Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ

Accurate and efficient protein embedding using multi-teacher distillation learning

Motivation: Protein embedding, which represents proteins as numerical vectors, is a crucial step in various learning-based protein annotation/classification problems, including gene ontology prediction, protein-protein interaction prediction, and protein structure prediction. However, existing protein embedding methods are often computationally expensive due to their large number of parameters, which can reach millions or even billions. The growing availability of large-scale protein datasets and the need for efficient analysis tools have created a pressing demand for efficient protein embedding methods. Results: We propose a novel protein embedding approach based on multi-teacher distillation learning, which leverages the knowledge of multiple pre-trained protein embedding models to learn a compact and informative representation of proteins. Our method achieves comparable performance to state-of-the-art methods while significantly reducing computational costs and resource requirements. Specifically, our approach reduces computational time by ~70\% and maintains almost the same accuracy as the original large models. This makes our method well-suited for large-scale protein analysis and enables the bioinformatics community to perform protein embedding tasks more efficiently.Comment: 3 pages; 1 figur

Parametrization of the calcaneus and medial cuneiform to aid potential advancements in flatfoot surgery

Introduction: Flatfoot is a condition commonly seen in children; however, there is general disagreement over its incidence, characterization and correction. Painful flatfoot accompanied with musculoskeletal and soft tissue problems requires surgery to avoid arthritis in adulthood, the most common surgical approach being two osteotomies to the calcaneus and medial cuneiform bones of the foot. Objectives: This study focuses on the parametrization of these two bones to understand their bone morphology differences in a population sample among 23 normal subjects. Population differences could help in understanding whether bone shape may be an important factor in aiding surgical planning and outcomes. Methods: A total of 45 sets of CT scans of these subjects were used to generate surface meshes of the two bones and converted to be iso-topological meshes, simplifying the application of Generalized Procrustes Analysis and Principal Component Analysis, allowing the main sources of variation between the subjects to be quantified. Results: For the calcaneus, 16 Principal Components (PCs) and, for the medial cuneiform, 12 PCs were sufficient to describe 90% of the dataset variability. The quantitative and qualitative analyses confirm that for the calcaneus PC1 describes the Achilles attachment location and PC2 largely describes the anterior part of the bone. For the medial cuneiform, PC1 describes the medial part of the bone, while PC2 mainly describes the superior part. Conclusion: Most importantly, the PCs did not seem to describe the osteotomy sites for both bones, suggesting low population variability at the bone cutting points. Further studies are needed to evaluate how shape variability impacts surgical outcomes. Future implications could include better surgical planning and may pave the way for complex robotic surgeries to become a reality.This work was supported by grant EP/R513027/1 from the EPSRC DTP 2018–201

Impact of rigid container material type and loading volume on the sterilization of thoracoscopic instruments

ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments.MethodsThoracoscopic instruments sterilized by STERRAD® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity 0.05).ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality

Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit

BACKGROUND: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. METHODS: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. RESULTS: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. CONCLUSIONS: Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients

Analysis on the constituent elements of competence of grassroots management cadres based on safeguarding national security

This article from a holistic approach to national security to the basic requirements of grassroots management cadres to maintain national security, the overall concept of national security to the basic requirements of grassroots management cadres to maintain national security, grassroots management cadres to maintain national security need to have competency, improve the grassroots cadres to maintain national security competency of several thinking to explore the elements of grassroots management cadres competency, To provide reference and reference for improving the security management ability of grassroots management cadres

Reconstructing viral haplotypes using long reads

Abstract Motivation Most RNA viruses lack strict proofreading during replication. Coupled with a high replication rate, some RNA viruses can form a virus population containing a group of genetically related but different haplotypes. Characterizing the haplotype composition in a virus population is thus important to understand viruses’ evolution. Many attempts have been made to reconstruct viral haplotypes using next-generation sequencing (NGS) reads. However, the short length of NGS reads cannot cover distant single-nucleotide variants, making it difficult to reconstruct complete or near-complete haplotypes. Given the fast developments of third-generation sequencing technologies, a new opportunity has arisen for reconstructing full-length haplotypes with long reads. Results In this work, we developed a new tool, RVHaplo to reconstruct haplotypes for known viruses from long reads. We tested it rigorously on both simulated and real viral sequencing data and compared it against other popular haplotype reconstruction tools. The results demonstrated that RVHaplo outperforms the state-of-the-art tools for viral haplotype reconstruction from long reads. Especially, RVHaplo can reconstruct the rare (1% abundance) haplotypes that other tools usually missed. Availability and implementation The source code and the documentation of RVHaplo are available at https://github.com/dhcai21/RVHaplo. Supplementary information Supplementary data are available at Bioinformatics online. </jats:sec

VirStrain: a strain identification tool for RNA viruses

AbstractViruses change constantly during replication, leading to high intra-species diversity. Although many changes are neutral or deleterious, some can confer on the virus different biological properties such as better adaptability. In addition, viral genotypes often have associated metadata, such as host residence, which can help with inferring viral transmission during pandemics. Thus, subspecies analysis can provide important insights into virus characterization. Here, we present VirStrain, a tool taking short reads as input with viral strain composition as output. We rigorously test VirStrain on multiple simulated and real virus sequencing datasets. VirStrain outperforms the state-of-the-art tools in both sensitivity and accuracy.</jats:p