bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning for Biometrics
Authors: Sundararajan Kalaivani , Woodard Damon L.
Published: May 2018

In the recent past, deep learning methods have demonstrated remarkable success for supervised learning tasks in multiple domains including computer vision, natural language processing, and speech processing. In this article, we investigate the impact of deep learning in the field of biometrics, given its success in other domains. Since biometrics deals with identifying people by using their characteristics, it primarily involves supervised learning and can leverage the success of deep learning in other related domains. In this article, we survey 100 different approaches that explore deep learning for recognizing individuals using various biometric modalities. We find that most deep learning research in biometrics has been focused on face and speaker recognition. Based on inferences from these approaches, we discuss how deep learning methods can benefit the field of biometrics and the potential gaps that deep learning approaches need to address for real-world biometric applications.
Self-Adaptive Filtering Algorithm with PCM-Based Memory Storage System
Authors: Yoon Su-Kyung , Yun Jitae , Kim Jung-Geun , Kim Shin-Dug
Published: May 2018

This article proposes a new phase change memory– (PCM) based memory storage architecture with associated self-adaptive data filtering for various embedded devices to support energy efficiency as well as high computing power. In this approach, PCM-based memory storage can be used as working memory and mass storage layers simultaneously, and a self-adaptive data filtering module composed of small DRAM dual buffers was designed to improve unfavorable PCM features, such as asymmetric read/write access latencies and limited endurance and enhance spatial/temporal localities. In particular, the self-adaptive data filtering algorithm enhances data reusability by screening potentially high reusable data and predicting adequate lifetime of those data depending on current victim time decision value. We also propose the possibility that a small amount of DRAM buffer is embedded into mobile processors, keeping this as small as possible for cost effectiveness and energy efficiency. Experimental results show that by exploiting a small amount of DRAM space for dual buffers and using the self-adaptive filtering algorithm to manage them, the proposed system can reduce execution time by a factor of 1.9 compared to the unified conventional model with same the DRAM capacity and can be considered comparable to 1.5× DRAM capacity.
CACF
Authors: Zhang Yang , Feng Dan , Tong Wei , Hua Yu , Liu Jingning , Tan Zhipeng , Wang Chengning , Wu Bing , Li Zheng , Xu Gaoxiang
Published: May 2018

Emerging Resistive Random Access Memory (ReRAM) is a promising candidate as the replacement for DRAM due to its low standby power, high density, high scalability, and nonvolatility. By employing the unique crossbar structure, ReRAM can be constructed with extremely high density. However, the crossbar ReRAM faces some serious challenges in terms of performance, reliability, and energy consumption. First, ReRAM’s crossbar structure causes an IR drop problem due to wire resistance and sneak currents, which results in nonuniform access latency in ReRAM banks and reduces its reliability. Second, without access transistors in the crossbar structure, write disturbance results in serious data reliability problem. Third, the access latency, reliability, and energy use of ReRAM arrays are significantly influenced by the data patterns involved in a write operation.

To overcome the challenges of the crossbar ReRAM, we propose a novel circuit architecture co-optimization framework for improving the performance, reliability, and energy use of ReRAM-based main memory system, called CACF. The proposed CACF consists of three levels, including the circuit level, circuit architecture level, and architecture level. At the circuit level, to reduce the IR drops along bitlines, we propose a double-sided write driver design by applying write drivers along both sides of bitlines and selectively activating the write drivers. At the circuit architecture level, to address the write disturbance with low overheads, we propose a RESET disturbance detection scheme by adding disturbance reference cells and conditionally performing refresh operations. At the architecture level, a region partition with address remapping method is proposed to leverage the nonuniform access latency in ReRAM banks, and two flip schemes are proposed in different regions to optimize the data patterns involved in a write operation. The experimental results show that CACF improves system performance by 26.1%, decreases memory access latency by 22.4%, shortens running time by 20.1%, and reduces energy consumption by 21.6% on average over an aggressive baseline. Meanwhile, CACF significantly improves the reliability of ReRAM-based memory systems.
Combining Software Cache Partitioning and Loop Tiling for Effective Shared Cache Management
Authors: Vasilios Kelefouras , Georgios Keramidas , Nikolaos Voros
Published: May 2018

One of the biggest challenges in multicore platforms is shared cache management, especially for data-dominant applications. Two commonly used approaches for increasing shared cache utilization are cache partitioning and loop tiling. However, state-of-the-art compilers lack efficient cache partitioning and loop tiling methods for two reasons. First, cache partitioning and loop tiling are strongly coupled together, and thus addressing them separately is simply not effective. Second, cache partitioning and loop tiling must be tailored to the target shared cache architecture details and the memory characteristics of the corunning workloads.

To the best of our knowledge, this is the first time that a methodology provides (1) a theoretical foundation in the above-mentioned cache management mechanisms and (2) a unified framework to orchestrate these two mechanisms in tandem (not separately). Our approach manages to lower the number of main memory accesses by an order of magnitude keeping at the same time the number of arithmetic/addressing instructions to a minimal level. We motivate this work by showcasing that cache partitioning, loop tiling, data array layouts, shared cache architecture details (i.e., cache size and associativity), and the memory reuse patterns of the executing tasks must be addressed together as one problem, when a (near)-optimal solution is requested. To this end, we present a search space exploration analysis where our proposal is able to offer a vast deduction in the required search space.
Extended Redundant-Digit Instruction Set for Energy-Efficient Processors
Authors: Amanollahi Saba , Jaberipur Ghassem
Published: May 2018

The impact of extending the instruction set architecture (ISA) of a conventional binary processor by a set of redundant-digit arithmetic instructions is studied. Selected binary arithmetic instructions within a given code sequence are replaced with appropriate redundant-digit ones. The selection criteria is so enforced to lead to overall reduction of execution energy and energy-delay product (EDP). A special branch and bound algorithm is devised to modify the dataflow graph (DFG) to a new one that takes advantage of the extended redundant-digit instruction set. The DFG is obtained, via an in-house tool, from the intermediate code representation that is normally produced by the utilized compiler. The required redundant-digit arithmetic operations (including a multiplier, a multiply accumulator, and three- to four-operand redundant-digit adders specially designed for this work) have been synthesized on 45nm NanGate technology by a Synopsys Design Compiler. To evaluate the impact of the proposed ISA augmentation on actual code execution, the simulation and evaluation platform of our choice is an MIPS processor whose ISA is extended by the proposed redundant-digit instructions. Several digital signal processing benchmarks are utilized as the source of the baseline MIPS codes, which are converted (via the aforementioned algorithm) to the equivalent mixed binary/redundant-digit codes. Our experiments, as such, show up to 26% energy and 44% EDP savings.
Risks of cryptocurrencies
Authors: Weaver Nicholas
Published: May 2018

Considering the inherent risks of cryptocurrency ecosystems.
An interview with Dave Parnas
Authors: Denning Peter J.
Published: May 2018

A discussion of ideas about software engineering.
Effectiveness of anonymization in double-blind review
Authors: Le Goues C. , Brun Y. , Apel S. , Berger E. , Khurshid S. , Smaragdakis Y.
Published: May 2018

Assessing the effectiveness of anonymization in the review process.
Identifying patterns in medical records through latent semantic analysis
Authors: Gefen David , Miller Jake , Armstrong Johnathon Kyle , Cornelius Frances H. , Robertson Noreen , Smith-McLallen Aaron , Taylor Jennifer A.
Published: May 2018

Text analysis can reveal patterns of association among medical terms and medical codes.
C-Arm Image-Based Surgical Path Planning Method for Distal Locking of Intramedullary Nails
Authors: Hsu Wei-En , Yu Ching-Hsiao , Chang Chih-Ju , Wu Hung-Kang , Yu Tsong-Han , Tseng Ching-Shiow
Published: May 2018

Due to the curvature of the bone marrow cavity, the intramedullary nail used in long bone fracture fixation can be deformed, causing displacement of the locking holes. In this study, an algorithm using only one C-arm image to determine the center positions and axial directions of locking holes was developed for drilling guidance. Based on conventional method that the axial direction of locking hole would be identified when locking hole contour is presented as a circle, the proposed method can locate the circle contour centroid by using one C-arm image including two elliptical contours. Then the two distal locking holes’ axial direction and centers would be determined. Three experiments were conducted to verify the performance of the proposed algorithm, which are (1) computer simulation, (2) use of real intramedullary nails, and (3) actual drilling test with the bone model. The experimental results showed that the average error of the axial direction and center position were 0.62 ± 0.6°, 0.73 ± 0.53 mm (simulation) and 3.16 ± 1.36°, 1.10 ± 0.50 mm (actual nail), respectively. The last ten drilling test sets were completed successfully (with an average duration of 48 seconds). Based on the experimental results, the proposed algorithm was feasible for clinic applications.
Application and Development of Enhanced Chaotic Grasshopper Optimization Algorithms
Authors: Saxena Akash , Shekhawat Shalini , Kumar Rajesh
Published: May 2018

In recent years, metaheuristic algorithms have revolutionized the world with their better problem solving capacity. Any metaheuristic algorithm has two phases: exploration and exploitation. The ability of the algorithm to solve a difficult optimization problem depends upon the efficacy of these two phases. These two phases are tied with a bridging mechanism, which plays an important role. This paper presents an application of chaotic maps to improve the bridging mechanism of Grasshopper Optimisation Algorithm (GOA) by embedding 10 different maps. This experiment evolves 10 different chaotic variants of GOA, and they are named as Enhanced Chaotic Grasshopper Optimization Algorithms (ECGOAs). The performance of these variants is tested over ten shifted and biased unimodal and multimodal benchmark functions. Further, the applications of these variants have been evaluated on three-bar truss design problem and frequency-modulated sound synthesis parameter estimation problem. Results reveal that the chaotic mechanism enhances the performance of GOA. Further, the results of the Wilcoxon rank sum test also establish the efficacy of the proposed variants.
Sensitivity Analysis of Microstructure Parameters and Mechanical Strength during Consolidation of Cemented Paste Backfill
Authors: Qin Xuebin , Wang Pai , Liu Lang , Wang Mei , Xin Jie
Published: May 2018

Parameter sensitivity is an important part of the quantitative model uncertainty, which helps to effectively identify the key parameters, reduce the uncertainty of the parameters, and then improve the efficiency of parameter optimization. In order to accurately and intuitively analyze the influence of the microscopic parameters and the mechanical response of consolidation process of cemented paste backfill (CPB), a method is used to characterize the geometric and morphological features of the CPB. In this paper, digital image processing technology is used to propose a method for the identification and quantitative analysis of microscopic pore images based on CPB. The pore images on the microscopic scale of CPB are obtained by the microscopic analysis of SEM images, binarization, denoising, and other operations; further, several microscopic parameters are calculated on the pore image, such as the porosity, uniformity coefficient, fractal dimension, probability entropy, and other quantitative parameters, realizing quantitative analysis of pore images. The microstructure of pore images of CPB is extracted under different curing times and then the parameter sensitivity between the microstructure parameters and the mechanical response based on the finite-difference method is analyzed. Set microstructure parameter software of consolidation process of CPB is developed based on this idea, which can be used to identify microscopic pore images and analyze the morphology quantitatively. The microcosmic parameters of CPB with strong sensitivity are uniformity coefficient, average shape coefficient, sorting coefficient, fractal dimension, average length of long axis, average pore area, weighted probability entropy, pore number, and porosity. The sensitivity of the remaining parameters is relatively low. Therefore, the CPB is preferably used in the strength testing process. The method provides a new method for the quantitative analysis of parameter sensitivity on the microscale of CPB.
Structural Changes Induced by Acupuncture in the Recovering Brain after Ischemic Stroke
Authors: Wu Ping , Zhou Yu-mei , Liao Chen-xi , Tang Yu-zhi , Li Yong-xin , Qiu Li-hua , Qin Wei , Zeng Fang , Liang Fan-rong
Published: May 2018

The aim of this study was to observe the grey matter (GM) tissue changes of ischemic stroke patients, to explore the therapy responses and possible mechanism of acupuncture. 21 stroke patients were randomly assigned to receive either acupuncture plus conventional (Group A) or only conventional (Group B) treatments for 4 weeks. All patients in both groups accepted resting‐state functional magnetic resonance (fMRI) scan before and after treatment, and the voxel‐based morphometry (VBM) analysis was performed to detect the cerebral grey structure changes. The modified Barthel index (MBI) was used to evaluate the therapeutic effect. Compared with the patients in Group B, the patients in Group A exhibited a more significant enhancement of the changes degree of MBI from pre‐ to post‐treatment intervention. VBM analyses found that after treatment the patients in Group A showed extensive changes in GMV. In Group A, the left frontal lobe, precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle temporal gyrus significantly increased, and the right frontal gyrus, inferior parietal gyrus, and middle cingulate cortex decreased (P < 0.05, corrected). In addition, left anterior cingulate cortex and left middle temporal gyrus are positively related to the increase in MBI score (P < 0.05, corrected). In Group B, right precentral gyrus and right inferior frontal gyrus increased (P < 0.05, corrected). In conclusion, acupuncture can evoke pronounced structural reorganization in the frontal areas and the network of DMN areas, which may be the potential therapy target and the potential mechanism where acupuncture improved the motor and cognition recovery.
Therapeutic Effects of Kangzhi Syrup in a Guinea Pig Model of Ovalbumin‐Induced Cough Variant Asthma
Authors: Wang Youpeng , Zhu Pengyu , Tan Jiejun , Liu Zhiwei , Qu Wanying , Liu Lujia , Li Zhijun
Published: May 2018

Purpose. This study aimed to investigate the possible effects and underlying mechanisms of Kangzhi syrup on ovalbumin‐ (OVA‐) induced cough variant asthma (CVA) in guinea pigs. Methods. All 48 guinea pigs were randomly assigned to four experimental groups: normal, OVA model with or without Kangzhi syrup (OVA and OVA + KZ), and OVA with Dexamethasone (OVA + DM). After sensitizing the guinea pigs, a cough challenge was performed by the inhalation of capsaicin. The antitussive effect, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue, and morphological changes were examined. Results. Compared with model group, Kangzhi syrup effectively exerted an antitussive effect (p < 0.0001) and reduced the pneumonic anaphylacticitis by inhibiting the infiltration of total inflammatory cells (p < 0.0001) and reducing the percentage of eosinophil in BALF (p < 0.0001). Moreover, evidence from morphological studies also demonstrated that Kangzhi syrup inhibited the infiltration of inflammatory cells and ameliorated the structure changes. NF‐κB and TGF‐β1 expression were attenuated in the OVA + KZ group versus the OVA group (p < 0.0001). Additionally, a semiquantitative analysis of TGF‐β1 expression also demonstrated that the Kangzhi syrup attenuated this profibrogenic growth factor (p < 0.001). Conclusions. The results demonstrated that Kangzhi syrup exerted a considerable antitussive effect in CVA animal model, which depended on its marked impact on the anti‐anaphylactic inflammation. Additionally, it could ameliorate the airway remodeling by inhibiting NF‐κB and TGF‐β1 signal pathway.
Fractional Derivative Regularization in QFT
Authors: Tarasov Vasily E.
Published: May 2018

We propose in this paper a new regularization, where integer-order differential operators are replaced by fractional-order operators. Regularization for quantum field theories based on application of the Riesz fractional derivatives of noninteger orders is suggested. The regularized loop integrals depend on parameter that is the order α>0 of the fractional derivative. The regularization procedure is demonstrated for scalar massless fields in φ4-theory on n-dimensional pseudo-Euclidean space-time.
A Security Scheme of 5G Ultradense Network Based on the Implicit Certificate
Authors: Chen Zhonglin , Chen Shanzhi , Xu Hui , Hu Bo
Published: May 2018

The ultradense network (UDN) is one of the most promising technologies in the fifth generation (5G) to address the network system capacity issue. It can enhance spatial reuse through the flexible, intensive deployment of small base stations. A universal 5G UDN architecture is necessary to realize the autonomous and dynamic deployment of small base stations. However, the security of the 5G UDN is still in its infancy, and the data communication security among the network entities is facing new challenges. In this paper, we proposed a new security based on implicit certificate (IC) scheme; the scheme solves the security problem among the access points (APs) in a dynamic APs group (APG) and between the AP and user equipment (UE). We present each phase regarding how two network entities obtain the Elliptic Curve Qu‐Vanstone (ECQV) implicit certificate scheme, verify each other’s identity, and share keys in an UDN. Finally, we extensively analyze our lightweight security communication model in terms of security and performance. The simulation on network bandwidth evaluation is also conducted to prove the efficiency of the solution.
Research on Kinematics and Pouring Law of a Mobile Heavy Load Pouring Robot
Authors: Li Long , Wang Chengjun , Wu Hongtao
Published: May 2018

In order to meet the requirement of continuous pouring in many varieties and small batches in casting production, a mobile heavy load pouring robot is developed based on a new 4-UPU parallel mechanism due to its strong carrying capacity. Firstly, the instantaneous motion characteristics of the novel 4-UPU parallel mechanism with four degrees of freedom (DOF) are analyzed using screw theory. By using the geometric method, both the forward and inverse kinematic solutions of the proposed robot system are given out. Secondly, based on a common pouring ladle, the volume change of pouring liquid in pouring process and the relationship between tilting angular velocity and flow rate are analyzed, and the results show that the shape of the ladle and the design of the pouring mouth have great influence on the tilting model. It is an important basis for the division of the sectional model. Finally, a numerical example is given to verify the effectiveness of the developed tilting model. The mapping relation between the tilting model and the parallel mechanism shows that the pouring flow can be adjusted by controlling the movement of parallel manipulator. The research of this paper provides an important theoretical basis for the position control of mobile heavy load pouring robot and the research of pouring speed control.
BET Inhibition Overcomes Receptor Tyrosine Kinase–Mediated Cetuximab Resistance in HNSCC
Authors: Leonard Brandon , Brand Toni M. , O'Keefe Rachel A. , Lee Eliot D. , Zeng Yan , Kemmer Jacquelyn D. , Li Hua , Grandis Jennifer R. , Bhola Neil E.
Published: May 2018

Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK. Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models. We hypothesized that, in HNSCC, targeting BRD4 could overcome cetuximab resistance by depleting alternative RTK expression. We generated independent models of cetuximab resistance in HNSCC cell lines and interrogated their RTK and BRD4 expression profiles. Cetuximab-resistant clones displayed increased expression and activation of several RTK, such as MET and AXL, as well as an increased percentage of BRD4-expressing cells. Both genetic and pharmacologic inhibition of BRD4 abrogated cell viability in models of acquired and intrinsic cetuximab resistance and was associated with a robust decrease in alternative RTK expression by cetuximab. Combined treatment with cetuximab and bromodomain inhibitor JQ1 significantly delayed acquired resistance and RTK upregulation in patient-derived xenograft models of HNSCC. These findings indicate that the combination of cetuximab and bromodomain inhibition may be a promising therapeutic strategy for patients with HNSCC.

Significance: Inhibition of bromodomain protein BRD4 represents a potential therapeutic strategy to circumvent the toxicities and financial burden of targeting the multiple receptor tyrosine kinases that drive cetuximab resistance in HNSCC and NSCLC.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4331/F1.large.jpg. Cancer Res; 78(15); 4331–43. ©2018 AACR.
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Authors: Dickler Maura N. , Saura Cristina , Richards Donald A. , Krop Ian E. , Cervantes Andrés , Bedard Philippe L. , Patel Manish R. , Pusztai Lajos , Oliveira Mafalda , Cardenas Alison K. , Cui Na , Wilson Timothy R. , Stout Thomas J. , Wei Michael C. , Hsu Jerry Y. , Baselga José
Published: May 2018

Purpose: This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer.

Patients and Methods: Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1.

Results: Median treatment duration was 4.6 (range: 0.9–40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of 60 patients had evaluable tissue for central PIK3CA mutation testing [20 had mutations, 27 had no mutation detected (MND)]. In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA mutations [best confirmed response rate: 38.5% (5/13; 95% CI, 13.9–68.4); clinical benefit rate (CBR): 38.5% (5/13; 95% CI, 13.9–68.4)], PIK3CA-MND [best confirmed response rate: 14.3% (3/21; 95% CI, 3.0–36.3); CBR: 23.8% (5/21; 95% CI, 8.2–47.2)], and unknown PIK3CA mutation status [best confirmed response rate: 20.0% (2/10; 95% CI, 2.5–55.6); CBR: 30.0% (3/10; 95% CI, 6.7–65.2)].

Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (vs. -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory phase III trial is ongoing. Clin Cancer Res; 24(18); 4380–7. ©2018 AACR.
Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma
Authors: Leijtens Jeroen W.A. , Koedam Thomas W.A. , Borstlap Wernard A.A. , Maas Monique , Doornebosch Pascal G. , Karsten Tom M. , Derksen Eric J. , Stassen Laurents P.S. , Rosman Camiel , de Graaf Eelco J.R. , Bremers André J.A. , Heemskerk Jeroen , Beets Geerard L. , Tuynman Jurriaan B. , Rademakers Kevin L.J.
Published: May 2018

Aim: Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. Methods: In this retrospective multicenter, observational cohort study, outcome after TEM-only (n = 41) and completion surgery (n = 40) following TEM for a pT2–3 rectal adenocarcinoma was compared. Results: Median follow-up was 29 months for the TEM-only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. Conclusions: Although local recurrence after TEM-only for pT2–3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended.
Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease
Authors: Conrad Erin C. , Mossner James M. , Chou Kelvin L. , Patil Parag G.
Published: May 2018

Background/Aims: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. Methods: In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. Results: We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Conclusion: Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS.
National Practice Patterns for Prenatal Monitoring in Gastroschisis: Gastroschisis Outcomes of Delivery (GOOD) Provider Survey
Authors: Amin Ruchi , Domack Aaron , Bartoletti Joseph , Peterson Erika , Rink Britton , Bruggink Jennifer , Christensen Melissa , Johnson Anthony , Polzin William , Wagner Amy J.
Published: May 2018

Background: Gastroschisis is an abdominal wall defect with increasing incidence. Given the lack of surveillance guidelines among maternal-fetal medicine (MFM) specialists, this study describes current practices in gastroschisis management. Materials and Methods: An online survey was administered to MFM specialists from institutions affiliated with the North American Fetal Therapy Network (NAFTNet). Questions focused on surveillance timing, testing, findings that changed clinical management, and delivery plan. Results: Responses were obtained from 29/29 (100%) NAFTNet centers, comprising 143/371 (39%) providers. The majority had a regimen for antenatal surveillance in patients with stable gastroschisis (94%; 134/141). Antenatal testing began at 32 weeks for 68% (89/131) of MFM specialists. The nonstress test (55%; 72/129), biophysical profile (50%; 63/126), and amniotic fluid index (64%; 84/131) were used weekly. Estimated fetal weight (EFW) was performed monthly by 79% (103/131) of providers. At 28 weeks, abnormal EFW (77%; 97/126) and Doppler ultrasound (78%; 99/127) most frequently altered management. In stable gastroschisis, 43% (60/140) of providers delivered at 37 weeks, and 29% (40/ 140) at 39 weeks. Discussion: Gastroschisis management differs among NAFTNet centers, although the majority initiate surveillance at 32 weeks. Timing of delivery still requires consensus. Prospective studies are necessary to further optimize practice guidelines and patient care.
Costaria costata Extract Suppresses Development of Atopic Dermatitis in chloro-2,4-dinitrobenzene-treated NC/Nga Mice
Authors: Kim Ok-Kyung , Lee Minhee , Kwon Han Ol , Lee Dasom , Park Jeongjin , Kim Eungpil , You Yanghee , Lim Young Tae , Jun Woojin , Lee Jeongmin
Published: May 2018

We investigated the potential effects of Costaria costata (CC) on atopic dermatitis (AD) development in chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. CC is a brown alga distributed across the seas of Korea, China, and Japan. A total of 40 mice were randomly assigned to 5 groups with 8 mice per group: untreated Balb/c mice, AD control (0.1% w/v DNCB-treated NC/Nga mice), positive control (i.e., DNCB-treated NC/Nga mice fed a dietary supplement of 66.6 mg/kg of body weight [b.w.] of CJLP133), DNCB-treated NC/Nga mice fed a dietary supplement of 100 mg/kg b.w. of CCE10 (CCE10 100), and DNCB-treated mice fed a dietary supplement of 300 mg/kg b.w. of CCE10 (CCE10 300) groups. The CCE10 100 and CCE10 300 treatment groups suppressed AD development including clinical and histopathological changes and a reduction in skin hydration induced by DNCB. In addition, Th2 cytokine production in primary splenocytes, serum IgE and histamine production, and mast cell infiltration into the skin were suppressed in the CCE10 300 mice compared to the CCE10 100 mice. Our finding demonstrated an inhibitory effect of CCE10 in AD development by means of improving the Th1/Th2 cytokine balance and anti-inflammatory effect in an in vivo model.
Differential Expression of MicroRNAs in Breast Cancers from Four Different Ethnicities
Authors: Pollard Jennifer , Burns Phil A. , Hughes Tom A. , Ho-Yen Colan , Jones J. Louise , Mukherjee Geetashree , Omoniyi-Esan Ganiat O. , Titloye Nicholas Akinwale , Speirs Valerie , Shaaban Abeer M.
Published: May 2018

Introduction: Breast cancer outcomes vary across different ethnic groups. MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression across a range of pathologies, including breast cancer. The aim of this study was to evaluate the presence and expression of miRs in breast cancer samples from different ethnic groups. Materials and Methods: Breast cancer tissue from 4 ethnic groups, i.e., British Caucasian, British Black, Nigerian, and Indian, were identified and matched for patients’ age, tumour grade/type, and 10 × 10 µm sections taken. Tumour areas were macrodissected, total RNA was extracted, and cDNA was synthesised. cDNA was applied to human miScript PCR arrays allowing the quantification of 84 of the most abundantly expressed/best-characterised miRs. Results: Differential expression of 9 miRs was seen across the 4 groups. Significantly higher levels of miR-140-5p, miR-194 and miR-423-5p (the last of which harbours the single-nucleotide polymorphism rs6505162) were seen in the breast tumours of Nigerian patients when compared with other ethnic groups (all p < 0.0001). miR-101 was overexpressed in breast cancers in the Indian patients. An in silico analysis of miR-423-5p showed that the AC genotype is mainly associated with Europeans (57%), while Asians display mostly CC (approx. 60%), and Africans mainly AA (approx. 60%). Conclusions: This study shows divergence in miR expression in breast cancers from different ethnic groups, and suggests that specific genetic variants in miR genes may affect breast cancer risk in these groups. Predicted targets of these miRs may uncover useful biomarkers that could have clinical value in breast cancers in different ethnic groups.
Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus
Authors: Turgut Mehmet , Baka Meral , Uyanıkgil Yiğit
Published: May 2018

Objective/Aim: Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats. Methods: In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment – group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis. Results: Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001). Conclusion: The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials.
Comparison of the Thermal Spread of Three Different Electrosurgical Generators on Rat Uterus: A Preliminary Experimental Study
Authors: Karacan Tolga , Usta Taner , Ozkaynak Aysel , Onur Cakir Omer , Kahraman Aslı , Ozyurek Eser
Published: May 2018

Background/Aims: The objective of this study was to compare the depth and width of thermal spread caused on rat uterine tissue after application of 3 different electrosurgical generators. Methods: Alsa Excell 350 MCDSe (Unit A), Meditom DT-400P (Unit M), and ERBE Erbotom VIO 300 D (Unit E) electrosurgical units (ESUs) were used. The number of Wistar Hannover rats required to obtain valid results was 10. The primary objective of the study was to compare the 3 ESUs using the same instrument and the same waveform. The secondary objective of the study was to compare the differences between monopolar and bipolar systems of each ESU separately using the same waveform. Results: The thermal spread caused by each ESU using monopolar instruments with continuous and interrupted waveforms was significantly different. Among the 3 devices, Unit A caused the largest thermal uterine tissue spread. On the other hand, Unit E caused the most superficial thermal tissue spread, and the smallest thermal spread among all ESUs. Conclusions: Surgeons should note that different ESUs used with the same power output might create different thermal effects especially in the monopolar configuration within the same waveform, for the same duration, and with the same instrument.
Sporadic Burkitt Lymphoma with Orbital Extramedullary Infiltration
Authors: Arepalli Sruthi , Flagg Aron , Venkat Arthi , Singh Arun D.
Published: May 2018

Background/Aims: Sporadic Burkitt lymphoma is rarely associated with orbital involvement. Methods: We present a case of sporadic Burkitt lymphoma with extramedullary subperiosteal leukemic infiltrates of the orbit and facial bones. Results: Follow-up examination after chemotherapy and disease remission reveals resolution of the subperiosteal infiltrates. Conclusion: Despite an aggressive presentation, cure is common with appropriate, intensive treatment. To our knowledge, this report is the first to photographically depict the resolution of extramedullary orbital subperiosteal leukemic infiltrates after appropriate chemotherapy.
A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression
Authors: Onyiah Joseph C. , Schaefer Rachel E.M. , Colgan Sean P.
Published: May 2018

In mucosal inflammatory disorders, the protective influence of heme oxygenase-1 (HO-1) and its metabolic byproducts, carbon monoxide (CO) and biliverdin, is a topic of significant interest. Mechanisms under investigation include the regulation of macrophage function and mucosal cytokine expression. While there is an increasing recognition of the importance of epithelial-derived factors in the maintenance of intestinal mucosal homeostasis, the contribution of intestinal epithelial cell (IEC) HO-1 on inflammatory responses has not previously been investigated. We examined the influence of modulating HO-1 expression on the inflammatory response of human IECs. Engineered deficiency of HO-1 in Caco-2 and T84 IECs led to increased proinflammatory chemokine expression in response to pathogenic bacteria and inflammatory cytokine stimulation. Crosstalk with activated leukocytes also led to increased chemokine expression in HO-1-deficient cells in an IL-1β dependent manner. Treatment of Caco-2 cells with a pharmacological inducer of HO-1 led to the inhibition of chemokine expression. Mechanistic studies suggest that HO-1 and HO-1-related transcription factors, but not HO-1 metabolic products, are partly responsible for the influence of HO-1 on chemokine expression. In conclusion, our data identify HO-1 as a central regulator of IEC chemokine expression that may contribute to homeo­stasis in the intestinal mucosa.
A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia
Authors: van der Wijst Jenny , Konrad Martin , Verkaart Sjoerd A.J. , Tkaczyk Marcin , Latta Femke , Altmüller Janine , Thiele Holger , Beck Bodo , Schlingmann Karl Peter , de Baaij Jeroen H.F.
Published: May 2018

Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations.
Canonical Wnt Signaling Promotes Macrophage Proliferation during Kidney Fibrosis
Authors: Feng Ye , Liang Yan , Ren Jiafa , Dai Chunsun
Published: May 2018

Background: Wnt/β-catenin, an evolutionary conserved signaling pathway, plays an essential role in modulating kidney injury and repair. Our previous studies demonstrated that Wnt/β-catenin signaling could stimulate macrophage M2 polarization and contribute to kidney fibrosis. However, whether canonical Wnt signaling activation leads to macrophage proliferation during kidney fibrosis remains to be determined. Methods: In this study, a mouse model with macrophage-specific β-catenin gene deletion was generated and a unilateral ureter obstruction (UUO) model was created. Results: In a mouse model with UUO nephropathy, deletion of β-catenin in macrophages attenuated macrophage proliferation and accumulation in kidney tissue. Wnt3a, a well-known canonical Wnt signaling stimulator, could markedly promote macrophage proliferation, whereas blocking canonical Wnt signaling with ICG-001 or ablating β-catenin could largely inhibit macrophage colony-stimulating factor-stimulated macrophage proliferation. Wnt3a treatment could time-dependently upregulate cyclin D1 protein expression and blocking β-catenin signaling could downregulate it. Conclusion: These results demonstrate that Wnt/ β-catenin signaling is essential for promoting macrophage proliferation during kidney fibrosis.
Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury
Authors: Fiorentino Marco , Kellum John A.
Published: May 2018

Background: Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. Summary: Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success.
Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study
Authors: Bikbov Boris , Perico Norberto , Remuzzi Giuseppe ,   on behalf of the GBD Genitourinary Diseases Expert Group
Published: May 2018

Background: Chronic kidney disease (CKD) imposes a substantial burden on health care systems. There are some especially vulnerable groups with a high CKD burden, one of which is women. We performed an analysis of gender disparities in the prevalence of all CKD stages and renal replacement therapy (defined as impaired kidney function [IKF]) in 195 countries. Methods: We used estimates produced by the Global Burden of Disease (GBD) Study 2016 revision using a Bayesian-regression analytic tool, DisMoD-MR 2.1. Data on gross domestic product based on purchasing power parity per capita (GDP PPP) was obtained via the World Bank International Comparison Program database. To estimate gender disparities, we calculated the male:female all-age prevalence rate ratio for each IKF condition. Results: In 2016, the global number of individuals with IKF reached 752.7 million, including 417.0 million females and 335.7 million males. The most prevalent form of IKF in both groups was albuminuria with preserved glomerular filtration rate. Geospatial analysis shows a very heterogeneous distribution of the male:female ratio for all IKF conditions, with the most prominent contrast found in kidney transplant patients. The median male:female ratio varies substantially according to GDP PPP quintiles; however, countries with different economic states could have similar male:female ratios. A strong correlation of GDP PPP with dialysis-to-transplant ratio was found. Conclusions: The GBD study highlights the prominent gender disparities in CKD prevalence among 195 countries. The nature of these disparities, however, is complex and must be interpreted cautiously taking into account all possible circumstances.
Tiberius in Capri: Power Struggles and Political Relationships between Emperor and Senate
Authors: Campos Rafael Da Costa
Published: May 2018

Por volta dos anos de 26 e 27 d.C., Tibério fixou-se em sua villa na ilha de Capri, de onde passou a governar até o fim de sua vida. Seu afastamento de Roma pode ser considerado um evento histórico relevante ao processo de consolidação do Principado como um dos passos de uma integração mediterrânica. A intenção desse artigo é observar as reações ocasionadas entre Princeps e Senado, e os efeitos relativos à sua legitimidade e a esta instituição política em construção.