bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Evaluation of Root Surface Roughness in The Use of an Ultrasonic Device with Different Tips Having Different Mechanism of Action: A Profilometric Study
Authors: ÖZKAN KARACA Ebru , TUNAR Ogül Leman 
Published: March 2022

Objective: The aim of this study was the profilometric evaluation of the changes in root surface roughness created by different types of ultrasonic tips and mechanism of action.
Methods: Thirty root dentine samples obtained from 15 maxillary premolars, extracted for orthodontic reasons, were included in the study. The sample surfaces were embedded into acrylic blocks, polished, and divided into 3 study groups as linear oscillating device (LOD) with straight tip (ST); LOD with perio-curette tip (PCT); conventional ultrasonic scaler tip (CUST). A calibrated clinician instrumented all surfaces in each group. The root surfaces were evaluated before and after instrumentations with a profilometer device.
Results: There were no statistical differences between the initial roughness values of the groups (p
Increased Systemic Inflammatory Response with Mast Cell Activation In Elder Children With Cerebral Palsy
Authors: DEMİR Cemalettin , BARANOĞLU KILINÇ Yasemin , KILINÇ Erkan 
Published: March 2022

Objective: Increased systemic inflammatory response during intrauterine period or period before the age of 3 is associated with cerebral palsy (CP) pathogenesis; however, effects of inflammatory processes involving mast cell activation in elder children with CP remain unclear. We aimed to investigate the role of mast cells and proinflammatory cytokines in children with CP at 3-18 years of age.
Methods: In this cross-sectional study, venous blood samples were obtained from 30 volunteers with CP and 26 healthy volunteers at 3-18 years of age. Plasma levels of proinflammatory cytokines (IL-1β, IL-6 and IL-9) and mast cell biomarkers (histamine and tryptase beta-2) were determined using ELISA.
Results: IL-1β, IL-6 and histamine levels were higher in individuals with CP compared to healthy controls. Likewise, IL-1β, IL-6, IL-9 and histamine levels were higher in the female patients with CP compared to the male patients, and in the female patients in adolescence compared to the female patients in pre-adolescence.
Conclusion: Our findings indicate that the increased inflammatory response contributes to the pathogenesis of the disease in children with CP who are older than 2 years of age. Moreover the increased inflammatory response is more effective in female patients than in male patients, suggesting that there may be a gender difference in CP. Additionally mast cell activation contributes to the exacerbation of systemic inflammatory response in children with CP at 3-18 years of age.
A Potential Diagnostic and Prognostic Biomarker TMEM176B and Its Relationship With Immune Infiltration in Skin Cutaneous Melanoma
Authors: Jiang Linlan , Yang Yanyin , Liu Fangming , Ma Mingyue , Gao Jie , Sun Lu , Chen Yuwen , Shen Zan , Wu Duojiao 
Published: March 2022

Background: Melanoma is a highly malignant and aggressive tumor. The search for new and effective biomarkers facilitates early diagnosis and treatment, ultimately improving the prognosis of melanoma patients. Although the transmembrane protein TMEM176B has been linked to a number of cancers, its role in cancer immunity remains unknown.Methods: Expression levels of TMEM176B in normal tissues and several cancers, including Skin Cutaneous Melanoma (SKCM), were collected from TCGA and GTEx. We used Receiver operating characteristic and Kaplan–Meier survival curves and performed regression analysis to elucidate the link between TMEM176B and clinicopathological features of SKCM in order to determine the prognostic significance of TMEM176B in SKCM. We then used the GEPIA and STRING websites to search for proteins and associated top genes that may interact with TMEM176B and enriched them for analysis. The link between TMEM176B and immune cells infiltration was then investigated using TIMER, CIBERSORT algorithm and GSVA package of R (v3.6.3). Finally, animal tests were conducted to confirm the expression of Tmem176b and its influence on T-cell immune infiltration.Results:TMEM176B expression was considerably elevated in SKCM compared to normal tissues. Particularly, TMEM176B expression was also linked to pathological stage, tumor ulceration and radiation therapy. Patients with elevated TMEM176B expression had a better prognosis, according to the survival analysis. The majority of tumor infiltrating lymphocytes (TILs) especially T cells in SKCM was positively linked with TMEM176B expression. Our animal experiments also verified that the T-cell infiltration was significantly inhibited in local melanoma tissue of Tmem176b knockout mice. At the same time deleting Tmem176b accelerated tumor progress and impaired T cells effector function.Conclusion: Upregulated expression of TMEM176B in SKCM is associated with a better prognosis and it has the potential to serve as a diagnostic and prognostic marker for the disease. It may serve as a target for SKCM immunotherapy by regulating CD8+ T cells although it requires more evidence.
NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics
Authors: Zheng Fan , Huang Xueyan , Ding Jipeng , Bi Anyao , Wang Shifen , Chen Fei , Zeng Wenbin 
Published: March 2022

Near-infrared (NIR, 650–1700 nm) bioimaging has emerged as a powerful strategy in tumor diagnosis. In particular, NIR-I fluorescence imaging (650–950 nm) has drawn more attention, benefiting from the high quantum yield and good biocompatibility. Since their biomedical applications are slightly limited by their relatively low penetration depth, NIR-I fluorescence imaging probes have been under extensive development in recent years. This review summarizes the particular application of the NIR-I fluorescent dye-contained bimodal probes, with emphasis on related nanoprobes. These probes have enabled us to overcome the drawbacks of individual imaging modalities as well as achieve synergistic imaging. Meanwhile, the application of these NIR-I fluorescence-based bimodal probes for cancer theranostics is highlighted.
Dual Loading Antiplatelet Therapy in Patients With Acute Coronary Syndrome and High Bleeding Risk Undergoing Percutaneous Coronary Intervention: Findings From the Improving Care for Cardiovascular Disease in China Project
Authors: Yan Yan , Gong Wei , Huang Xin , Li Siyi , Wang Ge , Ma Youcai , Hao Yongchen , Liu Jun , Nie Shaoping 
Published: March 2022

ObjectiveLoading dose of dual antiplatelet therapy (LD) is supported by the guidelines for patients with acute coronary syndrome (ACS). However, limited data is provided in the series of high bleeding risk (HBR) patients with ACS and percutaneous coronary intervention (PCI).MethodsUsing data from the Improving Care for Cardiovascular Disease in China—Acute Coronary Syndrome registry, conducted between 2014 and 2019, we stratified all ACS patients with HBR and PCI according to LD used within 24 h of first medical contact or not. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model with hospital as random effect were used to analyze differences in in-hospital clinical outcomes: the primary efficacy endpoint was mortality, and the primary safety endpoint was bleeding.ResultsOf 21,654 evaluable patients 14,322 (66.2%) were treated with LD, and were on average older, less likely to have comorbidities and higher hemoglobin, more often treated GPI and anticoagulant during hospitalization than those without LD. After IPTW adjustment for baseline differences, LD was associated with significantly increased risk of in-hospital mortality [1.89 vs. 1.02%; hazard ratio (HR): 1.71 (95% confidence interval 1.12, 2.42); p &lt; 0.001] and in-hospital bleeding [3.89 vs. 3.3%; HR: 1.25 (1.03, 1.53); p = 0.03].ConclusionsIn ACS patients with HBR, LD was associated with an increased risk of in-hospital mortality and bleeding complications after PCI. Dedicated randomized trials with contemporary ACS management are needed to confirm these findings.
Religious Affiliations and Clinical Outcomes in Korean Patients With Acute Myocardial Infarction
Authors: Oh Seok , Kim Ju Han , Cho Kyung Hoon , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Ahn Youngkeun , Jeong Myung Ho 
Published: March 2022

ObjectiveAlthough religion is expected to have a direct or indirect effect on various aspects of human life, information on the association between religion and acute myocardial infarction (AMI) is inadequate. Hence, in this study, we aimed to investigate the clinical effect of religion on clinical outcomes in patients with AMI.MethodsA total of 2,348 patients with AMI who were treated by percutaneous coronary intervention (PCI) were enrolled in the study, and they were categorized into two groups depending on their religious belief: religious and non-religious groups. The characteristics and clinical outcomes of both groups were compared.ResultsCompared with the religious group, the non-religious group was younger, included mostly men, was more likely to smoke, and was more likely to be diagnosed with ST-segment elevation myocardial infarction. However, the non-religious group was less likely to have a history of hypertension and tended to receive PCI more quickly with shorter door-to-balloon time. Regarding 1-year clinical outcomes, no differences were found between the two groups.ConclusionDespite a growing body of evidence that religious activities have positive effects on human physical health, our results showed a lack of significant differences in 1-year clinical outcomes in patients with AMI irrespective of their religious beliefs.
Alteration of N6-Methyladenosine mRNA Methylation in a Human Stem Cell-Derived Cardiomyocyte Model of Tyrosine Kinase Inhibitor-Induced Cardiotoxicity
Authors: Ma Yan , Liu Xian , Bi Yiming , Wang Tianhu , Chen Cheng , Wang Yabin , Han Dong , Cao Feng 
Published: March 2022

BackgroundN6-methyladenosine (m6A) plays important roles in various cardiovascular diseases (CVDs), including cardiac hypertrophy and heart failure. Sunitinib (SUN) is a tyrosine kinase inhibitor (TKI) that is widely used in the treatment of different types of solid and blood tumors, but its efficacy is restricted by a concomitant rise in cardiotoxicities. However, the methylation modification of m6A messenger RNA (mRNA) in cardiomyocytes treated with TKI has not been investigated.MethodsThe global m6A methylation level of SUN-induced cardiotoxicity was detected by m6A dot blot and colorimetric methylation assay. MeRIP-Seq (methylated RNA immunoprecipitation sequencing) and RNA-seq (RNA sequencing, input) were employed to depict the landscapes of transcriptome and epitranscriptome in TKI. Changes in major m6A-related enzymes were detected by qRT-PCR and Western blot. In addition, the effects of FTO on SUN-induced cardiotoxicity were evaluated by gain and loss of function studies.ResultsIn this study, we observed that the m6A methylation level was significantly elevated in SUN-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and paralleled a positively correlated cellular damage level. Through a genome-wide analysis of m6A mRNA methylation by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and input RNA sequencing (RNA-seq), we identified a total of 2,614 peaks with significant changes, of which 1,695 peaks were significantly upregulated and 919 peaks were significantly downregulated. Quantitative reverse transcription PCR (RT-qPCR), immunofluorescence, and Western blotting revealed that the RNA demethylase fat mass and obesity-associated protein (FTO) was downregulated, whereas the RNA methylases methyltransferase-like 14 (METTL14) and wilms' tumor 1-associating protein (WTAP) were upregulated. Furthermore, gain- and loss-of-function studies substantiated that FTO is cardioprotective in TKI.ConclusionThis study deciphered the methylation modification of m6A mRNA in hiPSC-CMs post-TKI treatment and determined that FTO may be a promising therapeutic target for TKI-induced cardiotoxicity.
Water-Sealed Blasting Control Measures of the Metro Station Undercrossing Existing Structures in Ultra-Close Distances: A Case Study
Authors: Shi Chenghua , Zhao Yiwei , Zhao Chenyang , Lou Yili , Sun Xiaohe , Zheng Xiaoyue 
Published: March 2022

Based on the project of People’s Hall Station of Qingdao Metro Line 4 in China, the method of water-sealed blasting construction for vibration damping is proposed, as the blasting vibration of adjacent structures (Qingdao Metro Line 3) does not meet the control requirements during the blasting construction of the existing site blasting scheme. The effects of blasting on adjacent structures with different water-sealed charge structures and different axial decoupled charge factors are first studied by using the three-dimensional dynamic numerical simulation method. On this basis, a multi-case parametric analysis is carried out on the maximum single detonation charge, initiation interval, vibration-damping hole settings, and other factors that affect the blasting seismic effect. The results demonstrate that water-sealed construction blasting can significantly reduce the vibration response of adjacent structures. The lower-water-decking charge structure, the two ends-water-decking charge structure, and the top-water-decking charge structure can reduce the vibration velocity response of adjacent structures by 2.8, 24.5, and 27.8%, respectively. As the axial decoupling coefficient increases, the peak resultant vibration velocity increases first and then decreases. The peak resultant vibration velocity reaches the minimum value of 1.27 cm/s, which is lowered by 29.5% when the decoupling coefficient is 2.6. The after-detonation vibration response can be reduced by decreasing the amount of a single detonation charge and setting damping holes. When the detonation charge is reduced to 2.7 kg or 100 mm damping holes are set up, the vibration velocities at Line 3 People’s Hall Station are 1.10 cm/s and 1.11 cm/s, respectively. Both velocities are less than the 1.2 cm/s resultant vibration velocity control tolerance requirements. The results of this study can play an important guiding role in construction blasting in on-site metro stations and can serve as a reference for future similar projects.
Are Farmers Willing to Pay for Centralized Mode Provision of Rural Domestic Sewage Treatment? A Large-Scale Assessment in North China
Authors: Jiao Jian , Yang Zihong , Zhang Yang , Shi Boyang , Dogot Thomas , Yin Changbin 
Published: March 2022

Evaluation of farmers’ willingness to participate (WTPP) and willingness to pay (WTP) for the centralized mode provision (CMP) of rural domestic sewage treatment (RDST) is imperative to improve the rural environment as well as to alleviate government financial pressures. This study adopted the contingent valuation method as well as face-to-face interview questionnaires to assess rural residents’ provision mode preferences, WTPP, and WTP for the CMP of RDST in China. Based on 761 samples collected from Shandong, Jilin, and Gansu provinces of China, we applied econometric models to estimate farmers’ WTPP and WTP for the CMP of RDST and explore the potential influencing factors, respectively. Results show that 1) 81.87% of the farmers would be willing to contribute to CMP of RDST; 2) farmers’ perceptions of the necessity of RDST, pollution of rural domestic sewage, and government propaganda significantly and positively affect their WTP; and 3) the expected WTP for CMP of RDST with the total respondents and the respondents with positive WTPP were estimated to be 7.59 USD/year and 10.10 USD/year (for a total of 20 years), accounting for 16.28 and 21.65% of construction costs, respectively. Based on these outcomes, it could be further estimated that the aggregate value was between 179.05 million USD/year and 238.26 million USD/year which implied that the farmers’ WTP may be a potentially non-negligible funding source for the CMP of RDST. The enhancement of environmental awareness of farmers and strengthening of propaganda should be the next priority of the Chinese government. Priority should also be assigned to villages closer to towns when the government formulates relevant strategies and policies. The results of this study provide references for policy formulation related to broadening the funding sources in RDST and exploring farmer payment mechanisms and implications for other developing countries.
Mxi1-0 Promotes Hypoxic Pulmonary Hypertension Via ERK/c-Myc-dependent Proliferation of Arterial Smooth Muscle Cells
Authors: Dong Liang , Liu Xinning , Wu Bo , Li Chengwei , Wei Xiaomin , Wumaier Gulinuer , Zhang Xiujuan , Wang Jing , Xia Jingwen , Zhang Yuanyuan , Yiminniyaze Ruzetuoheti , Zhu Ning , Li Jing , Zhou Daibing , Zhang Youzhi , Li Shuanghui , Lv Junzhu , Li Shengqing 
Published: March 2022

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality, and so far patients have failed to benefit from therapeutics clinically available. Max interacting protein 1–0 (Mxi1-0) is one of the functional isoforms of Mxi1. Although it also binds to Max, Mxi1-0, unlike other Mxi1 isoforms, cannot antagonize the oncoprotein c-Myc because of its unique proline rich domain (PRD). While Mxi1-0 was reported to promote cell proliferation via largely uncharacterized mechanisms, it is unknown whether and how it plays a role in the pathogenesis of HPH.Methods: GEO database was used to screen for genes involved in HPH development, and the candidate players were validated through examination of gene expression in clinical HPH specimens. The effect of candidate gene knockdown or overexpression on cultured pulmonary arterial cells, e.g., pulmonary arterial smooth muscle cells (PASMCs), was then investigated. The signal pathway(s) underlying the regulatory role of the candidate gene in HPH pathogenesis was probed, and the outcome of targeting the aforementioned signaling was evaluated using an HPH rat model.Results: Mxi1 was significantly upregulated in the PASMCs of HPH patients. As the main effector isoform responding to hypoxia, Mxi1-0 functions in HPH to promote PASMCs proliferation. Mechanistically, Mxi1-0 improved the expression of the proto-oncogene c-Myc via activation of the MEK/ERK pathway. Consistently, both a MEK inhibitor, PD98059, and a c-Myc inhibitor, 10058F4, could counteract Mxi1-0-induced PASMCs proliferation. In addition, targeting the MEK/ERK signaling significantly suppressed the development of HPH in rats.Conclusion: Mxi1-0 potentiates HPH pathogenesis through MEK/ERK/c-Myc-mediated proliferation of PASMCs, suggesting its applicability in targeted treatment and prognostic assessment of clinical HPH.
Construction of a Novel Immune-Related mRNA Signature to Predict the Prognosis and Immune Characteristics of Human Colorectal Cancer
Authors: Li Jianxin , Han Ting , Wang Xin , Wang Yinchun , Chen Xuan , Chen Wangsheng , Yang Qingqiang 
Published: March 2022

Background: Anti-cancer immunotherapeutic approaches have gained significant efficacy in multiple cancer types. However, not all patients with colorectal cancer (CRC) could benefit from immunotherapy due to tumor heterogeneity. The purpose of this study was to construct an immune-related signature for predicting the immune characteristics and prognosis of CRC.Methods: RNA-sequencing data and corresponding clinical information of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal (ImmPort). Then, we utilized univariate, lasso regression, and multivariate cox regression to identify prognostic IRGs and develop the immune-related signature. Subsequently, a nomogram was established based on the signature and other prognostic factors, and its predictive capacity was assessed by receiver operating characteristic (ROC) and decision curve analysis (DCA). Finally, associations between the signature and the immune characteristics of CRC were assessed.Results: In total, 472 samples downloaded from TCGA were divided into the training cohort (236 samples) and internal validation cohort (236 samples), and the GEO cohort was downloaded as an external validation cohort (122 samples). A total of 476 differently expressed IRGs were identified, 17 of which were significantly correlated to the prognosis of CRC patients. Finally, 10 IRGs were filtered out to construct the risk score signature, and patients were divided into low- and high-risk groups according to the median of risk scores in the training cohort. The high-risk score was significantly correlated with unfavorable survival outcomes and aggressive clinicopathological characteristics in CRC patients, and the results were further confirmed in the internal validation cohort, entire TCGA cohort, and external validation cohort. Immune infiltration analysis revealed that patients in the low-risk group infiltrated with high tumor-infiltrating immune cell (TIIC) abundances compared to the high-risk group. Moreover, we also found that the immune checkpoint biomarkers were significantly overexpressed in the low-risk group.Conclusion: The prognostic signature established by IRGs showed a promising clinical value for predicting the prognosis and immune characteristics of human CRC, which contribute to individualized treatment decisions.
Genomic Evidence Supports the Recognition of Endometriosis as an Inflammatory Systemic Disease and Reveals Disease-Specific Therapeutic Potentials of Targeting Neutrophil Degranulation
Authors: Bao Chaohui , Wang Hengru , Fang Hai 
Published: March 2022

BackgroundEndometriosis, classically viewed as a localized disease, is increasingly recognized as a systemic disease with multi-organ effects. This disease is highlighted by systemic inflammation in affected organs and by high comorbidity with immune-mediated diseases.ResultsWe provide genomic evidence to support the recognition of endometriosis as an inflammatory systemic disease. This was achieved through our genomics-led target prioritization, called ‘END’, that leverages the value of multi-layered genomic datasets (including genome-wide associations in disease, regulatory genomics, and protein interactome). Our prioritization recovered existing proof-of-concept therapeutic targeting in endometriosis and outperformed competing prioritization approaches (Open Targets and Naïve prioritization). Target genes at the leading prioritization revealed molecular hallmarks (and possibly the cellular basis as well) that are consistent with systemic disease manifestations. Pathway crosstalk-based attack analysis identified the critical gene AKT1. In the context of this gene, we further identified genes that are already targeted by licensed medications in other diseases, such as ESR1. Such analysis was supported by current interests targeting the PI3K/AKT/mTOR pathway in endometriosis and by the fact that therapeutic agents targeting ESR1 are now under active clinical trials in disease. The construction of cross-disease prioritization map enabled the identification of shared and distinct targets between endometriosis and immune-mediated diseases. Shared target genes identified opportunities for repurposing existing immunomodulators, particularly ﻿disease-modifying anti-rheumatic drugs (such as TNF, IL6 and IL6R blockades, and JAK inhibitors). Genes highly prioritized only in endometriosis revealed disease-specific therapeutic potentials of targeting neutrophil degranulation – the exocytosis that can facilitate metastasis-like spread to distant organs causing inflammatory-like microenvironments.ConclusionImproved target prioritization, along with an atlas of in silico predicted targets and repurposed drugs (available at https://23verse.github.io/end), provides genomic insights into endometriosis, reveals disease-specific therapeutic potentials, and expands the existing theories on the origin of disease.