bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells
Authors: Ding Xinmin , Wang Xiaolong , Han Li , Zhao Zhiyu , Jia Shuai , Tuo Yuanzhao 
Published: May 2021

BackgroundIntracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs).MethodsHBVSMCs were exposed to hydrogen peroxide (H2O2). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays.ResultsExposure to H2O2decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H2O2-treated HBVSMCs. Circ_DOCK1 overexpression rescued H2O2-caused reduction of proliferation and PCNA expression and attenuated H2O2-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H2O2-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H2O2-treated HBVSMCs. MCL1 was targetedviamiR-409-3p and downregulatedviaH2O2treatment. Circ_DOCK1 overexpression enhanced MCL1 expressionviamodulating miR-409-3p. MiR-409-3p knockdown weakened H2O2-induced proliferation reduction and apoptosis promotionviaregulating MCL1.ConclusionCirc_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.
Prognostic Role of High Sensitivity C-Reactive Protein in Patients With Acute Myocardial Infarction
Authors: Zhang Xiaoyuan , Wang Shanjie , Fang Shaohong , Yu Bo 
Published: May 2021

Background: High sensitivity CRP (hs-CRP) has attracted intense interest in risk assessment. We aimed to explore its prognostic value in patients with acute myocardial infarction (AMI).Methods and Results: We enrolled 4,504 consecutive AMI patients in this prospective cohort study. The associations between hs-CRP levels with the incidence of in-hospital HF was evaluated by logistic regression analysis. The association between hs-CRP levels and the cumulative incidence of HF after hospitalization were evaluated by Fine-Gray proportional sub-distribution hazards models, accounting for death without HF as competing risk. Cox proportional hazards regression models were constructed to estimate the association between hs-CRP levels and the risk of all-cause mortality. Over a median follow-up of 1 year, 1,112 (24.7%) patients developed in-hospital HF, 571 (18.9%) patients developed HF post-discharge and 262 (8.2%) patients died. In the fully adjusted model, the risk of in-hospital heart failure (HF) [95% confidence intervals (CI)] among those patients with hs-CRP values in quartile 3 (Q3) and Q4 were 1.36 (1.05–1.77) and 1.41 (1.07–1.85) times as high as the risk among patients in Q1 (p trend &lt; 0.001). Patients with hs-CRP values in Q3 and Q4 had 1.33 (1.00–1.76) and 1.80 times (1.37–2.36) as high as the risk of HF post-discharge compared with patients in Q1 respectively (p trend &lt; 0.001). Patients with hs-CRP values in Q3 and Q4 had 1.74 (1.08–2.82) and 2.42 times (1.52–3.87) as high as the risk of death compared with patients in Q1 respectively (p trend &lt; 0.001).Conclusions: Hs-CRP was found to be associated with the incidence of in-hospital HF, HF post-discharge and all-cause mortality in patients with AMI.
Programmed Cell Death 10 Mediated CXCL2-CXCR2 Signaling in Regulating Tumor-Associated Microglia/Macrophages Recruitment in Glioblastoma
Authors: Zhang Quan , Wang Junwen , Yao Xiaolong , Wu Sisi , Tian Weidong , Gan Chao , Wan Xueyan , You Chao , Hu Feng , Zhang Suojun , Zhang Huaqiu , Zhao Kai , Shu Kai , Lei Ting 
Published: May 2021

BackgroundProgrammed cell death 10 (PDCD10) plays a crucial role in regulating tumor phenotyping, especially in glioblastoma (GBM). Glioma-associated microglia/macrophages (GAMs) in tumor pathological microenvironment contribute to GBM progression. We previously found that the infiltration of GAMs was associated with PDCD10 expression in GBM patients. The present study aims to further explore the regulation of PDCD10 on GAMs in GBM.MethodsOverexpression of PDCD10 in human- and murine-GBM cells was established by lentiviral transduction. Cell behaviors and polarization of primary microglia, microglia- and macrophage-like cells were investigated through indirect co-culture with GBM cells in vitro respectively. The PDCD10-induced release of chemokines was identified by a chemokine protein array. The cross-talk between GBM and microglia as well as macrophages was further studied using selective antagonist SB225002. Finally, an orthotopic homograft mouse model was employed to verify the results of in vitro experiments.ResultsIndirect co-culture with PDCD10-overexpressed GBM cells promoted proliferation and migration of microglia- and macrophage-like cells, and stimulated pro-tumorigenic polarization of primary microglia, microglia- and macrophage-like cells. Pdcd10-upregulated GBM cells triggered a nearly 6-fold increase of CXC motif chemokine ligand 2 (CXCL2) release, which in turn activated CXC chemokine receptor 2 (CXCR2) and downstream Erk1/2 and Akt signaling in primary microglia, microglia- and macrophage-like cells. The blockage of CXCR2 signaling with specific inhibitor (SB225002) abolished microglia- and macrophage-like cell migration induced by PDCD10-upregulated GBM cells. Moreover, Pdcd10-upregulated GL261 cells promoted GAMs recruitment and tumor growth in vivo.ConclusionOur study demonstrates that overexpression of PDCD10 in GBM recruits and activates microglia/macrophages, which in turn promotes tumor progression. CXCL2-CXCR2 signaling mediated by PDCD10 is potentially involved in the crosstalk between GBM cells and GAMs.
Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature
Authors: Taguchi Kazumi , Okada Atsushi , Unno Rei , Hamamoto Shuzo , Yasui Takahiro 
Published: May 2021

BackgroundThe global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components in vivo, and in vitro including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.MethodsWe systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.ResultsAlthough several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages in vitro and ex vivo showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the ﻿NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.ConclusionsThis systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones via crystal phagocytosis.
Smiling, Yawning, Jaw Functional Limitations and Oral Behaviors With Respect to General Health Status in Patients With Temporomandibular Disorder—Myofascial Pain With Referral
Authors: Kuć Joanna , Szarejko Krzysztof Dariusz , Gołȩbiewska Maria 
Published: May 2021

Background: The temporomandibular joint is the one of the most important joints in the human body. It enables numerous orofacial functions such as mastication, swallowing, breathing, speech, emotional communication, and facial expressions. The aim of the study was to evaluate the prevalence of jaw functional limitations and oral behaviors with respect to general health status in patients with temporomandibular joint disorders—myofascial pain with referral.Materials and methods: The study group consisted of 50 individuals (37 females and 13 males) with complete natural dentition. The average age was 23.36 years with ± 0.30 as a standard error. All subjects underwent clinical examination and were diagnosed with myofascial pain with referral according to the Diagnostic Criteria for Temporomandibular Disorders. The survey was conducted in connection with the Jaw Functional Limitation Scale-8 (JFLS-8), Jaw Functional Limitation Scale-20 (JFLS-20), Patient Health Questionnaire-4 (PHQ-4), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-15 (PHQ-15), and Oral Behaviors Checklist (OBC).Results: The most common functional problems in the entire study group were chewing tough food and yawning. In terms of gender, statistically significant differences were noted for chewing tough food and smiling (p = 0.015451; p = 0.035978, respectively). With respect to Bonferroni correction and Benjamini-Hochberg procedure, the observed differences were not statistically significant. There were no statistically considerable differences in mastication, mandibular mobility, verbal and emotional communication, or global limitations (p &gt; 0.05). Over half (56%) of the respondents had depression of varying severity. Somatic symptoms of different severity were found in 78% of the patients, and 44% of the respondents declared anxiety disorders. The score of the Oral Behavior Checklist (OBC = 27.18) highlighted a high tendency for developing craniomandibular disorders.Conclusion: Patients with myofascial pain with referral, demonstrated a disturbed biopsychosocial profile. The restrictions in yawning and smiling as well as limitations in mastication, mobility, verbal and emotional communication, and global limitations appear to be significant predictors of craniomandibular dysfunction. Depression, stress, and somatic disorders are important factors predisposing patients to the occurrence of myofascial pain with referral. The progression of oral behaviors may indicate the role of somatosensory amplification.
Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison
Authors: Newman Nancy J. , Yu-Wai-Man Patrick , Carelli Valerio , Biousse Valerie , Moster Mark L. , Vignal-Clermont Catherine , Sergott Robert C. , Klopstock Thomas , Sadun Alfredo A. , Girmens Jean-François , La Morgia Chiara , DeBusk Adam A. , Jurkute Neringa , Priglinger Claudia , Karanjia Rustum , Josse Constant , Salzmann Julie , Montestruc François , Roux Michel , Taiel Magali , Sahel José-Alain 
Published: May 2021

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies.Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control.Subjects: The LHON subjects carried the m.11778G&gt;A ND4 mutation and were aged ≥15 years at onset of vision loss.Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences.Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4.Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p &lt; 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes (p &lt; 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (−0.32 LogMAR, p &lt; 0.0001).Conclusions: The m.11778G&gt;A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies.Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071.
A Systematic Review and Meta-Analysis of Autoantibodies for Diagnosis and Prognosis in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Guo Xiaoqian , Tang Lisha , Huang Qianyi , Tang Xiangqi 
Published: May 2021

Objectives: To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins.Background: Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody.Methods: We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and I2 statistics.Results: The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05–0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29–0.63) and 0.93 (95% CI: 0.86–0.97), respectively.Conclusions: For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test.Systematic Review Registration: PROSPERO, identifier: CRD42020203385 and CRD42020190789.
Is Contrast-Enhanced Ultrasound Superior to Computed Tomography for Differential Diagnosis of Gallbladder Polyps? A Cross-Sectional Study
Authors: Yuan Zhiqing , Liu Xuesong , Li Qiwei , Zhang Yunhe , Zhao Ling , Li Fenghua , Chen Tao 
Published: May 2021

ObjectiveTo compare the clinical value of contrast-enhanced ultrasonography (CEUS) versus computed tomography (CT) for distinguishing neoplastic and non-neoplastic gallbladder polyps. Given whether laparoscopic cholecystectomy is needed, differential diagnosis of neoplastic and non-neoplastic gallbladder polyps is more important than benign and malignant polyps.MethodsA total of 89 consecutive patients with polypoid lesions of the gallbladder &gt; 10 mm in size without local invasion or distant metastasis during primary screening were enrolled in this prospective and comparative study. All patients who met the inclusion criteria underwent CEUS and CT examinations prior to surgical resection. The enhancement patterns and microvascular imaging types were analyzed on CEUS. The maximum diameter and CT value of the lesions were also recorded and subjected to a comparative analysis. The clinical value of the two diagnostic methods is compared.ResultsOf the 89 patients, there were 58 (65.2%) cases of non-neoplastic polyps and 31 (34.8%) cases of neoplastic polyps. The average diameter of neoplastic polyps was significantly higher than that of non-neoplastic polyps (P&lt;0.001). The detection rate using CEUS was 100%. The proportion of perceived non-neoplastic polyps in the nonenhanced and arterial phases were 48.3% and 77.6%, respectively, which were significantly lower than those of neoplastic polyps (93.5%, P&lt;0.001 and 100.0%, P&lt;0.001, respectively). However, in the venous and delayed phases, all cholesterol polyps and neoplastic polyps were perceived. CT showed that non-neoplastic polyps exhibited delayed enhancement. On CEUS 29.0% neoplastic polyps showed a perfusion defect, whereas 6.9% non-neoplastic polyps showed a perfusion defect (P=0.005). The microvascular architecture of the lesions on CEUS was categorized into 4 types: spotty, linear, branched, and spinous, and there were significant differences between the two groups (P&lt;0.001). The sensitivities and specificities were 87.10% and 68.97% for CEUS and 83.87% and 77.59% for CT, respectively (P=0.406).ConclusionsCEUS and CT are useful for differential diagnosis of neoplastic and nonneoplastic polypoid lesions of the gallbladder. Diagnostic efficacy was comparable between CEUS and CT. Thus, CEUS is preferred over CT in the differential diagnosis of neoplastic and non-neoplastic gallbladder polyps due to its comparable diagnostic efficacy and lack of radiation dose.
Predicting Treatment Response to Neoadjuvant Chemoradiotherapy in Rectal Mucinous Adenocarcinoma Using an MRI-Based Radiomics Nomogram
Authors: Li Zhihui , Li Shuai , Zang Shuqin , Ma Xiaolu , Chen Fangying , Xia Yuwei , Chen Liuping , Shen Fu , Lu Yong , Lu Jianping 
Published: May 2021

ObjectiveTo build and validate an MRI-based radiomics nomogram to predict the therapeutic response to neoadjuvant chemoradiotherapy (nCRT) in rectal mucinous adenocarcinoma (RMAC).MethodsTotally, 92 individuals with pathologically confirmed RMAC administered surgical resection upon nCRT in two different centers were assessed retrospectively (training set, n = 52, validation set, n = 40). Rectal MRI was performed pre-nCRT. Radiomics parameters were obtained from high-resolution T2-weighted images and selected to construct a radiomics signature. Then, radiomics nomogram construction integrated patient variables and the radiomics signature. The resulting radiomics nomogram was utilized to assess the tumor regression grade (TRG). Diagnostic performance was determined by generating receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSix optimal features related to TRG were obtained to construct a radiomics signature. The nomogram combining the radiomics signature with age and mucin deposit outperformed the radiomics signature alone in the training (AUC, 0.950 vs 0.843, p &lt; 0.05) and validation (AUC, 0.868 vs 0.719, p &lt; 0.05) cohorts. DCA demonstrated a clinical utility for the radiomics nomogram model.ConclusionsThe established quantitative MRI-based radiomics nomogram is effective in predicting treatment response to neoadjuvant therapy in patients with RMAC.