bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Points of Elliptic Curve y2=x3+k3
Authors: Wu Xia , Qin Yan
Published: January 2018

Let E be an elliptic curve defined over the field of rational numbers ℚ. Let d be a square-free integer and let Ed be the quadratic twist of E determined by d. Mai, Murty and Ono have proved that there are infinitely many square-free integers d such that the rank of Ed(ℚ) is zero. Let E(k) denote the elliptic curve y2 = x3 + k. Then the quadratic twist E(1)d of E(1) by d is the elliptic curve [Formula: see text]. Let r = 1, 2, 5, 10, 13, 14, 17, 22. Ono proved that there are infinitely many square-free integers d ≡ r (mod 24) such that rank [Formula: see text], using the theory of modular forms. In this paper, we use the class number of quadratic field and Pell equation to describe these square-free integers k such that E(k3)(ℚ) has rank zero.
Automatic Software Repair
Authors: Monperrus Martin
Published: January 2018

This article presents a survey on automatic software repair. Automatic software repair consists of automatically finding a solution to software bugs without human intervention. This article considers all kinds of repairs. First, it discusses behavioral repair where test suites, contracts, models, and crashing inputs are taken as oracle. Second, it discusses state repair, also known as runtime repair or runtime recovery, with techniques such as checkpoint and restart, reconfiguration, and invariant restoration. The uniqueness of this article is that it spans the research communities that contribute to this body of knowledge: software engineering, dependability, operating systems, programming languages, and security. It provides a novel and structured overview of the diversity of bug oracles and repair operators used in the literature.
Prioritized Relationship Analysis in Heterogeneous Information Networks
Authors: Liang Jiongqian , Ajwani Deepak , Nicholson Patrick K. , Sala Alessandra , Parthasarathy Srinivasan
Published: January 2018

An increasing number of applications are modeled and analyzed in network form, where nodes represent entities of interest and edges represent interactions or relationships between entities. Commonly, such relationship analysis tools assume homogeneity in both node type and edge type. Recent research has sought to redress the assumption of homogeneity and focused on mining heterogeneous information networks (HINs) where both nodes and edges can be of different types. Building on such efforts, in this work, we articulate a novel approach for mining relationships across entities in such networks while accounting for user preference over relationship type and interestingness metric. We formalize the problem as a top-
k
lightest paths problem, contextualized in a real-world communication network, and seek to find the
k
most interesting path instances matching the preferred relationship type. Our solution, PROphetic HEuristic Algorithm for Path Searching (PRO-HEAPS), leverages a combination of novel graph preprocessing techniques, well-designed heuristics and the venerable A* search algorithm. We run our algorithm on real-world large-scale graphs and show that our algorithm significantly outperforms a wide variety of baseline approaches with speedups as large as 100X.

To widen the range of applications, we also extend PRO-HEAPS to (i) support relationship analysis between two groups of entities and (ii) allow pattern path in the query to contain logical statements with operators AND, OR, NOT, and wild-card “.”. We run experiments using this generalized version of PRO-HEAPS and demonstrate that the advantage of PRO-HEAPS becomes even more pronounced for these general cases. Furthermore, we conduct a comprehensive analysis to study how the performance of PRO-HEAPS varies with respect to various attributes of the input HIN. We finally conduct a case study to demonstrate valuable applications of our algorithm.
Large-Scale Bayesian Probabilistic Matrix Factorization with Memo-Free Distributed Variational Inference
Authors: Chen Guangyong , Zhu Fengyuan , Heng Pheng Ann
Published: January 2018

Bayesian Probabilistic Matrix Factorization (BPMF) is a powerful model in many dyadic data prediction problems, especially the applications of Recommender system. However, its poor scalability has limited its wide applications on massive data. Based on the conditional independence property of observed entries in BPMF model, we propose a novel distributed memo-free variational inference method for large-scale matrix factorization problems. Compared with the state-of-the-art methods, the proposed method is favored for several attractive properties. Specifically, it does not require tuning of learning rate carefully, shuffling the training set at each iteration, or storing massive redundant variables, and can introduce new agents into the computations on the fly. We conduct extensive experiments on both synthetic and real-world datasets. The experimental results show that our method can converge significantly faster with better prediction performance than alternative algorithms.
The next phase in the digital revolution
Authors: Zysman John , Kenney Martin
Published: January 2018

Digital technology determines how (and even whether) people work as much as it determines how information produces economic activity.
The Random Assignment Problem with Submodular Constraints on Goods
Authors: Fujishige Satoru , Sano Yoshio , Zhan Ping
Published: January 2018

Problems of allocating indivisible goods to agents in an efficient and fair manner without money have long been investigated in literature. The random assignment problem is one of them, where we are given a fixed feasible (available) set of indivisible goods and a profile of ordinal preferences over the goods, one for each agent. Then, using lotteries, we determine an assignment of goods to agents in a randomized way. A seminal paper of Bogomolnaia and Moulin (2001) shows a probabilistic serial (PS) mechanism to give an ordinally efficient and envy-free solution to the assignment problem.

In this article, we consider an extension of the random assignment problem to submodular constraints on goods. We show that the approach of the PS mechanism by Bogomolnaia and Moulin is powerful enough to solve the random assignment problem with submodular (matroidal and polymatroidal) constraints. Under the agents’ ordinal preferences over goods we show the following:

(1) The obtained PS solution for the problem with unit demands and matroidal constraints is ordinally efficient, envy-free, and weakly strategy-proof with respect to the associated stochastic dominance relation.

(2)For the multiunit demand and polymatroidal constraint problem, the PS solution is ordinally efficient and envy-free but is not strategy-proof in general. However, we show that under a mild condition (that is likely to be satisfied in practice) the PS solution is a weak Nash equilibrium.
Risks of trusting the physics of sensors
Authors: Fu Kevin , Xu Wenyuan
Published: January 2018

Protecting the Internet of Things with embedded security.
A Multiple Kernel Learning Model Based on p-Norm
Authors: Qi Jinshan , Liang Xun , Xu Rui
Published: January 2018

By utilizing kernel functions, support vector machines (SVMs) successfully solve the linearly inseparable problems. Subsequently, its applicable areas have been greatly extended. Using multiple kernels (MKs) to improve the SVM classification accuracy has been a hot topic in the SVM research society for several years. However, most MK learning (MKL) methods employ L1-norm constraint on the kernel combination weights, which forms a sparse yet nonsmooth solution for the kernel weights. Alternatively, the Lp-norm constraint on the kernel weights keeps all information in the base kernels. Nonetheless, the solution of Lp-norm constraint MKL is nonsparse and sensitive to the noise. Recently, some scholars presented an efficient sparse generalized MKL (L1- and L2-norms based GMKL) method, in which L1  L2 established an elastic constraint on the kernel weights. In this paper, we further extend the GMKL to a more generalized MKL method based on the p-norm, by joining L1- and Lp-norms. Consequently, the L1- and L2-norms based GMKL is a special case in our method when p=2. Experiments demonstrated that our L1- and Lp-norms based MKL offers a higher accuracy than the L1- and L2-norms based GMKL in the classification, while keeping the properties of the L1- and L2-norms based on GMKL.
Metabolic Profiling Analysis of the Alleviation Effect of the Fractions of Niuhuang Jiedu Tablet on Realgar Induced Toxicity in Rats
Authors: Xu Wenfeng , Pei Yuehu , Xu Shuo , Wang Haifeng , Jin Pengfei
Published: January 2018

Niuhuang Jiedu Tablet (NJT) is a classical formula in treating acute tonsillitis, pharyngitis, and so on. In the formula, significant level of Realgar as a potentially toxic element is contained. Our previous experiments revealed that it was less toxic for combined Realgar in NJT. However, the active fraction of this prescription with toxicity alleviation effect on Realgar was still obscure. NJT was divided into five different polar fractions (NJT‐PET, NJT‐25, NJT‐50, NJT‐75, and NJT‐95), and we explored the toxicity alleviation effect on Realgar. Based on 1H NMR spectra of urine and serum from rats, PCA and PLS‐DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. With pattern recognition analysis of metabolites in urine and serum, Realgar group showed a clear separation from control group, while the metabolic profiles of NJT‐PET, NJT‐25, NJT‐50, and NJT‐95 groups were similar to Realgar group, and the metabolic profiles of NJT and NJT‐75 groups were very close to control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work indicated that 75% EtOH fraction of NJT was the most valid fraction with the toxicity alleviation effect on Realgar.
Inexpensive Apparatus for Fabricating Microspheres for 5-Fluorouracil Controlled Release Systems
Authors: Barbosa Hanniman Denizard Cosme , Santos Bárbara Fernanda Figueiredo dos , Tavares Albaniza Alves , Barbosa Rossemberg Cardoso , Fook Marcus Vinícius Lia , Canedo Eduardo Luis , Silva Suédina Maria de Lima
Published: January 2018

The aim of this study was to develop an inexpensive apparatus for fabricating microspheres, based on chitosan, for 5-fluorouracil (5-FU) controlled release. Chitosan microspheres were prepared by precipitation method and the effects of manufacturing parameters (injection and airflow rates) on size distribution microspheres were analyzed by optical and scanning electron microscopy. The results show that the manufacturing parameters, injection and airflow rates, determine the microsphere size distribution. By modulating these parameters, it was possible to produce chitosan microspheres as small as 437 ± 44 μm and as large as 993 ± 18 μm. Chitosan microspheres loaded with 5-FU were also produced using the experimental equipment. The obtained microspheres presented 5-FU controlled release, indicating that the microspheres can be used orally, since they are capable of crossing the stomach barrier and of continuing with the process of 5-FU release.
Upper Extremity Compartment Syndrome in a Patient with Acute Gout Attack but without Trauma or Other Typical Causes
Authors: Skedros John G. , Smith James S. , Henrie Marshall K. , Finlinson Ethan D. , Trachtenberg Joel D.
Published: January 2018

We report the case of a 30-year-old Polynesian male with a severe gout flare of multiple joints and simultaneous acute compartment syndrome (ACS) of his right forearm and hand without trauma or other typical causes. He had a long history of gout flares, but none were known to be associated with compartment syndrome. He also had concurrent infections in his right elbow joint and olecranon bursa. A few days prior to this episode of ACS, high pain and swelling occurred in his right upper extremity after a minimal workout with light weights. A similar episode occurred seven months prior and was attributed to a gout flare. Unlike past flares that resolved with colchicine and/or anti-inflammatory medications, his current upper extremity pain/swelling worsened and became severe. Hand and forearm fasciotomies were performed. Workup included general medicine, rheumatology and infectious disease consultations, myriad blood tests, and imaging studies including Doppler ultrasound and CT angiography. Additional clinical history suggested that he had previously unrecognized recurrent exertional compartment syndrome that led to the episode of ACS reported here. Chronic exertional compartment syndrome (CECS) presents a difficult diagnosis when presented with multiple symptoms concurrently. This case provides an example of one such diagnosis.
Use of Next Generation Sequencing and Synergy Susceptibility Testing in Diagnosis and Treatment of Carbapenem-Resistant Klebsiella pneumoniae Blood Stream Infection
Authors: Yu Yuetian , Hu Fupin , Zhu Cheng , Chen Erzhen , Lu Liangjing , Gao Yuan
Published: January 2018

Early diagnosis and appropriate treatment for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infection is a big challenge for clinicians due to its high mortality. Every effort has been made to improve its clinical outcomes. However, treatment according to synergy susceptibility testing has never been reported in the literature. We reported a 29-year-old systemic lupus erythematosus female with CR-Kp blood stream infection. We highlighted the identification by next generation sequencing and treatment according to synergy susceptibility testing in the case.
Mistaken Diabetic Ulcers: A Case of Bilateral Foot Verrucous Carcinoma
Authors: Di Palma Vanessa , Stone Jill P. , Schell Andrew , Dawes Jeffrey C.
Published: January 2018

Verrucous carcinoma (VC) is a rare, low-grade, and well-differentiated variant of squamous cell carcinoma. These tumors are slow-growing and exophytic and have a negligible incidence of metastasis. Treatment is complete surgical resection, ideally by Mohs micrographic surgery, to ensure adequate clear margins. Cutaneous VC predominantly occurs on the plantar surface of the foot and rarely occurs in multiple sites. This case study describes the fourth reported occurrence of bilateral VC of the feet in a woman with chronic diabetic foot ulcers. The case provides further support for persistent wounds contributing to the development of this lesion and describes their role in the characteristic delay in diagnosis of VC.
Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine
Authors: Kuranishi Fumito , Imaoka Yuki , Sumi Yuusuke , Uemae Yoji , Yasuda-Kurihara Hiroko , Ishihara Takeshi , Miyazaki Tsubasa , Ohno Tadao
Published: January 2018

Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002) and in the nationwide population-based cohort study of Denmark (1999–2007). Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.
Identifying Frail-Related Biomarkers among Community-Dwelling Older Adults in Japan: A Research Example from the Japanese Gerontological Evaluation Study
Authors: Cable N. , Hiyoshi A. , Kondo N. , Aida J. , Sjöqvist H. , Kondo K.
Published: January 2018

We examined correlating clinical biomarkers for the physical aspect of frailty among community-dwelling older adults in Japan, using Japanese Gerontological Evaluation Study (JAGES). We used information from the JAGES participants (N = 3,128) who also participated in the community health screening in 2010. We grouped participants’ response to the Study of Osteoporotic Fracture (SOF) Frailty Index into robust (=0), intermediate frail (=1), and frail (=2+) ones to indicate physical aspect of frailty. Independent of sex and age, results from multinomial logistic regression showed above normal albumin and below normal HDL and haemoglobin levels were positively associated with intermediate frail (RRR = 1.99, 95% CI = 1.22–3.23; RRR = 1.36, 95% CI = 1.33–1.39; RRR = 1.36, 95% CI = 1.23–1.51, resp.) and frail cases (RRR = 2.27, 95% CI = 1.91–2.70; RRR = 1.59, 95% CI = 1.51–1.68; RRR = 1.40, 95% CI = 1.28–1.52, resp.). Limited to women, above normal Hb1Ac level was similarly associated with intermediate frail and frail cases (RRR = 1.18, 95% CI = 1.02, 1.38; RRR = 2.56, 95% CI = 2.23–2.95, resp.). Use of relevant clinical biomarkers can help in assessment of older adults’ physical aspect of frailty.
Analgesic and Anti‐Inflammatory Activities of Diethyl Ether and n‐Hexane Extract of Polyalthia suberosa Leaves
Authors: Yasmen Nelufar , Aziz Md. Abdullah , Tajmim Afsana , Akter Mst. Irin , Hazra Amit Kumar , Rahman S. M. Mushiur
Published: January 2018

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti‐HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti‐inflammatory activities of diethyl ether and n‐hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin‐induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene‐induced ear edema test was used to evaluate anti‐inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti‐inflammatory activities in mice. In formalin‐induced paw licking test, acetic acid induced writhing test, and xylene‐induced ear edema test, the extracts exhibited significant inhibition ( ⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant ( ⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti‐inflammatory agents which support its use in traditional medicine.
The Smoothing FR Conjugate Gradient Method for Solving a Kind of Nonsmooth Optimization Problem with l1-Norm
Authors: Chen Miao , Du Shou-qiang
Published: January 2018

We study the method for solving a kind of nonsmooth optimization problems with l1-norm, which is widely used in the problem of compressed sensing, image processing, and some related optimization problems with wide application background in engineering technology. Transformated by the absolute value equations, this kind of nonsmooth optimization problem is rewritten as a general unconstrained optimization problem, and the transformed problem is solved by a smoothing FR conjugate gradient method. Finally, the numerical experiments show the effectiveness of the given smoothing FR conjugate gradient method.
Evidence‐Based Study to Compare Daodi Traditional Chinese Medicinal Material and Non‐Daodi Traditional Chinese Medicinal Material
Authors: Yang Xingyue , Tian Xin , Zhou Yannan , Liu Yali , Li Xinlong , Lu Tingting , Yu Changhe , He Liyun
Published: January 2018

Background. Daodi medicinal material is widely used in Chinese herb medication. However, there is a lack of systematic methodology for identifying characteristics associated with good quality and reliable efficacy of Daodi med‐material. Purpose. The purpose of this study is to provide some evidence to further substantiate the use of Daodi medicinal materials. Methods. Seven relevant databases were searched before July 2014. Two evaluators were responsible for screening and categorizing the results. The data was analyzed with Microsoft Excel 2007 and SPSS 21.0 statistical software. Results. Overall, 107 articles were systematically analyzed. Of these studies, 55.1% (59/107) focused on the methodology to assess Daodi med‐material, and 38.3% (41/107) were interested in med‐material ingredients, soil physical and chemical properties, and the geological background system (GBS). Only 6.5% (7/107) of studies were mainly conducted as clinical trials and animal experiments. Conclusion. Comparisons between Daodi and non‐Daodi materials have been studied mainly in terms of the ingredients or composition of medical materials, soil physics and chemistry, and the GBS, and some identifying methodologies have been created to identify Daodi attributes. Until now, there is still no consensus of comparison criteria between Daodi and non‐Daodi medicinal material. Only a few studies were conducted through animal experiments and clinical trials to determine Daodi superiority.
Research on Pricing and Coordination Strategy of a Sustainable Green Supply Chain with a Capital‐Constrained Retailer
Authors: Zhao Liming , Li Ling , Song Yao , Li Cong , Wu Yujie
Published: January 2018

With the gradual deepening of environmental problems and the increase in consumer awareness of environmental protection, many enterprises have already begun to pay attention to green supply chain management. However, the price of green products is higher than that of nongreen products, which is an enormous challenge for many small‐ or medium‐sized enterprises. To study the pricing and coordination of green supply chains under capital constraints, a model consisting of a manufacturer and a capital‐constrained retailer is established; the manufacturer invests in green products and provides a deferred payment contract. Setting the situation without capital constraints as a benchmark, this study explores the impact of the retailer’s capital constraints on the manufacturer’s product greenness design; an interesting result shows that deferred payment can help encourage the retailer to order more products and improve the profit of the manufacturer and the efficiency of the entire supply chain as well as the product’s greenness level simultaneously. However, the profit of the retailer will be hurt by the deferred payment contract. Therefore, to guarantee the profit of the entire channel and to make the two agents obtain a win‐win outcome, a new two‐way revenue‐sharing contract is designed to coordinate the green supply chain.
Perceptual Hashing-Based Image Copy-Move Forgery Detection
Authors: Wang Huan , Wang Hongxia
Published: January 2018

This paper proposes a blind authentication scheme to identify duplicated regions for copy-move forgery based on perceptual hashing and package clustering algorithms. For all fixed-size image blocks in suspicious images, discrete cosine transform (DCT) is used to obtain their DCT coefficient matrixes. Their perceptual hash matrixes and perceptual hash feature vectors are orderly addressed. Moreover, a package clustering algorithm is proposed to replace traditional lexicographic order algorithms for improving the detection precision. Similar blocks can be identified by matching the perceptual hash feature vectors in each package and its adjacent package. The experimental results show that the proposed scheme can locate irregular tampered regions and multiple duplicated regions in suspicious images although they are distorted by some hybrid trace hiding operations, such as adding white Gaussian noise and Gaussian blurring, adjusting contrast ratio, luminance, and hue, and their hybrid operations.
Method of Resource Estimation Based on QoS in Edge Computing
Authors: Li Guangshun , Song Jianrong , Wu Junhua , Wang Jiping
Published: January 2018

With the development of Internet of Things, the number of network devices is increasing, and the cloud data center load increases; some delay‐sensitive services cannot be responded to timely, which results in a decreased quality of service (QoS). In this paper, we propose a method of resource estimation based on QoS in edge computing to solve this problem. Firstly, the resources are classified and matched according to the weighted Euclidean distance similarity. The penalty factor and Grey incidence matrix are introduced to correct the similarity matching function. Then, we use regression‐Markov chain prediction method to analyze the change of the load state of the candidate resources and select the suitable resource. Finally, we analyze the precision and recall of the matching method through simulation experiment, validate the effectiveness of the matching method, and prove that regression‐Markov chain prediction method can improve the prediction accuracy.
High‐Energy Impact Behaviors of Hybrid Composite Plates Strengthened with 3D‐UHMWPE Composites
Authors: Lee Sang-Youl , Kim Gyu-Dong , Kim Sung Jig , Chang Chun-Ho
Published: January 2018

This study deals with drop‐impact effects of new hybrid concrete plates strengthened with an ultrahigh molecular weight polyethylene (UHMWPE). The proposed 3D‐UHMWPE results in excellent mechanical properties such as high abrasion resistance, impact strength, and low coefficient of friction. These special properties allow the product to be used in several high‐performance applications. In this study, we used two kinds of high‐performance materials for the impact reinforcement of a structure made of conventional materials such as a concrete. In particular, the impact mechanism of a fiber‐concrete hybrid structure was studied using various parameters. The parametric studies are focused on the various effects of drop‐impact on the structural performance. The combined effects of using different fiber‐reinforced materials on the impact behavers are also investigated.
Respiratory Motion Correction for Compressively Sampled Free Breathing Cardiac MRI Using Smooth l1-Norm Approximation
Authors: Bilal Muhammad , Shah Jawad Ali , Qureshi Ijaz M. , Kadir Kushsairy
Published: January 2018

Transformed domain sparsity of Magnetic Resonance Imaging (MRI) has recently been used to reduce the acquisition time in conjunction with compressed sensing (CS) theory. Respiratory motion during MR scan results in strong blurring and ghosting artifacts in recovered MR images. To improve the quality of the recovered images, motion needs to be estimated and corrected. In this article, a two-step approach is proposed for the recovery of cardiac MR images in the presence of free breathing motion. In the first step, compressively sampled MR images are recovered by solving an optimization problem using gradient descent algorithm. The L1-norm based regularizer, used in optimization problem, is approximated by a hyperbolic tangent function. In the second step, a block matching algorithm, known as Adaptive Rood Pattern Search (ARPS), is exploited to estimate and correct respiratory motion among the recovered images. The framework is tested for free breathing simulated and in vivo 2D cardiac cine MRI data. Simulation results show improved structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and mean square error (MSE) with different acceleration factors for the proposed method. Experimental results also provide a comparison between k-t FOCUSS with MEMC and the proposed method.
Integration of Porous Carbon Nanowrinkles into Carbon Micropost Array for Microsupercapacitors
Authors: Xi Shuang , Liu Ying , Zhu Yinlong , Yang Yutu
Published: January 2018

Porous carbon nanowrinkles (PCW) coated on carbon micropost (CMP) arrays were successfully fabricated via three-step process, which took advantages of the large difference in elastic moduli between PCW and the raw material of CMP. The effect of nanowrinkle integration on the electrochemical performances was investigated, showing an improved electrochemical performance. The electrode also shows excellent cycling stability, which retains 84% of its initial discharge capacitance after 1700 cycles with >90% Coulombic efficiency. This enhanced electrochemical performance is ascribed to the synergistic effect of enlarged surface area and porous structure of PCW. The obtained PCW/CMP compositing electrode with the advantages of low cost and easy scaling-up has great potential for on-chip supercapacitors.
Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation
Authors: Huang Mengqi , Liao Bing , Xu Ping , Cai Huasong , Huang Kun , Dong Zhi , Xu Ling , Peng Zhenpeng , Luo Yanji , Zheng Keguo , Peng Baogang , Li Zi-Ping , Feng Shi-Ting
Published: January 2018

Objective. To investigate the imaging features observed in preoperative Gd-EOB-DTPA-dynamic enhanced MRI and correlated with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods. 66 HCCs in 60 patients with preoperative Gd-EOB-DTPA-dynamic enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, peritumor enhancement during mid-arterial phase, peritumor hypointensity during hepatobiliary phase, signal intensity ratio on DWI and apparent diffusion coefficients (ADC), T1 relaxation times, and the reduction rate between pre- and postcontrast enhancement images were assessed. Correlation between these features and histopathological presence of MVI was analyzed to establish a prediction model. Results. Histopathology confirmed that MVI were observed in 17 of 66 HCCs. Univariate analysis showed tumor size (p=0.003), margin (p=0.013), peritumor enhancement (p=0.001), and hypointensity during hepatobiliary phase (p=0.004) were associated with MVI. A multiple logistic regression model was established, which showed tumor size, margin, and peritumor enhancement were combined predictors for the presence of MVI (α=0.1). R2 of this prediction model was 0.353, and the sensitivity and specificity were 52.9% and 93.0%, respectively. Conclusion. Large tumor size, irregular tumor margin, and peritumor enhancement in preoperative Gd-EOB-DTPA-dynamic enhanced MRI can predict the presence of MVI in HCC.
Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki‐Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients
Authors: Yoo Jung-Hwa , Yim Sung-Vin , Lee Byung-Cheol
Published: January 2018

Background. Bojungikki‐tang (BJIKT) is a widely used traditional herbal formula in China, Japan, and Korea. There have been reports that several herbs among BJIKT have interactions with antiplatelet drugs, such as aspirin. This study aimed to assess whether BJIKT interacts with aspirin in terms of pharmacokinetics (PK) and pharmacodynamics (PD) in healthy subjects and ischemic stroke patients. Methods. The phase I interaction trial was a randomized, open‐label, crossover study of 10 healthy male subjects, and the phase III interaction trial was a randomized, placebo‐controlled, parallel study of 43 ischemic stroke patients. Each participant randomly received aspirin + BJIKT or aspirin + placebo. For PK analysis, plasma acetyl salicylic acid (ASA) and salicylic acid (SA) were evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2 (TxB2) were measured. Results. In the PK parameters, mean area under curve, maximum concertation, and peak concentration time of ASA and SA were not different between two groups in healthy subjects and ischemic stroke patients. In the PD profiles, TxB2 concentrations and platelet aggregation were not affected by coadministration of BJIKT in healthy subjects and ischemic stroke patients. Conclusions. These results suggest that coadministration of BJIKT with aspirin may not result in herb‐drug interaction.
Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas
Authors: Shea Michael P. , O'Leary Kathleen A. , Fakhraldeen Saja A. , Goffin Vincent , Friedl Andreas , Wisinski Kari B. , Alexander Caroline M. , Schuler Linda A.
Published: January 2018

Although antiestrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25% to 40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSC), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here, we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors. Like a subset of ERα+ patient cancers, the prolactin-induced adenocarcinomas contained two major tumor subpopulations that expressed markers of normal luminal and basal epithelial cells. CSC activity was distributed equally across these two tumor subpopulations. Treatment with the selective estrogen receptor downregulator (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive responses in CSC activity, increased markers of plasticity including target gene reporters of Wnt/Notch signaling and epithelial–mesenchymal transition, and increased double-positive (K8/K5) cells. In primary tumorsphere cultures, ICI stimulated CSC self-renewal and was able to overcome the dependence of self-renewal upon Wnt or Notch signaling individually, but not together. Our findings demonstrate that treatment of aggressive mixed lineage ERα+ breast cancers with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and regenerative CSC activity, predicting likely negative impacts on patient tumors with these characteristics.

Significance: This study suggests that treatment of a subset of ERα+ breast cancers with antiestrogen therapies may not only fail to slow growth but also promote aggressive behavior by evoking tumor cell plasticity and regenerative CSC activity. Cancer Res; 78(7); 1672–84. ©2018 AACR.
Keratin 19 Expression in Hepatocellular Carcinoma Is Regulated by Fibroblast-Derived HGF via a MET-ERK1/2-AP1 and SP1 Axis
Authors: Rhee Hyungjin , Kim Hye-Young , Choi Ji-Hye , Woo Hyun Goo , Yoo Jeong Eun , Nahm Ji Hae , Choi Jin-Sub , Park Young Nyun
Published: January 2018

Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC); however, regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of fibrous tumor stroma in KRT19-positive HCC, suggesting that cross-talk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an in vitro model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK–ERK1/2 pathway, which upregulated KRT19 expression in HCC cells. Furthermore, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (n = 339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.

Significance: These findings reveal KRT19 expression in hepatocellular carcinoma is regulated by cross-talk between cancer-associated fibroblasts and HCC cells, illuminating new therapeutic targets for this aggressive disease. Cancer Res; 78(7); 1619–31. ©2018 AACR.
Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus
Authors: Schrock Alexa B. , Pavlick Dean , Klempner Samuel J. , Chung Jon H. , Forcier Brady , Welsh Allison , Young Lauren , Leyland-Jones Bryan , Bordoni Rodolfo , Carvajal Richard D. , Chao Joseph , Kurzrock Razelle , Sicklick Jason K. , Ross Jeffrey S. , Stephens Philip J. , Devoe Craig , Braiteh Fadi , Ali Siraj M. , Miller Vincent A.
Published: January 2018

Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative.

Experimental Design: Hybrid capture–based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples.

Results: Evidence of ctDNA was detected in 344 of 417 samples (82%), and of these, ≥1 reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented.

Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with gastrointestinal carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced gastrointestinal cancers as a complementary approach to tissue testing, and further investigation is warranted. Clin Cancer Res; 24(8); 1881–90. ©2018 AACR.
Treatment of Metastatic Spindle Epithelial Tumor with Thymus-Like Differentiation (SETTLE) - Long-Term Disease Control by Multimodal Therapy
Authors: Quidde Julia , Alsdorf Winfried H. , von Amsberg Gunhild , Wilczak Waldemar , Bokemeyer Carsten
Published: January 2018

Background: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor that occurs mainly in pediatric patients and young adults. Only few of these patients develops metastatic disease; therefore, clinical data regarding treatment and outcome of metastatic SETTLE are extremely limited. Several chemotherapy agents have been used in SETTLE but due to the limited number of patients no evidence-based therapy exists. Case Report: We present a case of metastatic SETTLE presenting with high tumor burden and paraneoplastic hypercalcemia. Prolonged disease control with several lines of platinum-based chemotherapy, anti-epidermal growth factor receptor therapy and additional radiotherapy was achieved. Conclusion: Multi-agent chemotherapy is an active treatment in metastatic SETTLE and can induce sustained tumor control.
Is Surgical Excision Necessary in Breast Papillomas 10 mm or Smaller at Core Biopsy
Authors: Yang Yang , Fan Zhaoqing , Liu Yiqiang , He Yingjian , Ouyang Tao
Published: January 2018

Background: The objective of this study was to propose managements for breast papillomas of 10 mm or smaller initially diagnosed at core biopsy. Method: We reviewed the data of patients in our center from 2004 to 2013. 116 lesions of 10 mm or smaller as measured by ultrasound (US) were diagnosed as papillomas at core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). 74 of the papillomas diagnosed by CNB were surgically excised, the others were followed by imaging surveillance. Result: 13 of 116 lesions were found to be malignant, with an upgrade rate of 11.2%. Analyzing the difference between malignant and nonmalignant lesions, patients with malignant lesions were older than those with nonmalignant lesions (56.6 vs. 46.6 years, p = 0.002). Papillomas with atypia had a significantly higher upgrade rate than without, both in the surgical results (p = 0.030) and overall (p = 0.0392). None of 16 papillomas larger than 5 mm upgraded to malignancy. Breast papillomas diagnosed by CNB had a significantly higher upgrade rate (16.5%) than those diagnosed by VAB (0%) (p = 0.021). Conclusion: Our finding suggests that breast papillomas of 6-10 mm at initial CNB need additional surgical excision, but imaging surveillance may be suitable for papillomas no larger than 5 mm and papillomas detected by VAB.
Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series
Authors: Palumbo Raffaella , Licata Luca , Sottotetti Federico , Tagliaferri Barbara , Pozzi Emma , Teragni Cristina , Quaquarini Erica , Bernardo Antonio
Published: January 2018

Introduction: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy. Methods: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle. Our analysis aimed to examine the performance of vinflunine in terms of activity and safety in such a patient population. Results: 28 consecutive patients were studied. After a median follow-up of 25 months, vinflunine was associated with a median progression-free survival of 9 months (range 4 to > 16 months) and a disease control rate of 64%; median overall survival was not reached. Treatment was well tolerated, with no unexpected safety events. The most common adverse events of grade ≥ 3 were neutropenia (21%) and constipation (14%); no toxicity-related death occurred. Conclusions: Our results suggest that vinflunine may be a suitable maintenance treatment option for TCCU patients who received a maximum of 6 cycles of platinum-based chemotherapy commonly used as first-line treatment.
Value of Placental Volume and Vascular Flow Indices as Predictors of Early and Late Preeclampsia at First Trimester
Authors: González-González Nieves L. , González Dávila Enrique , Padrón Erika , Armas Gonzalez Marina , Plasencia Walter
Published: January 2018

Introduction: We evaluated the utility of placental volume and three-dimensional (3D) vascular flow indices to predict early and late preeclampsia. Material and Methods: In 1,004 pregnancies attending routine care, we recorded first-trimester screening program for aneuploidy (FTSA) parameter and measured uterine artery pulsatility index (uterine-a PI). Placental volume and vascular flow indices were obtained using 3D power Doppler and VOCAL techniques. Results: Placental volume was lower and uterine-a PI was higher in both early and late preeclampsia groups versus nonaffected pregnancies. The prediction rate of placental volume in late preeclampsia was higher than that of uterine-a PI (AUROC 0.707 vs. 0.581, p < 0.011). The inclusion of placental volume improved significantly the prediction rate of total and late preeclampsia in the models constructed with maternal characteristics, FTSA, and uterine-a PI (AUROC 0.745 vs. 0.818, p < 0.004, and 0.740 vs. 0.812, p < 0.012, respectively). The inclusion of vascular indices did not improve the predictive value of these models. Discussion: Placental volume was an independent predictor of total, early, and late preeclampsia and its inclusion in combined predictive models significantly improved prediction rates. Reduced placental volume observed at first trimester in women with early and late preeclampsia suggests that these entities are the clinical expression of a similar pathophysiological process.
Androgen Insensitivity Syndrome at Prepuberty: Marked Loss of Spermatogonial Cells at Early Childhood and Presence of Gonocytes up to Puberty
Authors: Aliberti Paula , Perez Garrido Natalia , Marino Roxana , Ramirez Pablo , Solari Alberto J. , Sciurano Roberta , Costanzo Mariana , Guercio Gabriela , Warman Diana Mónica , Bailez Marcela , Baquedano María Sonia , Rivarola Marco A , Belgorosky Alicia , Berensztein Esperanza
Published: January 2018

Androgen insensitivity syndrome (AIS) is a hereditary condition in patients with a 46,XY karyotype in which loss-of-function mutations of the androgen receptor (AR) gene are responsible for defects in virilization. The aim of this study was to investigate the consequences of the lack of AR activity on germ cell survival and the degree of testicular development reached by these patients by analyzing gonadal tissue from patients with AIS prior to Sertoli cell maturation at puberty. Twenty-three gonads from 13 patients with AIS were assessed and compared to 18 testes from 17 subjects without endocrine disorders. The study of the gonadal structure using conventional microscopy and the ultrastructural characteristics of remnant germ cells using electron microscopy, combined with the immunohistochemical analysis of specific germ cell markers (MAGE-A4 for premeiotic germ cells and of OCT3/4 for gonocytes), enabled us to carry out a thorough investigation of germ cell life in an androgen-insensitive microenvironment throughout prepuberty until young adulthood. Here, we show that germ cell degeneration starts very early, with a marked decrease in number after only 2 years of life, and we demonstrate the permanence of gonocytes in AIS testis samples until puberty, describing 2 different populations. Additionally, our results provide further evidence for the importance of AR signaling in peritubular myoid cells during prepuberty to maintain Sertoli and spermatogonial cell health and survival.
Do Signs of Attention-Deficit/Hyperactivity Disorder Increase the Odds of Dental Caries? A Case-Control Study
Authors: Mota-Veloso Isabella , Pordeus Isabela Almeida , Homem Márcio Alexandre , Ramos-Jorge Joana , Oliveira-Ferreira Fernanda , Ramos-Jorge Maria Letícia , Paiva Saul Martins
Published: January 2018

Attention-deficit/hyperactivity disorder (ADHD) is a behavioural disorder that can affect one’s performance in activities of daily living and can exert a negative impact on the oral health of children. Objective: The aim of this work was to determine the association between ADHD (signs and executive functions) and dental caries in children aged 7–12 years. Methods: A case-control study was conducted with 532 children in the city of Diamantina, Brazil. The case group was composed of children with caries and the control group was composed of children without caries. The children were submitted to a clinical oral examination for the determination of caries and neuropsychological evaluations of intellectual function and executive function. Other signs of attention deficit and hyperactivity were investigated using the Swanson, Nolan, and Pelham scale administered to parents/guardians and teachers. Socioeconomic and demographic characteristics were also evaluated. Statistical analysis involved the McNemar χ2 test and conditional logistic regression. Results: The multivariate logistic regression model demonstrated that monthly household income and parental reports of signs of attention deficit were significantly associated with the occurrence of dental caries. Conclusion: Children considered by their parents/guardians to have attention deficit have a greater chance of exhibiting dental caries, independently of household income.