Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in dilated cardiomyopathy with heart failure

The etiologies and pathogenesis of dilated cardiomyopathy (DCM) with heart failure (HF) remain to be defined. Thus, exploring specific diagnosis biomarkers and mechanisms is urgently needed to improve this situation. In this study, three gene expression profiling datasets (GSE29819, GSE21610, GSE17800) and one single-cell RNA sequencing dataset (GSE95140) were obtained from the Gene Expression Omnibus (GEO) database. GSE29819 and GSE21610 were combined into the training group, while GSE17800 was the test group. We used the weighted gene co-expression network analysis (WGCNA) and identified fifteen driver genes highly associated with DCM with HF in the module. We performed the least absolute shrinkage and selection operator (LASSO) on the driver genes and then constructed five machine learning classifiers (random forest, gradient boosting machine, neural network, eXtreme gradient boosting, and support vector machine). Random forest was the best-performing classifier established on five Lasso-selected genes, which was utilized to select out NPPA, OMD, and PRELP for diagnosing DCM with HF. Moreover, we observed the up-regulation mRNA levels and robust diagnostic accuracies of NPPA, OMD, and PRELP in the training group and test group. Single-cell RNA-seq analysis further demonstrated their stable up-regulation expression patterns in various cardiomyocytes of DCM patients. Besides, through gene set enrichment analysis (GSEA), we found TGF-β signaling pathway, correlated with NPPA, OMD, and PRELP, was the underlying mechanism of DCM with HF. Overall, our study revealed NPPA, OMD, and PRELP serving as diagnostic biomarkers for DCM with HF, deepening the understanding of its pathogenesis

Exploring Vision Transformers as Diffusion Learners

Score-based diffusion models have captured widespread attention and funded fast progress of recent vision generative tasks. In this paper, we focus on diffusion model backbone which has been much neglected before. We systematically explore vision Transformers as diffusion learners for various generative tasks. With our improvements the performance of vanilla ViT-based backbone (IU-ViT) is boosted to be on par with traditional U-Net-based methods. We further provide a hypothesis on the implication of disentangling the generative backbone as an encoder-decoder structure and show proof-of-concept experiments verifying the effectiveness of a stronger encoder for generative tasks with ASymmetriC ENcoder Decoder (ASCEND). Our improvements achieve competitive results on CIFAR-10, CelebA, LSUN, CUB Bird and large-resolution text-to-image tasks. To the best of our knowledge, we are the first to successfully train a single diffusion model on text-to-image task beyond 64x64 resolution. We hope this will motivate people to rethink the modeling choices and the training pipelines for diffusion-based generative models

An Advanced Adaptive Control of Lower Limb Rehabilitation Robot

Rehabilitation robots play an important role in the rehabilitation field, and effective human-robot interaction contributes to promoting the development of the rehabilitation robots. Though many studies about the human-robot interaction have been carried out, there are still several limitations in the flexibility and stability of the control system. Therefore, we proposed an advanced adaptive control method for lower limb rehabilitation robot. The method was devised with a dual closed loop control strategy based on the surface electromyography (sEMG) and plantar pressure to improve the robustness of the adaptive control for the rehabilitation robots. First, in the outer loop control, an advanced variable impedance controller based on the sEMG and plantar pressure was designed to correct robot's reference trajectory. Then, in the inner loop control, a sliding mode iterative learning controller (SMILC) based on the variable boundary saturation function was designed to achieve the tracking of the reference trajectory. The experiment results showed that, in the designed dual closed loop control strategy, a variable impedance controller can effectively reduce trajectory tracking errors and adaptively modify the reference trajectory synchronizing with the motion intention of patients; the designed sliding mode iterative learning controller can effectively reduce chattering in sliding mode control and excellently achieve the tracking of rehabilitation robot's reference trajectory. This study can improve the performance of the human-robot interaction of the rehabilitation robot system, and expand the application to the rehabilitation field

REX: Rapid Exploration and eXploitation for AI Agents

In this paper, we propose an enhanced approach for Rapid Exploration and eXploitation for AI Agents called REX. Existing AutoGPT-style techniques have inherent limitations, such as a heavy reliance on precise descriptions for decision-making, and the lack of a systematic approach to leverage try-and-fail procedures akin to traditional Reinforcement Learning (RL). REX introduces an additional layer of rewards and integrates concepts similar to Upper Confidence Bound (UCB) scores, leading to more robust and efficient AI agent performance. This approach has the advantage of enabling the utilization of offline behaviors from logs and allowing seamless integration with existing foundation models while it does not require any model fine-tuning. Through comparative analysis with existing methods such as Chain-of-Thoughts(CoT) and Reasoning viA Planning(RAP), REX-based methods demonstrate comparable performance and, in certain cases, even surpass the results achieved by these existing techniques. Notably, REX-based methods exhibit remarkable reductions in execution time, enhancing their practical applicability across a diverse set of scenarios

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Numerical simulation of water environment capacity from wet, normal, and dry years: taking the Luo River as an example

Water pollution is a globally significant issue. Water environment simulation is an important tool to study water pollution. In order to investigate the impact of hydrological periods, water quality indicators and cross-sections on the water environment capacity, we took the Luo River in Luoyang City as an example, and used MIKE21-coupled hydrodynamic and water quality model and the segmentation method to calculate the water environment capacity of COD, TP, and NH3-N in wet, normal, and dry periods under L1 (Gao Yazhai-Lilou), L2 (Li Lou-Baimasi), and L3 (Baimasi-G207 Highway Bridge) section. The results of the study showed that from the hydrological period, the water environmental capacity was the largest in the wet period due to the dilution effect caused by higher precipitation; from the water quality indexes, the COD concentration was the largest due to industrial pollution, but the higher degradation coefficients result in the largest water environment capacity for COD; from the cross-section, L1 has the longest channel, thus the highest capacity of the water environment was L1. This result can broaden ideas for the application of the MIKE21 model, provide a basis for the calculation of the dynamic water environment capacity and water pollution control in the river. HIGHLIGHTS Innovative hydrodynamic water quality model evaluates Luo River pollution across diverse flow scenarios.; Dry periods exhibit poorest water quality, while wet periods showcase the best.; Identified sections exceeding capacity emphasize pollution management during distinct hydrological conditions.

Identifying <i>OGN</i> as a Biomarker Covering Multiple Pathogenic Pathways for Diagnosing Heart Failure: From Machine Learning to Mechanism Interpretation

Background: The pathophysiologic heterogeneity of heart failure (HF) necessitates a more detailed identification of diagnostic biomarkers that can reflect its diverse pathogenic pathways. Methods: We conducted weighted gene and multiscale embedded gene co-expression network analysis on differentially expressed genes obtained from HF and non-HF specimens. We employed a machine learning integration framework and protein–protein interaction network to identify diagnostic biomarkers. Additionally, we integrated gene set variation analysis, gene set enrichment analysis (GSEA), and transcription factor (TF)-target analysis to unravel the biomarker-dominant pathways. Leveraging single-sample GSEA and molecular docking, we predicted immune cells and therapeutic drugs related to biomarkers. Quantitative polymerase chain reaction validated the expressions of biomarkers in the plasma of HF patients. A two-sample Mendelian randomization analysis was implemented to investigate the causal impact of biomarkers on HF. Results: We first identified COL14A1, OGN, MFAP4, and SFRP4 as candidate biomarkers with robust diagnostic performance. We revealed that regulating biomarkers in HF pathogenesis involves TFs (BNC2, MEOX2) and pathways (cell adhesion molecules, chemokine signaling pathway, cytokine–cytokine receptor interaction, oxidative phosphorylation). Moreover, we observed the elevated infiltration of effector memory CD4+ T cells in HF, which was highly related to biomarkers and could impact immune pathways. Captopril, aldosterone antagonist, cyclopenthiazide, estradiol, tolazoline, and genistein were predicted as therapeutic drugs alleviating HF via interactions with biomarkers. In vitro study confirmed the up-regulation of OGN as a plasma biomarker of HF. Mendelian randomization analysis suggested that genetic predisposition toward higher plasma OGN promoted the risk of HF. Conclusions: We propose OGN as a diagnostic biomarker for HF, which may advance our understanding of the diagnosis and pathogenesis of HF

Image3_Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in dilated cardiomyopathy with heart failure.JPEG

The etiologies and pathogenesis of dilated cardiomyopathy (DCM) with heart failure (HF) remain to be defined. Thus, exploring specific diagnosis biomarkers and mechanisms is urgently needed to improve this situation. In this study, three gene expression profiling datasets (GSE29819, GSE21610, GSE17800) and one single-cell RNA sequencing dataset (GSE95140) were obtained from the Gene Expression Omnibus (GEO) database. GSE29819 and GSE21610 were combined into the training group, while GSE17800 was the test group. We used the weighted gene co-expression network analysis (WGCNA) and identified fifteen driver genes highly associated with DCM with HF in the module. We performed the least absolute shrinkage and selection operator (LASSO) on the driver genes and then constructed five machine learning classifiers (random forest, gradient boosting machine, neural network, eXtreme gradient boosting, and support vector machine). Random forest was the best-performing classifier established on five Lasso-selected genes, which was utilized to select out NPPA, OMD, and PRELP for diagnosing DCM with HF. Moreover, we observed the up-regulation mRNA levels and robust diagnostic accuracies of NPPA, OMD, and PRELP in the training group and test group. Single-cell RNA-seq analysis further demonstrated their stable up-regulation expression patterns in various cardiomyocytes of DCM patients. Besides, through gene set enrichment analysis (GSEA), we found TGF-β signaling pathway, correlated with NPPA, OMD, and PRELP, was the underlying mechanism of DCM with HF. Overall, our study revealed NPPA, OMD, and PRELP serving as diagnostic biomarkers for DCM with HF, deepening the understanding of its pathogenesis.</p

Image7_Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in dilated cardiomyopathy with heart failure.JPEG

The etiologies and pathogenesis of dilated cardiomyopathy (DCM) with heart failure (HF) remain to be defined. Thus, exploring specific diagnosis biomarkers and mechanisms is urgently needed to improve this situation. In this study, three gene expression profiling datasets (GSE29819, GSE21610, GSE17800) and one single-cell RNA sequencing dataset (GSE95140) were obtained from the Gene Expression Omnibus (GEO) database. GSE29819 and GSE21610 were combined into the training group, while GSE17800 was the test group. We used the weighted gene co-expression network analysis (WGCNA) and identified fifteen driver genes highly associated with DCM with HF in the module. We performed the least absolute shrinkage and selection operator (LASSO) on the driver genes and then constructed five machine learning classifiers (random forest, gradient boosting machine, neural network, eXtreme gradient boosting, and support vector machine). Random forest was the best-performing classifier established on five Lasso-selected genes, which was utilized to select out NPPA, OMD, and PRELP for diagnosing DCM with HF. Moreover, we observed the up-regulation mRNA levels and robust diagnostic accuracies of NPPA, OMD, and PRELP in the training group and test group. Single-cell RNA-seq analysis further demonstrated their stable up-regulation expression patterns in various cardiomyocytes of DCM patients. Besides, through gene set enrichment analysis (GSEA), we found TGF-β signaling pathway, correlated with NPPA, OMD, and PRELP, was the underlying mechanism of DCM with HF. Overall, our study revealed NPPA, OMD, and PRELP serving as diagnostic biomarkers for DCM with HF, deepening the understanding of its pathogenesis.</p

Image6_Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in dilated cardiomyopathy with heart failure.JPEG

The etiologies and pathogenesis of dilated cardiomyopathy (DCM) with heart failure (HF) remain to be defined. Thus, exploring specific diagnosis biomarkers and mechanisms is urgently needed to improve this situation. In this study, three gene expression profiling datasets (GSE29819, GSE21610, GSE17800) and one single-cell RNA sequencing dataset (GSE95140) were obtained from the Gene Expression Omnibus (GEO) database. GSE29819 and GSE21610 were combined into the training group, while GSE17800 was the test group. We used the weighted gene co-expression network analysis (WGCNA) and identified fifteen driver genes highly associated with DCM with HF in the module. We performed the least absolute shrinkage and selection operator (LASSO) on the driver genes and then constructed five machine learning classifiers (random forest, gradient boosting machine, neural network, eXtreme gradient boosting, and support vector machine). Random forest was the best-performing classifier established on five Lasso-selected genes, which was utilized to select out NPPA, OMD, and PRELP for diagnosing DCM with HF. Moreover, we observed the up-regulation mRNA levels and robust diagnostic accuracies of NPPA, OMD, and PRELP in the training group and test group. Single-cell RNA-seq analysis further demonstrated their stable up-regulation expression patterns in various cardiomyocytes of DCM patients. Besides, through gene set enrichment analysis (GSEA), we found TGF-β signaling pathway, correlated with NPPA, OMD, and PRELP, was the underlying mechanism of DCM with HF. Overall, our study revealed NPPA, OMD, and PRELP serving as diagnostic biomarkers for DCM with HF, deepening the understanding of its pathogenesis.</p