bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyruvate Kinase Isoenzyme M2 Impairs Cognition in Systemic Lupus Erythematosus by Promoting Microglial Synaptic Pruning via β-Catenin Signaling Pathway
Authors: Lu Li , Wang Hailin , Liu Xuan , Tan Liping , Qiao Xiaoyue , Ni Jiali , Sun Yang , Liang Jun , Hou Yayi , Dou Huan 
Published: December 2020

Abstract
Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is the severest complication of SLE, which often involves pathological damage to the brain and cognitive function. Glucose metabolic changes are observed in SLE patients with cognitive impairments by medical imaging. Pyruvate kinase isoform M2 (PKM2) is a vital catalyzer of glucose catabolic pathways and in neurological diseases. However, PKM2 regarding the progress of NPSLE remains poorly studied. Thus, this study aimed to analyze and compare the central carbon metabolites in the validated neuropsychiatric lupus model and control mice. Methods MRL/Mp-Faslpr (MRL/lpr) female mice were used as NPSLE mouse model, C57BL6 as control. Metabolomics to assess hippocampa glycolysis level. Glucose, lactic acid, IL-6 and IL-1β of hippocampal were detected by ELISA. The expression of PKM2 was detected by qRT-PCR and western blotting, and the localization of PKM2 in microglia and neurons was assessed with IBA-1, NeuN and PKM2 immunohistochemistry. Flow cytometry was used to detect the number and phenotype of microglia. In vitro, after transfected PKM2 overexpression plasmid on BV2, the effect on microglia and β-catenin signaling pathway were detected. Finally, PKM2 inhibitor Shikonin was injected into MRL/lpr mice, behavioral testing were performed to assess cognition, HE and FJB staining were used to evaluate brain damage.Results Glycolysis was elevated in the hippocampal tissues from MRL/lpr lupus mice, accompanied by an increase in glucose consumption and lactate production. Based on these metabolic variations, PKM2 activation was revealed in hippocampal microglia from lupus mice. Furthermore, PKM2 facilitated microglial phagocytic activity and engulfment of neurons via β-catenin signaling. In vivo, an inhibitor of PKM2, Shikonin, was shown to reduce microglial activation, loss of neuronal synapses, and block β-catenin signaling. Accordingly, the cognitive impairment and brain damage of MRL/lpr mice were relieved. Conclusion These results indicated that abnormal glycolytic metabolism in the brain tissue of NPSLE mice was induced by PKM2 overexpression, which increased the activation of microglia and the ability of phagocytizing neuronal synapses, leading to neuronal loss and cognitive dysfunction in lupus. These phenomena indicated that inhibition on PKM2 would be a novel therapeutic target for the treatment of lupus encephalopathy.
Co-Culture with Chorionic Villous Mesenchymal Stem Cells Promote Endothelial Cell Proliferation and Angiogenesis via ABCA9-AKT Pathway
Authors: Chu Yijing , Zuo Jianxin , Zhang Yan , Gao Guoqiang , Hu Xiaoyu , Han Rendong , Liu Chong , Zhou Huansheng , Li Min , Peng Wei , Wang Yan 
Published: December 2020

Abstract
ObjectiveIt is found that human chorionic villous mesenchymal stem cells (CV-MSCs) are a promising and effective treatment for tissue injury. Trophoblast dysfunction during pregnancies obviously entangles to the pathogenesis of preeclampsia (PE). This work was to make it clear how CV-MSCs regulated vascular endothelial cell function. MethodsIn this study, we treated HUVEC with CV-MSC CM and RNA-seq analysis was used to understand the changes in HUVEC. We examined the levels of ABCA9 and AKT signaling in HUVEC by immunohistochemistry, western blot and qRT-PCR assays. CCK-8, colony formation and tube formation assays were used to understand the role of ABCA9 in the growth and angiogenesis of HUVEC mediated by CV-MSCs. ResultsThe CV-MSCs treatment significantly strengthened enhanced the HUVEC angiogenesis and proliferation. Furthermore, a significant increase of ABCA9 expression and activation of the AKT pathway in CV-MSCs -treated HUVEC was observed. Consistent with these findings, ABCA9 overexpression exhibited the same effect of promoting HUVEC proliferation and angiogenesis as induced by CV-MSC CM, also with the accompaniment of activation of AKT signaling. In addition, inhibition of ABCA9 inactivated the AKT signaling in HUVEC, and reduced the proliferation and angiogenesis of HUVEC. Importantly, the elevation of proliferation and angiogenesis induced by ABCA9 overexpression in HUVEC could be attenuated by ABCA9 overexpression. Conclusion﻿Our results suggest that ABCA9-dependent AKT signaling activation mediated by CV-MSCs could promote the proliferation and angiogenesis of HUVECs.
A Retrospective Longitudinal Analysis of Risk Factors, Treatment Outcomes and Imaging Parameters of Ventricular Collapse in Idiopathic Intracranial Hypertension
Authors: Serra Riccardo , Mahapatra Smruti , Huq Sakibul , Meggyesy Michael , Gorelick Noah Leviton , Manthripragada Lacie , Moghekar Abhay , Luciano Mark Gregory 
Published: December 2020

Abstract
ObjectiveVentricular collapse is a prevalent yet poorly understood complication of ventriculo-peritoneal shunting (VPS) in patients with idiopathic intracranial hypertension (IIH). By identifying and describing the risk factors of ventricular collapse (VC), this study aims to characterize the clinical progression, etiopathogenesis and treatment of IIH and its complications. The relationships between ventricular size, symptoms and treatments were also assessed longitudinally with ventricular segmentation on MRI/CT imaging, and correlated with other risk factors of IIH and VC. MethodsWe retrospectively reviewed records of 147 patients who underwent VPS for IIH at our Institution, and identified 73 shunt-naïve subjects included in the final analysis. Manual segmentation of CT/MRI scans was performed longitudinally at each clinical stage (baseline, post-shunting, post-collapse and after each intervention). Variables collected included valve type and opening-pressure, shunt revisions, use of anti-siphoning devices (ASD), comorbidities, venous sinus hypoplasia/stenosis and stenting, and general demographics. Linear univariate regression models were used to determine the association between individual risk factors and VC, and to quantitatively assess the effect of treatment. Two multivariate models were also tested, including Pre-Shunting and Post-Shunting variables, to quantify their association with VC. ResultsOf 73 IIH patients with new shunts, 32 experienced collapse (uni- or bilateral, 26.5% of the total). In shunt-naïve patients, collapse was associated with pre-shunting (rho=-0.36; p=0.001) and post-shunting ventricular size (rho=0.62; p=0.0002). Both collapse and ventricular area were correlated with shunt-related symptoms at 6 months (rho=-0.29; p=0.01). Shunt adjustment, addition of ASDs, and valve replacement proved to be the most effective strategies to re-expand the ventricles and reduce symptoms. Nonetheless, a significant fraction of patients remained symptomatic after multiple treatments, suggesting a complex and multifactorial etiology for VC. On univariate analysis, catheter revisions were more common in the VC group, while the multivariate model with Post-Shunting risk factors proved to be significantly associated with VC. ConclusionsIn newly VP-shunted IIH patients, small ventricular size predisposed to collapse and headaches, while higher valve OPs and ASDs may reduce the risk of collapse and promote symptomatic improvement. Within the restraints of a retrospective analysis, this study is the first to analyze the risk factors of VC in IIH patients, longitudinally integrating the clinical progression with ventricular imaging. Further prospective studies are warranted to better understand the etiopathogenesis and clinical progression of collapse.
The Effect of A 4-Week Vegan Diet on Adipokine Levels in Healthy Male and Female Participants: A Randomized-Controlled Trial
Authors: Lederer Ann-Kathrin , Hettich Manuel , Huber Roman , Hannibal Luciana , Neumann Elena 
Published: December 2020

Abstract
Background Vegan diet (VD) is reported to show beneficial health effects including cardiovascular and anti-inflammatory protection, but the underlying mechanisms remain unclear. We hypothesized that adipokines, a special type of cytokine produced by the white adipose tissue with known effects on metabolism and the immune system, may contribute to the observed anti-inflammatory effects of VD. Methods A parallel group interventional trial was designed to evaluate the effect of VD compared to meat-rich diet (MD) on serum levels of two central adipokines, leptin and adiponectin. Fifty-three healthy, omnivore participants (62% female, average age 31 years and BMI 23.1 kg/m2) were randomly assigned to VD or MD for 4 weeks. Results End value comparison between VD group and MD group showed a significantly lower level of adiponectin in the MD group (11.6 vs. 15.5 µg/mL, p = 0.025) indicating a moderate effect size (Cohen’s d = 0.524). Participants’ sex affected adipokine levels requiring a separate analysis of male and female participants. Leptin was increased by MD only in male participants (p = 0.019) whereas adiponectin remained stable. Female participants in VD group showed higher adiponectin levels at the end of trial (compared to VD-baseline, p = 0.023, as well as compared to MD group, p = 0.015). The end concentration of adiponectin depended on diet in female participants (p = 0.010). Conclusion The results of our trial suggest that plasma concentration of leptin and adiponectin do not explain the immunomodulatory potential of VD in healthy participants, but it appears that diet modifies adipokine levels in a sex-specific manner.Trial registration: German Clinical Trial register (DRKS00011963), registered 30 March 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011963.
Discovery of ABCG2/VEGFR2 Dual-Target Inhibitor With Anti-Drug Resistance Activity Based on the ATP Binding Site
Authors: Liang Jing-wei , Dai Ao-lun , Li Shi-long , Li Wan-qiu , Nian Qing-yang , Meng Fan-hao 
Published: December 2020

Abstract
Background: ABCG2 plays a critical role in multi-drug resistance in a variety of cancers. Its activity is influenced by ATP hydrolysis and substrate transport, which are synergistic processes but in two independent sites. However, there was no QSAR study of the ABCG2 inhibitors for the two binding sites respectively. Methods: in current study, a QSAR model of ATP binding site was built using DCG scoring strategy, it was used to optimize the structure of a tyrosine kinase inhibitor to avoid the potential drug resistance. Results: a series of novel dual target compounds with arylamide skeleton were obtained, which showed notable activity in enzyme activity test. Compound 7c and 7i showed significant inhibitory activity against drug-resistant cells. Conclusions: the QSAR of ATP binding site of ABCG2 was first discussed, the dual-target compound 7c proposed a new strategy to reverse drug resistance.
Impact of Tenofovir/Lamivudine/Dolutegravir (Tld) on the Health-Related Quality of Life and Clinical Outcomes of HIV/AIDS Patients at a Tertiary Health Facility in Niger State
Authors: Umar Danjuma , Waziri Bala , Ndagi Umar , Mohammed Shafiu , Usman Ndagi , Abubakar-Muhammad Hauwa 
Published: December 2020

Abstract
Background: Human Immuno-deficiency Virus (HIV) remains a major global public health issue. However, it is now considered a chronic infection which can be managed with new, well-tolerated and efficacious ARVs. The aim of the study was to evaluate the effect of Tenofovir/Lamivudine/Dolutrgravir (TLD) on the HRQoL and viral suppression over a short period.Method: The study was prospective, with a time frame of three (3) months. HRQoL was measured using a disease specific HIV/AID Targeted Quality of Life (HAT-QoL) tool and the clinical outcomes focused on viral load using structured data collection tool.Results: Most of the participants were female (62.1%), currently married 63.2% and no co-morbidity, mean age 43±SD (range 21-77years). There was a statistically significant improvement in HRQoL scores across all domain after 3months of transitioning to TLD. While 8 of the 9 domains namely; overall functions, life satisfaction, health worries, financial worries, medication worries, HIV mastery, Disclosure worries, Provider trust, (p <0.001) sexual function (p =0.015). Improvement was also seen in viral suppression (p <0.001).Using multiple linear regression analysis, predictors for overall HRQol scores include female gender (ᵝ= 3.59, 95%CI 1.30-5.78, p=0.002), older age, >65years (ᵝ= 4.12, 95%CI -1.42,9.67 p=0.08), living with family (ᵝ= -5.80, 95%CI -9.60,-2.00, p=0.003), higher family income, >N100,000 (ᵝ= 6.09, 95%CI 1.75,10.44, p=0.006) and duration on ART (ᵝ=0.52, 95%CI 0.12, 0.91, p=0.01). While determinants of viral suppression using multi-variant logistic regression analysis revealed living with family (AOR=18.03, 95%CI 3.32-97.85, p<0.001), Primary education (AOR= 0.16, 965%CI 0.029,0.93, P=0.041), being employed (AOR=0.16, 95%CI 0.028,0.91, P=0.008), income and baseline viral load (AOR= 0.53, 95%CI 0.44,0.69, p<0.001). However, living with family is major determinant of viral suppression.Conclusion: TLD help improved health related quality of life among HIV infected individual and essential in rapid viral suppression.
Effects of Ecological Water Conveyance Project on the Structure, Species Diversity and Stability of Desert Riparian Forest in the Lower Reaches of Tarim River, Northwest China
Authors: Wang Xiyi , Ma Tingting , Ling Hongbo , Peng Shuzhen 
Published: December 2020

Abstract
Background: The lower reaches of the Tarim River is an arid region of inland China. In this area, vegetation is sparse and the environment is fragile. Therefore, it is of great significance to study the structure and stability of the plant community and ecosystem in the lower reaches of the Tarim River. It is valuable to increase the understanding of ecological protection and restoration in arid areas. Methods: In this study, four sections, Yingsu, Karday, Alakan, and Yiganbjm, were selected as research sites, and 96 arbor and shrub quadrats and 288 herb quadrats were delimited in these sites. The ecological characteristics of all species in the quadrats were investigated. We selected the surveyed data from 2000, 2004, 2008, 2012, 2016, and 2019. Based on the data, we analyzed the variations in species composition. We also determined Shannon-Wiener indexes, Alatalo indexes, and ecological dominance to discuss the species diversity and uniformity of plant community. Plant community stability were also evaluated. Results: There were 17 species in 2000 and 31 species in 2019. The proportion of arbor and shrub species decreased, while the understory herbaceous species gradually increased; all of the species become balanced. The stability of the plant community gradually increased; however, it remained unstable. Conclusions: In general, water conveyance in an ecosystem plays a positive role in promoting the restoration of vegetation and ecological stability. This study provides a new method for the evaluation of ecological protection and restoration benefits in arid areas. Our findings can be a good reference for similar studies.
Mitochondrial Import of Malat1 Regulates Cardiac Mitochondrial Function in Type 2 Diabetes Mellitus through Interaction with MicroRNA-23b
Authors: Hathaway Quincy A. , Taylor Andrew D. , Kunovac Amina , Pinti Mark V. , Newman Mackenzie S. , Cook Chris C. , Winters Michael T. , Westemeier Emily , Fink Garrett K. , Durr Andrya J. , Shepherd Danielle L. , Robart Aaron R. , Martinez Ivan , Hollander John M. 
Published: December 2020

Abstract
Background: The pathogenesis of type 2 diabetes mellitus is known to alter cardiac mitochondrial bioenergetics, but the role of non-coding RNAs (ncRNAs) in regulating this process remains poorly understood, specifically within the mitochondrion. Here we characterized the mitochondrial localization of nuclear-encoded lncRNAs in the heart in an effort to understand how import of lncRNAs can modify mitochondrial function during diabetes mellitus.Methods: Human patient and FVB/NJ mouse cardiac tissues were collected from type 2 diabetics and non-diabetics. Immunoblotting was used to validate purity of mitochondrial fractionation. NcRNA from subcellular compartments (cytoplasmic and mitochondrial) were sequenced through the Illumina 2500 HiSeq. LncRNA mitochondrial targeting sequences were acquired through crosslinking immunoprecipitation (CLIP) with Polynucleotide Phosphorylase (PNPase) and secondary structures were analyzed using supervised and unsupervised machine learning algorithms. Fluorescence in situ hybridization (FISH) allowed for visualization of Malat1 localization. Mitochondrial function was assessed through oxygen consumption rate.Results: 2448 LncRNAs were discovered in human cardiac mitochondria. Malat1 and microRNA-23b abundance were significantly reduced in human and mouse diabetic mitochondria. Modification of the import protein PNPase in HL-1 cells decreased binding affinity (~80%) of transcript variant 4 of Malat1 (Malat1-204), with machine learning (AUC 0.75) identifying stem-loops as shared secondary structures of lncRNAs bound to PNPase. Knockdown of Malat1-204 and microRNA-23b in mitochondria decreased protein expression of mt-Nd4 (~55%), though showed little/no binding homology to the mt-Nd4 mRNA transcript. Malat1-204 and microRNA-23b were identified bound to mt-Rnr1 rRNA, which could influence translation of mt-Nd4 through the mitochondrial 12S rRNA pathway.Conclusions: Malat1-204 and microRNA-23b, decreased in cardiac diabetic mitochondria, likely stabilize the mitochondrial ribosomal complexes through binding of mt-Rnr1. The significant decrease in total abundance of lncRNAs in diabetic mitochondria could suggest maladaptation for regulating bioenergetics and managing future insults.
Impact of High-Risk Fertility Behaviour on Under-five Mortality in Asia and Africa: Evidence from Demographic and Health Surveys
Authors: Amir-ud-Din Rafi , Naz Lubna , Rubi Anila , Usman Muhammad , Ghimire Umesh 
Published: December 2020

Abstract
Background: Younger or older maternal age, short inter-pregnancy birth interval, and higher birth order of the child are considered to be high-risk fertility behaviour (HRFB). Under-five mortality being disproportionately concentrated in Asia and Africa, this study analyses the association between HRFB and under-five mortality in selected Asian and African countries.Methods: This study used Integrated Public Microdata Series-Demographic and Health Surveys (IPUMS-DHS) data from 32 countries in Sub-Saharan Africa, Middle East, North Africa, and South Asia from 1986 to 2017 (N=1,467,728). Previous evidence hints at four markers of HRFB: women’s age at the birth of index child <18 years or >34 years, short preceding birth interval (PBI) <24 months, and child’s birth order >3. Using logistic regression, we analysed the change in the odds of under-five mortality as a result of i) exposure to HRFB individually, ii) exposure to any single HRFB risk factor, iii) exposure to multiple HRFB risk factors, and iv) exposure to specific combinations of HRFB risk factors. Results: Mother’s age at the birth of index child <18 years and preceding birth interval (PBI) <24 months were significant risk factors of under-five mortality, while a child’s birth order >3 was a protective factor against under-five mortality. Presence of any single HRFB was associated with 1.067 times higher risk of under-five mortality (OR = 1.067; 95% CI: 1.042 - 1.090; P < 0.001). Presence of multiple HRFBs was associated with 1.392 times higher risk of under-five mortality (OR = 1.392; 95% CI: 1.355 - 1.431; P < 0.001). Some specific combinations of risky fertility behaviour such as younger maternal age (<18 years) and short preceding birth interval (PBI <24) significantly increased the odds of under-five mortality.Conclusion: Younger maternal age and short preceding birth interval significantly increase the risk of under-five mortality. This highlights the need for effective legislation to curb child marriages and increased public investment in reproductive healthcare with a focus on higher contraceptive use for an optimal interpregnancy interval.
WITHDRAWN: Knowledge, Preventative Practices and Depression of Chinese university students in Korea and China During the COVID-19 Pandemic: An Online Cross-sectional Study
Authors: ‍Zhao Bo , Kong Fanlei , Nam Eun Woo 
Published: December 2020

Abstract
Background: To investigate the knowledge, preventative practices, and depression of Chinese university students living in South Korea (‘International Group’) and Mainland China (‘Mainland Group’) during the Coronavirus Disease 2019 (COVID-19) outbreak, and furtherly explore the determinants of depression among these students; Methods: The study was conducted using an online questionnaire tool designed by the Yonsei Global Health Center, with preventative knowledge and practice questions on COVID-19, as well as PHQ-9 (used to diagnose depression for patients). 420 Chinese college students were finally included in the analysis (171 students in South Korea and 249 students in mainland China). This data was collected from March 23 to April 12, 2020; Results: Majority of these students had a good level of knowledge of COVID-19. The ‘International Group’ did better than the ‘Mainland Group’ students regarding preventative practices, but the percentage with moderate-to-severe depression was higher among the ‘International Group’. Highly concerned about family members, highly concerned about getting COVID-19, and having a suspicion of contact with patients increased the depression state among the respondents. Meanwhile, taking preventative behaviors more comprehensively decreased the depression state of both groups; Conclusions: During the pandemic of COVID-19, the depression status of ‘International Group’ students was significantly severer than that in ‘Mainland Group’ (χ2 = 5.50, p < 0.05). While the high-level of depression status of these two groups’ students was affected by highly concerning family members and getting COVID-19 and having a suspicion of contact with patients. Therefore, psychological counseling and education programs are needed in order to support and improve the mental health of ‘International Group’ students.
The role of Internet Financial Reporting (IFR) in mediating manufacturing firm value on Indonesia Stock Exchange (IDX)
Authors: Fuad Khoirul , Ariyani Nurlita Dwi , Handayani Retno Tri 
Published: December 2020

Purpose - This research aimed to determine the role of Internet Financial Reporting application for manufacturing companies on Indonesia stock exchange in the increase of firm value both directly and indirectly.Method - This research used a purposive sampling method. The number of data collected was 95 company samples. This research employed SPSS 25 for testing the data. Result - The results of this study indicated that Internet Financial Reporting can mediate the relationship between institutional ownership and profitability on firm value.Implication - Internet Financial Reporting application for companies today attracts investors to invest their capital to the companies because of the ease in getting the information needed at any time.Originality - This study used Internet Financial Reporting as mediation and source of the data year 2018.