bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of the Dynamically Linked Indices of Fosfomycin for Pseudomonas aeruginosa in the Hollow Fiber Infection Model
Authors: Louie Arnold , Maynard Michael , Duncanson Brandon , Nole Jocelyn , Vicchiarelli Michael , Drusano G. L.
Published: March 2018

Fosfomycin is the only expoxide antimicrobial and is currently under development in the United States as an intravenously administered product. We were interested in identifying the exposure indices most closely linked to its ability to kill bacterial cells and to suppress amplification of less susceptible subpopulations. We employed the hollow fiber infection model for this investigation and studied wild-type strain
Pseudomonas aeruginosa
PAO1. Because of anticipated rapid resistance emergence, we shortened the study duration to 24 h but sampled the system more intensively. Doses of 12 and 18 g/day and schedules of daily administration, administration every 8 h, and administration by continuous infusion for each daily dose were studied. We measured fosfomycin concentrations (by liquid chromatography-tandem mass spectrometry), the total bacterial burden, and the burden of less susceptible isolates. We applied a mathematical model to all the data simultaneously. There was a rapid emergence of resistance with all doses and schedules. Prior to resistance emergence, an initial kill of 2 to 3 log
10
(CFU/ml) was observed. The model demonstrated that the area under the concentration-time curve/MIC ratio was linked to total bacterial kill, while the time that the concentration remained above the MIC (or, equivalently, the minimum concentration/MIC ratio) was linked to resistance suppression. These findings were also seen in other investigations with
Enterobacteriaceae
(
in vitro
systems) and
P. aeruginosa
(murine system). We conclude that for serious infections with high bacterial burdens, fosfomycin may be of value as a new therapeutic and may be optimized by administering the agent as a continuous or prolonged infusion or by use of a short dosing interval. For indications such as ventilator-associated bacterial pneumonia, it may be prudent to administer fosfomycin as part of a combination regimen.
New Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A Streptococcal Infection
Authors: Ong Cheryl-lynn Y. , Berking Olga , Walker Mark J. , McEwan Alastair G.
Published: March 2018

Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation (“nutritional immunity”) to combat infections. Here, we investigate the role of zinc import and export in the protection of
Streptococcus pyogenes
(group A
Streptococcus
; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defense. In order to determine the role of GAS zinc import and export during infection, we utilized zinc import (Δ
adcA
Δ
adcAII
) and export (Δ
czcD
) deletion mutants in competition with the wild type in both
in vitro
and
in vivo
virulence models. We demonstrate that nutritional immunity is deployed extracellularly, while zinc toxicity is utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and azurophilic granules in neutrophils contain zinc stores for use against intracellular pathogens.
Effects of supplementation with carnosine and other histidine-containing dipeptides on chronic disease risk factors and outcomes: protocol for a systematic review of randomised controlled trials
Authors: Menon Kirthi , Mousa Aya , de Courten Barbora
Published: March 2018

Introduction

Ageing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors that contribute to these diseases is key in managing the global burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide with anti-inflammatory, antioxidative and antiglycating properties may have a role in the prevention of chronic diseases; however, no previous reviews have examined the effects of carnosine and other histidine-containing peptides (HCDs) on chronic disease risk factors and outcomes. We aim to conduct a comprehensive systematic review to examine the effects of supplementation with carnosine and other HCDs on chronic disease risk factors and outcomes and to identify relevant knowledge gaps.

Methods and analysis

Electronic databases including Medline, Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based Medicine will be systematically searched to identify randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing supplementation with carnosine and/or other HCDs versus placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will screen titles and abstracts for eligibility according to prespecified inclusion criteria, after which two independent reviewers will perform data extraction and quality appraisal. Meta-analyses, metaregression and subgroup analyses will be conducted where appropriate.

Ethics and dissemination

Ethics approval is not required as this review does not involve primary data collection. This review will generate level-one evidence regarding the effects of carnosine supplementation on chronic disease risk factors and outcomes and will be disseminated through peer-reviewed publications and at conference meetings to inform future research on the efficacy of carnosine supplementation for the prevention of chronic diseases.

PROSPERO registration number

CRD42017075354.
Modulation of hepatic gene expression profiles by vitamin B1, vitamin B2, and niacin supplementation in mice exposed to acute hypoxia
Authors: Liu Jin , Gao Weina , Pu Lingling , Wei Jingyu , Xin Zhonghao , Wang Yawen , Shi Tala , Guo Changjiang
Published: March 2018

This study was aimed to observe the effects of vitamin B1, vitamin B2, and niacin supplementation on hepatic gene expression profiles in mice exposed to acute hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute hypoxia plus vitamin B1, vitamin B2, and niacin supplementation groups and fed corresponding diets for 2 weeks and then exposed to a simulated altitude of 6000 m for 8 h. Hepatic gene expression profiles were analyzed using a microarray technique. Several biochemical markers were also assayed. The results showed that a total of 2476 genes were expressed differentially after acute hypoxia exposure (1508 upregulated genes and 968 downregulated genes). Compared with the acute hypoxia group, there were 1382 genes differentially expressed (626 upregulated genes and 756 downregulated genes) in the acute hypoxia plus vitamin B1, vitamin B2, and niacin supplementation group. Pathway analysis indicated that carbohydrate, lipid, and amino acid metabolism, as well as electron transfer chain, were improved to some extent after vitamin B1, vitamin B2, and niacin supplementation. Supportive results were obtained from biochemical assays. Our findings suggest that the supplementation of vitamin B1, vitamin B2, and niacin is beneficial in improving nutritional metabolism partly via gene expression under acute hypoxia condition.
Fractional Order Spatiotemporal Chaos with Delay in Spatial Nonlinear Coupling
Authors: Zhang Yingqian , Wang Xingyuan , Liu Liyan , Liu Jia
Published: March 2018

We investigate the spatiotemporal dynamics with fractional order differential logistic map with delay under nonlinear chaotic maps for spatial coupling connections. Here, the coupling methods between lattices are the nonlinear chaotic map coupling of lattices. The fractional order differential logistic map with delay breaks the limits of the range of parameter [Formula: see text] in the classical logistic map for chaotic states. The Kolmogorov–Sinai entropy density and universality, and bifurcation diagrams are employed to investigate the chaotic behaviors of the proposed model in this paper. The proposed model can also be applied for cryptography, which is verified in a color image encryption scheme in this paper.
Experimental and Theoretical Investigations of a Mechanical Lever System Driven by a DC Motor
Authors: Nana B. , Fautso Kuiate G. , Yamgoué S. B.
Published: March 2018

This paper presents theoretical and experimental results on the investigation of the dynamics of a nonlinear electromechanical system made of a lever arm actuated by a DC motor and controlled through a repulsive magnetic force. We use the method of harmonic balance to derive oscillatory solutions. Theoretical tools such as, bifurcation diagrams, Lyapunov exponents, phase portraits, are used to unveil the rich nonlinear behavior of the system including chaos and hysteresis. The experimental results are in close accordance with the theoretical predictions.
Existence of Homoclinic Cycles and Periodic Orbits in a Class of Three-Dimensional Piecewise Affine Systems
Authors: Wang Lei , Yang Xiao-Song
Published: March 2018

For a class of three-dimensional piecewise affine systems, this paper focuses on the existence of homoclinic cycles and the phenomena of homoclinic bifurcation leading to periodic orbits. Based on the spatial location relation between the invariant manifolds of subsystems and the switching manifold, a concise necessary and sufficient condition for the existence of homoclinic cycles is obtained. Then the homoclinic bifurcation is studied and the sufficient conditions for the birth of a periodic orbit are obtained. Furthermore, the sufficient conditions are obtained for the periodic orbit to be a sink, a source or a saddle. As illustrations, several concrete examples are presented.
Mean Proximality, Mean Sensitivity and Mean Li–Yorke Chaos for Amenable Group Actions
Authors: Yan Kesong , Zeng Fanping
Published: March 2018

We consider mean proximality and mean Li–Yorke chaos for [Formula: see text]-systems, where [Formula: see text] is a countable discrete infinite amenable group. We prove that if a countable discrete infinite abelian group action is mean sensitive and there is a mean proximal pair consisting of a transitive point and a periodic point, then it is mean Li–Yorke chaotic. Moreover, we give some characterizations of mean proximal systems for general countable discrete infinite amenable groups.
Bifurcation Analysis and Spatiotemporal Patterns in Unidirectionally Delay-Coupled Vibratory Gyroscopes
Authors: Li Li , Xu Jian
Published: March 2018

Time delay is inevitable in unidirectionally coupled drive-free vibratory gyroscope system. The effect of time delay on the gyroscope system is studied in this paper. To this end, amplitude death and Hopf bifurcation induced by small time delay are first investigated by analyzing the related characteristic equation. Then, the direction of Hopf bifurcations and stability of Hopf-bifurcating periodic oscillations are determined by calculating the normal form on the center manifold. Next, spatiotemporal patterns of these Hopf-bifurcating periodic oscillations are analyzed by using the symmetric bifurcation theory of delay differential equations. Finally, it is found that numerical simulations agree with the associated analytic results. These phenomena could be induced although time delay is very small. Therefore, it is shown that time delay is an important factor which influences the sensitivity and accuracy of the gyroscope system and cannot be neglected during the design and manufacture.
OVERVIEW OF THE EMF 32 STUDY ON U.S. CARBON TAX SCENARIOS
Authors: MCFARLAND JAMES R. , FAWCETT ALLEN A. , MORRIS ADELE C. , REILLY JOHN M. , WILCOXEN PETER J.
Published: March 2018

The Energy Modeling Forum (EMF) 32 study on carbon tax scenarios analyzed a set of illustrative policies in the United States that place an economy-wide tax on fossil-fuel-related carbon dioxide (CO[Formula: see text] emissions, a carbon tax for short. Eleven modeling teams ran these stylized scenarios, which vary by the initial carbon tax rate, the rate at which the tax escalates over time, and the use of the revenues. Modelers reported their results for the effects of the policies, relative to a reference scenario that does not include a carbon tax, on emissions, economic activity, and outcomes within the U.S. energy system. This paper explains the scenario design, presents an overview of the results, and compares results from the participating models. In particular, we compare various outcomes across the models, such as emissions, revenue, gross domestic product, sectoral impacts, and welfare.
POLICY INSIGHTS FROM THE EMF 32 STUDY ON U.S. CARBON TAX SCENARIOS
Authors: BARRON ALEXANDER R. , FAWCETT ALLEN A. , HAFSTEAD MARC A. C. , MCFARLAND JAMES R. , MORRIS ADELE C.
Published: March 2018

The Stanford Energy Modeling Forum exercise 32 (EMF 32) used 11 different models to assess emissions, energy, and economic outcomes from a plausible range of economy-wide carbon price policies to reduce carbon dioxide (CO[Formula: see text] emissions in the United States. Here we discuss the most policy-relevant results of the study, mindful of the strengths and weaknesses of current models. Across all models, carbon prices lead to significant reductions in CO2 emissions and conventional pollutants, with the vast majority of the reductions occurring in the electricity sector. Importantly, emissions reductions do not significantly depend on the rebate or tax cut used to return revenues to the economy. Expected economic costs, as modeled by either GDP or welfare, are modest, but vary across models. These costs are offset by benefits from avoided climate damages and health benefits from reductions in conventional air pollution. Using revenues to reduce preexisting capital or labor taxes reduces costs in most models relative to lump-sum rebates, but the size of the cost reductions varies significantly. Devoting at least some revenue to household rebates can significantly reduce adverse impacts on low income households. Carbon prices at $25/ton or even lower levels cause significant shifts away from coal as an energy source with responses of other energy sources highly dependent upon technology cost assumptions. Beyond 2030, we conclude that model uncertainties are too large to make quantitative results useful for near-term policy design. We close by describing recommendations for policymakers on interacting with model results in the future.
Paleozoic gas potential in the Weald Basin of southern England
Authors: Pullan Christopher P. , Butler Malcolm
Published: March 2018

Gas has been found in Mesozoic reservoirs in the Weald Basin, particularly along the northern margin. Most of the gas is dry, with a high methane content and often associated nitrogen. Isotopic evidence indicates that the gas is from a thermogenically mature marine source. Although there is evidence of some shallow, biogenic gas, only the lowermost Lias is projected to have reached the thermogenic gas window before Tertiary uplift. Estimated maturities from isotopic data from the main gas accumulations indicate significantly greater levels than those projected for Liassic shales: thus, the gas is thought to have originated from Paleozoic rocks.

Data on the distribution of Paleozoic rocks subcropping the Variscan unconformity is limited. However, available data suggest that their distribution owes more to Acadian erosion than to Variscan. It is thought that the Upper Devonian and Lower Carboniferous transgressed over a thick, folded Tremadocian shale sequence in the west, and over folded Silurian and Lower–Middle Devonian rocks in the central Weald. There is some evidence for the presence of isolated late Carboniferous or early Permian clastics but no significant coals have been encountered to date. Regional source studies suggest that the only Paleozoic rocks with potential are post-Acadian-aged Devonian shales.
Controlling the number of active instances in a cloud environment
Authors: Goldsztajn Diego , Ferragut Andres , Paganini Fernando , Jonckheere Matthieu
Published: March 2018

We study a cloud environment in which computing instances may either be reserved in advance, or dynamically spawned to serve a fluctuating or unknown load. We first consider a centralized scheme where a system operator maintains the job queue and controls the spawning of additional capacity; through queueing models and their fluid and diffusion counterparts we explore the tradeoff between queueing delay and the service capacity variability. Secondly, we consider the setting of a dispatcher who must immediately send jobs, with no delay, to decentralized instances, and in addition may summon extra capacity. Here the capacity scaling problem couples with one of load balancing. We show how the popular join-the-idle-queue policy can be combined with an adequate rule for spawning instances, yielding an equilibrium with no queuing delay and controlling service capacity variability; we accommodate as well the case where spawned instances incur startup delay. Finally, we analyze the question of deciding, for a given pricing structure for the cloud service, how many fixed instances should be reserved in advance. The behavior of these policies is illustrated by simulations.
Parsimonious Tomography
Authors: Tootaghaj Diman Zad , He Ting , La Porta Thomas
Published: March 2018

Network tomography using end-to-end probes provides a powerful tool for monitoring the performance of internal network elements. However, active probing can generate tremendous traffic, which degrades the overall network performance. Meanwhile, not all the probing paths contain useful information for identifying the link metrics of interest. This observation motivates us to study the optimal selection of monitoring paths to balance identifiability and probing cost. Assuming additive link metrics (e.g., delays), we consider four closely-related optimization problems: 1) Max-ILCost that maximizes the number of identifiable links under a probing budget, 2) Max-Rank-Cost that maximizes the rank of selected paths under a probing budget, 3) Min-Cost-IL that minimizes the probing cost while preserving identifiability, and 4) Min-Cost-Rank that minimizes the probing cost while preserving rank. While (1) and (3) are hard to solve, (2) and (4) are easy to solve, and the solutions give a good approximation for (1) and (3). Specifically, we provide an optimal algorithm for (4) and a (1?1/e)-approximation algorithm for (2). We prove that the solution for (4) provides tight upper/lower bounds on the minimum cost of (3), and the solution for (2) provides upper/lower bounds on the maximum identifiability of (1). Our evaluations on real topologies show that solutions to the rank-based optimization (2, 4) have superior performance in terms of the objectives of the identifiability-based optimization (1, 3), and our solutions can reduce the total probing cost by an order of magnitude while achieving the same monitoring performance.
A Statistical Property of Wireless Channel Capacity: Theory and Application
Authors: Sun Fengyou , Jiang Yuming
Published: March 2018

This paper presents a set of new results on wireless channel capacity by exploring its special characteristics. An appealing discovery is that the instantaneous and cumulative capacity distributions of typical fading channels are lighttailed. An implication of this property is that these distributions and subsequently the distributions of delay and backlog for constant arrivals can be upper-bounded by some exponential functions, which is often assumed but not justified in the literature of wireless network performance analysis. In addition, three representative dependence structures of the capacity process are studied, namely comonotonicity, independence, and Markovian, and bounds are derived for the cumulative capacity distribution and delay-constrained capacity. To help gain insights in the performance of a wireless channel whose capacity process may be too complex or detailed dependence information is lacking, stochastic orders are introduced to the capacity process, based on which, comparison results of delay and delay-constrained capacity are obtained. Moreover, the impact of self-interference in communication, which is an open problem in stochastic network calculus (SNC), is investigated and original results are derived. These results complement the SNC literature, easing its application to wireless networks and its extension towards a calculus for wireless networks.
Management Strategies for Industrial Laboratories with Knowledge Memory
Authors: Mitra Debasis , Wang Qiong
Published: March 2018

We present a simplified abstraction of an industrial laboratory consisting of a two-stage network, Research (R) and Development (D). Ideas and prototypes are incubated in the R stage, the projects departing this stage are assessed, and, if favorable, the project proceeds to the D stage. Revenue is generated from the sale of products/solutions that are outputs of the D stage, and the sale and licensing of patents that are generated at both stages. In our discrete time model, in each time period the managers of the industrial laboratory are given a constant amount of money to invest in the two stages. The investments determine the capacities of the stages based on linear unit costs. A novel feature of the model is "knowledge stocks" for the stages, which represent the accumulated know-how from practicing research and development activities; higher knowledge stock implies lower cost. The memory in knowledge stocks makes current investment decisions have long term impact on costs and profits. Three strategies for profit maximization are investigated. In myopic profit maximization we show the existence of multiple equilibria and the phenomenon of state entrapment in suboptimal regimes, which are absent in the other strategies. Numerical results illustrate the main features of the model.
The second conference
Authors: Abramov Sergei A. , Ryabenko Anna A. , Sadykov Timur M.
Published: March 2018

The second International conference is organized jointly by Dorodnicyn Computing Center of Federal Research Center "Computer Science and Control" of RAS and Plekhanov Russian University of Economics with a support of the Russian Foundation for Basic Research (project 17-01-20398 17). The first edition of the event [1] (http://www.ccas.ru/ca/conference2016) was held in 2016 at the Dorodnicyn Computing Center in cooperation with Russian University of Friendship of Peoples.

The conference website: http://www.ccas.ru/ca/conference.
Factors Affecting the Presence of Adequately Iodized Salt at Home in Wolaita, Southern Ethiopia: Community Based Study
Authors: Kumma Wondimagegn Paulos , Haji Yusuf , Abdurahmen Junayde , Mehretie Adinew Yohannes
Published: March 2018

Background. Universal use of iodized salt is a simple and inexpensive method to prevent and eliminate iodine deficiency disorders like mental retardation. However, little is known about the level of adequately iodized salt consumption in the study area. Therefore, the study was aimed at assessing the proportion of households having adequately iodized salt and associated factors in Wolaita Sodo town and its peripheries, Southern Ethiopia. Methods. A cross-sectional study was conducted from May 10 to 20, 2016, in 441 households in Sodo town and its peripheries. Samples were selected using the systematic sampling technique. An iodometric titration method (AOAC, 2000) was used to analyze the iodine content of the salt samples. Data entry and analysis were done using Epi Info version 3.5.1 and SPSS version 16, respectively. Result. The female to male ratio of the respondents was 219. The mean age of the respondents was 30.2 (±7.3 SD). The proportion of households having adequately iodized salt was 37.7%, with 95% CI of 33.2% to 42.2%. Not exposing salt to sunlight with [OR: 3.75; 95% CI: 2.14, 6.57], higher monthly income [OR: 3.71; 95% CI: 1.97–7.01], and formal education of respondents with [OR: 1.75; 95% CI: 1.14, 2.70] were found associated with the presence of adequately iodized salt at home. Conclusion. This study revealed low levels of households having adequately iodized salt in Wolaita Sodo town and its peripheries. The evidence here shows that there is a need to increase the supply of adequately iodized salt to meet the goal for monitoring progress towards sustainable elimination of IDD.
Sum Rate Maximization of D2D Communications in Cognitive Radio Network Using Cheating Strategy
Authors: Sun Yanjing , Cao Qi , Wang Bowen , Li Song
Published: March 2018

This paper focuses on the cheating algorithm for device‐to‐device (D2D) pairs that reuse the uplink channels of cellular users. We are concerned about the way how D2D pairs are matched with cellular users (CUs) to maximize their sum rate. In contrast with Munkres’ algorithm which gives the optimal matching in terms of the maximum throughput, Gale‐Shapley algorithm ensures the stability of the system on the same time and achieves a men‐optimal stable matching. In our system, D2D pairs play the role of “men,” so that each D2D pair could be matched to the CU that ranks as high as possible in the D2D pair’s preference list. It is found by previous studies that, by unilaterally falsifying preference lists in a particular way, some men can get better partners, while no men get worse off. We utilize this theory to exploit the best cheating strategy for D2D pairs. We find out that to acquire such a cheating strategy, we need to seek as many and as large cabals as possible. To this end, we develop a cabal finding algorithm named RHSTLC, and also we prove that it reaches the Pareto optimality. In comparison with other algorithms proposed by related works, the results show that our algorithm can considerably improve the sum rate of D2D pairs.
Research on Artificial Spider Web Model for Farmland Wireless Sensor Network
Authors: Wang Jun , Gao Song , Zhao Shimin , Hu Guang , Zhang Xiaoli , Xie Guowang
Published: March 2018

Through systematic analysis of the structural characteristics and invulnerability of spider web, this paper explores the possibility of combining the advantages of spider web such as network robustness and invulnerability with farmland wireless sensor network. A universally applicable definition and mathematical model of artificial spider web structure are established. The comparison between artificial spider web and traditional networks is discussed in detail. The simulation result shows that the networking structure of artificial spider web is better than that of traditional networks in terms of improving the overall reliability and invulnerability of communication system. A comprehensive study on the advantage characteristics of spider web has important theoretical and practical significance for promoting the invulnerability research of farmland wireless sensor network.
Nasal Septal Perforation in Propylthiouracil-Induced Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Authors: Ishii Yusho , Shirai Tsuyoshi , Hoshi Yousuke , Fujita Yoko , Shirota Yuko , Fujii Hiroshi , Ishii Tomonori , Harigae Hideo
Published: March 2018

Here, we present the case of a 29-year-old woman with nasal septal perforation and positive myeloperoxidase- (MPO-) anti-neutrophil cytoplasmic antibody (ANCA). She had been diagnosed with Graves’ disease and had been treated with propylthiouracil (PTU) for 14 months. A biopsy of the nasal septum revealed an infiltration of inflammatory cells, with no evidence of malignancy or granulomatous change. Because of the use of PTU, destructive nasal lesion, and positive MPO-ANCA, she was diagnosed with drug-induced ANCA-associated vasculitis (AAV) and was treated with prednisolone and methotrexate after the cessation of PTU. Although PTU is known to be the medicine that induces drug-induced AAV, the manifestation of nasal septal perforation in drug-induced AAV is poorly identified. This is the rare case of drug-induced AAV which manifested only nasal septal perforation.
Targeting Brain-Adaptive Cancer Stem Cells Prohibits Brain Metastatic Colonization of Triple-Negative Breast Cancer
Authors: Ren Ding , Zhu Xiaoping , Kong Ren , Zhao Zhen , Sheng Jianting , Wang Jiang , Xu Xiaoyun , Liu Jiyong , Cui Kemi , Zhang Xiang H.-F. , Zhao Hong , Wong Stephen T.C.
Published: March 2018

Triple-negative breast cancer (TNBC) exhibits more traits possessed by cancer stem cells (CSC) than other breast cancer subtypes and is more likely to develop brain metastases. TNBC patients usually have shorter survival time after diagnosis of brain metastasis, suggesting an innate ability of TNBC tumor cells in adapting to the brain. In this study, we establish novel animal models to investigate early tumor adaptation in brain metastases by introducing both patient-derived and cell line–derived CSC-enriched brain metastasis tumorsphere cells into mice. We discovered astrocyte-involved tumor activation of protocadherin 7 (PCDH7)-PLCβ-Ca2+-CaMKII/S100A4 signaling as a mediator of brain metastatic tumor outgrowth. We further identified and evaluated the efficacy of a known drug, the selective PLC inhibitor edelfosine, in suppressing the PCDH7 signaling pathway to prohibit brain metastases in the animal models. The results of this study reveal a novel signaling pathway for brain metastases in TNBC and indicate a promising strategy of metastatic breast cancer prevention and treatment by targeting organ-adaptive cancer stem cells.

Significance: These findings identify a compound to block adaptive signaling between cancer stem cells and brain astrocytes. Cancer Res; 78(8); 2052–64. ©2018 AACR.
The Influence of Cognitive Bias on Caries Lesion Detection in Preschool Children
Authors: Moro Bruna L.P. , Novaes Tatiane F. , Pontes Laura R.A. , Gimenez Thais , Lara Juan S. , Raggio Daniela P. , Braga Mariana M. , Mendes Fausto M.
Published: March 2018

We aimed to evaluate whether children’s caries experience exerts an influence on the performance of visual and radiographic methods in detecting nonevident proximal caries lesions in primary molars. Eighty children (3–6 years old) were selected and classified as having a lower (≤3 decayed, missing, or filled surfaces; dmf-s) or higher (> 3 dmf-s) caries experience. Two calibrated examiners then assessed 526 proximal surfaces for caries lesions using visual and radiographic methods. As a reference standard, 2 other examiners checked the surfaces after temporary separation. Noncavitated and cavitated lesion thresholds were considered and Poisson multilevel regression analyses were conducted to evaluate the influence of caries experience on the performance of diagnostic strategies. Accuracy parameters stratified by caries experience were also derived. A statistically significant influence of caries experience was observed only for visual inspection, with more false-positive results in children with a higher caries experience at the noncavitated lesion threshold, and more false results at the cavitated threshold. The detection of noncavitated caries lesions in children with a higher caries experience was overestimated (specificity = 0.696), compared to children with a lower caries experience (specificity = 0.918), probably due to confirmation bias. However, the examiners underestimated the detection of cavitated lesions in children with a higher caries experience (sensitivity = 0.143) compared to lower-caries-experience children (sensitivity = 0.222), possibly because of representativeness bias. The radiographic method was not influenced by children’s caries experience. In conclusion, children’s caries experience influences the performance of visual inspection in detecting proximal caries lesions in primary teeth, evidencing the occurrence of cognitive biases.
A Randomized Controlled Trial in Routine Clinical Practice Comparing Acceptance and Commitment Therapy with Cognitive Behavioral Therapy for the Treatment of Major Depressive Disorder
Authors: A-Tjak Jacqueline G.L. , Morina Nexhmedin , Topper Maurice , Emmelkamp Paul M.G.
Published: March 2018

Background: Since current therapies for depression are effective but not for all patients alike, we need to further improve available treatments. Existing research suggests that acceptance and commitment therapy (ACT) may effectively treat major depressive disorder (MDD). We compared ACT with cognitive behavioral therapy (CBT) for depression, testing the hypothesis that CBT would outperform ACT. Methods: We conducted a randomized controlled trial with 82 patients suffering from MDD. Data were collected before and after treatment and at the 6-month follow-up, assessing diagnosis, symptom levels of depression, and quality of life. Results: After treatment, the rates of remission from depression were 75 and 80% for the ACT and CBT conditions, respectively. Patients in both conditions further reported significant and large reductions in depressive symptoms and improvement in quality of life from before to after treatment as well as at the follow-up. Our findings indicated no significant differences between the two intervention groups. Conclusion: Our results indicate that CBT is not more effective in treating depression than ACT. Further research is needed to investigate whether ACT and CBT work differently for different groups of patients with depression.
The Trend of β3-Adrenergic Receptor in the Development of Septic Myocardial Depression: A Lipopolysaccharide-Induced Rat Septic Shock Model
Authors: Yang Ni , Shi Xiao-Lu  , Zhang Bing-Lun  , Rong Jian  , Zhang Tie-Ning , Xu Wei , Liu Chun-Feng
Published: March 2018

Septic shock with low cardiac output is very common in children. However, the mechanism underlying myocardial depression is unclear. The role of β3-AR in the development of myocardial depression in sepsis is unknown. In the present study, we generated an adolescent rat model of hypodynamic septic shock induced by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS to mimic myocardial depression in sepsis, which was confirmed via an in vivo left ventricular hemodynamic study, and measurements of contractility and the Ca2+ transient in isolated adolescent and neonatal cardiomyocytes. After 16 h of LPS treatment, cultured neonatal cardiomyocytes showed a diminished Ca2+ transient amplitude associated with an increase in the β3-AR level. With the addition of a β3-AR agonist, the Ca2+ transient in LPS-treated neonatal rat cardiomyocytes gradually decreased over time; such a change was absent in cells treated with nitric oxide synthase (NOS) inhibitors prior to treatment with a β3-AR agonist. In adolescent rats with septic myocardial depression, cardiac function declined as indicated by decreased MAP, dP/dtmax, and dP/dtmix for 6 h after LPS injection; however, the β3-AR level first increased 2 h after LPS treatment and then decreased 6 h after LPS treatment in the absence of exogenous catecholamines. The results indicate that, in vitro, at the cellular level β3-AR may be involved in the development of myocardial depression (Ca2+ transient depression) in sepsis through NOS signaling pathways; however, in vivo, a complicated mechanism for modulating β3-AR may exist.
Dermoscopic Features of Basal Cell Carcinoma on the Lower Limbs: A Chameleon!
Authors: Lombardi Mara , Pampena Riccardo , Borsari Stefania , Bombonato Caterina , Benati Elisa , Pellacani Giovanni , Longo Caterina
Published: March 2018

Background: Lower limbs represent an uncommon location for basal cell carcinoma (BCC) and only few reports have described dermoscopic features of BCC in this body site. Since BCCs of the lower limbs frequently display nonclassic BCC dermoscopic criteria, they can simulate other benign or malignant lesions. Objective: Our aim was to describe the dermoscopic features of BCC located on lower limbs and to define which criteria were more associated with their benign- or malignant-looking appearance. Methods: We conducted a retrospective study enrolling consecutive patients with histologically confirmed BCCs of the lower limbs. Lesions were classified in 7 categories according to the clinical and dermoscopic global appearance. Clear BCC, squamous cell carcinoma (SCC) or Bowen disease-like, Kaposi disease-like, melanoma-like, and aspecific pattern were considered malignant-looking lesions; however, seborrheic keratosis-like and dermatofibroma-like were considered benign-looking. To define which dermoscopic criteria were independently associated with benign- or malignant-looking appearance, we conducted a multivariate logistic regression analysis. Results: A total of 81 BCCs were enrolled: 18 (22%) were benign-looking lesions (of which 11 were seborrheic keratosis-like and 7 dermatofibroma-like) and 63 (78%) were malignant-looking BCCs (of which 24 were clear-cut BCCs, 23 SCC-like, 2 Kaposi disease-like, 9 melanoma-like, and 5 had aspecific pattern). Multivariate regression analysis showed that erosions/ulceration and vessels were independently associated with malignant-looking appearance. The most represented vessels were glomerular and polymorphic, which are more frequently encountered in SCC, together with ulceration. Conclusion: BCC of the lower legs frequently simulates other benign or malignant lesions, with SCC being the main differential diagnosis.
A Comprehensive Assessment of the Role of miRNAs as Biomarkers in Gastroenteropancreatic Neuroendocrine Tumors
Authors: Malczewska Anna , Kidd Mark , Matar Somer , Kos-Kudla Beata , Modlin Irvin M.
Published: March 2018

Background/Aims: A key issue in neuroendocrine neoplasia management is the identification of blood signatures that specifically define the activity of a cancer or local tumor microenvironment. MicroRNAs (miRNAs) may represent such a candidate. To evaluate their clinical utility as biomarkers in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we assessed their expression in tissue and blood. Methods: A systematic review of PubMed was undertaken to identify studies investigating miRNAs in GEP-NETs and their utility as blood or tissue biomarkers. Results: Twenty-two studies using a range of methodologies with different normalization protocols were identified: tumor – gastric NET type 1 (n = 1 study: MiR-222, regulates p27KIP1), pancreatic (n = 6: MiR-21 [inflammatory marker, oncogene] and MiR-144 [PI3K/AKT signaling], both up- and downregulated depending on the method), small intestinal (n = 7: no consistent signature), and colorectal (n = 3: no consistent signature); blood – gastric NET type 1 (n = 1: MiR-222), pancreatic (n = 3: MiR-21), and small intestinal (n = 3: no consistent signature). The studies all included heterogeneous cohorts, were insufficiently powered, and utilized different methodologies, and age- and gender-matched controls were not used. Different miRNA isolation methods and detection protocols resulted in inconsistent expression comparing tumor and blood. A scientific discrepancy was the downregulated expression of some circulating candidates compared to tissue levels, suggesting methodological issues or physiological responses to the tumor. Both are of concern in defining the biometrics of a marker. Conclusions: A potential biomarker for GEP-NETs included MiR-21 (small bowel and pancreas), but this epithelial tumor marker requires prospective validation. Overall, significant scientific investigation remains to identify and demonstrate neuroendocrine specificity and to validate candidate miRNA biomarkers.
Apabetalone Mediated Epigenetic Modulation is Associated with Favorable Kidney Function and Alkaline Phosphatase Profile in Patients with Chronic Kidney Disease
Authors: Kulikowski Ewelina , Halliday Christopher , Johansson Jan , Sweeney Mike , Lebioda Kenneth , Wong Norman , Haarhaus Mathias , Brandenburg Vincent , Beddhu Srinivasan , Tonelli Marcello , Zoccali Carmine , Kalantar-Zadeh Kamyar
Published: March 2018

Background/Aims: The association between serum alkaline phosphatase (ALP) with adverse cardiovascular outcomes, in Chronic Kidney Disease (CKD) patients has previously been reported and may be a result of increased vascular calcification and inflammation. Here we report, for the first time, the effects of pharmacologic epigenetic modulation on levels of ALP and kidney function via a novel oral small molecule BET inhibitor, apabetalone, in CKD patients. Methods: A post-hoc analysis evaluated patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2, who participated in the apabetalone phase 2 randomized controlled trials (SUSTAIN and ASSURE). 48 CKD subjects with a history of cardiovascular disease (CVD) were treated with 100mg twice-daily of 24 and 26 weeks of apabetalone or placebo. ALP and eGFR were measured prior to randomization and at final visits. Results: Patients who received apabetalone (n=35) versus placebo (n=13) over 6 months showed significantly (p=0.02) lowered serum ALP -14.0% (p<0.0001 versus baseline) versus -6.3% (p=0.9 versus baseline). The eGFR in the apabetalone group increased by 3.4% (1.7 mL/min/1.73 m2) (p=0.04 versus baseline) and decreased by 5.8% (2.9 mL/min/1.73 m2) (p=0.6 versus baseline) in the placebo group. Apabetalone was well tolerated. Conclusion: A post-hoc analysis of CKD subjects from the SUSTAIN and ASSURE randomized controlled trials demonstrated favorable effects of apabetalone on ALP and eGFR, and generated the hypothesis that epigenetic modulation by BET inhibition may potentially offer a novel therapeutic strategy to treat CVD and progressive kidney function loss in CKD patients. This is being examined in the phase III trial BETonMACE.
Індексна оцінка стану тканин пародонта у осіб молодого віку з хронічним катаральним гінгівітом на тлі скупчення зубів
Authors: Mandych A. V.
Published: March 2018

Summary. Today it is known that among maxillodental abnormalities crowded teeth have a leading position and often accompanied by periodontal diseases, lesions of the hard dental tissues, functional disorders of maxillodental system and psycho-emotional disorders of patients is a relevant problem in dentistry. The researchers ascertained the fact of increasing the activity of the course of periodontal disease in patients with maxillodental abnormalities.The aim of the study – to estimate the intensification of inflammatory processes in periodontal tissues of young individuals with crowding of the teeth using periodontal indices.Materials and Methods. The article presents the comparative estimation of the intensity of inflammatory processes in periodontal tissues from 104 people in the age of 18−35 years with chronic catarrhal gingivitis (CCG) on the background of crowding of teeth (main group) and 33 people with CCG without orthodontic pathology (comparison group). For the estimation of the state of periodontal tissues the indexes PMA, bleeding gums and СPI were used. The obtained data were worked out statistically. Results Discussion. It is set on the results of studies that in dependence on the degree of severity of CCG and with increase of the age of examined increases the intensity of inflammatory processes in tissues of teeth-restraint apparatus in both study groups, but in patients with CCG on the background of crowding of teeth this tendency was more pronounced. The average value of the PMA index by its criteria of index revealed to gingivitis of the average severity in the main and comparison groups of the study. With the increase of age of patients in both study groups the increase of the index of bleeding was set. In patients with crowding teeth the values of CPI index exceeded the values of the index in individuals without orthodontic pathology.Conclusions. In patients with crowded teeth on the background of chronic catarrhal gingivitis the intensification of inflammatory processes in periodontal tissues increased with age and depended on the severity of chronic catarrhal gingivitis and was higher than in patients without orthodontic pathology.
Optimizing the Usability of Brain-Computer Interfaces
Authors: Zhang Yin , Chase Steve M.
Published: March 2018

Brain-computer interfaces are in the process of moving from the laboratory to the clinic. These devices act by reading neural activity and using it to directly control a device, such as a cursor on a computer screen. An open question in the field is how to map neural activity to device movement in order to achieve the most proficient control. This question is complicated by the fact that learning, especially the long-term skill learning that accompanies weeks of practice, can allow subjects to improve performance over time. Typical approaches to this problem attempt to maximize the biomimetic properties of the device in order to limit the need for extensive training. However, it is unclear if this approach would ultimately be superior to performance that might be achieved with a nonbiomimetic device once the subject has engaged in extended practice and learned how to use it. Here we approach this problem using ideas from optimal control theory. Under the assumption that the brain acts as an optimal controller, we present a formal definition of the usability of a device and show that the optimal postlearning mapping can be written as the solution of a constrained optimization problem. We then derive the optimal mappings for particular cases common to most brain-computer interfaces. Our results suggest that the common approach of creating biomimetic interfaces may not be optimal when learning is taken into account. More broadly, our method provides a blueprint for optimal device design in general control-theoretic contexts.
Learning Not to Diversify: The Transformation of Graduate Business Education and the Decline of Diversifying Acquisitions
Authors: Jung Jiwook , Shin Taekjin
Published: March 2018

Once a preferred strategy, corporate diversification into disparate lines of business has gradually declined in the U.S. over the past several decades. We argue that changes that occurred in a closely related domain—graduate business education—are important in understanding variation in de-diversification across firms. Building on a historical account of the transformation of business education, we explain how the rise of financial economics and agency-theoretic logic in business education changed students’ views about diversification. Nearly 20 years later, these MBA graduates rose to top decision-making positions and put the brakes on diversification. Using data on CEOs who ran 640 large U.S. corporations from 1985 to 2015, we show that CEOs who earned an MBA before the 1970s actively pursued diversification, whereas the next cohort of CEOs, who had been exposed to agency-theoretic logic in financial economics, refrained from it. We also demonstrate that the degree of managerial discretion moderated the effect of the CEO’s MBA education. Our study shows that institutional change in one domain (i.e., business education) contributed to change in another domain (i.e., corporate diversification), albeit with a considerable time lag.
Making Sense of Refugees Online: Perspective Taking, Political Imagination, and Internet Memes
Authors: Glăveanu Vlad Petre , de Saint-Laurent Constance , Literat Ioana
Published: March 2018

There are many dimensions to the ongoing European refugee crisis, including economic, political, and humanitarian. Underlying them, however, is the issue of self–other relations and, in particular, the ways in which Western societies imagine others and otherness, defined in cultural, religious, and political terms. At the core of this political imagination, we propose, are certain understandings of refugees, of how they think, feel, and intend to act. In this article, we aim to unpack the social and psychological mechanisms involved in taking the perspective of refugees on digital platforms. The focus here is on refugee-related memes shared on Reddit, and the conversations around these visual artifacts. Our findings indicate that participants in these forums most often construct the perspective of refugees from an outside position, based on a commitment to difference, and rarely try to identify with the situation of refugees.