bluuebunny/crossref_metadata_2025 huggingface dataset:
Groups of the virtual trefoil and Kishino knots
Authors: Bardakov Valeriy G. , Mikhalchishina Yuliya A. , Neshchadim Mikhail V.
Published: November 2018

In the paper [13], for an arbitrary virtual link [Formula: see text], three groups [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] were defined. In the present paper, these groups for the virtual trefoil are investigated. The structure of these groups are found out and the fact that some of them are not isomorphic to each other is proved. Also, we prove that [Formula: see text] distinguishes the Kishino knot from the trivial knot. The fact that these groups have the lower central series which does not stabilize on the second term is noted. Hence, we have a possibility to study these groups using quotients by terms of the lower central series and to construct representations of these groups in rings of formal power series. It allows to construct an invariants for virtual knots.
The volume of a compact hyperbolic antiprism
Authors: Abrosimov Nikolay , Vuong Bao
Published: November 2018

We consider a compact hyperbolic antiprism. It is a convex polyhedron with [Formula: see text] vertices in the hyperbolic space [Formula: see text]. This polyhedron has a symmetry group [Formula: see text] generated by a mirror-rotational symmetry of order [Formula: see text], i.e. rotation to the angle [Formula: see text] followed by a reflection. We establish necessary and sufficient conditions for the existence of such polyhedra in [Formula: see text]. Then we find relations between their dihedral angles and edge lengths in the form of a cosine rule. Finally, we obtain exact integral formulas expressing the volume of a hyperbolic antiprism in terms of the edge lengths.
A Hybridization Approach for Optimal Feature Subset Selection in High Dimensional Data
Authors: Sharmili K. C. , Chilambuchelvan A.
Published: November 2018

Feature subset selection assumes an essential part in the fields of data mining and machine learning. A good feature subset selection algorithm can adequately expel unimportant and repetitive elements and consider feature interaction. This not just paves the way to an understanding comprehension of the information, additionally enhances the execution of a learner by improving the generalization capacity and the interpretability of the learning model. Initially, the input micro array dataset is selected from the medical database. Then preprocessing step is done in the input micro array dataset. The resultant output is fed to the second step; here the features are optimally selected using clustering and optimization process. In our proposed technique, the optimal hybrid fuzzy c-means clustering algorithm with artificial bee colony algorithm is applied on the high dimensional micro array dataset to select the important features. Here the proposed method is optimally select the features with the help of social spider optimization algorithm. After that, the classification is done through improved support vector machine classifier. At last, the experimentation is performed by means of different micro array dataset. Experimental results indicate that the proposed classification framework has outperformed by having better accuracy of 93.19% for GLA-BRA-180 dataset when compared existing SVM and neuro fuzzy classifier only achieved 90.69% and 89%.
Entrepreneur’s Social Capital and Firm Growth: The Moderating Role of Access to Finance
Authors: Boohene Rosemond
Published: November 2018

Social capital and access to finance have been identified as key resources that influence the growth of small firms however, these variables have rarely been studied. This paper, therefore, examines the relationship between social capital and firm growth with access to finance as a moderating role. 250 small firms in the Kumasi Metropolis in Ghana were used for the study. Structural Equation Modelling using Partial Least Square (PLS) was used to analyze the data collected using area sampling. The results indicated that social capital does not directly influence firm growth. In addition, access to finance does not moderate the relationship between social capital and firm growth. However, a positive relationship was found between social capital and access to finance. Access to finance and firm growth, though significant, had a negative relationship. It is recommended that since social capital influences the capability to access finance, entrepreneurs should be encouraged to build more relationships within their networks. Moreover, government agencies and financial institutions should devise strategies that will reduce the interest rates so that though these small firms in Ghana can access finance, the high interest rates will not erode the gains they may achieve in the long run.
CHANGE OF INDUCED STRESS WAVE ON COLLAGEN TISSUE FOR BIOSTIMULATION BY FREQUENCY-DOUBLED Nd:YAG LASER
Authors: OH HAN-BYEOL , KIM JI-SUN , JUNG GU-IN , BAEK JIN-YOUNG , KIM JUNGGIL , JUN JAE-HOON
Published: November 2018

In this research, thermoelastic effect was investigated for biostimulation without damage on the biological medium using laser. Thermoelastic effect was generated and mechanical stress was induced by laser irradiation on the collagen, the main protein in the human body, under various conditions with short pulsed laser. The threshold laser energy to induce stress wave in each medium thickness was examined with a piezo sensor. Based on the test, the stimulation strength can be controlled through the adjustment of medium thickness, laser energy and beam diameter. The result implies that precise stimulation with various strengths of stress waves can be generated at the target depth without direct contact with the biological medium. This research can be used valuably in various fields such as contactless biostimulation, low power laser treatment and laser haptic applications.
First-Principles Study on the Electronic Structure of Bulk and Single-Layer Boehmite
Authors: Son Seungwook , Kim Dongwook , Na-Phattalung Sutassana , Ihm Jisoon
Published: November 2018

Two-dimensional (2D) or layered materials have a great potential for applications in energy storage, catalysis, optoelectronics and gas separation. Fabricating novel 2D or quasi-2D layered materials composed of relatively abundant and inexpensive atomic species is an important issue for practical usage in industry. Here, we suggest the layer-structured AlOOH (Boehmite) as a promising candidate for such applications. Boehmite is a well-known layer-structured material and a single-layer can be exfoliated from the bulk boehmite by breaking the interlayer hydrogen bonding. We study atomic and electronic band structures of both bulk and single-layer boehmite, and also obtain the single-layer exfoliation energy using first-principles calculations.
Efficient parameter estimation for multivariate accelerated failure time model via the quadratic inference functions method
Authors: Fu Liya , Yang Zhuoran , Zhao Mingtao , Zhou Yan
Published: November 2018

A popular approach, generalized estimating equations (GEE), has been applied to the multivariate accelerated failure time (AFT) model of the clustered and censored data. However, this method needs to estimate the correlation parameters and calculate the inverse of the correlation matrix. Meanwhile, the efficiency of the parameter estimators is low when the correlation structure is misspecified and/or the marginal distribution is heavy-tailed. This paper proposes using the quadratic inference functions (QIF) with a mixture correlation structure to estimate the coefficients in the multivariate AFT model, which can avoid estimating the correlation parameters and computing the inverse matrix of the correlation matrix. Moreover, the estimator derived from the QIF is consistent and asymptotically normal. Simulation studies indicate that the proposed method outperforms the method based on GEE when the marginal distribution has a heavy tail. Finally, the proposed method is used to analyze a real dataset for illustration.
Imaginary People Representing Real Numbers
Authors: An J. , Kwak H. , Jung S. , Salminen J. , Admad M. , Jansen B.
Published: November 2018

We develop a methodology to automate creating imaginary people, referred to as personas, by processing complex behavioral and demographic data of social media audiences. From a popular social media account containing more than 30 million interactions by viewers from 198 countries engaging with more than 4,200 online videos produced by a global media corporation, we demonstrate that our methodology has several novel accomplishments, including: (a) identifying distinct user behavioral segments based on the user content consumption patterns; (b) identifying impactful demographics groupings; and (c) creating rich persona descriptions by automatically adding pertinent attributes, such as names, photos, and personal characteristics. We validate our approach by implementing the methodology into an actual working system; we then evaluate it via quantitative methods by examining the accuracy of predicting content preference of personas, the stability of the personas over time, and the generalizability of the method via applying to two other datasets. Research findings show the approach can develop rich personas representing the behavior and demographics of real audiences using privacy-preserving aggregated online social media data from major online platforms. Results have implications for media companies and other organizations distributing content via online platforms.
System Design through the Exploration of Contemporary Web Services
Authors: Delano John D. , Jain Hemant K. , Sinha Atish P.
Published: November 2018

In this article, we develop a Contemporary Web Service (CWS) repository of system designs, which are encoded as metadata of contemporary web services. We examine if this CWS repository serves as an effective design tool for initial CWS design and as an effective support tool for business users and analysts working together on system design. The CWS repository reduces the cognitive load of both the analyst and the business user as they jointly explore the CWS repository of system designs. It supports an evolutionary approach to system design through rapid selection of appropriate CWS metadata. To accomplish that, we introduce several new design characteristics for the CWS repository. The evaluation results demonstrate that the CWS repository is an effective tool for supporting designers during initial service design, as well as for supporting business users and analysts during system design.
(ECS 234th) Multiphysics Modeling Prediction of Electrochemically Machined Through-Hole Geometries
Authors: Skinn Brian , Hall Tim , Snyder Stephen , Rajurkar KP , Taylor Jennings E.
Published: November 2018

Electrochemical machining (ECM) is a manufacturing technology that allows metal to be precisely removed by electrochemical oxidation and dissolution into an electrolyte solution. ECM is suited for machining parts fabricated from “difficult to cut” materials and/or parts with complicated and intricate geometries. In ECM, the workpiece is the anode and the tool is the cathode in an electrochemical cell; by relative movement of the shaped tool into the workpiece, the mirror image of the tool is “copied” or machined into the workpiece. Compared to mechanical or thermal machining processes where metal is removed by cutting or electric discharge/laser machining, respectively, ECM does not suffer from tool wear or result in a thermally damaged surface layer on the workpiece. Consequently, ECM has strong utility as a manufacturing technology for fabrication of a wide variety of metallic parts and components, and includes machining, deburring, boring, radiusing and polishing processes. ECM provides particular value in that application is straightforward to high strength/tough and/or work-hardening materials such as high strength steel, chrome-copper alloy (C18200), nickel alloy (IN718), cobalt-chrome alloy (Stellite 25) and tantalum-tungsten alloy (Ta10W), since the material removal process involves no mechanical interaction between the tool and the part. A variety of production applications are envisioned as well suited for ECM techniques.One notable difficulty with ECM, common to a variety of manufacturing operations, is an inability to predict a priori the tool and process parameters required in order to satisfy the final specifications of the fabricated part. In this talk, Faraday will present results from ongoing development work of a physics-based design platform to predict optimal ECM tool shape using commercially available multiphysics simulation software. This predictive capability is anticipated to dramatically shorten the process/tooling development cycle, eliminating much or all of the iterative prototyping necessary in the absence of a predictive tool. The main focus of this talk will be a comparison of through-holes fabricated by CM in flat plate and/or tube geometries to those predicted by multiphysics simulation. The various physics included in the models to enable accurate simulations will be discussed, along with any (semi-)empirical simplifying assumptions made to accelerate execution of the simulations. The overarching objective of the current and future work, to demonstrate accurate modeling of ECM through-hole features of progressively increasing experimental complexity, will also be presented.
Investigation of Antioxidant/Oxidant Status and Antimicrobial Activities of Lentinus tigrinus
Authors: Sevindik Mustafa
Published: November 2018

In the present study, antioxidant and antimicrobial potential of the Lentinus tigrinus (Bull.) Fr. mushroom was determined. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) of the mushroom were measured with Rel Assay kits. Antimicrobial activities were tested on 9 standard bacterial and fungal strains (Staphylococcus aureus, Staphylococcus aureus MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida albicans, Candida krusei, and Candida glabrata) with a modified agar dilution method. It was determined that the TAS value of L. tigrinus was 1.748 ± 0.071, TOS value was 19.294 ± 0.237, and OSI was 1.106 ± 0.031. It was also found that mushroom extracts generally exhibited higher activity on Candida albicans, C. krusei, and C. glabrata. In conclusion, it was suggested that L. tigrinus can be used as a natural source due to its antioxidant and antimicrobial activities.
Generalization Bounds for Coregularized Multiple Kernel Learning
Authors: Wu Xinxing , Hu Guosheng
Published: November 2018

Multiple kernel learning (MKL) as an approach to automated kernel selection plays an important role in machine learning. Some learning theories have been built to analyze the generalization of multiple kernel learning. However, less work has been studied on multiple kernel learning in the framework of semisupervised learning. In this paper, we analyze the generalization of multiple kernel learning in the framework of semisupervised multiview learning. We apply Rademacher chaos complexity to control the performance of the candidate class of coregularized multiple kernels and obtain the generalization error bound of coregularized multiple kernel learning. Furthermore, we show that the existing results about multiple kennel learning and coregularized kernel learning can be regarded as the special cases of our main results in this paper.
Distribution Inference for Physical and Orbital Properties of Jupiter’s Moons
Authors: Gao F. B. , Zhu X. H. , Liu X. , Wang R. F.
Published: November 2018

According to the physical and orbital characteristics in Carme group, Ananke group, and Pasiphae group of Jupiter’s moons, the distributions of physical and orbital properties in these three groups are investigated by using one-sample Kolmogorov–Smirnov nonparametric test. Eight key characteristics of the moons are found to mainly obey the Birnbaum–Saunders distribution, logistic distribution, Weibull distribution, and t location-scale distribution. Furthermore, for the moons’ physical and orbital properties, the probability density curves of data distributions are generated; the differences of three groups are also demonstrated. Based on the inferred results, one can predict some physical or orbital features of moons with missing data or even new possible moons within a reasonable range. In order to better explain the feasibility of the theory, a specific example is illustrated. Therefore, it is helpful to predict some of the properties of Jupiter’s moons that have not yet been discovered with the obtained theoretical distribution inference.
Assessment of Ripening Degree of Avocado by Electrical Impedance Spectroscopy and Support Vector Machine
Authors: Islam Monzurul , Wahid Khan , Dinh Anh
Published: November 2018

Avocado, a climacteric fruit, exerts high rate of respiration and ethylene production and thereby subject to ripening during storage. Therefore, its ripening is a significant factor to impart optimum quality in postharvest storage. To understand the dynamics of ripening and to assess the degree of ripening in the avocado, electrical sensing technique is utilized in this study. In particular, electrical impedance spectroscopy (EIS) is found to uncover the physiological and structural characteristics in plants and vegetables and to follow physiological progressions due to environmental impacts. In this work, we present an approach that will integrate EIS and machine learning technique that allows us to monitor the ripening degree of the avocado. It is evident from our study that the impedance absolute magnitude of the avocado gradually decreases as the ripening stages (firm, breaking, ripe, and overripe) proceed at a particular frequency. In addition, principal component analysis shows that impedance magnitude (two principal components combined explain 99.95% variation) has better discrimination capabilities for ripening degrees compared to impedance phase angle, impedance real part, and impedance imaginary part. Our classifier utilizes two principal component features over 100 EIS responses and demonstrates classification over firm, breaking, ripe, and overripe stages with an accuracy of 90%, precision of 93%, recall of 90%, f1-score of 90%, and auc of 88%. The study offers plant scientists a low cost and nondestructive approach to monitor postharvest ripening process for quality control during storage.
Mutation-Based Harmony Search Algorithm for Hybrid Testing of Web Service Composition
Authors: Maythaisong Eckwijai , Songpan Wararat
Published: November 2018

Web service composition is a method of developing a new web service from an existing one based on business goals. Web services selected for composition should provide accurate operational results and reliable applications. However, most alternative service providers have not yet fulfilled users’ needs in terms of services and processes. Service providers, in fact, have focused on enhancing nonfunctional attributes, such as efficiencies of time, cost, and availability, which still face limitations. Furthermore, it remains advantageous to compose services and suitably plan them around business plans. Thus, this study introduces hybrid testing using a combination of the functional and nonfunctional testing approaches. The former was used to design a test case through the equivalence class partitioning technique, and the latter was used to select suitable services for the test results. We find defects and appropriate solutions for combining services based on business requirements. The mutation-based harmony search (MBHS) algorithm is proposed to select web services and to compose with minimum defects. The results of this study reveal that MBHS can support a combination of various services more efficiently and dramatically than other metaheuristic methodologies. Additionally, it helps find appropriate solutions to compose services based on business plans.
A Systematic Review of Translation and Cross-Cultural Adaptation of Instruments for the Selection of Assistive Technologies
Authors: de Lima Barroso Bárbara Iansã , Galvão Cláudia Regina Cabral , da Silva Luiz Bueno , Lancman Selma
Published: November 2018

This article presents a systematic review, for which research was carried out in the following electronic databases: Web of Science, Scopus, PubMed, and ERIC, in which several articles were found (n=560). The results were analyzed based on the information obtained in the titles and abstracts, and the remaining studies were read in full for the analysis. The aim of this article was to identify the different questionnaires used for selecting items of assistive technology, describe and evaluate the translation and transcultural adaptation procedures, characterize the thematic domains of each resource, evaluate the cultural adaptation process adopted, and describe the psychometric properties. Data extraction and evaluation of the methodological quality of the eligible studies were performed in accordance with the COSMIN verification list with a checklist of 4 points. The publication of systematic review studies and others that synthesize research results is fundamental to provide support for change in the behavior of professionals in the field of health, and not only to access the available literature but also to incorporate this information into daily clinical practice. The results of this review could provide subsidies that would enable the planning, execution, identification, and choice of specific instruments for a determined study within the context of assistive technology, with a view to helping researchers and health professionals in clinical and investigatory practices.
A New Special Function and Its Application in Probability
Authors: Rafik Zeraoulia , Salas Alvaro H. , Ocampo David L.
Published: November 2018

In this note we present a new special function that behaves like the error function and we provide an approximated accurate closed form for its CDF in terms of both Chèbyshev polynomials of the first kind and the error function. Also we provide its series representation using Padé approximant. We show a convincing numerical evidence about an accuracy of 10-6 for the approximants in the sense of the quadratic mean norm. A similar approach may be applied to other probability distributions, for example, Maxwell–Boltzmann distribution and normal distribution, such that we show its application using both of those distributions.
Usability Assessments for Augmented Reality Motor Rehabilitation Solutions: A Systematic Review
Authors: Cavalcanti Virgínia C. , Santana Maria I. de , Gama Alana E. F. Da , Correia Walter F. M.
Published: November 2018

This article aims to understand which methods and user assessment approaches are most commonly used in motor rehabilitation studies that use Augmented Reality (AR) applications. The way in which this was performed and discussed was through a systematic review of the area. Firstly, the different uses of AR in these treatments, and the importance of improving usability studies to evaluate these interfaces and their interactions with their users, were discussed. Then, the systematic review of the literature was structured according to previous studies and covered the period from 2007 to September 2017, using the main scientific journals of the area. Of the 666 results collected in the initial search, 32 articles were selected within the planned requirements and scope. These publications were classified by relevance, using the QualSyst evaluation tool for health technology research, and the type of evaluation, approach, and methods used were catalogued. It was found that most of the studies prioritise methods of data collection, such as task execution and performance analysis. However, through QualSyst, it was verified that the best-evaluated studies chose to use a combination of quantitative and qualitative analysis, through the application of methods such as user preference questionnaires, interviews, and observations. The results presented in this review may benefit designers who intend to design and conduct usability assessments for AR within this context.
Excessive Crossed Disparity Detection by Visual Evoked Potentials to Reduce Visual Discomfort in 3D Viewing
Authors: Wang Xiao , Yao Liuye , Qian Zhiyu , Xing Lidong , Li Weitao , Yang Yamin
Published: November 2018

As excessive crossed disparity is known to cause visual discomfort, this study aims to establish a classification model to discriminate excessive crossed disparity in stereoscopic viewing in combination with subjective assessment of visual discomfort. A stereo-visual evoked potentials (VEPs) experimental system was built up to obtain the VEPs evoked by stereoscopic stimulus with different disparities. Ten volunteers participated in this experiment, and forty VEP datasets in total were extracted when the viewers were under comfortable viewing conditions. Six features of VEPs from three electrodes at the occipital lobe were chosen, and the classification was established using the Fisher’s linear discriminant (FLD). Based on FLD results, the correct rate for determining the excessive crossed disparity was 70%, and it reached 80% for other stimuli. The study demonstrated cost-effective discriminant classification modelling to distinguish the stimulus with excessive crossed disparity which inclines to cause visual discomfort.
User Experiences from L2 Children Using a Speech Learning Application: Implications for Developing Speech Training Applications for Children
Authors: Uther Maria , Smolander Anna-Riikka , Junttila Katja , Kurimo Mikko , Karhila Reima , Enarvi Seppo , Ylinen Sari
Published: November 2018

We investigated user experiences from 117 Finnish children aged between 8 and 12 years in a trial of an English language learning programme that used automatic speech recognition (ASR). We used measures that encompassed both affective reactions and questions tapping into the children' sense of pedagogical utility. We also tested their perception of sound quality and compared reactions of game and nongame-based versions of the application. Results showed that children expressed higher affective ratings for the game compared to nongame version of the application. Children also expressed a preference to play with a friend compared to playing alone or playing within a group. They found that assessment of their speech is useful although they did not necessarily enjoy hearing their own voices. The results are discussed in terms of the implications for user interface (UI) design in speech learning applications for children.
Numerical Investigation of Rainfall-Induced Landslide in Mudstone Using Coupled Finite and Discrete Element Analysis
Authors: Hung Ching , Liu Chih-Hsuan , Chang Chia-Ming
Published: November 2018

In this study, the role of water infiltration on a rainfall-induced landslide in mudstone is investigated. Finite element analysis (FEA) and discrete element analysis (DEA) were employed to explore the driving mechanism in the prefailure regime and the dynamic runout process in the postfailure regime, respectively. The driving mechanism was revealed in terms of the pore water pressures, saturation, and displacement of the sliding zone. To account for water infiltration associated with the dynamic runout process of the landsliding, the sliding friction coefficient in DEA was examined. Based on the results, satisfactory agreement between the numerical analysis and landslide behavior was realized. In prefailure regime, the onset of landslide initiation was found through assessment of rapid change of source displacement (RCSD). The estimated seepage force was about 0.5 N at landslide initiation. In postfailure regime, the results demonstrate that water infiltration and transition in steepness play significant roles in the behavior of the dynamic runout process. The landsliding exhibited a maximum speed of 4.41 m/s and decelerated as it reached a more gentle slope. Overall, the study indicated that the coupling of FEA and DEA can be used to investigate the role of water infiltration and provide useful insights. The approach can be further applied for studies on many other rainfall-induced geohazards to disclose the role of water infiltration with the prefailure and postfailure characteristics.
Telemental Health in Low- and Middle-Income Countries: A Systematic Review
Authors: Acharibasam Jeremiah W. , Wynn Rolf
Published: November 2018

Introduction. The rising incidence of mental illness and its impact on individuals, families, and societies is becoming a major public health concern, especially in resource-constrained countries. Consequently, there is an increasing demand for mental health services in many middle- and low-income countries (LMIC). Challenges such as inequality in access, lack of staff and hospital beds, and underfunding, often present in the LMIC, might in part be addressed by telemental health services. However, little is known about telemental health in the LMIC. Methods. A systematic review was performed, drawing on several electronic databases, including PubMed, PsycINFO, Web of Science, Springer Link, and Google Scholar. Original English language studies on the practice of telemental health in LMIC, involving patients and published between 1 January 2000 and 16 February 2017, were included. Results. Nineteen studies met the inclusion criteria. Most of the articles were recent, which may reflect an increasing focus on telemental health in the LMIC. Eight of these studies were from Asia. Eight of the studies were interventional/randomized controlled trials, and 11 examined general mental health issues. Videoconferencing was the most frequently (6) studied telemental modality. Other modalities studied were online decision support systems (3), text messaging and bibliotherapy (1), e-chatting combined with videoconferencing (1), online therapy (2), e-counseling (1), store-and-forward technology (1), telephone follow-up (1), online discussion groups (1), audiovisual therapy and bibliotherapy (1), and computerized occupational therapy (1). Although many of the studies showed that telemental services had positive outcomes, some studies reported no postintervention improvements. Conclusion. The review shows a rising trend in telemental activity in the LMIC. There is a greater need for telemental health in the LMIC, but more research is needed on empirical and theoretical aspects of telemental activity in the LMIC and on direct comparisons between telemental activity in the LMIC and the non-LMIC.
CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial–Mesenchymal Plasticity in Breast Cancer
Authors: Nilchian Azadeh , Johansson Joel , Ghalali Aram , Asanin Sandra T. , Santiago Ana , Rosencrantz Oskar , Sollerbrant Kerstin , Vincent C. Theresa , Sund Malin , Stenius Ulla , Fuxe Jonas
Published: November 2018

Tight junctions (TJ) act as hubs for intracellular signaling pathways controlling epithelial cell fate and function. Deregulation of TJ is a hallmark of epithelial–mesenchymal transition (EMT), which contributes to carcinoma progression and metastasis. However, the signaling mechanisms linking TJ to the induction of EMT are not understood. Here, we identify a TJ-based signalosome, which controls AKT signaling and EMT in breast cancer. The coxsackie and adenovirus receptor (CXADR), a TJ protein with an essential yet uncharacterized role in organogenesis and tissue homeostasis, was identified as a key component of the signalosome. CXADR regulated the stability and function of the phosphatases and AKT inhibitors PTEN and PHLPP2. Loss of CXADR led to hyperactivation of AKT and sensitized cells to TGFβ1–induced EMT. Conversely, restoration of CXADR stabilized PHLPP2 and PTEN, inhibited AKT, and promoted epithelial differentiation. Loss of CXADR in luminal A breast cancer correlated with loss of PHLPP2 and PTEN and poor prognosis. These results show that CXADR promotes the formation of an AKT-inhibitory signalosome at TJ and regulates epithelial–mesenchymal plasticity in breast cancer cells. Moreover, loss of CXADR might be used as a prognostic marker in luminal breast cancer.

Significance:

The tight junction protein CXADR controls epithelial-mesenchymal plasticity in breast cancer by stabilizing the AKT regulators PTEN and PHLPP2.
Improving Cancer Preventive Behaviors: A Randomized Trial of Tailored Lifestyle Feedback in Colorectal Cancer Screening
Authors: Knudsen Markus Dines , Hjartåker Anette , Robb Kathryn A. , de Lange Thomas , Hoff Geir , Berstad Paula
Published: November 2018

Background:

Cancer screening provides an opportunity to increase awareness of cancer-preventive lifestyle behaviors such as nonsmoking, physical activity, low alcohol consumption, and a healthy diet. We tested the effect of standardized, individually tailored written feedback (TF), and a standard leaflet (SL) on 1-year lifestyle behaviors in a colorectal cancer screening setting.

Methods:

A total of 3,642 men and women aged 50–74 years invited to sigmoidoscopy screening were randomly assigned to: (i) TF; (ii) SL for cancer-preventive lifestyle behaviors; or (iii) control. Participants were mailed two self-reported lifestyle questionnaires (LSQ) 1 year apart. The TF intervention was based on the prescreening LSQ answers. We analyzed differences [with 95% confidence intervals (CI)] by comparing prescreening to 1-year follow-up of single cancer-preventive factors and the number of cancer-preventive lifestyle behaviors (range 0–4) between the groups by multivariable logistic regression and analysis of covariance (ANCOVA).

Results:

A total of 1,054 screening participants without neoplastic findings (29% of those invited to screening) were included in this study. Participants in the TF group increased their number of cancer-preventive lifestyle behaviors significantly compared with those in the control group by 0.11 (95% CI, 0.02 to 0.19). Overweight/obese individuals in the TF group had a −0.84 kg (95% CI, −1.47 to −0.22) larger reduction in body weight compared with the control group.

Conclusions:

TF at sigmoidoscopy screening led to small improvements in cancer-preventive behaviors.

Impact:

Colorectal cancer screening is a suitable setting for increasing awareness of cancer-preventive behavior.
Single-Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression
Authors: Bernard Vincent , Semaan Alexander , Huang Jonathan , San Lucas F. Anthony , Mulu Feven C. , Stephens Bret M. , Guerrero Paola A. , Huang Yanqing , Zhao Jun , Kamyabi Nabiollah , Sen Subrata , Scheet Paul A. , Taniguchi Cullen M. , Kim Michael P. , Tzeng Ching-Wei , Katz Matthew H. , Singhi Aatur D. , Maitra Anirban , Alvarez Hector A.
Published: November 2018

Purpose:

Early detection of pancreatic ductal adenocarcinoma (PDAC) remains elusive. Precursor lesions of PDAC, specifically intraductal papillary mucinous neoplasms (IPMNs), represent a bona fide pathway to invasive neoplasia, although the molecular correlates of progression remain to be fully elucidated. Single-cell transcriptomics provides a unique avenue for dissecting both the epithelial and microenvironmental heterogeneities that accompany multistep progression from noninvasive IPMNs to PDAC.

Experimental Design:

Single-cell RNA sequencing was performed through droplet-based sequencing on 5,403 cells from 2 low-grade IPMNs (LGD-IPMNs), 2 high-grade IPMNs (HGD-IPMN), and 2 PDACs (all surgically resected).

Results:

Analysis of single-cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of noninvasive dysplasia to invasive cancer. Although HGD-IPMNs expressed many core signaling pathways described in PDAC, LGD-IPMNs harbored subsets of single cells with a transcriptomic profile that overlapped with invasive cancer. Notably, a proinflammatory immune component was readily seen in low-grade IPMNs, composed of cytotoxic T cells, activated T-helper cells, and dendritic cells, which was progressively depleted during neoplastic progression, accompanied by infiltration of myeloid-derived suppressor cells. Finally, stromal myofibroblast populations were heterogeneous and acquired a previously described tumor-promoting and immune-evading phenotype during invasive carcinogenesis.

Conclusions:

This study demonstrates the ability to perform high-resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer. Notably, single-cell analysis provides an unparalleled insight into both the epithelial and microenvironmental heterogeneities that accompany early cancer pathogenesis and might be a useful substrate to identify targets for cancer interception.

See related commentary by Hernandez-Barco et al., p. 2027
Prognostic Models Turn the Heat(IT)up on FLT3ITD-Mutated AML
Authors: Gallipoli Paolo , Huntly Brian J.P.
Published: November 2018

The presence of internal tandem duplications (ITD) in the FLT3 receptor tyrosine kinase gene have long been known to confer a poor prognosis in patients with acute myeloid leukemia. Now, specific structural features of the ITDs are also suggested to alter patient outcome, including sensitivity to targeted therapies, prompting their evaluation in therapeutic algorithms.

See related article by Schwartz et al., p. 573
Performance with an Auditory Brainstem Implant and Contralateral Cochlear Implant in Pediatric Patients
Authors: Friedmann David R. , Asfour Leena , Shapiro William H. , Roland Jr. J. Thomas , Waltzman Susan B.
Published: November 2018

Objective: To assess bimodal auditory performance in children with a cochlear implant (CI) and contralateral auditory brainstem implant (ABI). Methods: This is a retrospective case review performed at a tertiary referral center. Four patients with cochlear nerve deficiency initially underwent cochlear implantation but were not benefiting from their devices and underwent ABI in the contralateral ear. The main outcome measures included age-appropriate speech perception and production assessments. Results: Three subjects performed better on their auditory perception assessments using both of their devices than with either device alone. One subject had only preliminary outcomes, but subjectively performed best with both devices. Conclusions: We observed continued improvement in CI performance over time, even if no benefit was evident before the decision for ABI. This could suggest that ABI and CI have a synergistic effect, or it could simply be the adaptive ability of the developing brain to utilize the signals coming from these devices. There is preliminary evidence to support choosing the ear contralateral to the CI for an ABI in a pediatric patient with bilateral cochlear nerve deficiency.
Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation
Authors: Jiao Wo-Er , Wei Jin-Feng , Kong Yong-Gang , Xu Yu , Tao Ze-Zhang , Chen Shi-Ming
Published: November 2018

Background: The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear. Objective: To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells. Method: The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice. Results: Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group. Conclusion: Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR.
Intralymphatic Immunotherapy: Update and Unmet Needs
Authors: Senti Gabriela , Freiburghaus Andreas U. , Larenas-Linnemann Désirée , Hoffmann Hans Jürgen , Patterson Amber M. , Klimek Ludger , Di Bona Danilo , Pfaar Oliver , Ahlbeck Lars , Akdis Mübeccel , Weinfeld Dan , Contreras-Verduzco Francisco A. , Pedroza-Melendez Alvaro , Skaarup Søren H. , Lee Sang Min , Cardell Lars-Olaf , Schmid Johannes M. , Westin Ulla , Dollner Ralph , Kündig Thomas M.
Published: November 2018

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes – intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.
Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?
Authors: Prasun Pankaj , Madan Raghav , Puthuraya Subhash , Subramanian Divya , Datta Ishita , Kalra Vaneet , Thomas Ronald , Stockton David W. , Sundaram Senthil , Callaghan Joseph , Callaghan Michael , Chouthai Nitin
Published: November 2018

Background: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. Methods: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). Results: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). Conclusion: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.
Up-Regulation Thioredoxin Inhibits Advanced Glycation End Products-Induced Neurodegeneration
Authors: Ren Xiang , Wang Ni-na , Qi Hui , Qiu Yuan-yuan , Zhang Cheng-hong , Brown Emily , Kong Hui , Kong Li
Published: November 2018

Background/Aims: Diabetic retinopathy (DR) is one of the most serious complications of diabetes and is the leading cause of adult blindness in developed countries. Advanced glycation end products (AGEs) accumulation in diabetes is associated with its complications. Thioredoxin (Trx) is a small molecule (12kDa) antioxidant protein widely distributed in mammalian tissues, which has important biological functions including anti-apoptosis and transcriptional regulation. In a previous study, we found that Trx plays a key role in retinal neurodegeneration prior to the occurrence of endothelial damage in diabetic mice. In this study, our aim is to determine the effect of Trx on neurodegeneration induced by AGEs in order to identify new therapeutic targets for the clinical treatment and prevention of DR. Methods: In vivo, a high-fat diet and Streptozotocin (STZ) injection were used to generate a mouse model of diabetes. Histology was utilized to examine tissue morphology and measure the outer nuclear layer (ONL) thickness. Electroretinography (ERG) was used to assess retinal function and Western blot was used to examine protein expression. In vitro, three methods of Trx up-regulation were used, including a stable cell line that overexpresses Trx, treatment with Sulforaphane, and shRNA down-regulation Txnip. Cells were treated with AGEs, and level of apoptosis was performed to quantify this by flow cytometry and TUNEL. Quantitative Reverse Transcription PCR (qRT-PCR), Western blotting and immunofluorescence were used to measure gene and protein expression. Transmission electron microscopy (TEM) was used to observe autophagosomes. Results: We found that diabetic mice display decreased retinal function and reduced ONL thickness with AGEs accumulation and a reduction of Trx expression. Up-regulation Trx can prevent the ONL thickness decrease in diabetic mice, as observed by H&E staining. In vitro, up-regulation Trx resulted in decreased intracellular ROS generation, reduced apoptosis by inhibited autophagy. Conclusion: Up-regulating Trx inhibited neurodegeneration induced by AGEs. The underlying mechanism may be related to inhibit Txnip/mTOR pathway-mediated autophagy.