bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling
Authors: Jin Jun , Zhai Hong-Feng , Jia Zhen-Hua , Luo Xiao-Hua
Published: August 2019

Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in keloid formation remains elusive. In this study, hematoxylin-eosin, Masson, and immunohistochemical staining of type I collagen (ColI) revealed abnormal arrangement and hyperplasia of fibers in keloid tissues along with increased ColI level. qRT-PCR and Western blot showed that HOXA11-AS and ColI were significantly upregulated, while miR-124-3p was decreased in both keloid tissues and human keloid fibroblasts (HKFs). Knockdown of HOXA11-AS inhibited cell proliferation (by CCK-8 and immunofluorescence staining of Ki67) and cell migration (by wound healing and transwell assays). Mechanistic experiments verified that HOXA11-AS acted as a sponge of micro-RNA (miR)-124-3p and Smad5 was a target of miR-124-3p. miR-124-3p sufficiently reversed the regulatory effects of HOXA11-AS, and Smad5 was involved in miR-124-3p-mediated biological functions. Furthermore, HOXA11-AS induced ColI synthesis via sponging miR-124-3p-mediated Smad5 signaling, thus promoting keloid formation. Overall, our study implied that HOXA11-AS induces ColI synthesis to promoted keloid formation via sponging miR-124-3p-mediated Smad5 signaling, which might offer a novel target for developing the therapy of keloid formation.
LC-MS-based metabolomics analysis to identify meprin-β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury
Authors: Gooding Jessica , Cao Lei , Ahmed Faihaa , Mwiza Jean-Marie , Fernander Mizpha , Whitaker Courtney , Acuff Zach , McRitchie Susan , Sumner Susan , Ongeri Elimelda Moige
Published: August 2019

Meprin metalloproteases have been implicated in the pathophysiology of diabetic kidney disease (DKD). Single-nucleotide polymorphisms in the meprin-β gene have been associated with DKD in Pima Indians, a Native American ethnic group with an extremely high prevalence of DKD. In African American men with diabetes, urinary meprin excretion positively correlated with the severity of kidney injury. In mice, meprin activity decreased at the onset of diabetic kidney injury. Several studies have identified meprin targets in the kidney. However, it is not known how proteolytic processing of the targets by meprins impacts the metabolite milieu in kidneys. In the present study, global metabolomics analysis identified differentiating metabolites in kidney tissues from wild-type and meprin-β knockout mice with streptozotocin (STZ)-induced type 1 diabetes. Kidney tissues were harvested at 8 wk post-STZ and analyzed by hydrophilic interaction liquid chromatography ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Principal component analysis identified >200 peaks associated with diabetes. Meprin expression-associated metabolites with strong variable importance of projection scores were indoxyl sulfate, N-γ-l-glutamyl-l-aspartic acid, N-methyl-4-pyridone-3-carboxamide, inosine, and cis-5-decenedioic acid. N-methyl-4-pyridone-3-carboxamide has been previously implicated in kidney injury, and its isomers, 4-PY and 2-PY, are markers of peroxisome proliferation and inflammation that correlate with creatinine clearance and glucose tolerance. Meprin deficiency-associated differentiating metabolites with high variable importance of projection scores were cortisol, hydroxymethoxyphenylcarboxylic acid- O-sulfate, and isovaleryalanine. The data suggest that meprin-β activity enhances diabetic kidney injury in part by altering the metabolite balance in kidneys, favoring high levels of uremic toxins such as indoxyl sulfate and N-methyl-pyridone-carboxamide.
Visual epidural field potentials possess high functional specificity in single trials
Authors: Fischer Benjamin , Schander Andreas , Kreiter Andreas K. , Lang Walter , Wegener Detlef
Published: August 2019

Recordings of epidural field potentials (EFPs) allow neuronal activity to be acquired over a large region of cortical tissue with minimal invasiveness. Because electrodes are placed on top of the dura and do not enter the neuronal tissue, EFPs offer intriguing options for both clinical and basic science research. On the other hand, EFPs represent the integrated activity of larger neuronal populations and possess a higher trial-by-trial variability and a reduced signal-to-noise ratio due the additional barrier of the dura. It is thus unclear whether and to what extent EFPs have sufficient spatial selectivity to allow for conclusions about the underlying functional cortical architecture, and whether single EFP trials provide enough information on the short timescales relevant for many clinical and basic neuroscience purposes. We used the high spatial resolution of primary visual cortex to address these issues and investigated the extent to which very short EFP traces allow reliable decoding of spatial information. We briefly presented different visual objects at one of nine closely adjacent locations and recorded neuronal activity with a high-density epidural multielectrode array in three macaque monkeys. With the use of receiver operating characteristics (ROC) to identify the most informative data, machine-learning algorithms provided close-to-perfect classification rates for all 27 stimulus conditions. A binary classifier applying a simple max function on ROC-selected data further showed that single trials might be classified with 100% performance even without advanced offline classifiers. Thus, although highly variable, EFPs constitute an extremely valuable source of information and offer new perspectives for minimally invasive recording of large-scale networks.

NEW & NOTEWORTHY Epidural field potential (EFP) recordings provide a minimally invasive approach to investigate large-scale neural networks, but little is known about whether they possess the required specificity for basic and clinical neuroscience. By making use of the spatial selectivity of primary visual cortex, we show that single-trial information can be decoded with close-to-perfect performance, even without using advanced classifiers and based on very few data. This labels EFPs as a highly attractive and widely usable signal.
Effect of Ethanol-Derived Clove Leaf Extract on the Oxidative Stress Response in Yeast Schizosaccharomyces pombe
Authors: Fauzya Anninda Faiz , Astuti Rika Indri , Mubarik Nisa Rachmania
Published: August 2019

Compared to the widely explored antioxidant activity from the clove bud extract, less data are available regarding the potential pharmacological use of clove leaves. Our study aimed to explore the antioxidant activity of clove leaves extract in the cellular level. Thus, we used the yeast Schizosaccharomyces pombe as model organisms. Our data indicate that, following extract treatment (100 ppm), the viability of the stationary phase cells of S. pombe was higher than without extract and that of calorie restriction treatments. 100 ppm extract treatment also increased cell viability against H2O2-induced oxidative stress. Those data indicate that the extract could promote oxidative stress tolerance response in yeast cells, which occurred either during the stationary phase or due to exogenous exposure. Higher dose of extract (500 ppm) showed opposite effects, as cell viability was lower than that without treatment. Analysis toward the mitochondrial activity revealed that the extract did not induce mitochondrial activity unlike the calorie restriction treatment. Based on our data, clove leaf extract promotes oxidative stress tolerance response in the yeast S. pombe, independent to that mitochondrial adaptive ROS signaling which commonly occurs in calorie restriction-induced oxidative stress tolerance response.
Quality and Nutritional Value of Functional Strawberry Marmalade Enriched with Chia Seed (Salvia hispanica L.)
Authors: Özbek Tuğba , Şahin-Yeşilçubuk Neşe , Demirel Birsen
Published: August 2019

The aim of the study was to develop and characterize marmalade having functional food ingredients such as omega-3 fatty acid, dietary fiber, protein, and antioxidants with the addition of chia seed (Salvia hispanica L.). During the development of marmalade formulations, sweetener type and chia content in the strawberry marmalade were decided by two-step sensory analysis. In the first step, four different formulas were prepared separately by using sorbitol, isomalt, commercial Stevia™ powder, and isomalt together with sorbitol. The control formula was prepared with sucrose (refined commercial sugar). In the first part of the study, sensorial parameters showed good acceptability for sorbitol. Thereafter, in the second step, marmalades were prepared with 2.5% and 5% (by weight) chia seed including sorbitol. According to sensory panels, sorbitol had the highest acceptance level and the chia seed content was chosen to be used as 5% in the formulations. Chia seed and sorbitol addition increased the phenolic content by 15.45% and the dietary fiber content by 168% and decreased the caloric value by 48% compared to the control prepared with sucrose and without chia seed. The final product had 1.5% omega-3 fatty acid and could be declared as “omega-3 source” in the label. The viscosity of chia-added marmalade was found to be slightly higher than the viscosity of control, even though there was no distinct difference between the two samples. The gel-like character was more dominant in chia-added strawberry marmalade compared to the control. The addition of chia at 5% may contribute to the crosslinking without formation of a gel structure.
The Effectiveness and Safety of Acupoint Catgut Embedding for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis
Authors: Huang Fan , Xie Yumin , Zhao Siyi , Feng Zitong , Chen Guizhen , Xu Yunxiang
Published: August 2019

Purpose. To evaluate the effectiveness and safety of acupoint catgut embedding therapy (ACET) in postmenopausal osteoporosis (PMOP). Methods. Review of some databases from their inception to June 2018 and randomized controlled trials (RCTs) in which ACET with PMOP were included. Two researchers extracted and evaluated the information independently. Cochrane Collaboration’s tool and Jadad scale were used to evaluate the quality of the studies. RevMan V.5.3.3 software was used to carry out the meta-analysis while trial sequential analysis (TSA) performed with TSA 0.9 software. Results. 12 RCTs with 876 participants were included in this review. Meta-analysis showed that ACET alone was not superior to medication in effectiveness rate (RR= 1.11; 95% CI (0.89, 1.40); P=0.35) and E2 (SMD= 0.20; 95% CI (-0.17, 0.57); P=0.28; I2=20%) while ACET combining medication was more effective on the effectiveness rate (RR= 1.32; 95% CI (1.20, 1.46); P<0.000 01) and E2 (SMD= 1.24; 95% CI (0.63, 1.84); P<0.0001). Additionally, ACET combining calcium could increase the bone mineral density (BMD) of the L2~4 vertebrae and femur-neck [WMDL2~4 = 0.03; 95% CI (0.01, 0.05); P=0.003; and WMDFemur-neck = 0.07; 95% CI (0.03, 0.10); P = 0.0006], reduce TCM syndrome score [WMD = -1.85; 95% CI (-2.13, -1.57); P<0.000 01], improve patient’s quality of life [WMDthree  months = 6.90; 95% CI (3.90, 9.89); P<0.000 01; and WMDsix  months = 12.34; 95% CI (5.09, 19.60); P=0.0009], and relieve pain [WMDVAS = -1.26; 95% CI (-1.66, -0.85); P<0.000 01; and WMDPain  score = -2.59; 95% CI (-4.76, -0.43); P= 0.02]. The TSA showed that the effectiveness of ACET for PMOP was demonstrated accurately. Conclusions. ACET combining medication but not ACET alone is more effective than medication as comparison in the treatment of PMOP. As a novel treatment, ACET shows the potential of effectiveness and deserves further high quality of well-designed study.
Application of Meridian Electrical Conductance in the Setting of Acute Ischemic Stroke: A Cross-Sectional Study
Authors: Chang Shih-An , Weng Yi-Xiang , Cheng Shu-Chen , Chang Yeu-Jhy , Lee Tsong-Hai , Chang Chien-Hung , Chang Ting-Yu , Huang Kuo-Lun , Liu Chi-Hung , Hsu Chung-Yuan
Published: August 2019

Acupuncture is widely used for improving poststroke care. Knowing the condition of meridian can help traditional Chinese medicine (TCM) doctors make a tailored choice of acupoints for every patient. The establishment of an objective meridian energy measurement for acute ischemic stroke that can be used for future acupuncture treatment and research is an important area in stroke-assisted therapy. In this study, a total of 102 subjects diagnosed with acute ischemic stroke within 7 days of onset were recruited, and the meridian energy analysis device (MEAD) was used to record the meridian electrical conductance (MEC) values of twelve meridians on unaffected and affected limbs. We found that the MEC value of the twelve meridians on the affected limbs was significantly higher than that on the unaffected limbs (P=0.001). Compared with the unaffected limbs, there was a higher value of MEC on the affected limbs of the lung meridian, heart meridian, pericardium meridian, and small intestine meridian, with significant differences (P<0.05, P<0.001, P<0.001, and P<0.05, respectively). Further analysis revealed that the MEC values of both Yin and Yang meridians of the affected limbs were significantly higher than those of the unaffected limbs (P=0.001 and P<0.05, respectively). Meanwhile, the mean of the index of sympathovagal balance in patients with acute ischemic stroke (5.49 ± 4.21) was higher than the normal range (1–1.5), indicating autonomic imbalance. The results of this study are consistent with TCM theory as well as clinical observation and pathological mechanisms, suggesting that the measurement of MEC values may be used as a supplementary diagnostic method for acupuncture in patients with acute ischemic stroke.
Antioxidant Capacity and Behavioral Relevance of a Polyphenolic Extract of Chrysanthellum americanum in a Rat Model of Irritable Bowel Syndrome
Authors: Cojocariu Roxana , Ciobica Alin , Balmus Ioana-Miruna , Guenne Samson , Trifan Anca , Stanciu Carol , Hrițcu Luminita , Lefter Radu
Published: August 2019

Chrysanthellum americanum L. (Vatke) is a medicinal plant from the Compositae family used in west-African traditional medicine, known for its flavonoid and saponin richness and for its strong antioxidant potential. In the present study, we assessed the effects of Chrysanthellum americanum polyphenolic extract in the psychological stress-induced rat model of irritable bowel syndrome (IBS), a chronic functional digestive tract disorder marked by immune and inflammatory-related disturbances of central nervous and peripheral intestinal systems, which is often associated with mood disorders including depression and anxiety. Consequently, memory impairment, anxiety and depression behavioral indicators, and cerebral oxidative stress biomarker dynamics were evaluated in a multifactorial heterotypic stress-exposed IBS rats after 6-day gavage with polyphenolic C. americanum extract (100 mg/kg body weight). Y-maze, elevated plus maze, and forced swimming tests were used for assessing behavioral responses. Administration of the extract exhibited significant anxiolytic and antidepressant-like effects coupled with significantly increased temporal lobe antioxidant enzyme specific activity (superoxide dismutase and glutathione peroxidase) and decreased malondialdehyde levels, a well-known lipid peroxidation marker. Furthermore, linear regression statistical analyses showed significant correlations between the oxidative stress parameters and behavioral tests. In conclusion, our results suggest that the administration of Chrysanthellum americanum polyphenolic extract could ameliorate mood and cognitive disturbances related to stress-induced in an IBS rat model. This could be also related to cerebral oxidative stress status attenuation.
Research on the Hydrochemistry and Fault Control Mechanism of Geothermal Water in Northwestern Zhangzhou Basin
Authors: Gan Haonan , Wang Guiling , Wang Xiao , Lin Wenjing , Yue Gaofan
Published: August 2019

The Zhangzhou Basin (ZB) is one of the most important hydrothermal regions in the southeast coast of China, with abundant underground thermal water resources. The hydrothermal region is located within widely scattered acid igneous rocks. Because of the low permeability of granitoids, the geothermal water flow is strongly controlled by fault structures. Previous studies mainly focused on the center of ZB and provided little understanding on the geochemistry and fault controlling mechanism of peripheral areas of the basin. In this study, the chemical compounds and elements of both thermal and cold underground waters of the Northwestern Zhangzhou Basin (NZB) were tested. Using cluster analysis, geochemical analysis, chemical geothermometers, silica vs. enthalpy mixing model, and structural interpretation of remote sensing, this study found that the thermal water in the research area mixes with shallow cold water in different proportions. The reservoir temperature ranges from 106°C to 147°C and differs between different sides of the Tianbao-Jinshan Fault (TJF) due to fault control. The difference in the circulation depth of underground thermal water causes this reservoir temperature disparity. The circulation depth of underground thermal water in research area ranges from 3.65 km to 5.44 km, which means the circulation depth of thermal water of the northwestern area is deeper than that of the central area of the basin.
Theoretical Modeling of Long-Time Drug Release from Nitrosalicyl-Imine-Chitosan Hydrogels through Multifractal Logistic Type Laws
Authors: Craciun Anda-Mihaela , Barhalescu Mihaela Luminita , Agop Maricel , Ochiuz Lăcrămioara
Published: August 2019

Drug release is a complex phenomenon due to the large number of interdependent side effects that occur simultaneously, involving strong nonlinear dynamics. Therefore, since their theoretical description is difficult in the classical mathematics modelling, we have built a theoretical model based on logistic type laws, validated by the correlations with the experimental data, in a special case of drug release from hydrogels. The novelty of our approach is the implementation of multifractality in logistic type laws, situation in which any chaotic system, characterized by a small number of nonlinear interactions, gets memory and, implicitly, characterization through a large number of nonlinear interactions. In other words, the complex system polymer-drug matrix becomes “pseudo-intelligent.”
Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule
Authors: Zhuang Ze , Yu Dongjie , Chen Zheng , Liu Dezhao , Yuan Guohui , Yirong Ni , Sun Linlin , Liu Yuangao , He Ronghan , Wang Kun
Published: August 2019

Joint contracture is increasingly regarded as a clinical problem that leads to irreversible dysfunction of the joint. It is a pathophysiological process following joint injury, which is marked by the activation of myofibroblasts. There is currently no effective treatment for the prevention of joint contracture. Curcumin is a polyphenol pigment extracted from turmeric, which possesses anti-inflammatory, antioxidative, and antitumor properties. In the present study, we demonstrated that curcumin exerts a protective effect against joint contracture via the inhibition of myofibroblast proliferation and migration in a time- and concentration-dependent manner. Moreover, we indicated that phosphatase and tension homolog (PTEN) was downregulated in myofibroblasts in vitro and in the contracture capsule tissues of patients in vivo. Additionally, western blot analysis revealed a negative correlation between the expression levels of PTEN and the fibrosis marker protein alpha smooth muscle cell actin. Methylation-specific PCR results suggested that curcumin was able to demethylate PTEN in a similar manner to the demethylation agent 5-azacytidine, increasing PTEN expression and further inhibiting phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling. In conclusion, our data illustrate part of the mechanism of curcumin inhibition in joint contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of joint contracture.
Prediction Algorithm of Parameters of Toe Clearance in the Swing Phase
Authors: Miyake Tamon , Fujie Masakatsu G. , Sugano Shigeki
Published: August 2019

The adaptive control of gait training robots is aimed at improving the gait performance by assisting motion. In conventional robotics, it has not been possible to adjust the robotic parameters by predicting the toe motion, which is considered a tripping risk indicator. The prediction of toe clearance during walking can decrease the risk of tripping. In this paper, we propose a novel method of predicting toe clearance that uses a radial basis function network. The input data were the angles, angular velocities, and angular accelerations of the hip, knee, and ankle joints in the sagittal plane at the beginning of the swing phase. In the experiments, seven subjects walked on a treadmill for 360 s. The radial basis function network was trained with gait data ranging from 20 to 200 data points and tested with 100 data points. The root mean square error between the true and predicted values was 3.28 mm for the maximum toe clearance in the earlier swing phase and 2.30 mm for the minimum toe clearance in the later swing phase. Moreover, using gait data of other five subjects, the root mean square error between the true and predicted values was 4.04 mm for the maximum toe clearance and 2.88 mm for the minimum toe clearance when the walking velocity changed. This provided higher prediction accuracy compared with existing methods. The proposed algorithm used the information of joint movements at the start of the swing phase and could predict both the future maximum and minimum toe clearances within the same swing phase.
N-Acetyl-L-cysteine Protects Human Retinal Pigment Epithelial Cells from Oxidative Damage: Implications for Age-Related Macular Degeneration
Authors: Terluk Marcia R. , Ebeling Mara C. , Fisher Cody R. , Kapphahn Rebecca J. , Yuan Ching , Kartha Reena V. , Montezuma Sandra R. , Ferrington Deborah A.
Published: August 2019

Age-related macular degeneration (AMD) involves the loss of retinal pigment epithelium (RPE) and photoreceptors and is one of the leading causes of blindness in the elderly. Oxidative damage to proteins, lipids, and DNA has been associated with RPE dysfunction and AMD. In this study, we evaluated oxidative stress in AMD and the efficacy of antioxidant, N-acetyl-L-cysteine (NAC), in protecting RPE from oxidative damage. To test this idea, primary cultures of RPE from human donors with AMD (n=32) or without AMD (No AMD, n=21) were examined for expression of NADPH oxidase (NOX) genes, a source of reactive oxygen species (ROS). Additionally, the cells were pretreated with NAC for 2 hours and then treated with either hydrogen peroxide (H2O2) or tert-butyl hydroperoxide (t-BHP) to induce cellular oxidation. Twenty-four hours after treatment, ROS production, cell survival, the content of glutathione (GSH) and adenosine triphosphate (ATP), and cellular bioenergetics were measured. We found increased expression of p22phox, a NOX regulator, in AMD cells compared to No AMD cells (p=0.02). In both AMD and No AMD cells, NAC pretreatment reduced t-BHP-induced ROS production and protected from H2O2-induced cell death and ATP depletion. In the absence of oxidation, NAC treatment improved mitochondrial function in both groups (p<0.01). Conversely, the protective response exhibited by NAC was disease-dependent for some parameters. In the absence of oxidation, NAC significantly reduced ROS production (p<0.001) and increased GSH content (p=0.02) only in RPE from AMD donors. Additionally, NAC-mediated protection from H2O2-induced GSH depletion (p=0.04) and mitochondrial dysfunction (p<0.05) was more pronounced in AMD cells compared with No AMD cells. These results demonstrate the therapeutic benefit of NAC by mitigating oxidative damage in RPE. Additionally, the favorable outcomes observed for AMD RPE support NAC’s relevance and the potential therapeutic value in treating AMD.
Cell Type- and Exposure-Specific Modulation of CD63/CD81-Positive and Tissue Factor-Positive Extracellular Vesicle Release in response to Respiratory Toxicants
Authors: Stassen Frank R. M. , van Eijck Pascalle H. , Savelkoul Paul H. M. , Wouters Emiel F. M. , Rohde Gernot G. U. , Briedé Jacco J. , Reynaert Niki L. , de Kok Theo M. , Benedikter Birke J.
Published: August 2019

Chronic exposure to respiratory stressors increases the risk for pulmonary and cardiovascular diseases. Previously, we have shown that cigarette smoke extract (CSE) triggers the release of CD63+CD81+ and tissue factor (TF)+ procoagulant extracellular vesicles (EVs) by bronchial epithelial cells via depletion of cell surface thiols. Here, we hypothesized that this represents a universal response for different pulmonary cell types and respiratory exposures. Using bead-based flow cytometry, we found that bronchial epithelial cells and pulmonary fibroblasts, but not pulmonary microvascular endothelial cells or macrophages, release CD63+CD81+ and TF+ EVs in response to CSE. Cell surface thiols decreased in all cell types upon CSE exposure, whereas depletion of cell surface thiols using bacitracin only triggered EV release by epithelial cells and fibroblasts. The thiol-antioxidant NAC prevented the EV induction by CSE in epithelial cells and fibroblasts. Exposure of epithelial cells to occupational silica nanoparticles and particulate matter (PM) from outdoor air pollution also enhanced EV release. Cell surface thiols were mildly decreased and NAC partly prevented the EV induction for PM10, but not for silica and PM2.5. Taken together, induction of procoagulant EVs is a cell type-specific response to CSE. Moreover, induction of CD63+CD81+ and TF+ EVs in bronchial epithelial cells appears to be a universal response to various respiratory stressors. TF+ EVs may serve as biomarkers of exposure and/or risk in response to respiratory exposures and may help to guide preventive treatment decisions.
Spatiotemporal Changes and Frequency Analysis of Multiday Extreme Precipitation in the Huai River Basin during 1960 to 2014
Authors: Yin Yixing , Pan Xin , Yang Xiuqin , Wang Xiaojun , Wang Guojie , Sun Shanlei
Published: August 2019

Floods and droughts are more closely related to the extreme precipitation over longer periods of time. The spatial and temporal changes and frequency analysis of 5-day and 10-day extreme precipitations (PX5D and PX10D) in the Huai River basin (HRB) are investigated by means of correlation analysis, trend and abrupt change analysis, EOF analysis, and hydrological frequency analysis based on the daily precipitation data from 1960 to 2014. The results indicate (1) PX5D and PX10D indices have a weak upward trend in HRB, and the weak upward trend may be due to the significant downward trend in the 21st century, (2) the multiday (5-day and 10-day) extreme precipitation is closely associated with flood/drought disasters in the HRB, and (3) for stations of nonstationary changes with significant upward trend after the abrupt change, if the whole extreme precipitation series are used for frequency analysis, the risk of future floods will be underestimated, and this effect is more pronounced for longer return periods.
Safety and Clinical Efficacy of Yangxue Qingnao Granules in the Treatment of Chronic Cerebral Circulation Insufficiency: A Systematic Review and Meta-Analysis
Authors: Guo Jianbo , Xiong Xingjiang , Cao Yu , Ding Yukun , He Qingyong
Published: August 2019

To evaluate the safety and clinical efficacy of Yangxue Qingnao (YXQN) granules in the treatment of chronic cerebral circulation insufficiency (CCCI), electronic databases—PubMed, Embase, CNKI, VIP, and Wangfang—were searched for randomized controlled trials (RCTs) published up to January 2019. GRADE and RevMan 5.3.0 were used for grading and analysis, respectively. Fifteen trials involving 1211 CCCI patients were included. Subgroup analysis was performed owing to study heterogeneity. Compared to nimodipine plus routine treatment, YXQN granules plus routine treatment were more effective in increasing basilar artery (BA) blood flow velocity (mean difference (MD) = 3.34, 95% confidence interval (CI) = [2.31, 4.37],P<0.00001), vertebral artery (VA) blood flow velocity (MD = 0.52, 95% CI = [0.27, 0.76],P<0.0001), and internal carotid artery (ICA) blood flow velocity (MD = 7.46, 95% CI = [2.01, 12.90],P=0.007). In improving the clinical efficacy of traditional Chinese medicine (TCM) for symptoms such as headache, dizziness, and insomnia, YXQN granules plus routine treatment were shown to be superior to the following control treatments: nimodipine plus routine treatment (mean difference (M-H) = 4.21, 95% CI = [2.49, 7.12],P<0.00001), flunarizine plus routine treatment (mean difference (M-H) = 3.92, 95% CI = [1.36, 11.29],P=0.01), troxerutin plus routine treatment (mean difference (M-H) = 4.79, 95% CI = [2.20, 10.42],P<0.00001), and routine treatment (mean difference (M-H) = 6.13, 95% CI = [1.48, 25.34],P=0.01). Risk of bias was assessed in 15 trials. One analysis was graded using GRADE and showed poor results. Adverse events were not reported explicitly in all but one trial. Thus, this meta-analysis suggests that YXQN granules may be beneficial for patients with CCCI. However, owing to the poor quality of the clinical trials and small sample sizes, a definite conclusion on the efficacy and safety of YXQN granules cannot be drawn from existing information.
Improvement in Glycemic and Lipid Profiles in Type 2 Diabetics with a 90-Day Ketogenic Diet
Authors: Walton Chase M. , Perry Katelyn , Hart Richard H. , Berry Steven L. , Bikman Benjamin T.
Published: August 2019

Because low-carbohydrate diets are effective strategies to improve insulin resistance, the hallmark of type 2 diabetes, the purpose of reporting these clinical cases was to reveal the meaningful changes observed in 90 days of low-carbohydrate (LC) ketogenic dietary intervention in female type 2 diabetics aged 18-45. Eleven women (BMI 36.3 kg/m2) who were recently diagnosed with type 2 diabetes based on HbA1c over 6.5% (8.9%) volunteered to participate in an intensive dietary intervention to limit dietary carbohydrates to under 30 grams daily for 90 days. The main outcome was to determine the degree of change in HbA1c, while secondary outcomes included body weight, blood pressure, and blood lipids. The volunteers lost significant weight (85.7±3.2 kg to 76.7±2.8 kg) and lowered systolic (134.0±1.6 to 123.3±1.1 mmHg) and diastolic (89.9±1.3 to 82.6±1.0 mmHg) blood pressure. HbA1c dropped to 5.6%. Most blood lipids were significantly altered, including HDL cholesterol (43.1±4.4 to 52.3±3.3 mg/dl), triglycerides (177.0±19.8 to 92.1±8.7 mg/dl), and the TG : HDL ratio (4.7±0.8 to 1.9±0.2). LDL cholesterol was not significantly different. AST and ALT, plasma markers of liver health, were reported for eight patients and revealed no significant changes. These findings indicate that a short-term intervention emphasizing protein and fat at the expense of dietary carbohydrate functionally reversed the diabetes diagnosis, as defined by HbA1c. Furthermore, the intervention lowered body weight and blood pressure, while eliciting favorable changes in blood lipids.
Active‐Side Calculation Method for a Backhoe Hydraulic Excavator with Incomplete Digging Resistance in a Normal State
Authors: Ren Zhigui , Wang Junli , Chen Jin , Zhang Junfeng , Liu Jurong , Liang Yang , Sun Haoran
Published: August 2019

The digging resistance in a normal state is the key to excavator design and automated excavation. It is difficult to accurately predict, simulate, or directly measure the digging resistance in a normal state due to uncertainties in the soil properties and excavation parameters. In this paper, a research idea is proposed that uses the working device as the entry point to indirectly calculate the digging resistance in a normal state by measuring the motion parameters and the cylinder pressure intensity. Based on the rule of combination for spatial force systems, a method for combining and projecting the system of the digging resistance is proposed in which the system is projected as six parts, and the tangential force, normal force, and bending moment in the plane of symmetry of the working device are the objects of the solution to avoid redundant equations. Based on kinematics and dynamics models of the excavator and the force and moment equilibrium conditions of the working device, equations for the active‐side calculation of the incomplete digging resistance are derived. Based on these equations, the motion parameters of the working device and data on the cylinder pressure intensity obtained by measurement are used to calculate the incomplete digging resistance. The validation scheme and process proposed use the incomplete digging resistance as the external load to obtain the simulated stress of the working device through transient analysis. The simulated stress and the measured stress corresponding to the position of the measurement point are extracted and compared. The results show that there is a difference in the size of the numerical value between the simulated and measured stress, but the variation law is highly consistent, which validates the calculation method. In this paper, an active‐side calculation method is provided for the incomplete digging resistance in a normal state without considering the soil‐tool interaction relationships, which lays a theoretical foundation for the study of the digging resistance characteristics in a normal state, as well as excavator design and automated excavation.
Expressiveness of Bone Markers in Breast Cancer with Bone Metastases
Authors: Zulauf Nicole , Brüggmann Dörthe , Groneberg David , Oremek Gerhard Maximilian
Published: August 2019

Introduction: On a global scale, the malignant growth of mammary gland is the most common type of cancer in women. In the progress of mammary carcinoma, osseous metastatic invasion has a pivotal significance because it is a frequent complication occurring at an early stage of the disease. Background: Bone metastases in breast cancer patients lead to increased mortality and decreased health-related quality of life. Therefore, early diagnostic assessment and treatment is requested. Meanwhile the progress of the disease should be monitored closely. Regarding health-related quality of life and lifetime prolongation, osseous metastases should be early diagnosed, therapied, and monitored. Up to date the gold standard is the whole-body scintigraphy. This kind of bone imaging features has high sensitivity but shows loss of specificity. Aim: This study aims to investigate the diagnostic versatility of bone markers in its resorption and formation function to detect bone metastases in patients with breast cancer. Patients, Materials, and Methods: For this purpose, the concentration of competing bone processing tumor markers in serums of 78 patients was detected and analyzed. Two groups of women with mammary carcinoma with and without osseous metastases were built to examine the presence (or absence) of statistically significant disparity of tumor marker concentration. The tumor markers employed in this study were the carboxyterminal collagen type I telopeptid (CTX), known as beta-crosslaps (β-CTx), the alkaline phosphatase (AP), and its isoenzymes (especially the bone-specific AP [B-AP]). Additionally, the tumor markers for breast cancer (CA 15-3 and CEA) were analyzed in both groups. Results: Our results provide evidence that in both groups, tumor markers such as β-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both β-CTx and B-AP are able to fulfill the conditions of a competent appliance to detect osseous metastases of patients with mammary carcinoma. Conclusion: Concerning the urgency of early and frequent detection, staging, and disease monitoring of mammary carcinoma with osseous metastases, this study renewed and underlined the importance of biochemical tumor markers – especially β-CTx and B-AP – and laid a clinical-based cornerstone to build up on a prospective research.
Electroencephalography in Psychiatric Surgery: Past Use and Future Directions
Authors: Mithani Karim , Meng Ying , Abrahao Agessandro , Mikhail Mirriam , Hamani Clement , Giacobbe Peter , Lipsman Nir
Published: August 2019

The last two decades have seen a re-emergence of surgery for intractable psychiatric disease, in large part due to increased use of deep brain stimulation. The development of more precise, image-guided, less invasive interventions has improved the safety of these procedures, even though the relative merits of modulation at various targets remain under investigation. With an increase in the number and type of interventions for modulating mood/anxiety circuits, the need for biomarkers to guide surgeries and predict treatment response is as critical as ever. Electroencephalography (EEG) has a long history in clinical neurology, cognitive neuroscience, and functional neurosurgery, but has limited prior usage in psychiatric surgery. MEDLINE, Embase, and Psyc-INFO searches on the use of EEG in guiding psychiatric surgery yielded 611 articles, which were screened for relevance and quality. We synthesized three important themes. First, considerable evidence supports EEG as a biomarker for response to various surgical and non-surgical therapies, but large-scale investigations are lacking. Second, intraoperative EEG is likely more valuable than surface EEG for guiding target selection, but comes at the cost of greater invasiveness. Finally, EEG may be a promising tool for objective functional feedback in developing “closed-loop” psychosurgeries, but more systematic investigations are required.
Accuracy of the Cognitive Assessment Battery in a Primary Care Population
Authors: Kvitting Anna S. , Johansson Maria M. , Marcusson Jan
Published: August 2019

Background: There are several cognitive assessment tools used in primary care, e.g., the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment. The Cognitive Assessment Battery (CAB) was introduced as a sensitive tool to detect cognitive decline in primary care. However, primary care validation is lacking. Therefore, we investigated the accuracy of the CAB in a primary care population. Objective: To investigate the accuracy of the CAB in a primary care population. Methods: Data from 46 individuals with cognitive impairment and 33 individuals who visited the primary care with somatic noncognitive symptoms were analyzed. They were investigated with the MMSE, the CAB, and a battery of neuropsychological tests; they also underwent consultation with a geriatric specialist. The accuracy of the CAB was assessed using c-statistics and the area under the receiver operating characteristic curve (AUC) was used to quantify the binary outcomes (“no cognitive impairment” or “cognitive impairment”). Results: The “cognitive impairment” group was significantly different from the unimpaired group for all the subtests of the CAB. When accuracy was based on binary significant reduction or not in one or several domains of the CAB, the AUC varied between 0.685 and 0.772. However, when a summation or logistic regression of several subcategories was performed, using the numerical values for each subcategory, the AUC was >0.9. For comparison, the AUC for the MMSE was 0.849. Conclusions: The accuracy of the CAB in a primary care population is poor to good when using binary cutoffs. Accuracy can be improved to high when using a summation or logistic regression of the numerical data of the subcategories. Considering CAB time, lack of adequate age norms, and a good accuracy for the MMSE, implementation of the CAB in primary care is not recommended at present based on the results of this study.
miR-29b Reverses T helper 1 cells/T helper 2 cells Imbalance and Alleviates Airway Eosinophils Recruitment in OVA-Induced Murine Asthma by Targeting Inducible Co-Stimulator
Authors: Yan Jurong , Zhang Xuemei , Sun Si , Yang Ting , Yang Jing , Wu Guangying , Qiu Yulan , Yin Yibing , Xu Wenchun
Published: August 2019

Asthma is a complex chronic disease and the pathogenesis is still not entirely clear. In this study, we aimed to clarify the role and mechanism of miR-29b in the development of asthma. We observed that miR-29b levels were decreased in the lung and spleen of OVA-induced asthmatic mice. Reverse transcription-quantitative polymerase chain reaction and flow cytometry demonstrated that the inducible co-stimulator (ICOS) expression at mRNA and protein levels was elevated in the lung of asthmatic mice, and miR-29b expression in the lung of asthmatic mice was negatively associated with ICOS mRNA levels by Pearson Correlation analysis. Additional, flow cytometry showed that the percentage of CD4+ICOS+ T cells in the lung and spleen was regulated by miR-29b, and dual luciferase reporter assay confirmed ICOS was a target gene of miR-29b. Furthermore, miR-29b overexpression in asthmatic mice was induced with miR-29b agomir by intranasal administration; miR-29b alleviated total inflammatory cell infiltration and CCL24 levels, decreased IL-5 levels in bronchoalveolar lavage fluid and serum, and upregulated IFN-γ expression in serum. This study demonstrates that miR-29b targets ICOS, thereby reverses the imbalance of T helper 1 cells (Th1)/Th2 responses and decreases eosinophils recruitment in the airway, which are key features of allergic airway inflammation. Therefore, miR-29b might be an attractive candidate target for asthma treatment.
Acordo de leniência na Lei Anticorrupção:
Authors: Marrara Thiago
Published: August 2019

O artigo examina o programa de leniência da Lei Anticorrupção, especialmente no tocante ao art. 16. Inicia com as definições de “acordo” e de “programa” de leniência. Em seguida, aborda o regime jurídico da leniência na Lei Anticorrupção, destacando seus benefícios gerais para os infratores colaboradores. Aponta e debate, ademais, as deficiências e falhas desse programa de leniência e como o governo buscou resolvê-los, por exemplo, com a frustrada Medida Provisória 703. Enfim, aborda-se o regime infralegal do acordo, no intuito de destacar seus avanços e situações em que a Administração Pública exorbitou de seu poder regulamentar.
A era Meiji nos textos de Eça de Queirós
Authors: Vanzelli José Carvalho
Published: August 2019

Best known as one of the major Lusophone novelists, Eça de Queirós (1845-1900) was also a prolific journalist. He wrote since the 60s of the nineteenth century to the end of his life in various Portuguese, Brazilian and French journals. Although he never visited Japan, the author of Os Maias dedicated some texts (or parts of texts) to the Meiji society. In this article we intend to examine how the famous Portuguese writer represented the “Land of the Rising Sun” to his readers, verifying if there is a consonant or dissonant discourse with the Japonistic aesthetics, present in Europe’s fin-de-siècle.
Os desafios para a eliminação da pena de morte no Japão
Authors: Yamamoto Lilian
Published: August 2019

Death penalty has been present in most part of Japanese history. In the opposite direction of the majority of the developed countries, there is not any short-medium term perspective it will be abolished from the Japanese penal system. This article intends to investigate what are the reasons for the predominance of its favorable position and its retention, in special, the public opinion and governmental politics. Before that, it will analyze the evolution of its execution methods, a discussion of its constitutionality, as well as its retentionist reasonings. Eventually, it aims to demonstrate that the public opinion polls can generate results according to the interests of those who carry them out.
Hagiwara Sakutarô, Buddhist realism, and the establishment of japanese modern poetry
Authors: Machado Roberto Pinheiro
Published: August 2019

This article approaches the works of poet Hagiwara Sakutarô (1886-1942) from a comparative perspective that engages philosophy and literature. The philosophical dimension of Sakutarô’s poetry is analyzed by means of inter-textual readings that draw on the tradition of Buddhist epistemology and on the texts of logicians Dignāga and Dharmakīrti (5th century). The comparative analysis is considered under the perspective of the influence of Naturalism and the use of description in the emergence of Japanese modern poetry. Pointing to the possibility of a Buddhist realism that shares some common characteristics with Naturalism, the article emphasizes the Buddhist dimension of Sakutarô’s poetry, which appears in spite of the poet’s turn to Western philosophy (notably to Schopenhauer, Nietzsche, and Kant), as well as to his overt rejection of Buddhism as a necessary step to the modernization of the Japanese letters.
Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation
Authors: Stratton Matthew S. , Bagchi Rushita A. , Felisbino Marina B. , Hirsch Rachel A. , Smith Harrison E. , Riching Andrew S. , Enyart Blake Y. , Koch Keith A. , Cavasin Maria A. , Alexanian Michael , Song Kunhua , Qi Jun , Lemieux Madeleine E. , Srivastava Deepak , Lam Maggie P.Y. , Haldar Saptarsi M. , Lin Charles Y. , McKinsey Timothy A.
Published: August 2019

Rationale:

Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear whether this chromatin reader protein functions in cell type-specific manner to control pathological myocardial fibrosis. Furthermore, the molecular mechanisms by which BRD4 stimulates the transcriptional program for cardiac fibrosis remain unknown.

Objective:

We sought to test the hypothesis that BRD4 functions in a cell-autonomous and signal-responsive manner to control activation of cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart.

Methods and Results:

RNA-sequencing, mass spectrometry, and cell-based assays employing primary adult rat ventricular fibroblasts demonstrated that BRD4 functions as an effector of TGF-β (transforming growth factor-β) signaling to stimulate conversion of quiescent cardiac fibroblasts into
Periostin
(
Postn
)-positive cells that express high levels of extracellular matrix. These findings were confirmed in vivo through whole-transcriptome analysis of cardiac fibroblasts from mice subjected to transverse aortic constriction and treated with the small molecule BRD4 inhibitor, JQ1. Chromatin immunoprecipitation-sequencing revealed that BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the
Sertad4
(SERTA domain-containing protein 4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 MAPK (mitogen-activated protein kinase) and provide evidence of a critical function for
Sertad4
in TGF-β-mediated cardiac fibroblast activation.

Conclusions:

These findings define BRD4 as a central regulator of the pro-fibrotic cardiac fibroblast phenotype, establish a p38-dependent signaling circuit for epigenetic reprogramming in heart failure, and uncover a novel role for
Sertad4
. The work provides a mechanistic foundation for the development of BRD4 inhibitors as targeted anti-fibrotic therapies for the heart.