bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimising the cost-effectiveness of speed limit enforcement cameras
Authors: Li Shukai , Jiao Boshen , Zafari Zafar , Muennig Peter
Published: March 2018

Background

Using the 140 speed cameras in New York City (NYC) as a case study, we explore how to optimise the number of cameras such that the most lives can be saved at the lowest cost.

Methods

A Markov model was built to explore the economic and health impacts of speed camera installations in NYC as well as the optimal number and placement. Both direct and indirect medical savings associated with speed cameras are weighed against their cost. Health outcomes are measured in terms of quality-adjusted life years (QALYs).

Results

Over the lifetime of an average NYC resident, the existing 140 speed cameras increase QALYs by 0.00044 units (95% credible interval (CrI) 0.00027 to 0.00073) and reduce costs by US$70 (95% CrI US$21 to US$131) compared with no speed cameras. The return on investment would be maximised where the number of cameras more than doubled to 300. This would further increase QALY gains per resident by 0.00083 units (95% CrI 0.00072 to 0.00096) while reducing medical costs by US$147 (95% CrI US$70 to US$221) compared with existing speed cameras. Overall, this increase in cameras would save 7000 QALYs and US$1.2 billion over the lifetime of the current cohort of New Yorkers.

Conclusion

Speed cameras rank among the most cost-effective social policies, saving both money and lives.
UK pet owners’ use of the internet for online pet health information
Authors: Kogan Lori , Oxley James A , Hellyer Peter , Schoenfeld Regina , Rishniw Mark
Published: March 2018

The internet has been found to be a popular source for human health information. However, there is a lack of information on pet owners’ use of the internet to source pet health information and implications for the owner–veterinarian relationship. Therefore, the aim of this study was to address this gap in knowledge by focusing on UK pet owners’ general use of the internet to find online pet health information and the impact of this behaviour on the owner–veterinarian relationship. An online survey targeting UK pet owners resulted in 571 respondents. Respondents reported the most frequently used source for pet health information was the internet (78.6 per cent), followed by their veterinarian (72 per cent). Veterinarians and other pet owners, however, were rated as the most trustworthy sources. The topics searched for most often online were specific medical problems (61.3 per cent) and diet/nutrition (58.5 per cent). Regarding the owner–veterinarian relationship, 42.1 per cent of participants reported discussing information they found online ‘sometimes’ with their veterinarian. When asked if their veterinarian recommended specific websites, nearly half (49.6 per cent) stated that their veterinarian ‘never’ made such recommendations, yet over 90 per cent said they would visit veterinarian‐recommended websites.
Unexpected diversity in the mobilome of aPseudomonas aeruginosastrain isolated from a dental unit waterline revealed by SMRT Sequencing
Authors: Vincent Antony T. , Charette Steve J. , Barbeau Jean
Published: March 2018

The Gram-negative bacterium Pseudomonas aeruginosa is found in several habitats, both natural and human-made, and is particularly known for its recurrent presence as a pathogen in the lungs of patients suffering from cystic fibrosis, a genetic disease. Given its clinical importance, several major studies have investigated the genomic adaptation of P. aeruginosa in lungs and its transition as acute infections become chronic. However, our knowledge about the diversity and adaptation of the P. aeruginosa genome to non-clinical environments is still fragmentary, in part due to the lack of accurate reference genomes of strains from the numerous environments colonized by the bacterium. Here, we used PacBio long-read technology to sequence the genome of PPF-1, a strain of P. aeruginosa isolated from a dental unit waterline. Generating this closed genome was an opportunity to investigate genomic features that are difficult to accurately study in a draft genome (contigs state). It was possible to shed light on putative genomic islands, some shared with other reference genomes, new prophages, and the complete content of insertion sequences. In addition, four different group II introns were also found, including two characterized here and not listed in the specialized group II intron database.
Crowd evacuation model based on bacterial foraging algorithm
Authors: Shibiao Mu , Zhijun Chen
Published: March 2018

To understand crowd evacuation, a model based on a bacterial foraging algorithm (BFA) is proposed in this paper. Considering dynamic and static factors, the probability of pedestrian movement is established using cellular automata. In addition, given walking and queue times, a target optimization function is built. At the same time, a BFA is used to optimize the objective function. Finally, through real and simulation experiments, the relationship between the parameters of evacuation time, exit width, pedestrian density, and average evacuation speed is analyzed. The results show that the model can effectively describe a real evacuation.
Cryptanalysis of a semi-quantum secret sharing scheme based on Bell states
Authors: Gao Gan , Wang Yue , Wang Dong
Published: March 2018

In the paper [Mod. Phys. Lett. B 31 (2017) 1750150], Yin et al. proposed a semi-quantum secret sharing scheme by using Bell states. We find that the proposed scheme cannot finish the quantum secret sharing task. In addition, we also find that the proposed scheme has a security loophole, that is, it will not be detected that the dishonest participant, Charlie attacks on the quantum channel.
Study of the time evolution of correlation functions of the transverse Ising chain with ring frustration by perturbative theory
Authors: Zheng Zhen-Yu , Li Peng
Published: March 2018

We consider the time evolution of two-point correlation function in the transverse-field Ising chain (TFIC) with ring frustration. The time-evolution procedure we investigated is equivalent to a quench process in which the system is initially prepared in a classical kink state and evolves according to the time-dependent Schrödinger equation. Within a framework of perturbative theory (PT) in the strong kink phase, the evolution of the correlation function is disclosed to demonstrate a qualitatively new behavior in contrast to the traditional case without ring frustration.
Hyperchaos-Based Spreading Codes Generator for DS-CDMA Communication Systems
Authors: Sadoudi Said , Fennouh Ibrahim , Tanougast Camel
Published: March 2018

In this paper, we propose a new hyperchaos-based spreading codes generator (HSCG) for multi-users direct sequence spread spectrum (DSSS) communication systems. For experimental validation, we implement the proposed generator in Xilinx FPGA Virtex-5 technology. Contrary to the traditional spreading codes, the proposed HSCG offers interesting statistical properties such as good autocorrelation, very small cross-correlation, no repetition of the generated spreading codes and high degree of security. In addition, the developed hardware architecture used for implementing the HSCG permits to generate simultaneously an infinite number of multi-length spreading codes with high hardware performances in terms of logic area consumption, throughput and latency. Real-time results are given for 32-, 64- and 128-bit chaotic spreading codes. All of these properties are validated and compared with that of classical codes (Gold sequences, Walsh–Hadamard) through bit error rate (BER) performance evaluation in a DS-CDMA system in AWGN and time-invariant multipath channels. With its interesting performances, the proposed HSCG is very useful for the next generations of mobile communication systems.
Image Edge Detectors under Different Noise Levels with FPGA Implementations
Authors: Bonny Talal , Henno Safaa
Published: March 2018

The process to locate objects in an image passes through different phases. At the forefront of these phases, and most importantly, is the edge detection. If edges in an image are identified accurately, all of the objects will be located correctly for further processing phases. Noisy images contain high-frequency contents which might be interfered with image edges that makes edge detection more difficult. In this paper, a software comparative analysis of the performance of three different edge detectors, namely, Roberts, Prewitt and Sobel, is presented. The comparative analysis is performed to check the performance robustness of the edge detectors when noise level fluctuates in the image. In addition, an embedded hardware (HW) system is developed to implement the three detectors on the Zedboard FPGA prototyping board. The purpose of this implementation is to have an embedded system for on-the-move applications where portability is desired. To exploit the new features of the Xilinx Zynq-7000 series, we partition the implementation into (1) hardware part (running on logic gates of FPGA) and (2) software (SW) part (running on ARM processor of FPGA). This heterogeneous HW/SW implementation allows for high accurate results with high speed and efficient area. Furthermore, a hardware comparative analysis of the speed and area of the detectors is presented. The evaluation is performed by using different images (with their ground truths) downloaded from the BSDS500 dataset. The tools used for FPGA implementation are MATLAB and Microsoft Visual Studio (as software tools), Vivado High-level synthesis (HLS) and Software Development Kit (SDK) (as hardware tools). The experimental results show that the Roberts detector achieves better edge detection when the noise level is higher than 40%. It is also faster and requires less capacity of logic gates among the other detectors employed in this study.
Asymptotically (A)dS dilaton black holes with nonlinear electrodynamics
Authors: Hajkhalili S. , Sheykhi A.
Published: March 2018

It is well known that with an appropriate combination of three Liouville-type dilaton potentials, one can construct charged dilaton black holes in an (anti)-de Sitter [(A)dS] spaces in the presence of linear Maxwell field. However, asymptotically (A)dS dilaton black holes coupled to nonlinear gauge field have not been found. In this paper, we construct, for the first time, three new classes of dilaton black hole solutions in the presence of three types of nonlinear electrodynamics, namely Born–Infeld (BI), Logarithmic (LN) and Exponential nonlinear (EN) electrodynamics. All these solutions are asymptotically (A)dS and in the linear regime reduce to the Einstein–Maxwell-dilaton (EMd) black holes in (A)dS spaces. We investigate physical properties and the causal structure, as well as asymptotic behavior of the obtained solutions, and show that depending on the values of the metric parameters, the singularity can be covered by various horizons. We also calculate conserved and thermodynamic quantities of the obtained solutions. Interestingly enough, we find that the coupling of dilaton field and nonlinear gauge field in the background of (A)dS spaces leads to a strange behavior for the electric field. We observe that the electric field is zero at singularity and increases smoothly until reaches a maximum value, then it decreases smoothly until goes to zero as [Formula: see text]. The maximum value of the electric field increases with increasing the nonlinear parameter [Formula: see text] or decreasing the dilaton coupling [Formula: see text] and is shifted to the singularity in the absence of either dilaton field ([Formula: see text]) or nonlinear gauge field ([Formula: see text]).
Shape phase transitions and isotopic shift in barium isotopes within covariant density functional theory
Authors: Karim Afaque , Naz Tabassum , Ahmad Shakeb
Published: March 2018

A systematic search of the shape phase transitions and isotopic shift of the neutron-rich barium (Ba; [Formula: see text]) isotopes, as a candidate for transitional nuclei, is done within the covariant density functional theory (CDFT). The relativistic Hartree–Bogoliubov (RHB) formalism with separable pairing and relativistic mean-field (RMF) with BCS pairing are used. The constraint calculations assuming the axial symmetry as well as triaxial symmetry clearly manifest the shape coexistence and the transitional behavior in these nuclei. A strong shell closure is observed at [Formula: see text] and weaker shell/subshell closure is observed at [Formula: see text]. Shape transition below and above the shell closure location at [Formula: see text] (from prolate to spherical to prolate) is there. The candidates for [Formula: see text] and [Formula: see text] dynamical symmetries are found to be [Formula: see text]Ba, [Formula: see text]Ba and [Formula: see text]Ba, [Formula: see text]Ba nuclei, respectively. The calculated results are compared with the available experimental data and are in good agreement. We have investigated the model dependence as well as dependence on various model parameters. A comparison is made with other theoretical models: infinite nuclear matter (INM) model, macro–microscopic finite-range droplet model (FRDM) and the self-consistent Hartree–Fock–Bogoliubov (HFB) model. Overall good agreement is found within the different models used and between the calculated and experimental results.
From a 3D Passive Biped Walker to a 3D Passivity-Based Controlled Robot
Authors: Beigzadeh Borhan , Sabaapour Mohammad Reza , Yazdi Mohammad Reza Hairi , Raahemifar Kaamran
Published: March 2018

Asymptotically stable control of biped robots, especially based on reproducing passive periodic motions, have become of interest nowadays. In this paper, firstly, a three-dimensional (3D) stable passive biped walker which is a compass gait one with flat feet, compliant ankles and particular arrangement of moments of inertia has been presented. Then, a passivity-based control of the related biped robot based on elaborating 3D form of potential energy shaping method has been applied. In other words, by adding minimal actuations to the aforementioned passive walker, its passive periodic gait that belongs to a particular slope has been reproduced on any arbitrary surface such as the level ground. Simulation results support the effectiveness of the proposed approach.
Classifying Innovative Activities Using Decision Tree and Gini Index
Authors: Arabshahi Hassan , Fazlollahtabar Hamed
Published: March 2018

This paper proposes a framework for classification of innovative activities in production systems based on corresponding calculated risk intensity using decision tree method. A three-step process is developed. The basis of the framework is the innovative activities collected from the literature. These activities are collected from the related literature and are classified by decision tree based on Gini Index. The configured tree is then used to extract and compose rules applying rule mining technique. The resulting rules can be useful sources of information for managers, investors and predictors of innovation domain to take the appropriate approaches for innovation risk management and innovation investment.
Electric Field Modulation of Spin Accumulation in Nb-doped SrTiO3 with Ni/AlOx Spin Injection Contacts
Authors: Das A. , Jousma S. T. , Banerjee T.
Published: March 2018

We demonstrate an electric field control of spin lifetime at room temperature, across a semiconducting interface of Nb:STO using Ni/AlOx as spin injection contacts. We achieve this by a careful tailoring of the potential landscape in Nb:STO, driven by the strong response of the intrinsically large dielectric permittivity in STO to electric fields. The built-in electric field at the Schottky interface with Nb:STO tunes the intrinsic Rashba spin–orbit fields leading to a bias dependence of the spin lifetime in Nb:STO. Such an electric field driven modulation of spin accumulation has not been reported earlier using conventional semiconductors. This not only underpins the necessity of a careful design of the spin injection contacts but also establishes the importance of Nb:STO as a rich platform for exploring spin–orbit driven phenomena in complex oxide based spintronic devices.
Microfluidic flow cytometry: The role of microfabrication methodologies, performance and functional specification
Authors: Shrirao Anil B. , Fritz Zachary , Novik Eric M. , Yarmush Gabriel M. , Schloss Rene S. , Zahn Jeffrey D. , Yarmush Martin L.
Published: March 2018

Flow cytometry is an invaluable tool utilized in modern biomedical research and clinical applications requiring high throughput, high resolution particle analysis for cytometric characterization and/or sorting of cells and particles as well as for analyzing results from immunocytometric assays. In recent years, research has focused on developing microfluidic flow cytometers with the motivation of creating smaller, less expensive, simpler, and more autonomous alternatives to conventional flow cytometers. These devices could ideally be highly portable, easy to operate without extensive user training, and utilized for research purposes and/or point-of-care diagnostics especially in limited resource facilities or locations requiring on-site analyses. However, designing a device that fulfills the criteria of high throughput analysis, automation and portability, while not sacrificing performance is not a trivial matter. This review intends to present the current state of the field and provide considerations for further improvement by focusing on the key design components of microfluidic flow cytometers. The recent innovations in particle focusing and detection strategies are detailed and compared. This review outlines performance matrix parameters of flow cytometers that are interdependent with each other, suggesting trade offs in selection based on the requirements of the applications. The ongoing contribution of microfluidics demonstrates that it is a viable technology to advance the current state of flow cytometry and develop automated, easy to operate and cost-effective flow cytometers.
Understanding Biological Regulation Through Synthetic Biology
Authors: Bashor Caleb J. , Collins James J.
Published: March 2018

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry—biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.
Time Not Our Time: Physical Controls on the Preservation and Measurement of Geologic Time
Authors: Paola Chris , Ganti Vamsi , Mohrig David , Runkel Anthony C. , Straub Kyle M.
Published: March 2018

Sadler's (1981) analysis of how measured sedimentation rate decreases with timescale of measurement quantified the vanishingly small fractional time preservation—completeness—of the stratigraphic record. Generalized numerical models have shown that the Sadler effect can be recovered, through the action of erosional clipping and time removal (the “stratigraphic filter”), from even fairly simple topographic sequences. However, several lines of evidence suggest that most of the missing time has not been eroded out but rather represents periods of inactivity or stasis. Low temporal completeness could also imply that the stratigraphic record is dominated by rare, extreme events, but paleotransport estimates suggest that this is not generally the case: The stratigraphic record is strangely ordinary. It appears that the organization of the topography into a hierarchy of forms also organizes the deposition into concentrated events that tend to preserve relatively ordinary conditions, albeit for very short intervals. Our understanding of time preservation would benefit from insight about how inactivity is recorded in strata; better ways to constrain localized, short-term rates of deposition; and a new focus on integrated time–space dynamics of deposition and preservation.
Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2–MEK1/2–ERK1/2 Signaling
Authors: Ji Cheng-Dong , Wang Yan-Xia , Xiang Dong-Fang , Liu Qiang , Zhou Zhi-Hua , Qian Feng , Yang Lang , Ren Yong , Cui Wei , Xu Sen-Lin , Zhao Xi-Long , Zhang Xia , Wang Yan , Zhang Peng , Wang Ji-Ming , Cui You-Hong , Bian Xiu-Wu
Published: March 2018

Potassium ion channels are emerging as promalignant factors involved in cancer progression. In this study, we found that invading human gastric cancer cells express high levels of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial–mesenchymal transition (EMT) of gastric cancer cells. The promalignant nature of Kir2.1 in gastric cancer cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2). Degradation of MEKK2 was mediated by small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1 (Smurf1), which resulted in activation of the MEK1/2–ERK1/2–Snail pathway in gastric cancer cells. In human gastric cancer tissues, expression was high and positively correlated with invasion depth and metastatic status of the tumors as well as poor overall patient survival. Cox regression analysis identified Kir2.1 as an independent prognostic indicator for patients with gastric cancer. Our results suggest that Kir2.1 is an important regulator of gastric cancer malignancy and acts as a novel prognostic marker and a therapeutic target for gastric cancer.

Significance: Kir2.1 contributes to invasion and metastasis by a noncanonical ion permeation–independent signaling pathway and may act as a novel prognostic marker and therapeutic target for gastric cancer. Cancer Res; 78(11); 3041–53. ©2018 AACR.
A Novel TGFβ Trap Blocks Chemotherapeutics-Induced TGFβ1 Signaling and Enhances Their Anticancer Activity in Gynecologic Cancers
Authors: Zhu Haiyan , Gu Xiang , Xia Lu , Zhou You , Bouamar Hakim , Yang Junhua , Ding Xiaofei , Zwieb Christian , Zhang Jianan , Hinck Andrew P. , Sun Lu-Zhe , Zhu Xueqiong
Published: March 2018

Purpose: We investigated the mechanisms of how TGFβ pathway is activated by chemotherapeutics and whether a novel TGFβ trap called RER can block chemotherapeutics-induced TGFβ pathway activation and enhance their antitumor activity in gynecologic cancer.

Patients and Methods: An unbiased bioinformatic analysis of differentially expressed genes in 31 ovarian cases due to chemotherapy was used to identify altered master regulators. Phosphorylated Smad2 was determined in 30 paired cervical cancer using IHC. Furthermore, the effects of chemotherapeutics on TGFβ signaling and function, and the effects of RER on chemotherapy-induced TGFβ signaling were determined in gynecologic cancer cells.

Results: Chemotherapy-induced transcriptome alteration in ovarian cancer was significantly associated with TGFβ signaling activation. Chemotherapy was found to activate TGFβ signaling as indicated by phosphorylated Smad2 in paired cervical tumor samples (pre- and post-chemotherapy). Similar to TGFβ1, chemotherapeutics were found to stimulate Smad2/3 phosphorylation, cell migration, and markers related to epithelial–mesenchymal transition (EMT) and cancer stem cells (CSC). These TGFβ-like effects were due to the stimulation of TGFβ1 expression and secretion, and could all be abrogated by TGFβ inhibitors including a novel TGFβ trap protein called RER both in vitro and in vivo. Importantly, combination treatment with RER and cisplatin showed a higher tumor inhibitory activity than either agent alone in a xenograft model of ovarian cancer.

Conclusions: Chemotherapeutics can stimulate TGFβ1 production and consequently enhance TGFβ signaling, EMT, and CSC features resulting in reduced chemo-sensitivity. Combination therapy with a TGFβ inhibitor should alleviate this unintended side effect of chemotherapeutics and enhance their therapeutic efficacy. Clin Cancer Res; 24(12); 2780–93. ©2018 AACR.
Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease
Authors: Fu Dongxia , Cui Haibin , Zhang Yunna
Published: March 2018

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2) is involved in high fat diet (HFD)-induced NAFLD and possible molecular mechanisms. Methods: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively. Western blotting was applied to detect the protein expressions of lipid synthesis-related enzymes and the phosphorylated level of IRS-1, Akt and mTOR. Results: ClC-2 mRNA level was significantly increased in patients with non-alcoholic steatohepatitis, which positively correlated with the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST) and insulin. Knockdown of ClC-2 in liver attenuated HFD-induced weight gain, obesity, hepatocellular ballooning, and liver lipid accumulation and fibrosis, accompanied by reduced plasma free fatty acid (FFA), triglyceride (TG), total cholesterol (TC), ALT, AST, glucose and insulin levels and homeostasis model of insulin resistance (HOMA-IR) value. Moreover, HFD-treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP)-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS), HMG-CoA reductase (HMGCR) and acetyl-Coenzyme A carboxylase (ACCα). In addition, in vivo and in vitro results demonstrated that ClC-2 downregulation in HFD-treated mice or HepG2 cells increased the sensitivity to insulin via activation of IRS-1/Akt/mTOR signaling pathway. Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing ClC-2 may be an attractive therapeutic strategy for the treatment of NAFLD.
Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer
Authors: Zhao Meng , Liu Yahui , Liu Ran , Qi Jin , Hou Yongwang , Chang Jiao , Ren Li
Published: March 2018

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.
Molecular Insights into hERG Potassium Channel Blockade by Lubeluzole
Authors: Gualdani Roberta , Cavalluzzi Maria Maddalena , Tadini-Buoninsegni Francesco , Convertino Marino , Gailly Philippe , Stary-Weinzinger Anna , Lentini Giovanni
Published: March 2018

Background/Aims: Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in preclinical models of ischemic stroke. However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. Since the cardiac cellular effects of lubeluzole have not been described thus far, an explanation for the lubeluzole-induced QT interval prolongation is lacking. Methods: We tested the affinity of lubeluzole, its enantiomer, and the racemate for hERG channel using the patch-clamp technique. We synthesized and tested two simplified model compounds corresponding to two moieties included in the lubeluzole structure. The obtained experimental results were rationalized by docking simulation on the recently reported cryo-electron microscopy (cryo-EM) structure of hERG. Group efficiency analysis was performed in order to individuate the fragment most contributing to binding. Results: We found that lubeluzole and its R enantiomer are highly potent inhibitors of human ether-ago-go-related gene (hERG) channel with an IC50 value of 12.9 ± 0.7 nM and 11.3 ± 0.8 nM, respectively. In the presence of lubeluzole, steady-state activation and inactivation of hERG channel were shifted to more negative potentials and inactivation kinetics was accelerated. Mutations of aromatic residues (Y652A and F656A) in the channel inner cavity significantly reduced the inhibitory effect of lubeluzole. Molecular docking simulations performed on the near atomic resolution cryo-electron microscopy structures of hERG supported the role of Y652 and F656 as the main contributors to high affinity binding. Group efficiency analysis indicated that both 1,3-benzothiazol-2-amine and 3-aryloxy-2-propanolamine moieties contribute to drug binding with the former giving higher contribution. Conclusions: This study suggests the possibility to modulate lubeluzole hERG blockade by introducing suitable substituents onto one or both constituting portions of the parent compound in order to either reduce potency (i. e. torsadogenic potential) or potentiate affinity (useful for class III antiarrhythmic and anticancer agent development).
Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury
Authors: Qian Yingying , Guo Xiangjiang , Che Lin , Guan Xuejing , Wu Bei , Lu Renhua , Zhu Mingli , Pang Huihua , Yan Yucheng , Ni Zhaohui , Gu Leyi
Published: March 2018

Background/Aims: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. Methods: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein and N-acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. Results: Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1β, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or H2O2. Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in both in vivo and in vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. Conclusion: Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition.
MiR-125b Inhibits LPS-Induced Inflammatory Injury via Targeting MIP-1α in Chondrogenic Cell ATDC5
Authors: Jia Jinling , Wang Jingyu , Zhang Junlei , Cui Mingxing , Sun Xiaohui , Li Qingjiang , Zhao Bin
Published: March 2018

Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). MicroRNAs (miRNAs) play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways.
A Role for Receptor-Interacting Protein Kinase-1 in Neutrophil Extracellular Trap Formation in Patients with Systemic Lupus Erythematosus: a Preliminary Study
Authors: Guo Ruru , Tu Yang , Xie Shaowei , Liu Xue song , Song Yang , Wang Suli , Chen Xiaoxiang , Lu Liangjing
Published: March 2018

Background/Aims: Neutrophil extracellular traps (NETs) are known to play an important role in systemic lupus erythematosus (SLE) by triggering innate and adaptive immune responses. The molecular mechanisms responsible for their formation in SLE are still unclear. In this study, we aim to characterize the role of the receptor-interacting protein kinase-1 (RIPK1), a homologous serine/threonine kinase previously implicated in the regulation of necroptosis and tissue injury, in decreasing neutrophil death and formation of NETs, and to investigate the clinical implications of RIPK1 in SLE. Methods: Patients with SLE (n = 50) and healthy donors (n = 35) were enrolled in in vitro studies. Management of SLE patients was evaluated using the SLE disease activity index 2000 (SLEDAI-2K) score and laboratory variables. The mRNA level of RIPKs was measured by quantitative polymerase chain reaction (qPCR). Intracellular RIPK1 and RIPK3 production by peripheral blood leukocytes was detected by four-color flow cytometry and confirmed by automatic western blotting. TNF-α, IFN-γ, IL-1β, IL-2, IL-8, IL-18, and RIPK1 were measured by enzyme-linked immunosorbent assay. Cell death was assayed by Sytox green dye from peripheral neutrophils stimulated by RIPK-1-stabilizer necrostatin-1 (nec-1) and phorbol 12-myristate 13-acetate (PMA). Immunofluorescence staining and confocal microscopy were used to detect NET formation ex vivo. Quantification of NETs was determined by fluorescence spectrometry. Results: IFN-γ, IL-1β, IL-8, and IL-18 levels in serum were increased in SLE patients compared to controls. However, the expression of TNF-α, IL-2, and RIPK1 were decreased. In addition, we observed significant differences in the expression of RIPK1 in peripheral blood leukocytes. Of all the leukocytes, RIPK1 expression was significantly lower in neutrophils. Furthermore, we studied NETs formation in neutrophils of SLE with decreased RIPK1 expression, and these show increased susceptibility to NETosis, when stimulated with PMA and/or nec-1. Importantly, RIPK1 expression in neutrophils negatively correlated with ESR, CRP, 24-hour urine total protein, and the disease activity index in SLE. Conclusion: These data represent the first report of decreased RIPK1 expression in neutrophils of SLE patients and imply that RIPK1 may be involved in neutrophil death and NET formation. We suggest that RIPK1 is a potential biomarker to predict disease activity.
Loneuroides García Aldrete (Psocodea: ‘Psocoptera’: Ptiloneuridae): new species and first record for Brazil
Authors: Silva Neto Alberto Moreira da , García Aldrete Alfonso Neri , Rafael José Albertino
Published: March 2018

Loneuroides is registered for the first time in Brazil. A new species from the Brazilian state of Bahia, is here described and illustrated. It differs from all the other species in the genus in details of the female ninth sternum and by number of primary branches in vein M of fore- and hind- wings. A map with the distribution of the species of Loneuroides is included.
Perfil epidemiológico de idosos hipertensos no Brasil: uma revisão integrativa
Authors: Bezerra Álef Lamark Alves , Bezerra Daniel Sarmento , Pinto Danielle Serafim , Bonzi André Ricardo Bezerra , Pontes Ricardo Montenegro Nóbrega de , Veloso José Artur De Paiva
Published: March 2018

O aumento da população idosa tem consequências diretas sobre os sistemas de saúde pública, uma vez que a velhice está mais intimamente ligada a condições patológicas que comprometem alguns sistemas, como o sistema vascular, por exemplo. Assim, com o envelhecimento, o indivíduo é suscetível a mais morbidades como a hipertensão, que é destacada como fator de risco para a qualidade de vida e declínio na função cognitiva. Por isso, realizou-se este estudo cujo objetivo é descrever o perfil epidemiológico de pacientes hipertensos e idosos matriculados no programa Hiperdia e residentes em estados do Brasil. Foi analisada sua associação com os principais fatores de risco como o tabagismo, o sedentarismo e o excesso de peso. Trata-se de uma revisão integrativa da literatura, composta por publicações relativas aos anos de 2012 a maio de 2016, em português, inglês ou espanhol, indexadas do portal da Biblioteca Virtual de Saúde, BVS, nos seguintes bancos de dados: LILACS; BDENF, MEDLINE e SciELO. A hipertensão é comum nos idosos e tem a sua prevalência aumentada pelo envelhecimento, condicionando assim a morbidade e a mortalidade desta população. Entre os principais fatores de risco encontrados em pesquisa e estudos estão a alta circunferência da cintura, o excesso de peso e, muitas vezes, o consumo de gorduras saturadas. Além destes, estão o hábito de fumar, beber álcool e fazer exercício de forma irregular. Cabe citar que a maioria dos estudos sugere que as mulheres mais velhas são o público mais danificado. Finalmente, o programa Hiperdia é decisivo para melhorar a qualidade de vida, pois faz a regulamentação do atendimento médico e fornece tanto controle quanto sinais para problemas que podem ocorrer dentro da população assistida e deve haver de parte da sociedade e do estado e esforço para aprimorar este programa.
Paraganglioma de corpo carotídeo: relato de caso
Authors: Melo Daiana Barbosa Dias , Hamade Ahmad Mohamad Ali , Coelho Ana Carolina Taveira Engler Raiz , Peres André De Carvalho Sales , Vivi Ayder Anselmo Gomes
Published: March 2018

Os paragangliomas são tumores neuroendócrinos raros com origem em células especializadas derivadas da crista neural. No corpo carotídeo são raros e devem fazer parte do diagnóstico diferencial de tumores da região cervical. Este relato de caso apresenta uma paciente de 24 anos, gênero feminino, com queixa de abaulamento cervical à direita. Foi realizado o tratamento cirúrgico no Hospital Padre Albino. Nesse artigo os autores apresentam um caso de paraganglioma de corpo carotídeo, dando ênfase nos aspectos clínicos, diagnóstico e tratamento.
Medical education assessment
Authors: Camargo Cristina P. , Gemperli Rolf , Auler Junior José Otavio Costa
Published: March 2018

One of the most critical steps for medical education is the assessment. The assessment can be divided into short-term memory, long-term memory, and retrieval memory. If the student acquires all these memories steps, the surgical skill will be mind incorporate for years. As a healthcare provider, the medical community needs to transform training and learning to a valid and reliable activity. Most of the medical evaluations are subjective; an objective assessment is difficult but most desirable. The authors described some objective surgical skill assessment based on OSAST, dexterity and global rating scale. Moreover, we discussed the formative and summative assessment roles to the medical learning process.
Treinamento de habilidades cirúrgicas para estudantes de medicina – papel da simulação
Authors: Motta Eduardo Vieira da , Baracat Edmund Chada
Published: March 2018

O emprego de simulação para o aprendizado das técnicas motoras para a prática cirúrgica é crescente nos programas de graduação, residência e pós-graduação. O desenvolvimento do conhecimento dos processos educacionais e das plataformas pedagógicas fez evoluir a formação educacional médica, com redução do emprego de animais de experimentação e maior utilização de modelos não biológicos e eletrônicos, presentes nos laboratórios de simulação. Além disto, os laboratórios de simulação permitem que novas tecnologias e conceitos educacionais sejam utilizados para ampliação do ensino de cirurgia, incluindo avaliação de conhecimento teórico, processos de tomada de decisão e avaliação de riscos, comunicação em equipe, trabalho em equipe, análise de custos e gestão. Neste contexto, a simulação favorece o ensino baseado em competências. Os modelos de simulação envolvem utilização desde modelos simples de material sintético, como plástico e borracha, até manequins de alta fidelidade com controle informatizado, caracterização de ambientes de sala cirúrgica, ambulatório, enfermaria, além da participação de atores como pacientes, familiares e outros membros da equipe médica. Os objetivos educacionais de diferentes currículos e instituições definirá o grau de sofisticação necessário. O uso de animais permanece como alternativa de treinamento, porém com crescente respeito a normas éticas para sua utilização, respeitando o emprego para situações cada vez mais específicas em que a complexidade é elevada.
Modelo sintético de traqueia para a realização de traqueostomia e cricotireoidostomia: melhorando as opções de treinamento com alternativa de baixo custo para o ensino na graduação médica
Authors: Anselmo Natássia Alberici , Cazon Kênia Maria Jordão , Pinto Amely Covalero da Silva , Guerra Junior Antonio Carlos Morale , Costa Carlos Dario da Silva , Raphe Raphael
Published: March 2018

Modelos experimentais sintéticos têm sido aplicados em diversas áreas de treinamento das habilidades. Nesse sentido, foi desenvolvido um modelo para treinamento de traqueostomia e cricotireoidostomia, reutilizável por até quatro vezes, com custo baixo (cinco reais), montado em tempo curto (cerca de 15 minutos). Trinta e sete alunos de um curso de medicina realizaram os procedimentos com o modelo sintético criado e, na sequência, opinaram anonimamente sobre sua eficácia, vantagens e desvantagens em relação ao treino de habilidades, por meio de um questionário semiestruturado. Como resultados, mais de 70% dos estudantes declararam que essa seria a melhor maneira de complementar o aprendizado das técnicas cirúrgicas e que o maior benefício se deu pela possibilidade de praticar diversas vezes o procedimento, visto que a aquisição de uma habilidade só pode ser obtida com de exaustivo treinamento. Entretanto, 40% dos alunos que responderam o questionário apontaram as dificuldades do material sintético, principalmente com relação à sua pouca maleabilidade. Vale observar também que o material de treinamento biológico possui muitas desvantagens, como durabilidade, dificuldade de armazenamento, alto custo, não ser reutilizável e o fato de as normas de sociedades protetoras dos animais estarem cada vez mais rigorosas. Concluindo, modelos de baixo custo que são reutilizáveis e o mais fidedigno possível à realidade, como o deste estudo, demonstram a sua importância na disciplina de habilidades como uma alternativa para complementar o aprendizado da técnica.
O RPG (roleplaying game) como ferramenta de ensino do suporte básico da vida
Authors: Alves César Henrique Morais , Castro Aldemar Araujo
Published: March 2018

Objetivo. Determinar a diferença de proporção de desempenhos satisfatórios nas avaliações de habilidades em Suporte Básico da Vida (SBV) em estudantes de medicina depois de utilizar o RPG (role-playing game) como ferramenta de ensino comparado com antes do RPG. A hipótese é que a diferença de proporção é de 10% a mais após o uso do RPG. Métodos. Tipo de estudo: antes-depois. Amostra: estudantes do curso de graduação em medicina, do primeiro ao último ano, estratificados por ano em uma amostra por conveniência. Procedimentos: Foram realizadas sessões de RPG simulando diferentes situações da parada cardiorrespiratória, com avaliação dos participantes imediatamente antes e depois destas sessões. Variável: a diferença de proporção de desempenhos satisfatórios nas avaliações de habilidades em SBV depois de utilizar o RPG como ferramenta de ensino comparado com antes. Foi utilizado um formulário padronizado para avaliar as habilidades e os conhecimentos. Método estatístico: o tamanho da amostra foi estimado em 77 participantes. A análise estatística foi realizada com o teste de McNemar, e foi calculado o intervalo de confiança de 95%. Resultados. A diferença de proporção de desempenhos satisfatórios nas avaliações de habilidades em SBV depois de utilizar o RPG como ferramenta de ensino comparado com antes foi de 58% (IC95% 45 a 71, P < 0,0001). A diferença de proporção de desempenhos satisfatórios nas avaliações de conhecimentos sobre SBV depois de utilizar o RPG comparado com antes foi de 36% (IC95% 24 a 48, P < 0,0001). Conclusões. O uso do RPG no ensino do SBV pode melhorar a aquisição de habilidades e conhecimentos em SBV.