bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the Nervous System of the Parasitic Worm, Haemonchus Contortus, With Quercetin.
Authors: Goel Vanshita , Chakroborty Neloy , Sharma Sunidhi , Singla Lachhman , Choudhury Diptiman 
Published: September 2021

Abstract
Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of quercetin in the adult worms, which eventually lead to the paralysis and death of the worms. Thus, altogether, this work demonstrates that the nervous system of the parasitic helminth, H. contortus, is a novel target of the drug quercetin.
Genomic Characteristics and Evolutionary Analysis of a Rare GI.1 Norovirus Isolate From Beijing, China
Authors: Zhang Weishan , Zhang Wei , Hu Xinling , Zhou Xintong , Tian Guobao , Xu Yinghua , Mi Kaixia 
Published: September 2021

Abstract
Noroviruses are one of the main pathogens of acute gastroenteritis, causing frequent outbreaks worldwide every year that seriously affect human health. The GII.4 genotype causes most norovirus (NoV) infections and large-scale outbreaks. By contrast, the GI genotype is relatively rare. In this study, the whole genome sequence of a newly isolated ZD strain from a patient in Beijing, China, was sequenced and analyzed. The ZD strain genome consisted of 7,597 nucleotides and contained three open reading frames. Whole-genomic analysis indicated the strain was a GI.1 genotype, and no recombination site was detected in the genome. The histo-blood group antigen (HBGA)binding site associated with invasion of the GI genotype did not change, implying relatively conservative evolution. Phylogenetic analysis indicated the VP1 sequence of GI.1 strains could be divided into three clusters according to time of appearance: older (1968-2011), earlier (2011-2015), and new (2017-2018). Each cluster showed distinctive amino acid substitution characteristics, and the number of substitutions increased with time. The isolated ZD strain was in the new cluster. This study is the first to conduct a phylogenetic analysis of a GI genotype NoV isolated from Beijing. The results improve understanding of NoV diversity in China and can be a reference for further study of nondominant epidemic strains of NoVs as well as epidemic prevention and control.
TGF-β activates NLRP3 Inflammasome by an Autocrine Production of TGF-β in LX-2 Human Hepatic Stellate Cells
Authors: Oh Yoon Sin , Kang Hwansu , Seo Eunhui , Jun Hee-Sook 
Published: September 2021

Abstract
Inflammation contributes to the pathogenesis of liver disease, and inflammasome activation has been identified as a major contributor to the amplification of liver inflammation. Transforming growth factor-beta (TGF-β) is a key regulator of liver physiology, contributing to all stages of liver disease. We investigated whether TGF-β is involved in inflammasome-mediated fibrosis in hepatic stellate cells. Treatment with TGF-β increased priming of NLRP3 inflammasome signaling by increasing NLRP3 levels and activating TAK1-NF-kB signaling. Moreover, TGF-β increased the expression of p-Smad2/3-NOX4 in LX-2 cells and consequently increased ROS content, which is a trigger for NLRP3 inflammasome activation. Elevated expression of NEK7 and active caspase-1 was also shown in TGF-β-induced LX-2 cells, and this level was reduced by (5Z)-oxozeaenol, a TAK inhibitor. Finally, TGF-β-treated cells significantly increased TGF-β secretion levels, and their production was inhibited by IL-1β receptor antagonist treatment. In conclusion, TGF-β may represent an endogenous danger signal to the active NLRP3 inflammasome, by which IL-1β mediates TGF-β expression in an autocrine manner. Therefore, targeting the NLRP3 inflammasome may be a promising approach for the development of therapies for TGF-β-induced liver fibrosis.
Preoperative and Postoperative Nomograms in Predicting Early Recurrence of Hepatocellular Carcinoma Without Macrovascular Invasion After Curative Resection
Authors: Zhang Yanfang , Xu Liangliang , Xu Mingqing , Tang Hong 
Published: September 2021

Abstract
This study aimed to establish pre- and postoperative nomograms in predicting postoperative early recurrence (ER) for hepatocellular carcinoma (HCC) without macrovascular invasion. The patients who underwent curative LR for HCC from January 2012 to December 2016 in our center were divided into training and internal prospective validation cohorts. Nomograms were constructed based on the independent risk factors derived from multivariate logistic regression analyses in training cohort. The predictive performance of nomograms was validated by internal prospective validation cohort. A total of 698 patients fulfilled with eligible criteria. Among them, 265 out of 482 patients (55.0%) in training cohort and 120 out 216 (55.6%) patients in validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha fetoprotein (AFP), tumor diameter, tumor number; the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvasular invasion (MVI) and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy with C-indices of 0.712 and 0.850 in training cohort, and 0.754 and 0.857 in validation cohort, respectively. The calibration curves showed optimal agreement between the prediction by the nomograms and actual observation. The area under the receiver operating characteristic curves of pre- and postoperative nomograms were 0.721 and 0.848 in training cohort, and 0.754 and 0.844 in validation cohort, respectively. Present nomograms showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery, which were helpful for doctors in designation of treatments and selection of patients for regularly surveillance or administration of neoadjuvant therapies.
MDO: A Computational Protocol for Accurate Prediction of Full Flexibility Receptor-Ligand Binding Mode Structures
Authors: Al-Ansi Amar Y. , Lin Zijing 
Published: September 2021

Abstract
Predicting the binding structure of bio-complex is essential for understanding its properties, functions, and mechanisms, but is rather difficult due to the huge sampling space involved. A new computational protocol, MDO, for finding the ligand binding structure is proposed. MDO consists of global sampling via MD simulation and clustering of the receptor configurations, local sampling via molecular docking and clustering of the ligand conformations, and binding structure optimization by the ONIOM (QM/QM) method. MDO is tested on 15 protein-ligand complexes with known accurate structures. The success rate of MDO predictions, with RMSD < 2 Å, is found to be 67%, substantially higher than the 40% success rate of conventional methods. The MDO success rate can be increased to 83% if the ONIOM calculations are applied only for the starting poses with ligands inside the binding cavities. The MDO protocol is a promising tool for the structure based drug design.
Fatigue of full crown monolithic CAD/CAM restorations for posterior teeth
Authors: Bataineh khaled , Alkarasneh assem Al 
Published: September 2021

Abstract
Objective

The purpose of this study is to estimate the fatigue life of five polycrystalline zirconia CAD/CAM ceramic materials used for posterior restoration. This study presents the first time methodology to translate raw data obtained from laboratory test into useful data to predict the clinical life of dental restoration.
Methods

A typical model for the first molar restored crown is built and transferred into finite element software ANSYS 18.1 flor execution FEA. The materials are: two Y-TZP zirconia (LAVA (LVs), and EVEREST (KVs); IPS e.max CAD; Suprinity PC; and Celtra Duo. Two types of loads are applied, axial load and axial load followed by the sliding motion of lower jaw. The fatigue resistance of various restorative materials is determined.
Results

Experimental findings show that all the samples have fractured between cusps at the same location, which is slightly off the symmetry fissure plane. For crowns made of LAVA and EVEREST, the life is longer than 10 years under an axial load of 1000 N, while the lives for IPS e.max CAD; Suprinity PC; and Celtra Duo were longer than 10 years under an axial load of 185 N. The life of all-ceramic crown materials was predicted by FEA and found to conform to previous experimental and clinical observations.
Conclusion

Crowns made of Y-TZP zirconia has superior fatigue resistance compared to other ceramic CAD/CAM materials.
Regional Living Conditions and the Prevalence, Awareness, Treatment, Control of Hypertension at the Individual Level in Russia
Authors: Maksimov Sergey Alekseevich , Balanova Yulia A. , Shalnova Svetlana A. , Muromtseva Galina A. , Kapustina Anna V. , Drapkina Oksana M. 
Published: September 2021

Abstract
Background. The objective of this study was to analyze the influence of the living characteristics of large regions on the possible presence, awareness, management and control of hypertension at the individual level in the Russian population.Methods. Regional characteristics were obtained from the official website of the Federal State Statistics Service of Russia. Principal component analysis was used to reduce the dimensionality of data; it allowed defining 5 integral regional indices: Socio-Geographical, Demographic, Industrial, Mixed, Economic. Presence, awareness, management and control of hypertension were assessed according to the data of the cross-sectional stage of ESSE-RF study that was conducted in 2013-2014. The final sample included 19,791 patients from 12 regions of Russia. Generalized estimation equations were used to determine associations between regional indices and presence, awareness, management and control of hypertension at the individual level taking into consideration nested data structures (individuals in regions).Results. The Socio-Geographic Index demonstrated the positive impact on hypertension among male (OR = 1.18; 95% CI: 1.05-1.32), undereducated individuals (OR = 1.14; 95% CI: 1.02-1.27) and elderly people (OR = 1.16; 95% CI: 1.02-1.32). Awareness of hypertension is positively associated with Demographic (OR = 1.13; 95% CI: 1.02-1.25) and Industrial Indices (OR = 1.15; 95% CI: 1.01-1.33). Worsening of social environment (Socio-Geographic Index) reduces adherence to management (OR = 0.76; 95% CI: 0.64-0.90) and control of hypertension (OR = 0.79; 95% CI: 0.69-0.90). Impact of regional living conditions on the prevalence of hypertension is not high, compared to the individual predictors, but for the awareness, treatment and control of hypertension, this influence is important.Conclusions: The study performed allowed assessing the influence of living characteristics of the population in the large regions of Russia on the prevalence of hypertension and on the awareness, management and control of this disease. The data obtained provide new knowledge not only in terms of epidemiology of cardiovascular diseases in Russia but also in general, that is, in the context of studying the influence of living conditions on the health of population.
Berberine improves hepatic insulin resistance by activating the SIRT1/Opa1 pathway: An in vitro and in vivo study
Authors: Xu Jia , Zhang Yining , Yu Zhiyi , Guan Yueqi , Lv Yuqian , Zhang Meishuang , Zhang Ming , Chen Li , Lv Xiaoyan , Guan Fengying 
Published: September 2021

Abstract
Aim: This study explored whether abnormality in the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) causes hepatic insulin resistance and whether berberine (BBR) can prevent hepatic insulin resistance through the SIRT1/Opa1 pathway. Method: High-fat diet (HFD)-fed mice and db/db mice were used as animal models to study hepatic insulin resistance in vivo . Insulin resistance, morphological changes, and mitochondrial injury of the liver were examined to explore the effects of BBR. SIRT1/Opa1 protein expressions were determined to confirm whether the signalling pathway was damaged in the model animals and involved in BBR treatment. A palmitate (PA)-induced hepatocyte insulin resistance model was established in HepG2 cells in vitro . Opa1 silencing and SIRT1 overexpression were induced to verify whether Opa1 abnormality causes hepatocyte insulin resistance and whether SIRT1 could improve this dysfunction. BBR treatment and SIRT1 silencing were employed to prove that BBR can prevent hepatic insulin resistance by activating the SIRT1/Opa1 pathway. Results: We found that Opa1 deficiency caused imbalance in mitochondrial fusion/fission and impaired insulin signalling in the HepG2 cells. SIRT1 and BBR overexpression ameliorated PA-induced insulin resistance, increased Opa1, and improved mitochondrial function. SIRT1 silencing could partly reverse the effects of BBR in the HepG2 cells. SIRT1 and Opa1 were downregulated in the animal models. BBR attenuated hepatic insulin resistance and enhanced SIRT1/Opa1 signalling in the the db/db mice. Conclusion: Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte insulin resistance. BBR may improve hepatic insulin resistance by regulating the SIRT1/Opa1 pathway, and thus, it may be used to treat type 2 diabetes.
Increased Peripheral Blood Eosinophils may Indicate Acute Infection in Neonates
Authors: Wang Weiying , Zhao Yuan , Yuan Bi-Fen 
Published: September 2021

Abstract
Objective To explore the association between increased blood eosinophils and frequent pathogens due to the infections in children. Methods A total of 2353 children with acute infections admitted to Guangzhou Women and Children's Medical Center from February 1, 2019 to January 31, 2020 were enrolled in the study. 277 children without infections were comprised the control group. Children’s age, peripheral blood parameters including white blood cells, eosinophils, C-reactive protein (CRP) were recorded. In addition, infection stage and departments the patients admitted to were investigated. Results Blood eosinophil numbers negatively correlated with the age of children, whereas had no relation to disease stage. The means of eosinophil for neonates (<0.1 year)，infancy (<1year) and children >1year with acute infections were 0.67±0.40, 0.40±0.68, 0.15±0.25 *109/L compared with control group matched for age(0.44±0.20, 0.45±0.27, 0.24±0.19*109/L, P <0.001, <0.001, 0.497, respectively). Among them, the mean of eosinophil in the neonates afflicted with acute infections was significantly higher than the others compared to age-matched controls (0.63±0.60 vs 0.44±0.20, P= 0.012). Areas under the curves (AUC) were 0.81 (95% CI 0.75–0.86) for eosinophil combined with CRP and 0.68 (95% CI 0.61–0.75) for CRP alone for acute infections in neonates (P=0.02). Patients admitted in ICU had higher eosinophils than outpatients (0.46±0.60 vs 0.16±0.24, P <0.001) but had no significant difference compared with control group (0.45±0.20, P >0.99). Conclusion Increased peripheral blood eosinophils may indicate acute infections among neonates. Eosinophil combined with CRP can contribute to evaluating this population.
Comprehensive Analysis of the Expression, Prognostic Value and Correlations with Immune Infiltration of PBX Family Members in Colorectal Cancer
Authors: Hu Yanping , Shen Yihang 
Published: September 2021

Abstract
Background: Colorectal cancer is the third commonest cancer and the second leading cause of cancer deaths globally. The Pre-B-cell leukemia transcription factor (PBX) family plays an essential biological role in the growth and development of the organism. PBX genes have been found to be implicated in the tumorigenesis of a variety of human tumors through multiple pathways, but its function in colorectal cancer is unclear. Methods: The expression pattern, prognostic value and relationship with immune infiltration of PBX genes in patients with colorectal cancer were investigated using the Oncomine, GEPIA, Kaplan-Meier Plotter and TIMER databases. In addition, gene mutation and interaction analysis of PBX family members in colorectal cancer patients using cBioPortal and GeneMANIA databases, respectively.Results: We revealed that a significantly lower expression level of PBX1, PBX2 and PBX3 in colorectal cancer tissues than in normal tissues, and the expression levels of PBX1 and PBX2 were significantly correlated with clinical tumor stage. Furthermore, survival analysis showed that high transcript levels of PBX4 were associated with overall survival in colon cancer patients, while low levels of PBX2 predicted improved disease-free survival in rectal cancer patients. In addition, in colon and rectal cancers, PBX proteins were notably associated with infiltration of multiple immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, B cells, and dendritic cells.Conclusion: These findings implies that PBX1 and PBX3 are potential targets for precision therapy of colorectal cancer patients and that PBX2 and PBX4 may be new prognostic markers for colorectal cancer patients.
High Performance Silicon Electrode Enabled by Titanicone Coating
Authors: Huertas Zahilia Cabán , Ramirez Daniel Settipani , Flox Cristina , Morante Joan Ramon , Kallio Tanja , Biendicho Jordi Jacas 
Published: September 2021

Abstract
This paper presents the electrochemical performance and characterization of nano Si electrodes coated with titanicone (TiGL) as an anode for Li-ion batteries. Atomic Layer Deposition (ALD) of the metal combined with the Molecular Layer Deposition (MLD) of the organic precursor is used to prepare coated electrodes at different temperatures with improved performance compared to the uncoated Si electrode. Coated electrodes prepared at 150° C delivers the highest capacity and best current response of 1800-1 mAhg-1 at 0.1 C and 150 mAhg-1 at 20 C. This represented a substantial improvement compared to the Si baseline which delivers a capacity of 1100 mAhg-1 at 0.1C but fails to deliver capacity at 20C. Moreover, the optimized coated electrode shows an outstanding capacity of 1200-1 at 1C for 350 cycles with a capacity decay of 93%. The improved discharge capacity, electrode efficiencies, rate capability and electrochemical stability for the Si-based electrode presented in this manuscript are directly correlated to the optimized TiGL coating layer deposited by the ALD/MLD processes, which enhances lithium kinetics as demonstrated by equivalent circuit analysis and low frequency data fitting. The coating strategy also stabilizes SEI film formation with better Coulombic efficiencies and improves long cycling stability by reducing capacity lost.
Enhanced Activity of Alzheimer Disease-associated Variant of
Protein Kinase Cα Drives Cognitive Decline
Authors: Lorden Gema , Wozniak Jacob , Doré Kim , Dozier Lara , Cates-Gatto Chelsea , Patrick Gentry , Gonzalez David , Roberts Amanda , Tanzi Rudolph , Newton Alexandra 
Published: September 2021

Abstract
Exquisitely tuned activity of protein kinase C (PKC) isozymes is essential to maintaining cellular homeostasis. Whereas loss-of-function mutations are generally associated with cancer, gain-of-function variants in one isozyme, PKCα, are associated with Alzheimer’s disease (AD). Here we show that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model. This variant causes a modest 30% increase in catalytic activity without altering on/off activation dynamics or stability, underscoring that enhanced catalytic activity is sufficient to drive the biochemical, cellular, and ultimately cognitive effects observed. Analysis of hippocampal neurons from the PKCα M489V mice reveals enhanced amyloid-β-induced synaptic depression and reduced spine density compared to wild-type mice. Behavioral studies reveal that this mutation alone is sufficient to impair cognition, and, when coupled to a mouse model of AD, further accelerates cognitive decline. The druggability of protein kinases positions PKCα as a new and promising therapeutic target in AD.
Design and Kinematic Analysis of a 4-SPS/U-based Four-level Rigid Trunk Mechanism
Authors: Pan Yi tao , Liu Gang Feng , Fan Jizhuang , Wang Shu Qi , Chen Yuan Yuan 
Published: September 2021

Abstract
A 4-SPS/U four-level rigid trunk mechanism, with SPS as the driving branch and U as the middle constrained driven branch, is innovatively proposed in this paper. It can improve the flexibility of hexapod mobile robots in posture adjustment in various motion modes such as walking, water propulsion, climbing, and rolling. Firstly, the screw theory is adopted to calculate the degree of freedom of the 4-SPS/U four-level rigid trunk mechanism. Secondly, a combination of closed vector method and decoupling method of eigenstructure assignment has been applied to constructing the inverse kinematics solution, and deriving the velocity and acceleration models as well as analyzing the high posture flexibility in workspace of the trunk mechanism. Thirdly, theoretical simulation data diagram of the movement branch chain displacement, end height, speed and acceleration of the trunk mechanism are calculated through theoretical numerical examples, and the excellent motion characteristics of the 4-SPS/U type four-level rigid trunk mechanism are analyzed. Finally, a quantitative comparison was made between the theoretical simulation data and the experimental data of the experimental prototype. The error rates of the variation curves of the displacement length, height, velocity and acceleration of the driving branch chain were 0.8%, 0.2%, 0.5% and 0.9%, which verified the correctness and reliability of the theoretical derivation.
Documentation of Body Mass Index is Associated with an Improvement of Mortality in Sepsis: Analysis of MIMIC-III Database
Authors: Wang Yuting , Ma Jiefei , Lin Xiaoming W , Huang Ting , Xie Rongcheng , Lin Xuefeng , Hong Xiangyu , Zhang Lianfang 
Published: September 2021

Abstract
Purpose: While improving outcomes in septic patients is currently becoming one of the hot research topics, the contribution of a body mass index (BMI) medical record to altering outcomes among septic patients in intensive care units (ICU) has not been examined. This study was designed to examine the association of BMI record with mortality specifically in ICU septic patients.Methods: The MIMIC-III database was employed to identify septic patients who had or had not measured height and weight to calculate BMI. Propensity score analysis was used to minimize confounders. The comparative risks of outcomes were further adjusted in the matched cohort with the use of a Cox proportional-hazards regression model. Kaplan-Meier survivor curve was plotted for outcomes in the propensity-score-matched cohort.Results: Among 10418 eligible septic patients, 4157 patients who had measured height and weight (BMI group) and 4157 patients who had not measured height and weight (No-BMI group) had similar propensity score. Significant benefit in terms of hospital mortality was observed among BMI group, compared to No-BMI group (19.24% vs. 24.44%, p<0.001). 30-day mortality (20.30% vs. 26.36%, p<0.001) and 1 year mortality (38.66% vs. 44.17%, p<0.001) was significantly higher in No-BMI group.Conclusions: In a general population of critically ill patients with sepsis, documentation of BMI is associated with an improvement of mortality