bioRxiv Science⌕ Search

Biology subjects

Muduli, D.

Publications and source records attributed to Muduli, D..

2 recordsLinked to original sources

Explainable AI-Driven Diagnosis Model for Early Glaucoma Detection Using Grey-Wolf Optimized Extreme Learning Machine Approach

Glaucoma is a prominent threat to vision and ranks as the third leading cause of blindness in India. Early detection is crucial to limit its progression. Retinal image analysis, particularly computer-aided diagnosis (CAD), has gained significant attention due to its potential in effectively screening for and managing glaucoma. Nowadays, Artificial intelligence (AI) has achieved significant progress has been made in medical image analysis across various applications. However, the main challenge hindering the widespread adoption of deep neural models in clinical settings is their lack of interpretability. In response to this need, we propose an enhanced CAD model with four key components: image pre-processing, feature extraction, feature dimensionality reduction, and classification. Utilizing the G1020 and ORIGA datasets, we employ a fast discrete curvelet transform with wrapping (FDCT-WRP) for curve-like feature extraction. A combined feature reduction technique, principal component analysis (PCA) and linear discriminant analysis (LDA), is applied to generate relevant features and reduce the feature dimensionality. Incorporating an improved grey wolf Optimization (IMGWO) with an Extreme Learning Machine (ELM) for classification. Then, IMGWO optimizes parameters, enhancing the efficiency of single-hidden-layer feedforward neural networks. Through a 10 x 5-fold stratified cross-validation (SCV) test on standard datasets, our CAD model demonstrates superior performance. The proposed CAD model achieved better classification result i.e., 93.87% and 95.38% on the G1020 and ORIGA datasets respectively. Additionally, we have proposed a framework named as GlaucoXAI (Glaucoma explainable artificial intelligence), which utilizes seven advanced explanation methods to improve the interpretability of deep learning models for medical experts trust. GlaucoXAI has been employed on glaucoma detection using fundus images. GlaucoXAIs adaptable design could aid ophthalmologists and medical professionals in detection of glaucoma. The experimental results demonstrate that the proposed model surpasses other existing models in classification accuracy, while significantly reducing the number of features.

bioengineering↗

NEK9 ablation rewires docetaxel resistance through induction of ERK-mediated cancer cell pyroptosis

Docetaxel alone or in combination with other drugs is the most common chemotherapy regimen for several neoplasms including advanced OSCC. Unfortunately, chemoresistance leads to relapse and continued tumor growth. It is therefore important to explore the causative factors for docetaxel resistance. In this study, we performed a CRISPR-based kinome screening that identified Never In Mitosis Gene-A Related Kinase-9 (NEK9) as a major player of docetaxel resistance in OSCC, prostate, and pancreatic cancer lines. NEK9 expression was upregulated in tumor samples of chemotherapy non-responders compared to responder OSCC patients. Our validation data suggests selectively knocking out NEK9 sensitizes cancer cells to docetaxel. Mechanistically, we found that ablation of NEK9 induces DNA damage, activating ERK(p-T202/Y204) that leads to Gasdermin-E mediated Cancer Cell pyroptosis. The in-vitro kinase activity assay identified fostamatinib as a potent inhibitor of NEK9. The xenograft data suggest that fostamatinib restores docetaxel sensitivity and facilitates a significant reduction of tumor burden. Overall, our data suggests a novel combination of fostamatinib and docetaxel needs further clinical investigation in advanced OSCC.

cancer biology↗