bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Profitabilitas, Likuiditas, Leverage dan Intensitas Aset Tetap Terhadap Agresivitas Pajak
Authors: Karlina Lilis
Published: October 2021

This study aims to empirically prove the effect of profitability, liquidity, leverage and intensity of fixed assets on tax aggressiveness (Empirical study on mining companies listed on the Indonesia Stock Exchange for the period 2012-2016). In this study there were a population of 46 mining companies listed on the Indonesia Stock Exchange for the period 2012-2016. The research method used in this study was quantitative. Through purposive sampling method, researchers obtained a sample of 12 companies listed on the Indonesia Stock Exchange for the period 2012-2016. The model in this study is panel regression using the Eviews 8 application. The data analysis technique in this study uses multiple linear analysis. The results of this study indicate that the profitability, liquidity and intensity of fixed assets have no significant effect on tax aggressiveness, while the leverage factor has a significant effect on tax aggressiveness. Profitability, liquidity, leverage and intensity of fixed assets together have a significant effect on tax aggressiveness.

Abstrak

Penelitian ini bertujuan untuk membuktikan secara empiris pengaruh profitabilitas, likuiditas, leverage dan intensitas aset tetap terhadap agresivitas pajak (Studi empiris pada perusahaan pertambangan yang terdaftar di Bursa Efek Indonesia periode 2012-2016). Populasi yang digunakan dalam penelitian ini sebanyak 46 perusahaan pertambangan yang terdaftar di Bursa Efek Indonesia periode 2012-2016. Metode penelitian yang digunakan yaitu kuantitatif, yakni melalui metode purposive sampling dengan sampel 12 perusahaan terdaftar di Bursa Efek Indonesia periode 2012-2016. Model dalam penelitian ini yaitu regresi panel dengan menggunakan aplikasi Eviews 8. Teknik analisis data yang digunakan dalam penelitian ini menggunakan analisis linear berganda. Hasilnya menunjukkan bahwa faktor profitabilitas, likuiditas dan intensitas asset tetap berpengaruh tidak signifikan terhadap agresivitas pajak. Sedangkan faktor leverage mempengaruhi secara signifikan terhadap agresivitas pajak. Dengan demikian, profitabilitas, likuiditas, leverage dan intensitas asset tetap secara bersama-sama berpengaruh signifikan terhadap agresivitas pajak.

Kata Kunci: Profitabilitas, Likuiditas, Leverage, Intensitas, Agresivitas Pajak
Development of A Decahedral Nanoenzyme Capable of Overcoming Hypoxia to Facilitate the Iodine-125 Radiosensitization of Esophageal Cancer
Authors: Jiao Dechao , Wu Kunpeng , Xu Kaihao , Liu Yiming , Zhao Deyao , Han Xinwei , Fan Ruitai
Published: October 2021

Radioisotopes have long been leveraged for internal radiotherapy-mediated cancer treatment. However, such therapeutic approaches are associated with serious side effects, and their efficacy is limited by intratumoral hypoxia. Herein, we prepared a folic acid-decorated palladium decahedral platform capable of enhancing the radiotherapeutic efficacy of iodine-125 (125I) seed treatment. This decahedral nanoenzyme was able to target tumor regions and catalyze the conversion of intracellular H2O2 to O2, thereby alleviating hypoxia within the tumor microenvironment. In addition, palladium was hypoxia can be alleviated, on the other hand, palladium was able to enhance the radiotherapeutic energy deposition within tumor tissues. The results of this analysis indicated that synthesized decahedral constructs can efficiently target and modify the hypoxic tumor microenvironment while simultaneously enhancing radiation energy deposition therein. Relative to palladium nanodots, the prolonged in vivo circulation of these decahedral constructs better enabled them to facilitate sustained radiosensitization. Overall, the results of this study highlight a novel approach to improving the therapeutic utility of 125I seed interstitial implantation, thus underscoring an important direction for future clinical research.
Optimal Trajectory Planning of the Variable-Stiffness Flexible Manipulator Based on CADE Algorithm for Vibration Reduction Control
Authors: Cheng Qiang , Xu Wenxiang , Liu Zhifeng , Hao Xiaolong , Wang Yi
Published: October 2021

Robotic manipulators are widely used for precise operation in the medical field. Vibration suppression control of robotic manipulators has become a key issue affecting work stability and safety. In this paper an optimal trajectory planning control method to suppress the vibration of a variable-stiffness flexible manipulator considering the rigid-flexible coupling is proposed. Through analyzing the elastic deformation of the variable-stiffness flexible manipulator, a distributed dynamic physical model of the flexible manipulator is constructed based on the Hamilton theory. Based on the mathematical model of the system, the design of the vibration damping controller of the flexible manipulator is proposed, and the control system with nonlinear input is considered for numerical analysis. According to the boundary conditions, the vibration suppression effect of the conventional and the variable-stiffness flexible manipulator is compared. The motion trajectory of the variable-stiffness flexible manipulator and compare the vibration response from different trajectories. Then, with minimum vibration displacement, minimum energy consumption and minimum trajectory tracking deviation as performance goals, the trajectory planning of the variable-stiffness flexible manipulator movement is carried out based on the cloud adaptive differential evolution (CADE) optimization algorithm. The validity of the proposed trajectory planning method is verified by numerical simulation.
P16INK4a Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency
Authors: Zhou Jiawen , Hou Chenxing , Chen Haiyun , Qin Ziyue , Miao Zi’an , Zhao Jingyu , Wang Qiuyi , Cui Min , Xie Chunfeng , Wang Rong , Li Qing , Zuo Guoping , Miao Dengshun , Jin Jianliang
Published: October 2021

This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1–deficient (Bmi-1–/–), Bmi-1 and p16INK4a double-knockout (Bmi-1–/–p16INK4a–/–), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)–dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1–/– and Bmi-1–/–p16INK4a–/– mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1–/– mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α–dependent barrier permeability and aging. Accumulated p16INK4a combined with occludin at the 1st–160th residue in cytoplasm of intestinal epithelium cells from Bmi-1–/– mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16INK4a deletion could maintain barrier function and microbiota balance in Bmi-1–/– mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16INK4a accumulation. The clearance of p16INK4a-positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1–160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16INK4a with occludin for protecting TJ.
High Resolution and Labeling Free Studying the 3D Microstructure of the Pars Tensa-Annulus Unit of Mice
Authors: Wu Jian-Ping , Yang Xiaojie , Wang Yilin , Swift Ben , Adamson Robert , Zheng Yongchang , Zhang Rongli , Zhong Wen , Chen Fangyi
Published: October 2021

Hearing loss is a serious illness affecting people’s normal life enormously. The acoustic properties of a tympanic membrane play an important role in hearing, and highly depend on its geometry, composition, microstructure and connection to the surrounding annulus. While the conical geometry of the tympanic membrane is critical to the sound propagation in the auditory system, it presents significant challenges to the study of the 3D microstructure of the tympanic membrane using traditional 2D imaging techniques. To date, most of our knowledge about the 3D microstructure and composition of tympanic membranes is built from 2D microscopic studies, which precludes an accurate understanding of the 3D microstructure, acoustic behaviors and biology of the tissue. Although the tympanic membrane has been reported to contain elastic fibers, the morphological characteristic of the elastic fibers and the spatial arrangement of the elastic fibers with the predominant collagen fibers have not been shown in images. We have developed a 3D imaging technique for the three-dimensional examination of the microstructure of the full thickness of the tympanic membranes in mice without requiring tissue dehydration and stain. We have also used this imaging technique to study the 3D arrangement of the collagen and elastic fibrillar network with the capillaries and cells in the pars tensa-annulus unit at a status close to the native. The most striking findings in the study are the discovery of the 3D form of the elastic and collagen network, and the close spatial relationships between the elastic fibers and the elongated fibroblasts in the tympanic membranes. The 3D imaging technique has enabled to show the 3D waveform contour of the collagen and elastic scaffold in the conical tympanic membrane. Given the close relationship among the acoustic properties, composition, 3D microstructure and geometry of tympanic membranes, the findings may advance the understanding of the structure—acoustic functionality of the tympanic membrane. The knowledge will also be very helpful in the development of advanced cellular therapeutic technologies and 3D printing techniques to restore damaged tympanic membranes to a status close to the native.
CD200 Blockade Modulates Tumor Immune Microenvironment but Fails to Show Efficacy in Inhibiting Tumor Growth in a Murine Model of Melanoma
Authors: Talebian Fatemeh , Yu Jianyu , Lynch Kimberly , Liu Jin-Qing , Carson William E. , Bai Xue-Feng
Published: October 2021

CD200-CD200R pathway regulates immune responses and has been implicated in the pathogenesis of a number of cancer types. CD200 blockade is considered a strategy for immunotherapy of CD200-positive cancers such as melanoma. Thus, it is critical to understand the potential impacts of CD200 blockade in a more human relevant tumor model. In this study, we evaluated these issues using the CD200+ Yumm1.7 mouse melanoma model. Yumm1.7 cells bear Braf/Pten mutations resembling human melanoma. We found that Yumm1.7 tumors grow significantly faster in CD200R–/– mice compared to wild type mice. Analysis of tumor immune microenvironment (TIME) revealed that tumors from CD200R–/– or anti-CD200 treated mice had downregulated immune cell contents and reduced TCR clonality compared to tumors from untreated wild type mice. T cells also showed impaired effector functions, as reflected by reduced numbers of IFN-γ+ and TNF-α+ T cells. Mechanistically, we found upregulation of the CCL8 gene in CD200R–/– tumors. In vitro co-culture experiments using Yumm1.7 tumor cells with bone marrow derived macrophages (BMDM) from WT and CD200R–/– mice confirmed upregulation of macrophage CCL8 in the absence of CD200-CD200R interaction. Finally, we found that anti-CD200 therapy failed to show efficacy either alone or in combination with checkpoint inhibitors such as anti-PD-1 or anti-CTLA4 in inhibiting Yumm1.7 tumor growth. Given that CD200R-deficiency or anti-CD200 treatment leads to reduced T cell responses in TME, using blockade of CD200 as an immunotherapy for cancers such as melanoma should be practiced with caution.
Paradoxical Roles of Leucine-Rich α2-Glycoprotein-1 in Cell Death and Survival Modulated by Transforming Growth Factor-Beta 1 and Cytochrome c
Authors: Jemmerson Ronald
Published: October 2021

Leucine-rich α2-glycoprotein-1 (LRG1) has been shown to impact both apoptosis and cell survival, pleiotropic effects similar to one of its known ligands, transforming growth factor-beta 1 (TGF-β1). Recent studies have given insight into the TGF-β1 signaling pathways involved in LRG1-mediated death versus survival signaling, i.e., canonical or non-canonical. Interaction of LRG1 with another ligand, extracellular cytochrome c (Cyt c), promotes cell survival, at least for lymphocytes. LRG1 has been shown to bind Cyt c with high affinity, higher than it binds TGF-β1, making it sensitive to small changes in the level of extracellular Cyt c within a microenvironment that may arise from cell death. Evidence is presented here that LRG1 can bind TGF-β1 and Cyt c simultaneously, raising the possibility that the ternary complex may present a signaling module with the net effect of signaling, cell death versus survival, determined by the relative extent to which the LRG1 binding sites are occupied by these two ligands. A possible role for LRG1 should be considered in studies where extracellular effects of TGF-β1 and Cyt c have been observed in media supplemented with LRG1-containing serum.
Meiotic Chromosome Dynamics in Zebrafish
Authors: Imai Yukiko , Olaya Ivan , Sakai Noriyoshi , Burgess Sean M.
Published: October 2021

Recent studies in zebrafish have revealed key features of meiotic chromosome dynamics, including clustering of telomeres in the bouquet configuration, biogenesis of chromosome axis structures, and the assembly and disassembly of the synaptonemal complex that aligns homologs end-to-end. The telomere bouquet stage is especially pronounced in zebrafish meiosis and sub-telomeric regions play key roles in mediating pairing and homologous recombination. In this review, we discuss the temporal progression of these events in meiosis prophase I and highlight the roles of proteins associated with meiotic chromosome architecture in homologous recombination. Finally, we discuss the interplay between meiotic mutants and gonadal sex differentiation and future research directions to study meiosis in living cells, including cell culture.
Comparative Techno-Economic and Exergetic Analysis of Circulating and Dual Bed Biomass Gasification Systems
Authors: Silva Ortiz Pablo , Maier Simon , Dietrich Ralph-Uwe , Pinto Mariano Adriano , Maciel Filho Rubens , Posada John
Published: October 2021

In this work, the techno-economic and exergy analyses of two gasification technologies with integration into heat and power combined cycles are presented: i). Circulating fluidized bed (CFB) and ii). Dual fluidized bed (DFB) systems. As feedstock, lignocellulosic biomass (sugarcane bagasse, SCB) was considered. The gasification process of the fluidized-bed systems (circulating and dual bed) and the syngas conversion were performed using Aspen Plus® software. The process design includes biomass drying and gasification, syngas cleaning, combustion, power generation, and heat recovery. The SCB-DFB system has the lowest irreversibility rate and, as a result, the highest overall performance and power generation (achieving 32% in the gasification system and 53% of exergy efficiency when coupled with the combined cycle). From the techno-economic assessment, the SCB-DFB system has the lowest total production costs per unit of energy. Hence, the dual fluidized bed systems could be a more competitive technology for the agro-industrial sector to generate power from lignocellulosic materials.
Potential Inhibitors of Fascin From A Database of Marine Natural Products: A Virtual Screening and Molecular Dynamics Study
Authors: Lin Lirui , Lin Kai , Wu Xiaodong , Liu Jia , Cheng Yinwei , Xu Li-Yan , Li En-Min , Dong Geng
Published: October 2021

Marine nature products are unique compounds that are produced by the marine environment including plants, animals, and microorganisms. The wide diversity of marine natural products have great potential and are versatile in terms of drug discovery. In this paper, we use state-of-the-art computational methods to discover inhibitors from marine natural products to block the function of Fascin, an overexpressed protein in various cancers. First, virtual screening (pharmacophore model and molecular docking) was carried out based on a marine natural products database (12015 molecules) and provided eighteen molecules that could potentially inhibit the function of Fascin. Next, molecular mechanics generalized Born surface area (MM/GBSA) calculations were conducted and indicated that four molecules have higher binding affinities than the inhibitor NP-G2-029, which was validated experimentally. ADMET analyses of pharmacokinetics demonstrated that one of the four molecules does not match the criterion. Finally, ligand Gaussian accelerated molecular dynamics (LiGaMD) simulations were carried out to validate the three inhibitors binding to Fascin stably. In addition, dynamic interactions between protein and ligands were analyzed systematically. Our study will accelerate the development of the cancer drugs targeting Fascin.
Synthesis of Ni/NiAlOx Catalysts for Hydrogenation Saturation of Phenanthrene
Authors: Liu Dao-Cheng , Chen Yu , Jing Jie-Ying , Rajendran Antony , Bai Hong-Cun , Li Wen-Ying
Published: October 2021

The saturation of octahydrophenanthrene was the rate-determining step in the hydrogenation process from phenanthrene to perhydrophenanthrene, which was due to the steric hindrance and competitive adsorption of octahydrophenanthrene. In this work, a series of Ni/NiAlOx catalysts with a uniform electron-deficient state of Ni derived from the nickel aluminate structure was synthesized to overcome the disadvantage of noble catalyst and the traditional sulfided catalysts in the saturation hydrogenation process of phenanthrene. Results showed that the catalyst calcinated at 650°C possessed more Ni2+ (∼98%) occupying octahedral sites and exhibited the highest robs (1.53 × 10−3 mol kg−1 s−1) and TOF (14.64 × 10−3 s−1) for phenanthrene hydrogenation. Furthermore, its ability to overcome steric hindrance and promote the rate-determining step was proven by octahydrophenanthrene hydrogenation. Comparing the evolution of hydrogenation activity with the change in the electronic structure of surface Ni sites, it was shown that the increase of metallic electron deficiency hindered the π-back bonding between surface Ni and aromatic rings, which was unfavorable for aromatic adsorption. As a result, the phenanthrene hydrogenation saturation performance can be enhanced by stabilizing the electron-deficient state of surface Ni on an optimal degree.
Analysis of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Effect on the Outcome of Early Infection After Kidney Transplantation
Authors: Zhang Fei , Zhong Jinbiao , Ding Handong , Pan Jiashan , Yang Jing , Lan Tianchi , Chen Yiding , Liao Guiyi
Published: October 2021

Background

Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections.

Methods

We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes.

Results

Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients.

Conclusions

In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.
Comparison of Red-Complex Bacteria Between Saliva and Subgingival Plaque of Periodontitis Patients: A Systematic Review and Meta-Analysis
Authors: Jiang Yaling , Song Bingqing , Brandt Bernd W. , Cheng Lei , Zhou Xuedong , Exterkate Rob A. M. , Crielaard Wim , Deng Dong Mei
Published: October 2021

The development of periodontitis is associated with an imbalanced subgingival microbial community enriched with species such as the traditionally classified red-complex bacteria (Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola). Saliva has been suggested as an alternative to subgingival plaque for the microbial analysis due to its easy and non-invasive collection. This systematic review aims to determine whether the levels of red-complex bacteria assessed using saliva reflect those in subgingival plaque from periodontitis patients. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to April 30, 2021. Studies were considered eligible if microbial data of at least one of the red-complex species were reported in both saliva and subgingival plaque from periodontitis patients, based on DNA-based methods. Of the 17 included studies, 4 studies used 16S rRNA gene sequencing techniques, and the rest used PCR-based approaches. The detection frequency of each red-complex species in periodontitis patients was reported to be > 60% in most studies, irrespective of samples types. Meta-analyses revealed that both detection frequencies and relative abundances of red-complex bacteria in saliva were significantly lower than those in subgingival plaque. Moreover, the relative abundances of all 3 bacterial species in saliva showed significantly positive correlation with those in subgingival plaque. In conclusion, current evidence suggests that one-time saliva sampling cannot replace subgingival plaque for microbial analysis of the red-complex bacteria in periodontitis patients. Given the positive microbial associations between saliva and subgingival plaque, a thorough review of longitudinal clinical studies is needed to further assess the role of saliva.
Investigating Origins of Ventricular Arrhythmia Arising From Right Ventricular Outflow Tract and Comparing Initial Ablation Strategies
Authors: Jiang Zhi , Liu Qifang , Tian Ye , Zhao Yidong , Liu Wei , Tian Longhai , Huang Jing , Tian Shui , Zheng Yaxi , Yang Long
Published: October 2021

Background: The origin distribution in right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs), as well as the initial ablation effectiveness of reversed U-curve method and antegrade method, remains unclear.

Objectives: To investigate the origin distribution of RVOT-type VAs and compare the initial ablation effectiveness of the two methods.

Method: Consecutive patients who had idiopathic RVOT-type VAs were prospectively enrolled. After activation mapping, patients were randomly assigned to supravalvular strategy using the reversed U-curve or subvalvular strategy using the antegrade method. The primary outcome was initial ablation (IA) success, defined as the successful ablation within the first three attempts.

Results: Sixty-one patients were enrolled from November 2018 to June 2020. Activation mapping revealed that 34/61 (55.7%) of the earliest ventricular activating (EVA) sites were above the pulmonary valves (PVs). The IA success rate was 25/33 (75.8%) in the patients assigned to supravalvular strategy as compared with 16/28 (57.1%) in those assigned to subvalvular strategy (p = 0.172). Multivariate analysis revealed a substantial and qualitative interaction between the EVA sites and IA strategies (pinteraction < 0.001). Either strategy had a remarkably higher IA success rate in treating its ipsilateral EVA sites than contralateral ones (p < 0.0083).

Conclusion: Of the idiopathic RVOT-type VA origins, half were located above the PV. The supravalvular and subvalvular strategies did not differ in IA success rates. However, they were complementary to reveal the EVA sites and facilitate ipsilateral ablation, which produces a significantly higher IA success rate.

Clinical Trial Registration: Chinese Clinical Trial Registry number, https://www.chictr.org.cn/showproj.aspx?proj=45623, ChiCTR2000029331.
Regulation of Cardiac-Specific Proteins Expression by Moderate-Intensity Aerobic Exercise Training in Mice With Myocardial Infarction Induced Heart Failure Using MS-Based Proteomics
Authors: Mi Shouling , Jiang Hao , Zhang Lei , Xie Zhonglei , Zhou Jingmin , Sun Aijun , Jin Hong , Ge Junbo
Published: October 2021

This study aims to systematically reveal the changes in protein levels induced by regular exercise in mice with ischemic-induced heart failure (HF). Aerobic exercise training for the ischemic-induced HF mice lasted for 4 weeks and then we used the liquid chromatography-mass spectrometry method to identify and quantify the protein profile in the myocardium of mice. As a whole, 1,304 proteins (597 proteins up-regulated; 707 proteins down-regulated) were differentially expressed between the exercise group and the sedentary group, including numerous proteins related to energy metabolism. The significant alteration of the component (E1 component subunit alpha and subunit beta) and the activity-regulating enzyme (pyruvate dehydrogenase kinase 2 and pyruvate dehydrogenase kinase 4) of pyruvate dehydrogenase complex and poly [ADP-ribose] polymerase 3, a nicotinamide adenine dinucleotide(+)-consuming enzymes, was further verified in targeted analysis. Generally, this proteomics profiling furnishes a systematic insight of the influence of aerobic exercise on HF.
PCSK9/LDLR System and Rheumatoid Arthritis-Related Atherosclerosis
Authors: Arida Aikaterini , Legaki Aigli-Ioanna , Kravvariti Evrydiki , Protogerou Athanasios , Sfikakis Petros P. , Chatzigeorgiou Antonios
Published: October 2021

Background/Aims: Rheumatoid arthritis (RA) is associated with the emergence of cardiovascular disease, while chronic inflammation is considered a common denominator for their parallel progression. The Proprotein convertase subtilisin/kexin type 9 (PCSK9)/LDL-Receptor (LDLR) system is of high importance during atherogenesis, via regulating the clearance of LDL from the circulation; nevertheless the role of this molecular mechanism during RA-related atheromatosis is not known.

Methods: Herein, high-resolution ultrasound measurements for arterial hypertrophy, atheromatosis and arterial stiffness as well as comprehensive biochemical profiling were performed in 85 RA patients. The circulating levels of PCSK9 and LDLR were measured and their potential associations as well as of the PCSK9/LDLR ratio with patients' characteristics and the degree of atherosclerosis were investigated.

Results: Increased LDLR levels and decreased PCSK9/LDLR ratio were found in RA patients with at least 2 atheromatic plaques as compared to the ones without any plaques. In addition the levels of both PCSK9 and LDLR were positively correlated with the presence of atheromatic plaques as an age- and gender- adjusted multivariate analysis revealed.

Conclusions: Our data imply that the PCSK9/LDLR system plays a significant role during RA-related atherosclerosis and may therefore be used as a screening tool for disease progression in the future.
Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form − 5 Years Follow-Up
Authors: Vladimirova-Kitova Lyudmila , Kitov Spas , Ganev Mihail , Chochkova-Bukova Lubov
Published: October 2021

The literature review we conducted reveals the limited use of proprotein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) in children with familial hypercholesterolemia (FH). In 2015, a 10-year-old boy presented with round, xanthochromic lesions on his right knee and elbow. The values of total and LDL-cholesterol (LDL-C)−18 and 15 mmol/l, respectively—along with normal triglycerides and HDL-cholesterol (HDL-C) confirmed the lesions were xanthomas. The data suggested a homozygous form of FH. The level of lipoprotein (a) was high: 270 mg/dl. Initial treatment, based on European recommendations, included Atorvastatin 20 mg and Ezetimibe 10 mg and led to a decrease in LDL-C by 46% for 5 months; however, the patient developed severe statin intolerance. Atorvastatin was replaced with Rosuvastatin 10 mg, but the symptoms persisted. Success was achieved by switching to an intermittent regimen: Rosuvastatin 10 mg three times a week with a daily intake of Ezetimibe 10 mg. However, the results were far from the desired LDL target. LDL-apheresis was advisable, but unfortunately, it is not performed in Bulgaria. In May 2017, a genetic analysis [two pathological mutations within the LDLR gene: c.1519A>G; p.(Lys507Glu) and c.2403_2406del; p.(Leu802Alafs*126)] confirmed the initial diagnosis: the patient had homozygous FH with compound heterozygosity indeed. Having turned 12 in September 2017, the patient was eligible for treatment with a PCSK9i: Evolocumab 140 mg. The mean reduction of LDL-C with the triple combination reached a reduction of 52.17% for the whole 2-year period. The LDL target was reached in January 2020. The triple therapy significantly reduced Apolipoprotein B by 29.16%. No statistically significant difference was found in Lp (a) levels (p > 0.05) Our clinical case demonstrates that the triple lipid-lowering combination in a patient with compound heterozygous FH is a good therapeutic option for reaching the LDL-target.
Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes
Authors: Bongiovanni Chiara , Sacchi Francesca , Da Pra Silvia , Pantano Elvira , Miano Carmen , Morelli Marco Bruno , D'Uva Gabriele
Published: October 2021

Despite considerable efforts carried out to develop stem/progenitor cell-based technologies aiming at replacing and restoring the cardiac tissue following severe damages, thus far no strategies based on adult stem cell transplantation have been demonstrated to efficiently generate new cardiac muscle cells. Intriguingly, dedifferentiation, and proliferation of pre-existing cardiomyocytes and not stem cell differentiation represent the preponderant cellular mechanism by which lower vertebrates spontaneously regenerate the injured heart. Mammals can also regenerate their heart up to the early neonatal period, even in this case by activating the proliferation of endogenous cardiomyocytes. However, the mammalian cardiac regenerative potential is dramatically reduced soon after birth, when most cardiomyocytes exit from the cell cycle, undergo further maturation, and continue to grow in size. Although a slow rate of cardiomyocyte turnover has also been documented in adult mammals, both in mice and humans, this is not enough to sustain a robust regenerative process. Nevertheless, these remarkable findings opened the door to a branch of novel regenerative approaches aiming at reactivating the endogenous cardiac regenerative potential by triggering a partial dedifferentiation process and cell cycle re-entry in endogenous cardiomyocytes. Several adaptations from intrauterine to extrauterine life starting at birth and continuing in the immediate neonatal period concur to the loss of the mammalian cardiac regenerative ability. A wide range of systemic and microenvironmental factors or cell-intrinsic molecular players proved to regulate cardiomyocyte proliferation and their manipulation has been explored as a therapeutic strategy to boost cardiac function after injuries. We here review the scientific knowledge gained thus far in this novel and flourishing field of research, elucidating the key biological and molecular mechanisms whose modulation may represent a viable approach for regenerating the human damaged myocardium.
Conversational Physical Activity Coaches for Spanish and English Speaking Women: A User Design Study
Authors: Figueroa Caroline A. , Luo Tiffany C. , Jacobo Andrea , Munoz Alan , Manuel Minx , Chan David , Canny John , Aguilera Adrian
Published: October 2021

Introduction: Digital technologies, including text messaging and mobile phone apps, can be leveraged to increase people's physical activity and manage health. Chatbots, powered by artificial intelligence, can automatically interact with individuals through natural conversation. They may be more engaging than one-way messaging interventions. To our knowledge, physical activity chatbots have not been developed with low-income participants, nor in Spanish—the second most dominant language in the U.S. We recommend best practices for physical activity chatbots in English and Spanish for low-income women.

Methods: We designed a prototype physical activity text-message based conversational agent based on various psychotherapeutic techniques. We recruited participants through SNAP-Ed (Supplemental Nutrition Assistance Program Education) in California (Alameda County) and Tennessee (Shelby County). We conducted qualitative interviews with participants during testing of our prototype chatbot, held a Wizard of Oz study, and facilitated a co-design workshop in Spanish with a subset of our participants.

Results: We included 10 Spanish- and 8 English-speaking women between 27 and 41 years old. The majority was Hispanic/Latina (n = 14), 2 were White and 2 were Black/African American. More than half were monolingual Spanish speakers, and the majority was born outside the US (>50% in Mexico). Most participants were unfamiliar with chatbots and were initially skeptical. After testing our prototype, most users felt positively about health chatbots. They desired a personalized chatbot that addresses their concerns about privacy, and stressed the need for a comprehensive system to also aid with nutrition, health information, stress, and involve family members. Differences between English and monolingual Spanish speakers were found mostly in exercise app use, digital literacy, and the wish for family inclusion.

Conclusion: Low-income Spanish- and English-speaking women are interested in using chatbots to improve their physical activity and other health related aspects. Researchers developing health chatbots for this population should focus on issues of digital literacy, app familiarity, linguistic and cultural issues, privacy concerns, and personalization. Designing and testing this intervention for and with this group using co-creation techniques and involving community partners will increase the probability that it will ultimately be effective.
Light-Absorbing Impurities on Urumqi Glacier No.1 in Eastern Tien Shan: Concentrations and Implications for Radiative Forcing Estimates During the Ablation Period
Authors: Zhang Xin , Li Zhongqin , You Xiaoni , She Yuanyang , Song Mengyuan , Zhou Xi
Published: October 2021

Light-absorbing impurities (LAIs) in surface snow and snow pits together with LAIs’ concentrations and their impacts on albedo reduction and sequent radiative forcing (RF) have been investigated in the past. Here, we focused on temporal–spatial distributions of LAIs, especially on the albedo reduction and radiative forcing caused by the LAIs in Urumqi Glacier No.1. Various snow samples, including fresh snow, aged snow, and granular ice were collected between 3,770 and 4,105 m a.s.l of Urumqi Glacier No.1 during the snowmelt season of 2015. For the surface snow samples, BC and OC concentrations were 582 and 1,590 ng g−1, respectively. Mineral dust (MD) concentrations were 110 μg g−1. Due to the different ablation status of the glacier surface, LAIs accumulate at the lower altitude of the glacier. The estimation by the Snow, Ice, and Aerosol Radiative (SNICAR) model indicated that BC and MD could reduce the albedo by 12.8 and 10.3% in fresh snow, aged snow by 23.3 and 5.9%, and granular ice by 22.4 and 26.7%, respectively. The RF of MD was higher than that of BC in fresh snow and granular ice, whereas the RF of BC exceeded MD in aged snow. These findings suggested that BC was the main forcing factor in snow melting and dust was the main forcing factor in accelerating glacier melt.
Crustal Structure of the Seismogenic Volume of the 2010–2014 Pollino (Italy) Seismic Sequence From 3D P- and S-Wave Tomographic Images
Authors: Napolitano Ferdinando , Amoroso Ortensia , La Rocca Mario , Gervasi Anna , Gabrielli Simona , Capuano Paolo
Published: October 2021

A tomographic analysis of Mt. Pollino area (Italy) has been performed using earthquakes recorded in the area during an intense seismic sequence that occurred between 2010 and 2014. 870 local earthquakes with magnitude ranging from 1.8 to 5.0 were selected considering the number of recording stations, the signal quality, and the hypocenter distribution. P- and S-wave arrival times were manually picked and used to compute 3D velocity models through tomographic seismic inversion. The resulting 3D distributions of VP and VS are characterized by high resolution in the central part of the investigated area and from surface to about 10 km below sea level. The aim of the work is to obtain high-quality tomographic images to correlate with the main lithological units that characterize the study area. The results will be important to enhance the seismic hazard assessment of this complex tectonic region. These images show the ductile Apennine platform (VP = 5.3 km/s) overlaying the brittle Apulian platform (VP = 6.0 km/s) at depth of around 5 km. The central sector of the area shows a clear fold and thrust interface. Along this structure, most of the seismicity occurred, including the strongest event of the sequence (MW 5.0). High VP (>6.8 km/s) and high VP/VS (>1.9) patterns, intersecting the southern edge of this western seismogenic volume, have been interpreted as water saturated rocks, in agreement with similar geological context in the Apennines. These fluids could have played a role in nucleation and development of the seismic sequence. A recent study revealed the occurrence of clusters of earthquakes with similar waveforms along the same seismogenic volume. The hypocenters of these cluster events have been compared with the events re-located in this work. Jointly, they depict a 10 km × 4 km fault plane, NW-SE oriented, deepening towards SW with a dip angle of 40–45°. Instead, the volume of seismicity responsible for the ML 4.3 earthquake developed as a mainshock-aftershock sequence, occurring entirely within the average-to-low VP/VS Apennine platform. Our results agree with other independent geophysical analyses carried out in this area, and they could significantly improve the actual knowledge of the main lithologic units of this complex tectonic area.
Electrical Resistivity Tomography (ERT) Monitoring for Landslides: Case Study in the Lantai Area, Yilan Taiping Mountain, Northeast Taiwan
Authors: Tsai Wu-Nan , Chen Chien-Chih , Chiang Chih-Wen , Chen Pei-Yuan , Kuo Chih-Yu , Wang Kuo-Lung , Lin Meei-Ling , Chen Rou-Fei
Published: October 2021

Water saturation in the bedrock or colluvium is highly related to most landslide hazards, and rainfall is likely a crucial factor. The dynamic processes of onsite rock/soil mechanics could be revealed via monitoring using the electrical resistivity tomography (ERT) technique and Archie’s law. This study aims to investigate water saturation changes over time using time-lapse ERT images, providing a powerful method for monitoring landslide events. A fully automatic remote resistivity monitoring system was deployed to acquire hourly electrical resistivity data using a nontraditional hybrid array in the Lantai area of Yilan Taiping Mountain in Northeast Taiwan from 2019 to 2021. Six subzones in borehole ERT images were examined for the temporal and spatial resistivity variations, as well as possible pathways of the groundwater. Two representative cases of inverted electrical resistivity images varying with precipitation may be correlated with water saturation changes in the studied hillslope, implying the process of rainfall infiltration. Layers with decreased and increased electrical resistivity are also observed before sliding events. Accordingly, we suggest that high-frequency time-lapse ERT monitoring could play a crucial role in landslide early warning.
Role of Professional Societies on Increasing Indigenous Peoples’ Participation and Leadership in STEMM
Authors: Ingram Jani C. , Castagno Angelina E. , Camplain Ricky , Blackhorse Davona
Published: October 2021

Indigenous people are the most underrepresented racial/ethnic group in Science, Technology, Engineering, Mathematics, and Medicine (STEMM) in the United States. Most prior research suggests this trend is the result broadly of settler colonialism, and more specifically of cultural differences between students and school/university environments; poor academic preparation in K-12 schools; vague constructs of educational or vocational goals; insufficient financial aid; unwelcoming school and university environments; prejudice and racism; and social isolation. There is also a vast body of published work on the unique epistemologies and knowledge systems held by Indigenous peoples, which are only recently being acknowledged within mainstream STEMM communities. One potential reason for lower participation in STEMM programs and professions by Indigenous people that has generally gone unexplored relates to unique cultural and spiritual factors that could deter Indigenous people from STEMM fields. Our research investigates the range and variation of cultural/spiritual/ethical practical issues that may be affecting Indigenous people’s success in STEMM. Our research provides valuable insights for policy and practices within higher education institutions and industry to provide flexible pathways for Indigenous people to reduce or eliminate barriers related to culturally- and spiritually-informed issues. In this paper, we explore how our findings can be used by professional societies to provide leadership to higher education institutions and industry in the area of changing some standard practices to be more inclusive of Indigenous people. An important mode of systemic change in STEMM fields is through professional societies that guide future practices in various STEMM disciplines.
Peritoneal Metastasis After Treated With Abemaciclib Plus Fulvestrant for Metastatic Invasive Lobular Breast Cancer: A Case Report and Review of the Literature
Authors: Gao Hong-Fei , Zhang Jun-Sheng , Zhang Qiang-Zu , Zhu Teng , Yang Ci-Qiu , Zhang Liu-Lu , Yang Mei , Ji Fei , Li Jie-Qing , Cheng Min-Yi , Niu Gang , Wang Kun
Published: October 2021

Peritoneal metastases from invasive lobular carcinoma (ILC) of breast are uncommon and usually related to poor prognosis due to difficulty of detection in clinical practice and drug resistance. Therefore, recognizing the entities of peritoneal metastases of ILC and the potential mechanism of drug resistance is of great significance for early detection and providing accurate management. We herein report a case of a 60-year-old female who presented with nausea and vomiting as the first manifestation after treated with abemaciclib (a CDK4/6 inhibitor) plus fulvestrant for 23 months due to bone metastasis of ILC. Exploratory laparotomy found multiple nodules in the peritoneum and omentum, and immunohistochemistry confirmed that the peritoneal metastatic lesions were consistent with ILC. Palliative therapy was initiated, but the patient died two months later due to disease progression with malignant ascites. Whole exome sequencing (WES) was used to detect the tumor samples and showed the peritoneal metastatic lesions had acquired ESR1 and PI3KCA mutations, potentially explaining the mechanism of endocrine therapy resistance. We argue that early diagnosis of peritoneal metastasis from breast cancer is crucial for prompt and adequate treatment and WES might be an effective supplementary technique for detection of potential gene mutations and providing accurate treatment for metastatic breast cancer patients.
Could Cytochrome P450 2D6, 3A4 and 3A5 Polymorphisms Explain the Variability in Clinical Response to Clomiphene Citrate of Anovulatory PCOS Women?
Authors: Robin Camille , Hennart Benjamin , Broly Franck , Gruchala Philippine , Robin Geoffroy , Catteau-Jonard Sophie
Published: October 2021

Introduction

Cytochrome P450 2D6, 3A4 and 3A5 are involved in the metabolism of many drugs. These enzymes have a genetic polymorphism responsible for different metabolic phenotypes. They play a role in the metabolism of clomiphene citrate (CC), which is used to induce ovulation. Response to CC treatment is variable, and no predictive factors have thus far been identified.

Objective

To study a possible link between the cytochrome P450 2D6, 3A4 and 3A5 polymorphisms and clinical response to CC.

Study Design

Seventy-seven women with anovulatory Polycystic Ovarian Syndrome (PCOS) treated with CC were included which determined their cytochrome P450 2D6, 3A4 and 3A5 genotypes and used the results to predict ovarian response to this drug. Predicted responses based on the cytochrome genotypes were compared with the observed clinical responses using the calculation of a weighted Kappa coefficient.

Main Outcome Measures

Number of dominant follicles assessed by ultrasound at the end of the follicular phase and confirmation of ovulation by blood progesterone assay in the luteal phase.

Results

Concordance between the predicted and observed responses for the combination of the three cytochromes was 36.71%, with a negative Kappa coefficient (K = -0.0240), which corresponds to a major disagreement. Similarly, for predictions based on the cytochrome P450 2D6 genotype alone, only 39.24% of predictions were verified (coefficient K = -0.0609).

Conclusion

The genetic polymorphism of cytochromes P450 2D6, 3A4 and 3A5 does not appear to influence clinical response to CC used to induce ovulation in anovulatory PCOS women.