bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning, expression, and bioinformatics analysis of a putative pigeon retinoid acid-inducible gene-I
Authors: Li Guoqin , Tian Yong , Chen Li , Shen Junda , Tao Zhengrong , Zeng Tao , Xu Jian , Lu Lizhi
Published: April 2018

Retinoid acid-inducible gene-I (RIG-I) is a major cytoplasmic RNA sensor, playing an essential role in detecting viral RNA and triggering antiviral innate immune responses. The objective of the present study was to characterize the structure and expression of the RIG-I gene in pigeons. The pigeon RIG-I (piRIG-I) was cloned from splenic lymphocytes of pigeons using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. The cDNA of piRIG-I contains a 147 bp 5′-untranslated regions (UTRs), a 2787 bp open reading frame, and 2962 bp 3′-UTRs. Based on this sequence, the encoded piRIG-I protein is predicted to consist of 928 amino acids, and it has conserved domains typical of RIG-I-like receptors (RLRs) including two tandem arranged N-terminal caspase recruitment domains, a domain with the signature of DExD/H box helicase (helicase domain), and a C-terminal repression domain similar to finch RIG-I, duck RIG-I, goose RIG-I, human RIG-I, and mouse RIG-I. The piRIG-I shows 82.1%, 78.6%, and 78.2% amino acid sequence identity with previously described finch RIG-I, duck RIG-I, and goose RIG-I, respectively, and 49.7%–53.8% sequence identity with mammalian homologs. Quantitative RT-PCR (qRT-PCR) analysis indicated that the piRIG-I mRNA is scarcely detected in healthy tissues, and it is strongly expressed in the thymus gland, kidney, spleen, and bursa of Fabricius. These findings lay the foundation for further research on the function and mechanism of avian RIG-I in innate immune response related to vaccinations and infectious diseases in the pigeon.
Teleparallel gravity with non-vanishing curvature
Authors: Wanas M.I. , Ammar Samah A. , Refaey Shymaa A.
Published: April 2018

Guided by the rules of Einstein’s geometrization philosophy, a pure geometric field theory is constructed. The Lagrangian used to derive the field equations of the theory is a curvature scalar of a version of absolute parallelism (AP) geometry known in the literature as the parameterized absolute parallelism (PAP) geometry. The linear connection of this version has simultaneously non-vanishing curvature and torsion. Analysis of the theory obtained shows clearly that it is a pure gravity theory. The theory is a teleparallel one, since the building blocks of both PAP and AP geometries are the same. It is shown analytically that the theory has a trivial version in the AP-geometry, if gravity is attributed to curvature not to torsion. In the case of spherical symmetry, solutions of the field equations give rise to the Schwarzschild exterior field. The theory depends on two principles: covariance and unification. The weak equivalence principle is satisfied under a certain condition. The work preserves Einstein’s main idea that gravity is just space–time curvature, although it is not a metric theory. It is shown that the theory reduces to vacuum general relativity upon taking the parameter of the geometry b = 0.
Mixing-rules calculations and AAMD simulations for EOSs of deuterium–xenon mixtures
Authors: He Zhencen , Hu Zhimin , Hou Yong , Yang Jiamin , Yuan Jianmin , Jiang Gang , Zhang Jiyan , Dong Yunsong , Huang Chengwu
Published: April 2018

We present the calculated equations of state (EOSs) for deuterium–xenon mixtures using mixing rules. Three mixing rules, which are the ideal rule, volume rule, and pressure rule, were used for the calculations, and the thermodynamic self-consistency was evaluated. The volume rule predicts the pressures of mixtures rather accurately, but it fails in the predictions of energies. The pressure ionization has an impact on energy and pressure. Furthermore, the calculated results of the mixing rules were compared with average-atom molecular dynamics (AAMD) simulations, and the pressure rule performs better than the ideal and volume rules over the investigated range.
Pull-in behavior of electrostatically actuated stepped microbeams
Authors: Zhu Junhua , Yao Ke , Dong Xianshan , Huang Qinwen , Liu Renhuai
Published: April 2018

The stepped microbeams are typical low stiffness structures widely used in MEMS devices. Approximated solutions of the natural frequency and the pull-in voltage of stepped microbeams, including clamped-free (CF) and clamped–clamped (CC) boundary conditions are developed, and the unique pull-in behavior of the stepped microbeams is investigated. The stepped microbeam is viewed as a beam with a rectangular electrode pad at its tip for CF beam and at its center for CC beam. The motion equations are deduced based on the Euler–Bernoulli beam and the modified couple stress theory. The natural frequency and the pull-in voltage are extracted with a one-degree-of-freedom model. The present model correctness is validated by comparing with the finite element results, and the effect of the length ratio of the electrode pad to the beam and the width ratio of the beam to the electrode pad are discussed. The results show that both the natural frequency and the pull-in voltage monotonously increase with the increase of the width ratio, and first decrease and then increase with the increase of the length ratio. The minimum value of them does not appear at the same time, but is determined by the width ratio. The results can be used to design and improve the performance of MEMS devices.
Propagation of ultrashort pulses in a two-level medium beyond the slowly varying envelope approximation
Authors: Wen Daqing , Lu Longzhao , Yu Xiangyang
Published: April 2018

The semiclassical Maxwell–Bloch equations beyond the slowly varying envelope approximation (SVEA) are derived in order to study the propagation of the ultrashort pulse in a two-level medium. The evolutions of the pulse shape, the group velocity and the pulse peak of 2[Formula: see text] ultrashort pulse are investigated as well as the pulse splitting of 4[Formula: see text] ultrashort pulse. By comparing the numerical results with those obtained using the SVEA, the error introduced by the approximation is quantitatively evaluated with respect to the pulse width and the applicable condition of the SVEA is discussed consequently. The envelope solutions presented by us allow clear observation on the evolution of the envelope.
Enhanced absorption of TM waves in conductive nanoparticles structure
Authors: Mousa H. M. , Shabat M. M. , Ouda A. K. , Schaadt D. M.
Published: April 2018

This paper tackles anti-reflection coating structure for silicon solar cell where conductive nanoparticle (CNP) film is sandwiched between a semi-infinite glass cover and a semi-infinite silicon substrate. The transmission and reflection coefficients are derived by the transfer matrix method and simulated for values of unit cell sizes, gab widths in visible and near-infrared radiation. We also illustrated the dependence of the absorption, transmission and reflection coefficients on several angles of incidence of the transverse magnetic polarized (TM) waves. We found out that reflection decreases by the increase of incident angle to 50[Formula: see text]. If nanoparticles are suitably located and sized at gab width of 3.5 nm, unit cell of 250 nm and CNP layer thickness of 150 nm, the absorptivity of the structure achieves 100%.
Multistate Reliability Evaluation of Bogie on High Speed Railway Vehicle Based on the Network Flow Theory
Authors: Kou Linlin , Qin Yong , Jia Limin , Fu Yong
Published: April 2018

Bogie is one of the most major mechanical part of railway train. Its security and reliability are of paramount importance. Since research in this field is still on the early stage, which focus on either mechanical structure without condition or binary coherent systems. A multistate network flow model has been proposed in this paper with consideration of components degradation level and functional interaction between them. Firstly, the structure and function of the bogie for CRH3 were made a detailed introduction. Then transmission paths of three types force on bogie were study to determine the network strcture. Different from other papers, arcs represent the components and nodes are the transitive relation. Arc capacity tends to be confirmed easily with utilization of performance deterioration of elements on bogie involved in force tranferring. Flow rate of each arc depends on both component' health status and the task it undertakes. Furthermore, the minimal paths (MPs) method and the recursive sum of disjoint products (RSDP) with ordering heuristics are used for system reliability calculation; and the relative probability importance of each basic component and system reliability with and without forehead information are given at last. The results show that the network flow model works well on CRH3 bogie, and can support as guidance of bogie system design, daily system operation and predictive maintenance.
A nuclear phenomenological study of the even–even Thorium Isotopes 228–232Th
Authors: Doma S. B. , El-Gendy H. S.
Published: April 2018

The rotational and vibrational energies and the electric transition probability B [Formula: see text] of the even–even [Formula: see text]Th isotopes are studied empirically in framework of a nuclear phenomenological approach by using the SU(3) dynamical symmetries of the Interacting Boson Model-1 (IBM-1). Furthermore, the potential energy surfaces for these isotopes are plotted as functions of the deformation parameters [Formula: see text] and [Formula: see text]. Moreover, we introduce empirical fit formulas for rotational and vibrational energies, which used to calculate these energies for the thorium isotopes. The obtained results by applying the IBM-1 and the authors’ formulas are in good agreement with the corresponding experimental data for most of the nuclear states.
AFFINE MAURER–CARTAN INVARIANTS AND THEIR APPLICATIONS IN SELF-AFFINE FRACTALS
Authors: YANG YUN , YU YANHUA
Published: April 2018

In this paper, we define the notion of affine curvatures on a discrete planar curve. By the moving frame method, they are in fact the discrete Maurer–Cartan invariants. It shows that two curves with the same curvature sequences are affinely equivalent. Conditions for the curves with some obvious geometric properties are obtained and examples with constant curvatures are considered. On the other hand, by using the affine invariants and optimization methods, it becomes possible to collect the IFSs of some self-affine fractals with desired geometrical or topological properties inside a fixed area. In order to estimate their Hausdorff dimensions, GPUs can be used to accelerate parallel computing tasks. Furthermore, the method could be used to a much broader class.
Symmetry analysis and invariant solutions of (3 + 1)-dimensional Kadomtsev–Petviashvili equation
Authors: Jadaun Vishakha , Kumar Sachin
Published: April 2018

Based on Lie symmetry analysis, we study nonlinear waves in fluid mechanics with strong spatial dispersion. The similarity reductions and exact solutions are obtained based on the optimal system and power series method. We obtain the infinitesimal generators, commutator table of Lie algebra, symmetry group and similarity reductions for the [Formula: see text]-dimensional Kadomtsev–Petviashvili equation. For different Lie algebra, Lie symmetry method reduces Kadomtsev–Petviashvili equation into various ordinary differential equations (ODEs). Some of the solutions of [Formula: see text]-dimensional Kadomtsev–Petviashvili equation are of the forms — traveling waves, Weierstrass’s elliptic and Zeta functions and exponential functions.
Synthesis of rGO/TiO2/CdS Nanocomposites and its Enhanced Photoelectrochemical Performance in Determination of Parathion-Methyl
Authors: Shi Jian-Jun , Wang Yan , Meng Li-Rong , Zhu Jing-Chun , Shu Rui-Wen , He Jie
Published: April 2018

A photoelectrochemical (PEC) sensor for the determination of organophosphate pesticides (OPs) was developed based on rGO/TiO2/CdS photoactive nanomaterials. The rGO/TiO2/CdS nanocomposites were prepared by solvothermal method and electrochemical deposition technique successively. The morphologies and structures of the as-prepared nanocomposites were extensively investigated by SEM and XRD. In alkaline condition, p-nitrophenol as the hydrolysate of parathion-methyl (PM) could be obtained by a simple hydrolyzation process. Under optimal conditions, the rGO/TiO2/CdS NPs modified ITO electrode exhibited a good PEC performance toward the hydrolysate of PM. The photocurrent intensity was enhanced with the increase of the concentration of the hydrolysate of PM. The proposed PEC method could detect PM in the range from 0.05[Formula: see text]nmol L[Formula: see text] to 10[Formula: see text]nmol L[Formula: see text] with a detection limit of 0.02[Formula: see text]nmol L[Formula: see text] ([Formula: see text]). Thus, the excellent performance of the rGO/TiO2/CdS nanocomposites serve as the matrix of the sensor, which provides a new way for the fabrication of high-sensitivity PEC sensing system.
Modeling and Numerical Characterization of High Sensitive Microcantilever Biosensors with Parabolic Piezoresistor
Authors: Ansari Mohd. Zahid , Kumar Shashank , Prajapati Sunil Kumar , Cho Chongdu
Published: April 2018

The biaxial and planar characteristics of surface stress produce a parabolic differential stress distribution inside the sensing zone of microcantilever biosensors, which can be used to design novel biosensors. The present work studies and compares the effect of parabolic and conventional rectangular-shaped piezoresistor placed inside this sensing zone on sensitivity of the biosensors. Two different cantilevers made of silicon and silicon dioxide with doped silicon as piezoresistor are used in five design variations. The cantilevers are characterized for their deflections, von Mises stresses, resonant frequencies and self-heating temperatures produced using ANSYS. Analytical models for predicting deflections in the cantilevers is presented and compared with numerical results obtained. Results show good compatibility between analytical and numerical values for deflection with a 4–5% average deviation and that parabolic designs have higher sensitivity.
Adaptation to Future Risks in Coastal Megacities — New York City Case Study: Local Assessment and Survey Findings in Water Front Neighborhoods
Authors: Link Hildegaard , Barrett Chris
Published: April 2018

Risk management regimes develop as stakeholders attempt to reduce vulnerability to hazards and limit the damage and disruption from disasters. Urban coastal regions are often hotspots of climate change-related risks. Analysis of different characteristics of vulnerability, resilience, and transformation is an important precursor to planning and decision making. While these concepts are not new, in many areas they remain very abstract. This paper offers a method to assess vulnerability at the individual household scale in different New York City water front neighborhoods that were extensively damaged during hurricane Sandy in 2012. Household Surveys were conducted in Red Hook, Brooklyn and Edgemere/Arverne, Queens in early 2016. Survey results suggest that at the household level, feelings of preparedness and trust in local government’s ability to effectively manage and respond to extreme weather differ with the varying political/economic climates of each neighborhood. Our survey results also indicate that residents are changing their emergency planning behavior, regardless of politics or economics. Responses show residents adapting their thinking to acknowledge the potential for increasing risk from extreme weather events in both locations studied.
Capsaicin-based analgesic balm attenuates the skeletal muscle metaboreflex in healthy humans
Authors: Vianna Lauro C. , Fernandes Igor A. , Barbosa Thales C. , Teixeira André L. , Nóbrega Antonio C. L.
Published: April 2018

The exercise pressor reflex (EPR) is comprised of group III and IV skeletal muscle afferents and is one of the principal mediators of the cardiovascular response to exercise. In animals, capsaicin-based analgesic balm (CAP) attenuates the pressor response to muscle contraction, indicating the transient receptor potential vanilloid 1 (TRPv1) receptor (localized on the group IV afferent neuron) as an important mediator of the EPR. However, whether these findings can be extrapolated to humans remains unknown. Here, we tested the hypothesis that CAP would attenuate blood pressure (BP) and muscle sympathetic nerve activity (MSNA) responses to isolated muscle metaboreflex activation in healthy men. MSNA (microneurography) and beat-to-beat heart hate (HR, by electrocardiography), and BP (finger photoplethysmography) were continuously measured in eight healthy males (23 ± 5 yr) at rest, during isometric handgrip exercise, and during postexercise ischemia (PEI). Trials were performed before and 30 and 60 min after the topical application of CAP (0.1%, CAPZASIN-HP) over the volar forearm of the subject’s exercising arm. Isometric exercise evoked increases in mean BP (∆32 ± 4 mmHg) and MSNA (∆26 ± 5 bursts/min; ∆19 ± 5 bursts/100 heart beats). The increases in BP during handgrip were not affected by CAP, but the increase in MSNA was lower after 60 min of CAP application. During PEI, the increases in BP and MSNA were all significantly less than those before CAP (all P < 0.05). In conclusion, CAP attenuated BP and sympathetic responses evoked by PEI in humans. These data provide evidence that transient receptor potential vanilloid 1 receptors potentially contribute to the EPR in humans, via its metabolic component.

NEW & NOTEWORTHY We found that topical application of capsaicin-based analgesic balm attenuates arterial blood pressure and muscle sympathetic nerve activity during isolated muscle metaboreflex activation following isometric handgrip exercise in healthy humans. These findings suggest that the transient receptor potential vanilloid 1 may contribute to the exercise pressor reflex in humans via its metabolic component.
Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications
Authors: Christidi Foteini , Migliaccio Raffaella , Santamaría-García Hernando , Santangelo Gabriella , Trojsi Francesca
Published: April 2018

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients’ management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson’s and Alzheimer’s diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients’ well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.
Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent
Authors: Szigeti Krisztián , Hegedűs Nikolett , Rácz Kitti , Horváth Ildikó , Veres Dániel S. , Szöllősi Dávid , Futó Ildikó , Módos Károly , Bozó Tamás , Karlinger Kinga , Kovács Noémi , Varga Zoltán , Babos Magor , Budán Ferenc , Padmanabhan Parasuraman , Gulyás Balázs , Máthé Domokos
Published: April 2018

Background. The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods. The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs) (iron(II);iron(III);octadecacyanide) doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3) were calculated from the SPECT scans for each dedicated volume of interest (VOI) of liver, kidneys, salivary glands, heart, lungs, and brain. Results. PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion. We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications.
Effects of Angiotensin-Converting Enzyme Inhibition on Circulating Endothelial Progenitor Cells in Patients with Acute Ischemic Stroke
Authors: Gołąb-Janowska Monika , Paczkowska Edyta , Machaliński Bogusław , Kotlęga Dariusz , Meller Agnieszka , Safranow Krzysztof , Maj Michał , Nowacki Przemysław
Published: April 2018

Background. Therapeutic neovascularization might represent an important strategy to salvage tissue after ischemia. Circulating bone marrow-derived endothelial progenitor cells (EPCs) were previously shown to augment the neovascularization of ischemic tissue. Angiotensin-converting enzyme inhibitors (ACEIs) might modulate EPC mobilization. We evaluated populations of circulating stem cells and early EPCs in acute ischemic stroke (AIS) patients and the effect of ACEI on circulating EPCs in these patients with respect to aspects of stroke pathogenesis. Methods. We studied 43 AIS patients (group I), comprising 33 treated with ACEI (group Ia) and 10 untreated (group Ib). Risk factor controls (group II) included 22 subjects. EPCs were measured by flow cytometry. Results. In AIS patients, the number of circulating stem cells and early EPCs upon admission was similar to that in control group individuals. There were no significant differences in the numbers of stem cells and early EPCs over subsequent days after AIS. There were also no significant differences in stem cell and early EPC numbers over the first 3 days between group Ia and group Ib. However, on day 7, these numbers were significantly higher in group Ib than in group Ia (p<0.05). In AIS patients chronically treated with ACEI, there was a negative correlation between CD133+ cell number and neurological deficit on the first, third, and seventh days (p<0.005). Conclusions. An increased number of circulating stem cells and early EPCs were not observed in stroke patients chronically treated with ACEI. In patients chronically treated with ACEI, a significant correlation was observed between decreased neurological deficit and higher levels of CD133+ cells; this could be due to the positive influence of these cells on the regeneration of the endothelium and improved circulation in the ischemic penumbra.
Exosomes: A Paradigm in Drug Development against Cancer and Infectious Diseases
Authors: Oves Mohammad , Qari Huda A. , Felemban Nadeen M. , Khan Aftab Aslam Parwaz , Rehan Mohd , Tabrez Shams , Ahmed Faheem , Haque Ashanul , Khan Mohd Shahnawaz , Khan Javed M. , Husain Fohad M. , Hussain Afzal , Warsi Mohiuddin Khan , Ismail Iqbal I. M.
Published: April 2018

Extracellular vesicles are small single lipid membrane entity secreted by eukaryotic and prokaryotic cells and play an important role in intercellular signaling and nutrient transport. The last few decades have witnessed a plethora of research on these vesicles owing to their ability to answer many hidden facts at the supramolecular level. These extracellular vesicles have attracted the researchers because they act as shuttle agents to transfer biomolecules/drugs between cells. Recently, studies have shown the application of exosomes in tumor therapy and infectious disease control. The present review article shows the importance of exosomes in cancer biology and infectious disease diagnoses and therapy and provides comprehensive account of exosomes biogenesis, extraction, molecular profiling, and application in drug delivery.
A Novel Method for Air Quality Data Imputation by Nuclear Norm Minimization
Authors: Chen Xiaobo , Xiao Yan
Published: April 2018

Missing data is a frequently encountered problem in environment research community. To facilitate the analysis and management of air quality data, for example, PM2.5concentration in this study, a commonly adopted strategy for handling missing values in the samples is to generate a complete data set using imputation methods. Many imputation methods based on temporal or spatial correlation have been developed for this purpose in the existing literatures. The difference of various methods lies in characterizing the dependence relationship of data samples with different mathematical models, which is crucial for missing data imputation. In this paper, we propose two novel and principled imputation methods based on the nuclear norm of a matrix since it measures such dependence in a global fashion. The first method, termed as global nuclear norm minimization (GNNM), tries to impute missing values through directly minimizing the nuclear norm of the whole sample matrix, thus at the same time maximizing the linear dependence of samples. The second method, called local nuclear norm minimization (LNNM), concentrates more on each sample and its most similar samples which are estimated from the imputation results of the first method. In such a way, the nuclear norm minimization can be performed on those highly correlated samples instead of the whole sample matrix as in GNNM, thus reducing the adverse impact of irrelevant samples. The two methods are evaluated on a data set of PM2.5concentration measured every 1 h by 22 monitoring stations. The missing values are simulated with different percentages. The imputed values are compared with the ground truth values to evaluate the imputation performance of different methods. The experimental results verify the effectiveness of our methods, especially LNNM, for missing air quality data imputation.
Adaptive Energy Harvesting Relaying Protocol for Two‐Way Half‐Duplex System Network over Rician Fading Channels
Authors: Nguyen Tan N. , Minh Tran Hoang Quang , Tran Phuong T. , Voznak Miroslav
Published: April 2018

We investigate the system performance of a two‐way amplify‐and‐forward (AF) energy harvesting relay network over the Rician fading environment. For details, the delay‐limited (DL) and delay‐tolerant (DT) transmission modes are proposed and investigated when both energy and information are transferred between the source node and the destination node via a relay node. In the first stage, the analytical expressions of the achievable throughput, ergodic capacity, the outage probability, and symbol error ratio (SER) were proposed, analyzed, and demonstrated. After that, the closed‐form expressions for the system performance are studied in connection with all system parameters. Moreover, the analytical results are also demonstrated by Monte Carlo simulation in comparison with the closed‐form expressions. Finally, the research results show that the analytical and the simulation results agree well with each other in all system parameters.
Preparation of 68Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression
Authors: Wang Yuebing , Shao Guoqiang , Wu Jianping , Cui Can , Zang Shimin , Qiu Fan , Jia Ruipeng , Wang Zizheng , Wang Feng
Published: April 2018

Objective. To synthesize 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) with a synthesis module and investigate PET-CT imaging to monitor PSMA expression during prostate cancer (PCa) progression and tumor growth in mice bearing subcutaneous PCa xenografts. Method. The radiochemical purity and stability of  68Ga-PSMA-11 were determined via radio-HPLC. The PCa cell lines of different PSMA expression levels (PC3, VCAP±, CWR22RV1+, and LNCaP++) were selected to mimic the PCa progression. 68Ga-PSMA-11 biodistribution was studied by dissection method and in vivo imaging with micro PET-CT. The expression levels of PSMA in tumor cells and tissues were analyzed by immunofluorescence, flow cytometry, and western blot. The correlation between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results. The radiochemical purity of  68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2 h. The equilibrium binding constant (Kd) of  68Ga-PSMA-11 to LNCaP, CWR22Rv1, PC-3, and VCAP cells was 4.3 ± 0.8 nM, 16.4 ± 1.3 nM, 225.3 ± 20.8 nM, and 125.6 ± 13.1 nM, respectively. Results of tumor uptake (% ID and % ID/g or % ID/cm3) of  68Ga-PSMA-11 in biodistribution and micro PET imaging were LNCaP > CWR22RV1 > PC-3 and VCAP due to different PSMA expression levels. It was confirmed by flow cytometry, western blot, and immunofluorescence. Tumor uptake (% ID/cm3) of  68Ga-PSMA-11 increased with the tumor anatomical volume in quadratic polynomial fashion and reached the peak (when tumor volume was 0.5 cm3) earlier than tumor uptake (% ID). Tumor uptake (% ID/cm3) of  68Ga-PSMA-11 based on functional volume correlated well with the PSMA expression in a linear manner (y=9.35x+2.59, R2=0.8924, and p<0.0001); however, low dose 2-PMPA causes rapid renal clearance of increased tumor/kidney uptake of  68Ga-PSMA-11. Conclusions. The 68Ga-PSMA-11 PET-CT imaging could invasively evaluate PSMA expression during PCa progression and tumor growth with % ID/cm3 (based on functional volume) as an important index. Low dose 2-PMPA preadministration might be a choice to decrease kidney uptake of  68Ga-PSMA-11.
Human Papillomavirus Seroprevalence and Association with Anal HPV Infection and Squamous Intraepithelial Lesions in Australian Gay and Bisexual Men
Authors: Poynten Isobel M. , Waterboer Tim , Jin Fengyi , Templeton David J. , Hillman Richard J. , Law Carmella , Cornall Alyssa , Tabrizi Sepehr , Roberts Jennifer M. , Garland Suzanne M. , Fairley Christopher K. , Grulich Andrew E.
Published: April 2018

Background: Gay and bisexual men (GBM) are at disproportionately high risk of anal cancer. The precursor lesions, high-grade squamous intraepithelial lesions (HSIL), are very common and it is evident that not all HSIL progresses to cancer. The serologic response to anal human papillomavirus (HPV) in GBM has not been well characterized.

Methods: The Study of the Prevention of Anal Cancer is an ongoing cohort study of GBM ages 35 years and older. At six visits over three years, anal samples are collected for cytology, HPV DNA testing, and histology. Baseline serum was tested for HPV L1, E6, and E7 antibodies for 10 HPV types. Seroprevalence and associated predictors were analyzed.

Results: A total of 588 of 617 participants were included in this analysis. A total of 436 (74.2%) were seropositive for at least one of the 10 HPV types. Almost half had L1 antibodies to HPV6 (48.5%), over a third to HPV11 (36.4%) and HPV16 (34.5%). HIV-positive men were more likely to be HPV L1 seropositive. HSIL detection was highest among participants who were HPV serology and DNA positive. There was a borderline significant association between presence of HPV16 E6 antibodies and prevalent HSIL (OR = 2.97; 95% confidence interval, 0.92–9.60; P = 0.068).

Conclusions: HPV L1 seropositivity was common in this cohort of older GBM. These results suggest that HPV L1 seropositivity, in conjunction with anal HPV DNA detection, predicts concurrent HSIL. The apparent association between HPV16 E6 antibodies and prevalent HSIL is a finding with potential clinical significance that needs further exploration.

Impact: HPV seropositivity with concurrent DNA detection predicted anal HSIL detection. Cancer Epidemiol Biomarkers Prev; 27(7); 768–75. ©2018 AACR.
Smoking and Prostate Cancer–Specific Mortality after Diagnosis in a Large Prospective Cohort
Authors: Gansler Ted , Shah Roma , Wang Ying , Stevens Victoria L. , Yang Baiyu , Newton Christina C. , Gapstur Susan M. , Jacobs Eric J.
Published: April 2018

Background: Prior studies of prostate cancer survivors suggest that smoking might be associated with higher prostate cancer–specific mortality (PCSM) after diagnosis with prostate cancer. However, most of these studies were small, and questions remain regarding this association's strength and whether it persists after adjustment for stage and Gleason score.

Methods: This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992–1993 and June 2013. Cigarette smoking was self-reported at enrollment and updated in 1997 and every 2 years thereafter. Analyses of pre-diagnosis and post-diagnosis smoking included 9,781 and 9,111 prostate cancer cases, respectively, with vital status follow-up through 2014.

Results: There were 672 deaths from prostate cancer in analyses of pre-diagnosis smoking and 554 in analyses of post-diagnosis smoking. In multivariable-adjusted Cox proportional hazards regression models including stage and Gleason score, both current smoking before diagnosis [HR = 1.50; 95% confidence interval (CI), 1.06–2.13] and current smoking after diagnosis (HR = 1.71; 95% CI, 1.09–2.67) were associated with higher PCSM compared to never smoking. Prostate cancer survivors who quit smoking <20 years before diagnosis were also at significantly higher risk of PCSM (HR = 1.29; 95% CI, 1.04–1.61).

Conclusions: This large prospective study suggests that current smoking both before and after diagnosis of prostate cancer is associated with higher PCSM, even after accounting for stage and Gleason score.

Impact: Our results provide evidence that smoking is a relevant prognostic factor for prostate cancer patients and that prostate cancer may be among the causes of death attributable to smoking. Cancer Epidemiol Biomarkers Prev; 27(6); 665–72. ©2018 AACR.
Real-Time Elastography: Noninvasive Diagnostic Tool in the Evaluation of Liver Stiffness in Patients with Chronic Viral Hepatitis, Correlation with Histological Examination
Authors: Ippolito Davide , Schiavone Valentina , Talei Franzesi Cammillo Roberto , Casiraghi Alessandra Silvia , Drago Silvia Girolama , Riva Luca , Sironi Sandro
Published: April 2018

Purpose: To determine the value of real-time elastography (RTE) in the assessment of liver stiffness in patients with chronic viral hepatitis, correlating RTE data with the extent of fibrosis based on biopsy findings (Ishak score). Methods: We evaluated 98 patients (45–75 years) with chronic viral hepatitis (51 HCV, 47 HBV) by using ultrasonography (US) study combined with RTE analysis. In the RTE images, relative tissue stiffness is expressed, according to color scale, with soft areas represented in green/red colors and hard areas in blue. We divided the patients into 2 groups based on the fibrosis degree: soft degree (D1, corresponding to F1–F3 Ishak score) and hard degree (D2, corresponding to F4–F6). Before RTE, all patients underwent a US-guided percutaneous liver biopsy (right lobe). Results: Quantitative RTE data were compared with liver biopsy by using the Spearman correlation coefficient in order to assess the correlation between the RTE (D) and fibrosis, according to Ishak score (F) at histology. At RTE, out of 98 patients 55 had degree D1 and 43 had degree D2; at histological analysis, we observed the following: 15 patients with F1, 28 with F2, 17 with F3, 16 with F4, 12 with F5, and 10 with F6. The Spearman’s coefficient showed significant correlation between D and F degree, obtaining rho = 0.573, p = 0.003. Conclusions: RTE analysis showed high diagnostic accuracy in the assessment of fibrosis, and it appears to be a useful diagnostic tool for noninvasive quantification of fibrosis in patients with chronic viral hepatitis.
Imaging Care Requirements: Use of Functional Neuroimaging to Predict Dementia Caregiver Burden
Authors: Prosser Angus M.J. , Spreadbury John H. , Tossici-Bolt Livia , Kipps Christopher M.
Published: April 2018

Background: Dementia caregivers frequently report high stress, with increased burden associated with worse outcomes for both patients and caregivers. Although many studies relate clinical phenotypes to burden, the relationship between imaging pathology and burden, irrespective of diagnosis, is unknown. This study investigated the relationship between caregiver burden and patient regional cerebral blood flow in dementia. Methods: Seventy-sev en patients with cognitive impairment undergoing brain perfusion single-photon emission computed tomography imaging in normal clinical care and their caregivers were recruited. Caregiver burden was ranked from “little” to “severe” using the Zarit Burden Interview and perfusion values extracted from the patient images for predefined regions of interest. The associations between burden score and regional function on imaging were tested. Results: Burden score was significantly higher for caregivers of patients with abnormal perfusion compared to those with normal perfusion in the left and right frontal, right parietal, and right temporal lobes. No difference in burden was found in the left parietal or temporal groups. Correlations showed that a higher caregiver burden was associated with lower patient perfusion scores in the same regions. Conclusion: Caregiver burden is strongly related to the extent of frontal or right-predominant parietal or temporal lobe dysfunction. Regional abnormality on perfusion imaging can be used to facilitate identification of individuals who are likely to create a high burden on caregivers.
Long-Term Hearing Outcomes following Stapedotomy in Patients with Otosclerosis and Preoperative Small Air-Bone Gap
Authors: Alberti Anna , Figuerola Enric , Romero-Farina Guillermo , Quer Miquel , Larrosa Francisco
Published: April 2018

Objectives: To assess the long-term effectiveness of stapedotomies performed on patients with otosclerosis and preoperative small air-bone gaps (ABGs). Methods: Retrospective study comparing the 10-year postoperative hearing outcomes after primary stapedotomies in patients with small (≤20 dB) and large ABGs (> 20 dB). Ninety out of 175 stapedotomies (22 and 68 in the small and large ABG groups, respectively) were monitored with long-term follow-ups. Results: Ten years after the operation, hearing measurements were similar for both groups, although a significant decline of bone conduction thresholds was evident (p = 0.007 and p < 0.001, respectively). An improvement of ≥10 dB in the postoperative ABG (clinical improvement) was achieved only in the large ABG group. Conclusions: Even though long-term hearing levels will evolve similarly in patients with ≤20 and > 20 dB preoperative ABGs, the lack of clinical improvement found in the small ABG group is not in favor of an early surgery.
Combined Systemic Chemotherapy and CT-Guided High-Dose-Rate Brachytherapy for Isolated Local Manifestation of Pancreatic Cancer after Surgical Resection
Authors: Franck Caspar , Hass Peter , Malfertheiner Peter , Ricke Jens , Seidensticker Max , Venerito Marino
Published: April 2018

Background: Prospective data on the optimal management of patients with pancreatic ductal adenocarcinoma (PDA) and isolated local manifestation (ILM) after surgery are lacking. Hence, no statements with respect to this entity have been released from most international guidelines including European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society for Clinical Oncology. Methods: We report for the first time a case-series of 3 patients with PDA and ILM receiving combined systemic chemotherapy and CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT). Results: CT-HDRBT allowed in all patients with pronounced chemotherapy-induced side effects either a pause of cytostatic treatment or de-escalation to a “maintenance” therapy (dose reduction, interval prolongation, scheme modification with withdrawal of most toxic drugs). Conclusion: Combining CT-HDRBT to systemic chemotherapy in patients with PDA and ILM is feasible and safe. As for patients with PDA and ILM no standard of care exists, designing an appropriate randomized prospective trial for this highly selected group of patients is challenging.
Effects of a Voice Therapy Program for Patients with Muscle Tension Dysphonia
Authors: de Oliveira Lemos Isadora , da Cunha Pereira Gabriela , Druck SantAnna Geraldo , Cassol Mauriceia
Published: April 2018

Objective: This study aimed to verify the effects of a voice therapy program focusing on patients with muscle tension dysphonia (MTD). Patients and Methods: The sample comprised 30 participants diagnosed with MTD, 8 men and 22 women, none of whom was a voice professional. The assessments and reassessments employed the perceptual-auditory protocol GRBASI, measures of maximum phonation times, s/z ratio, and acoustic voice analysis. The voice therapy program included indirect and direct therapy approaches. Results: All parameters assessed using the GRBASI protocol improved following treatment, particularly in regard to lowering voice strain, which is important when treating MTD. The average overall maximum phonation times increased from 8.15 to 10.8 s, while the average s/z ratio did not significantly change. Among the various acoustic parameters, a positive difference was observed for vocal jitter and shimmer. Conclusions: The therapeutic approach adopted in this study proved effective in the treatment of primary and secondary MTD. Speech therapy favored lower phonation effort, lowered vocal strain, and adequacy of adjustment of laryngeal muscles.
Driving Cessation in Patients Attending a Young-Onset Dementia Clinic: A Retrospective Cohort Study
Authors: Velayudhan Latha , Baillon Sarah , Urbaskova Gabriela , McCulloch Laura  , Tromans Samuel  , Storey Mathew  , Lindesay James , Bhattacharyya Sagnik
Published: April 2018

Background: Although driving by persons with dementia is an important public health concern, little is known about driving cessation in younger people with dementia. We aimed to determine the prevalence and factors affecting driving cessation in individuals with and without dementia aged under 65 years attending a memory clinic in a European setting. Methods: Subjects were consecutive patients assessed at a specialist memory service at a university teaching hospital between 2000 and 2010. The data collected included demographic, clinical, standardized cognitive assessments as well as information on driving. Dementia diagnosis was made using ICD-10 criteria. Results: Of the 225 people who were or had been drivers, 32/79 (41%) with young-onset dementia (YOD) stopped driving compared to 25/146 (17%) patients who had cognitive impairment due to other causes. Women were more likely to cease driving and voluntarily than men (p < 0.001). Diagnosis of YOD was associated with driving cessation (1.193, 95% CI 0.570–1.815, p ≤ 0.001), and was mediated by impairment in praxis with the highest indirect mediation effect (0.754, 95% CI 0.183–1.401, p = 0.009). Conclusions: YOD diagnosis, female gender, and impairment in praxis have a higher probability for driving cessation in those under 65 years of age with cognitive impairment.
The Influence of Reactive Oxygen Species and Glucocorticoids on Dry Skin in a Mouse Model of Arthritis
Authors: Goto Kenji , Hiramoto Keiichi , Kawakita Mayu , Yamaoka Miyu , Ooi Kazuya
Published: April 2018

Background: Dry skin induced by rheumatoid arthritis (RA) causes itching, which negatively influences a patient’s quality of life. We previously reported that mast cells are related to dry skin in arthritic mice. However, the mechanism of mast cell activation is unclear. In this study, we examined the mechanism underlying the formation of dry skin induced by mast cells in arthritis that involves thymic stromal lymphopoietin (TSLP), neutrophils, reactive oxygen species (ROS), and glucocorticoids. Methods: Mice with DBA/1JJmsSlc collagen-induced arthritis were treated with inhibitors or neutralizing antibodies. We measured transepidermal water loss (TEWL) to examine the modulating signal of mast cells. Results: TEWL, the number of mast cells, and the plasma levels of TSLP, ROS, and corticosterone in the arthritic mice were increased when compared with the control mice. However, the mice treated with TSLP- and neutrophil-neutralizing antibodies and ROS and glucocorticoid receptor inhibitors (N-acetyl-L-cysteine [NAC] and RU-486, respectively) experienced an improvement. The ameliorating effect was most remarkable following treatment with NAC + RU-486. Conclusion: This study suggested that inhibiting ROS and glucocorticoids is important to ameliorate dry skin in arthritis, which may provide a novel treatment option for dry skin in RA patients.
Efficacy and Safety of MLC601 in Patients with Mild to Moderate Alzheimer Disease: An Extension 4-Year Follow-Up Study
Authors: Pakdaman Hossein , Gharagozli Koroush , Abbasi Mehdi , Sobhanian Ali , Bakhshandehpour Ali , Ashrafi Farzad , Khalilzad Mitra , Amini Harandi Ali
Published: April 2018

Background and Aim: Alzheimer disease (AD) is the most common cause of dementia. Currently, there is no disease-modifying therapy for AD. We aimed to evaluate the long-term efficacy and safety of MLC601 in the treatment of AD. Methods: In this open-label extension study, patients with mild to moderate AD according to DSM-IV criteria were recruited. Patients received MLC601 capsules 3 times a day for 4 years. Cognitive function was assessed every 6 months using Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores. Safety profiles, including adverse events (AEs), and treatment-related abnormality in laboratory tests were also reported. Results: Of a total of 122 patients, 105 completed the study. The mean age was 66.8 ± 6.3 years at the beginning of the study. Sixty-five (61.9%) were female. The mean (±SD) change in MMSE and ADAS-Cog scores at the end of the study was 2.1 (±3.8) and –5.1 (±8.7), respectively. Repeated measure analysis revealed a statistically significant change in both scores (p < 0.001). No patient left the study due to an AE. No abnormality was noted in lab tests. Gastrointestinal symptoms were the most commonly reported AEs. Conclusion: The efficacy of treating AD patients with MLC601 over 4 years has been demonstrated in the present study. Overall, it seems that the safety and efficacy of MLC601 is promising compared to currently prescribed treatments.
Impact of Serum Vancomycin Trough Levels in the Treatment of Central Nervous System Shunt Infections Caused by Coagulase-Negative Staphylococci
Authors: Gibson Ashley , Kaplan Sheldon L. , Vallejo Jesus G.
Published: April 2018

Coagulase-negative staphylococci (CoNS) are a common cause of pediatric ventricular shunt infections. The Infectious Diseases Society of America recommends vancomycin serum troughs of 15–20 µg/mL when treating CoNS shunt infections in adult patients. We report a series of pediatric cases of CoNS shunt infections in which clinical cure was obtained with troughs < 15 µg/mL. These findings question the relevance of this recommendation in pediatric patients.