A hybrid quantum-classical fusion neural network to improve protein-ligand binding affinity predictions for drug discovery

The field of drug discovery hinges on the accurate prediction of binding affinity between prospective drug molecules and target proteins, especially when such proteins directly influence disease progression. However, estimating binding affinity demands significant financial and computational resources. While state-of-the-art methodologies employ classical machine learning (ML) techniques, emerging hybrid quantum machine learning (QML) models have shown promise for enhanced performance, owing to their inherent parallelism and capacity to manage exponential increases in data dimensionality. Despite these advances, existing models encounter issues related to convergence stability and prediction accuracy. This paper introduces a novel hybrid quantum-classical deep learning model tailored for binding affinity prediction in drug discovery. Specifically, the proposed model synergistically integrates 3D and spatial graph convolutional neural networks within an optimized quantum architecture. Simulation results demonstrate a 6% improvement in prediction accuracy relative to existing classical models, as well as a significantly more stable convergence performance compared to previous classical approaches.Comment: 5 pages, 3 figure

Cognitive neuroscience of delusions in aging

Assessments and clinical understanding of late-onset delusions in the elderly are inconsistent and often incomplete. In this review, we consider the prevalence, neurobehavioral features, and neuroanatomic correlations of delusions in elderly persons – those with documented cognitive decline and those with no evidence of cognitive decline. Both groups exhibit a common phenotype: delusions are either of persecution or of misidentification. Late-onset delusions show a nearly complete absence of the grandiose, mystical, or erotomanic content typical of early onset psychoses. Absent also from both elderly populations are formal thought disorders, thought insertions, and delusions of external control. Neuroimaging and behavioral studies suggest a frontotemporal localization of delusions in the elderly, with right hemispheric lateralization in delusional misidentification and left lateralization in delusions of persecution. We propose that delusions in the elderly reflect a common neuroanatomic and functional phenotype, and we discuss applications of our proposal to diagnosis and treatment

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Psoriasis vulgaris occurring in a known case of neurofibromatosis type I: A rare association

Neurofibromatosis type 1 (NF-1) is an autosomal dominantly inherited neurocutaneous disorder due to mutations in the neurofibromin (NF) gene that encodes protein NF. NF regulates signal transduction by inactivating RAS proteins. Mutations in the NF-1 gene increases RAS activity causing increased transduction of many growth factors and kinase pathways leading to increased mitosis and occurrence of neoplasms and proliferative conditions such as psoriasis. Psoriasis is a chronic, inflammatory proliferative condition of the skin in which both genetic and environmental factors have a vital role. The underlying pathogenesis is epidermal proliferation, vascular changes, and inflammatory changes mediated by multiple growth factors of which in particular are epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, tumor necrosis factor (TNF)-alpha etc. We report a rare association of NF-1 with psoriasis occurring by chance or due to decreased NF protein

Focality of the induced e-field is a contributing factor in the choice of tms parameters: Evidence from a 3d computational model of the human brain

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm3 between the selected nine clinically relevant coil locations. Coil orientation also changed the induced E-field by a maximum of 10%, and we noted the least optimal values at the standard coil orientation pointing to the nose. The volume of gray matter activated varied by 10% on average between stimulation sites in homologous brain areas in the two hemispheres of the brain. This FEM simulation model clearly demonstrates the importance of TMS parameters for optimal results in clinically relevant brain areas. The results show that TMS parameters cannot be interchangeably used between individuals, hemispheres, and brain areas. The focality of the TMS induced E-field along with its optimal magnitude should be considered as critical TMS parameters that should be individually optimized