Prototypical Fine-tuning: Towards Robust Performance Under Varying Data Sizes

In this paper, we move towards combining large parametric models with non-parametric prototypical networks. We propose prototypical fine-tuning, a novel prototypical framework for fine-tuning pretrained language models (LM), which automatically learns a bias to improve predictive performance for varying data sizes, especially low-resource settings. Our prototypical fine-tuning approach can automatically adjust the model capacity according to the number of data points and the model's inherent attributes. Moreover, we propose four principles for effective prototype fine-tuning towards the optimal solution. Experimental results across various datasets show that our work achieves significant performance improvements under various low-resource settings, as well as comparable and usually better performances in high-resource scenarios.Comment: Published as a conference paper at AAAI 202

Use of gene therapy for optic nerve protection: Current concepts

Gene therapy has become an essential treatment for optic nerve injury (ONI) in recent years, and great strides have been made using animal models. ONI, which is characterized by the loss of retinal ganglion cells (RGCs) and axons, can induce abnormalities in the pupil light reflex, visual field defects, and even vision loss. The eye is a natural organ to target with gene therapy because of its high accessibility and certain immune privilege. As such, numerous gene therapy trials are underway for treating eye diseases such as glaucoma. The aim of this review was to cover research progress made in gene therapy for ONI. Specifically, we focus on the potential of gene therapy to prevent the progression of neurodegenerative diseases and protect both RGCs and axons. We cover the basic information of gene therapy, including the classification of gene therapy, especially focusing on genome editing therapy, and then we introduce common editing tools and vector tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -Cas9 and adeno-associated virus (AAV). We also summarize the progress made on understanding the roles of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), phosphatase-tensin homolog (PTEN), suppressor of cytokine signal transduction 3 (SOCS3), histone acetyltransferases (HATs), and other important molecules in optic nerve protection. However, gene therapy still has many challenges, such as misalignment and mutations, immunogenicity of AAV, time it takes and economic cost involved, which means that these issues need to be addressed before clinical trials can be considered

CompeteAI: Understanding the Competition Behaviors in Large Language Model-based Agents

Large language models (LLMs) have been widely used as agents to complete different tasks, such as personal assistance or event planning. While most work has focused on cooperation and collaboration between agents, little work explores competition, another important mechanism that fosters the development of society and economy. In this paper, we seek to examine the competition behaviors in LLM-based agents. We first propose a general framework to study the competition between agents. Then, we implement a practical competitive environment using GPT-4 to simulate a virtual town with two types of agents, including restaurant agents and customer agents. Specifically, restaurant agents compete with each other to attract more customers, where the competition fosters them to transform, such as cultivating new operating strategies. The results of our experiments reveal several interesting findings ranging from social learning to Matthew Effect, which aligns well with existing sociological and economic theories. We believe that competition between agents deserves further investigation to help us understand society better. The code will be released soon.Comment: Technical report; 21 page

Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine Model of Oxygen-Induced Retinopathy

Galectin-1 (Gal-1) has been proved to be an important factor in the process of tumor angiogenesis recently. As a small molecule, OTX008 serves as a selective inhibitor of Gal-1. In this study, the role of Gal-1 and the antiangiogenic effect of OTX008 on retinal neovascularization (RNV) were investigated using a mouse model of oxygen-induced retinopathy. The outcome indicated that Gal-1 was overexpressed and closely related to retinal neovessels in OIR. After intravitreal injection of OTX008 at P12, the RNV was significantly reduced at P17, measuring by cross-sectional H&E staining and whole-mount fluorescence. Our results demonstrate the inhibitory function of OTX008 on RNV, which provides a promising strategy of treating retinal angiogenic diseases such as retinopathy of prematurity and proliferative diabetic retinopathy

Research progress of retinal neurovascular unit injury in glaucoma

Glaucoma is one of the leading causes of vision loss worldwide. More and more studies have suggested that glaucoma is a complicated retinal neurovascular disease. The homeostasis imbalance of retinal neurovascular unit(RNVU)composed of neurons, glial cells and microvascular cells not only induces changes in microvascular structure and glial cells, but also affects the nerve tissue of the retina, resulting in vision loss, which there is no effective treatment to reverse, currently. Exploring the cellular composition and molecular structure of RNVU and investigating the destruction mechanism of normal cellular environment and intercellular connections in glaucoma are of great significance in exploring the pathogenesis and the treatment of glaucoma. The research progress on structural changes and dysfunction of RNVU in glaucoma are reviewed, hoping to provide new ideas for the treatment of glaucoma

Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa

Abstract Background This study aimed to identify the gene variants and molecular etiologies in 76 unrelated Chinese families with retinitis pigmentosa (RP). Methods In total, 76 families with syndromic or nonsyndromic RP, diagnosed on the basis of clinical manifestations, were recruited for this study. Genomic DNA samples from probands were analyzed by targeted panels or whole exome sequencing. Bioinformatics analysis, Sanger sequencing, and available family member segregation were used to validate sequencing data and confirm the identities of disease‐causing genes. Results The participants enrolled in the study included 62 families that exhibited nonsyndromic RP, 13 that exhibited Usher syndrome, and one that exhibited Bardet–Biedl syndrome. We found that 43 families (56.6%) had disease‐causing variants in 15 genes, including RHO, PRPF31, USH2A, CLRN1, BBS2, CYP4V2, EYS, RPE65, CNGA1, CNGB1, PDE6B, MERTK, RP1, RP2, and RPGR; moreover, 12 families (15.8%) had only one heterozygous variant in seven autosomal recessive RP genes, including USH2A, EYS, CLRN1, CERKL, RP1, CRB1, and SLC7A14. We did not detect any variants in the remaining 21 families (27.6%). We also identified 67 potential pathogenic gene variants, of which 24 were novel. Conclusion The gene variants identified in this study expand the variant frequency and spectrum of RP genes; moreover, the identification of these variants supplies foundational clues for future RP diagnosis and therapy

Identification of Diagnostic Biomarkers and Their Correlation with Immune Infiltration in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the central retina, with no suitable biomarkers for early diagnosis and treatment. This study aimed to find potential diagnostic biomarker candidates for AMD and investigate their immune-related roles in this pathology. Weight gene correlation analysis was first performed based on data from the Gene Expression Omnibus database and 20 hub genes were identified. The functional enrichment analyses showed that the innate immune response, inflammatory response, and complement activation were key pathways associated with AMD. Complement C1s (C1S), adrenomedullin (ADM), and immediate early response 5 like (IER5L) were identified as the crucial genes with favorable diagnostic values for AMD by using LASSO analysis and multiple logistic regression. Furthermore, a 3-gene model was constructed and proved to be of good diagnostic and predictive performance for AMD (AUC = 0.785, 0.840, and 0.810 in training, test, and validation set, respectively). Finally, CIBERSORT was used to evaluate the infiltration of immune cells in AMD tissues. The results showed that the NK cells, CD4 memory T cell activation, and macrophage polarization may be involved in the AMD process. C1S, ADM, and IER5L were correlated with the infiltration of the above immune cells. In conclusion, our study suggests that C1S, ADM, and IER5L are promising diagnostic biomarker candidates for AMD and may regulate the infiltration of immune cells in the occurrence and progression of AMD