Feasibility and effect of para-right bundle branch pacing in patients with atrial fibrillation and complete atrioventricular block

Background: Chronic right ventricular apex (RVA) pacing can induce negative clinical effects. The aim of the present study was to compare RVA pacing with para-right bundle branch (para-RBB) pacing in terms of electrocardiogram (ECG) and echocardiographic (ECHO) features. Methods: Forty-one consecutive persistent atrial fibrillation patients with an indication for permanent pacing treatment due to complete atrioventricular block were randomly assigned to receive a screw-in lead either in the RVA (n = 22) or at the para-RBB (n = 19). Para-RBB pacing leads were located according to the RBB potential recorded by electrophysiology catheter. ECG was recorded before and after implantation. All patients underwent the pacemaker pro­gramming at 1 day, 6 months, 12 months and 24 months after implantation. ECHO examina­tion was performed during follow-up at 6, 12 and 24 months after implantation to assess the heart function and synchronism. Results: There was no significant difference in pacing lead parameters between para-RBB pacing group and RVA pacing group. Compared with RVA pacing group, the para-RBB pacing group obtained a narrower QRS complex, more synchronic ventricular systole, and less nega­tive effect on heart function (p < 0.05). Conclusions: Para-RBB pacing has potential clinical benefits and may be a physiological pacing site.

Identification and association of the single nucleotide polymorphisms in calpain3 (CAPN3) gene with carcass traits in chickens

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to screen single nucleotide polymorphisms (SNP) of chicken <it>Calpain3 </it>(<it>CAPN3</it>) gene and to analyze the potential association between <it>CAPN3 </it>gene polymorphisms and carcass traits in chickens. We screened <it>CAPN3 </it>single nucleotide polymorphisms (SNP) in 307 meat-type quality chicken from 5 commercial pure lines (S01, S02, S03, S05, and D99) and 4 native breeds from Guangdong Province (Huiyang Huxu chicken and Qingyuan Ma chicken) and Sichuan Province (Caoke chicken and Shandi Black-bone chicken), China.</p> <p>Results</p> <p>Two SNPs (11818T>A and 12814T>G) were detected by single strand conformation polymorphism (SSCP) method and were verified by DNA sequencing. Association analysis showed that the 12814T>G genotypes were significantly associated with body weight (BW), carcass weight (CW), breast muscle weight (BMW), and leg muscle weight (LMW). Haplotypes constructed on the two SNPs (H1, TG; H2, TT; H3, AG; and H4, AT) were associated with BW, CW (<it>P </it>< 0.05), eviscerated percentage (EP), semi-eviscerated percentage (SEP), breast muscle percentage (BMP), and leg muscle percentage (LMP) (<it>P </it>< 0.01). Diplotype H1H2 was dominant for BW, CW, and LMP, and H2H2 was dominant for EP, SEP, and BMP.</p> <p>Conclusion</p> <p>We speculated that the <it>CAPN3 </it>gene was a major gene affecting chicken muscle growth and carcass traits or it was linked with the major gene(s). Diplotypes H1H2 and H2H2 might be advantageous for carcass traits.</p

Lattice and QR decomposition-based algorithms for recursive least squares adaptive nonlinear filters

Journal ArticleThis paper presents a lattice structure for adaptive Volterra systems. The stucture is applicable to arbitrary planes of support of the Volterra kernels. A fast least squares lattice and a fast QR-lattice adaptive nonlinear filtering algorithms based on the lattice structure are also presented. These algorithms share the fast convergence property of fast least squares transversal Volterra filters; however, unlike the transversal filters they do not suffer from numerical instability

Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels

Tissue-Specific Expression of the Chicken Calpain2 Gene

We quantified chicken calpain 2 (CAPN2) expression in two Chinese chicken breeds (mountainous black-bone chicken breed [MB] and a commercial meat type chicken breed [S01]) to discern the tissue and ontogenic expression pattern and its effect on muscle metabolism. Real-time quantitative PCR assay was developed for accurate measurement of the CAPN2 mRNA expression in various tissues from chickens of different ages (0, 2, 4, 6, 8, 10, and 12 weeks). Results showed that the breast muscle and leg muscle tissues had the highest expression of CAPN2 compared to the other tissues from the same individual (P < .05). Overall, the CAPN2 mRNA level exhibited a “rise” developmental change in all tissues. The S01 chicken had a higher expression of the CAPN2 mRNA in all tissues than the MB chicken. Our results suggest that chicken CAPN2 expression may be related to chicken breeds and tissues

Large language models in biomedical natural language processing: benchmarks, baselines, and recommendations

Biomedical literature is growing rapidly, making it challenging to curate and extract knowledge manually. Biomedical natural language processing (BioNLP) techniques that can automatically extract information from biomedical literature help alleviate this burden. Recently, large Language Models (LLMs), such as GPT-3 and GPT-4, have gained significant attention for their impressive performance. However, their effectiveness in BioNLP tasks and impact on method development and downstream users remain understudied. This pilot study (1) establishes the baseline performance of GPT-3 and GPT-4 at both zero-shot and one-shot settings in eight BioNLP datasets across four applications: named entity recognition, relation extraction, multi-label document classification, and semantic similarity and reasoning, (2) examines the errors produced by the LLMs and categorized the errors into three types: missingness, inconsistencies, and unwanted artificial content, and (3) provides suggestions for using LLMs in BioNLP applications. We make the datasets, baselines, and results publicly available to the community via https://github.com/qingyu-qc/gpt_bionlp_benchmark

Natural Transformation of Zinc Oxide Nanoparticles and Their Cytotoxicity and Mutagenicity

With rapid development of the nanoindustry, studies focusing on the transformation of nanoparticles (NPs) are required to understand their stability and toxicity after being released into the environment. Here, we characterized the physicochemical properties of ZnO NPs and found that they are naturally alkalized in the presence of air (without the addition of exogenous alkaline substances). Energy dispersive X-ray/X-ray powder diffraction/Fourier transform infrared (EDX/XRD/FTIR)/Raman spectroscopy gave evidence for the formation of hydrozincite (Zn5(CO3)2(OH)6) and zinc hydroxide (Zn(OH)2). Further, we comparatively evaluated the cellular toxicity of pristine and alkalized ZnO NPs. Cell viability testing (colony formation) showed that alkalization time-dependently decreased cytotoxicity. Alkalized NPs exhibited mutagenicity at multiple concentrations, as shown by a CD59 gene loci mutation assay. Variations in toxicity were associated with the chemical transformation of ZnO NPs, and Zn2+ played a key role in the mutagenicity of alkalized NPs. These results indicate that NPs are chemically transformed in the environment. These transformations result in obvious variations in toxicity, suggesting that the NP transformation process should be considered more thoroughly when evaluating toxicity

Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis

BACKGROUND: It is known that amyloid-β peptide (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Interaction between Aβ and the receptor for advanced glycation end products (RAGE) has been implicated in neuronal degeneration associated with this disease. Pinocembrin, a flavonoid abundant in propolis, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that pinocembrin has neuroprotective effects on ischemic and vascular dementia in animal models. It has been approved by the State Food and Drug Administration of China for clinical use in stroke patients. Against this background, we investigated the effects of pinocembrin on cognitive function and neuronal protection against Aβ-induced toxicity and explored its potential mechanism. METHODS: Mice received an intracerebroventricular fusion of Aβ(25-35). Pinocembrin was administrated orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance, cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE expression were assessed. Further, a RAGE-overexpressing cell model and an AD cell model were used for investigating the mechanisms of pinocembrin. The mechanisms underlying the efficacy of pinocembrin were conducted on target action, mitochondrial function and potential signal transduction using fluorescence-based multiparametric technologies on a high-content analysis platform. RESULTS: Our results showed that oral administration of pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex in Aβ(25-35)-treated mice. Pinocembrin did not have a significant effect on inhibiting Aβ(1-42 )production and scavenging intracellular reactive oxygen species (ROS). However, pinocembrin significantly inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and also markedly depressed the activation of p38 mitogen-activated protein kinase (MAPK)-MAPKAP kinase-2 (MK2)-heat shock protein 27 (HSP27) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)-c-Jun pathways and the downstream nuclear factor κB (NFκB) inflammatory response subsequent to Aβ-RAGE interaction. In addition, pinocembrin significantly alleviated mitochondrial dysfunction through improving mitochondrial membrane potential and inhibiting mitochondrial oxidative stress, and regulated mitochondrion-mediated apoptosis by restoration of B cell lymphoma 2 (Bcl-2) and cytochrome c and inactivation of caspase 3 and caspase 9. CONCLUSIONS: Pinocembrin was shown to infer cognitive improvement and neuronal protection in AD models. The mechanisms of action of the compound were illustrated on RAGE-dependent transduction inhibition and mitochondrion protection. It appears to be a promising candidate for the prevention and therapy of AD