retrograde pyelography and ureteroscopy. However, apart from slight left ureteropelvic junction obstruction, there was no hydronephrosis. Since malignant disease could not be completely denied, computed tomography-guided biopsy was performed. However, the tissue did not show evidence of malignancy. As the patient continued to have lumbago, we measured serum IgG4 levels because of suspicion of retroperitoneal fibrosis secondary to IgG4-related disease, which proved to be high. Further, immunostaining of the renal pelvic biopsy samples showed IgG4-positive cells. Therefore, diagnosing IgG4-related retroperitoneal fibrosis, we administered corticosteroids. The patient responded favorably to the drug, with gradual regression of the lesion.
Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study
Authors: Mearini Luigi , Ferri Carla , Lazzeri Massimo , Bini Vittorio , Nunzi Elisabetta , Fiorini Doriana , Costantini Elisabetta , Manasse Gianluca Carlo , Porena Massimo
Published: April 2014

Objective: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa). Patients and Methods: This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis. Results: PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID signiﬁcantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05). Conclusions: Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.
Long-Term Mortality in a Cohort of Home-Dwelling Elderly with Mild Alzheimer's Disease and Lewy Body Dementia
Authors: Oesterhus Ragnhild , Soennesyn Hogne , Rongve Arvid , Ballard Clive , Aarsland Dag , Vossius Corinna
Published: April 2014

Objective: To study mortality in subjects with mild dementia in Norway with a special focus on patients with Lewy body dementia (LBD) compared to Alzheimer's disease (AD). Methods: All referrals of mild dementia patients to dementia clinics in western Norway from March 2005 to March 2007 were included and followed until December 2012. Diagnoses were based on a comprehensive standardized assessment program. Results: Of 209 patients, 137 (66%) had AD and 53 (25%) had LBD. Dementia was associated with increased mortality (standardized mortality ratio = 1.8, AD 1.5, LBD 2.6). The median survival time was 6.2 years (95% CI 5.4-6.9). Predictors of mortality were age at diagnosis (HR 1.1 per year) and LBD diagnosis (HR 2.4). Conclusion: Dementia patients had an increased mortality, particularly those with LBD.
Prognostic Value of Metastatic Nodal Volume and Lymph Node Ratio in Patients with Cervical Lymph Node Metastases from an Unknown Primary Tumor
Authors: Park G.C. , Jung J.H. , Roh J.-L. , Lee J.H. , Cho K.-J. , Choi S.-H. , Nam S.Y. , Kim S.Y.
Published: April 2014

Objective: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. Methods: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. Results: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). Conclusion: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.
Evaluation of the New Consensus Criteria for the Diagnosis of Primary Progressive Aphasia Using Fluorodeoxyglucose Positron Emission Tomography
Authors: Matias-Guiu Jordi A. , Cabrera-Martín Maria Nieves , García-Ramos Rocío , Moreno-Ramos Teresa , Valles-Salgado Maria , Carreras José Luis , Matias-Guiu Jorge
Published: April 2014

Background: New consensus criteria have been proposed to classify primary progressive aphasia (PPA) into three variants: agrammatic, semantic, and logopenic. Some studies have subsequently addressed the usefulness of these criteria, with controversial results. We aimed to determine the correlation between the clinical diagnosis according to the new criteria and brain topography in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Patients meeting the PPA criteria were prospectively recruited in a single center during a period of 18 months. They were clinically classified according to the new criteria and underwent FDG-PET. The cerebral metabolism of each patient was compared to a healthy control group using statistical parametric mapping. The expected variant according to the analysis of PET imaging was compared with the clinical diagnosis using the consensus criteria. Results: 32 patients were included. 90% of them fulfilled the consensus criteria and could be classified into one of the three clinical variants. The correlation with the cerebral metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in the semantic variant, and 0.74 in the logopenic variant. Conclusions: A high correlation with the diagnosis obtained using FDG-PET was found. However, an overdiagnosis of the logopenic variant was observed. These results support the use of the new criteria, but some modifications or complementary studies may still be necessary.
Complement Factor I Polymorphism Is Not Associated with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Chinese Population
Authors: Yang Fei , Sun Yaoyao , Jin Zhongtian , Cheng Yong , Li Shanshan , Bai Yujing , Huang Lvzhen , Li Xiaoxin
Published: April 2014

Purpose: To identify the associations of the two complement factor I (CFI) polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a Chinese case-control study. Methods: A total of 900 subjects - 300 controls, 300 cases with nAMD and 300 cases with PCV - were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs10033900 and rs2285714 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between the cases and controls were tested by a χ2 test with age and gender adjusted for by logistic regression analysis. We also performed a meta-analysis of the case-control studies of rs10033900 and rs2285714 based on the currently available evidence from the literature. The meta-analysis was conducted via an inverse-variance, fixed-effects model, as previously described. Results: No statistically significant association was observed between the two polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05 for all comparisons). By meta-analysis, we detected significant associations between both of the SNPs and late AMD, which is consistent with previous results (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221, p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less reliable due to its heterogeneity. Conclusions: In our case-control study, neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing nAMD or PCV in a Chinese population. Additional large, comprehensive and well-designed association studies are needed to better understand the role of ethnicity and other gene interactions in the association between the CFI gene and AMD.
Correlation between both Morphologic and Functional Changes and Anxiety in Alzheimer's Disease
Authors: Tagai Kenji , Nagata Tomoyuki , Shinagawa Shunichiro , Nemoto Kiyotaka , Inamura Keisuke , Tsuno Norifumi , Nakayama Kazuhiko
Published: April 2014

Introduction: Although anxiety symptoms are often observed in Alzheimer's disease (AD), little attention has been paid to this symptom compared with other neuropsychiatric symptoms. Methods: Twenty-six patients with mild AD underwent both magnetic resonance imaging and single photon emission tomography with technetium-99m ethyl cysteinate dimer. Neuropsychiatric symptoms were evaluated using the Behavioral Pathology in Alzheimer's Disease Scale (Behave-AD). We investigated the relationship between anxiety and neuroimaging using Statistical Parametric Mapping 8 software. Results: The Behave-AD anxiety score was correlated with hyperperfusion in the bilateral anterior cingulate cortices and a reduction in the gray matter volume in the right precuneus and inferior parietal lobule. Conclusion: Our results suggest that anxiety in AD could overlap with the neural correlates of anxiety disorders, and that the specific degeneration associated with AD might be associated with anxiety.
Mouse Genetic Background Influences the Dental Phenotype
Authors: Li Yong , Konicki William S. , Wright J. Timothy , Suggs Cynthia , Xue Hui , Kuehl Melissa A. , Kulkarni Ashok B. , Gibson Carolyn W.
Published: April 2014

Dental enamel covers the crown of the vertebrate tooth and is considered to be the hardest tissue in the body. Enamel develops during secretion of an extracellular matrix by ameloblast cells in the tooth germ, prior to eruption of the tooth into the oral cavity. Secreted enamel proteins direct mineralization patterns during the maturation stage of amelogenesis as the tooth prepares to erupt. The amelogenins are the most abundant enamel proteins and are required for normal enamel development. Phenotypic differences were observed between incisors from individual Amelx (amelogenin) null mice that had a mixed 129xC57BL/6J genetic background and between inbred wild-type (WT) mice with different genetic backgrounds (C57BL/6J, C3H/HeJ, FVB/NJ). We hypothesized that this could be due to modifier genes, as human patients with a mutation in an enamel protein gene causing the enamel defect amelogenesis imperfecta (AI) can also have varied appearance of dentitions within a kindred. Enamel density measurements varied for all WT inbred strains midway during incisor development. Enamel thickness varied between some WT strains, and, unexpectedly, dentin density varied extensively between incisors and molars of all WT and Amelx null strains studied. WTFVB/NJ incisors were more similar to those of Amelx null mice than to those of the other WT strains in terms of incisor height/width ratio and pattern of enamel mineralization. Strain-specific differences led to the conclusion that modifier genes may be implicated in determining both normal development and severity of enamel appearance in AI mouse models and may in future studies be related to phenotypic heterogeneity within human AI kindreds reported in the literature.
Expression of Bone Morphogenetic Protein-6 in Dental Follicle Stem Cells and Its Effect on Osteogenic Differentiation
Authors: Yao Shaomian , He Hongzhi , Gutierrez Dina L. , Rezai Rad Maryam , Liu Dawen , Li Chunhong , Flanagan Michael , Wise Gary E.
Published: April 2014

The dental follicle (DF) plays an essential role in tooth eruption via regulation of bone resorption and bone formation. Bone morphogenetic protein-6 (BMP6) expression in the DF is coincident with bone growth in the tooth crypt. DF stem cells (DFSCs) have been shown to possess strong osteogenic capability. This study aims to determine the expression of BMP6 in DFSCs and to elucidate the role of BMP6 in the osteogenesis of DFSCs. DFSCs and their non-stem cell counterpart, DF cells (DFCs), were obtained from the DFs of rat pups. We showed that expression of BMP6 was significantly higher in the DFSCs than in the DFCs. DFSCs lost osteogenic capability during in vitro expansion, and DFSCs in late passages had reduced BMP6 expression as compared to early passages of DFSCs when they were subjected to osteogenic induction. Addition of exogenous human recombinant BMP6 (hrBMP6) to the osteogenic medium dramatically enhanced the osteogenesis of the late-passage DFSCs. Knockdown of BMP6 by short interfering RNA in the DFSCs in early passages resulted in a decrease in osteogenesis, which could be restored by addition of hrBMP6. We concluded that DFSCs need to express high levels of BMP6 to maintain their osteogenesis capability. Increased BMP6 expression seen in vivo in the DF may reflect the activation of DFSCs for osteogenic differentiation for bone growth during tooth eruption.
Inpatient and Emergent Resource Use of Patients on Dialysis at an Academic Medical Center
Authors: Chow Eric , Wong Hannah , Hahn-Goldberg Shoshana , Chan Christopher T. , Morra Dante
Published: April 2014

Background/Aim: End-stage renal disease patients require resources for emergent and inpatient care in addition to ambulatory dialysis. There are two dialysis modalities and settings which patients switch between. Our aim was to characterize the patterns and reasons for switching, as well as the emergent and inpatient utilization of these patients at the University Health Network. Methods: Patients who received chronic dialysis between March 1, 2006, and April 30, 2011, were identified. Utilization was measured by emergency department (ED) visits, inpatient hospitalizations, and bed-days occupied per year. Results: Out of 576 patients identified, 18.6% switched modality and/or setting. The majority of switches occurred during the first year of dialysis. Patients who switched had increased utilization compared to those on a continuous modality/setting. Overall, patients had a median rate of 0.91 ED visits per patient-year, compared to 1.56 for patients who switched modality and setting. Median inpatient bed resource requirement was 4.46 bed-days/patient-year overall, compared to 8.91 for patients who switched modality and setting. Conclusions: Emergent and inpatient utilization is related to the setting and modality of dialysis, although differences are partly explained by comorbidities. Patients who switch modalities use more resources and may be a prime population for interventions.
Causal Discovery via Reproducing Kernel Hilbert Space Embeddings
Authors: Chen Zhitang , Zhang Kun , Chan Laiwan , Schölkopf Bernhard
Published: April 2014

Causal discovery via the asymmetry between the cause and the effect has proved to be a promising way to infer the causal direction from observations. The basic idea is to assume that the mechanism generating the cause distribution p(x) and that generating the conditional distribution p(y|x) correspond to two independent natural processes and thus p(x) and p(y|x) fulfill some sort of independence condition. However, in many situations, the independence condition does not hold for the anticausal direction; if we consider p(x, y) as generated via p(y)p(x|y), then there are usually some contrived mutual adjustments between p(y) and p(x|y). This kind of asymmetry can be exploited to identify the causal direction. Based on this postulate, in this letter, we define an uncorrelatedness criterion between p(x) and p(y|x) and, based on this uncorrelatedness, show asymmetry between the cause and the effect in terms that a certain complexity metric on p(x) and p(y|x) is less than the complexity metric on p(y) and p(x|y). We propose a Hilbert space embedding-based method EMD (an abbreviation for EMbeDding) to calculate the complexity metric and show that this method preserves the relative magnitude of the complexity metric. Based on the complexity metric, we propose an efficient kernel-based algorithm for causal discovery. The contribution of this letter is threefold. It allows a general transformation from the cause to the effect involving the noise effect and is applicable to both one-dimensional and high-dimensional data. Furthermore it can be used to infer the causal ordering for multiple variables. Extensive experiments on simulated and real-world data are conducted to show the effectiveness of the proposed method.
Risk-Sensitive Reinforcement Learning
Authors: Shen Yun , Tobia Michael J. , Sommer Tobias , Obermayer Klaus
Published: April 2014

We derive a family of risk-sensitive reinforcement learning methods for agents, who face sequential decision-making tasks in uncertain environments. By applying a utility function to the temporal difference (TD) error, nonlinear transformations are effectively applied not only to the received rewards but also to the true transition probabilities of the underlying Markov decision process. When appropriate utility functions are chosen, the agents’ behaviors express key features of human behavior as predicted by prospect theory (Kahneman & Tversky, 1979 ), for example, different risk preferences for gains and losses, as well as the shape of subjective probability curves. We derive a risk-sensitive Q-learning algorithm, which is necessary for modeling human behavior when transition probabilities are unknown, and prove its convergence. As a proof of principle for the applicability of the new framework, we apply it to quantify human behavior in a sequential investment task. We find that the risk-sensitive variant provides a significantly better fit to the behavioral data and that it leads to an interpretation of the subject's responses that is indeed consistent with prospect theory. The analysis of simultaneously measured fMRI signals shows a significant correlation of the risk-sensitive TD error with BOLD signal change in the ventral striatum. In addition we find a significant correlation of the risk-sensitive Q-values with neural activity in the striatum, cingulate cortex, and insula that is not present if standard Q-values are used.
Intrinsic Graph Structure Estimation Using Graph Laplacian
Authors: Noda Atsushi , Hino Hideitsu , Tatsuno Masami , Akaho Shotaro , Murata Noboru
Published: April 2014

A graph is a mathematical representation of a set of variables where some pairs of the variables are connected by edges. Common examples of graphs are railroads, the Internet, and neural networks. It is both theoretically and practically important to estimate the intensity of direct connections between variables. In this study, a problem of estimating the intrinsic graph structure from observed data is considered. The observed data in this study are a matrix with elements representing dependency between nodes in the graph. The dependency represents more than direct connections because it includes influences of various paths. For example, each element of the observed matrix represents a co-occurrence of events at two nodes or a correlation of variables corresponding to two nodes. In this setting, spurious correlations make the estimation of direct connection difficult. To alleviate this difficulty, a digraph Laplacian is used for characterizing a graph. A generative model of this observed matrix is proposed, and a parameter estimation algorithm for the model is also introduced. The notable advantage of the proposed method is its ability to deal with directed graphs, while conventional graph structure estimation methods such as covariance selections are applicable only to undirected graphs. The algorithm is experimentally shown to be able to identify the intrinsic graph structure.
Spiking Neural P Systems with Thresholds
Authors: Zeng Xiangxiang , Zhang Xingyi , Song Tao , Pan Linqiang
Published: April 2014

Spiking neural P systems with weights are a new class of distributed and parallel computing models inspired by spiking neurons. In such models, a neuron fires when its potential equals a given value (called a threshold). In this work, spiking neural P systems with thresholds (SNPT systems) are introduced, where a neuron fires not only when its potential equals the threshold but also when its potential is higher than the threshold. Two types of SNPT systems are investigated. In the first one, we consider that the firing of a neuron consumes part of the potential (the amount of potential consumed depends on the rule to be applied). In the second one, once a neuron fires, its potential vanishes (i.e., it is reset to zero). The computation power of the two types of SNPT systems is investigated. We prove that the systems of the former type can compute all Turing computable sets of numbers and the systems of the latter type characterize the family of semilinear sets of numbers. The results show that the firing mechanism of neurons has a crucial influence on the computation power of the SNPT systems, which also answers an open problem formulated in Wang, Hoogeboom, Pan, Păun, and Pérez-Jiménez ( 2010 ).