Radiomics-based discrimination of coronary chronic total occlusion and subtotal occlusion on coronary computed tomography angiography.

OBJECTIVES: Differentiating chronic total occlusion (CTO) from subtotal occlusion (SO) is often difficult to make from coronary computed tomography angiography (CCTA). We developed a CCTA-based radiomics model to differentiate CTO and SO. METHODS: A total of 66 patients with SO underwent CCTA before invasive angiography and were matched to 66 patients with CTO. Comprehensive imaging analysis was conducted for all lesioned vessels, involving the automatic identification of the lumen within the occluded segment and extraction of 1,904 radiomics features. Radiomics models were then constructed to assess the discriminative value of these features in distinguishing CTO from SO. External validation of the model was performed using data from another medical center. RESULTS: Compared to SO patients, CTO patients had more blunt stumps (internal: 53/66 (80.3%) vs. 39/66 (59.1%); external: 36/50 (72.0%) vs. 20/50 (40.0%), both p < 0.01), longer lesion length (internal: median length 15.4 mm[IQR: 10.4-22.3 mm] vs. 8.7 mm[IQR: 4.9-12.6 mm]; external:11.8 mm[IQR: 6.1-23.4 mm] vs. 6.2 mm[IQR: 3.5-9.1 mm]; both p < 0.001). Sixteen unique radiomics features were identified after the least absolute shrinkage and selection operator regression. When added to the combined model including imaging features, radiomics features provided increased value for distinguishing CTO from SO (AUC, internal: 0.772 vs. 0.846; p = 0.023; external: 0.718 vs. 0.781, p = 0.146). CONCLUSIONS: The occluded segment vessels of CTO and SO have different radiomics signatures. The combined application of radiomics features and imaging features based on CCTA extraction can enhance diagnostic confidence.

The relationship between epicardial adipose tissue volume on coronary computed tomography angiography and idiopathic ventricular tachycardia: a propensity score matching case-control study in Chinese population.

Background: Large epicardial adipose tissue (EAT) volume is associated with the incidence of premature ventricular beats. The relationship between EAT volume and idiopathic ventricular tachycardia (IVT) is not yet clear. We aimed to investigate the effect of EAT volume on the risk of IVT. Methods: This is a retrospective consecutive case-control study from January 2020 to September 2022. IVT patients (n=81) and control patients (n=162) undergoing coronary computed tomography angiography (CCTA) were retrospectively recruited. The patients in the control group were all hospitalized patients for different reasons, such as chest tightness, shortness of breath, chest pain, and so on. Demographic parameters and clinical characteristics of each individual were collected from the patient's medical records. We selected evaluation criteria for the conduct of a 1:1 propensity score (PS)-adjusted analysis. Multivariable logistic analysis was used to investigate risk factors for IVT. Furthermore, the impact of EAT volume on cardiac repolarization indices was assessed in IVT patients. Results: Patients with IVT had a larger EAT volume than control group patients in the unadjusted cohort. Variables with P<0.10 in the univariable analysis and important factors were included in the multivariable analysis model, including body mass index (BMI), left ventricular ejection fraction (LVEF), early peak/artial peak (E/A) ratios <1, EAT attenuation, and EAT volume (per increase 10 mL). The multivariable logistic analysis found that EAT volume [per increase 10 mL, odds ratio (OR): 1.29, 95% confidence interval (CI): 1.17-1.41, P<0.001] was an independent risk factor for IVT. EAT volume (per increase 10 mL, OR: 1.43, 95% CI: 1.25-1.64, P<0.001) independent effect was demonstrated in the PS adjusted cohort (n=57 in both groups). The area under the curve of EAT volume to predict the risk of IVT patients in the PS adjusted cohort was 0.859. The sensitivity and specificity were 86.0%, and 75.4%, respectively. Furthermore, A large EAT volume of IVT patients had a longer time in Tp-e, and Tp-e/QTc, compared with low EAT volume. Conclusions: Patients with IVT had increased EAT volume compared to control subjects. Our study revealed that large EAT volume is associated with an extended repolarization process in IVT patients. These insights are essential for understanding the mechanisms linking EAT with IVT.

The relationship between frequent premature ventricular complexes and epicardial adipose tissue volume.

Background: Epicardial adipose tissue (EAT) is related to atrial fibrillation. The association between EAT volume and premature ventricular complexes (PVCs) remains unclear. Our study aimed to investigate the effect of EAT volume on the risk of frequent PVCs and burden levels of PVCs. Methods: This observational study retrospectively recruited consecutive patients who had consultation between 2019 and 2021 at the First Affiliated Hospital of Zhengzhou University. Frequent PVC patients (n = 402) and control patients (n = 402) undergoing non-contrast computed tomography (CT) were enrolled. We selected evaluation criteria for the conduct of a 1:1 propensity score matching (PSM) analysis. Multivariable logistic analysis was used to investigate factors related to frequent PVCs. Furthermore, the determinants of EAT volume and the burden levels of PVCs were evaluated. Results: Patients with PVCs had a significantly larger EAT volume than control patients. EAT volume was significantly larger in male PVC patients with BMI ≥24 kg/m2, diabetes mellitus, and E/A ratio <1. EAT volume was independently associated with PVCs. Moreover, the larger EAT volume was an independent predictor for the high burden level of PVCs. We revealed that the risk of high PVC burden level was increased with the rising of EAT volume by restricted cubic splines. Conclusions: EAT volume was larger in frequent PVC patients than in control patients, regardless of other confounding factors. A large EAT volume was independently associated with high burden levels of PVCs. EAT volume may be a new mechanism to explain the pathogenesis of PVCs.

Exploring the Associations Between Non-Traditional Lipid Parameters and Epicardial Adipose Tissue Volume.

The aim of this retrospective study was to determine the relationship between non-traditional lipid parameters and epicardial adipose tissue (EAT). A total of 770 patients with coronary computed tomography angiography examinations were included. The non-traditional lipid parameters included the atherogenic index of plasma (AIP), the atherogenic coefficient (AC), monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR), and lipoprotein combined index (LCI). To investigate the association between non-conventional lipid markers and the EAT-volume (EAT-v), a univariate and multivariate analyses were conducted. The receiver operating characteristic (ROC) analysis was used to compare the predictive ability among the four non-traditional lipid parameters. In the univariate analysis, we identified factors that might have effects on EAT-v (all P<.05) and adjusted for these in the multivariate analysis. We found that except for MHR, other non-traditional lipid parameters were still associated with high EAT-v after adjustment (all P<.05). In the ROC analysis, the area under the curve (AUC) of AIP was greater than that of other non-traditional lipid parameters and lipid profiles. There was an association between both non-traditional lipid parameters and EAT-v. After adjustment, the AIP remained an independent predictor of EAT-v and it outperformed other non-traditional lipid parameters.

Impact of pericoronary adipose tissue attenuation on recurrence after radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Inflammation plays a vital role in the occurrence and progression of atrial fibrillation (AF). The association between pericoronary adipose tissue attenuation (PCATA) and AF recurrence following ablation has not been fully clarified. HYPOTHESIS: We aimed to evaluate the association between PCATA and AF recurrence after radiofrequency catheter ablation (RFCA). METHODS: Patients who underwent the first RFCA for AF and performed coronary computed tomography angiography before ablation between 2018 and 2021 were enrolled. The predictive values of PCATA for AF recurrence after ablation were investigated. The area under curve (AUC), relative integrated discrimination improvement (IDI), and categorical free net reclassification improvement (NRI) were used to assess the discrimination ability of different models for AF recurrence. RESULTS: During 1-year follow-up, 34.1% patients experienced AF recurrence. The multivariable analysis model revealed that PCATA of the right coronary artery (RCA) was an independent risk factor for AF recurrence. Patients with a high level of RCA-PCATA had a high risk of recurrence, after adjusting for other risk factors by restricted cubic splines. The performance in predicting AF recurrence was significantly improved by adding the marker of RCA-PCATA to the clinical model (AUC: 0.724 vs. 0.686, p = .024), with a relative IDI of 0.043 (p = .006) and continuous NRI of 0.521 (p < .001). CONCLUSIONS: PCATA of RCA was independently associated with AF recurrence after ablation. PCATA may be helpful for risk classification for AF ablation patients.

An expanded landscape of human long noncoding RNA.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

Discovery of microRNAs during early spermatogenesis in chicken.

Spermatogenesis is a complex process that involves many elements. However, until now, little is known at the molecular level about spermatogenesis in poultry. Here we investigated microRNAs and their target genes that may be involved in germ cell development and spermatogonial in chicken. We used next-generation sequencing to analyze miRNA expression profiles in three types of germline cells: primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and spermatogonia (Sp) during early stage of spermatogenesis. After validated the candidate miRNAs and corresponding genes' expression in three types of cells, we found 15 miRNAs that were enriched 21 target genes that may be involved in spermatogenesis. Among the enriched miRNAs, miR-202-5p/3p were up-regulated in the Sp library and down-regulated in the PGCs library. Through RT-qPCR and Dual-Luciferase reporter assay, we confirmed that miR-202-5p bind to LIMK2 and involved in germ cell development. Collectively, we firstly discover the novel miRNAs, like miR-202-5p, and its related genes and pathways, expressed during the early spermatogonial stage in chicken, which will provide new clues for deciphering the molecular mechanism of the miRNAs regulating germline stem cell differentiation and spermatogenesis in chicken.

DNA methylation-mediated transcription factors regulate Piwil1 expression during chicken spermatogenesis.

The P-element induced wimpy testis (Piwi) protein family is responsible for initiating spermatogenesis and maintaining the integrity of germ cells and stem cells, but little is known regarding its transcriptional regulation in poultry. Here, we characterized the methylation status of the Piwil1 promoter in five different spermatogenic cell lines using direct bisulfite pyrosequencing and determined that methylation correlates negatively with germ cell type-specific expression patterns of piwil1. We demonstrated that methylation of the -148 CpG site, which is the predicted binding site for the transcription factors TCF3 and NRF1, was differentially methylated in different spermatogenic cells. This site was completely methylated in PGCs (primordial germ cells), but was unmethylated in round spermatids. A similar result was obtained in the region from +121 to +139 CpG sites of the Piwil1 promoter CpG island, which was predicted to contain SOX2 binding sites. In addition, demethylation assays further demonstrated that DNA methylation indeed regulates Piwil1 expression during chicken spermatogenesis. Combined with transcription factor binding site prediction, we speculate that methylation influences the recruitment of corresponding transcription factors. Collectively, we show the negative correlation between promoter methylation and piwil1 expression and that the spatiotemporal expression of chicken Piwil1 from the PGC stage to the round spermatid stage is influenced by methylation-mediated transcription factor regulation.

Piwil1 mediates meiosis during spermatogenesis in chicken.

Piwil1 mediates spermatogenesis and ensures stable cell division rates in germline cells in mammals. However, the involvement of Piwil1 in poultry spermatogenesis and meiosis is poorly understood. In the present study, we used TaqMan RT-qPCR to characterize Piwil1 mRNA expression in different types of spermatogenic cells, including primordial germ cells (PGCs), spermatogonial stem cells (SSCs), spermatogonia cells (Sa), tetraploid cells (Tp), round sperm cells (Rs), mature sperm, and in PGCs treated with retinoic acid. Our results revealed that Piwil1 is differentially expressed during spermatogenesis in chicken. Compared to PGCs, SSCs, Tp, and Sa, Rs cells presented the highest Piwil1 mRNA expression levels. Retinoic acid significantly upregulated Piwil1 and Stra8 mRNA expression as well as Piwil1 levels in chicken PGCs. In addition, retinoic acid induced PGCs to progress through all the meiotic stages, eventually leading to haploid cell formation, which was determined using flow cytometry and western blot analysis. Taken together, our results showed that during spermatogenesis, Piwil1 was first expressed at low levels in germ stem cells, PGCs, and SSCs. Its expression levels increased during later meiosis stages. Finally, no expression was detected in mature sperm after meiosis. Treatment of PGCs with retinoic acid further demonstrated that Piwil1 plays a key role in meiosis during chicken spermatogenesis.

Systematically profiling and annotating long intergenic non-coding RNAs in human embryonic stem cell.

BACKGROUND: While more and more long intergenic non-coding RNAs (lincRNAs) were identified to take important roles in both maintaining pluripotency and regulating differentiation, how these lincRNAs may define and drive cell fate decisions on a global scale are still mostly elusive. Systematical profiling and comprehensive annotation of embryonic stem cells lincRNAs may not only bring a clearer big picture of these novel regulators but also shed light on their functionalities. RESULTS: Based on multiple RNA-Seq datasets, we systematically identified 300 human embryonic stem cell lincRNAs (hES lincRNAs). Of which, one forth (78 out of 300) hES lincRNAs were further identified to be biasedly expressed in human ES cells. Functional analysis showed that they were preferentially involved in several early-development related biological processes. Comparative genomics analysis further suggested that around half of the identified hES lincRNAs were conserved in mouse. To facilitate further investigation of these hES lincRNAs, we constructed an online portal for biologists to access all their sequences and annotations interactively. In addition to navigation through a genome browse interface, users can also locate lincRNAs through an advanced query interface based on both keywords and expression profiles, and analyze results through multiple tools. CONCLUSIONS: By integrating multiple RNA-Seq datasets, we systematically characterized and annotated 300 hES lincRNAs. A full functional web portal is available freely at http://scbrowse.cbi.pku.edu.cn. As the first global profiling and annotating of human embryonic stem cell lincRNAs, this work aims to provide a valuable resource for both experimental biologists and bioinformaticians.

Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation.

BACKGROUND: The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features. RESULTS: In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental-pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable. CONCLUSION: Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis.