Identification and exploration of aging-related subtypes and distinctive role of SERPINE1 in heart failure based on single-cell and bulk RNA sequencing data.

Aging is a major risk factor for heart failure (HF) and is the leading cause of death worldwide. Currently, the nature of the relationship between aging and HF is not entirely clear. Herein, this study aimed to explore new diagnostic biomarkers, molecular typing and therapeutic strategies for HF by investigating the biological significance of aging-related genes in HF. A total of 157 differentially expressed genes (DEGs) were screened totally between HF and normal samples, and functional enrichment analysis of DEGs revealed the strong association of HF progression with aging, immune processes and metabolism. Six HF-specific aging-related genes were further identified, and a diagnostic model was developed and validated for good diagnostic efficacy. In addition, we collected blood samples from 10 normal controls and 10 HF patients for RT-qPCR analysis to verify the bioinformation. We also identified two aging-associated subtypes with distinctly different immune infiltration and metabolic microenvironment. Further single-cell sequencing analysis conducted in the study identified SERPINE1 as a key gene in HF. The distinctive role of SERPINE1 fibroblasts was revealed, including three main findings: (I) fibroblasts had a higher proportion and expression of SERPINE1 levels in HF; (II) the ligand-receptor pair MDK-LRP1 made the most contributions in high interactions with other cell types in SERPINE1 fibroblasts; and (III) SERPINE1 fibroblasts were associated with the interaction of extracellular matrix and receptor and may be regulated by the transcription factor EGR1. In conclusion, this study highlights the importance of aging-related genes in diagnosing HF and regulating immune infiltration. We also identified different HF subtypes and a potentially crucial gene, which may provide a better understanding of the molecular-level mechanisms of aging-related HF and aid in developing effective therapeutic strategies.

Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure.

OBJECTIVE: Inflammation and immune cells are closely intertwined mechanisms that contribute to the progression of heart failure (HF). Nonetheless, there is a paucity of information regarding the distinct features of dysregulated immune cells and efficient diagnostic biomarkers linked with HF. This study aims to explore diagnostic biomarkers related to immune cells in HF to gain new insights into the underlying molecular mechanisms of HF and to provide novel perspectives for the detection and treatment of HF. METHOD: The CIBERSORT method was employed to quantify 22 types of immune cells in HF and normal subjects from publicly available GEO databases (GSE3586, GSE42955, GSE57338, and GSE79962). Machine learning methods were utilized to screen for important cell types. Single-cell RNA sequencing (GSE145154) was further utilized to identify important cell types and hub genes. WGCNA was employed to screen for immune cell-related genes and ultimately diagnostic models were constructed and evaluated. To validate these predictive results, blood samples were collected from 40 normal controls and 40 HF patients for RT-qPCR analysis. Lastly, key cell clusters were divided into high and low biomarker expression groups to identify transcription factors that may affect biomarkers. RESULTS: The study found a noticeable difference in immune environment between HF and normal subjects. Macrophages were identified as key immune cells by machine learning. Single-cell analysis further showed that macrophages differed dramatically between HF and normal subjects. This study revealed the existence of five subsets of macrophages that have different differentiation states. Based on module genes most relevant to macrophages, macrophage differentiation-related genes (MDRGs), and DEGs in HF and normal subjects from GEO datasets, four genes (CD163, RNASE2, LYVE1, and VSIG4) were identified as valid diagnostic markers for HF. Ultimately, a diagnostic model containing two hub genes was constructed and then validated with a validation dataset and clinical samples. In addition, key transcription factors driving or maintaining the biomarkers expression programs were identified. CONCLUSION: The analytical results and diagnostic model of this study can assist clinicians in identifying high-risk individuals, thereby aiding in guiding treatment decisions for patients with HF.

From deterministic to stochastic: an interpretable stochastic model-free reinforcement learning framework for portfolio optimization.

As a fundamental problem in algorithmic trading, portfolio optimization aims to maximize the cumulative return by continuously investing in various financial derivatives within a given time period. Recent years have witnessed the transformation from traditional machine learning trading algorithms to reinforcement learning algorithms due to their superior nature of sequential decision making. However, the exponential growth of the imperfect and noisy financial data that is supposedly leveraged by the deterministic strategy in reinforcement learning, makes it increasingly challenging for one to continuously obtain a profitable portfolio. Thus, in this work, we first reconstruct several deterministic and stochastic reinforcement algorithms as benchmarks. On this basis, we introduce a risk-aware reward function to balance the risk and return. Importantly, we propose a novel interpretable stochastic reinforcement learning framework which tailors a stochastic policy parameterized by Gaussian Mixtures and a distributional critic realized by quantiles for the problem of portfolio optimization. In our experiment, the proposed algorithm demonstrates its superior performance on U.S. market stocks with a 63.1% annual rate of return while at the same time reducing the market value max drawdown by 10% when back-testing during the stock market crash around March 2020.

Effects of chronic intermittent hypoxia on left cardiac function in young and aged mice.

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease that is characterized by chronic intermittent hypoxia (CIH), and its impact is related to age. This study aims to assess the age-related impact of CIH on cardiac function and to further explore the mechanism. After 8 wk of severe CIH exposure, the hearts of young mice showed slight physiological hypertrophy, decreased diastolic function, and collagen I accumulation but no obvious change in contractile function. However, the contractile function of the hearts of aged mice was severely decreased. CIH exposure promoted the fragmentation of mitochondria in the hearts of aged mice and decreased the mitochondrial membrane potential of cardiomyocytes, but these effects were not observed in young mice exposed to the same conditions. CIH induced significant decreases in basal respiration, maximum respiration, and ATP production in cardiac mitochondria of aged mice compared with those of young mice. The assessment of mitochondrial-related proteins showed that young mouse hearts had upregulated adaptive nuclear respiratory factors (Nrf)1/2 sirtuin (SIRT)1/3 and transcription factor A (TFAM) expression that stabilized mitochondrial function in response to CIH exposure. Aged mouse hearts exhibited maladaptation to CIH exposure, and downregulation of SIRT1 and TFAM expression resulted in mitochondrial dysfunction.

DualStreamFoveaNet: A Dual Stream Fusion Architecture with Anatomical Awareness for Robust Fovea Localization.

Accurate fovea localization is essential for analyzing retinal diseases to prevent irreversible vision loss. While current deep learning-based methods outperform traditional ones, they still face challenges such as the lack of local anatomical landmarks around the fovea, the inability to robustly handle diseased retinal images, and the variations in image conditions. In this paper, we propose a novel transformer-based architecture called DualStreamFoveaNet (DSFN) for multi-cue fusion. This architecture explicitly incorporates long-range connections and global features using retina and vessel distributions for robust fovea localization. We introduce a spatial attention mechanism in the dual-stream encoder to extract and fuse self-learned anatomical information, focusing more on features distributed along blood vessels and significantly reducing computational costs by decreasing token numbers. Our extensive experiments show that the proposed architecture achieves state-of-the-art performance on two public datasets and one large-scale private dataset. Furthermore, we demonstrate that the DSFN is more robust on both normal and diseased retina images and has better generalization capacity in cross-dataset experiments.

GAMMA challenge: Glaucoma grAding from Multi-Modality imAges.

Glaucoma is a chronic neuro-degenerative condition that is one of the world's leading causes of irreversible but preventable blindness. The blindness is generally caused by the lack of timely detection and treatment. Early screening is thus essential for early treatment to preserve vision and maintain life quality. Colour fundus photography and Optical Coherence Tomography (OCT) are the two most cost-effective tools for glaucoma screening. Both imaging modalities have prominent biomarkers to indicate glaucoma suspects, such as the vertical cup-to-disc ratio (vCDR) on fundus images and retinal nerve fiber layer (RNFL) thickness on OCT volume. In clinical practice, it is often recommended to take both of the screenings for a more accurate and reliable diagnosis. However, although numerous algorithms are proposed based on fundus images or OCT volumes for the automated glaucoma detection, there are few methods that leverage both of the modalities to achieve the target. To fulfil the research gap, we set up the Glaucoma grAding from Multi-Modality imAges (GAMMA) Challenge to encourage the development of fundus & OCT-based glaucoma grading. The primary task of the challenge is to grade glaucoma from both the 2D fundus images and 3D OCT scanning volumes. As part of GAMMA, we have publicly released a glaucoma annotated dataset with both 2D fundus colour photography and 3D OCT volumes, which is the first multi-modality dataset for machine learning based glaucoma grading. In addition, an evaluation framework is also established to evaluate the performance of the submitted methods. During the challenge, 1272 results were submitted, and finally, ten best performing teams were selected for the final stage. We analyse their results and summarize their methods in the paper. Since all the teams submitted their source code in the challenge, we conducted a detailed ablation study to verify the effectiveness of the particular modules proposed. Finally, we identify the proposed techniques and strategies that could be of practical value for the clinical diagnosis of glaucoma. As the first in-depth study of fundus & OCT multi-modality glaucoma grading, we believe the GAMMA Challenge will serve as an essential guideline and benchmark for future research.

RC-Net: Regression Correction for End-To-End Chromosome Instance Segmentation.

Precise segmentation of chromosome in the real image achieved by a microscope is significant for karyotype analysis. The segmentation of image is usually achieved by a pixel-level classification task, which considers different instances as different classes. Many instance segmentation methods predict the Intersection over Union (IoU) through the head branch to correct the classification confidence. Their effectiveness is based on the correlation between branch tasks. However, none of these methods consider the correlation between input and output in branch tasks. Herein, we propose a chromosome instance segmentation network based on regression correction. First, we adopt two head branches to predict two confidences that are more related to localization accuracy and segmentation accuracy to correct the classification confidence, which reduce the omission of predicted boxes in NMS. Furthermore, a NMS algorithm is further designed to screen the target segmentation mask with the IoU of the overlapping instance, which reduces the omission of predicted masks in NMS. Moreover, given the fact that the original IoU loss function is not sensitive to the wrong segmentation, K-IoU loss function is defined to strengthen the penalty of the wrong segmentation, which rationalizes the loss of mis-segmentation and effectively prevents wrong segmentation. Finally, an ablation experiment is designed to evaluate the effectiveness of the chromosome instance segmentation network based on regression correction, which shows that our proposed method can effectively enhance the performance in automatic chromosome segmentation tasks and provide a guarantee for end-to-end karyotype analysis.

FECTS: A Facial Emotion Cognition and Training System for Chinese Children with Autism Spectrum Disorder.

Traditional training methods such as card teaching, assistive technologies (e.g., augmented reality/virtual reality games and smartphone apps), DVDs, human-computer interactions, and human-robot interactions are widely applied in autistic rehabilitation training in recent years. In this article, we propose a novel framework for human-computer/robot interaction and introduce a preliminary intervention study for improving the emotion recognition of Chinese children with an autism spectrum disorder. The core of the framework is the Facial Emotion Cognition and Training System (FECTS, including six tasks to train children with ASD to match, infer, and imitate the facial expressions of happiness, sadness, fear, and anger) based on Simon Baron-Cohen's E-S (empathizing-systemizing) theory. Our system may be implemented on PCs, smartphones, mobile devices such as PADs, and robots. The training record (e.g., a tracked record of emotion imitation) of the Chinese autistic children interacting with the device implemented using our FECTS will be uploaded and stored in the database of a cloud-based evaluation system. Therapists and parents can access the analysis of the emotion learning progress of these autistic children using the cloud-based evaluation system. Deep-learning algorithms of facial expressions recognition and attention analysis will be deployed in the back end (e.g., devices such as a PC, a robotic system, or a cloud system) implementing our FECTS, which can perform real-time tracking of the imitation quality and attention of the autistic children during the expression imitation phase. In this preliminary clinical study, a total of 10 Chinese autistic children aged 3-8 are recruited, and each of them received a single 20-minute training session every day for four consecutive days. Our preliminary results validated the feasibility of the developed FECTS and the effectiveness of our algorithms based on Chinese children with an autism spectrum disorder. To verify that our FECTS can be further adapted to children from other countries, children with different cultural/sociological/linguistic contexts should be recruited in future studies.

Intention Understanding in Human-Robot Interaction Based on Visual-NLP Semantics.

With the rapid development of robotic and AI technology in recent years, human-robot interaction has made great advancement, making practical social impact. Verbal commands are one of the most direct and frequently used means for human-robot interaction. Currently, such technology can enable robots to execute pre-defined tasks based on simple and direct and explicit language instructions, e.g., certain keywords must be used and detected. However, that is not the natural way for human to communicate. In this paper, we propose a novel task-based framework to enable the robot to comprehend human intentions using visual semantics information, such that the robot is able to satisfy human intentions based on natural language instructions (total three types, namely clear, vague, and feeling, are defined and tested). The proposed framework includes a language semantics module to extract the keywords despite the explicitly of the command instruction, a visual object recognition module to identify the objects in front of the robot, and a similarity computation algorithm to infer the intention based on the given task. The task is then translated into the commands for the robot accordingly. Experiments are performed and validated on a humanoid robot with a defined task: to pick the desired item out of multiple objects on the table, and hand over to one desired user out of multiple human participants. The results show that our algorithm can interact with different types of instructions, even with unseen sentence structures.