bluuebunny/crossref_metadata_2025_split huggingface dataset:
F2RL3 Methylation in the Peripheral Blood as a Potential Marker for the Detection of Coronary Heart Disease: A Case-Control Study
Authors: Zhao Xiaojing , Zhu Liya , Yin Qiming , Xu Zhenguo , Jia Qian , Yang Rongxi , He Kunlun 
Published: March 2022

Background and Aims: Previous work has shown the association between blood-based methylation of coagulation factor II receptor-like 3 gene (F2RL3) and cardiovascular mortality in Caucasians. However, the diagnostic value of F2RL3 methylation for CHD is still unknown. The aim of our study was to evaluate the association between blood-based F2RL3 methylation and the risk of CHD in the Chinese population.Methods: The methylation level of F2RL3 was quantified by mass spectrometry in a case-control study with 180 CHD cases and 184 controls. The association between F2RL3 methylation intensity and CHD was assessed by logistic regression models, controlling confounding factors.Results: The hypomethylation in F2RL3_A amplicon was significantly associated with CHD (odds ratio (ORs) per -10% methylation: 1.22–1.42, p &lt; 0.035 for six out of seven CpG loci). Specifically, this significant association was observed in elderly CHD patients (≥60 years), myocardial infarction (MI) patients, heart failure patients and the patients with minor to medium cardiac function impairment (NYHA Ⅰ&amp;Ⅱ CHD cases) (ORs per -10% methylation: 1.35–1.58, 1.32–2.00, 1.29–1.43, 1.25–1.44; p &lt; 0.024, 0.033, 0.035, 0.025, respectively). However, F2RL3_B CpG sites showed no or very weak association with CHD. The combination of F2RL3_A_CpG_1 and F2RL3_A_CpG_3 methylation levels could efficiently discriminate CHD, MI, heart failure, NYHA I&amp;II CHD, and elderly CHD patients from controls (area under curve (AUC) = 0.75, 0.79, 0.75, 0.76, and 0.82, respectively).Conclusion: We propose blood-based F2RL3 methylation as a potential biomarker for CHD, especially for people with older age or with the status of MI. The combination of F2RL3 methylation and conventional risk factors might be an approach to evaluate CHD at early stage.
A Mendelian Randomization Study of the Effect of Tea Intake on Type 2 Diabetes
Authors: Zhang Yanan , Wang Ruiqing , Tang Xinhua , Wang Yanjun , Guo Ping , Wang Shukang , Liu Jing 
Published: March 2022

Background: The association reported between tea intake and type 2 diabetes (T2D) is inconsistent in previous studies and remains controversial. We aimed to explore the causal relationship between tea intake, T2D, and glycemic traits including hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model of insulin resistance (HOMA-IR) levels.Methods: A 2-sample Mendelian randomization (MR) was performed using summary statistics from large-scale genome-wide association studies of tea intake from the UK Biobank, T2D from the DIAGRAM consortium, and glycemic traits from the Magic consortium. The findings were verified through sensitivity analyses using various MR methods with different model assumptions and by comprehensively evaluating the influence of pleiotropy effects and outliers.Results: With the use of a two-sample MR with inverse variance-weighted method, the odds ratio per unit SD change of tea intake (SD: 2.85 cups/day) for T2D, HbA1c, FPG, FSI, and HOMA-IR levels was 0.949 (95% CI 0.844–1.067, p = 0.383), 0.994 (95% CI 0.975–1.013, p = 0.554), 0.996 (95% CI 0.978–1.015, p = 0.703), 0.968 (95% CI 0.948–0.986, p = 0.001), and 0.953 (95% CI 0.900–1.009, p = 0.102), respectively. The results were consistent with those of the other six methods that we used with different model assumptions, suggesting that the findings were robust and convincing. We also performed various sensitivity analyses for outlier removal, pleiotropy detection, and leave-one-out analysis.Conclusion: Our MR results did not support the causal effect of tea intake on T2D and crucial glycemic traits. These findings suggest that previous observational studies may have been confounded.
Case Report: Identification of a De novo C19orf12 Variant in a Patient With Mitochondrial Membrane Protein–Associated Neurodegeneration
Authors: Yang Yue , Zhang Shijie , Yang Wenming , Wei Taohua , Hao Wenjie , Cheng Ting , Wang Jiuxiang , Dong Wei , Qian Nannan 
Published: March 2022

Background: Mitochondrial membrane protein–associated neurodegeneration (MPAN) mostly arises as an autosomal recessive disease and is caused by variants in the chromosome 19 open reading frame 12 (C19orf12) gene. However, a few C19orf12 monoallelic truncating de novo variants have been reported and segregated as autosomal dominant traits in some cases.Methods: We performed whole-exome sequencing and analyzed genes related to neurodegeneration associated with brain iron accumulation for pathogenic variants. The identified variants were confirmed by Sanger sequencing and tested using in silico tools.Results: The patient had an onset of depression at the age of 22 years, which rapidly progressed to severe dystonia, dementia, and bladder and bowel incontinence. Neuroimaging showed hypointensity in the substantia nigra and the globus pallidum, with additional frontotemporal atrophy. Genetic analysis revealed a single complex de novo variant [c.336_338delinsCACA (p.Trp112CysfsTer40)] in the C19orf12 gene.Conclusion: This study enriches the genetic spectrum and clinical features of C19orf12 variants and provides additional evidence of the variable inheritance pattern of MPAN.
Construction and Bioinformatics Analysis of circRNA-miRNA-mRNA Network in Acute Myocardial Infarction
Authors: Zhou Jin , He Shaolin , Wang Boyuan , Yang Wenling , Zheng Yuqi , Jiang Shijiu , Li Dazhu , Lin Jibin 
Published: March 2022

Background: Acute myocardial infarction (AMI) is one of the main fatal diseases of cardiovascular diseases. Circular RNA (circRNA) is a non-coding RNA (ncRNA), which plays a role in cardiovascular disease as a competitive endogenous RNA (ceRNA). However, their role in AMI has not been fully clarified. This study aims to explore the mechanism of circRNA-related ceRNA network in AMI, and to identify the corresponding immune infiltration characteristics.Materials and Methods: The circRNA (GSE160717), miRNA (GSE24548), and mRNA (GSE60993) microarray datasets of AMI were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified by the “limma” package. After integrating the circRNA, miRNA and mRNA interaction, we constructed a circRNA-miRNA-mRNA network. The “clusterProfiler” package and String database were used for functional enrichment analysis and protein-protein interaction (PPI) analysis, respectively. After that, we constructed a circRNA-miRNA-hub gene network and validated the circRNAs and mRNAs using an independent dataset (GSE61144) as well as qRT-PCR. Finally, we used CIBERSORTx database to analyze the immune infiltration characteristics of AMI and the correlation between hub genes and immune cells.Results: Using the “limma” package of the R, 83 DEcircRNAs, 54 DEmiRNAs, and 754 DEmRNAs were identified in the microarray datasets of AMI. Among 83 DEcircRNAs, there are 55 exonic DEcircRNAs. Then, a circRNA-miRNA-mRNA network consists of 21 DEcircRNAs, 11 DEmiRNAs, and 106 DEmRNAs were predicted by the database. After that, 10 hub genes from the PPI network were identified. Then, a new circRNA-miRNA-hub gene network consists of 14 DEcircRNAs, 7 DEmiRNAs, and 9 DEmRNAs was constructed. After that, three key circRNAs (hsa_circ_0009018, hsa_circ_0030569 and hsa_circ_0031017) and three hub genes (BCL6, PTGS2 and PTEN) were identified from the network by qRT-PCR. Finally, immune infiltration analysis showed that hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI.Conclusion: Our study constructed a circRNA-related ceRNA networks in AMI, consists of hsa_circ_0031017/hsa-miR-142-5p/PTEN axis, hsa_circ_0030569/hsa-miR-545/PTGS2 axis and hsa_circ_0009018/hsa-miR-139-3p/BCL6 axis. These three hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI. It helps improve understanding of AMI mechanism and provides future potential therapeutic targets.
pitpβ_w Encoding Phosphatidylinositol Transfer Protein Is Involved in Female Differentiation of Chinese Tongue Sole, Cynoglossus semilaevis
Authors: Sun Yuxuan , Zhang Mengqian , Cheng Peng , Gong Zhihong , Li Xihong , Wang Na , Wei Min , Xu Xiaodong , Xu Wenteng 
Published: March 2022

Phosphatidylinositol transfer protein (pitp) plays an important role in phospholipid transfer in animals. A pitp variant (pitpβ_w) in Chinese tongue sole was identified by transcriptomic analysis for its female-biased expression. The coding sequence of pitpβ_w was 816 bp, encoding a 371-amino-acid protein. pitpβ_w showed female-biased expression and was relatively high in brain, muscle, and ovary tissues. In different developmental stages of the ovary, pitpβ_w could be detected from 40 days until 3 years post hatching, and the highest expression was observed at 90 days. In situ hybridization revealed that pitpβ_w was predominantly localized in early-stage oocytes (I–III stages). After siRNA-mediated knockdown of pitpβ_w in an ovarian cell line, the expression of sox9a was reduced, while that of figla_tv1 and sox9b was significantly increased. Our findings suggest that pitpβ_w might be involved in female differentiation and early oogenesis.
Tropisetron Preconditioning Decreases Myocardial Biomarkers in Patients Undergoing Heart Valve Replacement Surgery
Authors: Yu Di , Gong Xingrui , Zhang Yufei , Li Qing , Zhang Mazhang 
Published: March 2022

BackgroundCardioplegic arrest during the heart valve replacement surgery frequently leads to myocardial damage. Tropisetron (TRP) has been demonstrated to reduce myocardial ischemia-reperfusion injury and inflammation in animals. We examined the efficacy of TRP in lowering myocardial biomarkers in patients undergoing heart valve replacement surgery.MethodsA total of seventy-five patients, scheduled for elective heart valve replacement surgery, were randomly chosen to receive either 10 ml of normal saline or 10 mg/10 ml of TRP immediately after anesthesia induction. Blood samples for the measurement of cardiac troponin I (cTnI), creatine kinase (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were taken before anesthesia, as well as 4, 12, and 24 h after aortic cross-clamp release to evaluate myocardial injury using two-way ANOVA for repeated measurements. The study was registered at www.chictr.org.cn (number, ChiCTR-1800018681).ResultsTreatment with TRP decreased the increment of cTnI (Fgroup = 4.911, p = 0.030; Ftime = 55.356, p = 0.001; Fgroup × time = 5.340, p = 0.002) at 12 and 24 h; of CK-MB (Fgroup = 6.552, p = 0.013; Ftime = 49.276, p = 0.001; Fgroup × time = 7.627, p = 0.003) at 4, 12, and 24 h; of TNF-α (Fgroup = 4.153, p = 0.046; Ftime = 28.244, p = 0.002; Fgroup × time = 4.692, p = 0.006) at 4 and 12 h; and of LDH (Fgroup = 4.275, p = 0.043; Ftime = 63.225, p = 0.001; Fgroup × time = 2.501, p = 0.083) at 24 h after the release of the aortic cross-clamp. It increased IL-10 (Fgroup = 5.958, p = 0.018; Ftime = 31.226, p = 0.002; Fgroup × time = 1.464, p = 0.236) at 12 h after the release of the aortic cross-clamp. Multiple linear regression analysis showed that cardiopulmonary bypass (CPB) time was a risk factor, and that TRP treatment was a protective factor for postoperative cTNI change (β = 4.449, 95% CI [0.97–7.92], p = 0.013 for CPB time; and β = −381, 95% CI [−613.4 to −148.5], p = 0.002 for TRP treatment).ConclusionsTropisetron had cardioprotective and anti-inflammatory effects in patients undergoing heart valve replacement surgery with cardioplegic arrest. The addition of TRP and reduction of CPB time should be considered for myocardial protection in heart valve replacement surgery.Clinical Trial Registration[www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018681].
The Value of the Frog Lateral View Radiograph for Detecting Collapse of Femur Head Necrosis: A Retrospective Study of 1001 Cases
Authors: Yang Fan , Deng Xiaoqiang , Xin Pengfei , Hong Zhinan , Pang Fengxiang , He Wei , Wei Qiushi , Li Ziqi 
Published: March 2022

AimsThe collapse in femur head necrosis is generally detected by CT or MRI which are not primary routine examination at every follow-up in developing countries. The purpose of this study was to verify the reliability of the frog lateral view radiograph in detecting the collapse of femoral head.MethodsWe retrospectively included 1001 hips of 620 patients with femur head necrosis. The anteroposterior view and frog lateral view of X-ray standard radiographs, CT and MRI of patients were collected and simultaneously evaluated by three orthopedists to evaluate the condition of collapse according to the unified standard. The inter-observer reliability of each view of X-ray for detecting the collapse were analyzed through the weighted Cohen's kappa index. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of each evaluation method were also calculated.ResultsA moderate or substantial reliability was indicated in the evaluation of frog lateral view radiograph, whereas the anteroposterior view only showed fair or poor reliability. Using the CT or MRI results of collapse as the gold standard, the frog lateral view indicated higher sensitivity and accuracy than the anteroposterior view (sensitivity: 82.8 vs. 64.9%; accuracy: 87.1 vs. 73.9%). The combination of the anteroposterior view and frog lateral view indicated higher reliability than individual views.ConclusionThe frog lateral view radiograph has higher sensitivity and accuracy than anteroposterior view. It is a complementary method to AP view for detecting the collapse in femur head necrosis during the follow-up, which has moderate or substantial inter-observer reliability.
Hyperinflammatory State and Low T1 Adaptive Immune Response in Severe and Critical Acute COVID-19 Patients
Authors: Garcia-Gasalla Mercedes , Berman-Riu María , Pons Jaime , Rodríguez Adrián , Iglesias Amanda , Martínez-Pomar Natalia , Llompart-Alabern Isabel , Riera Melchor , Ferré Beltrán Adrián , Figueras-Castilla Albert , Murillas Javier , Ferrer Joana M. 
Published: March 2022

BackgroundA better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.ObjectiveWe aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.Methods139 hospitalized patients with COVID-19−58 mild/moderate and 81 severe/critical—and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8–12 weeks after discharge.ResultsA National Early Warning Score 2 &gt;2 (OR:41.4; CI:10.38–167.0), ferritin &gt;583 pg/mL (OR:16.3; CI: 3.88–69.9), neutrophil/lymphocyte ratio &gt;3 (OR: 3.5; CI: 1.08–12.0), sIL-2rα (sCD25) &gt;512 pg/mL (OR: 3.3; CI: 1.48–7.9), IL-1Ra &gt;94 pg/mL (OR: 3.2; IC: 1.4–7.3), and IL-18 &gt;125 pg/mL (OR: 2.4; CI: 1.1–5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases.ConclusionA characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a “low T1 lymphocyte signature” was found in severe/critical COVID-19 patients.
The Value of the Antibody Detection in the Diagnosis of Ocular Toxocariasis and the Aqueous Cytokine Profile Associated With the Condition
Authors: Zhang Xiang , Yang Yuan , Zheng Yan , Hu Yiqian , Rao Yuqing , Li Jiakai , Zhao Peiquan , Li Jing 
Published: March 2022

IntroductionTo evaluate and compare the specificity of Toxocara canis-specific antibody detection in the serum and aqueous samples for the diagnosis of ocular toxocariasis (OT) and explore the cytokine profiles associated with the condition in children.Materials and MethodsThis is a prospective cohort study. The inclusion criteria were the clinical presentations of OT, which included unilateral vision reduction, typical peripheral or posterior pole granuloma with variable degrees of vitritis, and exclusion of other diagnoses. The titer of antibody against the excretory-secretory antigen of Toxocara canis [T-immunoglobulin G (IgG)] was measured in serum and aqueous samples that were taken from the affected eyes. The diagnosis of OT was made upon positive detection of T-IgG either in the serum or aqueous. The rest with typical clinical presentations as described above but a positive serum or aqueous T-IgG could not be confirmed were diagnosed as suspected OT. Cytokines were measured using multiplexed cytometric bead array system.ResultsTwo hundred and eleven eyes of 211 patients had participated in the study. One hundred and twenty-eight eyes were diagnosed as OT. The median age of the cohort was 7.7 years with a male to female ratio of 2.5:1. Major initial symptoms were decreased vision (74%) and strabismus (22%). The percentages of eyes with peripheral granuloma, posterior granuloma, and endophthalmitis were 40, 18, and 41%, respectively. Vitritis (100%), vitreous strands (64%), retinal fibrotic bands (57%), and retinal detachment (42%) were the most common signs. T-IgG was positive in 66.7% of the aqueous and 57.2% of the serum samples. Forty-four patients were diagnosed T-IgG negative in both serum and aqueous of the affected eyes. Interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, eosinophil chemotactic protein (Eotaxin), MCP-1β, and vascular endothelial growth factor (VEGF) were higher in T-IgG negative eyes when compared to controls and further increased in T-IgG positive eyes. However, only T-IgG positive eyes showed increased IL-5, IL-13, and IL-10. IL-1β, tumor necrosis factor-alpha (TNF-α), IL-12, IL-2, interferon-gamma (IFN-γ), and IL-4 were undetectable in all eyes.ConclusionsPediatric OT is often present with severe retinal complications. Polarized intraocular Th2 response was only found in aqueous T-IgG positive eyes. Our results supported an aqueous sample-based antibody test for the more specific diagnosis of OT.
Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study
Authors: Xing Huiwu , Tan Bingqian , Yang Chenyu , Zhang Mingman 
Published: March 2022

BackgroundIntrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer characterized by rapid progression and poor prognosis. There are few effective tools for evaluating the prognosis of ICCA patients, and the use of liver transplantation (LT) of the treatment for ICCA is still controversial.MethodsWe analyzed ICCA incidence data and clinicopathological data from the Surveillance, Epidemiology, and End Results database. Prognostic predictors were identified by univariate and multivariate Cox regression analyses and then used to establish a nomogram. The prediction performance of the nomogram was evaluated with receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA) plots. Propensity score matching (PSM) was used to balance the baseline data of patients undergoing LT and other operations, and then, univariate Cox regression analysis was used to evaluate the therapeutic value of LT for ICCA.ResultsThe incidence of ICCA increased significantly, from 0.6 per 100,000 in 2,000 to 1.3 per 100,000 in 2018. The median overall survival (OS) of the patients was 13 months, and the 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively. Cox regression analysis showed that age under 60 years old, female, tumor size ≤ 50 mm, better differentiation, smaller range of tumor invasion, lack of distant metastasis, regional lymph node surgery and treatment were associated with a better prognosis. The ROC curves, calibration plots, and DCA plots showed that the nomogram had good discrimination and calibration power, as well as clinical utility. After PSM, the univariate Cox regression analysis showed no significant difference in OS between patients treated with LT and patients treated with other operations.ConclusionThe incidence of ICCA increased significantly. A nomogram with good predictive performance was developed to predict the OS of ICCA patients. LT might be considered as a potential option for some ICCA patients.
Metagenomic Next-Generation Sequencing to Investigate Infectious Endophthalmitis of Brucella: A Case Report
Authors: Xi Huiyu , Zhang Lishuai , Xu Bo , Liu Haiyang , Li Suyan 
Published: March 2022

IntroductionBrucellosis is a systemic disease that exists prevalently in clinical manifestations. The symptoms present in organs such as the eyes (in ocular brucellosis) can lead to misdiagnosis or even failure to diagnose. Metagenomic Next-Generation Sequencing (mNGS), a high-throughput sequencing approach, could be applied for the detection of microorganisms.Case PresentationA 57-year-old female with acute right-eye vision loss, treated with clindamycin and dexamethasone sodium phosphate for 1.5 months, was difficult to diagnose using regular methods. mNGS was utilized for the aqueous fluid from the patient, and Brucella melitensis was identified. The inflammation was treated with 3 months of antibiotherapy. However, even with specific medicine and surgery, the vision remained poor because severe ocular conditions last for a long time.ConclusionIt suggests that brucella should still be a probable pathogen in endophthalmitis despite its low incidence in non-epidemic areas. Moreover, mNGS can achieve early diagnosis and timely treatment for difficult-to-diagnose ocular infections.