bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhodiola crenulata Suppresses High Glucose-Induced Matrix Metalloproteinase Expression and Inflammatory Responses by Inhibiting ROS-Related HMGB1-TLR4 Signaling in Endothelial Cells
Authors: Huang Li-Yen , Yen I-Chuan , Tsai Wei-Cheng , Lee Shih-Yu
Published: January 2020

Rhodiola crenulata, a popular folk medicine for anti-altitude sickness in Tibet, has been shown to have protective effects against high glucose (HG)-induced endothelial cell dysfunction in human umbilical vein endothelial cells (HUVECs). However, its mechanisms of action are unclear. Here, we aimed to examine the effects and the mechanisms of action of Rhodiola crenulata extract (RCE) on matrix metalloproteinases (MMPs) and inflammatory responses under HG conditions. HUVECs were pretreated with RCE or untreated and then exposed to 33[Formula: see text]mM glucose medium for 24[Formula: see text]h. The levels of oxidative stress markers, MMPs, endogenous tissue inhibitors of MMPs (TIMPs), and adhesion molecules were determined. Zymography assays were also carried out. We found that RCE significantly decreased HG-induced increases in reactive oxygen species (ROS) and activation of MAPK and NF-[Formula: see text]B pathways. In addition, RCE not only significantly reduced the expression and activities of MMPs but also upregulated TIMP protein levels. Consistently, HG-induced activation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein (MyD88) signaling pathway, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and high mobility group box 1 (HMGB1) as well as endothelial cell apoptosis was inhibited by RCE treatment. RCE exerts protective effects on endothelial cells against HG insult, partially by suppressing the HMGB1/TLR4 axis. These findings indicate that Rhodiola crenulata may be a potential therapeutic agent for diabetes-associated vascular diseases.
Constructing black hole solutions in supergravity theories
Authors: Gallerati Antonio
Published: January 2020

We perform a detailed analysis of black hole solutions in supergravity models. After a general introduction on black holes in general relativity and supersymmetric theories, we provide a detailed description of ungauged extended supergravities and their dualities. Therefore, we analyze the general form of black hole configurations for these models, their near-horizon behavior and characteristic of the solution. An explicit construction of a black hole solution with its physical implications is given for the STU-model. The second part of this review is dedicated to gauged supergravity theories. We describe a step-by-step gauging procedure involving the embedding tensor formalism to be used to obtain a gauged model starting from an ungauged one. Finally, we analyze general black hole solutions in gauged models, providing an explicit example for the [Formula: see text], [Formula: see text] case. A brief review on special geometry is also provided, with explicit results and relations for supersymmetric black hole solutions.
Ultrahigh brightness attosecond electron beams from intense X-ray laser driven plasma photocathode
Authors: Hu Ronghao , Gong Zheng , Yu Jinqing , Shou Yinren , Lv Meng , Sheng Zhengming , Tajima Toshiki , Yan Xueqing
Published: January 2020

The emerging intense attosecond X-ray lasers can extend the Laser Wakefield Acceleration mechanism to higher plasma densities in which the acceleration gradients are greatly enhanced. Here we present simulation results of high quality electron acceleration driven by intense attosecond X-ray laser pulses in liquid methane. Ultrahigh brightness electron beams can be generated with 5-dimensional beam brightness over [Formula: see text]. The pulse duration of the electron bunch can be shorter than 20 as. Such unique electron sources can benefit research areas requiring crucial spatial and temporal resolutions.
Demonstration of thin film compression for short-pulse X-ray generation
Authors: Farinella D. M. , Stanfield M. , Beier N. , Nguyen T. , Hakimi S. , Tajima T. , Dollar F. , Wheeler J. , Mourou G.
Published: January 2020

Thin film compression to the single-cycle regime combined with relativistic compression offers a method to transform conventional ultrafast laser pulses into attosecond X-ray laser pulses. These attosecond X-ray laser pulses are required to drive wakefields in solid density materials which can provide acceleration gradients of up to TeV/cm. Here we demonstrate a nearly 99% energy efficient compression of a 6.63 mJ, 39 fs laser pulse with a Gaussian mode to 20 fs in a single stage. Further, it is shown that as a result of Kerr-lensing, the focal spot of the system is slightly shifted on-axis and can be recovered by translating the imaging system to the new focal plane. This implies that with the help of wave-front shaping optics the focusability of laser pulses compressed in this way can be partially preserved.
Wakefield acceleration towards ZeV from a black hole emanating astrophysical jets
Authors: Ebisuzaki T. , Tajima T.
Published: January 2020

We consider that electromagnetic pulses produced in the jets of this innermost part of the accretion disk accelerate charged particles (protons, ions, electrons) to very high energies via wakefield acceleration, including energies above 10[Formula: see text] eV for the case of protons and nucleus and 10[Formula: see text] eV for electrons by electromagnetic wave-particle interaction. Thereby, the wakefield acceleration mechanism supplements the pervasive Fermi’s stochastic acceleration mechanism (and overcomes its difficulties in the highest energy cosmic ray generation). The episodic eruptive accretion in the disk by the magneto-rotational instability gives rise to the strong Alfvenic pulses, which acts as the driver of the collective accelerating pondermotive force. This pondermotive force drives the wakes. The accelerated hadrons (protons and nuclei) are released to the intergalactic space to be ultra-high energy cosmic rays. The high-energy electrons, on the other hand, emit photons to produce various non-thermal emissions (radio, IR, visible, UV, and gamma-rays) of active galactic nuclei in an episodic manner, giving observational telltale signatures.
Probing correlation between photon orbits and phase structure of charged AdS black hole in massive gravity background
Authors: Chabab M. , El Moumni H. , Iraoui S. , Masmar K.
Published: January 2020

The phase structure of charged anti-de Sitter black hole in massive gravity is investigated using the unstable circular photon orbits formalism, concretely we establish a direct link between the null geodesics and the critical behavior thermodynamic of such black hole solution. Our analysis reveals that the radius and the impact parameter corresponding to the unstable circular orbits can be used to probe the thermodynamic phase structure. We also show that the latter are key quantities to characterize the order of Van der Waals-like phase transition. Namely, we found a critical exponent around [Formula: see text]. All these results support further that the photon trajectories can be used as a useful and crucial tool to probe the thermodynamic black holes criticality.
The hypergeometric system for one-loop triangle integral
Authors: Yang Xiu-Yi , Li Hong-Na
Published: January 2020

We derive the holonomic hypergeometric system for the [Formula: see text] function with two equal virtual masses, and present the expression of [Formula: see text] in hypergeometric series in corresponding convergent region. Combining the Horn’s convergence theory with Gröbner basis of polynomial ideal, one can calculate the convergence region of the corresponding multiple series concretely. Using the system given here, one can analytically continue [Formula: see text] to whole parameter space.
Label propagation algorithm based on node similarity driven by local information
Authors: Song Chen , Huang Guoyan , Yin Bo , Zhang Bing , Liu Xinqian
Published: January 2020

Label propagation algorithm (LPA) attracts wide attention in community detection field for its near linear time complexity in large scale network. However, the algorithm adopts a random selection scheme in label updating strategy, which results in unstable division and poor accuracy. In this paper, five different indicators of node similarity are introduced based on network local information to distinguish nodes and a new label updating method is proposed. When there are multiple maximum neighbor labels in the propagation process, the maximum label corresponding to the most similar node is selected for updating instead of a random one. Five different forms of improved LPA are proposed which are named as SAL-LPA, SOR-LPA, JAC-LPA, SOR-LPA, HDI-LPA and HPI-LPA. The experiment results on real-world and artificial benchmark networks show that the improved LPA greatly improves the performance of the original algorithm, among which HPI-LPA is the best.
Studies on thermo-electro-mechanical coupling bandgaps of a piezoelectric phononic crystal nanoplate with surface effects
Authors: Qian Denghui , Bao Siyuan , Shen Feng
Published: January 2020

Applying surface piezoelectricity theory and plane wave expansion (PWE) method to the model of Kirchhoff plate, the calculation method of band structure of a piezoelectric phononic crystal (PC) nanoplate with surface effects is proposed and formalized. In order to investigate the bandgap properties of first order in the nanoplate in detail, the corresponding influence rules of thermo-electro-mechanical coupling fields, surface effects and geometric parameters on bandgaps are studied. During the researches, temperature variation, electrical voltage and external axial force are picked as the influencing parameters corresponding to thermo-electro-mechanical coupling fields. Residual surface stress and material intrinsic length are chosen as the influencing parameter related to surface effects. Lattice constant, radius of PZT-4 hole and thickness of nanoplate are picked as the influencing parameters of geometric parameters. All the results are expected to be helpful for the design of micro and nanodevices based on piezoelectric periodic nanoplates.
Strategies of motion under the black hole horizon
Authors: Toporensky A. V. , Zaslavskii O. B.
Published: January 2020

In this methodological paper, we consider two problems an astronaut faces under the black hole horizon in the Schwarzschild metric. (1) How to maximize the survival proper time. (2) How to make a visible part of the outer universe as large as possible before hitting the singularity. Our consideration essentially uses the concept of peculiar velocities based on the “river model.” Let an astronaut cross the horizon from the outside. We reproduce from the first principles the known result that point (1) requires that an astronaut turn off the engine near the horizon and follow the path with the momentum equal to zero. We also show that point (2) requires maximizing the peculiar velocity of the observer. Both goals (1) and (2) require, in general, different strategies inconsistent with each other that coincide at the horizon only. The concept of peculiar velocities introduced in a direct analogy with cosmology and its application for the problems studied in this paper can be used in advanced general relativity courses.
WEIERSTRASS-TYPE FUNCTIONS IN p-ADIC LOCAL FIELDS
Authors: LI YIN
Published: January 2020

The Weierstrass nowhere differentiable function has been studied often as example of functions whose graphs are fractals in [Formula: see text]. This paper investigates the Weierstrass-type function in the [Formula: see text]-adic local field [Formula: see text] whose graph is a repelling set of a discrete dynamical system, and proves that there exists a linear connection between the orders of the [Formula: see text]-adic calculus and the dimensions of the corresponding graphs.
SYMMETRY ANALYSIS FOR A SEVENTH-ORDER GENERALIZED KdV EQUATION AND ITS FRACTIONAL VERSION IN FLUID MECHANICS
Authors: WANG GANGWEI , LIU YIXING , WU YANBIN , SU XING
Published: January 2020

KdV types of equations play an important role in many fields. In this paper, we study a seventh-order generalized KdV equation and its fractional version in fluid mechanics using symmetry. From symmetry, the corresponding vectors, symmetry reduction and conservation laws are derived. Potential equation is also analyzed with regard to the symmetry method. Based on the symmetry, similarity reductions and conservation laws are also presented. Subsequently, the fractional version of the seventh-order KdV equation is discussed. Finally, differential invariants are constructed for the special case.
FINITE PATTERN PROBLEMS RELATED TO LÜROTH EXPANSION
Authors: TIAN ZHIGANG , WU MIN , LOU MAN-LI
Published: January 2020

Let [Formula: see text] be a set of countable many functions, where every function [Formula: see text] satisfies [Formula: see text] and [Formula: see text] as [Formula: see text]. This paper studies the size of the set consisting of those numbers whose Lüroth digit sequence is strictly increasing and contains any finite pattern of [Formula: see text]. We prove that the Hausdorff dimension of such set is [Formula: see text] and give several applications.
THE SCALE-FREE AND SMALL-WORLD PROPERTIES OF COMPLEX NETWORKS ON SIERPINSKI-TYPE HEXAGON
Authors: CHENG KUN , CHEN DIRONG , XUE YUMEI , ZHANG QIAN
Published: January 2020

In this paper, a network is generated from a Sierpinski-type hexagon by applying the encoding method in fractal. The criterion of neighbor is established to quantify the relationships among the nodes in the network. Based on the self-similar structures, we verify the scale-free and small-world effects. The power-law exponent on degree distribution is derived to be [Formula: see text] and the average clustering coefficients are shown to be larger than [Formula: see text]. Moreover, we give the bounds of the average path length of our proposed network from the renewal theorem and self-similarity.
How Sociology’s Three Identity Theory Traditions Clarify the Process of Entrepreneurial Identity Formation
Authors: Davis Daniel
Published: January 2020

The sociological literature on identity construction falls into three broad traditions. One, rooted in social psychology, underscores how individuals internalize identities that become stable self-structures. The second, rooted in dramaturgy, emphasizes how individuals contextually perform their identities through various scripts. The third, rooted in social movements literature, stresses how collective identity is nurtured and mobilized. Through 56 interviews with undergraduate entrepreneurs, I show that the three traditions are not contradictory, but rather highlight complementary processes and divergent layers of analysis. This synthesis is pedagogically and analytically useful, providing a heuristic for designing future empirical inquiry on entrepreneurial identity construction.
Fabrication of ZnO@CeO2 core–shell hetero-structural nanofibers and enhanced gas sensing performance for acetone
Authors: Diao Quan , Yin Yuna , Zhang Xiaomei , Li Jie , Jiao Mingli , Cao Jian , Qin Qi , Yang Kai , Zhu Genxing , Xu Xiumei
Published: January 2020

ZnO@CeO2 core–shell hetero-structural nanofibers (NFs) were synthesized by a coaxial electrospinning method and the materials characterization results proved that the core–shell hetero-structure was formed. Furthermore, the sensing properties test indicated that the ZnO@CeO2 NFs exhibited higher response values and enhanced selectivity to acetone in low concentration range (0.2–10[Formula: see text]ppm) compared with ZnO and CeO2 NFs, which showed the potential value in the field of diabetes diagnose. It is suggested that the enhanced sensitivity to acetone is attributed to the synergistic effect of one-dimensional (1D) structure and the formation of ZnO and CeO2 hetero-structure.
Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function
Authors: Lacombe Julie , Al Rifai Omar , Loter Lorraine , Moran Thomas , Turcotte Anne-Frédérique , Grenier-Larouche Thomas , Tchernof André , Biertho Laurent , Carpentier André C. , Prud’homme Denis , Rabasa-Lhoret Rémi , Karsenty Gerard , Gagnon Claudia , Jiang Weiping , Ferron Mathieu
Published: January 2020

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.
Skeletal muscle lipid droplets are resynthesized before being coated with perilipin proteins following prolonged exercise in elite male triathletes
Authors: Jevons Emily F. P. , Gejl Kasper D. , Strauss Juliette A. , Ørtenblad Niels , Shepherd Sam O.
Published: January 2020

Intramuscular triglycerides (IMTG) are a key substrate during prolonged exercise, but little is known about the rate of IMTG resynthesis in the postexercise period. We investigated the hypothesis that the distribution of the lipid droplet (LD)-associated perilipin (PLIN) proteins is linked to IMTG storage following exercise. Fourteen elite male triathletes (27 ± 1 yr, 66.5 ± 1.3 mL·kg−1·min−1) completed 4 h of moderate-intensity cycling. During the first 4 h of recovery, subjects received either carbohydrate or H2O, after which both groups received carbohydrate. Muscle biopsies collected pre- and postexercise and 4 and 24 h postexercise were analyzed using confocal immunofluorescence microscopy for fiber type-specific IMTG content and PLIN distribution with LDs. Exercise reduced IMTG content in type I fibers (−53%, P = 0.002), with no change in type IIa fibers. During the first 4 h of recovery, IMTG content increased in type I fibers ( P = 0.014), but was not increased more after 24 h, where it was similar to baseline levels in both conditions. During recovery the number of LDs labeled with PLIN2 (70%), PLIN3 (63%), and PLIN5 (62%; all P < 0.05) all increased in type I fibers. Importantly, the increase in LDs labeled with PLIN proteins only occurred at 24 h postexercise. In conclusion, IMTG resynthesis occurs rapidly in type I fibers following prolonged exercise in highly trained individuals. Furthermore, increases in IMTG content following exercise preceded an increase in the number of LDs labeled with PLIN proteins. These data, therefore, suggest that the PLIN proteins do not play a key role in postexercise IMTG resynthesis.
Prevalence, Risk Factors, and Antimicrobial Resistance Profiles of Thermophilic Campylobacter Species in Humans and Animals in Sub-Saharan Africa: A Systematic Review
Authors: Gahamanyi Noel , Mboera Leonard E. G. , Matee Mecky I. , Mutangana Dieudonné , Komba Erick V. G.
Published: January 2020

Thermophilic Campylobacter species are clinically important aetiologies of gastroenteritis in humans throughout the world. The colonization of different animal reservoirs by Campylobacter poses an important risk for humans through shedding of the pathogen in livestock waste and contamination of water sources, environment, and food. A review of published articles was conducted to obtain information on the prevalence and antimicrobial resistance (AMR) profiles of thermophilic Campylobacter species in humans and animals in sub-Saharan Africa (SSA). Electronic databases, namely, PubMed, Google Scholar, Research4life-HINARI Health, and Researchgate.net, were searched using the following search terms “thermophilic Campylobacter,” “Campylobacter jejuni,” “Campylobacter coli,” “diarrhea/diarrhoea,” “antimicrobial resistance,” “antibiotic resistance,” “humans,” “animals,” “Sub-Saharan Africa,” and “a specific country name.” Initially, a total of 614 articles were identified, and the lists of references were screened in which 22 more articles were identified. After screening, 33 articles on humans and 34 on animals and animal products were included in this review. In humans, Nigeria reported the highest prevalence (62.7%), followed by Malawi (21%) and South Africa (20.3%). For Campylobacter infections in under-five children, Kenya reported 16.4%, followed by Rwanda (15.5%) and Ethiopia (14.5%). The country-level mean prevalence in all ages and under-five children was 18.6% and 9.4%, respectively. The prevalence ranged from 1.7%–62.7% in humans and 1.2%–80% in animals. The most reported species were C. jejuni and C. coli. The AMR to commonly used antimicrobials ranged from 0–100% in both humans and animals. Poultry consumption and drinking surface water were the main risk factors for campylobacteriosis. The present review provides evidence of thermophilic Campylobacter occurrence in humans and animals and high levels of AMR in SSA, emphasizing the need for strengthening both national and regional multisectoral antimicrobial resistance standard surveillance protocols to curb both the campylobacteriosis burden and increase of antimicrobial resistance in the region.
Effects and Correction of Atmospheric Pressure Loading Deformation on GNSS Reference Stations in Mainland China
Authors: Yue Caiya , Dang Yamin , Xu Changhui , Gu Shouzhou , Dai Huayang
Published: January 2020

Atmospheric pressure loading (APL) deformation is one component of nontectonic deformation for Global Navigation Satellite System (GNSS) time series and is a kind of deformation response caused by a redistribution of atmospheric pressure. In this paper, we present an atmospheric data processing strategy to compute the APL based on a spherical harmonic expansion of the global atmosphere pressure changes. We also provide a sample model to describe the relativity between the global atmosphere pressure changes and APL vertical deformation. The results show that the variation of air mass has a major impact on the north-eastern area of East China, the eastern area of North China, and Northeast China, and the vertical crustal displacement caused by the atmosphere changes in these regions can reach about 20 mm. The correction of APL for vertical time series of GNSS reference stations in different regions indicates that the arid area of the Northwest China, Northeast China, Central China, and North China are greatly affected by APL. While for the station located in Sichuan-Yunnan region, the amplitude and period change are small after correction of APL for vertical time series of GNSS reference stations, which reveals that the area is seriously affected by tectonic movement and water migration loading. The correlation between atmospheric pressure changes and crustal deformation is analyzed, which shows that APL has a serious impact on the north-eastern area of North China, the Northeast China, and the eastern area of Central China when the variations in atmospheric pressure in mainland China are the same. The research results of this paper will provide some reference value for the study of crustal structural deformation and the establishment of geodetic datum.
Modified Atom Search Optimization Based on Immunologic Mechanism and Reinforcement Learning
Authors: Fu Yanming , Li Zhuohang , Qu Chiwen , Chen Haiqiang
Published: January 2020

Atom search optimization algorithm has good searching ability and has been successfully applied to calculate hydrogeological parameters and groundwater dispersion coefficient. Since the atom search optimization algorithm is only based on the atom force motion model in molecular dynamics, it has some shortcomings such as slow search speed and low precision during the later stage of iteration. A modified atom search optimization based on the immunologic mechanism and reinforcement learning is proposed to overcome the abovementioned shortcomings in this paper. The proposed algorithm introduces a vaccine operator to better utilize the dominant position in the current atom population so that the speed, accuracy, and domain search ability of the atom search optimization algorithm can be strengthened. The reinforcement learning operator is applied to dynamically adjust the vaccination probability to balance the global exploration ability and local exploitation ability. The test results of 21 benchmark functions confirm that the performance of the proposed algorithm is superior to seven contrast algorithms in search accuracy, convergence speed, and robustness. The proposed algorithm is used to optimize the permutation flow shop scheduling problem. The experimental results indicate that the proposed algorithm can achieve better optimization results than the seven comparative algorithms, so the proposed algorithm has good practical application value.
Semicarbazide-Sensitive Amine Oxidase Increases in Calcific Aortic Valve Stenosis and Contributes to Valvular Interstitial Cell Calcification
Authors: Mercier Nathalie , Pawelzik Sven-Christian , Pirault John , Carracedo Miguel , Persson Oscar , Wollensack Bastien , Franco-Cereceda Anders , Bäck Magnus
Published: January 2020

Introduction. Calcific aortic valve stenosis (CAVS) is a common disease associated with aging. Oxidative stress participates in the valve calcification process in CAVS. Semicarbazide-sensitive amine oxidase (SSAO), also referred to as vascular adhesion protein 1 (VAP-1), transforms primary amines into aldehydes, generating hydrogen peroxide and ammonia. SSAO is expressed in calcified aortic valves, but its role in valve calcification has remained largely unexplored. The aims of this study were to characterize the expression and the activity of SSAO during aortic valve calcification and to establish the effects of SSAO inhibition on human valvular interstitial cell (VIC) calcification. Methods. Human aortic valves from n=80 patients were used for mRNA extraction and expression analysis, Western blot, SSAO activity determination, immunohistochemistry, and the isolation of primary VIC cultures. Results. SSAO mRNA, protein, and activity were increased with increasing calcification within human aortic valves and localized in the vicinity of the calcified zones. The valvular SSAO upregulation was consistent after stratification of the subjects according to cardiovascular and CAVS risk factors associated with increased oxidative stress: body mass index, diabetes, and smoking. SSAO mRNA levels were significantly associated with poly(ADP-ribose) polymerase 1 (PARP1) in calcified tissue. Calcification of VIC was inhibited in the presence of the specific SSAO inhibitor LJP1586. Conclusion. The association of SSAO expression and activity with valvular calcification and oxidative stress as well as the decreased VIC calcification by SSAO inhibition points to SSAO as a possible marker and therapeutic target to be further explored in CAVS.
Sclerotherapy Induced Takotsubo Syndrome
Authors: Patel Sunny , Nabatian Sepideh , Goyfman Michael
Published: January 2020

A 66-year-old female was brought to the emergency department for acute-onset left-sided chest pain. Prior to arrival, she was at an outpatient appointment with a vascular surgeon for elective sclerotherapy treatment of her lower extremity varicose veins. After receiving an IV injection of polidocanol, she developed severe chest pain with left arm and jaw numbness for the first time in her life. Upon arrival to the ED, the patient reported that her symptoms had resolved. Electrocardiogram (ECG) on presentation was significant for T-wave inversions in leads V1-V3. An initial set of cardiac enzymes showed a troponin I level of 0.62 ng/mL, which subsequently increased to 2.26 ng/mL. Her echocardiogram was significant for mild left ventricular systolic dysfunction with apical hypokinesis (ejection fraction 50%). A repeat ECG showed new T-wave inversions compared to that from the time of admission. The patient eventually agreed to cardiac catheterization, which revealed patent vessels without coronary artery disease, supporting our diagnosis of Takotsubo syndrome and what is the first reported case of likely polidocanol-induced Takotsubo syndrome in the United States.
c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells
Authors: Yue Chun , Guo Zi , Luo Yufang , Yuan Jingjing , Wan Xinxing , Mo Zhaohui
Published: January 2020

Objective. Mesenchymal stem cells (MSCs) are considered a promising therapy for wound healing. Here, we explored the role of c-Jun in diabetic wound healing using human umbilical cord-derived MSCs (hUC-MSCs). Methods. Freshly isolated hUC-MSCs were subjected to extensive in vitro subcultivation. The cell proliferative and migratory capacities were assessed by the Cell Counting Kit-8 and scratch assays, respectively. c-Jun expression was evaluated by RT-PCR and western blot analysis. The function of c-Jun was investigated with lentivirus transduction-based gene silencing and overexpression. Diabetes mellitus was induced in SD rats on a high-glucose/fat diet by streptozocin administration. Wounds were created on the dorsal skin. The effects of c-Jun silencing and overexpression on wound closure by hUC-MSCs were examined. Reepithelialization and angiogenesis were assessed by histological and immunohistochemical analysis, respectively. Platelet-derived growth factor A (PDGFA), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) levels were determined by western blot analysis. Results. hUC-MSCs showed gradually decreased cell proliferation, migration, and c-Jun expression during subcultivation. c-Jun silencing inhibited cell proliferation and migration, while c-Jun overexpression enhanced proliferation but not migration. Compared with untransduced hUC-MSCs, local subcutaneous injection of c-Jun-overexpressing hUC-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased PDGFA and HGF levels in wound tissues. Conclusion. c-Jun overexpression promoted hUC-MSC proliferation and migration in vitro and accelerated diabetic wound closure, reepithelization, and angiogenesis by hUC-MSCs in vivo. These beneficial effects of c-Jun overexpression in diabetic wound healing by hUC-MSCs were at least partially mediated by increased PDGFA and HGF levels in wound tissues.
Alterations of Several Serum Parameters Are Associated with Preeclampsia and May Be Potential Markers for the Assessment of PE Severity
Authors: Duan Zhongliang , Li Cui , Leung Wing Ting , Wu Jiangnan , Wang Mingyan , Ying Chunmei , Wang Ling
Published: January 2020

The precise pathophysiological mechanisms of preeclampsia (PE) and preventative strategies remain unknown. Laboratory markers which can help in identifying PE patients from pregnant women and assessing the severity of PE during pregnancy are worthy to be explored. In this study, a retrospective case-control study was designed to assess whether the serum levels of albumin (ALB), total protein (TP), prealbumin (PA), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), D-dimer, fibrinogen (Fbg), platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) can help in assessing PE and evaluate its severity. 256 pregnant women were enrolled and classified into 3 groups: mild preeclampsia (mPE,n=85), severe preeclampsia (sPE,n=78), and healthy normotensive controls (control,n=93). Our result showed that the serum levels of ALP, LDH, and D-dimer were significantly higher in mild or severe PE patients compared with the healthy controls (66 (52.5-76.5) vs. 168 (141.5-201.25) vs. 182.5 (120-191.5), 152 (139.75-166.25) vs. 183.5 (163.25-307) vs. 282 (215.25-306), 1.05 (0.65-1.57) vs. 3.05 (2.25-4.08) vs. 5.65 (2.29-7.71)), while ALB, TP, and PA are lower (38 (37-42) vs. 31.5 (25.5-34.5) vs. 28.5 (24-33), 65 (63-68.25) vs. 56.5 (52-61) vs. 51.5 (49-58),219.14±68.25vs.167.88±52.21vs.143.22±50.46). On the other hand, compared with the mPE group, the sPE group showed significantly lower PLT count but higher level of LDH, D-dimer, and Fbg. No significant differences in MPV or PDW were found between any of the two groups. In conclusion, the above markers except for the MPV and PDW may be correlated with PE severity in this patient cohort, indicating possible values of these potential biomarkers in auxiliary diagnosis and severity assessment of PE.
Comparison of Bending Fatigue of NiTi and CuAlMn Shape Memory Alloy Bars
Authors: Huang Haoyu , Zhu Yuan-Zhi , Chang Wen-Shao
Published: January 2020

The behaviour under cyclic bending and in particular the fatigue properties of shape memory alloy (SMA) bars are important for civil engineering applications. In this paper, structural and functional fatigue is studied for both NiTi‐ and copper‐based shape memory alloys. The results are presented from cyclic bending tests on 7 mm diameter NiTi and 12 mm diameter CuAlMn SMA bars targeted at 100,000 cycles. During the tests, dynamic loading at 1 Hz, 5 Hz, and 8 Hz was applied for different strain levels (0.5%, 1%, 2%, and 6%). The stress‐strain curve, damping ratio, and secant stiffness were analysed for material characterisation, and the evolution of these parameters was studied to assess functional fatigue. The fatigue life is extended dramatically when the strain is below 1%, and the structural fatigue life of CuAlMn is shown to be better than that of NiTi and to depend on the loading rate. However, decay in stiffness can be found in the CuAlMn SMA, which is considered to be caused particularly by its long grain boundary.
Speech Encryption Algorithm Based on Nonorthogonal Quantum State with Hyperchaotic Keystreams
Authors: Farsana F. J. , Gopakumar K.
Published: January 2020

With the advancement in modern computational technologies like cloud computing, there has been tremendous growth in the field of data processing and encryption technologies. In this contest there is an increasing demand for successful storage of the data in the encrypted domain to avoid the possibility of data breach in shared networks. In this paper, a novel approach for speech encryption algorithm based on quantum chaotic system is designed. In the proposed method, classical bits of the speech samples are initially encoded in nonorthogonal quantum state by the secret polarizing angle. In the quantum domain, encoded speech samples are subjected to bit-flip operation according to the Controlled–NOT gate followed by Hadamard transform. Complete superposition of the quantum state in both Hadamard and standard basis is achieved through Hadamard transform. Control bits for C-NOT gate as well as Hadamard gate are generated with a modified Lu˙-hyperchaotic system. Secret nonorthogonal rotation angles and initial conditions of the hyperchaotic system are the keys used to ensure the security of the proposed algorithm. The computational complexity of the proposed algorithm has been analysed both in quantum domain and classical domain. Numerical simulation carried out based on the above principle showed that the proposed speech encryption algorithm has wider keyspace, higher key sensitivity and robust against various differential and statistical cryptographic attacks.
The Total Flavonoid Extract from Glycyrrhiza inflat Bat. Suppresses Atrophic Gastritis in Rats through the Akt/MAPK Pathway
Authors: Liu Junshan , Zheng Jun , Lin Xiaochun , Bai Shuntong , Deng Qiudi , Gao Wanjiao , Zhou Hongling , Tong Li
Published: January 2020

Ethnopharmacological Relevance. Glycyrrhiza inflat Bat. is widely used to treat gastric ulcer and gastritis in clinic in China. Aim of the Study. To investigate the protective effects and possible mechanisms of the total flavonoid extract (TFE) from G. inflat Bat. on atrophic gastritis (AG) rats. Materials and Methods. The rat AG model was established by providing sodium deoxycholate and alcohol, and then, AG rats were treated with TFE for 30 days. Pathologic changes in gastric specimens were observed using hematoxylin and eosin staining, and the capability of gastric mucosa to secrete mucus was examined by alcian blue‐periodic acid Schiff staining. Apoptosis induction in gastric tissues was measured by the TUNEL assay. The expressions of Bcl‐2, Bax, and proteins in the Akt/MAPK pathway in gastric tissues were examined by immunohistochemistry and/or Western blotting. Results. Compared with the AG group, TFE attenuated the damage of gastric mucosa as reflected by the thickening of the lamina propria and the thinning of the muscularis mucosae. Moreover, TFE induced apoptosis in gastric mucosa with increasing Bax/Bcl‐2 expression ratio. Concomitantly, the degrees of p‐ErkThr202/Tyr204 and p‐AktThr308 were decreased, whereas those of p‐p38Thr180/Tyr182 and p‐JNKThr183/Tyr185 were increased. Conclusion. We demonstrated the anti‐AG effect of G. inflat Bat. in vivo and elucidated the underlying mechanisms that involve gastric mucosa protection through the Akt/MAPK pathway. The study provides a rationale for the application of G. inflat Bat. in the treatment of AG.
The Impact of Statins before High-Risk CABG on Postoperative Multiple Organ Function
Authors: Wang Jiayang , Yuan Wen , Zhang Kui , Liu Nan , Liu Dong , Zhou Yujie
Published: January 2020

Background. The purpose of this cohort study was to investigate the independent relationship between preoperative statin therapy (PST) and postoperative severe multiorgan failure, measured by the Sequential Organ Failure Assessment (SOFA) maximum greater than 11, in high-risk patients undergoing isolated coronary artery bypass grafting (CABG). Methods. The present study is a perspective, single-center, cohort analysis enrolling high-risk patients undergoing CABG from Jan 1, 2018, to Dec 31, 2018, in Beijing Anzhen hospital. Results. Among a total of 880 high-risk patients undergoing isolated CABG included in this study, 503 (57.2%) experienced statin therapy before CABG. The SOFA maximum was significantly lower in the PST group compared with the control group (7.8 ± 3.0 v 9.2 ± 3.4, P<0.0001). Multivariate logistic regression analysis demonstrated the incidence of the severe multiorgan dysfunction, measured by SOFA maximum ≥11, was dramatically reduced in the PST group (OR, 0.68, 95% CI 0.50–0.92, P=0.013). Furthermore, preoperative statin therapy (PST) might be associated with a decreased risk of postoperative major adverse cardiovascular and cerebral events and acute kidney injury, but an increased risk of postoperative hepatic inadequacy. Conclusion. SOFA maximum was significantly lower in the PST group compared with the control group and the incidence of the severe multiorgan dysfunction was dramatically reduced in the PST group. The findings of this study might shed new light on questions of positive or negative effects of PST on multiple organ function after high-risk CABG, so as to ultimately improve high-risk patient in-hospital outcomes from CABG.
Multivariate Regression Analysis to Predict Postoperative Refractive Astigmatism in Cataract Surgery
Authors: Kawahara Atsushi , Sato Tatsuhiko , Hayashi Ken
Published: January 2020

Purpose. To assess the correlation between postoperative refractive astigmatism and preoperative parameters in cataract surgery. Methods. Left eyes of 100 consecutive patients scheduled for cataract surgery with a 2.4 mm clear corneal incision were examined prospectively. Refractive astigmatism was measured using an autokerato/refractometer. Corneal astigmatism of the total cornea was calculated using a Scheimpflug camera. The vertical/horizontal component (J0) and oblique component (J45) of refractive and total corneal astigmatism were determined using power vector analysis. Refractive astigmatism at 8 weeks postoperatively was estimated using multivariate linear regression analysis. Independent variables analyzed included age, sex, refractive astigmatism, total corneal astigmatism, sphere, intraocular pressure, corneal thickness, anterior chamber depth, lens thickness, axial length, and pupil diameter. Results. Multivariate regression analysis identified total corneal J0 and age as significant contributors to postoperative refractive J0 (P<0.001 and P=0.029, respectively). The standard partial regression coefficients in the multiple regression analysis were 0.59 and −0.16 for total corneal J0 and age, respectively. Significant contributors to postoperative refractive J45 were total corneal J45 and lens thickness (P<0.001 and P=0.015, respectively). The standard partial regression coefficients were 0.79 and −0.15 for total corneal J45 and lens thickness, respectively. Conclusion. These results suggest that preoperative total corneal astigmatism is the most significant predictor of postoperative refractive astigmatism when performing astigmatism correction in cataract surgery.
Deep Learning to Distinguish Benign from Malignant Renal Lesions Based on Routine MR Imaging
Authors: Xi Ianto Lin , Zhao Yijun , Wang Robin , Chang Marcello , Purkayastha Subhanik , Chang Ken , Huang Raymond Y. , Silva Alvin C. , Vallières Martin , Habibollahi Peiman , Fan Yong , Zou Beiji , Gade Terence P. , Zhang Paul J. , Soulen Michael C. , Zhang Zishu , Bai Harrison X. , Stavropoulos S. William
Published: January 2020

Purpose:

With increasing incidence of renal mass, it is important to make a pretreatment differentiation between benign renal mass and malignant tumor. We aimed to develop a deep learning model that distinguishes benign renal tumors from renal cell carcinoma (RCC) by applying a residual convolutional neural network (ResNet) on routine MR imaging.

Experimental Design:

Preoperative MR images (T2-weighted and T1-postcontrast sequences) of 1,162 renal lesions definitely diagnosed on pathology or imaging in a multicenter cohort were divided into training, validation, and test sets (70:20:10 split). An ensemble model based on ResNet was built combining clinical variables and T1C and T2WI MR images using a bagging classifier to predict renal tumor pathology. Final model performance was compared with expert interpretation and the most optimized radiomics model.

Results:

Among the 1,162 renal lesions, 655 were malignant and 507 were benign. Compared with a baseline zero rule algorithm, the ensemble deep learning model had a statistically significant higher test accuracy (0.70 vs. 0.56, P = 0.004). Compared with all experts averaged, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.60, P = 0.053), sensitivity (0.92 vs. 0.80, P = 0.017), and specificity (0.41 vs. 0.35, P = 0.450). Compared with the radiomics model, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.62, P = 0.081), sensitivity (0.92 vs. 0.79, P = 0.012), and specificity (0.41 vs. 0.39, P = 0.770).

Conclusions:

Deep learning can noninvasively distinguish benign renal tumors from RCC using conventional MR imaging in a multi-institutional dataset with good accuracy, sensitivity, and specificity comparable with experts and radiomics.
Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in EGFR Mutation–Positive Non–Small Cell Lung Cancer
Authors: Isomoto Kohsuke , Haratani Koji , Hayashi Hidetoshi , Shimizu Shigeki , Tomida Shuta , Niwa Takashi , Yokoyama Toshihide , Fukuda Yasushi , Chiba Yasutaka , Kato Ryoji , Tanizaki Junko , Tanaka Kaoru , Takeda Masayuki , Ogura Takashi , Ishida Tadashi , Ito Akihiko , Nakagawa Kazuhiko
Published: January 2020

Purpose:

The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non–small cell lung cancer (NSCLC) is unclear.

Experimental Design:

We retrospectively identified 138 patients with EGFR-mutated NSCLC who underwent rebiopsy after progression during EGFR-TKI treatment. PD-L1 and CD73 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density at baseline and after progression were determined by IHC. Tumor mutation burden (TMB) was determined by next-generation sequencing.

Results:

The proportion of patients with a PD-L1 expression level of ≥50% (high) increased from 14% before to 28% after EGFR-TKI (P = 0.0010). Whereas CD8+ and FOXP3+ TIL densities were significantly lower after EGFR-TKI treatment than before, CD8+ TIL density was maintained in tumors with a high PD-L1 expression level. Expression of CD73 in tumor cells after EGFR-TKI treatment was higher than that before in patients with a high PD-L1 expression level. TMB tended to be higher after EGFR-TKI treatment than before (3.3→4.1 mutations/Mbp, P = 0.0508). Median progression-free survival for subsequent treatment with antibodies to PD-1 was longer for patients with a high than for those with a low PD-L1 expression after EGFR-TKI (7.1 vs. 1.7 months, P = 0.0033), and two of five patients whose PD-L1 expression level changed from low to high after EGFR-TKI treatment achieved a PFS of >6 months.

Conclusions:

EGFR-TKI treatment was associated with changes in the TME of EGFR-mutated NSCLC, and such changes may provide clues for optimization of subsequent PD-1 inhibitor treatment.
First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma
Authors: Wen Patrick Y. , Cloughesy Timothy F. , Olivero Alan G. , Morrissey Kari M. , Wilson Timothy R. , Lu Xuyang , Mueller Lars U. , Coimbra Alexandre F. , Ellingson Benjamin M. , Gerstner Elizabeth , Lee Eudocia Q. , Rodon Jordi
Published: January 2020

Purpose:

GDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma.

Patients and Methods:

GDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses.

Results:

Forty-seven heavily pretreated patients enrolled in eight cohorts (2–65 mg). Dose-limiting toxicities included 1 case of grade 2 bradycardia and grade 3 myocardial ischemia (15 mg), grade 3 stomatitis (45 mg), and 2 cases of grade 3 mucosal inflammation (65 mg); the MTD was 45 mg/day. GDC-0084 demonstrated linear and dose-proportional PK, with a half-life (∼19 hours) supportive of once-daily dosing. At 45 mg/day, steady-state concentrations exceeded preclinical target concentrations producing antitumor activity in xenograft models. FDG-PET in 7 of 27 patients (26%) showed metabolic partial response. At doses ≥45 mg/day, a trend toward decreased median standardized uptake value in normal brain was observed, suggesting central nervous system penetration of drug. In two resection specimens, GDC-0084 was detected at similar levels in tumor and brain tissue, with a brain tissue/tumor-to-plasma ratio of >1 and >0.5 for total and free drug, respectively. Best overall response was stable disease in 19 patients (40%) and progressive disease in 26 patients (55%); 2 patients (4%) were nonevaluable.

Conclusions:

GDC-0084 demonstrated classic PI3K/mTOR–inhibitor related toxicities. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood–brain barrier.