bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial hematoma following ruptured anterior communicating artery aneurysms: risk factors, outcome, and prognostic factors after management of coiling first
Authors: Ni Heng , Zhao Lin-Bo , Liu Sheng , Jia Zhen-Yu , Cao Yue-Zhou , Shi Hai-Bin
Published: June 2021

Background

To determine the risk factors for intracranial hematoma (ICH) development following ruptured anterior communicating artery (AcomA) aneurysms and to determine prognostic factors associated with unfavorable outcomes after coiling first.

Methods

From March 2014 to February 2020, 235 patients with ruptured AcomA aneurysms underwent endovascular treatment in our department. The clinical and radiographic conditions were collected retrospectively. Modified Rankin Scale (mRS) scores of ≤ 2 were accepted as favorable outcomes. Univariate and multivariate logistic regressions were performed to identify significant factors contributing to the incidence of ICHs and to unfavorable outcomes.

Results

Of these 235 patients, 68 had additional ICHs. A posterior orientation of ruptured AcomA aneurysms was the independent variable associated with the incidence of ICHs (OR 3.675; p<0.001). Furthermore, having preoperative Hunt–Hess grades Ⅳ–Ⅴ was an independent variable associated with unfavorable outcomes for ICH patients (OR 80.000; p<0.001). Among the 68 patients with ICHs, 40% (27/68) had Hunt–Hess grades IV–V. Four percent of patients (3/68) underwent surgical hematoma evacuation after the coiling procedure and 15% of the patients (10/68) underwent external ventricular drainage. A favorable outcome was achieved in 72% (49/68) of patients with ruptured AcomA aneurysms. The mortality rate was 21% (14/68) at 6 months.

Conclusion

A posterior orientation of ruptured AcomA aneurysms was associated with the incidence of ICHs. Coiling first with surgical management if necessary seems to be an acceptable treatment for ruptured AcomA aneurysms with ICHs. The clinical outcome was associated with the clinical neurological status on admission.
Molecular diet analysis of the marine fish-eating bat (Myotis vivesi) and potential mercury exposure
Authors: Drinkwater Rosie , Goodwin Alice , Cush Jake , Korstian Jennifer M. , Chumchal Matthew M. , Herrera M. L. Gerardo , Valdez Martha , Otálora-Ardila Aída , Flores-Martinez José Juan , Clare Elizabeth L.
Published: June 2021

Mercury is a toxic element acquired by animals through feeding which can accumulate within food chains through biomagnification. This possesses particular risks to higher trophic levels and may unduly impact marine foraging species or individuals. The fish-eating bat (Myotis vivesi Menegaux, 1901) inhabits islands in the Gulf of California and can act as a predator in the marine environment. A predominantly marine diet and a high trophic position increase the risk of mercury exposure owing to increased bioaccumulation. Using molecular techniques to reconstruct diet, we show that M. vivesi regularly feeds on small fishes and crustaceans, particularly on the Californian anchovy (Engraulis mordax Girard, 1854) and a krill species (Nyctiphanes simplex Hansen, 1911). Additionally, we identify significant interannual variation in diet composition within this population, but measured levels of total mercury in faecal samples were not related to dietary diversity or trophic level.
Fathead minnow exposed to environmentally relevant concentrations of metformin for one life cycle show no adverse effects
Authors: Parrott Joanne L. , Pacepavicius Grazina , Shires Kallie , Clarence Stacey , Khan Hufsa , Gardiner Madelaine , Sullivan Cheryl , Alaee Mehran
Published: June 2021

Metformin is a glucose-lowering drug taken for diabetes. It is excreted by humans in urine and detected in municipal wastewater effluents and rivers. Fathead minnows ( Pimephales promelas) were exposed over a life cycle to measured concentrations of metformin: 3.0, 31, and 322 μg/L. No significant changes were observed in survival, maturation, growth, condition factor, or liver size. Relative ovary size of females exposed to 322 μg/L metformin was significantly larger than controls. There was no induction of vitellogenin in plasma of minnows, and gonad maturation was not statistically different from controls. The start of breeding was delayed by 9–10 d in the mid- and high metformin treatments (statistically significant only in the mid-concentration), but numbers and quality of eggs were not statistically different from controls. There were no effects of metformin on survival or growth of offspring. Exposure to metformin at environmentally relevant concentrations (i.e., 3.0 and 31 μg/L metformin) caused no adverse effects in fathead minnows exposed for a life cycle, with the exception of a delay in time to first breeding (that did not impact overall egg production). The results of the study are important to help understand whether metformin concentrations in rivers and lakes can harm fishes.
Demand Information Sharing in the Presence of B2B Spot Market
Authors: Ma Shanshan , Wang Liyan
Published: June 2021

Companies have started to use a business-to-business (B2B) spot market in combination with their traditional long-term procurement contracts to procure intermediate goods. This study investigates whether or not the market players should share their demand forecast information with one another in a supplier — manufacturer supply chain and assess the benefits of sharing information in the presence of the B2B spot market. First, the supplier and manufacturer make forecast on the demand, and during this period they select an information-sharing arrangement, that is, whether to share information or not. Then, the supplier sets the wholesale price and the manufacturer submits an order after observing the wholesale price. Both the supplier and manufacturer can trade their intermediate goods in a B2B spot market. We find that the manufacturer can infer the supplier’s demand forecast from the wholesale price in the non-information-sharing case, but the supplier cannot enjoy such an advantage. We also find that information sharing benefits both the supplier and the manufacturer, if and only if demand and spot price are positively correlated and the supplier’s expectation of the manufacturer’s forecast is medium. By contrast, obtaining more demand forecast information can hurt supply chain players. Information sharing benefits the manufacturer but hurts the supplier when the supplier’s expectation of the manufacturer’s forecast is high. However, when the supplier’s expectation of the manufacturer’s forecast is low, information sharing benefits the supplier but hurts the manufacturer.
First-order phase transition in 97,98Mo isotopes
Authors: Rahmatinejad A. , Razavi R. , Elahizadeh L.
Published: June 2021

Experimental evidences of a first-order phase transition from a superfluid to a non-interacting Fermi gas system are studied for [Formula: see text]Mo isotopes. The experimental observations are compared with the semi-empirical macroscopic model and superfluid formalism. We have shown that the entropy excess ratio introduced in our previous publications within the superfluid model can describe the first-order phase transition due to pair-breaking in atomic nuclei.
Painlevé analysis of Fokas–Lenells equation with fractal temporal evolution
Authors: Raza Nauman , Yasmeen Adeela
Published: June 2021

This paper presents new optical solitons of a fractal Fokas–Lenells equation that models the dynamics of optical fibers. The Painlevé technique is employed to identify kink soliton solutions. The constraint conditions guarantee the existence of these solitons. The outcomes of this research give new solutions that are not achieved using some already defined algorithms. The derived method is efficient and its applications are promising for other nonlinear problems. The 3D graphical illustrations of obtained results are depicted for various values of the fractal parameter.
Improved Redundant Binary Adder Realization in FPGA
Authors: Sahu Satya Ranjan , Bhoi Bandan Kumar , Pradhan Manoranjan
Published: June 2021

This paper presents the design of improved redundant binary adder (IRBA) by utilizing positive–negative encoding rules in FPGA platform. The proposed design deals with inverted encoding of negative binary (IEN) and positive binary number to get addition result using readily available standard hardware module. The Verilog hardware description language is used as design entry for synthesis of the proposed architecture in Xilinx ISE Desisn Suite 14.4 software. This structure is realized on Vertex-4 xc4vfx12-12sf363 FPGA device. The proposed IRBA is found to be time efficient in comparison with the performance parameters such as propagation delay and area over previous reported architecture.
Intent Identification in Unattended Customer Queries Using an Unsupervised Approach
Authors: Rebelo Hugo D. , de Oliveira Lucas A. F. , Almeida Gustavo M. , Sotomayor César A. M. , Rochocz Geraldo L. , Melo Willian E. D.
Published: June 2021

Customer’s satisfaction is crucial for companies worldwide. An integrated strategy composes omnichannel communication systems, in which chabot is widely used. This system is supervised, and the key point is that the required training data are originally unlabelled. Labelling data manually is unfeasible mainly nowadays due to the considerable volume. Moreover, customer behaviour is often hidden in the data even for experts. This work proposes a methodology to find unknown entities and intents automatically using unsupervised learning. This is based on natural language processing (NLP) for text data preparation and on machine learning (ML) for clustering model identification. Several combinations for preprocessing, vectorisation, dimensionality reduction and clustering techniques, were investigated. The case study refers to a Brazilian electric energy company, with a data set of failed customer queries, that is, not met by the company for any reason. They correspond to about 30% (4,044 queries) of the original data set. The best identified intent model employed stemming for preprocessing, word frequency analysis for vectorisation, latent Dirichlet allocation (LDA) for dimensionality reduction, and mini-batch [Formula: see text]-means for clustering. This system was able to allocate 62% of the failed queries in one of the seven found intents. For instance, this new labelled data can be used for the training of NLP-based chatbots contributing to a greater generalisation capacity, and ultimately, to increase customer satisfaction.
Nonlinear Analysis of Frames with Shear Deformation using Higher-Order Mixed Finite Elements
Authors: Petrolito J. , Ionescu D.
Published: June 2021

Until recently, linear analysis has been considered sufficient for the static analysis of structural frames. Nonlinear effects, if included, have tended to be considered at the element level rather than at the complete structure level. However, recent changes in codes of practice have been introduced that require a more complete nonlinear analysis to be performed. While these requirements should lead to a more accurate analysis, there has been little guidance given to the type and implementation of such an analysis. Moreover, different implementations have been adopted by various commercial software. In this paper, we discuss the use of mixed finite elements for the large deflection analysis of two-dimensional frames including shear deformation. In particular, we develop a family of elements that can be combined with different nonlinear models and discuss the effects of various assumptions and approximations that are commonly used to simplify the analysis. Examples are given to illustrate the various issues discussed.
Geographical, Molecular, and Computational Analysis of Migraine-Causing Genes
Authors: Naveed Muhammad , Bukhari Bakhtawar , Afzal Nadia , Sadia Haleema , Meer Bisma , Riaz Tanzeela , Ali Urooj , Ahmed Naveed
Published: June 2021

Migraine is a re-occurring type of headache and causes moderate-to-severe pain that is troubling or pulsing. The pain occurs in half of the head, and common symptoms are photophobia, phonophobia, nausea, depression, anxiety, vomiting, etc. This study evaluates the prevalence of migraine and responsible genes through molecular modeling in the region of Bahawalpur, Pakistan. This research was aimed to determine the prevalence of migraine-causing genes in the population of Bahawalpur and also to do molecular and in-silico analysis of migraine-causing gene as no similar research was conducted before. The disease was characterized and diagnosed under the criteria of the Second Edition of the International Classification of Headache Disorders and molecular identification of migraine-causing genes, i.e. GRIA1, GRIA3, and ESR1, by PCR amplification. The total number of samples collected for migraine patients was 230, out of which 30 were positive for PCR amplification of the genes GRIA1, GRIA3, and ESR1. Therapeutic potentials of commercial drugs, namely Cyclobenzaprine, Divalproex, Ergotamine, and Sumatriptan, were analyzed in silico through molecular docking. Ergotamine demonstrated the highest binding affinity of [Formula: see text]8.4 kcal/mol for the target molecule and, hence, the highest potential. The bivariate analysis showed that the prevalence of migraine concerning gender and age was significantly correlated ([Formula: see text], [Formula: see text]). It was observed that almost 31.4% of women suffered from headaches daily, 70% weekly, 28.1% monthly, and 23.5% rarely. Comparatively, only 8.3% of males suffered from daily headaches, 34% weekly, 12.8% monthly, and 14.9% rarely. The study shows promising results and encourages future researchers to conduct such a comprehensive epidemiological study on an even larger population to justify a more precise association of risk factors involved in migraine pathophysiology.
A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely
Authors: Suhail Mohd.
Published: June 2021

It has been a great challenge for scientists to develop an anti-Covid drug/vaccine with fewer side effects, since the coronavirus pandemic began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle facing the world is not only the positive test of the patient recovered from coronavirus, but also the second wave of Covid-19. Hence, the world demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also ejects it or its material from the body completely. The current computational study not only utilizes a structure-based drug design approach to find possible drug candidates but also explains (i) why the prescription of chiral drugs was not satisfactory, (ii) what types of modification can make their prescription satisfactory, (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M[Formula: see text]) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the M[Formula: see text] of JC virus and SARS-CoV-2 were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The M[Formula: see text] of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The prescription of a combination of S-[Formula: see text]-hydroxychloroquine and [Formula: see text]-mefloquine is considered as a boon by the predicted study.
Elucidation of Ligand/Protein Interactions between BCR-ABL Tyrosine Kinase and Some Commercial Anticancer Drugs Via DFT Methods
Authors: İş Yusuf Serhat
Published: June 2021

In this study, the interactions of 7 commercially available BCR-ABL tyrosine kinase enzyme inhibitors with amino acids in the active site of the relevant enzyme were investigated quantum mechanically. Here a per-residue study was carried out. Interaction energies were calculated by using the coordinates of the critical residues in the binding site of the enzyme and the drug molecules docked in this region. DFT methods were used during the QM processes. All interaction energies were calculated via M06-2X functional and 6-31G (d,p) basis set in vacuum. Based on the results obtained, it was tried to be determined which of the important residues in the binding cavity of the enzyme could better interact with the examined ligands. It is thought that this study may contribute to the development of tyrosine kinase enzyme inhibitors.
Understanding the Transport of Atmospheric Gases in Liquid Electrolytes for Lithium–Air Batteries
Authors: Haas Ronja , Murat Michael , Weiss Manuel , Janek Jürgen , Natan Amir , Schröder Daniel
Published: June 2021

In metal–air batteries, carbon dioxide (CO2) and nitrogen (N2) are, apart from oxygen (O2), also present as dissolved species in the liquid electrolyte. These dissolved gases can strongly influence the battery performance, as they affect the discharge mechanism and the stability of the lithium metal anode. Therefore, their solubility and diffusivity are important parameters, that are rarely considered in the development of electrolytes for metal–air batteries. In this work, the diffusion coefficients (D) and Henry’s law solubility constants (H

cp
) of O2, N2 and CO2 in common ether-based (diglyme (2G), triglyme (3G) and tetraglyme (4G)) and DMSO-based electrolytes are measured by means of gas uptake measurements. Additionally, the diffusion coefficients are calculated through molecular dynamics simulations. The results agree well with the experimental data. Furthermore, the influence of solvent parameters, such as surface tension and viscosity, on the solubility and the diffusivity as well as the impact of the addition of LiTFSI as conducting salt are investigated. The reported data will help to assess the impact of dissolved gases on the cell chemistry of nonaqueous lithium–air batteries, especially on the solid electrolyte interphase (SEI) at the lithium anode, and to predict diffusivity and gas solubility in other electrolytes.
Government Subsidies and Enterprise Innovation: Evidence from China's Photovoltaic Industry
Authors: Jiang Cailou , Liu Dehai , Zhu Qin , Wang Lu
Published: June 2021

Government subsidies (GSs) have triggered a remarkable increase in the production capacity of photovoltaic (PV) electricity in China. However, the lack of core technologies has limited PV enterprises’ competitiveness in the global market. This research investigates the impacts of R&D subsidies and non-R&D subsidies on the innovation in PV enterprises. With samples of Chinese listed PV enterprises from 2010 to 2019, this study finds R&D subsidies exert a notable positive impact on the innovation in PV enterprises. In small and medium enterprises (SMEs) and enterprises without state-owned shares, both R&D subsidies and non-R&D subsidies have positive impacts on the innovation. Considering the policy orientation, R&D subsidies granted under demand-orientation policies promote the innovation in PV enterprises. The government should increase the amount of R&D subsidies, optimize the R&D subsidies’ evaluation mechanism, and reasonably grant R&D subsidies from the demand side.
Uncovering the Protective Mechanism of the Volatile Oil of Acorus tatarinowii against Acute Myocardial Ischemia Injury Using Network Pharmacology and Experimental Validation
Authors: Zang Zhen-Zhong , Chen Li-Mei , Liu Yuan , Guan Yong-Mei , Du Qing , Xu Pan , Shen Qian , Yang Ming , Liu Hong-Ning , Liao Zheng-Gen
Published: June 2021

Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.
Edge Detection of Agricultural Products Based on Morphologically Improved Canny Algorithm
Authors: Yu Xiaokang , Wang Zhiwen , Wang Yuhang , Zhang Canlong
Published: June 2021

The traditional canny edge detection algorithm has its limitations in the aspect of antinoise interference, and it is susceptible to factors such as light. To solve these defects, the Canny algorithm based on morphological improvement was proposed and applied to the detection of agricultural products. First, the algorithm uses the open and close operation of morphology to form a morphological filter instead of the Gaussian filter, which can remove the image noise and strengthen the protection of image edge. Second, the traditional Canny operator is improved to increase the horizontal and vertical templates to 45° and 135° to improve the edge positioning of the image. Finally, the adaptive threshold segmentation method is used for rough segmentation, and on this basis, double detection thresholds are used for further segmentation to obtain the final edge points. The experimental results show that compared with the traditional algorithm applied to the edge detection of agricultural products, this algorithm can effectively avoid the false contour caused by illumination and other factors and effectively improve the antinoise interference while more accurate and fine detection of the edge of real agricultural products.
Refinement of a Deflection Basin Area Index Method for Rigid Pavement
Authors: Zhang Jin , Lv Qiuzhen , Shi Wei , Li Guangsheng , Zhang Jiafeng
Published: June 2021

The accuracy of the prediction and reliability of the deflection basin area index method for rigid pavement heavily depend on the sensor layout scheme and the calculation theory. A total of 154 groups of deflection data were generated by the finite element software in different conditions, and the simulated results were in good agreement with the analytical solutions of thin plates on elastic foundation. The accuracy of several types of deflection basin area index methods was assessed with the database of pavement deflection results. It is found that, apart from densifying the distal sensor layouts locally, replacing the deflection value of a specific point with the average of all measured points in the deflection basin area index was also an effective measure to improve the back‐calculation accuracy of pavement structural parameters up to 40%. Finally, a new deflection basin area index method was proposed based on the deflection database with the regression analysis. Comparisons between the theoretical calculations of several models and the practical deflection data of an airport in northern China revealed that the newly proposed method performs better on the back‐calculation accuracy and efficiency, which can provide a valuable guideline for the practical engineering in the design.
Woody Species Diversity and Structure of Protected Woodlands Adjacent to Free Grazing Land Woodland at Dugda Woreda, Oromia, Ethiopia
Authors: Ereso Denbel Tsegu
Published: June 2021

The study was conducted in protected woodland and free graze woodland located in Dugda Woreda, Oromia state, Ethiopia. The objective of the study was to explore the floristic composition, structure, and regeneration of woody species. In the park, the vegetation ecology has not been studied up to date, which is necessary for conservation. The systematic sampling technique was used to collect vegetation and human disturbance (presence and absence) data from August to December 2017. The vegetation data were collected from 30 plots from each woodland with a size of 900 m2 (30 m × 300 m) for tree/shrub, while subplots of size 400 m2 (20 m × 20 m) for sapling, respectively, were established in the main plots. Individual tree and shrub diameters at breast height (DBH) ≥2.5 cm and height ≥ 2 m were measured using a tape meter and clinometer, respectively. Diameter at breast height (DBH), frequency, density, basal area, and importance value index (IVI) were used for vegetation structure description, while the densities of mature trees, sapling, and seedling were used for regeneration. A total of 446 individual stems from free grazed woodland and 641 individual stems from protected woodland with a DBH of ≥2.5 cm were encountered from 30 studied sample plots that are protected and free grazed woodlands. Of these, from the total woody species, 68.42% were trees and 31.57% shrubs found in protected woodland; 76.92% were trees and 23.07% shrubs found in free grazed woodland. The total basal area of the woody plant was 3.1 ± 1 m2/ha in free grazed woodland and 4.2 ± 2 m2/ha in protected woodland, calculated for 19 woody species. Fabaceae, Balanitaceae, Capparidaceae, Verbenaceae, and Boraginaceae families were the most abundant families in both woodlands. However, there is a good initiation for the conservation of the park; still, the vegetation of the park was threatened by human-induced fire following intensive farming, gold mining, and overgrazing.
Application of High-Dimensional Outlier Mining Based on the Maximum Frequent Pattern Factor in Intrusion Detection
Authors: Shen Limin , Sun Zhongkui , Chen Lei , Feng Jiayin
Published: June 2021

As the Internet applications are growing rapidly, the intrusion detection system is widely used to detect network intrusion effectively. Aiming at the high-dimensional characteristics of data in the intrusion detection system, but the traditional frequent-pattern-based outlier mining algorithm has the problems of difficulty in obtaining complete frequent patterns and high time complexity, the outlier set is further analysed to get the attack pattern of intrusion detection. The NSL-KDD dataset and UNSW-NB15 dataset are used for evaluating the proposed approach by conducting some experiments. The experiment results show that the method has good performance in detection rate, false alarm rate, and recall rate and effectively reduces the time complexity.
A New Method for the Aggregate Proportion Calculation and Gradation Optimization of Asphalt-Treated Base (ATB-25)
Authors: Zhu Fu , Han Jianbo , Zhang Shuang , Dong Weizhi
Published: June 2021

Asphalt-treated base (ATB-25) is a widely used flexible base material. The composition and gradation of mineral aggregate are important factors affecting pavement performance of asphalt treated base. In this study, two new methods were proposed to address the problems of existing aggregate proportion calculation for asphalt mixtures: (1) the combination of generalized inverse solution of the normal equation and spreadsheet trial and (2) quadratic programming. Both methods can calculate mass ratios of various aggregates in a quick and accurate manner. The orthogonal test was used to design nine aggregate gradations within the range of asphalt treated base (ATB-25) stated in the industrial standard. The aggregate proportion was calculated by two new methods. The Marshall test, water weight test, rutting test, and water-soaked Marshall test were carried out on the asphalt mixture specimens. The pavement performance test results were fuzzified using the fuzzy mathematics method, and the weights of pavement performance evaluation indexes were determined through the analytic hierarchy process. Taking the fuzzy comprehensive evaluation values as the objective function, test results were analyzed and evaluated. Finally, the optimal aggregate gradation was determined considering factors of compactness, high-temperature rutting resistance, and water stability.
Association of Prx4, Total Oxidant Status, and Inflammatory Factors with Insulin Resistance in Polycystic Ovary Syndrome
Authors: Mazloomi Sahar , Sheikh Nasrin , Sanoee Farimani Marzieh , Pilehvari Shamim
Published: June 2021

Introduction. Chronic inflammation and oxidative stress conditions have been reported in women with polycystic ovary syndrome (PCOS). Peroxiredoxin 4 (Prx4) is a related antioxidant in insulin synthesis. We hypothesized that insulin resistance in these women is associated with total oxidant status (TOS) and inflammatory factors. Materials and Methods. Two hundred three people including 104 PCOS patients and 99 healthy women, who were matched for age and body mass index (BMI), entered the study. Waist circumference of the participants was measured; serum glucose, lipid profile, insulin, Prx4, TOS, hs-CRP, and TNF-α were also evaluated. Results. The Prx4 level was significantly lower in PCOS than in the control group. In addition, marked increase was observed in the concentration of TOS, hs-CRP, and TNF-α in PCOS, compared to the healthy women. There was a positive correlation of TOS with hs-CRP, TNF-α, and HOMA-IR. The risk of PCOS for subjects with high hs-CRP was 60 times greater than those who had low serum hs-CRP concentration; after performing multiple logistic regression analyses with the backward method, TNF-α was considered as an effective biomarker to predict PCOS β = 49.087 (all

p
<
0.05

). Conclusion. This study identified increased oxidative stress and inflammation in PCOS; this may be due to decrease in the antioxidants, such as Prx4.
The Research on the Treatment of Metastatic Skin Cutaneous Melanoma by Huanglian Jiedu Decoction Based on the Analysis of Immune Infiltration Analysis
Authors: Li Ding , Li Shi-Fang , Li Xiao-Yuan , Sun Xiao-Wei , Sun Tian-Yue , Hu Guo-Jie
Published: June 2021

Objective. To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis. Methods. The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis. Results. HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets. Conclusions. Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.
Prognostic Value of Albumin to D-Dimer Ratio in Advanced Gastric Cancer
Authors: Zhang Liqun , Wang Zhuo , Xiao Jiawen , Zhang Zhiyan , Li Haijing , Li Fang , Zhang Lisha , Wang Yuanhe
Published: June 2021

Gastric cancer (GC) is one of the most common malignancies worldwide. Notably, patients with advanced GC have a poor prognosis and quality of life, prompting the need for further studies on its prognostic markers. Among these, albumin and D-dimer are often used as prognostic factors in the prediction of a variety of tumors. Moreover, the albumin to D-dimer ratio (ADR) may be an improved predictor of chemotherapy effect and survival compared to albumin and D-dimer alone, but few studies have investigated this issue. Thus, we explored the relationship between pretreatment ADR and prognosis in advanced GC treated with first-line chemotherapy. A total of 247 advanced unresectable GC patients treated with first-line chemotherapy were retrospectively included. The cut-off value for ADR was determined using the receiver operating characteristic (ROC) curve. The ADR had a cut-off value of 41.64. Compared to albumin and D-dimer alone, ADR had the highest area under curve (AUC) value (AUC = 0.730), followed by albumin (AUC = 0.659) and D-dimer (AUC = 0.719). Additionally, we found that patients with a low ADR (<41.64) had a lower disease control rate (77.9% vs. 92.5%,

P
<
0.01

), shorter overall survival (OS) (271 vs. 389 days), and shorter progression-free survival (PFS) (118 vs. 192 days) than patients with a high ADR (≥41.64). Similar results were also found on subgroup analysis, and ADR was found to be an independent advanced GC prognostic factor on multivariate analysis (all

P
<
0.001

). Low ADR was found to be correlated with poor therapeutic effects of chemotherapy and shortened OS and PFS. Therefore, pretreatment ADR may be a useful tool for predicting the effect of chemotherapy and prognosis in advanced GC patients treated with first-line chemotherapy.
C/EBPβ/AEP Signaling Regulates the Oxidative Stress in Malignant Cancers, Stimulating the Metastasis
Authors: Lei Kecheng , Kang Seong Su , Ahn Eun Hee , Chen Chun , Liao Jianming , Liu Xia , Li Hua , Edgington-Mitchell Laura E. , Jin Lingjing , Ye Keqiang
Published: June 2021

Solid tumors start as a local disease, but some are capable of metastasizing to the lymph nodes and distant organs. The hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating cancer progression and metastasis. However, the molecular mechanisms mediating the disseminated cancer cell metastasis remain incompletely understood. Here, we show that C/EBPβ/AEP signaling that is upregulated in breast cancers mediates oxidative stress and lung metastasis, and inactivation of asparagine endopeptidase (AEP, also known as legumain) robustly regulates breast cancer reactive oxygen species (ROS) and metastasis. AEP, a protease activated in acidic conditions, is overexpressed in numerous types of cancer and promotes metastasis. Employing a breast cancer cell line MDA-MD-231, we show that C/EBPβ, an oxidative stress or inflammation-activated transcription factor, and its downstream target AEP mediate ROS production as well as migration and invasion in cancer cells. Deficiency of AEP in the MMTV-PyMT transgenic breast cancer mouse model significantly regulates oxidative stress and suppresses lung metastasis. Administration of an innovative AEP inhibitor substantially mitigates ROS production and cancer metastasis. Hence, our study demonstrates that pharmacologic inhibition of AEP activity might provide a disease-modifying strategy to suppress cancer metastasis.
SOHLH2 Suppresses Angiogenesis by Downregulating HIF1α Expression in Breast Cancer
Authors: Cui Weiwei , Xiao Yunling , Zhang Ruihong , Zhao Na , Zhang Xianghong , Wang Fuwu , Liu Yang , Zhang Xiaoli , Hao Jing
Published: June 2021

SOHLH2 has been demonstrated the downregulation in various cancers and the involvement in tumor growth and metastasis. However, the function of SOHLH2 on tumor angiogenesis and the underlying molecular mechanisms have not been interrogated. IHC staining results revealed that SOHLH2 was negatively associated with microvessel density (MVD), tumor size, histology grade, and metastasis. Overexpression of SOHLH2 inhibited the angiogenic behavior of human umbilical vein endothelial cells (HUVEC) by a tumor cell–mediated paracrine signal, while knockdown of SOHLH2 promoted HUVEC angiogenic behavior. Ectopic SOHLH2 expression remarkably suppressed tumor growth and MVD in xenograft tumors, downregulated the expression of hypoxia inducible factor-1 alpha (HIF1α)-mediated proangiogenic genes in vivo and in vitro, while knockdown of SOHLH2 had an opposite result. Furthermore, we found that upregulation of HIF1α reversed SOHLH2-induced suppression of breast cancer angiogenesis, while KC7F2, the inhibitor of HIF1α, could attenuate the promotion of angiogenesis by SOHLH2 silencing. Using Chromatin immunoprecipitation and luciferase reporter assays, we validated that SOHLH2 could directly bind to HIF1α promoter and repress its transcriptional activity. Collectively, SOHLH2 suppresses breast cancer angiogenesis by downregulating HIF1α transcription and may be a potential biomarker for anti-angiogenesis therapy.

Implications:

SOHLH2 directly represses HIF1α–mediated angiogenesis and serves as an important inhibitor of angiogenesis in breast cancer.
Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells
Authors: Wang Qinglin , Wu Hao , Hu Jian , Fu Haijuan , Qu Yanghui , Yang Yijun , Cai Kathy Q. , Efimov Andrey , Wu Minghua , Yen Tim , Wang Yuan , Yang Zeng-Jie
Published: June 2021

Nestin, a class IV intermediate filament protein, is generally considered as a putative marker of neural stem and progenitor cells in the central nervous system. Glioma is a common type of adult brain tumors, and glioblastoma (GBM) represents the most aggressive form of glioma. Here, we report that Nestin expression is significantly upregulated in human GBM, compared with other types of glioma. Nestin knockdown or deletion in U251 cells and tumor cells from GBM patients derived xenografts resulted in G2–M arrest, finally leading to apoptosis in tumor cells. Using proximity-dependent biotin identification method, we identified βII-tubulin as an interacting protein of Nestin in U251 cells. Nestin stabilized βII-tubulin in U251 cells through physical interaction. Knockdown of Nestin or βII-tubulin disrupted spindle morphology in tumor cells. Our studies further revealed that Nestin deficiency in U251 cells and GBM PDX cells repressed tumor growth upon transplantation. Finally, we found that Nestin deficiency sensitized GBM cells to microtubule-destabilizing drugs such as vinblastine and vincristine. Our studies demonstrate the essential functions and underlying mechanisms of Nestin in the growth and drug response of GBM cells.

Implications:

Through interaction with βII-tubulin, Nestin facilitates cell-cycle progression and spindle assembly of tumor cells in glioblastoma.
PARP-1 Regulates Estrogen-Dependent Gene Expression in Estrogen Receptor α–Positive Breast Cancer Cells
Authors: Gadad Shrikanth S. , Camacho Cristel V. , Malladi Venkat , Hutti Charles R. , Nagari Anusha , Kraus W. Lee
Published: June 2021

Poly(ADP-ribose) polymerase-1 (PARP-1) has gained considerable attention as a target for therapeutic inhibitors in breast cancers. Previously we showed that PARP-1 localizes to active gene promoters to regulate histone methylation and RNA polymerase II activity (Pol II), altering the expression of various tumor-related genes. Here we report a role for PARP-1 in estrogen-dependent transcription in estrogen receptor alpha (ERα)-positive (ER+) breast cancers. Global nuclear run-on and sequencing analyses functionally linked PARP-1 to the direct control of estrogen-regulated gene expression in ER+ MCF-7 breast cancer cells by promoting transcriptional elongation by Pol II. Furthermore, chromatin immunoprecipitation sequencing analyses revealed that PARP-1 regulates the estrogen-dependent binding of ERα and FoxA1 to a subset of genomic ERα binding sites, promoting active enhancer formation. Moreover, we found that the expression levels of the PARP-1– and estrogen-coregulated gene set are enriched in the luminal subtype of breast cancer, and high PARP-1 expression in ER+ cases correlates with poor survival. Finally, treatment with a PARP inhibitor or a transcriptional elongation inhibitor attenuated estrogen-dependent growth of multiple ER+ breast cancer cell lines. Taken together, our results show that PARP-1 regulates critical molecular pathways that control the estrogen-dependent gene expression program underlying the proliferation of ER+ breast cancer cells.

Implications:

PARP-1 regulates the estrogen-dependent genomic binding of ERα and FoxA1 to regulate critical gene expression programs by RNA Pol II that underlie the proliferation of ER+ breast cancers, providing a potential therapeutic opportunity for PARP inhibitors in estrogen-responsive breast cancers.
Effects of Stimulus Intensity and Frequency on the Force and Timing of Sensorimotor Synchronisation
Authors: Todd Neil P. M. , Keller Peter E. , Govender Sendhil , Colebatch James G.
Published: June 2021

We report an experiment to investigate possible vestibular effects on finger tapping to an auditory anapaest rhythm. In a sample of 10 subjects, index finger acceleration and tapping force were recorded along with extensor/flexor activity and the associated electroencephalographic activity measured at central and cerebellar surface electrodes. In a prior session with a standard short air-conducted 500-Hz pip, vestibular evoked myogenic potential thresholds were measured and subsequently used to set the acoustic intensity. During the main experiment subjects were asked to synchronise tapping to the pips arranged in the anapaest at two different frequencies, 500 Hz vs 5 kHz, so that only the low-frequency high-intensity condition was a vestibular, as well as an auditory stimulus. We hypothesised that a vestibular effect would manifest in an interaction between the frequency and intensity factors for a range of dependent measures of tapping performance. No clear evidence was found for vestibular effects, but this was likely due to the confounding effects of an independent effect of intensity and the relative weakness of the acoustic vestibular stimulus. However, the data did show novel evidence for two distinct timing processes for the flexion and extension stages of a tap cycle and two distinct timing strategies, which we refer to as ‘staccato’ and ‘legato’, characterised by different profiles of force and extension.
Effect of Parecoxib on Hippocampus and Hypothalamic Orexin Neurons in Rats with Cerebral Infarction
Authors: Guo Yapeng , Xu Heng , Li Xuyi , Zhou Zhiming
Published: June 2021

Cerebral infarction has seriously threatened human life and health. Parecoxib is the first nonsteroidal analgesic for surgical analgesia. However, its effect on orexin neurons during cerebral infarction treatment is unclear. In this study, a rat model of cerebral infarction was established
by suture method. The experiment was assigned into sham operation group, cerebral infarction model group (MCAO), high and low dose group of parecoxib. Western blotting and immunofluorescence staining was used to evaluate the activity of orexin neurons. The infarct size was evaluated by TTC
staining. The apoptosis of neurons in hypothalamus and hippocampus was determined by AV-PI staining. TTC staining suggested that parecoxib treatment significantly reduced cerebral infarct size, increased orexin neuronal activity, and decreased neuronal apoptosis in hypothalamus and hippocampus,
which were significantly different from sham-operated groups. This study demonstrates that parecoxib has a protective effect on cerebral infarction rats, which can inhibit the apoptosis of hypothalamic and hippocampal neurons through the orexin neuron pathway. It provides a theoretical basis
for the protective effect of parecoxib, indicating that it might be a new target for the treatment of cerebral infarction.
Research on the Expression and Regulatory Mechanism of Breast Cancer Susceptibility Gene-1 on Cell of Skin Cancer in Different Classification
Authors: Li Le , Zhao Pei , Zhang Xiaoying , Chen Xiongwen , Zhao Ran
Published: June 2021

The expression condition of breast cancer susceptibility gene-1 (BRCA1) in tissue of skin cancer in different classification was assessed in our study with analysis of the correlation between BRCA1 and classification of skin cancer. The influence of BRCA1 on the tyrosine kinase receptors
(c-kit) was detected to discuss the possible-existing regulatory mechanism. The skin cancer was classified according to the clinical symptoms and was divided into zero to the fifth phase. Then the expression of BRCA1 and c-kit in tissue of skin cancer in different classification was detected
by RT-PCR. The cell line of skin cancer HS-4 cultured in vitro was transfected with high-BRCA1-expressed vector. There was negative correlation between the expression of BRCA1 and the classification of skin cancer. There was no significant difference among the zero phase, the first
phase and the second phase when the value of P was less than 0.05. There was no significant difference between the third phase and the fourth phase when the value of P was larger than 0.05. But there was significant difference between the latter two groups and the former three
groups when the value of P was less than 0.05. The expression of c-kit was increased along with the elevation of classification of skin cancer with significant difference among groups. The reducing of expression of BRCA1 could affect the expression of c-kit from the cell experiment.
There was negative correlation between the expression of BRCA1 and the expression of c-kit. There was correlation between the expression of BRCA1 and c-kit and the development of skin cancer. There was negative correlation between BRCA1 expression and c-kit level. It was illustrated that the
BRCA1 could develop certain regulatory effect on skin cancer by influencing the expression level of c-kit.
Humanin-S14G Ameliorates Vascular Dementia Through Regulating miR-134
Authors: Zhuang Yuan , Wang Xutang
Published: June 2021

Humanin-S14G is a synthetic derivative of Humanin with neuroprotective effects. miR-134 involves in the regulation of the nervous system. However, whether Humanin-S14G ameliorates VD through miR-134 remains poorly understood. Healthy male rats were assigned into sham group; VD group and Humanin-S14G group followed by analysis of learning ability by the Morris water maze test, expression of miR-134, Bcl-2 and Bax by Real time PCR, BDNF protein level by Western blot, IL-6 secretion by ELISA as well as pathological changes of hippocampal nerve region by HE staining. In VD model group, the learning and cognitive ability of the rats was significantly decreased and miR- 134 and IL-6 was significantly upregulated along with downregulated Bcl-2 and BDNF and upregulated Bax expression compared to sham group (P<0.05). Humanin-S14G significantly improved the learning and cognitive ability of VD model rats, decreased miR-134 and IL-6 level, increased Bcl-2 and BDNF expression, as well as inhibited Bax expression (P<0.05) and nerve damage was significantly improved. Humanin-S14G regulates miR-134 expression in the brain tissue of VD rats, promote the expression of BDNF, regulate cell apoptosis, inhibit inflammation, improve the learning function of vascular dementia, and delay the occurrence and development of vascular dementia.