bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgenic TRPM8 activity drives sexual dimorphism in a murine model of chronic migraine
Authors: Alarcón-Alarcón David , Cabañero David , de Andrés-López Jorge , Fernández-Ballester Gregorio , Fernández-Carvajal Asia , Ferrer-Montiel Antonio 
Published: October 2021

Abstract
The mechanisms contributing to the high prevalence of chronic migraine in females are yet elusive. Here, we used a mouse model of nitroglycerin-induced chronic migraine that displays a sexual dimorphic phenotype and unveiled a role of TRPM8 as a testosterone receptor that provides antinociceptive resilience exclusively in males. Nitroglycerin induced similar mechanosensitivity to both sexes trough activation of TRPA1 channels, but triggered persistent hypersensitivity solely in females, as males readily recovered from the migraine crisis. Notably, we found that testosterone exerted an antinociceptive activity through its interaction with the TRPM8 channel. Downregulation of this protective mechanism in males led to persistent mechanical hypersensitivity, whereas administration of testosterone to females favoured their recovery. Thus, our findings reveal a novel protective function of TRPM8 through pre-clinical models of acute and chronic pain and highlights the interest of molecular solutions mimicking the pain-relieving activity of testosterone on TRPM8.
Inflammatory Biomarkers after an Exercise Intervention in Acute Lymphoblastic Leukemia Survivors
Authors: Lähteenmäki Tuomas , Järvelä Liisa , Niinikoski Harri , Huurre Anu , Harila-Saari Arja 
Published: October 2021

Abstract
BackgroundCancer survivors show increased risk for non-communicable diseases and chronic low-grade inflammation characterizes the development of such diseases. We investigated inflammatory plasma protein profiles of survivors of acute lymphoblastic leukemia (ALL) in comparison to healthy controls and after an intervention with a home-based exercise program. ProcedureSurvivors of ALL aged 16-30 years (n=21) with a median time of 15.9 years from diagnosis, and sex- and age-matched healthy controls (n=21), were studied. Stored plasma samples were analyzed with Olink’s 92-protein-wide Inflammation panel in 21 ALL long-term survivors at baseline, after a 16-week home-based exercise intervention (n=17) and in 21 age- and sex-matched controls at baseline. Protein expression levels were compared between the groups. ResultsInflammatory protein levels did not differ between the survivors and controls at baseline. Significantly reduced levels after the intervention were found in 11 proteins related to either vascular inflammation, insulin resistance, or both: TNFSF14, OSM, MCP-1, MCP-2, FGF-21, CCL4, TGF-alpha, TRAIL, ADA, CXCL6, and LAP TGF-beta-1. ConclusionsThe ALL survivors were not significantly more affected by inflammation than controls at baseline. The survivors’ 16-week physical exercise intervention led to significant beneficial change in inflammation protein levels. Physical exercise should be promoted for survivors of cancer.
Knowledge of human papillomavirus vaccines among university students in Angola
Authors: Rocha Joao Wilson , Vasconcelos Ana Morais , Simões Honolfo Elves , Soqui Elizandra , Rosa Nilton Helibrando 
Published: October 2021

Abstract
Cervical cancer is the first most common cancer among women in Angola and accounts for 37.6% of cancers among women in Angola. The human papillomavirus (HPV) is a causative agent of the disease. Recent advances in technology have led to the introduction of vaccines to prevent HPV infection. This study aims to assess the awareness of university students about HPV infection as a causal factor for cervical cancer and their knowledge about HPV vaccination. Assessing knowledge about vaccination among university students helps us to understand the level of awareness about it. Methods:A questionnaire-based study was carried out on 106 university students, from May 10th to July 26th, 2021. The questionnaire consisted of 10 multiple-choice questions and the results were analyzed using percentages. Results:Knowledge about HPV as a causative agent of cervical cancer was found in 84.2% of students.Awareness of the availability of the HPV vaccine was observed in 55.3%. Complete vaccination status was verified in 0% male students and 13% female students. No male students and 13 female students received incomplete vaccination. 33 men and 73 women were willing to be vaccinated with the HPV vaccine. Conclusion:The present study concludes that there is not a good knowledge of university students about cervical cancer and its prevention. There is also little knowledge about the HPV vaccine, meaning the availability of the vaccine, the right age group for vaccination and the recommended vaccination for men need to be improved. Vaccination status is poor among men and women because it is not on the national vaccination calendar. The desire to get vaccinated in male students was lower compared to female students. Thus, there seems to be a need to motivate male students for vaccination. Therefore, more awareness should be created about the HPV vaccine among students. The government through the Ministry of Health must incorporate the HPV vaccine in the vaccination calendar.
Select the Optimal Development Strategy for Layered Sandstone Reservoir by Creating System Economic Model and the Accumulated Oil Production Prediction Method
Authors: wang fulin , zhao yunfei , fang yanjun 
Published: October 2021

Abstract
To determine the development mode of different oil field in layered sandstone reservoir, a system economic model was established, including the primary production layer section and the upper layer. The cumulative oil production limits of the primary layer were described under different oil prices, using the existing well method (UEWM) and drilling new well method (DNWM). The first layer’s oil production limit for DNWM and UEWM was determined. The established economic ultimate water cut (EUWC) model, the solution prediction model of water cut arctangent, and the water drive curve were combined, to calculate the accumulative oil production from planning time of the upper layer production to the economic limited water cut of block. When the oil price is 40$/BBL, the SME block should be developed by UEWM method. While for 70$/BBL, DNWM should be adopted. This work provides theoretical support for the optimization of up (down) layer return development mode. It is of great significance to guide the development of layered sandstone reservoir.
Anti-UBE2T antibody: a novel biomarker of progressive-fibrosing interstitial lung disease
Authors: Hikichi Mari , Gon Yasuhiro , Mizumura Kenji , Hashimoto Shu , Ph.D. M.D. M Shuichiro 
Published: October 2021

Abstract
Background

Antifibrotic therapy has demonstrated efficacy against progressive-fibrosing interstitial lung disease (PF-ILD); therefore, it has become a priority to identify disease behavior before disease presentation. As autoimmunity is implicated in the pathogenesis of various ILDs, we explored the possibility of a circulating biomarker that can predict the chronic progressive behavior of ILDs.
Methods

A single-center retrospective cohort study was conducted to investigate a biomarker of PF-ILD. Circulating autoantibodies against 9,483 purified full-length human recombinant proteins of patients with interstitial pneumonia were screened by microarray analysis. The candidate auto-antibodies were verified their existence by multiples solution assay. In addition, enzyme-linked immunosorbent assay (ELISA) was performed in larger sample sets to evaluate accurate sensitivity, specificity and clinical significance in ILDs.
Results

In total, 61 healthy subjects and 87 patients with various ILDs enrolled in this study. Anti-UBE2T antibody was discovered by performing protein microarray and multiplex solution assay as a candidate biomarker of ILDs. By measuring its concentration by ELISA, anti-ubiquitin-conjugating enzyme E2T (UBE2T) antibody levels were significantly higher in patients with idiopathic interstitial pneumonias (IIPs), especially in those with PF-ILDs, than in healthy participants. The receiver operating characteristic analysis of anti-UBE2T antibody in diagnosing PF-ILD was calculated. The area under the curve was 0.85 and yielded a cut-off value of 238.1 ng/mL. Anti-UBE2T antibody-positive IIP patients demonstrated significantly higher ILD-gender age physiology scores, PF-ILD diagnosis rates and were more likely to develop honeycomb structures than anti-UBE2T-negative IIP patients after two years of follow up. The anti-UBE2T antibody positivity did not correlate with other commercial biomarkers such as KL-6 and commercial autoantibodies, suggesting the presence of anti-UBE2T antibody was independent of the others. Immunohistochemical staining of UBE2T in normal lungs was observed sparsely in the bronchiole epithelium and macrophages. Controversially, idiopathic pulmonary fibrosis lung tissue showed robust expression of the UBE2T protein in the lining epithelium of honeycomb structures.
Conclusion

This is the first report to describe anti-UBE2T antibody, a new biomarker that is significantly elevated in idiopathic PF-ILDs. This new antibody may constitute a sensitive biomarker to detect cases of PF-ILDs that are not currently detected by commercially available biomarkers.
Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia
Authors: Sha Hong Xi , Veerapen Kumar , Chow Sook Khuan , Gun Suk Chyn , Lau Ing Soo , Lim Renee Lay Hong , Zulkifli Zaliha , Yow Yoon Yen , Peh Suat Cheng , Hwang Jung Shan 
Published: October 2021

Abstract
Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR=0.5478, 95%CI=0.3396-0.8835, p=0.01321) and ATIC T675C (rs4673993) (OR=0.5247, 95%CI=0.3248-0.8478, p=0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene-gene and gene-environment interactions.
A higher rate of adverse pregnancy outcome in HBsAg-positive pregnant woman
Authors: Huang Zhi-Hao , Peng Ting-Ting , Yan Sheng-Guang , Yan Hao-Zhen , Yu Dong-Dong , Qiu Jun-Chao , Liu Mei-Ling , Huang Xin-Yue , Xu Guo-Jun , Ouyang Shi 
Published: October 2021

Abstract
Objective

The aim of this study was to study the relationship between adverse pregnant outcomes(APO) with chronic hepatitis B virus (HBV) infection in pregnant women.
Method

From 2017 to 2019, we studied HBsAg (+) pregnant women and HBsAg (-) who gave birth at our hospital in Guangzhou City, China. We compared of the outcomes of pregnant women with HBsAg(+) or HBsAg(-). Further, among HBsAg(+) pregnant women, We compared of the outcomes of pregnant women with HBeAg(+) group or HBeAg(-) group, HBV DNA above 2×10e5IU/mL group or HBV DNA below 2×10e5IU/mL) group, respectively. Finally, multivariate logistic regression analysis was used to evaluate the independent association between HBV infection and the risk of developing APO.
Result

First, Our research Indicates that the rates of gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), premature rupture of membrane (PROM), Fetal distress (FD), Oligohydramnios, Premature delivery (PD), Low birth weight (LBW), Meconium contamination (MC), Neonatal hyperbilirubinemia(NH) in HBsAg(+) group were higher than those in HBsAg(-) group (P<0.05). Second, among 711 HBsAg(+) pregnant women, the rates of GDM and ICP in HBV DNA above 2ⅹ10e5 IU/mL were higher than those in HBV DNA below 2×10e5 IU/mL group (P<0.05). Similarly, The rates of ICP in HBeAg(+) group were higher than those in HBeAg(-) group. Further, through multivariable logistical regression model analysis, we observed maternal HBsAg carrier (OR, 6.758; 95% CI, 2.358-19.369) had an independent risk for ICP. Similarly, HBsAg carrier(OR, 1.101; 95% CI, 1.066-1.137) ,advanced age (OR, 1.407; 95% CI,1.033-1.917) and abortion(OR,1.446; 95% CI, 1.062-1.969) had independent risk for GDM.
Conclusions

Chronic HBV infection can increase the rate of host adverse pregnancy outcomes (APO). The maternal viral load and HBeAg status were significantly associated with the appearance of GDM and ICP. Maternal HBsAg carrier had an independent risk for GDM and ICP.
Detection and Validation of Novel Human Targets for EBV-miR-BART10-3p
Authors: Jerud Julie Tro , Sognnes Vibeke , Hofsli Eva , Mjelle Robin 
Published: October 2021

Abstract
Epstein-Barr virus (EBV) miRNAs are expression in various human tissues, including the human colon. We have previously shown that the EBV miRNA miR-BART10-3p is higher expressed in colon cancer tissue compared to adjacent normal tissue. Here, we aim to identify and validate novel human targets of miR-BART10-3p. MiR-BART10-3p mimics were transfected into the two colon cancer cell lines, SW620 and LS411N, and changes in RNA expression were evaluated by RNA-seq. Several genes showed significant changes in gene expression upon miR-BART10-3p transfection, and genes that were significantly differentially expressed in both cell lines were more often down-regulated in miR-BART10-3p transfected cells, indicating regulation by miR-BART10-3p. Candidate human targets of miR-BART10-3p were predicted using TargetScan, and two genes with predicted target sites, MAT2B and CCND1, were functionally validated as miR-BART10-3p targets. Together, we here present several novel candidate human targets of miR-BART10-3p, thereby increasing the understanding of miR-BART10-3p in colon cancer.
A miR-205-5p/GGCT/CD44 axis controls the progression of papillary thyroid cancer
Authors: Li Han-ning , Zhang Hui-min , Li Xing-rui , Wang Jun , Xu Tao , Li Shu-yu , Dong Meng-lu , Wang Ge , Cui Xiao-qing , Yang Xue , Wu Yong-lin , Liao Xing-hua , Du Ya-ying 
Published: October 2021

Abstract
Background

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, despite marked achieves in recent decades, the mechanisms underlying the pathogenesis and progression for PTC are incomplete. Accumulating evidence shows that γ-glutamylcyclotransferase (GGCT), an enzyme participated in glutathione homeostasis that is elevated in multiple types of tumors, represents an attractive therapeutic target.
Methods

Bioinformatics, immunohistochemistry (IHC), qRT-PCR and western blot (WB) assays were used to determine the elevation of GGCT in PTC. The biological functions of GGCT were examined using CCK8, wound healing and transwell assays. Subcutaneous xenograft and tail vein pulmonary metastatic mouse models were constructed to determine the effect of GGCT on tumorigenicity and metastasis in vivo. The effect of miR-205-5p on GGCT and the relationship between these two molecules were examined by dual luciferase reporter assay, RNA-RNA pull down assay as well as the rescue experiments both in vitro and in vivo. The interaction between GGCT and CD44 was assessed by co-immunoprecipitation (Co-IP) and IHC assays.
Results

Our results showed that GGCT expression is upregulated in PTC, correlates with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the cell proliferation, migratory and invasion ability of PTC cells and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP-2 and MMP9) while increased epithelial marker (E-cadherin) in PTC cells. We confirmed binding of miR-205-5p on the 3’-UTR regions of GGCT and delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found GGCT interacted with and stabilized CD44 in PTC cells.
Conclusions

Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.
Do COVID-19 Pandemic-Related Behavior Changes Affect Perioperative Respiratory Adverse Events in Children Undergoing Cardiac Interventional Catheterization?
Authors: Ji Wei , Zhang Kan , Li Mengqi , Wang Siyuan , Sun Liping , Huang Yue , Bai Jie , Zhang Mazhong , Zheng Jijian 
Published: October 2021

Abstract
Background: The Novel Coronavirus Disease (COVID-19) pandemic-related behavior changes could affect the perioperative respiratory adverse events in children with congenital heart disease (CHD). This study was designed to compare the incidence of perioperative respiratory adverse events (PRAEs) in children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during COVID-19 pandemic.Methods：COVID-19 was outbreak in January 2020 in China. 260 pediatric patients scheduled for elective therapeutic cardiac catheterization were included from January 2019 to March 2021 and 154 were completed during the pandemic. Recent URI was diagnosed by the attending anesthesiologist owing to different PRAEs incidence in non-URI and URI children. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing the elective cardiac catheterization were compared before and during the COVID-19 pandemic. Logistic regression model was fitted to identify the potential risk factors associated with PRAEs.Results: Of 564 children enrolled, 359 completed the study and was analyzed finally. URI incidence decreased substantially during the COVID-19 pandemic (14% vs. 41%, P<0.001). Meanwhile, the overall PRAEs also significantly declined no matter whether or not the child had recent URI (22.3% vs. 42.3%, P=0.001 for non-URI and 29.2% vs. 58.7%, P=0.012 for URI respectively). Post-operative agitation in non-URI children occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P=0.001). Behaviors before the COVID-19 pandemic (odd ratio=2.84, 95%CI 1.76 to 4.58) and recent URI (odd ratio =1.79, 95%CI 1.09 to 2.92) were associated with the PRAEs.Conclusions: COVID-19 pandemic-related behavior changes were associated with the reduction of PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.
Modification of Mesenchymal Stem Cells by HMGB1 Promotes the Activity of Cav3.2 T-type Calcium Channel via PKA/β-catenin/γ-cystathionase Pathway
Authors: Wu Hao , Xie Xiaodong , Sun Mingyang , Chen Min , Tao Xuan , Fang Xin , Meng Xiaohu , Wei Wei , Yu Min 
Published: October 2021

Abstract
Background: Mesenchymal stem cells (MSC) hold great promise for treating cardiovascular disease. Recently, we genetically modified MSCs with high mobility group box 1 (HMGB1), and these cells demonstrated high mobility by efficient migrating and homing to target neointima. The possible mechanism was investigated in the current study. Methods: Rat MSCs were transfected with lentivirus containing HMGB1 cDNA to yield MSC-H cell line stably overexpressing HMGB1. The MSC-C cells which were transfected with empty lentivirus served as negative control, and the differentially expressed genes were analyzed by microarray. The cell mobility was determined by transwell migration assay. Intracellular free calcium and the expression of Cav3.2 T-type calcium channel (CACNA1H) were assayed to analyze activity of CACNA1H-mediated calcium influx. H2S production and γ-cystathionase expression were examined to assess the activity of γ-cystathionase/H2S signaling. The interaction of HMGB1 with γ-cystathionase in MSC-H cells was analyzed by co-immunoprecipitation. Luciferase reporter assay was performed to determine whether the promoter activity of γ-cystathionase was regulated by interaction of β-catenin and TCF/LEF binding site. Intercellular cAMP, PKA activity, phosphorylation of β-catenin and GSK3β were investigated to reveal cAMP/PKA mediated β-catenin activation. Result: Microarray analysis revealed that differentially expressed genes were enriched in cAMP signaling and calcium signaling. CACNA1H was upregulated to increase intracellular free calcium and MSC-H cell migration. Blockage of CACNA1H by ABT-639 significantly reduced intracellular free calcium and cell migration. The γ-cystathionase/H2S signaling was responsible for CACNA1H activation. H2S production was increased with high expression of γ-cystathionase in MSC-H cells, which was blocked by γ-cystathionase inhibitor DL-propargylglycine. Upregulation of γ-cystathionase was not attributed to interaction with HMGB1 overexpressed in MSC-H cells although γ-cystathionase was suggested to co-immunoprecipitate with oxidized HMGB1. Bioinformatics analysis identified a conserved TCF/LEF binding site in the promoter of γ-cystathionase gene. Luciferase reporter assay confirmed that the promoter had positive response to β-catenin which was activated in MSC-H cells. Finally, cAMP/PKA was activated to phosphorylate β-catenin at Ser657 and GSK3β, enabling persisting activation of Wnt/β-catenin signaling in MSC-H cells. Conclusion: Our study revealed that modification of MSCs with HMGB1 promoted CACNA1H-mediated calcium influx via PKA/β-catenin/γ-cystathionase pathway. This was a plausible mechanism for high mobility of MSC-H cell line.
Assessment of neutrophil-lymphocyte ratios in patients with dry age-related macular degeneration
Authors: SANNAN NAIF , Ramadhan Majed , Elsayid Mohieldin Abass , Ghamdi Hanan Khalid Ahmad Al , Alghamdi Lamis Abdulkhaliq A , Alqahtani Maha Badr 
Published: October 2021

Abstract
Purpose

To assess the significance of neutrophil-lymphocyte ratio (NLR) as an indicator of inflammation in Saudi patients with dry age-related macular degeneration (AMD).
Study design:
A retrospective case-control study.
Methods

Clinical diagnosis along with complete blood count (CBC) results were extracted from hospital and laboratory information systems for patients with dry AMD and age- gender- matched controls attending the ophthalmology clinic at King Abdulaziz medical city, Jeddah, between January 2018 and December 2020. NLR was calculated by dividing the neutrophil by the lymphocyte count.
Results

This study captured 90 patients diagnosed with dry AMD and 270 control subjects without AMD. The mean of ages 70 and 71 years old for cases and controls, respectively. In univariate analysis, there were no significant differences in CBC results between cases and control. In NLR, dry AMD patients have a slightly higher mean than the control group; however, this increase was not statistically significant (P-value 0.8). In the NLR model, age and gender were statistically significant factors affecting the NLR values in dry AMD (P-value 0.03, 0.01 respectively).
Conclusion

as a systemic inflammatory biomarker, NLR alone could not predict dry AMD. However, the slight increase in the NLR values may be helpful if augmented with other laboratory measurements to aid in early disease prediction.