Assessing post-TAVR cardiac conduction abnormalities risk using an electromechanically coupled beating heart.

Transcatheter aortic valve replacement (TAVR) has rapidly displaced surgical aortic valve replacement (SAVR). However, certain post-TAVR complications persist, with cardiac conduction abnormalities (CCA) being one of the major ones. The elevated pressure exerted by the TAVR stent onto the conduction fibers situated between the aortic annulus and the His bundle, in proximity to the atrioventricular (AV) node, may disrupt the cardiac conduction leading to the emergence of CCA. In this study, an in silico framework was developed to assess the CCA risk, incorporating the effect of a dynamic beating heart and preprocedural parameters such as implantation depth and preexisting cardiac asynchrony in the new onset of post-TAVR CCA. A self-expandable TAVR device deployment was simulated inside an electromechanically coupled beating heart model in five patient scenarios, including three implantation depths and two preexisting cardiac asynchronies: (i) a right bundle branch block (RBBB) and (ii) a left bundle branch block (LBBB). Subsequently, several biomechanical parameters were analyzed to assess the post-TAVR CCA risk. The results manifested a lower cumulative contact pressure on the conduction fibers following TAVR for aortic deployment (0.018 MPa) compared to nominal condition (0.29 MPa) and ventricular deployment (0.52 MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34 MPa) compared to the nominal condition and preexisting LBBB (0.25 MPa). Deeper implantation and preexisting RBBB cause higher stresses and contact pressure on the conduction fibers leading to an increased risk of post-TAVR CCA. Conversely, implantation above the MS landmark and preexisting LBBB reduces the risk.

Glycerophospholipid-driven lipid metabolic reprogramming as a common key mechanism in the progression of human primary hepatocellular carcinoma and cholangiocarcinoma.

Metabolic reprogramming, a key mechanism regulating the growth and recurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), still lacks effective clinical strategies for its integration into the precise screening of primary liver cancer. This study utilized ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry to conduct a comprehensive, non-targeted metabolomics analysis, revealing significant upregulation of lipid metabolites such as phosphatidylcholine and lysophosphatidylcholine in patients with HCC and CCA, particularly within the glycerophospholipid metabolic pathway. Hematoxylin and eosin and immunohistochemical staining demonstrated marked upregulation of phospholipase A2 in tumor tissues, further emphasizing the potential of lipid metabolism as a therapeutic target and its important part in the course of cancer. This work provides a new viewpoint for addressing the clinical challenges associated with HCC and CCA, laying the groundwork for the broad application of early diagnosis and personalized treatment strategies, and ultimately aiming to provide tailored and precise therapeutic options for patients.

Filter bank temporally delayed CCA for uncalibrated SSVEP-BCI.

The uncalibrated brain-computer interface (BCI) system based on steady-state visual evoked potential (SSVEP) can omit the training process and is closer to the practical application. Filter bank canonical correlation analysis (FBCCA), as a classical approach of uncalibrated SSVEP-based BCI, extracts the fundamental and harmonic ingredients through filter bank decomposition. Nevertheless, this method fails to fully leverage the temporal feature of the signal. The paper suggested utilizing reconstructed data with temporal delay in the computation of the canonical correlation coefficient, and the different combinations of the time-delayed embedding and FBCCA were discussed. We selected the data from seven participants in the Benchmark dataset for parameter optimization and evaluated the method across all participants. The experimental results showed that only embedding the time-delayed version into the first subband (FBdCCA) was better than embedding it into all subbands (FBdCCA(all)), and the accuracy of FBdCCA surpassed that of FBCCA significantly. This suggests that the approach of time-delayed embedding can further enhance the performance of FBCCA.

Missense variants of FBN2 associated with congenital arachnodactyly in three Chinese families.

Background: Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder caused by pathogenic variants of Fibrillin-2 (FBN2) gene. This study aimed to investigate the variants in three Chinese families with CCA. Methods: Next-generation sequencing analysis and Sanger sequencing of exons 24-35 of FBN2 (NM_001999.4) were performed on the three CCA pedigrees. The pathogenicity of the variants was assessed using ACMG criteria and predicted using an in-silico program. Results: A novel heterozygous substitution (NM_001999.4: c.3230G > A; NP_001990.2 p. Cys1077Tyr) was identified in all patients from pedigree A, but not in healthy family members. The variant was found to be pathogenic. Additionally, in pedigree B (NM_001999.4: c.4222G > A; NP_001990.2: p.Asp1408Asn) and C (NM_001999.4: c.3170G > A; NP_001990.2: p.Gly1057Asp), and the previously reported variants were detected. Variants affecting cysteine residues may disrupt disulfide bridging, leading to a weakened microfibril scaffold, resulting in CCA phenotypes. High phenotypic heterogeneity was observed among different families, and there was little correlation between the genotype and phenotype. Conclusion: This study describes three large families with CCA caused by missense variants in the FBN2 gene. Phenotypic variations were observed among different pedigree groups, and further research is needed to investigate the underlying reasons for these variations.

An Audiovisual Correlation Matching Method Based on Fine-Grained Emotion and Feature Fusion.

Most existing intelligent editing tools for music and video rely on the cross-modal matching technology of the affective consistency or the similarity of feature representations. However, these methods are not fully applicable to complex audiovisual matching scenarios, resulting in low matching accuracy and suboptimal audience perceptual effects due to ambiguous matching rules and associated factors. To address these limitations, this paper focuses on both the similarity and integration of affective distribution for the artistic audiovisual works of movie and television video and music. Based on the rich emotional perception elements, we propose a hybrid matching model based on feature canonical correlation analysis (CCA) and fine-grained affective similarity. The model refines KCCA fusion features by analyzing both matched and unmatched music-video pairs. Subsequently, the model employs XGBoost to predict relevance and to compute similarity by considering fine-grained affective semantic distance as well as affective factor distance. Ultimately, the matching prediction values are obtained through weight allocation. Experimental results on a self-built dataset demonstrate that the proposed affective matching model balances feature parameters and affective semantic cognitions, yielding relatively high prediction accuracy and better subjective experience of audiovisual association. This paper is crucial for exploring the affective association mechanisms of audiovisual objects from a sensory perspective and improving related intelligent tools, thereby offering a novel technical approach to retrieval and matching in music-video editing.

Surgical strategy and long-term outcomes of dissected carotid artery with false lumen thrombus in acute type A aortic dissection.

Background: Optimal management of involved common carotid artery (CCA) with false-lumen thrombus remains unclear in aortic dissection patients. We aim to investigate outcomes and compare different surgical strategies. Methods: This is a retrospective cohort study and the institutional database of acute type A aortic dissection was reviewed. The patients with CCA involvement and extended false-lumen thrombus were enrolled and grouped according to the management of CCA: extra-thoracic carotid artery replacement (CAR) and reconstruction in situ (RIS). Multivariate logistic regression analysis was used to investigate the effect of management on neurological outcomes. Kaplan-Meier method was used for survival analysis and log-rank test was used to compare the difference on survival rate. Results: From March 2011 to December 2019, 68 patients were enrolled (24 in the CAR group and 44 in the RIS group). The overall operative mortality was 7.4% (5 patients) and 21 patients had the incidence of postoperative neurological deficit was (30.9%). The rates of main postoperative complications were similar between the two groups. Twenty-five (56.8%) patients in the RIS group had residual false-lumen thrombus at discharge. In multivariate analysis, CAR was the only independent protective factor of postoperative neurological deficit [odds ratio (OR) =0.03, 95% confidence interval (CI): 0.0-0.61, P=0.02] and age was the only risk factor (OR =1.34, 95% CI: 1.11-1.62, P=0.002). The median follow-up time was 40 (interquartile range, 24-69) months and some of the patients received imaging follow-up. The overall survival rates at 5 and 10 years were 95.8%, and 95.8% in the CAR group and 84.1%, and 76.4% in the RIS group, with no significant difference (P=0.22). No cerebrovascular accident and reintervention occurred and 20 (90.9%) patients with residual false-lumen thrombus had reabsorption of thrombus during the follow-up period. Conclusions: CAR was a thorough technique and could protect patients from postoperative neurological deficit than RIS. Patients in either group could have a satisfying long-term prognosis after surviving from perioperative period. Most patients had reabsorption of residual false-lumen thrombus after anticoagulant therapy.

Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression.

Cholangiocarcinoma (CCA) is a rare but highly invasive cancer, with its incidence rising in recent years. Currently, surgery remains the most definitive therapeutic option for CCA. However, similar to other malignancies, most CCA patients are not eligible for surgical intervention at the time of diagnosis. The chemotherapeutic regimen of gemcitabine combined with cisplatin is the standard treatment for advanced CCA, but its effectiveness is often hampered by therapeutic resistance. Recent research highlights the remarkable plasticity of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). TAMs play a crucial dual role in either promoting or suppressing tumor development, depending on the factors that polarize them toward pro-tumorigenic or anti-tumorigenic phenotypes, as well as their interactions with cancer cells and other stromal components. In this review, we critically examine recent studies on TAMs in CCA, detailing the expression patterns and prognostic significance of different TAM subtypes in CCA, the mechanisms by which TAMs influence CCA progression and immune evasion, and the potential for reprogramming TAMs to enhance anticancer therapies. This review aims to provide a framework for deeper future research.

CO2-Free On-Stage Incubator for Live Cell Imaging of Cholangiocarcinoma Cell Migration on Microfluidic Device.

Long-term live cell imaging requires sophisticated and fully automated commercial-stage incubators equipped with specified inverted microscopes to regulate temperature, CO2 content, and humidity. In this study, we present a CO2-free on-stage incubator specifically designed for use across various cell culture platforms, enabling live cell imaging applications. A simple and transparent incubator was fabricated from acrylic sheets to be easily placed on the stages of most inverted microscopes. We successfully performed live-cell imaging of cholangiocarcinoma (CCA) cells and HeLa cell dynamics in both 2D and 3D microenvironments over three days. We also analyzed directed cell migration under high serum induction within a microfluidic device. Interesting phenomena such as "whole-colony migration", "novel type of collective cell migration" and "colony formation during cell and colony migration" are reported here for the first time, to the best of our knowledge. These phenomena may improve our understanding of the nature of cell migration and cancer metastasis.

Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.

Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells.

We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3ß/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.