bluuebunny/crossref_metadata_2025 huggingface dataset:
Half-Elliptical UWB Planar Monopole with Reconfigurable Slot Antenna for Cognitive Radio Front-End
Authors: Koley Santasri , Pant Himanshu , Murmu Lakhindar
Published: March 2018

In this paper, a half-elliptical disc ultra-wideband (UWB) monopole antenna integrated with a reconfigurable rectangular slot antenna is presented. It consists of a half-elliptical disc radiator to operate in the UWB mode whereas the etched rectangular slot on the half-elliptical patch is designed to operate as a reconfigurable narrowband slot antenna which is fed through a microstrip line from the back side of the patch. Both the antennas are placed in such a way that they are isolated to each other. Frequency reconfigurability has been achieved by inserting three lumped elements (two PIN diodes and a varactor diode) in the slot. An approximate transmission line model of the proposed slot antenna is derived to calculate the proper positioning of the diodes, and the design has been verified through numerical simulations. The simple compact proposed antenna covers a wide frequency range from 0.75 to 12[Formula: see text]GHz. Additionally, a wide tuning range from 0.8 to 2.9[Formula: see text]GHz (with the frequency ratio of 3.625:1) has been achieved. This compact integrated antenna is a good choice to be implemented in Cognitive Radio (CR) devices.
Theoretical study on the effect of different π-linker on the performance of sensitizer in carbazole-based dyes
Authors: Guo Huixia , Xi Xiaohua , Yan Renxiang , Lu Xiaoquan
Published: March 2018

Derived from diarylamine sensitizer diphenyl-(7-pyridin-4-yl-9H-carbazol-2-yl)-amine (N13), a series of novel D[Formula: see text]A carbazole-based organic dye sensitizers with different [Formula: see text]-linkers were designed for searching more effective sensitizers in dye-sensitized solar cells (DSSCs) design. Optimized geometries, electronic structure, and other parameters, which can evaluate the performance of DSSCs effectively and intuitively, were theoretically calculated by density functional theory (DFT) and time-dependent DFT methods at the M06/6-31G(d,p) level. The results indicated that the maximum absorption wavelength of designed dye was red-shifted and the molar absorption coefficient ([Formula: see text]) became higher. This phenomenon can be explained by the modification of the [Formula: see text]-bridge. The simulated Ultraviolet–visible spectroscopy (UV-Vis) absorption spectrum showed that the designed N,N-diphenyl-7-(5-(7-(5-(pyridin-4-yl)thiophen-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)-9H-carbazol-2-amine (N22) dye presents the largest red-shifted absorption band and the designed (E)-N,N-diphenyl-7-(2-(5[Formula: see text]-(pyridin-4-yl)-[2,2[Formula: see text]-bithiophene]-5-yl)vinyl)-9H-carbazol-2-amine (N21) dye showed the largest [Formula: see text], both of them depicted a high short-circuit photocurrent density ([Formula: see text]. Meanwhile, the charge separation hampered by long [Formula: see text]-linkers was also observed. These results are helpful for designing new sensitizers and providing effective guiding to experimental synthesis.
The Use of Cyberbullying Mobile Application to Increase Perceived Knowledge of Cyberbullying Among Adolescents
Authors: Thinnukool Orawit , Khuwuthyakorn Pattaraporn , Sittichai Ruthaychonnee
Published: March 2018

The aim of this study was to develop a research-based mobile application to increase perceived knowledge of Thai adolescents on cyberbullying. The proposed mobile application is called Cyberbullying Mobile Application (CBMA) which is the first research-based CBMA developed in Thailand. The research focused on the lack of adolescent perceived knowledge on the above, at the undergraduate level. Two hundred and fifty-three samples were surveyed from high schools and universities. After releasing the CBMA for real use to the same group of users as the samples, the study found that users appreciated it and had confidence in the application; while in some cases, users claimed they would use it in their lives. The CBAM and questionnaire outcomes were analyzed by using independent sample [Formula: see text]-test analysis on [Formula: see text] program to test hypothesis. Therefore, the CBMA is an appropriate tool recommended for adolescents to educate themselves to handle and be aware of cyberbullying.
An algorithm for computing the reduction of 2-dimensional crystalline representations of Gal(ℚ¯p/ℚp)
Authors: Rozensztajn Sandra
Published: March 2018

We describe an algorithm to compute the reduction modulo [Formula: see text] of a crystalline Galois representation of dimension [Formula: see text] of [Formula: see text] with distinct Hodge–Tate weights via the semi-simple modulo [Formula: see text] Langlands correspondence. We give some examples computed with an implementation of this algorithm in SAGE.
Diophantine approximation with mixed powers of primes
Authors: Ge Wenxu , Liu Huake
Published: March 2018

Let [Formula: see text] be an integer with [Formula: see text], and [Formula: see text] be any real number. Suppose that [Formula: see text] are nonzero real numbers, not all the same sign and [Formula: see text] is irrational. It is proved that the inequality [Formula: see text] has infinitely many solutions in primes [Formula: see text], where [Formula: see text], and [Formula: see text] for [Formula: see text]. This generalizes earlier results. As application, we get that the integer parts of [Formula: see text] are prime infinitely often for primes [Formula: see text].
Exact generating functions for the number of partitions into distinct parts
Authors: Baruah Nayandeep Deka , Begum Nilufar Mana
Published: March 2018

Let [Formula: see text] denote the number of partitions of a non-negative integer into distinct (or, odd) parts. We find exact generating functions for [Formula: see text], [Formula: see text] and [Formula: see text]. We deduce some congruences modulo 5 and 25. We employ Ramanujan’s theta function identities and some identities for the Rogers–Ramanujan continued fraction.
Generalized cyclotomic numbers with respect to prime powers
Authors: Choe Chunghyok
Published: March 2018

In this paper, we study the generalized cyclotomic numbers with respect to the powers of odd primes, where at most one prime is of the form [Formula: see text]. We calculate the generalized cyclotomic numbers of order [Formula: see text] with respect to [Formula: see text] when the odd primes [Formula: see text] and the positive integers [Formula: see text] satisfy [Formula: see text] for [Formula: see text] and [Formula: see text] for [Formula: see text].
Containers will not fix your broken culture (and other hard truths)
Authors: Kromhout Bridget
Published: March 2018

Complex socio-technical systems are hard; film at 11.
Business ecosystems
Authors: Sako Mari
Published: March 2018

Considering the significant interrelationship of innovation, corporate strategy, and public policy for business ecosystems.
Realizing the potential of data science
Authors: Berman Francine , Rutenbar Rob , Hailpern Brent , Christensen Henrik , Davidson Susan , Estrin Deborah , Franklin Michael , Martonosi Margaret , Raghavan Padma , Stodden Victoria , Szalay Alexander S.
Published: March 2018

Data science promises new insights, helping transform information into knowledge that can drive science and industry.
Vocal Resonance
Authors: Liu Rui , Cornelius Cory , Rawassizadeh Reza , Peterson Ronald , Kotz David
Published: March 2018

We observe the advent of body-area networks of pervasive wearable devices, whether for health monitoring, personal assistance, entertainment, or home automation. For many devices, it is critical to identify the wearer, allowing sensor data to be properly labeled or personalized behavior to be properly achieved. In this paper we propose the use of vocal resonance, that is, the sound of the person's voice as it travels through the person's body -- a method we anticipate would be suitable for devices worn on the head, neck, or chest. In this regard, we go well beyond the simple challenge of speaker recognition: we want to know who is wearing the device. We explore two machine-learning approaches that analyze voice samples from a small throat-mounted microphone and allow the device to determine whether (a) the speaker is indeed the expected person, and (b) the microphone-enabled device is physically on the speaker's body. We collected data from 29 subjects, demonstrate the feasibility of a prototype, and show that our DNN method achieved balanced accuracy 0.914 for identification and 0.961 for verification by using an LSTM-based deep-learning model, while our efficient GMM method achieved balanced accuracy 0.875 for identification and 0.942 for verification.
Third-Eye
Authors: Liu Liang , Liu Wu , Zheng Yu , Ma Huadong , Zhang Cheng
Published: March 2018

Air pollution has raised people's public health concerns in major cities, especially for Particulate Matter under 2.5μm (PM2.5) due to its significant impact on human respiratory and circulation systems. In this paper, we present the design, implementation, and evaluation of a mobile application, Third-Eye, that can turn mobile phones into high-quality PM2.5 monitors, thereby enabling a crowdsensing way for fine-grained PM2.5 monitoring in the city. We explore two ways, crowdsensing and web crawling, to efficiently build large-scale datasets of the outdoor images taken by mobile phone, weather data, and air-pollution data. Then, we leverage two deep learning models, Convolutional Neural Network (CNN) for images and Long Short Term Memory (LSTM) network for weather and air-pollution data, to build an end-to-end framework for training PM2.5 inference models. Our App has been downloaded more than 2,000 times and runs more than 1 year. The real user data based evaluation shows that Third-Eye achieves 17.38 μg/m3 average error and 81.55% classification accuracy, which outperforms 5 state-of-the-art methods, including three scattered interpolations and two image based estimation methods. The results also demonstrate how Third-Eye offers substantial enhancements over typical portable PM2.5 monitors by simultaneously improving accessibility, portability, and accuracy.
Riskalyzer
Authors: Singh Vivek K. , Goyal Rushil , Wu Shenghao
Published: March 2018

An individual's risk-taking propensity is "the stable tendency to choose options with a lower probability of success, but greater rewards". This risk propensity plays a central role in decision making by customers as well as managers, and is a mediator in behavior associated with security, privacy, health, finance, and well-being. Most common approach to understanding an individual's risk propensity remain lab-based games and surveys. Administering such surveys and games is a manual, time, and money intensive process that is also fraught with multiple biases. Recently, smartphones are increasingly seen as large-scale sensors of human activity, recording data related to physical and social aspects of people's lives. Building on this trend we investigate the potential of passive phone-based data for automatically inferring an individual's risk propensity. Specifically, we describe a novel approach to model an individual's risk propensity based on her mobile phone usage. Based on a 10-week field + lab study involving 50 participants, we report that: (1) multiple phone-based features (e.g., average gyradius) are intricately associated with participants' risk propensity; and (2) a phone-based model outperforms demography-based models by 39% in terms of accuracy of predicting risk propensity. In organizational terms, a better understanding of risk behavior could contribute significantly to risk management programs. At the same time, such results could open doors for more nuanced understanding of the underlying human risk phenomena and their interconnections with social and mobility behavior.
Smartwatch-based Early Gesture Detection 8 Trajectory Tracking for Interactive Gesture-Driven Applications
Authors: Vu Tran Huy , Misra Archan , Roy Quentin , Wei Kenny Choo Tsu , Lee Youngki
Published: March 2018

The paper explores the possibility of using wrist-worn devices (specifically, a smartwatch) to accurately track the hand movement and gestures for a new class of immersive, interactive gesture-driven applications. These interactive applications need two special features: (a) the ability to identify gestures from a continuous stream of sensor data early--i.e., even before the gesture is complete, and (b) the ability to precisely track the hand's trajectory, even though the underlying inertial sensor data is noisy. We develop a new approach that tackles these requirements by first building a HMM-based gesture recognition framework that does not need an explicit segmentation step, and then using a per-gesture trajectory tracking solution that tracks the hand movement only during these predefined gestures. Using an elaborate setup that allows us to realistically study the table-tennis related hand movements of users, we show that our approach works: (a) it can achieve 95% stroke recognition accuracy. Within 50% of gesture, it can achieve a recall value of 92% for 10 novice users and 93% for 15 experienced users from a continuous sensor stream; (b) it can track hand movement during such strokeplay with a median accuracy of 6.2 cm.
Accurate and Efficient Indoor Location by Dynamic Warping in Sequence-Type Radio-map
Authors: Ye Xuehan , Wang Yongcai , Guo Yuhe , Hu Wei , Li Deying
Published: March 2018

An efficient way to overcome the calibration challenge and RSS dynamics in radio-map-based indoor localization is to collect radio signal strength (RSS) along indoor paths and conduct localization by sequence matching. But such sequence-based indoor localization suffers problems including indoor path combinational explosion, random RSS miss-of-detection during user movement, and user moving speed disparity in online and offline phases. To address these problems, this paper proposes an undirected graph model, called WarpMap to efficiently calibrate and store the sequence-type radio-map. It reduces RSS sequence signature storage complexity from O(2N) to O(N) where N is the number of path crosses. An efficient on-line candidate path extraction algorithm is developed in it to find a set of the most possible candidate paths for matching with the on-line collected RSS sequence. Then, to determine the user's exact location, a sub-sequence dynamic time warping (SDTW) algorithm is proposed, which matches the online collected RSS sequence with the sequential RSS signatures of the candidate paths. We show the SDTW algorithm is highly efficient and adaptive, which localizes user without backtracking of warping path. Extensive experiments in office environments verified the efficiency and accuracy of WarpMap, which can be calibrated within thirty minutes by one person for 1100m2 area and provides overall nearly 20% accuracy improvements than the state-of-the-art of radio-map method.
Detecting Urban Anomalies Using Multiple Spatio-Temporal Data Sources
Authors: Zhang Huichu , Zheng Yu , Yu Yong
Published: March 2018

Urban anomalies, such as abnormal movements of crowds and accidents, may result in loss of life or property if not handled properly. It would be of great value for governments if anomalies can be automatically alerted in their early stage. However, detecting anomalies in urban area has two main challenges. First, the criteria to determine an anomaly on different occasions (e.g. rainy days vs. sunny days, or holidays vs. workdays) and in different places (e.g. tourist attractions vs. office areas) are distinctly different, as these occasions and places have their own definitions on normal patterns. Second, urban anomalies often exhibit complex forms (e.g. road closure may cause decrease in taxi flow and increase in bike flow). We need an algorithm that not only models the anomaly degree of individual data source but also the combination of changes in multiple data sources. In this paper, we propose a two-step method to tackle those challenges. In the first step, we use a similarity-based algorithm to estimate an anomaly score for each individual data source in each region and time slot based on the values of historically similar regions. Those scores are fed into the second step, where we propose an algorithm based on one-class Support Vector Machine to capture rare patterns occurred in multiple data sources, nearby regions or time slots, and give a final, integrated anomaly score for each region. Evaluations based on both synthetic and real world datasets show the advantages of our method beyond baseline techniques such as distance-based, probability-based methods.
Use of Natural Selection and Evolution to Develop New Starter Cultures for Fermented Foods
Authors: Johansen Eric
Published: March 2018

The fermented foods industry is constantly seeking new starter cultures to deal with changing consumer preferences and new fermentation processes. New cultures can either be composed of strains isolated from nature or improved derivatives of existing isolates. A variety of techniques involving natural selection and evolution are available to enhance the performance of existing strains, including the isolation of mutants with desired properties, adaptive laboratory evolution, genome shuffling, and genome editing. Numerous examples of traits that can be improved are provided. These include resistance to bacteriophages; the secretion of glucose to increase sweetness; the production of vitamins, antifungal compounds, bacteriocins, texture, or aroma; enhancement of acidification rates and acid tolerance; and elimination of biofilm formation. Careful consideration is required to ensure the developed strains are suitable for the desired purpose, as some approaches may lead to regulatory concerns.
Stability and Stabilization of Enzyme Biosensors: The Key to Successful Application and Commercialization
Authors: Reyes-De-Corcuera José I. , Olstad Hanna E. , García-Torres Rosalía
Published: March 2018

Fifty-five years have passed and more than 100,000 articles have been published since the first report of an electrochemical enzyme biosensor. However, very few biosensors have reached practical application and commercialization. The bulk of the research effort has been on increasing sensitivity and selectivity. In contrast, the number of publications dealing with stability or stabilization of enzyme biosensors is very small. Here, we critically review enzyme stabilization strategies as well as the progress that has been done in the past 20 years with respect to enzyme biosensor stabilization. Glucose oxidase, lactate oxidase, alcohol oxidase, and xanthine oxidase are the focus of this review because of their potential applications in food. The inconsistency in reporting biosensor stability was identified as a critical hurdle to research progress in this area. Fundamental questions that remain unanswered are outlined.
A Novel Association of Polymorphism in theITGA4Gene Encoding the VLA-4α4 Subunit with Increased Risk of Alzheimer’s Disease
Authors: Durmanova Vladimira , Parnicka Zuzana , Javor Juraj , Minarik Gabriel , Vrazda Lubomir , Vaseckova Barbora , Gmitterova Karin , Kralova Maria , Pecenak Jan , Filipcik Peter , Shawkatova Ivana
Published: March 2018

Alzheimer’s disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin moleculeα4β1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in theITGA4gene encoding theα4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped forITGA4gene SNP polymorphism rs113276800 (−269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for theAPOE-ε4, which is a known genetic factor associated with increased risk of AD developing.ITGA4polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P≤0.05). Following theAPOE-ε4 stratification of study groups, the association remained significant only inAPOE-ε4 noncarriers. Our study suggests a novel association ofITGA4+3061A/G polymorphism with AD and its possible contribution to the disease pathology.
Production of Adult Human Synovial Fluid-Derived Mesenchymal Stem Cells in Stirred-Suspension Culture
Authors: Jorgenson Kristen D. , Hart David A. , Krawetz Roman , Sen Arindom
Published: March 2018

The chondrogenic potential of synovial fluid-derived mesenchymal stem cells (SF-MSCs) supports their use in cartilage regeneration strategies. However, their paucity in synovial fluid necessitates their proliferation in culture to generate clinically relevant quantities. Here it was determined that 125 mL stirred suspension bioreactors utilizing Cytodex-3 microcarrier beads represent a viable platform for the proliferation of these cells. During the inoculation phase, a bead loading of 2 g/L, an inoculation ratio of 4.5 cells/bead, and continuous agitation at 40 rpm in a medium with 5% serum resulted in high cell attachment efficiencies and a subsequent overall cell fold expansion of 5.7 over 8 days. During the subsequent growth phase, periodic addition of new microcarriers and fresh medium increased culture longevity, resulting in a 21.3 cell fold increase over 18 days in the same vessel without compromising the defining characteristics of the cells. Compared to static tissue culture flasks, a bioreactor-based bioprocess requires fewer handling steps, is more readily scalable, and for the same cell production level, has a lower operating cost as it uses approximately half the medium. Therefore, stirred suspension bioreactors incorporating microcarrier technology represent a viable and more efficient platform than tissue culture flasks for the generation of SF-MSCs in culture.
Efficacy of Suxiao Jiuxin Pill on Coronary Heart Disease: A Meta‐Analysis of Randomized Controlled Trials
Authors: Ren Li , Wang Jie , Feng Ling , Wang Shuli , Li Jun
Published: March 2018

Suxiao jiuxin pill is considered an effective ancillary drug in patients with coronary heart disease. Although numerous small, single‐center clinical trials have been conducted, the benefits and harms of suxiao jiuxin pill remain controversial. We performed a meta‐analysis to clarify the efficacy of suxiao jiuxin pill on patients with coronary heart disease. Randomized controlled trials were identified by using the Cochrane Library, PubMed, Web of Science, Embase, Wanfang, Weipu, and China Knowledge Resource Integrated databases (until June 2016). Pooled relative risks (RR), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were estimated using random‐effects models. Forty‐one trials involving 6276 patients were included in our analysis. Administration of suxiao jiuxin pill significantly improved electrocardiogram (ECG) results when compared with other therapies (RR 1.32, 95% CI 1.26 to 1.38, and P < 0.001). Subgroup analyses revealed that suxiao jiuxin pills improve ECG results more than salvia tablets (RR 1.54, 95% CI 1.41 to 1.67, and P < 0.001), isosorbide dinitrate (RR 1.14, 95% CI 1.21 to 1.44, and P = 0.001), nitroglycerin (RR 1.35, 95% CI 1.16 to 1.56, and P < 0.001), and other drugs (RR 1.32, 95% CI 1.21 to 1.44, and P < 0.001). Available evidence additionally suggests that suxiao jiuxin pills could significantly reduce total cholesterol (WMD −0.62 mmol/L, 95% CI −1.06 to –0.18 mmol/L, and P = 0.005) and low‐density lipoprotein (LDL) levels (WMD −1.12 mmol/L, 95% CI −1.42 to −0.82 mmol/L, and P < 0.001) and increase high‐density lipoprotein (HDL) levels (WMD 0.32 mmol/L, 95% CI 0.07 to 0.58 mmol/L, and P = 0.014). However, no significant differences were observed in total triglyceride levels, plasma viscosity, hematocrit, and fibrinogen. No incidences of adverse reactions were observed after administration of suxiao jiuxin pill. Improvements in ECG results and lipid profiles were also observed after suxiao jiuxin administration compared to other therapies. It also decreased low‐cut and high‐cut whole blood viscosity without significant adverse reactions.
IκB Kinase α Is Required for Development and Progression of KRAS-Mutant Lung Adenocarcinoma
Authors: Vreka Malamati , Lilis Ioannis , Papageorgopoulou Maria , Giotopoulou Georgia A. , Lianou Marina , Giopanou Ioanna , Kanellakis Nikolaos I. , Spella Magda , Agalioti Theodora , Armenis Vasileios , Goldmann Torsten , Marwitz Sebastian , Yull Fiona E. , Blackwell Timothy S. , Pasparakis Manolis , Marazioti Antonia , Stathopoulos Georgios T.
Published: March 2018

Although oncogenic activation of NFκB has been identified in various tumors, the NFκB–activating kinases (inhibitor of NFκB kinases, IKK) responsible for this are elusive. In this study, we determined the role of IKKα and IKKβ in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane and by respiratory epithelial expression of oncogenic KRASG12D. Using NFκB reporter mice and conditional deletions of IKKα and IKKβ, we identified two distinct early and late activation phases of NFκB during chemical and genetic lung adenocarcinoma development, which were characterized by nuclear translocation of RelB, IκBβ, and IKKα in tumor-initiated cells. IKKα was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung adenocarcinoma, and respiratory epithelial IKKα-deficient mice were markedly protected from the disease. IKKα specifically cooperated with mutant KRAS for tumor induction in a cell-autonomous fashion, providing mutant cells with a survival advantage in vitro and in vivo. IKKα was highly expressed in human lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK function delivered superior effects against KRAS-mutant lung adenocarcinoma compared with a specific IKKβ inhibitor. These results demonstrate an actionable requirement for IKKα in KRAS-mutant lung adenocarcinoma, marking the kinase as a therapeutic target against this disease.

Significance: These findings report a novel requirement for IKKα in mutant KRAS lung tumor formation, with potential therapeutic applications. Cancer Res; 78(11); 2939–51. ©2018 AACR.
A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53
Authors: Mao Chao , Wang Xiang , Liu Yating , Wang Min , Yan Bin , Jiang Yiqun , Shi Ying , Shen Yi , Liu Xiaoli , Lai Weiwei , Yang Rui , Xiao Desheng , Cheng Yan , Liu Shuang , Zhou Hu , Cao Ya , Yu Weishi , Muegge Kathrin , Yu Herbert , Tao Yongguang
Published: March 2018

Long noncoding RNAs (lncRNA) have been associated with various types of cancer; however, the precise role of many lncRNAs in tumorigenesis remains elusive. Here we demonstrate that the cytosolic lncRNA P53RRA is downregulated in cancers and functions as a tumor suppressor by inhibiting cancer progression. Chromatin remodeling proteins LSH and Cfp1 silenced or increased P53RRA expression, respectively. P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA–G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis. P53RRA promoted ferroptosis and apoptosis by affecting transcription of several metabolic genes. Low P53RRA expression significantly correlated with poor survival in patients with breast and lung cancers harboring wild-type p53. These data show that lncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression.

Significance: A cytosolic lncRNA functions as a tumor suppressor by activating the p53 pathway. Cancer Res; 78(13); 3484–96. ©2018 AACR.
ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer
Authors: Lev Avital , Lulla Amriti R. , Ross Brian C. , Ralff Marie D. , Makhov Petr B. , Dicker David T. , El-Deiry Wafik S.
Published: March 2018

Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel.

Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754–66. ©2018 AACR.
Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature
Authors: Benzel Julia , Fendrich Volker
Published: March 2018

Background: Pancreatic ductal adenocarcinoma is one of the most lethal types of cancer with a 5-year survival rate of around 7%. Due to the relatively poor prognosis, the potential need of an effective chemoprevention is highly needed. Summary: Different risk factors like smoking or hereditary tumour syndromes should be known for early detection of pancreatic intraepithelial neoplasia. Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas potential chemopreventive drugs compromise aspirin, metformin or statins. This review aims to give an overview on potential risk factors for the development of pancreatic cancer. Furthermore, we try to summarise known chemopreventive agents to support the fight against this lethal disease. Key Messages: On the one hand, there are natural agents that exhibit preventive properties and can lead to the prohibition of pancreatic cancer. On the other hand, there are drugs and agents that are currently used in other contexts and are thus already approved and studied in terms of their mechanisms of effects and the related secondary effects.
Medical Therapy of Gastroesophageal Reflux Disease Beyond Proton Pump Inhibitors: Where Are We Heading
Authors: Koop Herbert
Published: March 2018

Proton pump inhibitors (PPI) have greatly improved the treatment of gastroesophageal reflux disease. However, recent investigations have revealed that reflux symptoms persist in a substantial number of patients. Therefore, treatment strategies beyond PPI are urgently required. One such strategy may involve more reliable acid suppression, e.g., with new acid inhibitory drugs. Furthermore, the rapid appearance of an acidic compartment in the proximal stomach after a meal, which is largely responsible for postprandial heartburn, requires a specific kind of therapy in addition to PPI which still needs to be established. Pharmacological augmentation of the lower esophageal sphincter may represent another approach to diminish reflux, but the clinical efficacy of compounds tested so far is limited. Altered e-sophageal perception represents a major component involved in the generation of reflux symptoms, particularly in non-erosive reflux disease, but effective pharmacological intervention is largely lacking. Presumed reflux-induced respiratory symptoms (cough, laryngitis, etc.) in the absence of typical esophageal symptoms (e.g., heartburn) remain a hot topic, but recent research points towards a hypersensitivity syndrome and only a minor role of gastroesophageal reflux. Treatment options for this condition are still pending.
Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals
Authors: Muniyappa Ranganath , Noureldin Radwa A. , Abd-Elmoniem Khaled Z. , El Khouli Riham H. , Matta Jatin Raj , Hamimi Ahmed , Ranganath Siri , Hadigan Colleen , Nieman Lynnette K. , Gharib Ahmed M.
Published: March 2018

Background: Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR10 benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. Aims: In this study, we compared the predicted ARR10 obtained in each individual with plaque burden detected by coronary computed tomography angiography. Methods and Results: Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (n = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR10 with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR10 benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (p = 0.02). Conclusion: These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk.
Efficacy Analysis of Capsaicin 8% Patch in Neuropathic Peripheral Pain Treatment
Authors: Tenreiro Pinto Joana , Pereira Frederico C. , Loureiro Maria C. , Gama Ricardo , Fernandes Hugo L.
Published: March 2018

Background/Aims: Several guidelines for neuropathic pain management and various effective drugs are available; however, neuropathic pain remains undertreated. This retrospective study aimed to evaluate the efficacy of topical capsaicin 8% in peripheral neuropathic pain in a routine clinical setting. Methods: Therapeutic efficacy was evaluated through pain intensity, using numerical pain rating scale at baseline and 7–14 days after each treatment, and using pain treatment area (PTA) assessed immediately before each treatment. Results: A total of 43 patients with either post-herpetic neuralgia or post-traumatic/post-surgical neuropathic pain were enrolled. The median percentage reduction in numerical pain rating scale score and in PTA was –40.0 (–50.0 to –33.3; 95% CI, bootstrap) and –35.1 (–50.9 to 3.4; 95% CI, bootstrap), respectively. Pain intensity and PTA were equally improved and reduced in both treated conditions. Conclusion: This study suggests that topical capsaicin 8% reduces peripheral neuropathic pain as well as treatment pain area.
Gemcitabine-Induced Radiation Recall Myositis: Case Report and Review of the Literature
Authors: Ravishankar Adarsh , Park Sean S. , Olivier Kenneth R. , Corbin Kimberly S.
Published: March 2018

Gemcitabine-induced radiation recall (GIRR) is a phenomenon wherein the administration of gemcitabine induces an inflammatory reaction within an area of prior radiation. We present the case of a 39-year-old female patient with metastatic breast cancer who experienced GIRR myositis 3 months following postoperative radiotherapy, with additional potential paraspinal myositis following ablative radiotherapy to the thoracic spine. A review of previously published cases of GIRR myositis was performed. The case and literature review describe the clinical course and presentation of GIRR, and highlight the importance of including radiation recall as part of a differential diagnosis when a patient undergoing chemotherapy experiences an inflammatory reaction at a prior site of radiation.
Longitudinal Half-and-Half Nails: Case Report and Review
Authors: Cohen Philip R.
Published: March 2018

Half-and-half nails were originally described as a transverse leukonychia in patients with chronic renal disease; other conditions (such as Behcet’s and Crohn’s disease) and medications (such as isoniazid) have also been associated with the nail changes. However, longitudinal half-and-half nails (affecting the medial aspects of the nails) have previously been reported on the great toes of an older woman and, in the present case, on the thumbs of an elderly man; neither person had Behcet’s, Crohn’s, or kidney disease or was receiving isoniazid. The woman had a true leukonychia, bilateral hallux valgus deformity, and chronic trauma to her medial nail folds. The man had a nontraumatic apparent leukonychia and bilateral koilonychia; the non-white lateral area of his left thumb also had a linear groove (resulting from a digital mucous cyst on the proximal nail fold) and subun gual hyperkeratosis. In conclusion, longitudinal half-and-half nails are a rare phenomenon that has not been associated with either a systemic disease or medication; the acquired nail change can present either as an idiopathic finding or occur secondary to chronic trauma.
Hemicrania Continua Associated with Classic Scintillating Scotoma
Authors: Auffenberg Eva , Bender Friedemann , Freilinger Tobias
Published: March 2018

Hemicrania continua (HC) is a rare primary headache disorder, characterized by persistent unilateral pain associated with cranial autonomic symptoms and prompt response to indomethacin. While migrainous features (including aura) have been recognized in cluster headache, there have been only single reports of HC with aura. Here, we report the case of a 53-year-old man with constant right-sided headache and superimposed exacerbations to severe pain lasting for several hours. Secondary etiologies were excluded, and a diagnosis of HC was established after prompt and complete response to treatment with indomethacin. During an episode of pain exacerbation, for the first time the patient experienced an episode of transient visual disturbances compatible with scintillating scotoma. We propose a potential link between HC and visual aura, which parallels similar observations in other trigeminal autonomic cephalalgias and more specifically confirms previous observational data on aura in HC, thus highlighting potentially shared pathophysiological mechanisms.
Functions of the Signal Transducer and Activator of Transcription 6 in a Behavioral Animal Model of Depression
Authors: Nam Sun-Young , Kim Hee-Yun , Lee Hyung Eun , Ryu Jong Hoon , Jang Jae-Bum , Kim Hyung-Min , Jeong Hyun-Ja
Published: March 2018

Aims: Depression is one of the most common inflammatory and mental disorders. Signal transducer and activator of transcription 6 (STAT6) plays a crucial role in the pathology of mental disorders as well as inflammatory diseases. Methods: Here we determined the role of STAT6 in the pathogenesis of depression using STAT6-deficient mice in a forced swimming test. Results: The immobility time was significantly decreased in STAT6-deficient mice compared to wild-type mice without alteration of locomotor activity. STAT6-deficient mice exhibited a significantly enhancing dopamine and 5-hydroxytryptamine (5-HT, serotonin) in brain. In addition, the expression of serotonin transporter in the hippocampus was markedly downregulated in STAT6-deficient mice. These results provide the first evidence that STAT6 affects depressive-like behavior through downregulating monoamines, including dopamine and 5-HT in the hippocampus of brain. Conclusions: In conclusion, identification of STAT6 signaling pathways on depression might open new perspectives for antidepressant therapies.
A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network
Authors: Bohmann Ferdinand O. , Tahtali Damla , Kurka Natalia , Wagner Marlies , You Se-Jong , du Mesnil de Rochemont Richard , Berkefeld Joachim , Hartmetz Ann-Kathrin , Kuhlmann Andrea , Lorenz Matthias W. , Schütz Ansgar , Kress Bodo , Henke Christian , Tritt Stephanie , Meyding-Lamadé Uta , Steinmetz Helmuth , Pfeilschifter Waltraud
Published: March 2018

Background and Purpose: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. Methods: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January – June 2015, n = 80 vs. July 2015 – June 2016, n = 184). Results: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25–75% interquartile range [IQR] 231–381 min to 254 min, IQR 215.25–341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35–102 min to 43.5 min, IQR 27.75–81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5–170.5 min to 114.5 min, IQR 66.5–151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). Conclusions: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.
Fats in Foods: Current Evidence for Dietary Advice
Authors: Nettleton Joyce A. , Brouwer Ingeborg A. , Mensink Ronald P. , Diekman Connie , Hornstra Gerard
Published: March 2018

Current discussion of the importance of food fats in the risk of coronary heart disease (CHD) often suffers from preconceptions, misunderstandings, insufficient knowledge, and selective reasoning. As a result, the sustained controversy about dietary fat recommendations can be contradictory and confusing. To clarify some of these issues, the International Expert Movement to Improve Dietary Fat Quality in cooperation with the International Union of Nutritional Sciences (IUNS) organized a symposium at the 21st meeting of the IUNS, October 17, 2017, Buenos Aires, Argentina, to summarize the key scientific evidence underlying the controversy on the relationship between the saturated and unsaturated fat consumption and CHD risk. Presenters also discussed, using examples, the rationale for and implications of the partial replacement of foods rich in saturated fats by those rich in unsaturated fats. Presentations included strategies to fit healthier fats into meals. This report summarizes the symposium presentations.
Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum from Patients with Peripheral Artery Diseases
Authors: Sosińska-Zawierucha Patrycja , Maćkowiak Beata , Staniszewski Ryszard , Sumińska-Jasińska Katarzyna , Maj Magdalena , Krasiński Zbigniew , Bręborowicz Andrzej
Published: March 2018

Background/Aims: Aging of the arterial endothelial cells results in the appearance of their inflammatory phenotype, which may predispose patients to the acceleration of arteriosclerosis. We studied the effect of serum from patients with peripheral artery disease (PAD) on the senescence of human aortic endothelial cells (HAEC) and how that process is modulated by sulodexide. Methods: HAEC replicative aging in vitro was studied in the presence of 10% PAD-serum (PAD Group) or10%PAD serum and Sulodexide 0.5 LRU/mL (PAD-SUL group). In control group cells were cultured in medium supplemented with 10% fetal bovine serum. All studied parameters were evaluated at the beginning and at the end of the study, in all experimental groups. Population doubling time (PDT) was studied from the cells growth rate after repeated passages, and senescence-associated beta- galactosidase activity (SA-β gal activity) was measured with the fluorescence flow cytometry. Expression of IL6, vWF, p21 and p53 genes was measured with the real-time polymerase chain reaction (Real-Time PCR). Concentrations of IL6 and vWF were measured with the standard ELISA kits. Results: PAD serum accelerated the senescence of HAEC as reflected by increased, compared to control, expression of the IL6 gene (+43%, p<0.05) vWF gene (+443%, p<0.01), p21 gene (+ 124%, p<0.01) and p53 gene (+ 85%, p<0.01). Secretion of IL6 and vWF was higher in that group: + 101%, p<0.01 and + 78%, p<0.01, respectively, as compared to control. Also, SA-β gal activity was higher in the PAD group (+33%, p<0.05) than in the control group. In the PAD group PDT was longer (+108%, p<0.01) as compared to control. Simultaneous use of Sulodexide with PAD serum significantly reduced all the above described senescent changes in HAEC. Conclusions: PAD serum accelerates the aging of HAEC which may result in the faster progression of arteriosclerosis. Sulodexide reduces PAD induced senescence of HAEC, which results in lower inflammatory and thrombogenic activity of these cells.