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Alzheimer's disease (AD), a progressive dementia, is the neurodegenerative disorder that worsens memory and mental capabilities mostly in aged people. Currently, clinical and psychometric assessments are being used to diagnose the disease in patients. In clinical procedures, 30 Magnetic Resonance Image qualitative parameters are analyzed to identify the abnormality in brain shape, volume, texture, and cortical thickness. This paper presents a robust approach for categorizing 30 MR images into multiple stages of AD using hybrid features viz., Gray Level Cooccurrence Matrix (GLCM), 30 Scale and rotation Invariant Feature Transform (30 SIFT), Histogram of Oriented Gradients-Three Orthogonal Planes (HOG-TOP), and Complete Local Binary Pattern of Sign and Magnitude-Three Orthogonal Planes (CLBPSM-TOP). The proposed algorithm is validated using Open Access Series of Imaging Studies (OASIS) datasets to classify the subjects into AD, Mild Cognitive Impairment (MCI), and Cognitive Normal (CN) categories using various classifiers. Moreover, this approach is also evaluated and compared with the state-of the-art approaches. 87 .84% diagnosis accuracy is achieved with Ensemble classifier using hybrid features to diagnose the severity of AD. This approach also outperforms the majority of these techniques in key parameters, namely, accuracy, precision, recalI, and F1-score. [ABSTRACT FROM AUTHOR]

Several toll-like receptors (TLRs) reside inside endosomes of specific immune cells-among them, aberrant activation of TLR7 and TLR9 is implicated in myriad contexts of autoimmune diseases, making them promising therapeutic targets. However, small-molecule TLR7 and TLR9 antagonists are not yet available for clinical use. We illustrate here the importance of C2, C6, and N9 substitutions in the purine scaffold for antagonism to TLR7 and TLR9 through structure-activity relationship studies using cellular reporter assays and functional studies on primary human immune cells. Further in vitro and in vivo pharmacokinetic studies identified an orally bioavailable lead compound 29 , with IC 50 values of 0.08 and 2.66 μM against TLR9 and TLR7, respectively. Isothermal titration calorimetry excluded direct TLR ligand-antagonist interactions. In vivo antagonism efficacy against mouse TLR9 and therapeutic efficacy in a preclinical murine model of psoriasis highlighted the potential of compound 29 as a therapeutic candidate in relevant autoimmune contexts.