bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythropoietin alters the pharmacokinetics of organic anions mainly eliminated by the kidney in rats
Authors: Severin María Julia , Hazelhoff María Herminia , Bulacio Romina Paula , Mamprin María Eugenia , Brandoni Anabel , Torres Adriana Mónica
Published: March 2021

Erythropoietin (EPO) is a cytokine originally used for its effects on the hematopoietic system, and is widely prescribed around the world. In the present study, the effects of EPO administration on p-aminohippurate (PAH, a prototype organic anion) pharmacokinetics and on the renal expression of PAH transporters were evaluated. Male Wistar rats were treated with EPO or saline (control group). After 42 h, PAH was administered, and plasma samples were obtained at different time points to determine PAH levels. PAH levels in renal tissue and urine were also assessed. The renal expression of PAH transporters was evaluated by Western blotting. EPO-treated rats showed an increase in PAH systemic clearance, in its elimination rate constant, and in urinary PAH levels, while PAH in renal tissue was decreased. Moreover, EPO administration increased the expression of the transporters of the organic anions evaluated. The EPO-induced increase in PAH clearance is accounted for by the increase in its renal secretion mediated by the organic anion transporters. The goal of this study is to add important information to the wide knowledge gap that exists regarding drug–drug interactions. Owing to the global use of EPO, these results are useful in terms of translation into clinical practice.
BIOMECHANICAL ASSESSMENT OF WEAR IN CERAMIC ON CERAMIC AND CERAMIC ON XLPE THAs
Authors: TRIANTAFYLLOU ATHANASIOS , PAPAGIANNIS GEORGIOS , STASI SOPHIA , GEORGIOS PAPATHANASIOU , KOULOUVARIS PANAYIOTIS , PAPAGELOPOULOS PANAYIOTIS J. , BABIS GEORGE C.
Published: March 2021

Total Hip Arthroplasty (THA) is an effective treatment for severe hip arthritis, with patients reporting high rates of satisfactory results postoperatively. There are a variety of choices regarding THA implant designs. Ceramic on Ceramic and Ceramic on Highly Cross-Linked Polyethylene (XLPE) THAs are the materials of choice nowadays. The purpose of this study is to review the effect of kinematics and kinetics on wear (in vivo and in vitro testing) that affect wear in Ceramic on Ceramic and Ceramic on XLPE total hip arthroplasties and identify possible advantages amongst them. The study hypothesis was that THA kinematics and/or kinetics, since they directly affect THA wear, could provide data for possible advantages between the examined implant designs. A systematic review of the literature identified no significant evidence for biomechanical advantages between these two prostheses in terms of wear. Further research is proposed with the use of gait analysis systems combined with surface electromyography to further investigate THA biomechanics at a laboratory set up. Wearable sensors technology could also identify detailed biomechanical parameters in more complex daily activities.
Improving parameter precision of estimation by no-knowledge feedback control
Authors: Rao Huang-yun , Huang Xiao-Ze
Published: March 2021

We investigate a scheme to improve the precision of parameter estimation using no-knowledge measurement-based feedback control. The scheme shows that combination of no-knowledge measurement-based feedback control and quantum weak measurement is the optimal way to suppress decoherence. Our results indicate that compared with knowledge quantum feedback control, under the same weak measurement condition, the precision of parameter estimation can be improved more effectively with no knowledge quantum feedback control. Further, based on numerical simulation, we find that the feedback operator is chosen as [Formula: see text] (or both [Formula: see text] and [Formula: see text], which can protect quantum Fisher information (QFI) for a long time.
Addressing Spacer Channel Resistances in MCDI Using Porous and Pliable Ionic Conductors
Authors: Palakkal Varada Menon , Jordan Matthew L. , Bhattacharya Deepra , Lin Yupo J. , Arges Christopher G.
Published: March 2021

Membrane capacitive deionization (MCDI) is a unique electrochemical separations platform that allows for energy recovery during electrode regeneration. Similar to other electrochemical separation technologies producing deionized water (e.g. electrodialysis), ohmic resistances in the spacer channel significantly hampers the performance and energy efficiency of the process. This work devised a series of ionomer coated nylon mesh nets to address spacer channel resistances in MCDI. Under constant current operation, the ionomer coated nylon meshes displayed a 300 mV lower cell voltage rise during deionization while sustaining the same deionization rate. Furthermore, energy recovery was improved by 1.4x to 5.5x depending on the saline feed concentration. The lower cell voltage rise during deionization combined with the greater energy recovery with ionomer coated meshes resulted in energy normalized adsorbed salt (ENAS) values that were 2x to 3x greater. Addressing the spacer channel resistances in MCDI allowed for 8% to 19% increase in current density without the cell voltage exceeding 1.6 V—the upper bound set for mitigating parasitic reactions. Operating at higher current density leads to smaller MCDI units for a given deionization requirement and has implications for reducing the capital costs of the MCDI unit.
Altering Electronic and Optical Properties of Novel Benzothiadiazole Comprising Homopolymers via π Bridges
Authors: Karaman Cansu Zeytun , Göker Seza , Hacioğlu Serife O. , Hacıefendioğlu Tuğba , Yıldırım Erol , Toppare Levent
Published: March 2021

Four novel benzo[c][1,2,5]thiadiazole comprising monomers namely 5-fluoro-6-((2-octyldodecyl)oxy)-4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole (TBTT), 5-fluoro-4,7-bis(4-hexylthiophen-2-yl)-6-((2-octyldodecyl)oxy)benzo[c][1,2,5]thiadiazole (HTBTHT), 5-fluoro-4,7-di(furan-2-yl)-6-((2-octyldodecyl)oxy)benzo- [c][1,2,5]thiadiazole (FBTF), and 5-fluoro-6-((2-octyldodecyl)oxy)-4,7-bis(thieno[3,2-b]thiophen-2-yl)benzo[c][1,2,5]thiadiazole (TTBTTT) were designed, and synthesized successfully via Stille polycondensation reaction. The structural characterizations of the monomers were performed by 1H and 13C NMR spectroscopy and High Resolution Mass Spectroscopy (HRMS). The monomers were then electropolymerized in a three electrode cell system via cyclic voltammetry. The electrochemical, and spectroelectrochemical characterization of the polymers were reported in detail. Besides, theoretical calculations were performed to elucidate observed experimental properties. According to the cyclic voltammogram of the polymers, HOMO and LUMO energy levels were calculated as −5.68 eV/−3.91 eV, −5.71 eV/−3.72 eV, −5.61 eV/−4.04 eV, and −5.51 eV/−3.71 eV and the electronic band gaps were 1.77 eV, 1.99 eV, 1.57 eV, and 1.80 eV for PTBTT, PHTBTHT, PFBTF, and PTTBTTT, respectively.
MPC-Based Arctan Droop Control Strategy of the Parallel Inverter System in an Islanded AC Microgrid
Authors: Iyakaremye J. D. D. , Nyakoe G. N. , Wekesa C. W.
Published: March 2021

Distributed generations (DG) are one of the upcoming technologies recently used by many electric utilities in all corners of the world. Most of those DG form the microgrid (MG) to serve local loads and can be connected to the grid. This DG’s technology is enabled by utilizing renewable energy sources (REs) that are ecofriendly; however, these REs are intermittent by their nature, so controlling a power electronic device interfaced with them to be connected to the grid is another challenge. Many researchers have worked on the inverters’ control in MG. This study also elaborates on the control strategy for inverters adapted to REs for proper control of voltage and frequency used in an islanded microgrid. The study proposes a hybrid control strategy made of the virtual impedance droop control with arctan function and model predictive control. Extensive simulations have been carried out to validate the proposed control strategy’s effectiveness in terms of rapid transient response and stabilization of voltage, frequency, and power equitability among the microsources in the islanded microgrid.
Observed Shear-Relative Rainfall Asymmetries Associated with Landfalling Tropical Cyclones
Authors: Wang Xiang , Jiang Haiyan , Li Xun , Zhang Jun A.
Published: March 2021

This study examines the shear-relative rainfall spatial distribution of tropical cyclones (TCs) during landfall based on the 19-year (1998–2016) TRMM satellite 3B42 rainfall estimate dataset and investigates the role of upper-tropospheric troughs on the rainfall intensity and distribution after TCs make a landfall over the six basins of Atlantic (ATL), eastern and central Pacific (EPA), northwestern Pacific (NWP), northern Indian Ocean (NIO), southern Indian Ocean (SIO), and South Pacific (SPA). The results show that the wavenumber 1 perturbation can contribute ∼ 50% of the total perturbation energy of total TC rainfall. Wavenumber 1 rainfall asymmetry presents the downshear-left maxima in the deep-layer vertical wind shear between 200 and 850 hPa for all the six basins prior to making a landfall. In general, wavenumber 1 rainfall tends to decrease less if there is an interaction between TCs and upper-level troughs located at the upstream of TCs over land. The maximum TC rain rate distributions tend to be located at the downshear-left (downshear) quadrant under the high (low)-potential vorticity conditions.
Analysing the Vulnerability of Public Transport Networks
Authors: Mouronte-López Mary Luz
Published: March 2021

This paper analyses the robustness of specific public transport networks. Common attributes and which of them have more influence on the networks’ vulnerability are established. Initially, the structural properties of the networks in two graphical representations (L-Space and P-Space) are checked. Afterwards, the spread of problems (traffic jams, etc.) are simulated, employing a model based on a propagation and recovery mechanism, similar to those used in the epidemiological processes. Next, the size of the largest connected subset of stops of the network (giant component) is measured. What is shown is that the faults randomly happened at stops or links, also displaying that those that occurred in the highest weighted links spread slower than others. These others appear at stops with the largest level of betweenness, degree, or eigenvector centralities and PageRank. The modification of the giant component, when several stops and links are removed, proves that the removal of stops with the highest interactive betweenness, PageRank, and degree centralities has the most significant influence on the network’s integrity. Some equivalences in the degree, betweenness, PageRank, and eigenvector centrality parameters have been found. All networks show high modularity with values of index Q close to 1. The networks with the highest assortativity and lowest average number of stops are the ones which a passenger can use to travel directly to their destination, without any change. The Molloy–Reed parameter is higher than 2 in all networks, demonstrating that high integrity exists in them. All stops were characterized by low k-cores ≤3.
Prefabricated Urban Underground Utility Tunnels: A Case Study on Mechanical Behaviour with Strain Monitoring and Numerical Simulation
Authors: Xiao Yonggang , Zhang Jubing , Cao Jie , Li Changhong
Published: March 2021

The prefabricated urban utility tunnels (UUTs) have many advantages such as short construction period, low cost, high quality, and small land occupation. However, there is still a lack of in‐depth analysis of the mechanical performance of the prefabricated urban utility tunnel (UUT) structure with bolted connections under different working conditions. In this paper, the force performance of a prefabricated UUT in Tongzhou District, Beijing, was studied under different working conditions using two methods: field monitoring and numerical simulation. The multichannel strain monitor was used for monitoring, and the internal wall concrete and bolt strain change data under the two conditions of installation and backfill were obtained. Combined with the construction process of the UUTs, a three‐dimensional numerical model was established by COMSOL, where the build‐in bolt assembly was used to simulate the longitudinal connection of the tunnel. The simulation results were compared with the measured data to verify the rationality of the computational model. The simulation results showed that the concrete and bolts on the inner wall of the tunnel work well under the two conditions of installation and backfilling; The deformation of the top plate of the prefabricated tunnel was approximately parabolic, with the largest vertical displacement (0.37 mm) in the middle and the most sensitive to the vertical load in the central part of the roof. The central portion of the side wall had the largest displacement (0.17 mm) in the inner concave. The tensile stress of bolt 3 increased the most (30.75 MPa) but was still much smaller than the yield strength of the bolt. The concrete and bolts of the UUT were found to work well through force analysis under operating conditions. In conclusion, analysis of structural forces and deformation failure modes will help design engineers understand the basic mechanisms and select the appropriate UUT structure.
Study on the Seismic Performance of Small‐Diameter Bolts Reinforced in Grottoes
Authors: Peng Ningbo , Sun Bo , Huang Jizhong , Dong Yun , Zhu Ye
Published: March 2021

The Yungang Grottoes, a World Heritage Site in Datong, consist of 252 caves that are noted for their collection of 5th‐ and 6th‐century Buddhist grotto sculptures and reliefs. Various diseases have appeared in the grottoes under the general influence of natural and artificial factors. Bolt support is a commonly employed method for grotto reinforcement and has been widely applied in many projects. Small‐diameter bolts have also been used in the reinforcement projects at the Yungang Grottoes, but the corresponding effect on the seismic performance of grottoes is still unclear. In this paper, a dynamic analysis via the numerical modelling of an ear grotto of the 19th grotto in Yungang is established, and the rock displacement, acceleration, and bolt axial force responses under a seismic wave are analyzed. The results show that the seismic dynamic responses of grottoes are greatly affected by the cliff structure. The displacement and acceleration responses of the cliff body vary greatly within the abrupt transition of the cliff structure. Based on this variation, the seismic capacity of small‐diameter bolts in the vertical direction is greater than that in the horizontal direction. The axial force of a bolt is small at both ends of the bolt, large in the middle of the bolt, small on the top of a cliff, and large at the bottom of the cliff. Although the axial force is small, the upper rock mass of the grotto has a tendency to undergo relative movement compared with the outer rock mass. The results also indicate that based on the structural defects in the vertical direction of the cliff body caused by grotto excavation, the inclined angle of the bolt should be increased as far as possible or vertical support should be adopted to enhance the stability of the rock mass at the top of the grotto.
Use of Security Logs for Data Leak Detection: A Systematic Literature Review
Authors: Ávila Ricardo , Khoury Raphaël , Khoury Richard , Petrillo Fábio
Published: March 2021

Security logs are widely used to monitor data, networks, and computer activities. By analyzing them, security experts can pick out anomalies that reveal the presence of cyber attacks or information leaks and stop them quickly before serious damage occurs. This paper presents a systematic literature review on the use of security logs for data leak detection. Our findings are fourfold: (i) we propose a new classification of information leaks, which uses the GDPR principles; (ii) we identify the twenty most widely used publicly available datasets in threat detection; (iii) we describe twenty types of attacks present in public datasets; and (iv) we describe thirty algorithms used for data leak detection. The selected papers point to many opportunities that can be investigated by researchers interested in contributing to this area of research.
Traditional Chinese Medicine Strategy for Patients with Tourette Syndrome Based on Clinical Efficacy and Safety: A Meta‐Analysis of 47 Randomized Controlled Trials
Authors: Wang Na , Qin Dong-dong , Xie Yu-huan , Wu Xin-chen , Wang Ding-yue , Hang-Yang  , Li Xiao-xuan , Xiong Lei , Liang Jing-hong
Published: March 2021

Objective. Although increasing evidence reveals the efficacy of traditional Chinese medicine (TCM) and its safety on Tourette Syndrome (TS) patients, whether TCM is indeed improving TS remains unclear. The purpose of the current study is to perform a meta‐analysis to evaluate the efficacy and safety of TCM on treating TS patients. Method. An elaborate search strategy was conducted based on several databases including Medline, Embase, Cochrane, Web of Science, CINAHL, CBM, VIP, CNKI, and Wanfang Data in order to identify the relevant randomized controlled trials (RCTs) from their inception to as late as May 1st, 2020. General information and data needing analysis were extracted simultaneously for the necessity of various analyses such as descriptive analysis and metaquantitative analysis. Results. Forty‐seven trials with 5437 TS patients in total were eventually included according to our criteria. All trials were conducted in China, and the publication years ranged from 2004 to 2017. In terms of clinical efficacy, clinical symptoms of patients with TCM were more likely to be improved compared with the control group (odds ratio, OR = −1.29, 95% confidence interval, CI: ‐2.54 to ‐0.06, I2 = 0.00%). As to the outcome of recurrence rate, the pooled results revealed that the TCM group was more inclined to stabilize the recurrence (OR = 0.44, 95% CI: 0.24 to 0.78, I2 = 0.00%). Similar results were observed in adverse reaction (OR = 0.32, 95% CI: 0.24 to 0.43, I2 = 32.90%). Conclusion. The results of our study recommend applying TCM to treat TS patients for better efficacy and safety. Results need to be interpreted cautiously due to certain limitations in our study.
Association of Matrix Metalloproteinase‐2 mRNA Expression with Subtypes of Pediatric Cholesteatoma
Authors: Kan Taichi , Ueda Hiromi , Takahara Taishi , Tsuchiya Yoshimasa , Kishimoto Mayuko , Uchida Yasue , Ogawa Tetsuya , Ohashi Wataru , Tsuzuki Toyonori , Fujimoto Yasushi
Published: March 2021

Objective. Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase‐2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA‐in situ hybridization in formalin‐fixed, paraffin‐embedded (FFPE) tissue samples. Methods. Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University’s Otolaryngology Department, were analyzed for MMP2 expression level, using RNA‐in situ hybridization. Results. There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. Conclusion. Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.
Permeability and Microstructure of a Saline Intact Loess after Dry‐Wet Cycles
Authors: Xu Jian , Ren Chang , Wang Songhe , Gao Jingyu , Zhou Xiangang
Published: March 2021

Influenced by both dry‐wet cycles and salt weathering, the loess will exhibit significant changes in microstructure and permeability, which threatens the stability of loess slopes. Triaxial permeability tests and industrial computed tomography (CT) scans were carried out on saline intact loess with sodium sulfate. The relationship between permeability and pore structure of the loess after dry‐wet cycles was discussed. Results show that the permeability coefficient of loess increases after dry‐wet cycles, with the increment declining. After specified dry‐wet cycles, the permeability coefficient increases approximately linearly with sodium sulfate content. However, the permeability coefficient significantly declines at higher confining pressures, while its attenuation rate decreases. An empirical relationship based on log10(1 + e) −   log10(k) was proposed to estimate the permeability coefficient of saline intact loess considering dry‐wet cycles and salt content. Comparisons of measured and calculated results proved its rationality. CT scan images imply the damage to soil microstructure induced by dry‐wet cycles and salt weathering, corresponding to the decline of the mean CT value (ME) and the increase of both crack ratio and fractal dimension of crack network.
Model Test Research on the Influence of Gate Blocking in Siltation Environment
Authors: Li Hua , Wang Yifeng , Zhang Jingyu , Wan Liangpeng , Jiang Qiao , Pan Hongyue , Hu Yuanyuan , Wang Kun
Published: March 2021

Aiming at the clogging problems encountered in the operation of deep‐hole gates in high water level reservoirs and dams, this paper carried out a model test study on the influence of different materials and different siltation environments on the lifting of the gates and analyzed the rules of the effects of blockages in different siltation environments. An analysis model of the pull‐out force of the gate (blocked object) considering the siltation environment was proposed in an innovative way and the similarity ratio relationship was verified. The results of the study show that (1) the size and time of the siltation and other factors have a significant influence on the pulling force of the blocked object. It increases with the increase of the siltation area. The longer the siltation goes on, the greater the pulling force will be. (2) As the similarity ratio n increases, the calculation result of the analysis model is closer to the target value n2 and it indicates that the theoretical model is reliable. The research results of this paper can provide certain guidance for deep‐hole siltation dispatch to ensure project safety.
Estimation of Newly Established Iterative Scheme for Generalized Nonexpansive Mappings
Authors: Hussain Aftab , Hussain Nawab , Ali Danish
Published: March 2021

We introduce a new iterative method in this article, called the

D

iterative approach for fixed point approximation. Analytically, and also numerically, we demonstrate that our established

D

I.P is faster than the well-known I.P of the prior art. Finally, in a uniformly convex Banach space environment, we present weak as well as strong convergence theorems for Suzuki’s generalized nonexpansive maps. Our findings are an extension, refinement, and induction of several existing iterative literatures.
An Inelastic Theoretical Model regarding the Load‐Carrying Capacity of PSL Bending Component
Authors: Sheng Baolu , Bian Yuling , He Dong , Zhou Aiping
Published: March 2021

Parallel strand lumber (PSL) is an attractive structural wood composite which may have prospective use in building constructions. Conducting nonlinear analysis for the bending of PSL beams is a critical step in the determination of ultimate strength and deflection of them, which is an essential requirement of the building design philosophy based on probability of ultimate state. For the purposes of this article, an inelastic theoretical model regarding the load‐carrying capacity of the PSL bending component has been developed. Based on the uniaxial loading tests, the stress‐strain behaviors of PSL composite in the grain direction were measured. 4‐point bending experiments were also performed in this study to investigate the failure mechanism of the PSL components. The results show that the tensile stress‐strain relationship of PSL materials in the grain direction remains linear until breaking, while the compressive stress‐strain relationship exhibits nonlinear characteristics once the compressive stress exceeds the proportional limit, which can be expressed by a quadratic polynomial. The failure mode of the PSL beam can be summarized that the fibres in the top of the broken section were buckling and those in the bottom of the section were broken when failure occurred. Significant nonlinear behavior was exhibited based on the load‐deflection curves of the PSL beams. To predict the nonlinear bending performance of the PSL beams, a theoretical model that could consider the nonlinear stress‐strain relations of PSL and predict the damage modes of the PSL beams was developed. Well agreements can be observed between the results of calculations and experiments.
Fucoxanthin Prevents 6‐OHDA‐Induced Neurotoxicity by Targeting Keap1
Authors: Wu Wei , Han Hui , Liu Jingwangwei , Tang Min , Wu Xiaoyu , Cao Xiaojun , Zhao Tiantian , Lu Yujia , Niu Tingting , Chen Juanjuan , Chen Haimin
Published: March 2021

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin (FUC) is considered to have excellent neuroprotective activity. However, the target of FUC for its neuroprotective properties remains largely unclear. Oxidative stress is one of the initiating factors causing neuronal cell loss and necrosis, and it is also an important inducement of Parkinson’s disease (PD). In the present study, the neuroprotective effect of FUC was assessed using a 6‐hydroxydopamine‐ (6‐OHDA‐) induced neurotoxicity model. FUC suppressed 6‐OHDA‐induced accumulation of intracellular ROS, the disruption of mitochondrial membrane potential, and cell apoptosis through the Nrf2‐ARE pathway. Keap1 as a repressor of Nrf2 can regulate the activity of Nrf2. Here, the biolayer interferometry (BLI) assay demonstrated that FUC specifically targeted Keap1 and inhibited the interaction between Keap1 and Nrf2. FUC bound to the hydrophobic region of Keap1 pocket and formed hydrogen bonding interactions with Arg415 and Tyr525. Besides, it also dose‐dependently upregulated the expressions of antioxidant enzymes, such as nicotinamide heme oxygenase‐1, glutamate‐cysteine ligase modifier subunit, and glutamate‐cysteine ligase catalytic subunit, in 6‐OHDA‐induced PC12 cells. In 6‐OHDA‐exposed zebrafish, FUC pretreatment significantly increased the total swimming distance of zebrafish larvae and improved the granular region of the brain tissue damage. These results suggested that FUC could protect the neuronal cells against 6‐OHDA‐induced injury via targeting Keap1.
Proposed Modification of the pN2 Classification of the 8th Edition AJCC Staging System for Esophageal Squamous Cell Carcinoma: A Preliminary Study Based on the Chinese Population
Authors: Xi Kexing , Yu Hui
Published: March 2021

Objective. To evaluate the efficacy of the nodal staging of the 8th edition AJCC staging system for esophageal squamous cell carcinoma (ESCC) and propose a modification of the current pN2 classification. Methods. 1188 patients who underwent esophagectomy for ESCC at Sun Yat-sen University Cancer Center in Guangzhou (Guangdong, China) between January 2005 and June 2010 were reviewed. We used the X-tile software to determine the optimal cutoff points. Kaplan–Meier method and log-rank test were used to compare the differences of survival. Multivariate Cox regression analysis was performed for the factors that were statistically significant in univariate analysis. Result. In multivariate Cox regression analysis, alcohol consumption, pT status, and pN status were independent prognostic factors for overall survival (OS) according to the current pN classifications. And the observed 5-year OS rates for groups pN0, pN1, pN2, pN3 were 66.7%, 45.0%, 31.5%, and 21.5%, respectively (P<0.001). Based on the above results, the current pN2 classification was further subdivided as pN2a [3 metastatic lymph nodes (LNs)] and pN2b (4−6 metastatic LNs) groups. The 5-year OS rates for groups pN0, pN1, pN2a, pN2b, and pN3 were 66.7%, 45.0%, 37.7%, 26.3% and 21.5%, respectively (P<0.001). The rate of 5-year disease-free survival (DFS) was 60.0% for patients with pN0, compared with 36.8%, 29.3%, 20.8%, and 14.3% for those with pN1, pN2a, pN2b, and pN3, respectively (P<0.001).The current pN2 classification should be subdivided as pN2a (3 metastatic LNs) and pN2b (4–6 metastatic LNs) groups. The modified pN2 classification could better discriminate the survival differences between patients with 3–6 metastatic LNs for ESCC in the Chinese population.
Linalool Alleviates Aβ42‐Induced Neurodegeneration via Suppressing ROS Production and Inflammation in Fly and Rat Models of Alzheimer’s Disease
Authors: Yuan Chunyu , Shin Myeongcheol , Park Youngjae , Choi Byoungyun , Jang Seokhui , Lim Chaejin , Yun Hye Sup , Lee Im-Soon , Won So-Yoon , Cho Kyoung Sang
Published: March 2021

Terpenes are vital metabolites found in various plants and animals and known to be beneficial in the treatment of various diseases. Previously, our group identified terpenes that increased the survival of Alzheimer’s disease (AD) model flies expressing human amyloid β (Aβ) and identified linalool as a neuroprotective terpene against Aβ toxicity. Linalool is a monoterpene that is commonly present as a constituent in essential oils from aromatic plants and is known to have anti‐inflammatory, anticancer, antihyperlipidemia, antibacterial, and neuroprotective properties. Although several studies have shown the beneficial effect of linalool in AD animal models, the mechanisms underlying the beneficial effect of linalool on AD are yet to be elucidated. In the present study, we showed that linalool intake increased the survival of the AD model flies during development in a dose‐dependent manner, while the survival of wild‐type flies was not affected even at high linalool concentrations. Linalool also decreases Aβ‐induced apoptosis in eye discs as well as the larval brain. Moreover, linalool intake was found to reduce neurodegeneration in the brain of adult AD model flies. However, linalool did not affect the total amount of Aβ42 protein or Aβ42 aggregation. Rather, linalool decreased Aβ‐induced ROS levels, oxidative stress, and inflammatory response in the brains of AD model flies. Furthermore, linalool attenuated the induction of oxidative stress and gliosis by Aβ1-42 treatment in the rat hippocampus. Taken together, our data suggest that linalool exerts its beneficial effects on AD by reducing Aβ42‐induced oxidative stress and inflammatory reactions.
Pro- and Antitumorigenic Capacity of Immunoproteasomes in Shaping the Tumor Microenvironment
Authors: Leister Hanna , Luu Maik , Staudenraus Daniel , Lopez Krol Aleksandra , Mollenkopf Hans-Joachim , Sharma Arjun , Schmerer Nils , Schulte Leon N. , Bertrams Wilhelm , Schmeck Bernd , Bosmann Markus , Steinhoff Ulrich , Visekruna Alexander
Published: March 2021

Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1, and LMP7 is expressed in most immune cells. In this study, we describe opposing roles for immunoproteasomes in regulating the tumor microenvironment (TME). During chronic inflammation, immunoproteasomes modulated the expression of protumorigenic cytokines and chemokines and enhanced infiltration of innate immune cells, thus triggering the onset of colitis-associated carcinogenesis (CAC) in wild-type mice. Consequently, immunoproteasome-deficient animals (LMP2/MECL-1/LMP7–null mice) were almost completely resistant to CAC development. In patients with ulcerative colitis with high risk for CAC, immunoproteasome-induced protumorigenic mediators were upregulated. In melanoma tumors, the role of immunoproteasomes is relatively unknown. We found that high expression of immunoproteasomes in human melanoma was associated with better prognosis. Similarly, our data revealed that the immunoproteasome has antitumorigenic activity in a mouse model of melanoma. The antitumor immunity against melanoma was compromised in immunoproteasome-deficient mice because of the impaired activity of CD8+ CTLs, CD4+ Th1 cells, and antigen-presenting cells. These findings show that immunoproteasomes may exert opposing roles with either pro- or antitumoral properties in a context-dependent manner.
Smooth Muscle Cell–Specific PKM2 (Pyruvate Kinase Muscle 2) Promotes Smooth Muscle Cell Phenotypic Switching and Neointimal Hyperplasia
Authors: Jain Manish , Dhanesha Nirav , Doddapattar Prakash , Nayak Manasa K. , Guo Liang , Cornelissen Anne , Lentz Steven R. , Finn Aloke V. , Chauhan Anil K.
Published: March 2021

Objective:

The role of glycolytic enzyme PKM2 (pyruvate kinase muscle 2) in smooth muscle cell (SMC) phenotype switching and neointimal hyperplasia is poorly understood. We determined the role of PKM2 in SMC phenotype switching and neointimal hyperplasia.

Approach and Results:

We show that PKM2 is expressed in the SMC-rich neointima of the murine carotid artery and peri-strut areas in bare-metal stented human coronary arteries. PDGF-BB (platelet-derived growth factor-BB) stimulation upregulates the expression of PKM2 in cultured murine and human coronary SMC. To provide conclusive evidence for PKM2 in SMC function, we generated SMC-specific PKM2
−/−
mutant strain. We report that PKM2 deletion in SMC reduces injury-induced neointimal hyperplasia by inhibiting SMC proliferation and migration, suppressing synthetic phenotype, and reducing aerobic glycolysis associated with decreased ERK (extracellular signal-regulated kinase), mTOR (mammalian target of rapamycin), and STAT3 (signal transducer and activator of transcription 3) signaling. Furthermore, we show that nuclear PKM2 interacts with STAT3 and β-catenin and regulates transcription of MEK5 (mitogen/extracellular signal-regulated kinase kinase-5), cyclin D1, GLUT1 (glucose transporter 1), and LDHA (lactate dehydrogenase A). Treatment of human coronary SMC with ML265, an activator that induces PKM2 tetramerization and blocks its nuclear translocation, inhibited proliferation, migration, and phenotypic switching. Perivascular application of PKM2 activator reduced neointimal hyperplasia in mice.

Conclusions:

These findings reveal that PKM2 is a key regulator of SMC function in vascular remodeling and implicates PKM2 as a potential target to reduce neointimal hyperplasia.
Care of the Patient With Acute Ischemic Stroke (Posthyperacute and Prehospital Discharge): Update to 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association
Authors: Green Theresa L. , McNair Norma D. , Hinkle Janice L. , Middleton Sandy , Miller Elaine T. , Perrin Stacy , Power Martha , Southerland Andrew M. , Summers Debbie V. ,   on behalf of the American Heart Association Stroke Nursing Committee of the Council on Cardiovascular and Stroke Nursing and the Stroke Council
Published: March 2021

In 2009, the American Heart Association/American Stroke Association published a comprehensive scientific statement detailing the nursing care of the patient with an acute ischemic stroke through all phases of hospitalization. The purpose of this statement is to provide an update to the 2009 document by summarizing and incorporating current best practice evidence relevant to the provision of nursing and interprofessional care to patients with ischemic stroke and their families during the acute (posthyperacute phase) inpatient admission phase of recovery. Many of the nursing care elements are informed by nurse-led research to embed best practices in the provision and standard of care for patients with stroke. The writing group comprised members of the Stroke Nursing Committee of the Council on Cardiovascular and Stroke Nursing and the Stroke Council. A literature review was undertaken to examine the best practices in the care of the patient with acute ischemic stroke. The drafts were circulated and reviewed by all committee members. This statement provides a summary of best practices based on available evidence to guide nurses caring for adult patients with acute ischemic stroke in the hospital posthyperacute/intensive care unit. In many instances, however, knowledge gaps exist, demonstrating the need for continued nurse-led research on care of the patient with acute ischemic stroke.
Abstract 17: Time-Benefit Association is Magnified in Door-To-Puncture Window: Lose 1 Second, Lose 2.2 Hours of Healthy Life
Authors: Almekhlafi Mohammed A , GOYAL MAYANK , Dippel Diederik W , Majoie Charles B , Campbell Bruce , Muir Keith W , Demchuk Andrew M , Bracard Serge , guillemin francis , Jovin Tudor G , Mitchell Peter J , White Philip , Hill Michael D , Brown Scott , Saver Jeffrey L
Published: March 2021

Background:
The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the magnitude of the time-benefit relation because time of onset (last known well ”LKW”) is imprecisely known, and analyses including late-arriving patients have under-representation of “fast-progressors.”

Methods:
Patient level data were pooled by the HERMES Investigators from all 7 RCTs of stent retriever thrombectomy devices (entirely or predominantly) versus medical therapy. Analysis was confined to early-treated patients (LKW-to-puncture≤4h). Exposures: last known well-to-door (LKWTD) time; door-to-puncture (DTP) time; door-to-reperfusion (DTR) time. Outcomes: stroke-related quality of life at 3m (utility-weighted modified Rankin Scale); years of healthy life lost [disability-adjusted life years (DALYs)].

Results:
Among the 781 EVT-treated patients, 406 (52.0%) were treated within 4h of LKW, with LKW-to-Door time median 188 minutes (IQR 151-215) and DTP time 105 minutes (IQR 76-135). Among the 295/372 (79.3%) with substantial reperfusion, DTR time was median 145 minutes (IQR 111-186). Care process delays were more strongly associated with worse clinical outcomes in the DTP and DTR epochs than the LKW-To-Door epoch (Table 1A), e.g., for each 10 minute delay, healthy life-years lost were: DTP 1.8 months vs LKW-to-Door 0.0 months, p < 0.0001. Considering granular time increments, the amount of healthy life-years lost associated with each 1 second of delay was: DTP 2.2 hours, DTR 2.1 hours.(Table 1B)

Conclusion:
Post-arrival care delays are strongly associated with worse EVT patient outcomes in the early post-arrival time period. With every 1 second of delay in EVT delivery, patients lose 2.2 hours of healthy life-years. Continuous quality improvement to minimize delays in DTP and DTR for endovascular thrombectomy is warranted.
Abstract 2: Acute Stroke Care During The Covid-19 Pandemic: The Society Of Vascular And Interventional Neurology Collaboration
Authors: Siegler James E , Zha Alicia , Czap Alexandra L , Ortega-Gutierrez Santiago , Farooqui Mudassir , Liebeskind David S , Desai Shashvat , Hassan Ameer E , Starosciak Amy K , Linfante Italo , Rai Vivek , Thon Jesse M , Then Ryna , Heslin Mark , Thau Lauren , Khandelwal Priyank , Mohammaden Mahmoud , Haussen Diogo C , Nogueira Raul G , Jillella Dinesh V , Kaliaev Artem , Nguyen Thanh , Zaidat Osama O , Jovin Tudor G , Jadhav Ashutosh
Published: March 2021

Background:
We sought to evaluate whether the coronavirus disease 2019 (COVID-19) pandemic may have contributed to delays in acute stroke management at Comprehensive Stroke Centers (CSCs).

Methods:
Pooled clinical data of consecutive adult stroke patients from 12 U.S. CSCs (1/1/2019-5/31/2020) were queried. The rate of thrombolysis for non-transferred patients within the Target: Stroke goal of 60min was compared between patients admitted 3/1/2019-5/31/2019 (pre-COVID-19) and 3/1/2020-5/31/2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed.

Results:
Of the 7906 patients included, 1319 were admitted pre-COVID-19 and 933 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. There was no difference in the rate of thrombolysis within 60min during COVID-19 (OR 0.88, 95%CI 0.42-1.86, p=0.74), despite adjustment for variables associated with earlier treatment (adjusted OR 0.82, 95%CI 0.38-1.76, p=0.61). There was no significant overall delay to thrombolysis during the COVID-19 period vs. pe-COVID-19 (p=0.42), even after multivariable adjustment (p=0.63) or after comparison across months leading to COVID-19 (Figure). The only independent predictor of delayed treatment time between periods was the use of emergency medical services (adjusted β=-6.93, 95%CI -12.83 - -1.04, p=0.03). There was no significant delay from hospital arrival to imaging in all patients, or imaging to skin puncture in patients who underwent thrombectomy.

Conclusions:
There was no independent effect of the COVID-19 period on delays in acute care with respect to thrombolysis or thrombectomy in this multicenter observational cohort. Further studies are warranted to externally validate these findings, and determine if site volume or center accreditation may mediate a collateral effect of the pandemic on stroke care paradigms.
Abstract 22: Risk and Predictors of Depression Following Acute Ischemic Stroke in the Elderly: Comparison With Acute Myocardial Infarction
Authors: Mayman Naomi , Stein Laura K , Tuhrim Stanley , Jette Nathalie , Dhamoon Mandip S
Published: March 2021

Introduction:
Post-stroke depression (PSD) occurs commonly following stroke and is associated with worse outcomes and higher mortality. Previous research has not identified consistent predictors of PSD, and debate remains about whether PSD differs from other types of depression, including depression following other ischemic vascular events.

Objective:
We sought to comprehensively evaluate predictors of PSD in the US population and compare the hazard of developing PSD to post-myocardial infarction (MI) depression.

Methods:
Retrospective cohort study of 100% de-identified inpatient, outpatient, and subacute nursing Medicare data from 2016-2017 for US patients aged ≥65 years from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio for diagnosis of depression up to 1.5 years post-stroke vs. MI, as well as independent predictors of PSD, and controlled for patient demographics, comorbidities, length of stay and acute stroke interventions.

Results:
In fully adjusted models, stroke patients (n=174,901) were approximately 50% more likely than MI patients (n=193,418) to develop depression during the 1.5-year follow-up period (Kaplan-Meier cumulative risk 0.1596 ± 0.001 in stroke patients versus 0.0973 ± 0.000778 in MI patients, log-rank p<0.0001). History of anxiety was the strongest predictor of PSD, while discharge home was most protective. Female patients, White patients, and patients younger than 75 years were more likely to be diagnosed with depression post-stroke.

Conclusions:
Despite the similarities between MI and stroke, patients who suffer from stroke were significantly more likely to develop depression. There were several predictors of post-stroke depression, most significantly history of anxiety. Our findings lend credibility to a stroke-specific process causing depression and highlight the need for consistent depression screening in all stroke patients.
Abstract 24: Predicting Persistent Upper Extremity Impairment in Ischemic Stroke Patients
Authors: de Havenon Adam H , Braun Robynne , Sunmonu N Abimbola , Heitsch Laura , Mistry Eva , Cole John W , Lindgren Arne , Worrall Bradford B , Cramer Steven C
Published: March 2021

Background:
Motor impairment after ischemic stroke is common and has variable recovery that depends on patient factors and stroke severity. An important challenge in rehabilitation research is enrolling patients who may benefit from interventions to improve recovery because they will not recover with standard care.

Hypothesis:
We can accurately predict persistent upper extremity motor impairment at 90 days after acute ischemic stroke.

Methods:
The primary outcome was an NIHSS arm domain score of 2-4 at 90 days in patients with a 24-hour NIHSS arm score of 1-4, which we termed persistent arm impairment. With the NINDS tPA trial dataset we used LASSO regression to select baseline demographics and 24-hour NIHSS score domains for a predictive model. We gave one point each for age ≥60 years and 24-hour NIHSS values of worst arm=4, worst leg>2, facial palsy=3, and total NIHSS≥10. The optimal cutpoint for a positive Persistent UPPer extremity Impairment (PUPPI) Score was ≥3 points. We validated the PUPPI score in the ALIAS Part 2, IMS-III, and DEFUSE 3 trials.

Results:
We included 431, 383, 331, and 71 patients from the NINDS tPA, ALIAS Part 2, IMS-III, and DEFUSE 3 trials. PUPPI was most common in the NINDS tPA trial (62%) and least common in ALIAS (31.3%). The PUPPI Score accurately predicted PUPPI with an area under the receiver operating curve (AUC) of >0.75 for all trials (Table 1). The positive predictive value was 74.6%, 90.9%, 86.1%, and 74.5% in the NINDS tPA, ALIAS Part 2, IMS-III, and DEFUSE 3 trials (Table 1).

Conclusion:
The PUPPI score uses readily available information to provide accurate prediction of patients who will have persistent upper extremity motor impairment at 90 days from stroke onset.