bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone marrow solid core biopsy needle: a critical assessment of the utility, benefits and limitations of the instruments employed in current day haematology and oncology
Authors: Islam Anwarul
Published: December 2017

The optimal clinical evaluation of the bone marrow requires an examination of air-dried and well-stained films of the aspirated tissue along with a histopathological evaluation of adequately processed and properly stained core biopsy specimens. A bone marrow evaluation can be essential in establishing a diagnosis, determining the efficacy of treatment in haematological disorders and to monitor haematological status of patients following bone marrow/stem cell transplantation. It is also an essential component of the staging process for newly diagnosed malignancies. Currently available bone marrow aspiration needles are quite satisfactory and if properly used provide good-quality specimens for morphological evaluation. However, if a bone marrow core biopsy is concerned, several needles are currently in use but not all of them provide good-quality biopsy specimens for histological evaluation or are user friendly. We have compared the recently introduced Moeller Medical single use bone marrow core biopsy needle with the Jamshidi needle with marrow acquisition cradle (CareFusion), J-needle (Cardinal Health) and OnControl device (Vidacare). It is concluded that the Moeller Medical needle system has definite advantages over others and is recommended for routine use.
Ataxia with oculomotor apraxia type 2: an evolving axonal neuropathy
Authors: Choudry Tahira N , Hilton-Jones David , Lennox Graham , Houlden Henry
Published: December 2017

A 23-year-old woman had presented initially to a podiatrist complaining of poorly fitting shoes during her adolescence. After extensive neurological review, she was diagnosed with ataxia with oculomotor apraxia type 2. This is a progressive autosomal recessive ataxia associated with cerebellar atrophy, peripheral neuropathy and an elevated serum α-fetoprotein. Within Europe, it is the most frequent autosomal recessive ataxia after Friedreich’s ataxia and is due to mutations in the senataxin (SETX) gene. The age of onset is approximately 15 years.

The diagnosis of oculomotor apraxia type 2 is often challenging. We provide a framework for assessing a young ataxic patient with or without oculomotor apraxia and review clues that will aid diagnosis. The prognosis, level of disability, cancer and immunosuppression risk all markedly differ between the conditions. Patients and their families need the correct diagnosis for genetic counselling, management and long-term surveillance with appropriate subspecialty services.
Comparison of 2 weekly-equalized volume resistance-training routines using different frequencies on body composition and performance in trained males
Authors: Yue Fu (Leon) , Karsten Bettina , Larumbe-Zabala Eneko , Seijo Marcos , Naclerio Fernando
Published: December 2017

The present study compared the effects of 2 weekly-equalized volume and relative load interventions on body composition, strength, and power. Based on individual baseline maximal strength values, 18 recreationally trained men were pair-matched and consequently randomly assigned to one of the following experimental groups: a low volume per session with a high frequency (LV-HF, n = 9) group who trained for 4 days (Mondays, Tuesdays, Thursdays, and Fridays) or a high volume per session and low frequency (HV-LF, n = 9) group who trained for 2 days (Mondays and Thursdays). Both groups performed 2 different routines over 6 weeks. Participants were tested pre- and post- intervention for maximal strength, upper body power, fat-free mass, limb circumferences, and muscle thickness. Compared with baseline values, both groups increased their fat-free mass (HV-LF: +1.19 ± 1.94; LV-HF: +1.36 ± 1.06 kg, p < 0.05) and vastus medialis thickness (HV-LF: +2.18 ± 1.88, p < 0.01; LV-HF: +1.82 ± 2.43 mm, p < 0.05), but only the HV-LF group enhanced arm circumference (1.08 ± 1.47 cm, p < 0.05) and elbow flexors thickness (2.21 ± 2.81 mm, P < 0.01) values and decreased their fat mass (–2.41 ± 1.10, P < 0.01). Both groups improved (p < 0.01) the maximal loads lifted in the bench press (LV-HF: +0.14 ± 0.01; HV-LF: +0.14 ± 0.01 kg·body mass−1) and the squat (LV-HF: +0.14 ± 0.06; HV-LF: 0.17 ± 0.01 kg·body mass−1) exercises as well as in upper body power (LV-HF: +0.22 ± 0.25; HV-LF: +0.27 ± 0.22 W·body mass−1) Although both training strategies improved performance and lower body muscle mass, only the HV-LF protocol increased upper body hypertrophy and improved body composition.
Evaluating a hierarchical approach to landscape-level harvest scheduling
Authors: Eyvindson Kyle , Rasinmäki Jussi , Kangas Annika
Published: December 2017

Forest planning at the landscape level has the potential to become a large intractable problem. In Finland, Metsähallitus (the state enterprise that manages federally owned land) creates strategic plans to determine the appropriate harvest level. While these plans are feasible, they are not implementable in practice as the harvests are scattered temporally and spatially. Requiring that harvests be organized both temporally and spatially for practical implementation can result in an intractable problem. Through a hierarchical approach, the problem can be organized into steps in which the intractable problem is broken down into smaller easily solvable parts. As an approximation technique, the hierarchical approach may not find a solution close to optimality. To meet this challenge, we combine the top hierarchical level problems with a limited selection of lower hierarchical level problems into a single optimization problem. An iterative process is then used to improve the link between the hierarchical levels. We evaluate the landscape-level management plans developed by the iterative approach with a solution to the complete problem. The iterative process dramatically improves the strategic solution, performing near the global optimum. This suggests that the process can be applied to more computationally challenging problems such as spatial planning and stochastic programming.
N-Reciprocity Property for Interval-Valued Fuzzy Relations with an Application to Group Decision Making Problems in Social Networks
Authors: Bentkowska Urszula , Pȩkala Barbara , Bustince Humberto , Fernandez Javier , Jurio Aranzazu , Balicki Krzysztof
Published: December 2017

In this paper we study interval-valued fuzzy relations. We consider preference relations, i.e. a triplet consisting of strict preference, indifference and incomparability which are defined with the use of a fuzzy negation. We analyze the preservation of the fuzzy negation based reciprocity property of interval-valued fuzzy relations by aggregation functions and by some basic interval-valued fuzzy relations. We use diverse representa-tions of aggregation functions. We also consider the connection between N-reciprocal relations and transitivity properties. We provide a numerical example where the final alternative is chosen with the use of generalized voting method, where admissible linear orders for intervals are applied.
Multicriteria Design of Cost-Conscious Fuzzy Rule-Based Classifiers
Authors: Cocaña-Fernández Alberto , Ranilla José , Gil-Pita Roberto , Sánchez Luciano
Published: December 2017

Many real-world classification systems must comply with a series of inherent restrictions to the problem at hand such as response times, power consumptions or computational costs. This poses a fundamental limitation to traditional performance-driven classifiers and learning algorithms by restraining their applicability in cost-sensitive scenarios. Because of this, fuzzy systems are leveraged to learn cost-conscious multi-stage classifiers through multiobjective optimization to find a set of optimal tradeoffs between accuracy and any related cost. This approach allows find a suitable balance between all objectives regardless of the scenario. Experimental evaluations were done for Sound Environment Classification in modern battery-powered hearing aids by jointly optimising classification accuracy and computational costs.
A REVIEW OF TWO-DIMENSIONALIN VITROCELL STRETCH PLATFORMS
Authors: GHAZIZADEH H. , ARAVAMUDHAN S.
Published: December 2017

The focus of this paper is to describe the mechanism and behavior of two-dimensional in vitro cell stretch platforms, as well as discussing designs for the evaluation of mechanical properties of cells. It is extremely important to understand the cellular response to extrinsic mechanical forces as living biological system is constantly subjected to mechanical forces in vivo. In addition, this mechanistic understanding of cellular response will provide valuable information towards the design and fabrication of bioengineered tissues and organs, which are expected to replace and/or aid bodily functions. This paper will primarily focus on the development, advantages and limitations of two-dimensional cell stretch platforms.
EFFICIENT DETECTION OF MICRO-ANEURYSMS IN RETINAL IMAGES FOR EARLY DIAGNOSIS OF DIABETIC RETINOPATHY
Authors: FEROUI A. , MESSADI M. , LAZOUNI A. , BESSAID A.
Published: December 2017

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus and one of the major causes of blindness worldwide. As the number of diabetic patients increases, early detection of DR for regular screening can prevent loss of vision and blindness. The development of algorithms for detecting dark lesions may turn very useful in the early diagnosis and screening of retinopathy diseases. In this paper, a novel hybrid algorithm for the microaneurysms (MAs) detection is developed. This task is based on mathematical morphology, which is followed by a classification step. Although some algorithms have been developed, the accurate detection of MAs in color retinal images is still a challenging problem. The proposed approach aims to increase the number of true positives and minimize the false positives compared with methods developed in the literature. The new approach is tested on a set of 219 ophthalmologic images. A total of 12 microaneurysm features are considered in this study and selected for KNN classification. The validity of detection process is checked through comparisons at the pixel level with ophthalmologists’ hand-drawn ground truth. Sensitivity, specificity, prediction rate, and accuracy achieved by the proposed approach are 98.13%, 99.71%, 99.63% and 99.01% respectively.
Superposition and entanglement of two-mode squeezed vacuum states
Authors: Karimi Amir
Published: December 2017

In this paper, by using the parity operator as well as the two-mode squeezing operator, we define new operators which by the action of them on the vacuum state of the two-mode radiation field, superposition of two two-mode squeezed vacuum states and entangled two-mode squeezed vacuum states are generated.
Experiences in calibrating and evaluating lumped karst hydrological models
Authors: Hartmann Andreas
Published: December 2017

Karst systems play an important part in providing clean drinking water for many countries worldwide. Their sustainable management often requires the application of karst hydrological models to quantify the water volumes available and to assess their sensitivity to changes in climate or land use. The available literature provides a broad overview of different modelling approaches to simulate karst hydrology, but guidance for the application of these approaches is scarce. This paper provides personal insights into the application, calibration and evaluation of lumped karst hydrological models. An introduction to model calibration and sensitivity analysis is given, with links to further reading and ready-to-use toolboxes. It is followed by three case studies of karst model applications at three different scales (the plot scale, aquifer scale and continental scale), which apply model calibration and sensitivity analysis to obtain realistic simulations. These three case studies elaborate how the necessary trade-off between the available data and process representation in the model structures was achieved. General recommendations and a workflow for future karst model applications are given.
Design and Solution of a Surrogate Model for Portfolio Optimization Based on Project Ranking
Authors: Fernandez Eduardo , Gómez-Santillán Claudia , Cruz-Reyes Laura , Rangel-Valdez Nelson , Bastiani Shulamith
Published: December 2017

Characterizing the preferences of a decision maker in a multicriteria decision is a complex task that becomes even harder if the information available is limited. This paper addresses a particular case of project portfolio selection; in this case, the measures of project impacts are not assumed, and the available information is only projects’ ranking and costs. Usually, resource allocation follows the ranking priorities until they are depleted. This action leads to a feasible solution, but not necessarily to a good portfolio. In this paper, a good portfolio is found by solving a multiobjective problem. To effectively address such dimensionality, the decision maker’s preferences in the form of a fuzzy relational system are incorporated in an ant-colony algorithm. The Region of Interest is approached by solving a surrogate triobjective problem. The results show that the reduction of the dimensionality supports the decision maker in choosing the best portfolio.
Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis
Authors: Liao Huan , Wang Hongxuan , Rong Xiaoming , Li Enqin , Xu Ren-He , Peng Ying
Published: December 2017

Radiation-induced brain injury (RI) commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs) on it. BALB/c male mice (6–8 weeks) were cranially irradiated (15 Gy), and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy) were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1β. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.
Vibration Analysis of Plate with Irregular Cracks by Differential Quadrature Finite Element Method
Authors: Xu Zhongyuan , Chen Wei
Published: December 2017

A universal method combining the differential quadrature finite element method with the virtual spring technique for analyzing the free vibration of thin plate with irregular cracks is proposed. Translational and rotational springs are introduced to restrain the vertical displacement and orientation of the plate. The mass matrix and stiffness matrix for each element are deduced involving the effects of the virtual springs. The connection relationships between elements can be modified by setting the stiffness of the virtual springs. The vibration of two rectangular plates with three irregular shaped cracks and different boundary conditions are presented. The results are compared with those obtained by ANSYS, where the good agreement between the results validates the accuracy and efficiency of the present method.
A PCBM-Modified TiO2 Blocking Layer towards Efficient Perovskite Solar Cells
Authors: Lu Gang , He Fengqin , Pang Shangzheng , Yang Haifeng , Chen Dazheng , Chang Jingjing , Lin Zhenhua , Zhang Jincheng , Zhang Chunfu
Published: December 2017

Organometal halide perovskite as a promising absorber in solar cells has caught tremendous attention in the past few years. Herein, a hydrophobic PCBM layer was introduced into planar heterojunction perovskite solar cells to form the TiO2/PCBM double blocking layer. The bilayer structure assures the formation of a dense, smooth, and pinhole-free blocking layer. And the PCBM layer can also be in favor of larger grain size perovskite film and further passivate the TiO2 blocking layer. Scanning electron microscope, atomic force microscope, and X-ray diffraction (XRD) results suggest the formation of a uniform and compact CH3NH3PbI3−xClx perovskite layer on the PCBM-modified TiO2 blocking layer. The solar cell has reached a PCE up to 16.37%, which is greatly larger than the control device with a PCE of 10.81%.
Influence of Institution-Based Factors on Preoperative Blood Testing Prior to Low-Risk Surgery: A Bayesian Generalized Linear Mixed Approach
Authors: Ide Kazuki , Yonekura Hiroshi , Kawasaki Yohei , Kawakami Koji
Published: December 2017

To optimize delivery of health care services in clinical practice, the use of unnecessary interventions should be reduced. Although recommendations for this reduction have been accepted worldwide, recent studies have revealed that the use of such procedures continues to increase. We conducted a retrospective cohort study using a nationwide claim-based database to evaluate factors influencing preoperative blood testing prior to low-risk surgery, via a Bayesian generalized linear mixed approach. The study period was set from April 1, 2012, to March 31, 2016, and 69,252 surgeries performed at 9,922 institutions were included in the analysis. Mean patient age was 44.3 ± 11.3 years (57% female). Preoperative blood tests were performed for 59.0% of procedures. Among institutional factors, the number of beds was strongly associated with preoperative blood testing (odds ratio [95% highest posterior density interval (HPD interval)], 2.64 [2.53 to 2.75]). The difference (95% credible interval) in the rate of preoperative blood testing between institutions with <100 beds and ≥100 beds was 0.315 [0.309 to 0.322], and the Bayesian indexθwas 1.00. This indicated that preoperative blood tests are strongly influenced by institutional factors, suggesting that specific guidelines should be developed to avoid excessive preoperative testing for low-risk surgery.
Possible Effect of Concomitant Prokinetics and Herbal Medicines against Nausea in Patients Taking Lubiprostone
Authors: Yamamoto Takatsugu , Osumi Shun , Yanagisawa Daisuke , Yamato Hiroshi , Aoyagi Hitoshi , Isono Akari , Abe Koichiro , Kita Hiroto
Published: December 2017

Background and Aim. Lubiprostone is a novel laxative that sometimes causes nausea, but preventive strategies remain unconfirmed. Methods. We retrospectively chose 126 patients prescribed lubiprostone from 2013 to 2016. Medical records were reviewed to clarify whether nausea developed after administration of the drug. Background characteristics, including concomitant medicines, were also reviewed. Results. The most common adverse symptom was diarrhea (23.8%). Nausea occurred in 16 patients (12.7%). Patients taking either prokinetics or herbal medicines or both were unlikely to develop nausea (p=0.007). Conclusions. Concomitant prokinetics and/or herbal medicines may help alleviate lubiprostone-induced nausea.
Open Abdomen Management and Candida Infections: A Very Likely Link
Authors: Occhionorelli Savino , Zese Monica , Cultrera Rosario , Lacavalla Domenico , Albanese Marco , Vasquez Giorgio
Published: December 2017

Objective. Laparostomy can be applied in trauma, abdominal sepsis, intra-abdominal hypertension, or compartment syndrome. Systemic infections, especially if complicated by Candida, are associated with a high risk of mortality. Methods. This is a single-centre retrospective case series of 47 cases admitted to our Department, which required laparostomy procedure; we analyzed the type of surgery, temporary abdominal closure, duration of open abdomen, complications, SOFA score, mortality with Candida infections, and empirical or targeted antifungal therapy. Results. We found that patients with Candida infection were related with a statistically significant difference (p<0.05) with a complication after OA closure, total complications, time elapsed after OA application, time spent on the first surgical OA application, type of temporary abdominal closure that is used, and duration of the open abdomen. The use of empirical and targeted antifungal therapy is related to the duration of open abdomen too. Conclusions. Management of the OA is often burdened by sepsis or septic shock, especially when complicated by Candida infection. Candida score is a validated tool to identify patients who can be treated empirically, but every situation must be considered on an individual basis.
Layout Optimization of Two Autonomous Underwater Vehicles for Drag Reduction with a Combined CFD and Neural Network Method
Authors: Tian Wenlong , Mao Zhaoyong , Zhao Fuliang , Zhao Zhicao
Published: December 2017

This paper presents an optimization method for the design of the layout of an autonomous underwater vehicles (AUV) fleet to minimize the drag force. The layout of the AUV fleet is defined by two nondimensional parameters. Firstly, three-dimensional computational fluid dynamics (CFD) simulations are performed on the fleets with different layout parameters and detailed information on the hydrodynamic forces and flow structures around the AUVs is obtained. Then, based on the CFD data, a back-propagation neural network (BPNN) method is used to describe the relationship between the layout parameters and the drag of the fleet. Finally, a genetic algorithm (GA) is chosen to obtain the optimal layout parameters which correspond to the minimum drag. The optimization results show that (1) the total drag of the AUV fleet can be reduced by 12% when the follower AUV is located directly behind the leader AUV and (2) the drag of the follower AUV can be reduced by 66% when it is by the side of the leader AUV.
Performance Improvement of a Micro Impulse Water Turbine Based on Orthogonal Array
Authors: Tang Lingdi , Yuan Shouqi , Tang Yue
Published: December 2017

The study on structural design and efficiency improvement of the micro impulse water turbine with the super‐low specific speed has rarely been reported in literature. In this paper, a micro impulse water turbine was optimized on the base of the orthogonal array of L18(37) with six factors. The range analysis and variance analysis were conducted to present the significance ranking of factors and the optimal combinations of factors, aiming to improve the water turbine efficiency taken as the experimental indicator in the orthogonal experiment. And then the optimal parameter combination for the water turbine was calculated by orthogonal experiment. Moreover, the internal flow field and hydraulic performance were simulated numerically to investigate the principle of performance improvement by comparing the optimized water turbine with the original. Also, the numerical method was verified by experimental result from performance tests of the original water turbine. As a result, the runner torque of the optimized water turbine was 13% higher than that of the original and the water turbine efficiency was improved by 5.8 percentage points at the rated operating condition.
Comparison of Optic Nerve Head Blood Flow Autoregulation among Quadrants Induced by Decreased Ocular Perfusion Pressure during Vitrectomy
Authors: Hashimoto Ryuya , Sugiyama Tetsuya , Maeno Takatoshi
Published: December 2017

Purpose. The present study aimed to examine changes in optic nerve head (ONH) blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in order to determine whether there is a significant difference of autoregulatory capacity in response to OPP decrease at each ONH quadrant. Methods. This study included 24 eyes with an epiretinal membrane or macular hole that underwent vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean tissue MBRs in the four quadrants were generated automatically in the software analysis report. Measurements were conducted before and 5 and 10 min after intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects without systemic disorders. Results. The baseline tissue MBR of the temporal quadrant was significantly lower than that of the other 3 quadrants (all P<0.05). However, the time courses of tissue MBR in response to OPP decrease were not significantly different among the four quadrants during vitrectomy (P=0.23). Conclusions. There is no significant difference in the autoregulatory capacity of the four ONH quadrants in patients without systemic disorders during vitrectomy.
Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal Muscle Repair and Regeneration
Authors: Wright Craig R. , Ward Alister C. , Russell Aaron P.
Published: December 2017

Granulocyte colony-stimulating factor (G-CSF) was originally discovered in the context of hematopoiesis. However, the identification of the G-CSF receptor (G-CSFR) being expressed outside the hematopoietic system has revealed wider roles for G-CSF, particularly in tissue repair and regeneration. Skeletal muscle damage, including that following strenuous exercise, induces an elevation in plasma G-CSF, implicating it as a potential mediator of skeletal muscle repair. This has been supported by preclinical studies and clinical trials investigating G-CSF as a potential therapeutic agent in relevant disease states. This review focuses on the growing literature associated with G-CSF and G-CSFR in skeletal muscle under healthy and disease conditions and highlights the current controversies.
Semantic Annotation of Unstructured Documents Using Concepts Similarity
Authors: Pech Fernando , Martinez Alicia , Estrada Hugo , Hernandez Yasmin
Published: December 2017

There is a large amount of information in the form of unstructured documents which pose challenges in the information storage, search, and retrieval. This situation has given rise to several information search approaches. Some proposals take into account the contextual meaning of the terms specified in the query. Semantic annotation technique can help to retrieve and extract information in unstructured documents. We propose a semantic annotation strategy for unstructured documents as part of a semantic search engine. In this proposal, ontologies are used to determine the context of the entities specified in the query. Our strategy for extracting the context is focused on concepts similarity. Each relevant term of the document is associated with an instance in the ontology. The similarity between each of the explicit relationships is measured through the combination of two types of associations: the association between each pair of concepts and the calculation of the weight of the relationships.
New Method for the Development of Plasmonic Metal-Semiconductor Interface Layer: Polymer Composites with Reduced Energy Band Gap
Authors: Aziz Shujahadeen B. , Mamand Soran M. , Saed Salah R. , Abdullah Ranjdar M. , Hussein Sarkawt A.
Published: December 2017

Silver nanoparticles within a host polymer of chitosan were synthesized by using in situ method. Ultraviolet-visible spectroscopy was then carried out for the prepared chitosan : silver triflate (CS : AgTf) samples, showing a surface plasmonic resonance (SPR) peak at 420 nm. To prepare polymer composites with reduced energy band gap, different amounts of alumina nanoparticles were incorporated into the CS : AgTf solution. In the present work, the results showed that the reduced silver nanoparticles and their adsorption on wide band gap alumina (Al2O3) particles are an excellent approach for the preparation of polymer composites with small optical band gaps. The optical dielectric loss parameter has been used to determine the band gap experimentally. The physics behind the optical dielectric loss were interpreted from the viewpoint of quantum mechanics. From the quantum-mechanics viewpoint, optical dielectric loss was also found to be a complex equation and required lengthy numerical computation. From the TEM investigation, the adsorption of silver nanoparticles on alumina has been observed. The optical micrograph images showed white spots (silver specks) with different sizes on the surface of the films. The second semicircle in impedance Cole-Cole plots was found and attributed to the silver particles.
Dispersion and Sensitivity Analysis of Quasi-Scholte Wave Liquid Sensing by Analytical Methods
Authors: Önen Onursal
Published: December 2017

Ultrasonic-guided wave sensing relies on perturbation of wave propagation by changing physical properties of the target media. Solid waveguides, through which guided waves can be transduced between the transducer and the target media, are frequently employed for liquid sensing and several other applications. In this manuscript, liquid sensing sensitivity of dispersive quasi-Scholte waves, which are guided interface waves that travel at the solid-liquid boundary, is investigated. Dispersion analysis of quasi-Scholte waves is done and sensitivities of quasi-Scholte waves to changes in fluid density and speed of sound in a dipstick configuration are analyzed. An experimentally verified analytical model based on a global matrix approach is employed in a nondimensional manner to generate representative dispersion and sensitivity surfaces. Optimum configurations with respect to the material properties of the liquid and of the waveguide are illustrated, which would enable optimal quasi-Scholte liquid sensing.
SIRT6 Is a Target of Regulation by UBE3A That Contributes to Liver Tumorigenesis in an ANXA2-Dependent Manner
Authors: Kohli Saishruti , Bhardwaj Abhishek , Kumari Richa , Das Sanjeev
Published: December 2017

UBE3A is an E3 ubiquitin ligase well known for its role in the proteasomal degradation of p53 in human papillomavirus (HPV)-associated cancers. Here we report that UBE3A ubiquitylates and triggers degradation of the tumor-suppressive sirtuin SIRT6 in hepatocellular carcinoma. UBE3A ubiquitylated the highly conserved Lys160 residue on SIRT6. FOXO1-mediated transcriptional repression of UBE3A was sufficient to stabilize SIRT6 and to epigenetically repress ANXA2, a key mediator of UBE3A oncogenic function. Thus, UBE3A-mediated SIRT6 degradation promoted the proliferative capacity, migration potential, and invasiveness of cells. In mouse models of hepatocellular carcinoma, SIRT6 downregulation and consequent induction of ANXA2 were critical for UBE3A-mediated tumorigenesis. Furthermore, in clinical specimens, increased UBE3A levels correlated with reduced SIRT6 levels and elevated ANXA2 levels in increasing tumor grades. Overall, our findings show how the tumor suppressor SIRT6 is regulated in hepatocellular carcinoma and establish the mechanism underlying UBE3A-mediated tumorigenesis in this disease.

Significance: These findings provide mechanistic insights into regulation of the tumor suppressive sirtuin SIRT6 and its implications for the development of hepatocellular carcinoma. Cancer Res; 78(3); 645–58. ©2017 AACR.
Tumor-Associated Fatigue in Cancer Patients Develops Independently of IL1 Signaling
Authors: Grossberg Aaron J. , Vichaya Elisabeth G. , Christian Diana L. , Molkentine Jessica M. , Vermeer Daniel W. , Gross Phillip S. , Vermeer Paola D. , Lee John H. , Dantzer Robert
Published: December 2017

Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it is generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion is mostly correlational. In this study, we directly tested the hypothesis that fatigue results from propagation of tumor-induced inflammation to the brain and activation of the central proinflammatory cytokine, IL1. The heterotopic syngeneic murine head and neck cancer model (mEER) caused systemic inflammation and increased expression of Il1b in the brain while inducing fatigue-like behaviors characterized by decreased voluntary wheel running and exploratory activity. Expression of Il1b in the brain was not associated with any alterations in motivation, measured by responding in a progressive ratio schedule of food reinforcement, depression-like behaviors, or energy balance. Decreased wheel running occurred prior to Il1b detection in the brain, when systemic inflammation was minimal. Furthermore, mice null for two components of IL1β signaling, the type 1 IL1 receptor or the receptor adapter protein MyD88, were not protected from tumor-induced decreases in wheel running, despite attenuated cytokine action and expression. Behavioral and inflammatory analysis of four additional syngeneic tumor models revealed that tumors can induce fatigue regardless of their systemic or central nervous system inflammatory potential. Together, our results show that brain IL1 signaling is not necessary for tumor-related fatigue, dissociating this type of cancer sequela from systemic cytokine expression.

Significance: These findings challenge the current understanding of fatigue in cancer patients, the most common and debilitating sequela associated with malignancy. Cancer Res; 78(3); 695–705. ©2017 AACR.
Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes
Authors: Colunga Aric , Pulliam Thomas , Nghiem Paul
Published: December 2017

Merkel cell carcinoma (MCC) is a rare (∼2,000 U.S. cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year), suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in approximately 80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic. Indeed, antigen-specific T cells detected in patients are frequently dysfunctional/“exhausted,” and the inhibitory ligand, PD-L1, is often present in MCC tumors. These findings led to recent clinical trials involving PD-1 pathway blockade in advanced MCC. The combined data from these trials involving three PD-1 pathway blocking agents—avelumab, pembrolizumab, and nivolumab—indicated a high frequency of durable responses in treated patients. Of note, prior treatment with chemotherapy was associated with decreased response rates to PD-1 checkpoint blockade. Over the past year, these striking data led to major changes in advanced MCC therapy, including the first-ever FDA drug approval for this disease. Despite these successes, approximately 50% of patients with MCC do not persistently benefit from PD-1 pathway blockade, underscoring the need for novel strategies to broaden antitumor immune responses in these patients. Here, we highlight recent progress in MCC including the underlying mechanisms of immune evasion and emerging approaches to augment the efficacy of PD-1 pathway blockade. Clin Cancer Res; 24(9); 2035–43. ©2017 AACR.
FAM198B Is Associated with Prolonged Survival and Inhibits Metastasis in Lung Adenocarcinoma via Blockage of ERK-Mediated MMP-1 Expression
Authors: Hsu Chia-Ying , Chang Gee-Chen , Chen Yi-Ju , Hsu Yi-Chiung , Hsiao Yi-Jing , Su Kang-Yi , Chen Hsuan-Yu , Lin Chien-Yu , Chen Jin-Shing , Chen Yu-Ju , Hong Qi-Sheng , Ku Wen-Hui , Wu Chih-Ying , Ho Bing-Ching , Chiang Ching-Cheng , Yang Pan-Chyr , Yu Sung-Liang
Published: December 2017

Purpose: The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer.

Experimental Design: FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro cellular assays and in vivo mouse models. In addition, the N-glycosylation–defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression.

Results: We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities in vitro. FAM198B also attenuated tumor growth and metastasis in vivo. We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability.

Conclusions: Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma. Clin Cancer Res; 24(4); 916–26. ©2017 AACR.
The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations—The Lung Cancer Mutation Consortium (LCMC2)
Authors: Aisner Dara L. , Sholl Lynette M. , Berry Lynne D. , Rossi Michael R. , Chen Heidi , Fujimoto Junya , Moreira Andre L. , Ramalingam Suresh S. , Villaruz Liza C. , Otterson Gregory A. , Haura Eric , Politi Katerina , Glisson Bonnie , Cetnar Jeremy , Garon Edward B. , Schiller Joan , Waqar Saiama N. , Sequist Lecia V. , Brahmer Julie , Shyr Yu , Kugler Kelly , Wistuba Ignacio I. , Johnson Bruce E. , Minna John D. , Kris Mark G. , Bunn Paul A. , Kwiatkowski David J.
Published: December 2017

Purpose: Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas.

Experimental Design: Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC.

Results: The use of targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK, ROS1, or RET rearrangements, or MET amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in EGFR/ALK/ROS1, when compared with 75 never smokers with the same alterations. In addition, coexisting TP53 mutations were associated with shorter survival among patients with EGFR, ALK, or ROS1 alterations.

Conclusion: Patients with adenocarcinoma of the lung and an oncogenic driver mutation treated with effective targeted therapy have a longer survival, regardless of prior smoking history. Molecular testing should be performed on all individuals with lung adenocarcinomas irrespective of clinical characteristics. Routine use of massively parallel sequencing enables detection of both targetable driver alterations and tumor suppressor gene and other alterations that have potential significance for therapy selection and as predictive markers for the efficacy of treatment. Clin Cancer Res; 24(5); 1038–47. ©2017 AACR.
Prognostic Factors and Efficacy for Continuous Renal Replacement Therapy in Critically Ill Patients: A Chinese Single-Center Retrospective Study
Authors: Zhang Jing , Li Yiming , Peng Zhiyong
Published: December 2017

Background: There is controversy about the efficacy and prognostic factors for continuous renal replacement therapy (CRRT) in China due to practice variation. Our aim is to investigate these questions. Method: A total of 613 adult patients receiving CRRT in last 3 years from one Chinese ICU were enrolled. The analysis of demographic data, vital signs, and laboratory tests prior to CRRT and outcomes were performed. The data between pre- and post-CRRT were compared for efficacy analysis. Results: Prior to CRRT, partial pressure of carbon dioxide (PCO2), systolic blood pressure (SBP), gender, age, bilirubin, cystatin C, and mechanical ventilation were correlated with in-hospital mortality. In a binary logistic regression, PCO2, SBP, age, and gender were significant in predicting mortality. Cox regression analysis demonstrated PCO2 independent association with mortality, and lower SBP worse mortality. CRRT could eliminate the fluid and metabolites. Conclusion: CO2 retention and low SBP prior to CRRT were associated with increased mortality. CRRT significantly improved hemeostasis.
Swan Neck Deformity Mimicking Claw Hand Caused by Arthritis in Leprosy
Authors: Gunawan Hendra , Haryati Nia Srie , Suwarsa Oki
Published: December 2017

Swan neck deformity is a hyperextension of the proximal interphalangeal (PIP) joints and flexion of the distal interphalangeal (DIP) joints. Claw hand is a hyperextension of the metacarpal joints and flexion of the PIP joints, accompanied by reduced motor strength. A 23-year-old female, who was released from leprosy treatment, presented with a bend of the second to fifth fingers of both hands. There was hyperextension of the PIP joints and flexion of the DIP joints from the second to fifth fingers of both hands, thickening of the ulnar nerves, and hypoesthesia without motor impairment of the fourth and fifth fingers of both hands. Radiograph examination revealed cupping of the base of the proximal phalangeal joints of the second, third, and fifth fingers of the left hand and of the second and fifth fingers of the right hand. Additionally, narrowing of the metacarpophalangeal joints of the second, third, and fifth fingers of the right hand and sclerosis of the second and fifth fingers of the right hand were also observed. Claw hand is frequently reported in leprosy, while swan neck deformity is frequently reported in rheumatoid arthritis. To our knowledge, this is the first reported case with swan neck deformity caused by arthritis in leprosy.
Emerging Treatment Options in Atopic Dermatitis: Topical Therapies
Authors: Nygaard Uffe , Deleuran Mette , Vestergaard Christian
Published: December 2017

Atopic dermatitis is a chronic inflammatory skin disorder affecting children and adults, with the majority presenting mild to moderate disease severity. The use of topical corticosteroids (TCSs) in combination with emollients has been the mainstay for treating mild to moderate atopic dermatitis since the 1950s, and as a supplement to systemic treatment in severe disease. However, while very effective, TCSs are often accompanied by poor adherence due to corticophobia (fear of using corticosteroids in patients or doctors), unwanted side effects, and in some cases insufficient clinical response. Topical calcineurin inhibitors (TCIs) are able to inhibit the activation of T-lymphocytes and thereby diminish inflammation. In some patients the use of TCIs has been limited due to a localized burning sensation on the first days of treatment, and also due to fear of other adverse effects. Consequently, there has been a need for the development of new topical products for atopic dermatitis. Novel topical therapies are in the pipeline and comprise both new doses and formulations of well-known pharmaceutical molecules and novel approaches targeting unique inflammatory pathways and mechanisms of disease, with a promise of higher efficacy and less harmful side effects. We review topical drugs in the pipeline for atopic dermatitis, and focus on those available in the clinicaltrials.gov database with a first received date from January 1, 2014 to May 31, 2017.
Effect of Cinacalcet Combined with Calcitriol on the Clinical Outcome and Bone Metabolism in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism
Authors: Yuan Fang , Chen Xing , Wang Chang , Li Zheng , Liu Hong
Published: December 2017

Objective: To observe the clinical outcome and the effect of bone metabolism of cinacalcet combined with calcitriol in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT). Methods: Thirty MHD patients with SHPT were enrolled into the study. All patients were given cinacalcet 25–75 mg and 0.5 μg calcitriol daily. Serum Ca, P, intact parathyroid hormone (iPTH), and bone metabolic markers were measured. The clinical symptoms and their changes were investigated. Results: The baseline levels of iPTH, Ca, and P were 1,787.3 ± 1,321 pg/mL, 2.54 ± 0.19 mmol/L, and 2.06 ± 0.15 mmol/L respectively. After 3 months treatment, iPTH decreased by 70%. Serum Ca and P fell to 2.39 ± 0.17 and 1.56 ± 0.50 mmol/L (p < 0.05), respectively. After 6 months, the bone-specific alkaline phosphatase, osteocalcin, and β-cross levels were decreased by 50, 37, and 49% respectively compared with corresponding values before treatment. A decline in the bone density patients was inhibited. Conclusion: Cinacalcet combined with low dose calcitriol can improve high calcium, high phosphorus, and high iPTH in MHD patients with severe SHPT and also improve bone metabolism. It can be used as a favorable choice for SHPT treatment.
Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study
Authors: McNamara Robert K. , Schurdak Jennifer D. , Asch Ruth H. , Peters Bart D. , Lindquist Diana M.
Published: December 2017

Neuropsychiatric disorders that frequently initially emerge during adolescence are associated with deficits in the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA), elevated proinflammatory signaling, and regional reductions in white matter integrity (WMI). This study determined the effects of altering brain DHA accrual during adolescence on WMI in the rat brain by diffusion tensor imaging (DTI), and investigated the potential mediating role of proinflammatory signaling. During periadolescent development, male rats were fed a diet deficient in n-3 fatty acids (DEF, n = 20), a fish oil-fortified diet containing preformed DHA (FO, n = 20), or a control diet (CON, n = 20). In adulthood, DTI scans were performed and brain WMI was determined using voxelwise tract-based spatial statistics (TBSS). Postmortem fatty acid composition, peripheral (plasma IL-1β, IL-6, and C-reactive protein [CRP]) and central (IL-1β and CD11b mRNA) proinflammatory markers, and myelin basic protein (MBP) mRNA expression were determined. Compared with CON rats, forebrain DHA levels were lower in DEF rats and higher in FO rats. Compared with CON rats, DEF rats exhibited greater radial diffusivity (RD) and mean diffusivity in the right external capsule, and greater axial diffusivity in the corpus callosum genu and left external capsule. DEF rats also exhibited greater RD than FO rats in the right external capsule. Forebrain MBP expression did not differ between groups. Compared with CON rats, central (IL-1β and CD11b) and peripheral (IL-1β and IL-6) proinflammatory markers were not different in DEF rats, and DEF rats exhibited lower CRP levels. These findings demonstrate that deficits in adolescent DHA accrual negatively impact forebrain WMI, independently of elevated proinflammatory signaling.