bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Vanadium-Loaded Ordered Collagen Scaffold Promotes Osteochondral Differentiation of Bone Marrow Progenitor Cells
Authors: Cortizo Ana M. , Ruderman Graciela , Mazzini Flavia N. , Molinuevo M. Silvina , Mogilner Ines G.
Published: May 2016

Bone and cartilage regeneration can be improved by designing a functionalized biomaterial that includes bioactive drugs in a biocompatible and biodegradable scaffold. Based on our previous studies, we designed a vanadium-loaded collagen scaffold for osteochondral tissue engineering. Collagen-vanadium loaded scaffolds were characterized by SEM, FTIR, and permeability studies. Rat bone marrow progenitor cells were plated on collagen or vanadium-loaded membranes to evaluate differences in cell attachment, growth and osteogenic or chondrocytic differentiation. The potential cytotoxicity of the scaffolds was assessed by the MTT assay and by evaluation of morphological changes in cultured RAW 264.7 macrophages. Our results show that loading of VOAsc did not alter the grooved ordered structure of the collagen membrane although it increased membrane permeability, suggesting a more open structure. The VOAsc was released to the media, suggesting diffusion-controlled drug release. Vanadium-loaded membranes proved to be a better substratum thanC0for all evaluated aspects of BMPC biocompatibility (adhesion, growth, and osteoblastic and chondrocytic differentiation). In addition, there was no detectable effect of collagen or vanadium-loaded scaffolds on macrophage viability or cytotoxicity. Based on these findings, we have developed a new ordered collagen scaffold loaded with VOAsc that shows potential for osteochondral tissue engineering.
Finite-Time Consensus of Networked Multiagent Systems with Time-Varying Linear Control Protocols
Authors: Wen Jiayan , Wang Chen , Luo Wenguang , Xie Guangming
Published: May 2016

Finite-time consensus problems for networked multiagent systems with first-order/second-order dynamics are investigated in this paper. The goal of this paper is to design local information based control protocols such that the systems achieve consensus at any preset time. In order to realize this objective, a class of linear feedback control protocols with time-varying gains is introduced. We prove that the multiagent systems under such kinds of time-varying control protocols can achieve consensus at the preset time if the undirected communication graph is connected. Numerical simulations are presented to illustrate the effectiveness of the obtained theoretic results.
Preparation and Evaluation of Emamectin Benzoate Solid Microemulsion
Authors: Feng Lei , Cui Bo , Yang Dongsheng , Wang Chunxin , Zeng Zhanghua , Wang Yan , Sun Changjiao , Zhao Xiang , Cui Haixin
Published: May 2016

The solid microemulsions of emamectin benzoate with the same content of surfactants were prepared by a self-emulsifying method. Emulsifier 600#and emulsifier 700#(3/2, w/w) screened from eleven kinds of commonly used surfactants displayed great emulsifying properties. The redispersed solution of the solid microemulsion presented aqueous microemulsion characteristic. The mean particle size and polydispersity index were 10.34 ± 0.10 nm and 0.283 ± 0.013, respectively. The solid microemulsion showed excellent storage stability and the bioassay compared with water dispersible granules against diamondback moths provided a proof of its improved biological activities. This formulation could significantly reduce surfactants and is perspective in plant protection for improving bioavailability and environmental friendliness.
Chamaecyparis obtusa Suppresses Virulence Genes in Streptococcus mutans
Authors: Kim Eun-Hee , Kang Sun-Young , Park Bog-Im , Kim Young-Hoi , Lee Young-Rae , Hoe Jin-Hee , Choi Na-Young , Ra Ji-Young , An So-Youn , You Yong-Ouk
Published: May 2016

Chamaecyparis obtusa (C. obtusa) is known to have antimicrobial effects and has been used as a medicinal plant and in forest bathing. This study aimed to evaluate the anticariogenic activity of essential oil of C. obtusa on Streptococcus mutans, which is one of the most important bacterial causes of dental caries and dental biofilm formation. Essential oil from C. obtusa was extracted, and its effect on bacterial growth, acid production, and biofilm formation was evaluated. C. obtusa essential oil exhibited concentration‐dependent inhibition of bacterial growth over 0.025 mg/mL, with 99% inhibition at a concentration of 0.2 mg/mL. The bacterial biofilm formation and acid production were also significantly inhibited at the concentration greater than 0.025 mg/mL. The result of LIVE/DEAD® BacLight™ Bacterial Viability Kit showed a concentration‐dependent bactericidal effect on S. mutans and almost all bacteria were dead over 0.8 mg/mL. Real‐time PCR analysis showed that gene expression of some virulence factors such as brpA, gbpB, gtfC, and gtfD was also inhibited. In GC and GC‐MS analysis, the major components were found to be α‐terpinene (40.60%), bornyl acetate (12.45%), α‐pinene (11.38%), β‐pinene (7.22%), β‐phellandrene (3.45%), and α‐terpinolene (3.40%). These results show that C. obtusa essential oil has anticariogenic effect on S. mutans.
l1-Induced State-Feedback Controller Design for Positive Fuzzy Systems
Authors: Chen Xiaoming , Chen Mou , Shen Jun
Published: May 2016

The problem ofl1-induced state-feedback controller design is investigated for positive Takagi-Sugeno (T-S) fuzzy systems with the use of linear Lyapunov function. First, a novel performance characterization is established to guarantee the asymptotic stability of the closed-loop system withl1-induced performance. Then, the sufficient conditions are presented to design the required fuzzy controllers and iterative convex optimization approaches are developed to solve the conditions. Finally, one example is presented to show the effectiveness of the derived theoretical results.
The Effects of Taoren‐Honghua Herb Pair on Pathological Microvessel and Angiogenesis‐Associated Signaling Pathway in Mice Model of CCl4‐Induced Chronic Liver Disease
Authors: Xi Shengyan , Yue Lifeng , Shi Mengmeng , Peng Ying , Xu Yangxinzi , Wang Xinrong , Li Qian , Kang Zhijun , Li Hanjing , Wang Yanhui
Published: May 2016

Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren‐Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain‐containing receptor (KDR), Flt‐1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt‐1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis‐associated VEGF and its upstream and downstream signaling pathways.
Analysis of Muscle Activity Utilizing Bench Presses in the AnyBody Simulation Modelling System
Authors: Ji Zhongqiu , Wang Huihui , Jiang Guiping , Li Lin
Published: May 2016

Using the AnyBody human modeling system with identical weights and varying grip distance (40.0 cm, 50.0 cm, and 60.0 cm), the stress distribution for the pectoralis and the muscle of upper extremity during a bench press was simulated, and the surface myoelectricity (EMG) method was validated.Methods.The physical parameters driving the model of the human body were selected as weights of 35.0% (25.0 kg) and grip distances.Conclusion.The validation of AnyBody software was proved as a high validity by using EMG test of four muscles’ activity compared to AnyBody software. During a bench press, the pectoralis major is the main muscle, the pectoralis major discharge increases with the height of barbell increases, and the pectoralis major discharge decreases as the short grip width increases. When the grip width equals the shoulder width, the value of pectoralis minor is lowest; when the grip width is smaller or larger than the shoulder width, the value is larger. As the short grip distance increases, the discharge of posterior deltoid muscle and triceps surface myoelectricity increases; thus, as the short grip distance increases, the deltoid muscle and triceps assist the pectoralis major during a bench press.
Cytotoxicity and Genotoxicity Assessment of Sandalwood Essential Oil in Human Breast Cell Lines MCF‐7 and MCF‐10A
Authors: Ortiz Carmen , Morales Luisa , Sastre Miguel , Haskins William E. , Matta Jaime
Published: May 2016

Sandalwood essential oil (SEO) is extracted from Santalum trees. Although α‐santalol, a main constituent of SEO, has been studied as a chemopreventive agent, the genotoxic activity of the whole oil in human breast cell lines is still unknown. The main objective of this study was to assess the cytotoxic and genotoxic effects of SEO in breast adenocarcinoma (MCF‐7) and nontumorigenic breast epithelial (MCF‐10A) cells. Proteins associated with SEO genotoxicity were identified using a proteomics approach. Commercially available, high‐purity, GC/MS characterized SEO was used to perform the experiments. The main constituents reported in the oil were (Z)‐α‐santalol (25.34%), (Z)‐nuciferol (18.34%), (E)‐β‐santalol (10.97%), and (E)‐nuciferol (10.46%). Upon exposure to SEO (2–8 μg/mL) for 24 hours, cell proliferation was determined by the MTT assay. Alkaline and neutral comet assays were used to assess genotoxicity. SEO exposure induced single‐ and double‐strand breaks selectively in the DNA of MCF‐7 cells. Quantitative LC/MS‐based proteomics allowed identification of candidate proteins involved in this response: Ku70 (p = 1.37E − 2), Ku80 (p = 5.8E − 3), EPHX1 (p = 3.3E − 3), and 14‐3‐3ζ (p = 4.0E − 4). These results provide the first evidence that SEO is genotoxic and capable of inducing DNA single‐ and double‐strand breaks in MCF‐7 cells.
Improved Adaptive Vibe and the Application for Segmentation of Complex Background
Authors: Chang Le , Liu Zhenghua , Ren Yan
Published: May 2016

To solve the problems that basic Vibe algorithm cannot effectively eliminate the influence of background noise, follower shadow, and ghost under complex background effectively, an adaptive threshold algorithm, AdaVibe, based on the framework of basic Vibe is proposed. Aiming at the shortage of the basic algorithm, this paper puts forward some improvement measures in threshold setting, shadow eliminating, and ghost suppression. Firstly, judgment threshold takes adjustment with the changes of background. Secondly, a fast eliminating ghost algorithm depending on adaptive threshold is introduced. Finally, follower shadow is detected and inhibited effectively through the gray properties and texture characteristics. Experiments show that the proposed AdaVibe algorithm works well in complex environment without affecting computing speed and has stronger robustness and better adaptability than the basic algorithm. Meanwhile, the ghost and follower shadow can be absorbed quickly as well. Therefore, the accuracy of target detection is effectively improved.
Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation
Authors: Moen Aurora , Lind Anne-Li , Thulin Måns , Kamali-Moghaddam Masood , Røe Cecilie , Gjerstad Johannes , Gordh Torsten
Published: May 2016

Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ullevål, Norway, during the period 2007–2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation.
Epigenetics: The New Frontier in the Landscape of Asthma
Authors: Chogtu Bharti , Bhattacharjee Dipanjan , Magazine Rahul
Published: May 2016

Over the years, on a global scale, asthma has continued to remain one of the leading causes of morbidity, irrespective of age, sex, or social bearings. This is despite the prevalence of varied therapeutic options to counter the pathogenesis of asthma. Asthma, as a disease per se, is a very complex one. Scientists all over the world have been trying to obtain a lucid understanding of the machinations behind asthma. This has led to many theories and conjectures. However, none of the scientific disciplines have been able to provide the missing links in the chain of asthma pathogenesis. This was until epigenetics stepped into the picture. Though epigenetic research in asthma is in its nascent stages, it has led to very exciting results, especially with regard to explaining the massive influence of environment on development of asthma and its varied phenotypes. However, there remains a lot of work to be done, especially with regard to understanding how the interactions between immune system, epigenome, and environment lead to asthma. But introduction of epigenetics has infused a fresh lease of life in research into asthma and the mood among the scientific community is that of cautious optimism.
Differences in Nanosecond Laser Ablation and Deposition of Tungsten, Boron, and WB2/B Composite due to Optical Properties
Authors: Moscicki Tomasz
Published: May 2016

The first attempt to the deposition of WB3films using nanosecond Nd:YAG laser demonstrated that deposited coatings are superhard. However, they have very high roughness. The deposited films consisted mainly of droplets. Therefore, in the present work, the explanation of this phenomenon is conducted. The interaction of Nd:YAG nanosecond laser pulse with tungsten, boron, and WB2/B target during ablation is investigated. The studies show the fundamental differences in ablation of those materials. The ablation of tungsten is thermal and occurs due to only evaporation. In the same conditions, during ablation of boron, the phase explosion and/or fragmentation due to recoil pressure is observed. The deposited films have a significant contribution of big debris with irregular shape. In the case of WB2/B composite, ablation is significantly different. The ablation seems to be the detonation in the liquid phase. The deposition mechanism is related mainly to the mechanical transport of the target material in the form of droplets, while the gaseous phase plays marginal role. The main origin of differences is optical properties of studied materials. A method estimating phase explosion occurrence based on material data such as critical temperature, thermal diffusivity, and optical properties is shown. Moreover, the effect of laser wavelength on the ablation process and the quality of the deposited films is discussed.
Vane Clocking Effects on Stator Suction Side Boundary Layers in a Multistage Compressor
Authors: Smith Natalie R. , Key Nicole L.
Published: May 2016

The stator inlet flow field in a multistage compressor varies in the pitchwise direction due to upstream vane wakes and how those wakes interact with the upstream rotor tip leakage flows. If successive vane rows have the same count, then vane clocking can be used to position the downstream vane in the optimum circumferential position for minimum vane loss. This paper explores vane clocking effects on the suction side vane boundary layer development by measuring the quasi-wall shear stress on the downstream vane at three spanwise locations. Comparisons between the boundary layer transition on Stator 1 and Stator 2 are made to emphasize the impact of rotor-rotor interactions which are not present for Stator 1 and yet contribute significantly to transition on Stator 2. Vane clocking can move the boundary layer transition in the path between the wakes by up to 24% of the suction side length at midspan by altering the influence of the Rotor 1 wakes in the 3/rev modulation from rotor-rotor interactions. The boundary layer near the vane hub and tip experiences earlier transition and separation due to interactions with the secondary flows along the shrouded endwalls. Flow visualization and Stator 2 wakes support the shear stress results.
Sensitivity Analysis for the Mechanical Properties of DNA Bundles
Authors: Kim Young-Joo , Kim Do-Nyun
Published: May 2016

In structural DNA nanotechnology, programming a three-dimensional shape into DNA bundles has been a primary design objective. However, the mechanical properties of these DNA bundle structures are another important factor to be considered in the design process. While the mechanics of the individual DNA double helix has been explored extensively and hence its properties are well known, the mechanical properties of structural motifs such as DNA junctions and strand breaks important to bundle mechanics have not been well characterized due to experimental limitations, rendering it difficult to predict the mechanical properties of DNA bundles. Here, we investigate the effect of these structural motifs on the global bundle rigidities by performing sensitivity analysis on a six-helix DNA bundle structure using the finite element modeling approach. Results reveal the primary structural features and their parametric values required to reproduce the experimental bundle rigidities.
Use of Mechanical Turk as a MapReduce Framework for Macular OCT Segmentation
Authors: Lee Aaron Y. , Lee Cecilia S. , Keane Pearse A. , Tufail Adnan
Published: May 2016

Purpose. To evaluate the feasibility of using Mechanical Turk as a massively parallel platform to perform manual segmentations of macular spectral domain optical coherence tomography (SD-OCT) images using a MapReduce framework.Methods.A macular SD-OCT volume of 61 slice images was map-distributed to Amazon Mechanical Turk. Each Human Intelligence Task was set to$0.01 and required the user to draw five lines to outline the sublayers of the retinal OCT image after being shown example images. Each image was submitted twice for segmentation, and interrater reliability was calculated. The interface was created using custom HTML5 and JavaScript code, and data analysis was performed using R. An automated pipeline was developed to handle the map and reduce steps of the framework.Results.More than 93,500 data points were collected using this framework for the 61 images submitted. Pearson’s correlation of interrater reliability was 0.995 (p<0.0001) and coefficient of determination was 0.991. The cost of segmenting the macular volume was$1.21. A total of 22 individual Mechanical Turk users provided segmentations, each completing an average of 5.5 HITs. Each HIT was completed in an average of 4.43 minutes.Conclusions.Amazon Mechanical Turk provides a cost-effective, scalable, high-availability infrastructure for manual segmentation of OCT images.
Chronic Q Fever in Alberta: A Case ofCoxiella burnetiiMycotic Aneurysm and Concomitant Vertebral Osteomyelitis
Authors: Stokes William , Janvier Jack , Vaughan Stephen
Published: May 2016

Chronic Q fever is a potentially life-threatening infection from the intracellular, Gram-negativeCoxiella burnetii. It presents most commonly as endocarditis or vascular infection in people with underlying cardiac or vascular disease. We discuss a case of a 67-year-old male withCoxiella burnetiivascular infection of a perirenal abdominal aortic graft. The patient had a history of an abdominal aortic aneurysm (AAA) repair 5 years earlier. He presented with a 12 × 6 × 8 cm perirenal pseudoaneurysm and concomitant L1, L2, and L3 vertebral body discitis. He underwent an open repair which revealed a grossly infected graft perioperatively. Q fever serology revealed phase I serological IgG titer of 1 : 2048 and phase II 1 : 1024 consistent with chronic Q fever. Polymerase chain reaction (PCR) on infected vascular tissue was positive forC. burnetii. The patient was started on doxycycline and hydroxychloroquine with good clinical response and decreasing serological titers. Recognizing chronic Q fever is a difficult task as symptoms are nonspecific, exposure risk is difficult to ascertain, and diagnosis is hidden from conventional microbiological investigations. Its recognition, however, is critical asC. burnetiiis inherently resistant to standard empiric therapies used in cardiovascular infections.
Medical Application of Spirulina platensis Derived C‐Phycocyanin
Authors: Liu Qian , Huang Yinghong , Zhang Ronghua , Cai Tiange , Cai Yu
Published: May 2016

Along with the development of marine biological pharmaceutical research, high‐effective and low‐toxic drugs and functional foods isolated from marine organisms have become a new field of pharmacy and bromatology. The pharmacological actions, such as anti‐inflammation, antioxidation, antitumor, immunological enhancement, and hepatorenal protection of C‐phycocyanin (C‐PC) from Spirulina platensis, have been reported, and C‐PC has important value of development and utilization either as drug or as functional food. There are many researches about the various pharmacological actions and mechanisms of C‐PC, but related reports are only to some extent integrated deeply and accurately enough, which put some limitations to the further application of C‐PC in medicine. Particularly, with the improvement of living standards and attention to health issues, C‐PC being a functional food is preferred by more and more people. C‐PC is easy to get, safe, and nontoxic; thus, it has a great potential of research and development as a drug or functional food. Here, the separation and purification, physicochemical properties, physiological and pharmacological activities, safety, and some applications are reviewed to provide relevant basis for the development of natural medicine and applied products.
Spatial Finite Element Analysis for Dynamic Response of Curved Thin-Walled Box Girder Bridges
Authors: Wang Yinhui , Xu Yidong , Luo Zheng , Wu Haijun , Yan Liangliang
Published: May 2016

According to the flexural and torsional characteristics of curved thin-walled box girder with the effect of initial curvature, 7 basic displacements of curved box girder are determined. And then the strain-displacement calculation correlations were established. Under the curvilinear coordinate system, a three-noded curved girder finite element which has 7 degrees of freedom per node for the vibration characteristic and dynamic response analysis of curved box girder is constructed. The shape functions are used as the interpolation functions of variable curvature and variable height to accommodate to the variation of curvature and section height. A MATLAB numerical analysis program has been implemented.
Development and Testing of Screen-Based and Psychometric Instruments for Assessing Resident Performance in an Operating Room Simulator
Authors: McNeer Richard R. , Dudaryk Roman , Nedeff Nicholas B. , Bennett Christopher L.
Published: May 2016

Introduction. Medical simulators are used for assessing clinical skills and increasingly for testing hypotheses. We developed and tested an approach for assessing performance in anesthesia residents using screen-based simulation that ensures expert raters remain blinded to subject identity and experimental condition.Methods. Twenty anesthesia residents managed emergencies in an operating room simulator by logging actions through a custom graphical user interface. Two expert raters rated performance based on these entries using custom Global Rating Scale (GRS) and Crisis Management Checklist (CMC) instruments. Interrater reliability was measured by calculating intraclass correlation coefficients (ICC), and internal consistency of the instruments was assessed with Cronbach’s alpha. Agreement between GRS and CMC was measured using Spearman rank correlation (SRC).Results. Interrater agreement (GRS: ICC = 0.825, CMC: ICC = 0.878) and internal consistency (GRS: alpha = 0.838, CMC: alpha = 0.886) were good for both instruments. Subscale analysis indicated that several instrument items can be discarded. GRS and CMC scores were highly correlated (SRC = 0.948).Conclusions. In this pilot study, we demonstrated that screen-based simulation can allow blinded assessment of performance. GRS and CMC instruments demonstrated good rater agreement and internal consistency. We plan to further test construct validity of our instruments by measuring performance in our simulator as a function of training level.
The Effect of Structural Properties of Cu2Se/Polyvinylcarbazole Nanocomposites on the Performance of Hybrid Solar Cells
Authors: Govindraju S. , Ntholeng N. , Ranganathan K. , Moloto M. J. , Sikhwivhilu L. M. , Moloto N.
Published: May 2016

It has been said that substitution of fullerenes with semiconductor nanocrystals in bulk heterojunction solar cells can potentially increase the power conversion efficiencies (PCE) of these devices far beyond the 10% mark. However new semiconductor nanocrystals other than the potentially toxic CdSe and PbS are necessary. Herein we report on the synthesis of Cu2Se nanocrystals and their incorporation into polyvinylcarbazole (PVK) to form polymer nanocomposites for use as active layers in hybrid solar cells. Nearly monodispersed 4 nm Cu2Se nanocrystals were synthesized using the conventional colloidal synthesis. Varying weight % of these nanocrystals was added to PVK to form polymer nanocomposites. The 10% polymer nanocomposite showed retention of the properties of the pure polymer whilst the 50% resulted in a complete breakdown of the polymeric structure as evident from the FTIR, TGA, and SEM. The lack of transport channels in the 50% polymer nanocomposite solar cell resulted in a device with no photoresponse whilst the 10% polymer nanocomposite resulted in a device with an open circuit voltage of 0.50 V, a short circuit current of 7.34 mA/cm2, and a fill factor of 22.28% resulting in a PCE of 1.02%.
Cancer Stem-like Properties in Colorectal Cancer Cells with Low Proteasome Activity
Authors: Munakata Koji , Uemura Mamoru , Tanaka Shinji , Kawai Kenji , Kitahara Tomohiro , Miyo Masaaki , Kano Yoshihiro , Nishikawa Shinpei , Fukusumi Takahito , Takahashi Yusuke , Hata Taishi , Nishimura Junichi , Takemasa Ichiro , Mizushima Tsunekazu , Ikenaga Masakazu , Kato Takeshi , Murata Kohei , Carethers John M. , Yamamoto Hirofumi , Doki Yuichiro , Mori Masaki
Published: May 2016

Purpose: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs.

Experimental Design: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs. LPACs were isolated by flow cytometry. Treatment resistance (radio- and chemotherapy) and the capacity of LPACs to act as CSCs were analyzed. Microarray analysis was performed to reveal genes related to treatment resistance. The prognostic impact of potent genes was examined in 190 patients with colorectal cancer.

Results: LPACs had a significantly increased capacity for radioresistance and chemoresistance (5-fluorouracil and oxaliplatin), significantly lower reactive oxygen species activity, and significantly increased sphere formation capacity compared with non-LPACs. The number of cells in the G0–G1 phase was significantly higher among LPACs. Subcutaneous injection of as few as 20 LPACs led to tumor formation in immunologically incompetent mice. Microarray analysis revealed that the expression of EP300-interacting inhibitor of differentiation 3 (EID3) was significantly increased in LPACs. In vitro assay revealed that EID3 positively controlled cell proliferation and treatment resistance. The high expression of EID3 was an adverse prognostic indicator in patients with colorectal cancer (P = 0.0400).

Conclusions: LPACs have characteristic treatment resistance and act as CSCs in colorectal cancer. In addition, EID3 is one of the potential regulators of treatment resistance in colorectal cancer and may be a potential therapeutic target. Clin Cancer Res; 22(21); 5277–86. ©2016 AACR.
Analytic Validation of RNA In Situ Hybridization (RISH) for AR and AR-V7 Expression in Human Prostate Cancer
Authors: Guedes Liana B. , Morais Carlos L. , Almutairi Fawaz , Haffner Michael C. , Zheng Qizhi , Isaacs John T. , Antonarakis Emmanuel S. , Lu Changxue , Tsai Harrison , Luo Jun , De Marzo Angelo M. , Lotan Tamara L.
Published: May 2016

Purpose: RNA expression of androgen receptor splice variants may be a biomarker of resistance to novel androgen deprivation therapies in castrate-resistant prostate cancer (CRPC). We analytically validated an RNA in situ hybridization (RISH) assay for total AR and AR-V7 for use in formalin-fixed paraffin-embedded (FFPE) prostate tumors.

Experimental Design: We used prostate cell lines and xenografts to validate chromogenic RISH to detect RNA containing AR exon 1 (AR-E1, surrogate for total AR RNA species) and cryptic exon 3 (AR-CE3, surrogate for AR-V7 expression). RISH signals were quantified in FFPE primary tumors and CRPC specimens, comparing to known AR and AR-V7 status by IHC and RT-PCR.

Results: The quantified RISH results correlated significantly with total AR and AR-V7 levels by RT-PCR in cell lines, xenografts, and autopsy metastases. Both AR-E1 and AR-CE3 RISH signals were localized in nuclear punctae in addition to the expected cytoplasmic speckles. Compared with admixed benign glands, AR-E1 expression was significantly higher in primary tumor cells with a median fold increase of 3.0 and 1.4 in two independent cohorts (P < 0.0001 and P = 0.04, respectively). While AR-CE3 expression was detectable in primary prostatic tumors, levels were substantially higher in a subset of CRPC metastases and cell lines, and were correlated with AR-E1 expression.

Conclusions: RISH for AR-E1 and AR-CE3 is an analytically valid method to examine total AR and AR-V7 RNA levels in FFPE tissues. Future clinical validation studies are required to determine whether AR RISH is a prognostic or predictive biomarker in specific clinical contexts. Clin Cancer Res; 22(18); 4651–63. ©2016 AACR.
Testosterone in Androgen Receptor Signaling and DNA Repair: Enemy or Frenemy?
Authors: Chua Melvin Lee Kiang , Bristow Robert G.
Published: May 2016

Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 3124–6. ©2016 AACR.

See related article by Hedayati et al., p. 3310
Syntactic Awareness and Text Production in Brazilian Portuguese Students with Learning Disabilities
Authors: Rocha de Vasconcellos Hage Simone , Crepaldi Azevedo Natally , Nicolielo-Carrilho Ana Paola , Merighi Tabaquim Maria de Lourdes
Published: May 2016

Aims: This study compared the syntactic awareness and textual production skills of school children and teenagers with and without learning disabilities (LD) and related their performances in both skills. Methods: The study group consisted of 15 children with an LD and 15 without language and learning alterations. To compare the performance of both groups, data were statistically analyzed using Fisher's exact test, and the association between the evidence in each group was demonstrated by Spearman's correlations, with a significance level of 5% (p < 0.05). Results: Most subjects with LD showed a lower performance in tests of syntactic awareness and textual production. Statistical analysis indicated a significant difference in the performance of children with and without language disorders for both tested skills. A positive relationship was found between the children's performance in the test of textual production and the tasks of syntactic awareness. Conclusion: Our findings suggest that the ability to judge and correct grammatical structures can be an important factor in the development of the skills used to produce a text.
Acute Pericarditis-Associated Hospitalization in the USA: A Nationwide Analysis, 2003-2012
Authors: Kumar Nilay , Pandey Ambarish , Jain Priyank , Garg Neetika
Published: May 2016

Background and Objectives: Epidemiologic data on hospitalizations for acute pericarditis are scarce. We sought to study the trends in these hospitalizations and outcomes in the USA over a 10-year period. Methods: We used the 2003-2012 Nationwide Inpatient Sample database to identify admissions with a primary diagnosis of acute pericarditis. Outcomes included hospitalization rate, case fatality rate (CFR), length of stay (LOS), hospital charges, complications and diagnostic and therapeutic procedures. Results: We observed an estimated 135,710 hospitalizations for acute pericarditis among patients ≥16 years during the study period (mean age 53.5 ± 18.5 years; 40.5% women). The incidence of acute pericarditis hospitalizations was significantly higher for men than for women [incidence rate ratio (IRR) 1.56; 95% confidence interval (CI) 1.54-1.58; p < 0.001]; it decreased from 66 to 54 per million person-years (p < 0.001). CFR and LOS declined significantly during the study period (CFR: 2.2% in 2003 to 1.4% in 2012; LOS: 4.8 days in 2003 to 4.1 days in 2012; p < 0.001 for both). The average inflation-adjusted health-care charge increased from USD 31,242 to 38,947 (p < 0.001). Conclusion: The hospitalization rate, CFR and LOS associated with acute pericarditis have declined significantly in the US population. Average charges for acute pericarditis hospitalization have increased.
Longitudinal Study of Sustained-Release Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema
Authors: Aknin Isabelle , Melki Laurent
Published: May 2016

Observational studies are needed to confirm the long-term efficacy and safety of Ozurdex® intravitreal implant in real life. Among 29 patients with persistent diabetic macular edema (DME), of whom 14 (48%) patients did not have any previous treatments and 22 (76%) any previous antivascular endothelial growth factor (anti-VEGF) injections, significant visual acuity (VA) improvement was observed with a mean gain of 13.8 letters at month 6 (p < 0.0001), 12.7 letters at month 12 (p = 0.0032) and 16.5 letters at month 18 (p = 0.0313). During the follow-up, a total of 17 (59%) patients had a VA improvement of ≥15 letters. Significant central macular thickness decrease was observed with a mean reduction of 159.07 μm at month 6 (p < 0.0001), 181.8 μm at month 12 (p < 0.0001) and 236.17 μm at month 18 (p = 0.0313). No serious adverse events were reported. With a good efficacy and safety, manageable adverse events and an injection rate much lower compared to that of anti-VEGF, this study confirms the use of Ozurdex® for the treatment of persistent DME.
Watchful Waiting in Continuous-Flow Left Ventricular Assist Device Patients With Ongoing Hemolysis Is Associated With an Increased Risk for Cerebrovascular Accident or Death
Authors: Levin Allison P. , Saeed Omar , Willey Joshua Z. , Levin Charles J. , Fried Justin A. , Patel Snehal R. , Sims Daniel B. , Nguyen Jenni D. , Shin Julia J. , Topkara Veli K. , Colombo Paolo C. , Goldstein Daniel J. , Naka Yoshifumi , Takayama Hiroo , Uriel Nir , Jorde Ulrich P.
Published: May 2016

Background—

Management of hemolysis in the setting of suspected device thrombosis in continuous-flow left ventricular assist device patients varies widely, ranging from watchful waiting with intensified antithrombotic therapy to early surgical device exchange. The aim of this study was to compare the outcomes of hemolysis events treated with surgical interventions versus medical management alone.

Methods and Results—

A retrospective review of Heartmate II continuous-flow left ventricular assist device patients at 2 centers from January 2009 to September 2014 was completed. Patients were categorized as surgical management if hemolysis refractory to intensification of standard antithrombotic therapy was treated surgically. The primary end point was the first occurrence of cerebrovascular accident (CVA) or death. Sixty-four hemolysis events occurred in 49/367 patients implanted with Heartmate II continuous-flow left ventricular assist devices. Of 49 primary hemolysis events, 24 were treated with surgical interventions. After surgical treatment, 1 patient died and 2 experienced CVAs, as compared with 3 deaths and 9 CVAs in the 25 patients who remained on intensified antithrombotic therapy alone. The 1-year freedom from CVA or death was 87.5% and 49.5% in the surgical and medical cohorts, respectively (
P
=0.027). Resolution of a primary hemolysis event without CVA or death occurred in 21/24 patients treated with surgical interventions and in 13/25 who remained on medical therapy alone. A similar association between treatment and outcome was noted in the 15 recurrent hemolysis events.

Conclusions—

Hemolysis refractory to intensification of antithrombotic therapy identifies continuous-flow left ventricular assist device patients at major risk for CVA and death. Early device exchange should be considered to minimize these risks.
Proton Pump Inhibitors Accelerate Endothelial Senescence
Authors: Yepuri Gautham , Sukhovershin Roman , Nazari-Shafti Timo Z. , Petrascheck Michael , Ghebre Yohannes T. , Cooke John P.
Published: May 2016

Rationale:

Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, which are now available for long-term use without medical supervision. Recent reports suggest that PPI use is associated with cardiovascular, renal, and neurological morbidity.

Objective:

To study the long-term effect of PPIs on endothelial dysfunction and senescence and investigate the mechanism involved in PPI-induced vascular dysfunction.

Methods and Results:

Chronic exposure to PPIs impaired endothelial function and accelerated human endothelial senescence by reducing telomere length.

Conclusions:

Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal, and neurological morbidity and mortality.
White Matter Hyperintensities Are Under Strong Genetic Influence
Authors: Sachdev Perminder S. , Thalamuthu Anbupalam , Mather Karen A. , Ames David , Wright Margaret J. , Wen Wei , Bowden Jocelyn , Lee Teresa , Brodaty Henry , Crawford John , Duckworth Tanya , Kang Kristan , Garden Natalie , Martin Nick , Lemmon Christel
Published: May 2016

Background and Purpose—

The genetic basis of white matter hyperintensities (WMH) is still unknown. This study examines the heritability of WMH in both sexes and in different brain regions, and the influence of age.

Methods—

Participants from the Older Australian Twins Study were recruited (n=320; 92 monozygotic and 68 dizygotic pairs) who volunteered for magnetic resonance imaging scans and medical assessments. Heritability, that is, the ratio of the additive genetic variance to the total phenotypic variance, was estimated using the twin design.

Results—

Heritability was high for total WMH volume (0.76), and for periventricular WMH (0.64) and deep WMH (0.77), and varied from 0.18 for the cerebellum to 0.76 for the occipital lobe. The genetic correlation between deep and periventricular WMH regions was 0.85, with one additive genetics factor accounting for most of the shared variance. Heritability was consistently higher in women in the cerebral regions. Heritability in deep but not periventricular WMH declined with age, in particular after the age of 75.

Conclusions—

WMH have a strong genetic influence but this is not uniform through the brain, being higher for deep than periventricular WMH and in the cerebral regions. The genetic influence is higher in women, and there is an age-related decline, most markedly for deep WMH. The data suggest some heterogeneity in the pathogenesis of WMH for different brain regions and for men and women.
Blood Pressure and Risk of Vascular Dementia
Authors: Emdin Connor A. , Rothwell Peter M. , Salimi-Khorshidi Gholamreza , Kiran Amit , Conrad Nathalie , Callender Thomas , Mehta Ziyah , Pendlebury Sarah T. , Anderson Simon G. , Mohseni Hamid , Woodward Mark , Rahimi Kazem
Published: May 2016

Background and Purpose—

Vascular dementia is the second most common form of dementia but reliable evidence on age-specific associations between blood pressure (BP) and risk of vascular dementia is limited and some studies have reported negative associations at older ages.

Methods—

In a cohort of 4.28 million individuals, free of known vascular disease and dementia and identified from linked electronic primary care health records in the United Kingdom (Clinical Practice Research Datalink), we related BP to time to physician-diagnosed vascular dementia. We further determined associations between BP and dementia in a prospective population-based cohort of incident transient ischemic attack and stroke (Oxford Vascular Study).

Results—

For a median follow-up of 7.0 years, 11 114 initial presentations of vascular dementia were observed in the primary care cohort after exclusion of the first 4 years of follow-up. The association between usual systolic BP and risk of vascular dementia decreased with age (hazard ratio per 20 mm Hg higher systolic BP, 1.62; 95% confidence interval, 1.13–2.35 at 30–50 years; 1.26, 1.18–1.35 at 51–70 years; 0.97, 0.92–1.03 at 71–90 years;
P
trend=0.006). Usual systolic BP remained predictive of vascular dementia after accounting for effect mediation by stroke and transient ischemic attack. In the population-based cohort, prior systolic BP was predictive of 5-year risk of dementia with no evidence of negative association at older ages.

Conclusions—

BP is positively associated with risk of vascular dementia, irrespective of preceding transient ischemic attack or stroke. Previous reports of inverse associations in old age could not be confirmed.
Does Contralesional Hand Function After Neonatal Stroke Only Depend on Lesion Characteristics?
Authors: Dinomais Mickael , Hertz-Pannier Lucie , Groeschel Samuel , Delion Matthieu , Husson Béatrice , Kossorotoff Manoelle , Renaud Cyrille , Chabrier Stéphane , The Tich Sylvie Nguyen
Published: May 2016

Background and Purpose—

In children having suffered from neonatal arterial ischemic stroke, the relationship between contralesional hand performance and structural changes in brain areas remote from the infarct site was examined.

Methods—

Using voxel-based morphometry, we correlated contralesional gross manual dexterity assessed by the box and block test and whole-brain gray and white-matter volume changes on high-resolution magnetic resonance imaging in 37 7-year-old post–neonatal arterial ischemic stroke children. We also compared the volume of the identified structures with magnetic resonance imaging data of 10 typically developing age-matched children.

Results—

Areas showing the highest positive correlation with the box and block test scores were ipsilesional mediodorsal thalamus, contralesional cerebellar lobule VIIa Crus I, and ipsilesional corticospinal tract at the level of superior corona radiata, the posterior limb of the internal capsule, and the cerebral peduncle and the ipsilesional body of corpus callosum. When compared with typically developing age-matched children, post–neonatal arterial ischemic stroke children with severe contralesional hand motor deficit exhibited significant volume reductions in these structures (except the cerebellum), whereas no differences were found with those with good manual dexterity. No negative correlation was found between box and block test scores and brain areas.

Conclusions—

Contralesional hand performance after neonatal arterial ischemic stroke is correlated with atrophy in brain areas directly or functionally connected but anatomically remote from the infarct. Our study suggests a role of the cerebellar lobule VIIa Crus I and mediodorsal thalamus in manual dexterity.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT02511249.
Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage
Authors: Lattanzi Simona , Cagnetti Claudia , Provinciali Leandro , Silvestrini Mauro
Published: May 2016

Background and Purpose—

Increasing evidence suggests that inflammatory mechanisms are involved in the intracerebral hemorrhage–induced brain injury. We evaluated the prognostic role of the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) in patients with intracerebral hemorrhage.

Methods—

Patients with acute spontaneous intracerebral hemorrhage were retrospectively identified. Total white blood cells, absolute neutrophil count, and absolute lymphocyte count were obtained and the NLR computed from the admission blood work. The study end point was the occurrence of death or major disability at 3 months.

Results—

One hundred seventy-seven subjects were enrolled. Ninety-four (53.1%) had unfavorable outcome. The absolute neutrophil count, absolute lymphocyte count, and NLR were independently associated with the 3-month status. The NLR resulted the best discriminating variable and the best predictive cut-off value was 4.58.

Conclusions—

In patients with acute intracerebral hemorrhage, higher neutrophils, lower lymphocytes, and higher NLRs predicted worse 3-month outcome.