bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3&nbsp;Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease
Authors: Ahmed Sahabuddin , Panda Samir Ranjan , Kwatra Mohit , Sahu Bidya Dhar , Naidu VGM 
Published: March 2021

Abstract
Several activators of NLRP3 inflammasome have been described; however, the central mechanisms of NLRP3 inflammasome activation in brain microglia, especially at the activating step through free radical generation, still require further clarification. Hence the present study aimed to investigate the role of free radicals in activating NLRP3 inflammasome driven neurodegeneration and elucidated the neuroprotective role of perillyl alcohol (PA) in vitro and in vivo models of Parkinson’s disease. Initial priming of microglial cells with lipopolysaccharide (LPS) following treatment with hydrogen peroxide (H2O2) induces NF-κB translocation to nucleus with robust generation of free radicals that act as Signal 2 in augmenting NLRP3 inflammasome assembly and its downstream targets. PA treatment suppresses nuclear translocation of NF-κB and maintains cellular redox homeostasis in microglia that limits NLRP3 inflammasome activation along with processing active caspase-1, IL-1β and IL-18. To further correlates the in vitro study with in vivo MPTP model, treatment with PA also inhibits the nuclear translocation of NF-κB and downregulates the NLRP3 inflammasome activation. PA administration upregulates various antioxidant enzymes levels and restored the level of dopamine and other neurotransmitters in the striatum of the mice brain with improved behavioural activities. Additionally, treatment with Mito-TEMPO (a mitochondrial ROS inhibitor) was also seen to inhibit NLRP3 inflammasome and rescue dopaminergic neuron loss in the mice brain. Therefore, we conclude that NLRP3 inflammasome activation requires a signal from damaged mitochondria for its activation. Further pharmacological scavenging of free radicals restricts microglia activation and simultaneously supports neuronal survival via targeting NLRP3 inflammasome pathway in Parkinson’s disease.
Psychological Effects on Healthcare Workers in Syria During COVID-19
Authors: Alhaffar MHD Bahaa Aldin , Alhaffar MHD Alaa Aldin , Kouchaji Chaza , Alsuliman Tamim 
Published: March 2021

Abstract
Introduction:Since the declaration of COVID-19 as a global pandemic, there has been a dramatic increase in the number of infected cases. Thus, the number of hospital admissions has peaked during a short period, which in return has created a huge burden on healthcare workers. The effect of this pandemic on HCWs can be more severe in war-torn countries. This research aims to explore the psychological effects of the current pandemic on healthcare providers in Syria and compare it with the situation of Syrian HCP outside Syria.Materials and methods:660 has participated in this cross-sectional study using an online questionnaire during two phases (two months apart). The first sample included 76 participants which were used for comparison only, and the second sample consisted of 584 participants (118 outside Syria, 466 inside Syria). The study included demographic, social, and workplace-related questions, as well as three scoring systems including The Pittsburgh, Sleep quality index (PSQI), Kessler Psychological Distress Scale (K10), and Generalized Anxiety Disorder (GAD 7).Results: 72.4% of the first sample had poor sleep quality compared to 80% for the second sample, while over 40% of the first sample had scored well on the Kessler scale and 17% scored severe stress disorder, the second sample scored 29.8% and 27.9% on the same index retrospectively. Over 70% of the two samples scored mild on the generalized stress disorder index. Both inside and outside Syria samples had very similar results on the three indices, and no significant difference was noticed between the sample inside Syria and the sample outside Syria for the Pittsburgh Sleep Quality Index (P=0.900), and for the Generalized Anxiety Disorder score (P=0.798), and no significant difference was noticed between the two samples for the Kessler Psychological Distress Scale (P=0.231). Conclusion: The current pandemic has imposed new concerns related to the preparedness of health systems worldwide but especially in countries with limited resources. Additionally, addressing mental health issues has become vital to ensure that healthcare systems are more effective.Regions of low income and those suffering from armed conflict may benefit from the conclusions of this study to ameliorate the medical practice conditions in the setting of such pandemics as COVID-19.
Lithium Prevents Telomere Shortening in Cortical Neurons in Amyloid-Beta Induced Toxicity
Authors: Themoteo Rafael Martins , de Paula Vanessa , Kimberly Nikole , Brentani Helena , Forlenza Orestes Vicente 
Published: March 2021

Abstract
BackgroundThere is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. MethodsCortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2mM, 0.2mM and 0.02mM) for seven days. Amyloid toxicity was induced 24 hours before the end of lithium treatment. ResultsLithium resulted in 120% (2mM), 180% (0.2mM) and 140% (0.02mM) increments in telomere length as compared to untreated controls. Incubation with Aβ1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. ConclusionsLithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils.
Sceptic priors and climate consensus
Authors: McDermott Grant 
Published: March 2021

Abstract
How much evidence would it take to convince sceptics that they are wrong about climate change? I explore this question within a Bayesian framework. I consider a group of stylised sceptics and examine how these individuals update their beliefs in the face of current and continuing climate change. I find that available evidence in the form of instrumental climate data tends to overwhelm all but the most extreme priors. Most sceptics form up dated beliefs about climate sensitivity that correspond closely to estimates from the scientific literature. However, belief convergence is a non-linear function of prior strength. It thus becomes increasingly difficult to convince the remaining pool of sceptics. I discuss necessary conditions for consensus formation under Bayesian learning and show how apparent deviations from the Bayesian ideal still be accommodated within the same conceptual framework. I argue that a generalized Bayesian model thus provides a bridge between competing theories of climate scepticism as a social phenomenon.
Performance Measurement for New Mobile Data Services During Generation Upgrading Period: A Case of China's Telecom Industry
Authors: Du Yu , Zhang Xiaohang , Li Zhengren , Guo Yijun 
Published: March 2021

Abstract
For the global telecom operators, mobile data services have gradually taken the part of traditional voice services to become the main revenue growth point. However, during the upgrading period of new generation networks (Such as 5G), new mobile data services are still at the stage of exploration, the network capabilities and the application scenarios are unmatured. In this phase, it is incomplete and misleading to simply measure the performance of new services from one dimension, such as data traffic or revenue, and the measurement should be dynamically changed according to the development of the new services. Therefore, telecom operators want to improve the existing performance measurement from the aspect of integrity and dynamics. In this paper, we propose Mobile-data-service Development Index (MDDI), and build a quantitative model to dynamic measure the overall performance of mobile data services. To approach a fuller understanding, we creatively bring investment indicators and networks reliability indicators into performance indicators system, and discuss the relationships among subindices and the selection of outcome criteria in MDDI. In the part of empirical research, we use the model to analyze the dynamic characteristics of a new mobile data service in China, and summarize the development strategies of every stage. The findings can also give guidelines for new services of 5G and other new generation networks in the future.
Study on the Relationship Between Myocardial Microcirculation Perfusion and Electrocardiogram ST Segment Depression in Patients With Hypertrophic Cardiomyopathy
Authors: Guan Lina , Yuan Chao , Mu Yuming , Abdullah Guri Qiman Hoga 
Published: March 2021

Abstract
Objective: To investigate the correlation between myocardial microcirculation perfusion status and the ST-segment depression(STD) in patients with hypertrophic cardiomyopathy (HCM)Method: Myocardial microcirculation perfusion of 32 patients with HCM (HCM group) and 28 healthy volunteers (control group) were examined using MCE, and the parameters including peak intensity (PI), area under the curve (AUC), rising slope (RS), and the time to peak (TTP) were analyzed. All subjects were examined by electrocardiogram, and the amplitude of downward movement of ST segment was measured. Then patients were divided into 3 groups according to the degree of downward movement of ST segment: ST1 group (0<ST≤0.1 MV); ST2 group (0.1 MV<ST≤0.2MV); ST3 group (0.2< MV<ST≤0.3 MV). At last, the relationship between myocardial microcirculation disorder and the degree of ST segment depression was explored.Results: Patents with HCM exhibit lower PI and AUC than their healthy counterparts (P < 0.001). No significant difference was found in RS and TTP between two groups (P > 0.05). ST depression was found in all the patients in the HCM group (P < 0.001). There was no significant linear correlation between PI and the degree of ST segment depression (r = -0.348). Then PI value was compared among ST1, ST2, ST3 and control group. The results showed that the PI value in both ST1 group and ST2 group differs from ST3 group (P < 0.01), while there was no significant difference between ST1 and ST2 group (P < 0.05). Conclusion: When ST depressed more than 0.20 mV, the STD is related to the decrease of microcirculation perfusion in hypertrophic myocardium.
Potential Diagnostic Value of Circulating miR-1183 and CHURC1 Biomarkers in Early-Onset Preeclampsia
Authors: Altındirek Didem , Gunel Tuba , Benian Ali , Aydınlı Kılıç 
Published: March 2021

Abstract
BackgroundPreeclampsia (PE) is a multi-systemic disease of pregnancy and leading cause of maternal and fetal mortality and morbidity worldwide. The differential expression of circulating microRNAs (miRs) were reported in maternal plasma of pregnant women and they could be stabilized in plasma. The aim of this study was to characterize the molecular mechanism of PE development through miR-1183.Methods and ResultsPlasma samples were obtained between 26 and 32 weeks of gestation from early-onset PE cases (n=31) and women with normotensive pregnancies (controls, n=22). The expressions of miR-1183 and Churchill containing domain 1 (CHURC1) were measured in maternal plasma. CHURC1 3’ untranslated region was determined as the target of miR-1183 using in silico analysis. miR-1183 and CHURC1 expression levels were assessed by real-time polymerase chain reaction (RT-PCR). An inverse correlation was found between circulating miR-1183 and CHURC1 expression levels with, miR-1183 up-regulated (p=0.002) and CHURC1 down-regulated (p<0.001) in maternal plasma of preeclamptic women compared to controls. The accuracy of levels of miR-1183 and CHURC1 according to area under receiver operating curve (ROC) analysis were characteristic curve analysis: the area under the curve (AUC) were: 0.79; (CI: 0.62-0.91) and 0.96; (CI: 0.78-0.99), respectively.ConclusionThese findings not only characterize a new mechanism for the disease, but also provide potential therapeutic targets.
Curcumin Induces MCF-7 Cells Pyroptosis Via Autophagy/CTSB/NLRP3/Caspase-1/GSDMD Signaling Pathway In Vitro And Vivo
Authors: Duan Haonan , Jiang Liping , Sun Xiance , Liu Xiaofang , Yang Guang , Sun Xianzhi , Cheng Tingting , Ji Yuchen , Zhang Fan , Du Yue , Ou Shu , Ma Rufei , Guan Xiuliang , Teng Nan , Li xiaofeng 
Published: March 2021

Abstract
Background: Curcumin, as a lipid-lowering drug, has been reported to be effective in the treatment of breast cancer. However, the underlying molecular mechanisms have not been completely investigated. Methods: MTT assay was used to determine the effect of curcumin on survival rate of MCF-7 cells. The effects of curcumin on tumor growth were observed in animal models of breast cancer. The positive reactions of Caspase-1, IL-1β and IL-18 were detected by immunohistochemistry. LC3, p62, CTSB, ASC, Pro-Caspase-1, GSDMD, NLRP3, Caspase-1, GSDMD-N, IL-1β and IL-18 were determined by Western blot in vitro and vivo. The release of extracellular IL-1β and IL-18 was determined by ELISA. LDH release was measured. The expression level of CTSB in cytoplasm were determined by immunofluorescence assay. Cell proliferation, cell migration and tube formation assays were used to determine the abilities of cells. In this study, NLRP3 inflammasome inhibitor MCC950, cathepsin B inhibitor CA-074 ME and autophagy inhibitor 3-MA were used to act on cells to investigate the role of NLRP3 inflammasome, cathepsin B and autophagy in curcumin-induced pyroptosis of MCF-7 breast cancer cells.Results: In mouse model of breast cancer, we observed that curcumin treatment significantly induced cell autophagy and pyroptosis. In human breast cancer MCF-7 cells, we found that curcumin induced pyroptotic cell death was dependent on the activation of NLRP3/Caspase-1/GSDMD signaling pathway, which was CTSB-dependent. In addition, curcumin-induced cell autophagy caused lysosomal rupture and CTSB release. Furthermore, NLRP3 inhibitor (MCC950) significantly suppressed curcumin-induced pyroptosis, as well as CTSB inhibitor (CA074 Me) and autophagy inhibitor (3-MA). Besides, we also found that curcumin suppressed cell proliferation, cell migration and tube formation, which could be reversed by inhibitors. Conclusions: In summary, our results demonstrated that curcumin induced MCF-7 cell pyroptosis by the activation of autophagy/CTSB/NLRP3/Caspase-1/GSDMD signaling pathway. These findings offer novel insights into the potential molecular mechanisms of curcumin in treatment of breast cancer.
Longitudinal Associations Between TPO Gene Variants and TPOAb Seroconversion in a Population Based Study: Tehran Thyroid Study (TTS)
Authors: Ghanooni Amir Hossein , Zadeh-Vakili Azita , Rezvankhah Boshra , Nodushan Somayeh Jafary , Akbarzadeh Mahdi , Amouzegar Atieh , Daneshpoor Maryam Sadat , Khalili Davood , Mehrabi Yadollah , Sarvghadi Farzaneh , Ebadi Seyed Alireza , Azizi Fereidoun 
Published: March 2021

Abstract
Background: Autoimmune thyroid diseases are among the most common autoimmune diseases in the world. They are usually accompanied by the presence of anti-thyroid antibodies as the early predictive marker. Genetic determinants of the susceptibility to develop thyroid antibodies are still poorly understood. This study aimed to investigate the relation between thyroid peroxidase (TPO) gene variants (53 SNPs) and positive TPOAb and also to evaluate the effect of some environmental factors on changes from negative to positive TPOAb (Seroconversion). Methods: Participants from the Tehran Thyroid Study (TTS) in phases 1 and 2 (N=5317, ≥ 20 years) were evaluated for the positive TPOAb and its relationship with 53 SNPs from TPO gene (a cross-sectional approach). At the second stage of the study (a longitudinal approach), negative TPOAb participants (control group, N= 4815) were followed up for about 5.5 (5.54±1.62) years until they have had positive results for TPOAb (“TPOAb seroconversion”). The association between TPO gene polymorphisms and TPOAb seroconversion was evaluated using logistic regression analysis and SKAT package (sequence kernel association test). Results: In cross-sectional analyses, 17 SNPs were associated with TPOAb positivity (521 positive TPOAb participants) after the adjustment for age, sex, body mass index (BMI), smoking, the number of parity and oral contraceptive consumption (P <0.05). In longitudinal analyses, there was an association between TPOAb seroconversion and four SNPs before, and three SNPs after adjustment (P <0.05). Conclusions: TPOAb seroconversion could be affected by some thyroid peroxidase gene variants.
Breast Cancer Risk factors in Relation to Molecular Subtypes in Breast Cancer Patients from Kenya.
Authors: Sayed Shahin , Fan Shaoqi , Moloo Zahir , Wasike Ronald , Bird Peter , Saleh Mansoor , Shaikh Asim Jamal , Figueroa Jonine , Naidoo Richard , Makokha Francis , Gardner Kevin , Oigara Raymond , Njoroge Faith Wambui , Magangane Pumza , Mutebi Miriam , Chauhan Rajendra , Mwanzi Sitna , Govender Dhirendra , Yang Xiaohong Rose 
Published: March 2021

Abstract
BackgroundFew studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. MethodsWe conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.ResultsThe median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3 and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and Triple Negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER positive tumors, ER negative patients were more likely to have higher parity (OR=2.03, 95% CI= (1.11, 3.72), p=0.021, comparing ≥5 to <2 children) and younger age at first pregnancy (ORtrend=0.77, 95% CItrend=0.61, 0.98, Ptrend=0.032, comparing older to younger age). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR=0.45, 95% CI= 0.23, 0.87, p=0.018, comparing ≥5 to <2 children); HER2-enriched patients were less likely to be obese (OR=0.36, 95% CI=0.16, 0.81, p=0.013) or older age at menopause (OR=0.38, 95% CI=0.15, 0.997, p=0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies are needed to develop population and subtype specific risk prediction/prevention strategies.
The association between serum sodium levels and tuberculous meningitis compared to viral and bacterial meningitis: Multicenter retrospective cohort study
Authors: Na Seunghee , Kim Taewon , Song In-Uk , Chung Sung-Woo , Kim Seong-Hoon , Oh Yoon-Sang , Oh Juhee , Kim Woojun 
Published: March 2021

Abstract
We evaluated the association between hyponatremia and tuberculous meningitis (TBM) in hopes of providing additional information for the differential diagnosis of TBM from other types of infectious meningitis, especially from viral meningitis (VM). Cross-sectional and longitudinal data involving 5,026 participants more than 18 years of age were analyzed in the total population and the propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, VM, and bacterial meningitis (BM) patients were compared. The initial serum sodium levels were significantly lower in the TBM patients than in the VM and BM patients (136.9 ± 5.9 vs. 139.0 ± 3.1, p < 0.001 for TBM vs. VM, and 138.3 ± 4.7 mmol/L and p < 0.001 for TBM vs. BM) and it dropped significantly more steeply to lower levels in both the TBM and BM patients compared to the VM patients. Consequently, the lowest serum sodium levels were in the order of the TBM < BM < VM patients, which were also statistically significant in all subgroups. (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). The participants with lower serum sodium levels were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium levels than the initial sodium levels (OR 8.4 (95% CI: 4.5–15.8, p < 0.001)). The baseline and longitudinal evaluation of serum sodium levels can provide supportive information for the differential diagnosis of TBM from VM or BM.
Based on Network Pharmacology and Bioinformatics to Explore the Mechanism of Bazhen Decoction in the Treatment of Clear-Cell Renal Cell Carcinoma
Authors: Liu Yu , Li Mingquan , Teh LaiKuan , zhao Liangbin , Ye Naijing 
Published: March 2021

Abstract
Objective: To explore the mechanism of Bazhen Decoction in the treatment of Clear-cell renal cell carcinomaCRCC）through the methods of network pharmacology and bioinformatics.Methods: The active ingredients of Bazhen decoction were identified through TCMSP, Targets of each active ingredients were accessed through TCMSP and Swiss Target Prediction. The target gene by CRCC was obtained from GEO database and interlinked of both active ingredient and cancer gene was performed to obtain drug-disease protein target gene. Cytoscape 3.7.1 software was used to draw the active ingredient-target network. The protein interaction network was drawn using the String database and Cytoscape 3.7.1 software. Gene Ontology (GO) and KEGG pathway analysis on the target were performed using R language.Results: From analysis, 160 of active ingredients were found from Bazhen Decoction with 5002 of predicted targets; 544 of disease targets and 39 drug-disease protein target genes.Network analysis on drug-disease protein interaction found out the targets were mainly involve mechanisms such as positive regulation of angiogenesis, positive regulation of vasculature development, epithelial cell proliferation,growth factor receptor and growth factor binding activity, as well as prostanoid receptor binding activity. Treatment of clear-cell renal cell carcinoma can be controlled through regulating the signaling pathways in relation to bladder cancer, MicroRNAs in cancer, focal adhesion, Human cytomegalovirus infection, Ovarian steroidogenesis and HIF-1 signaling pathway.Conclusion: The mechanism of Bazhen Decoction in the treatment of CRCC reflects the characteristics of multiple ingredients, multiple targets, and multiple pathways of traditional Chinese medicine. The findings from this study able to provide a theoretical basis on anti-cancer mechanism.