bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐210 promotes lung adenocarcinoma proliferation, migration, and invasion by targeting lysyl oxidase‐like 4
Authors: Xie Songping , Liu Gaoli , Huang Jie , Hu Hai‐Bo , Jiang Wanli 
Published: January 2019

AbstractAccumulating evidence has revealed that various microRNAs are deregulated and involved in lung cancer development and metastasis. miR‐210 is implicated in several cancer progression. However, the detailed biological function and role of miR‐210 in lung adenocarcinoma remains unclear. Our current study was aimed to investigate the mechanism of miR‐210 in lung adenocarcinoma progression. We observed that miR‐210 was significantly upregulated in lung cancer cell lines (A549 and H1650) in comparison to BEAS‐2B cells. In addition, we found that miR‐210 was greatly elevated in lung adenocarcinoma tissues. Then, it was shown that overexpression of miR‐210 was able to promote lung cancer cell proliferation and colony formation ability while inhibitors of miR‐210 exhibited a reversed phenomenon. Subsequently, A549 and H1650 cell migration and invasion capacity were obviously restrained by miR‐210 inhibition whereas induced by miR‐210 mimics. Lysyl oxidase‐like 4 (LOXL4), a member of the secreted copper‐dependent amine oxidases has been found to be increased or decreased in different cancer types. Here, we confirmed that LOXL4 could serve as a downstream target of miR‐210 and miR‐210 promoted lung cancer progression via targeting LOXL4. In A549 and H1650 cells, knockdown of LOXL4 dramatically repressed lung cancer cell proliferation, migration, and invasion. In conclusion, our study implied that miR‐210 might indicate a new perspective for lung cancer.
RETRACTED: PNU‐74654 enhances the antiproliferative effects of 5‐FU in breast cancer and antagonizes thrombin‐induced cell growth via the Wnt pathway
Authors: Rahmani Farzad , Amerizadeh Forouzan , Hassanian Seyed Mahdi , Hashemzehi Milad , Nasiri Seyedeh‐Najibeh , Fiuji Hamid , Ferns Gordon A. , Khazaei Majid , Avan Amir 
Published: January 2019

AbstractThe Wnt/β‐catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential‐therapeutic target. We have investigated the effects of PNU‐74654 in breast cancer, as a Wnt/β‐catenin inhibitor, either alone or in combination with fluorouracil (5‐FU). PNU‐74654 suppressed cell growth at an IC
50 of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU‐74654 caused tumor shrinkage. It reduced the migration of MCF‐7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU‐74654 through perturbation of E‐cadherin and MMP3/9. PNU‐74654/5‐FU combination enhanced the percentages of cells in S‐phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU‐74654 plus 5‐FU. These data show the ability of PNU‐74654 to specifically target Wnt pathway, interfere with cell proliferation, induce‐apoptosis, reduce‐migration, and synergistically interact with 5‐FU, supporting further studies on this novel therapeutic‐approach for breast cancer.
Use of Physiologically Based Pharmacokinetic Modeling to Identify Physiological and Molecular Characteristics Driving Variability in Axitinib Exposure: A Fresh Approach to Precision Dosing in Oncology
Authors: Sorich Michael J. , Mutlib Fayzah , van Dyk Madelé , Hopkins Ashley M. , Polasek Thomas M. , Marshall Jean‐Claude , Rodrigues A. David , Rowland Andrew 
Published: January 2019

AbstractAxitinib is a second‐generation small‐molecule vascular endothelial growth factor receptor inhibitor. An axitinib steady‐state area under the plasma concentration–time curve (AUCSS) >300 ng/mL/hr is associated with superior progression‐free and overall survival. This study sought to characterize the physiological and molecular characteristics driving variability in axitinib AUCSS using physiologically based pharmacokinetic modeling to identify exposure biomarkers for this drug. The capacity to predict subjects likely to fail to achieve an axitinib AUCSS >300 ng/mL/hr was evaluated as a secondary outcome. A full physiologically based pharmacokinetic model incorporating mechanistic absorption was developed and verified for axitinib in accordance with the US Food and Drug Administration Guidance using Simcyp (Version 17.1). This model was used to simulate axitinib exposure over 7 days with twice‐daily dosing (5 mg) in a cohort of 1000 virtual cancer patients. Multiple linear regression modeling was used to identify patient characteristics associated with differences in axitinib exposure. A multivariable linear regression model incorporating hepatic cytochrome P450 (CYP) 3A4 abundance, albumin concentration, hepatic CYP1A2 abundance, hepatic CYP2C19 abundance, and intestinal CYP2C19 abundance provided robust prediction of axitinib AUCSS (R2 = 0.890; P < .001). By accounting for these variables, it was possible to identify subjects who would fail to achieve an effective axitinib AUCSS with a specificity of 88.7% and a sensitivity of 92.6%. Variability in axitinib AUCSS is primarily driven by differences in hepatic CYP3A4 abundance and albumin concentration. Consideration of these 2 characteristic is likely to be sufficient to individualize axitinib dosing.
Brain aging: A Ianus‐faced player between health and neurodegeneration
Authors: Vanni Silvia , Colini Baldeschi Arianna , Zattoni Marco , Legname Giuseppe 
Published: January 2019

AbstractNeurodegenerative diseases are incurable debilitating disorders characterized by structural and functional neuronal loss. Approximately 30 million people are affected worldwide, and this number is predicted to reach more than 150 million by 2050. Neurodegenerative disorders include Alzheimer’s, Parkinson’s, and prion diseases among others. These disorders are characterized by the accumulation of aggregating proteins forming amyloid, responsible for the disease‐associated pathological lesions. The aggregation of amyloidogenic proteins can result either in gaining of toxic functions, derived from the damage provoked by these deposits in affected tissue, or in a loss of functions, due to the sequestration and the consequent inability of the aggregating protein to ensure its physiological role. While it is widely accepted that aging represents the main risk factor for neurodegeneration, there is still no clear cut‐off line between the two conditions. Indeed, many of the pathways that are commonly altered in neurodegeneration—misfolded protein accumulation, chronic inflammation, mitochondrial dysfunction, impaired iron homeostasis, epigenetic modifications—have been often correlated also with healthy aging. This overlap could be explained by the fact that the continuous accumulation of cellular damages, together with a progressive decline in metabolic efficiency during aging, makes the neurons more vulnerable to toxic injuries. When a given threshold is exceeded, all these alterations might give rise to pathological phenotypes that ultimately lead to neurodegeneration.
A pollen–climate calibration from western Patagonia for palaeoclimatic reconstructions
Authors: Montade Vincent , Peyron Odile , Favier Charly , Francois Jean Pierre , Haberle Simon G. 
Published: January 2019

ABSTRACTPalaeoecological studies of sediment records from the western margins of southern South America have revealed vegetation dynamics to be under the influence of major regional climate drivers such as the Southern Westerly Winds, Southern Annular Mode and El Niño Southern Oscillation. Despite the substantial number of palynological records in this region, very few quantitative pollen‐based climate reconstructions using surface samples have been made. In this context, our objective was first to investigate the modern pollen–vegetation–climate relationships in the western Patagonian. The results show that the modern pollen dataset reflects the main vegetation types and that summer precipitation and winter temperature represent the main climate parameters controlling vegetation distribution. Secondly using this pollen–climate dataset we evaluate and compare the performance of two models (Weighted Averaging Partial Least Squares and Modern Analog Technique). We used these models to make climate reconstructions from two oceanic pollen records from western Patagonia. Compared with independent climate indicators, our pollen‐inferred climate reconstructions reveal the same overall trends, showing the potential of pollen–climate transfer functions applied to this region. This study provides much needed data for quantitative climate reconstructions in South America, but which also needs to be improved by enlarging the modern pollen dataset.
Infrared sensors using poly‐Si thin‐film transistors for proximity sensors integrated in smartphone displays
Authors: Kito Katsuya , Kitajima Shuhei , Matsuda Tokiyoshi , Inoue Masahide , Tamura Mitsuo , Kimura Mutsumi 
Published: January 2019

AbstractWe have developed infrared sensors using poly‐Si thin‐film transistors (TFTs) for proximity sensors integrated in smartphone displays. Initially, we evaluate the infrared sensitivities of the poly‐Si TFTs, and it is found that a pin‐type TFT is suitable for the infrared sensors. Next, we propose three types of the infrared sensors. First, an analog current detection‐type sensor has a simple structure, and it is found that it can detect presence of a hand. Second, a lock‐in detection‐type sensor has tolerance against ambient light, and it is found that it can detect a target signal under noise signals. Third, a frequency detection‐type sensor has an advantage that only a digital circuit is necessary for detection, and it is found that it can detect the infrared intensity because the oscillation frequency increases monotonically with the intensity. We can utilize these infrared sensors on demand.
Laryngeal mask versus intubation for adenoidectomies in children: Analysis of 1,500 operations
Authors: Gehrke Thomas , Hackenberg Stephan , Steinhübel Bernhard , Hagen Rudolf , Scherzad Agmal 
Published: January 2019

Objectives/HypothesisTo evaluate whether endotracheal intubations are superior to the use of laryngeal masks in the airway management for adenoidectomies in pediatric patients in terms of safety and duration of surgery.Study DesignRetrospective case series.MethodsA retrospective analysis of 1,500 adenoidectomies in children using laryngeal mask or endotracheal intubation for intraoperative ventilation between 2009 and 2017. Data collected included complications, duration of surgery, and duration of induction and emergence from anesthesia.ResultsThe use of laryngeal masks did not accelerate the time needed for induction and emergence of anesthesia although significantly increasing the duration of surgery itself. There also were significantly more complications during and after anesthesia when using a laryngeal mask. In 10% of the children, the laryngeal mask had to be replaced by an endotracheal tube intraoperatively.ConclusionsThere is no reason to recommend the use of a laryngeal mask as the first choice of airway management regarding adenoidectomies in children.Level of Evidence3 Laryngoscope, 129:E383–E388, 2019
Semi‐Nonlinear Nanophotonic Waveguides for Highly Efficient Second‐Harmonic Generation
Authors: Luo Rui , He Yang , Liang Hanxiao , Li Mingxiao , Lin Qiang 
Published: January 2019

AbstractQuadratic optical parametric processes form the foundation for various applications related to classical and quantum frequency conversion, and have attracted significant interest recently in on‐chip implementation. These processes rely on phase matching among the interacting guided modes, and refractive index engineering is a primary approach for this purpose. Unfortunately, modal phase‐matching approaches developed so far only produce parametric generation with fairly low efficiencies, due to the intrinsic modal mismatch of spatial symmetries. Here, a universal design and operation principle is proposed for highly efficient optical parametric generation on integrated photonic platforms. By breaking the spatial symmetry of the optical nonlinearity of the device, nonlinear parametric interactions can be dramatically enhanced. This principle is then employed to design and fabricate a heterogeneous titanium oxide/lithium niobate nanophotonic waveguide that is able to offer second‐harmonic generation with a theoretical normalized conversion efficiency as high as 2900, which enables the measurement of an experimental efficiency of 650, significantly beyond the reach of conventional modal phase‐matching approaches. Unlike nonlinearity domain engineering that is material selective, the proposed operation principle can be flexibly applied to any other on‐chip quadratic nonlinear platform, to support ultra‐highly efficient optical parametric generation.
Increased Dynamin‐Related Protein 1–Dependent Mitochondrial Fission Contributes to High‐Fat‐Diet‐Induced Cardiac Dysfunction and Insulin Resistance by Elevating Tafazzin in Mouse Hearts
Authors: Chang Wenguang , Xiao Dandan , Ao Xiang , Li Mengyang , Xu Tao , Wang Jianxun 
Published: January 2019

ScopeHigh fat (HF)‐diet‐induced insulin resistance is a major contributor to the pathogenesis of cardiovascular diseases. However, the molecular mechanisms that regulate cardiac insulin signaling are not fully understood. The regulatory role of tafazzin in the hearts of HF‐diet‐fed mice is investigated.Methods and resultsMice are fed a HF diet or low fat (LF) diet for up to 24 weeks. After 24 weeks, it is found that HF‐diet‐induced cardiac dysfunction is linked to overexpression of the mitochondrial protein tafazzin. Increased tafazzin promotes mitochondrial fission and impairs insulin signaling, which is mediated by dynamin‐related protein 1 (Drp‐1) translocation from the cytosol to the mitochondria. Furthermore, knockdown of tafazzin with siRNA inhibits palmitic‐acid–induced mitochondrial fission and restores insulin sensitivity. Moreover, miR‐125b‐5p as an upstream regulator targeting tafazzin is identified and palmitate‐induced insulin resistance further rescued.ConclusionIn HF‐diet‐fed mouse hearts, increased tafazzin contributes to insulin resistance via mediating Drp‐1 translocation to the mitochondria, and a small non‐coding RNA, miR‐125b‐5p, at least partially regulates this signaling pathway and alleviates insulin resistance.
Redox Proteomic Analysis Reveals Oxidative Modifications of Proteins by Increased Levels of Intracellular Reactive Oxygen Species during Hypoxia Adaptation of Aspergillus fumigatus
Authors: Shekhova Elena , Ivanova Lia , Krüger Thomas , Stroe Maria C. , Macheleidt Juliane , Kniemeyer Olaf , Brakhage Axel A. 
Published: January 2019

AbstractAspergillus fumigatus faces abrupt changes in oxygen concentrations at the site of infection. An increasing number of studies has demonstrated that elevated production of intracellular reactive oxygen species (ROS) under low oxygen conditions plays a regulatory role in modulating cellular responses for adaptation to hypoxia. To learn more about this process in A. fumigatus, intracellular ROS production during hypoxia has been determined. The results confirm increased amounts of intracellular ROS in A. fumigatus exposed to decreased oxygen levels. Moreover, nuclear accumulation of the major oxidative stress regulator AfYap1 is observed after low oxygen cultivation. For further analysis, iodoTMT labeling of redox‐sensitive cysteine residues is applied to identify proteins that are reversibly oxidized. This analysis reveals that proteins with important roles in maintaining redox balance and protein folding, such as the thioredoxin Asp f 29 and the disulfide‐isomerase PdiA, undergo substantial thiol modification under hypoxia. The data also show that the mitochondrial respiratory complex IV assembly protein Coa6 is significantly oxidized by hypoxic ROS. Deletion of the corresponding gene results in a complete absence of hypoxic growth, indicating the importance of complex IV during adaptation of A. fumigatus to oxygen‐limiting conditions.
Automated control of inspired oxygen (FiO2) in preterm infants: Literature review
Authors: Dani Carlo 
Published: January 2019

AbstractThe vast majority (95%) of very preterm infants receive oxygen‐therapy monitored by oxygen pulse saturation (SpO2). However, they spend a significant percentage of time out of the SpO2 target with a high risk of severe complications such as bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). Recently, systems allowing the automated control of inspired oxygen (FiO2) for patient delivery to maintain target SpO2 has been become commercially available. We reviewed literature and individuated sixteen studies on the effectiveness of automated control of FiO2 in preterm infants. These studies demonstrate that automated devices are significantly more effective than manual control in maintaining target SpO2 and in preventing hyperoxia, while they seem to be less effective in preventing hypoxia. The studies were very heterogeneous for design, population size, duration, and device used, and this precludes firm conclusions regarding effectiveness and best setting of these systems. Moreover, none of the studies investigated if automated control of FiO2 can actually improve outcome in preterm infants. We conclude that further large‐scale studies are warranted to assess the actual clinical relevance of these devices and to decide if they should become the standard of care.
Shock Initiation of Nano‐TATB Explosives under Short‐Duration Pulses
Authors: Guo Xiangli , Wang Jun , Ran Jianlong , Zhao Lulu , Han Yong , Cao Wei 
Published: January 2019

AbstractBecause of the potential of nano‐TATB as a charge in slapper detonator, the shock initiation threshold of nano‐TATB explosive was studied over short pulse durations (down to 0.017 μs) and high pressure ranges (up to 17 GPa). The pulses were produced by the impact of thin plastic flyer plates, which were accelerated by electrically exploded metal foils. Nano‐TATB powders with a mean particle size of 60 nm were prepared and pressed into cylindrical sample charges with three densities (1.56, 1.64 and 1.74 g/cm3). The flyer impact velocity data versus charging voltages was measured with different flyer thicknesses. Together with the Hugoniot relationships of flyer and samples, the impact pressures and pulse durations were calculated. By using Langlie method, the threshold pressures for shock initiation were determined. In case of the identical flyer plate, the threshold pressure increases with increasing density. In case of the identical explosive density, the threshold pressure increases as the thickness of the flyer decreases (i. e. the pulse duration decreases) except for the highest tested density. These data are represented well by a constant P2τ initiation criterion for the short, high‐pressure pulses and deviate from the P2τ behavior at lower pressures. Finally, nano‐TATB is proved to be a little more sensitive to short‐duration pulses than superfine TATB, but much more sensitive than production grade TATB.
Anticancer properties of erucin, an H2S‐releasing isothiocyanate, on human pancreatic adenocarcinoma cells (AsPC‐1)
Authors: Citi Valentina , Piragine Eugenia , Pagnotta Eleonora , Ugolini Luisa , Di Cesare Mannelli Lorenzo , Testai Lara , Ghelardini Carla , Lazzeri Luca , Calderone Vincenzo , Martelli Alma 
Published: January 2019

Plants of the Brassicaceae family are well‐known for containing the glucosinolate myrosinase system, which is able to release isothiocyanates after plant biotic and abiotic lesions. Erucin (ERU; 1‐isothiocyanato‐4‐(methylthio)‐butane), an isothiocyanate particularly abundant in arugula (Eruca sativa Mill., Eruca vesicaria L., etc.), derives from the hydrolysis of the glucosinolate glucoerucin by the enzyme myrosinase. Many other natural isothiocyanates influence cancer cells and, in particular, induce antiproliferative effects at relatively high concentrations. Similar antiproliferative effects have also been shown by the newly emerging gasotransmitter hydrogen sulfide (H2S) and by H2S‐releasing compounds. In a previous study, our group demonstrated that isothiocyanates release H2S in biological environments. In this work, we demonstrated the H2S‐donor properties of ERU in pancreatic adenocarcinoma cells (AsPC‐1) and delineated its profile as a chemopreventive or anticancer agent. Indeed, ERU showed significant antiproliferative effects: ERU inhibited AsPC‐1 cell viability at relatively high concentrations (30–100 μM). Moreover, ERU inhibited cell migration, altered the AsPC‐1 cell cycle, and exhibited proapoptotic effects. Finally, ERU inhibited ERK1/2 phosphorylation. This mechanism is particularly important in AsPC‐1 cells because they are characterized by a mutation in KRAS that determines KRAS hyperactivation followed by MAP‐kinase hyperphosphorylation, which plays a pivotal role in pancreatic cancer proliferation, growth, and survival.
Metabolic effect of berberine–silymarin association: A meta‐analysis of randomized, double‐blind, placebo‐controlled clinical trials
Authors: Fogacci Federica , Grassi Davide , Rizzo Manfredi , Cicero Arrigo F.G. 
Published: January 2019

The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta‐analysis of the available randomized, double‐blind, placebo‐controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed‐Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random‐effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: −25.3, 95% CI [−39.2, −11.4] mg/dl; p < 0.001), TG (MD: −28, 95% CI [−35.3, −20.6] mg/dl; p < 0.001), HDL‐C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL‐C (MD: −29.1, 95% CI [−39.7, −18.6] mg/dl; p < 0.001), and FPG (MD: −7.5, 95% CI [−13, −1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health.
Robust stability analysis of fractional‐order interval systems with multiple time delays
Authors: Mohsenipour Reza , Fathi Jegarkandi Mohsen 
Published: January 2019

SummaryThis paper investigates the robust stability analysis of fractional‐order interval systems with multiple time delays, including retarded and neutral systems. A bound on the poles of fractional‐order interval systems of retarded and neutral type is obtained. Then, the concept of the value set and zero exclusion principle is extended to these systems, and a necessary and sufficient condition is produced for checking the robust stability of them. The value set of the characteristic equation of the systems is obtained analytically and, based on it, an auxiliary function is introduced to check the zero exclusion principle. Finally, two numerical examples are given to illustrate the effectiveness of the results presented.