Background
The diagnostic work‐up for cardiac arrest from ventricular tachyarrhythmias occurring in younger adults and structurally normal hearts is variable and often incomplete.
Methods
We reviewed ...records for all recipients of a secondary prevention implantable cardiac defibrillator (ICD) younger than 60 years at a single quaternary referral hospital from 2010 to 2021. Patients with unexplained ventricular arrhythmias (UVA) were identified as those with no structural heart disease on echocardiogram, no obstructive coronary disease, and no clear diagnostic features on ECG. We specifically evaluated the adoption rate of five modalities of “second‐line” cardiac investigations: cardiac magnetic resonance imaging (CMR), exercise ECG, flecainide challenge, electrophysiology study (EPS), and genetic testing. We also evaluated patterns of antiarrhythmic drug therapy and device‐detected arrhythmias and compared them with secondary prevention ICD recipients with a clear etiology found on initial assessment.
Results
One hundred and two recipients of a secondary prevention ICD under the age of 60 were analyzed. Thirty‐nine patients (38.2%) were identified with UVA and were compared with the remaining 63 patients with VA of clear etiology (61.8%). UVA patients were younger (35.6 ± 13.0 vs. 46.0 ± 8.6 years, p < .001) and were more often female (48.7% vs. 28.6%, p = .04). CMR was performed in 32 patients with UVA (82.1%), whereas flecainide challenge, stress ECG, genetic testing, and EPS were only performed in a minority of patients. Overall, the use of a second‐line investigation suggested an etiology in 17 patients with UVA (43.5%). Compared to patients with VA of clear etiology, UVA patients had lower rates of antiarrhythmic drug prescription (64.1% vs. 88.9%, p = .003) and had a higher rate of device‐delivered tachy‐therapies (30.8% vs. 14.3%, p = .045).
Conclusion
In this real‐world analysis of patients with UVA, the diagnostic work‐up is often incomplete. While CMR was increasingly utilized at our institution, investigations for channelopathies and genetic causes appear to be underutilized. Implementation of a systematic protocol for work‐up of these patients requires further study.
Diagnotic yield of second‐line investigations in the workup of unexplained ventricular tachyarrhythmia. Of 102 recipients of secondary prevention implantable cardiac defibrillators aged under the age of 60 years, 39 patients met criteria for unexplained ventricular arrhythmia. Seventeen of these 39 patients had an underlying diagnosis suggested by a second‐line investigation. Cardiac MRI was the most frequently utilized test, while the remaining investigations were utilized less commonly.
Alcohol and Atrial Fibrillation: A Sobering Review Voskoboinik, Aleksandr; Prabhu, Sandeep; Ling, Liang-Han ...
Journal of the American College of Cardiology,
12/2016, Letnik:
68, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Alcohol is popular in Western culture, supported by a perception that modest intake is cardioprotective. However, excessive drinking has detrimental implications for cardiovascular disease. Atrial ...fibrillation (AF) following an alcohol binge or the "holiday heart syndrome" is well characterized. However, more modest levels of alcohol intake on a regular basis may also increase the risk of AF. The pathophysiological mechanisms responsible for the relationship between alcohol and AF may include direct toxicity and alcohol's contribution to obesity, sleep-disordered breathing, and hypertension. We aim to provide a comprehensive review of the epidemiology and pathophysiology by which alcohol may be responsible for AF and determine whether alcohol abstinence is required for patients with AF.
The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily ...hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.
Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely ...unknown.
By using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull-down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer.
Together, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy.
Background
A high rate of postoperative recurrence, especially early recurrence (ER) occurring within 1 year, seriously impedes patients with hepatocellular carcinoma (HCC) from achieving long-term ...survival. This study aimed to establish a genomic-clinicopathologic nomogram for precisely predicting ER in HCC patients after R0 resection.
Methods
Two reliable datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were selected as the training and validation cohorts, respectively. The prognostic genes related to ER were screened out by univariate Cox regression analysis and differential expression analysis. The gene-based prognostic index was constructed using LASSO and Cox regression analyses, and its independent prognostic value was assessed by Kaplan-Meier and multivariate Cox analyses. Gene set enrichment analysis (GSEA) was performed to explore the biological pathways related to the prognostic index. Finally, the nomogram integrating all the independent prognostic factors was established and comprehensively evaluated by calibration plots, the C-index, receiver operating characteristic curves, and decision curve analysis.
Results
Nine dysregulated and prognostic genes related to ER (ZNF131, TATDN2, TXN, DDX55, KPNA2, ZNF30, TIMELESS, SFRP1, and COLEC11) were identified (all
P
< 0.05). The prognostic index model based on the 9 genes was successfully constructed using the TCGA cohort and showed a certain capability to discriminate the ER group from the non-ER group (
P
< 0.05) and good independent prognostic value in terms of predicting poor early recurrence-free survival (
P
< 0.05). Eight biological pathways significantly related to ER were identified by GSEA, such as “cell cycle”, “homologous recombination” and “p53 signaling pathway.” The genomic-clinicopathologic nomogram integrating the 9-gene-based prognostic index and TNM stage displayed significantly higher predictive accuracy and clinical application value than that of TNM stage model both in the training and validation cohorts (all
P
< 0.05).
Conclusions
The novel genomic-clinicopathologic nomogram may be a convenient and powerful tool for accurately predicting ER in HCC patients after R0 resection.
MicroRNAs (miRNAs) function as endogenous translational repressors of protein-coding genes in animals by binding to target sites in the 3' UTRs of mRNAs. Because a single nucleotide change in the ...sequence of a target site can affect miRNA regulation, naturally occurring SNPs in target sites are candidates for functional variation that may be of interest for biomedical applications and evolutionary studies. However, little is known to date about variation among humans at miRNAs and their target sites. In this study, we analyzed publicly available SNP data in context with miRNAs and their target sites throughout the human genome, and we found a relatively low level of variation in functional regions of miRNAs, but an appreciable level of variation at target sites. Approximately 400 SNPs were found at experimentally verified target sites or predicted target sites that are otherwise evolutionarily conserved across mammals. Moreover, almost equal to250 SNPs potentially create novel target sites for miRNAs in humans. If some variants have functional effects, they might confer phenotypic differences among humans. Although the majority of these SNPs appear to be evolving under neutrality, interestingly, some of these SNPs are found at relatively high population frequencies even in experimentally verified targets, and a few variants are associated with atypically long-range haplotypes that may have been subject to recent positive selection.
In this paper we reported that pea protein isolate (PPI) at pH 3.0 exhibits a novel Pickering stabilization for oil-in-water emulsions. At pH 3.0, most of the proteins in PPI were present in the ...nanoparticle form, with the hydrodynamic diameter of 134–165 nm depending on the concentration (c; 0.25–3.0 g/100 mL). For the emulsions formed at a specific oil fraction of 0.2, increasing the c from 0.25 to 3.0 g/100 mL resulted in a considerable reduction in the emulsion size, while their creaming stability progressively increased, and especially at c values higher than 2 g/100 mL, no creaming occurred even after storage of 20 days. Confocal laser scanning microscopy observations showed that increasing the c resulted in a progressive increase in extent of droplet flocculation, and at higher c values, a network consisting of flocculated droplets could be formed. The emulsions formed at c values above 1.0 g/100 mL exhibited extraordinary stability against coalescence. The flocculated droplet network formation was closely associated with the increased amount of adsorbed proteins at the interface. The results suggest that pea proteins exhibit a good potential to act as a kind of Pickering stabilizers for oil-in-water emulsions at acidic pHs.
•Pea protein isolate (PPI) at pH 3.0 was present in the nanoparticle form with sizes of 100–200 nm.•The PPI emulsions at pH 3.0 exhibited similar characteristics to classic Pickering emulsions.•Increasing the concentration (c) progressively reduced the emulsion size.•These emulsions exhibited excellent stability against coalescence and even creaming.•The improvement of creaming stability was closely due to the formation of flocculated droplet network.
•Property variations and buoyancy greatly affect supercritical CO2 heat transfer.•We develop forced and mixed convection correlations for semicircular channel PCHE.•The correlation combined with GMTD ...method can be applied to the PCHE design.•We develop a dimensionless parameter to evaluate deviations of LMTD method.
The local heat transfer characteristics of supercritical CO2 flowing in horizontal semicircular straight channel of the printed circuit heat exchanger (PCHE) geometries during cooling under forced and mixed convection conditions have been numerically investigated in the present study. A new local heat transfer correlation accounting for the thermophysical property variations and the buoyancy effects has been developed based on analysis of the thermophysical property variations and the buoyancy effects on the local heat transfer performance. It predicts 93% of the data with errors of less than ±15%. The developed correlation is further adopted to a preliminary design calculation of typical PCHE channels based on a generalized mean temperature difference (GMTD) method instead of the conventional logarithmic mean temperature difference (LMTD) method. The design calculation results agree fairly well with the CFD results. Moreover, a dimensionless parameter, Cvp, is developed to evaluate the deviations induced by the constant property assumptions on which the conventional LMTD method is based. Results show that the deviation is generally between −15% and 15% when Cvp is in the range of 0.6 to 1.6.
To reduce the risk of head trauma to workers working in high-risk workplaces such as construction sites, we designed a new automated lightweight end-to-end convolutional neural network to identify ...whether all people on a construction site are wearing helmets. Firstly, we used GhostNet as the backbone feature extraction network to take advantage of its low running cost and make the model lighter overall while ensuring efficient automatic feature extraction. Secondly, we designed a multi-scale segmentation and feature fusion network (MSFFN) in the feature-processing stage to improve the algorithm’s robustness in detecting objects at different scales. In contrast, the design of the feature fusion network can enrich the diversity of helmet features and improve the accuracy of helmet detection when distance changes, viewpoint changes, and occlusion phenomena occur. Thirdly, we proposed an improved version of the attention mechanism, the lightweight residual convolutional attention network version 2 (LRCA-Netv2). The main idea of the improvement is implemented around the spatial dimension by fusing the combined features along with the horizontal and vertical directions and then weighting them separately. Such an operation allows the establishment of dependencies between the more distant features with improved accuracy compared to the original LRCA-Net. Finally, when tested on the dataset, the proposed lightweight helmet-wearing detection network has a mAP and FPS of 93.5% and 42.
This paper considers the inference problems in nonlinear quantile regressions with both stationary and nonstationary covariates. The nonparametric local constant quantile estimator is proposed to ...estimate the unknown quantile regression function, whose asymptotic properties are established under quite general conditions. Specification testing of the quantile regression function is further considered through a statistic constructed based on the integrated squared distance between the parametric and the nonparametric estimators for the regression function. The test statistic is shown to converge to a random variable related to the local time of an Ornstein–Uhlenbeck process under the parametric null. The power of the test against local alternatives is also investigated. Additional asymptotic results on the null parametric quantile estimators and a bootstrap test are developed as well. Numerical results demonstrate that the proposed nonparametric estimator and the specification test enjoy attractive finite sample performance.
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