bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Vascular Network Connectivity of Hepatocellular Carcinoma Using Graph-Based Approach
Authors: Liu Qiaoyu , Zhang Boyu , Wang Luna , Zheng Rencheng , Qiang Jinwei , Wang He , Yan Fuhua , Li Ruokun 
Published: July 2021

BackgroundThe angiogenesis of liver cancer is a key condition for its growth, invasion, and metastasis. This study aims to investigate vascular network connectivity of hepatocellular carcinoma (HCC) using graph-based approach.MethodsOrthotopic HCC xenograft models (n=10) and the healthy controls (n=10) were established. After 21 days of modeling, hepatic vascular casting and Micro-CT scanning were performed for angiography, followed by blood vessels automatic segmentation and vascular network modeling. The topologic parameters of vascular network, including clustering coefficient (CC), network structure entropy (NSE), and average path length (APL) were quantified. Topologic parameters of the tumor region, as well as the background liver were compared between HCC group and normal control group.ResultsCompared with normal control group, the tumor region of HCC group showed significantly decreased CC [(0.046 ± 0.005) vs. (0.052 ± 0.006), P=0.026], and NSE [(0.9894 ± 0.0015) vs. (0.9927 ± 0.0010), P&lt;0.001], and increased APL [(0.433 ± 0.138) vs. (0.188 ± 0.049), P&lt;0.001]. Compared with normal control group, the background liver of HCC group showed significantly decreased CC [(0.047 ± 0.004) vs. (0.052 ± 0.006), P=0.041] and increased NSE [0.9938 (0.9936~0.9940) vs. (0.9927 ± 0.0010), P=0.035]. No significant difference was identified for APL between the two groups.ConclusionGraph-based approach allows quantification of vascular connectivity of HCC. Disrupted vascular topological connectivity exists in the tumor region, as well as the background liver of HCC.
Balloon Test Occlusion of Internal Carotid Artery in Recurrent Nasopharyngeal Carcinoma Before Endoscopic Nasopharyngectomy: A Single Center Experience
Authors: Yang Renhao , Wu Hui , Chen Binghong , Sun Wenhua , Hu Xiang , Wang Tianwei , Guo Yubin , Qiu Yongming , Dai Jiong 
Published: July 2021

ObjectivesEndoscopic nasopharyngectomy (ENPG) is a promising way in treating recurrent nasopharyngeal carcinoma (rNPC), but sometimes may require therapeutic internal carotid artery (ICA) occlusion beforehand. Balloon test occlusion (BTO) is performed to evaluate cerebral ischemic tolerance for ICA sacrifice. However, absence of neurological deficits during BTO does not preclude occur of delayed cerebral ischemia after permanent ICA occlusion. In this study, we evaluate the utility of near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) monitoring during ICA BTO to quantify cerebral ischemic tolerance and to identify the valid cut-off values for safe carotid artery occlusion. This study also aims to find out angiographic findings of cerebral collateral circulation to predict ICA BTO results simultaneously.Material and Methods87 BTO of ICA were performed from November 2018 to November 2020 at authors’ institution. 79 angiographies of collateral flow were performed in time during BTO and classified into several Subgroups and Types according to their anatomic and collateral flow configurations. 62 of 87 cases accepted monitoring of cerebral rSO2. Categorical variables were compared by using Fisher exact tests and Mann–Whitney U tests. Receiver operating characteristic curve analysis was used to determine the most suitable cut-off value.ResultsThe most suitable cut-off △rSO2 value for detecting BTO-positive group obtained through ROC curve analysis was 5% (sensitivity: 100%, specificity: 86%). NIRS rSO2 monitoring wasn’t able to detect BTO false‐negative results (p = 0.310). The anterior Circle was functionally much more important than the posterior Circle among the primary collateral pathways. The presence of secondary collateral pathways was considered as a sign of deteriorated cerebral hemodynamic condition during ICA BTO. In Types 5 and 6, reverse blood flow to the ICA during BTO protected patients from delayed cerebral ischemia after therapeutic ICA occlusion (p = 0.0357). In Subgroup IV, absence of the posterior Circle was significantly associated with BTO-positive results (p = 0.0426).ConclusionAngiography of cerebral collateral circulation during ICA BTO is significantly correlated with ICA BTO results. Angiographic ICA BTO can be performed in conjunction with NIRS cerebral oximeter for its advantage of being noninvasive, real-time, cost-effective, simple for operation and most importantly for its correct prediction of most rSO2 outcomes of ICA sacrifice. However, in order to ensure a safe carotid artery occlusion, more quantitative adjunctive blood flow measurements are recommended when angiography of cerebral collateral circulation doesn’t fully support rSO2 outcome among clinically ICA BTO-negative cases.
m6A Regulator-Mediated Methylation Modification Model Predicts Prognosis, Tumor Microenvironment Characterizations and Response to Immunotherapies of Clear Cell Renal Cell Carcinoma
Authors: Xu Wenhao , Tian Xi , Liu Wangrui , Anwaier Aihetaimujiang , Su Jiaqi , Zhu Wenkai , Wan Fangning , Shi Guohai , Wei Gaomeng , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei 
Published: July 2021

BackgroundThis study aims to establish an N6-methyladenosine (m6A) RNA methylation regulators-mediated methylation model and explore its role in predicting prognostic accuracy of immune contexture and characterizations of clear cell renal cell carcinoma (ccRCC).MethodsThe m6A modification subclasses (m6AMS) were identified by unsupervised cluster analysis and three clusters were determined by consensus clustering algorithm in a discovering cohort. Testing and real-world validation cohorts were used to identify predictive responses for immune checkpoint therapies (ICTs) of m6AMS.ResultsPrognostic implications landscape of m6A regulators in cancers and its differential expression levels in ccRCC patients were identified. Based on discovering cohort, ccRCC were automatically divided into three m6AMS, and cluster 3 showed significant worse survival than cluster 1/2. Importantly, it was found that the immune checkpoint molecules expression was significantly elevated in cluster 3. Besides, m6A scoreLow group (cluster 1&amp;2) have significantly elevated TIDE score compared with m6A scoreHigh group (cluster 3). There was conspicuous tertiary lymphoid tissue, aggressive phenotype, elevated glycolysis, expression of PD-L1, abundance of CD8+ T cells, CD4+ FOXP3+ Treg cells and TCRn immune cells infiltration in the high m6A score group. Interestingly, there are significantly increased patients with clinical benefit in m6A scoreHigh group in 368 patients receiving ICTs from testing IMvigor210 (n = 292) and validation FUSCC (n = 55) cohorts.ConclusionOur discovery highlights the relationship between tumor epigenetic heterogeneity and immune contexture. Immune-rejection cluster 3 has pro-tumorigenic immune infiltration, and shows significant clinical benefits for ccRCC patients receiving ICTs, enabling patient selection for future clinical treatment.
The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier
Authors: Li Mengting , Ke Jia , Deng Yiqing , Chen Chunxiang , Huang Yichen , Bian Yuefeng , Guo Shufen , Wu Yang , Zhang Hong , Liu Mingyuan , Han Yan 
Published: July 2021

Background: Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM).Methods: The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion in vivo while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed.Results: LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found.Conclusions: Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.
Cocaine-Induced Changes in Tonic Dopamine Concentrations Measured Using Multiple-Cyclic Square Wave Voltammetry in vivo
Authors: Yuen Jason , Goyal Abhinav , Rusheen Aaron E. , Kouzani Abbas Z. , Berk Michael , Kim Jee Hyun , Tye Susannah J. , Blaha Charles D. , Bennet Kevin E. , Jang Dong-Pyo , Lee Kendall H. , Shin Hojin , Oh Yoonbae 
Published: July 2021

For over 40 years, in vivo microdialysis techniques have been at the forefront in measuring the effects of illicit substances on brain tonic extracellular levels of dopamine that underlie many aspects of drug addiction. However, the size of microdialysis probes and sampling rate may limit this technique’s ability to provide an accurate assessment of drug effects in microneural environments. A novel electrochemical method known as multiple-cyclic square wave voltammetry (M-CSWV), was recently developed to measure second-to-second changes in tonic dopamine levels at microelectrodes, providing spatiotemporal resolution superior to microdialysis. Here, we utilized M-CSWV and fast-scan cyclic voltammetry (FSCV) to measure changes in tonic or phasic dopamine release in the nucleus accumbens core (NAcc) after acute cocaine administration. Carbon-fiber microelectrodes (CFM) and stimulating electrodes were implanted into the NAcc and medial forebrain bundle (MFB) of urethane anesthetized (1.5 g/kg i.p.) Sprague-Dawley rats, respectively. Using FSCV, depths of each electrode were optimized by determining maximal MFB electrical stimulation-evoked phasic dopamine release. Changes in phasic responses were measured after a single dose of intravenous saline or cocaine hydrochloride (3 mg/kg; n = 4). In a separate group, changes in tonic dopamine levels were measured using M-CSWV after intravenous saline and after cocaine hydrochloride (3 mg/kg; n = 5). Both the phasic and tonic dopamine responses in the NAcc were augmented by the injection of cocaine compared to saline control. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. These increases were largely consistent with previous studies using FSCV and microdialysis. However, the minimal disruption/disturbance of neuronal tissue by the CFM may explain why the baseline tonic dopamine values (134 ± 32 nM) measured by M-CSWV were found to be 10-fold higher when compared to conventional microdialysis. In this study, we demonstrated phasic dopamine dynamics in the NAcc with acute cocaine administration. M-CSWV was able to record rapid changes in tonic levels of dopamine, which cannot be achieved with other current voltammetric techniques. Taken together, M-CSWV has the potential to provide an unprecedented level of physiologic insight into dopamine signaling, both in vitro and in vivo, which will significantly enhance our understanding of neurochemical mechanisms underlying psychiatric conditions.
Nanoformulations of Ursolic Acid: A Modern Natural Anticancer Molecule
Authors: Wang Longyun , Yin Qianqian , Liu Cun , Tang Ying , Sun Changgang , Zhuang Jing 
Published: July 2021

Background: Ursolic acid (UA) is a natural pentacyclic triterpene derived from fruit, herb, and other plants. UA can act on molecular targets of various signaling pathways, inhibit the growth of cancer cells, promote cycle stagnation, and induce apoptosis, thereby exerting anticancer activity. However, its poor water-solubility, low intestinal mucosal absorption, and low bioavailability restrict its clinical application. In order to overcome these deficiencies, nanotechnology, has been applied to the pharmacological study of UA.Objective: In this review, we focused on the absorption, distribution, and elimination pharmacokinetics of UA in vivo, as well as on the research progress in various UA nanoformulations, in the hope of providing reference information for the research on the anticancer activity of UA.Methods: Relevant research articles on Pubmed and Web of Science in recent years were searched selectively by using the keywords and subheadings, and were summarized systematically.Key finding: The improvement of the antitumor ability of the UA nanoformulations is mainly due to the improvement of the bioavailability and the enhancement of the targeting ability of the UA molecules. UA nanoformulations can even be combined with computational imaging technology for monitoring or diagnosis.Conclusion: Currently, a variety of UA nanoformulations, such as micelles, liposomes, and nanoparticles, which can increase the solubility and bioactivity of UA, while promoting the accumulation of UA in tumor tissues, have been prepared. Although the research of UA in the nanofield has made great progress, there is still a long way to go before the clinical application of UA nanoformulations.
Does Procrastination Always Predict Lower Life Satisfaction? A Study on the Moderation Effect of Self-Regulation in China and the United Kingdom
Authors: Yang Zeyang 
Published: July 2021

Aims: Studies have shown the predictive effects of procrastination and self-regulation on wellbeing. However, little is known about the interactive effect between procrastination and self-regulation. This study explores whether self-regulation moderates the link between procrastination and wellbeing among British and Chinese young adults.Methods: This study adopted self-reported questionnaire survey among two hundred and sixty-five British and four hundred and seventy-five Chinese participants. SPSS and AMOS were used to test the moderation effect. Multi-group path analysis was used to compare the two countries.Results: Data analysis shows that self-regulation was a significant moderator of the relationship between procrastination and life satisfaction in the Chinese sample but not in the British sample. Procrastination predicted low life satisfaction only among the Chinese students with low self-regulation.Discussion: This study indicates that the effects of procrastination on wellbeing could be changed at different levels of self-regulation. Cultural difference can be an important factor when investigating procrastination and its impacts.
Value of Perampanel as Adjunctive Treatment for Partial-Onset Seizures in Epilepsy: Cost-Effectiveness and Budget Impact Analysis
Authors: Zhang Donger , Li Xia , Ding Jing , Ke Xiatong , Ding Wenpei , Ren Yinan , Xu He , Li Hongchao , Ma Aixia , Tang Wenxi 
Published: July 2021

Introduction:China has ~6 million patients with active epilepsy every year, around 60% of whom suffer from partial-onset seizures. Perampanel (PER) is a novel anti-epileptic drug for partial-onset seizures. PER has been included in the latest Chinese National Reimbursement Drug List (NRDL) in 2020. However, there is still a lack of evaluation evidence on the value of PER in China.Methods:This study selected a health system perspective. A Markov model was established to simulate the lifelong transition of different response levels and calculate the number of seizures in Chinese patients. Based on the utility value and mortality risk, the life years and quality-adjusted life years (QALYs) of patients using PER vs. lacosamide (LCM) were estimated. Efficacy data were derived from clinical trials and the literature. Cost data (in US dollars) included drug costs and medical service costs. A lifetime horizon was adopted. Health outcomes and costs were discounted at an annual discount rate of 5%. Deterministic sensitivity analysis, probability sensitivity analysis, and scenario analysis were performed. The impact of the inclusion of PER in the NRDL on the medical insurance budget over 3 years (2021–2023) was also estimated.Results:Cost-effectiveness analysis indicates that 8 mg/day of PER increases QALYs by 0.054 and saves costs by $2,390 compared with 400 mg/day of LCM. 4 mg/day of PER increases QALYs by 0.010 and saves costs by $860 compared with 200 mg/day of LCM. Deterministic sensitivity analysis reveals that utility value and the extreme discount rate are the factors with the greatest impact on the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis and scenario analysis show that the results are robust. Budget impact analysis indicates that after inclusion of PER in the NRDL, the incremental budget would be $1.28, $2.83, and $4.56 million from 2021 to 2023, respectively, but covering more eligible epileptic patients in the same time (1,918, 4,287, and 8,983, respectively).Conclusion:PER (8 or 4 mg/day) is of relatively high value as an add-on therapeutic regimen for partial-onset seizures in China because of its dominate advantage of cost-effectiveness over LCM and acceptable budget impact.
Policy-Relevant Attitudes Toward COVID-19 Vaccination: Associations With Demography, Health Risk, and Social and Political Factors
Authors: Paul Katharina T. , Eberl Jakob-Moritz , Partheymüller Julia 
Published: July 2021

Background: Vaccination is considered to be a key public health intervention to end the COVID-19 pandemic. Yet, the success of the intervention is contingent on attitudes toward vaccination and the design of vaccination policies.Methods: We conduct cross-sectional analyses of policy-relevant attitudes toward COVID-19 vaccination using survey data of a representative sample of Austrian residents collected by the Austrian Corona Panel Project (ACPP). As outcomes, we examine the individual readiness to get vaccinated, the support for compulsory vaccinations, and the preference for making the vaccine available free of charge. The independent variables include demographics, objective and perceived health risks, and social and political factors.Results: Although there is broad public support for making the vaccine available free of charge, vaccine hesitancy and the opposition to a vaccine mandate are widespread. The protective function of the vaccine for the individual only motivates limited support for vaccinations. Opposition to COVID-19 vaccination also stems from a lack of sense of community and an ongoing politicization of the issue through conspiracy theories and party politics.Conclusion: We propose that overcoming the inherent free-rider problem of achieving sufficiently high vaccination rates poses a potential dilemma for policymakers: Given the politicized nature of the issue, they may find themselves having to choose between making vaccinations compulsory at political costs and a lingering pandemic at high costs for public health and the economy. We propose that promoting a sense of community and addressing potential practical constraints will be key in designing an effective COVID-19 vaccination policy.
Synthesis of Carbon-Supported MnO2 Nanocomposites for Supercapacitors Application
Authors: Jablonskiene Jolita , Simkunaite Dijana , Vaiciuniene Jurate , Stalnionis Giedrius , Drabavicius Audrius , Jasulaitiene Vitalija , Pakstas Vidas , Tamasauskaite-Tamasiunaite Loreta , Norkus Eugenijus 
Published: July 2021

In this study, carbon-supported MnO2 nanocomposites have been prepared using the microwave-assisted heating method followed by two different approaches. The MnO2/C nanocomposite, labeled as sample S1, was prepared directly by the microwave-assisted synthesis of mixed KMnO4 and carbon powder components. Meanwhile, the other MnO2/C nanocomposite sample labeled as S2 was prepared indirectly via a two-step procedure that involves the microwave-assisted synthesis of mixed KMnO4 and MnSO4 components to generate MnO2 and subsequent secondary microwave heating of synthesized MnO2 species coupled with graphite powder. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma optical emission spectroscopy have been used for characterization of MnO2/C nanocomposites morphology, structure, and composition. The electrochemical performance of nanocomposites has been investigated using cyclic voltammetry and galvanostatic charge/discharge measurements in a 1 M Na2SO4 solution. The MnO2/C nanocomposite, prepared indirectly via a two-step procedure, displays substantially enhanced electrochemical characteristics. The high specific capacitance of 980.7 F g−1 has been achieved from cyclic voltammetry measurements, whereas specific capacitance of 949.3 F g−1 at 1 A g−1 has been obtained from galvanostatic charge/discharge test for sample S2. In addition, the specific capacitance retention was 93% after 100 cycles at 20 A g−1, indicating good electrochemical stability.
Selective Laser Melting of 316L Austenitic Stainless Steel: Detailed Process Understanding Using Multiphysics Simulation and Experimentation
Authors: Ansari Peyman , Rehman Asif Ur , Pitir Fatih , Veziroglu Salih , Mishra Yogendra Kumar , Aktas Oral Cenk , Salamci Metin U. 
Published: July 2021

The parameter sets used during the selective laser melting (SLM) process directly affect the final product through the resulting melt-pool temperature. Achieving the optimum set of parameters is usually done experimentally, which is a costly and time-consuming process. Additionally, controlling the deviation of the melt-pool temperature from the specified value during the process ensures that the final product has a homogeneous microstructure. This study proposes a multiphysics numerical model that explores the factors affecting the production of parts in the SLM process and the mathematical relationships between them, using stainless steel 316L powder. The effect of laser power and laser spot diameter on the temperature of the melt-pool at different scanning velocities were studied. Thus, mathematical expressions were obtained to relate process parameters to melt-pool temperature. The resulting mathematical relationships are the basic elements to design a controller to instantly control the melt-pool temperature during the process. In the study, test samples were produced using simulated parameters to validate the simulation approach. Samples produced using simulated parameter sets resulting in temperatures of 2000 K and above had acceptable microstructures. Evaporation defects caused by extreme temperatures, unmelted powder defects due to insufficient temperature, and homogenous microstructures for suitable parameter sets predicted by the simulations were obtained in the experimental results, and the model was validated.