Complex Integration Research Articles

Integrating Machine Learning in Metabolomics: A Path to Enhanced Diagnostics and Data Interpretation.

Metabolomics, leveraging techniques like NMR and MS, is crucial for understanding biochemical processes in pathophysiological states. This field, however, faces challenges in metabolite sensitivity, data complexity, and omics data integration. Recent machine learning advancements have enhanced data analysis and disease classification in metabolomics. This study explores machine learning integration with metabolomics to improve metabolite identification, data efficiency, and diagnostic methods. Using deep learning and traditional machine learning, it presents advancements in metabolic data analysis, including novel algorithms for accurate peak identification, robust disease classification from metabolic profiles, and improved metabolite annotation. It also highlights multiomics integration, demonstrating machine learning's potential in elucidating biological phenomena and advancing disease diagnostics. This work contributes significantly to metabolomics by merging it with machine learning, offering innovative solutions to analytical challenges and setting new standards for omics data analysis.

Examining the Effectiveness of Educational Tools and Elements Used in Medical Textbooks: Students' Perspective.

Background As textbooks constitute a foundational component of medical education, it is imperative to conduct a rigorous evaluation of their efficacy by examining the fundamental elements and tools utilized within these textbooks and how multiple factors may alter the effectiveness of such components. Materials and methods We conducted a cross-sectional, survey-based study where 251 subjects anonymously rated the effectiveness of different tools and elements/factors used in medical textbooks using 5-point Likert scales. The population surveyed included year 1 to 5 medical students at Alfaisal University, where students are admitted to medical school directly after high school, with an approximately equal male-to-female admission rate. Students were asked to rate the effectiveness of the following tools: chapter summary, end-of-chapter questions, tables of contents, graphic elements, diagrams, tables, flowcharts, mind maps, sidebars, and links to online resources. In admission, they were asked to rate textbooks regarding the following elements/factors: text clarity, directness to the concept intended, flow of ideas, language complexity, and clinical (vertical) and multidisciplinary (horizontal) integration. The Chi-square, post-hoc, Spearman's correlation, and Kruskall-Wallis tests were used in the statistical analysis to determine the differences and correlations in the students' self-ratings of different variables. Results The students rated tools such as diagrams and graphic elements as the most effective. Graphic elements were rated as significantly more effective by first- and fourth-year students. This corresponds to being exposed to new environments (the first exposure to the study of medicine and the first exposure to clinical clerkship), indicating their effectiveness in introducing new concepts and setting of change. Furthermore, end-of-chapter summaries and questions were rated significantly as being more effective by females (P<0.05). The aim behind using textbooks and the frequency might be governed by how students rate textbooks regarding multiple elements or factors, including directness to the concept intended, flow of ideas, and language complexity. Interestingly, all the above findings were consistent throughout all grade point average groups. Discussion In the rising age of e-learning, our study shows that the tools employed by textbooks remain effective. Our findings are partially consistent with existing literature, which underscores correlations between demographic variables and learning styles. We show that the effectiveness of various tools employed in textbooks can vary depending on the educational setting. While demographic factors generally did not impact students' perceptions of tool effectiveness, gender-specific differences were observed in the perceived effectiveness of end-of-chapter summaries and questions, with female students rating them as more effective, which aligns with existing literature. Conclusions Our study shows that students still perceive the tools employed by textbooks as effective. The perceived effectiveness of various tools utilized within textbooks may be influenced by certain demographic factors and settings, with graphics often proving the most efficacious. This study provides valuable insights for authors of medical textbooks, helping them optimize the usage of various tools by considering the specific characteristics and requirements of the intended audience.

TorchQL: A Programming Framework for Integrity Constraints in Machine Learning

Finding errors in machine learning applications requires a thorough exploration of their behavior over data. Existing approaches used by practitioners are often ad-hoc and lack the abstractions needed to scale this process. We present TorchQL, a programming framework to evaluate and improve the correctness of machine learning applications. TorchQL allows users to write queries to specify and check integrity constraints over machine learning models and datasets. It seamlessly integrates relational algebra with functional programming to allow for highly expressive queries using only eight intuitive operators. We evaluate TorchQL on diverse use-cases including finding critical temporal inconsistencies in objects detected across video frames in autonomous driving, finding data imputation errors in time-series medical records, finding data labeling errors in real-world images, and evaluating biases and constraining outputs of language models. Our experiments show that TorchQL enables up to 13x faster query executions than baselines like Pandas and MongoDB, and up to 40% shorter queries than native Python. We also conduct a user study and find that TorchQL is natural enough for developers familiar with Python to specify complex integrity constraints.

Small countries facing the technological revolution: fostering synergies between economic complexity and foresight research

Purpose Although the significance of technological progress in economic development is well-established in theory and policy, it has remained challenging to agree upon shared priorities for strategies and policies. This paper aims to develop a model of how policymakers can develop effective and easy to communicate strategies for science, technology and economic development. Design/methodology/approach By integrating insights from economic complexity, competitiveness and foresight literature, a replicable research framework for analysing the opportunities and challenges of technological revolutions for small catching-up countries is developed. The authors highlight key lessons from piloting this framework for informing the strategy and policies for bioeconomy in Estonia towards 2030–2050. Findings The integration of economic complexity research with traditional foresight methods establishes a solid analytical basis for a data-driven analysis of the opportunities for industrial upgrading. The increase in the importance of regional alliances in the global economy calls for further advancement of the analytical toolbox. Integration of complexity, global value chains and export potential assessment approaches offers valuable direction for further research, as it enables discussion of the opportunities of moving towards more knowledge-intensive economic activities along with the opportunities for winning international market share. Originality/value The research merges insights from the economic complexity, competitiveness and foresight literature in a novel way and illustrates the applicability and priority-setting in a real-life setting.

Beyond Efficiency: The Strategic Role of Project Managers in an Automated World

The rise of automation in project execution raises a critical question: will project managers become obsolete? This paper argues against that notion, positing a shift in their role from efficiency-driven task management to strategic leadership. We explore how automation while streamlining routine tasks, creates new challenges: navigating complex integrations, ensuring data integrity, and managing human-machine collaboration. The paper delves into the evolving skillset required for project managers to thrive in this automated landscape. This includes strategic planning, risk mitigation for unforeseen technical issues, and fostering a culture of innovation to leverage automation effectively. By embracing these strategic responsibilities, project managers can become vital change agents, ensuring projects not only meet deadlines and budgets but also achieve their full potential in an increasingly automated world.

Examination of sensory reception and integration abilities in children with and without Prader-Willi syndrome

BackgroundGood postural stability control is dependent upon the complex integration of incoming sensory information (visual, somatosensory, vestibular) with neuromotor responses that are constructed in advance of a voluntary action or in response to an unexpected perturbation. AimsTo examine whether differences exist in how sensory inputs are used to control standing balance in children with and without Prader-Willi syndrome (PWS). Methods and ProceduresIn this cross-sectional study, 18 children with PWS and 51 children categorized as obese but without PWS (without PWS) ages 8–11 completed the Sensory Organization Test®. This test measures the relative contributions of vision, somatosensory, and vestibular inputs to the control of standing balance. The composite equilibrium score (CES) derived from performance in all sensory conditions, in addition to equilibrium scores (EQs) and falls per condition were compared between groups. Outcomes and ResultsThe CES was lower for children with PWS compared to children without PWS (M=53.93, SD=14.56 vs. M=66.17, SD=9.89, p = .001) while EQs declined in both groups between conditions 1 and 4 (F (1.305, 66.577) = 71.381, p < .001). No group differences in the percent of falls were evident in condition 5 but more children with PWS fell in condition 6 (χ2 (1) = 7.468, p = .006). Group differences in frequency of repeated falls also approached significance in conditions 5 (χ2 (3) = 4.630, p = .099) and 6 (χ2 (3) = 5.167, p = .076). Conclusions and ImplicationsChildren with PWS demonstrated a lower overall level of postural control and increased sway when compared to children with obesity. Both the higher incidence and repeated nature of falls in children with PWS in conditions 5 and 6 suggest an inability to adapt to sensory conditions in which vestibular input must be prioritized. Postural control training programs in this population should include activities that improve their ability to appropriately weight sensory information in changing sensory environments, with a particular focus on the vestibular system. What does this study add?This study shows that children with PWS demonstrate a lower level of postural stability. The results suggest that children with PWS show inability to adapt to sensory conditions that require prioritizing vestibular information to maintain postural control. This information can be used to help guide training programs in this population.

Eco-innovative development of industrial ecosystems based on the quintuple helix

This article explores how eco-innovation practices are integrated into different industrial ecosystems in different national and regional contexts, and the role of the quintuple helix model in this integration. The research examines the collaborative interaction of academia, industry, government, civil society, and the natural environment in fostering an integrated eco-innovation ecosystem. The findings underscore the central role of the Quintuple Helix framework in effectively managing eco-innovation, suggesting a comprehensive approach that integrates environmental and societal concerns into a dynamic system for sustainable progress. The study shows that an ecosystem-based approach, underpinned by the quintuple helix, facilitates the rapid exchange of knowledge and resources essential to overcoming eco-innovation challenges, such as high R&D expenditures and the complex integration of sustainable technologies. The quintuple helix model emerges as a strategic imperative for concerted action to achieve eco-efficiency and eco-effectiveness. The study employs an innovative methodological framework based on Quintuple Helix projections using the Eco-Innovation Index (Eco-IS) and highlights significant trends in the roles of academia, industry, government, civil society, and the natural environment in eco-innovation, with a particular focus on their contributions to eco-innovation leaders, average performers, and catching-up groups. The article describes the different roles and interdependencies of the actors within the ecosystem and urges a coherent, networked strategy for managing eco-innovation, which is crucial for sustainable and responsible growth. Acknowledging the issue of externalities that complicate eco-innovation management, the article posits that the quintuple helix framework can better address these challenges by enabling shared R&D investments and broad diffusion of innovations. This research contributes to the discourse on sustainable industrial development by proposing the quintuple helix as a transformative model for improving eco-innovation performance and fostering a culture of sustainability.

Nonlinear elasticity with the Shifted Boundary Method

We propose a new unfitted/immersed computational framework for nonlinear solid mechanics, which bypasses the complexities associated with the generation of CAD representations and subsequent body-fitted meshing. This approach allows to speed up the cycle of design and analysis in complex geometry and requires relatively simple computer graphics representations of the surface geometries to be simulated, such as the Standard Tessellation Language (STL format). Complex data structures and integration on cut elements are avoided by means of an approximate boundary representation and a modification (shifting) of the boundary conditions to maintain optimal accuracy. An extensive set of computational experiments in two and three dimensions is included.

Developing campus digital twin using interactive visual analytics approach

AbstractDigital Twins (DTs) are increasingly recognized for their potential to improve efficiency and decision-making in various domains of the built environment. Despite their promise, challenges like cost, complexity, interoperability, and data integration remain. This paper introduces a novel interactive visual analytics system that tackles these issues, using a case study of simulating class distribution and campus building capacity at a large public university. The system leverages enrollment data, converting it into a spatial-temporal format for interactive exploration and analysis of class distribution and resource utilization. Through case studies, we demonstrate the system's effectiveness, adaptability, and real-world applicability, highlighting its role in practical DT implementation for built environments.

Gd(HB-DO3A)]: Equilibrium, Dissociation Kinetic and Structural Differences in a Simple Homolog of [Gd(HP-DO3A)] (Prohance®).

[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance® is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)]. It was deemed of interest to assess how minor structural/electronic changes associated to the ligand structure may affect basic properties of the metal complex with several [Gd(HP-DO3A)] analogues synthesized and characterized in the last years. We recently reported that the closest homolog of [Gd(HP-DO3A)], i. e.: [Gd(HB-DO3A)], in which a (±)-2-hydroxy-1-propyl pendant arm is replaced by a (±)-2-hydroxy-1-butyl moiety, showed a significantly different retention behaviour in the model interaction with collagen, despite the apparently very minor structural difference. In this paper we report a comprehensive study of the structural, thermodynamic, kinetic and relaxation properties of [Gd(HB-DO3A)], compared to the parent [Gd(HP-DO3A)] and to other closely related macrocyclic GBCAs to assess whether very minor structural changes can modulate the physico-chemical properties of Gd3+ complexes.

Improving Population Health and Health Equity: The Potential of Transitioning Public Open Spaces to Optimise the Production of Urban Ecological Services in Adelaide, South Australia

ABSTRACT This research examines the potential of transitioning public “green spaces” to optimise health benefiting urban ecological services in metropolitan Adelaide, South Australia. The research found strengths but also significant weaknesses. The major weaknesses observed were poor quality amenities and facilities within open spaces, low landscape complexity, poor maintenance and inadequate integration with the built form and pedestrian networks of the surrounding neighbourhoods. Previous research has shown that the weaknesses we observed are adversely affecting the health and wellbeing of many residents. In addition, our research shows there are far more strengths and fewer weaknesses in pre-1945 and high-income neighbourhoods.

Экосистема как механизм государственно- частного партнерства

This very study considers the background and possibilities of implementation ecosystem in the governmental toolbar for the strategic projects. &#x0D; The urgency of the problem is caused by the list of factors, including:&#x0D; - negative external background, affecting the availability of resources, technologies and specialists for the implementation of transformation tasks;&#x0D; - lack of socio-economic institutes which are ready to ensure the realization strategic goals at the operational level;&#x0D; - the need for rapid restructuring of the national economy, which can be provided through mechanisms of operational interaction between the government, business and the population.&#x0D; Most modern studies don’t analyze ecosystems as a tool for the supporting of strategic goals of the national economy.&#x0D; The purpose of the study is to identify opportunities and risks for the government and society while using ecosystems in realization strategic state goals. &#x0D; The purpose of the study predetermined the following tasks:&#x0D; - Determination of the impact of negative external factors of the transformation of the national economy.&#x0D; - The role and functions of ecosystems in the implementation of strategic objectives of the national economy.&#x0D; - Scenarios and risks of ecosystem impact growth.&#x0D; The following tools are used in the study: structural and institutional analyze, modeling and forecasting. The ecosystem is considered as a complex integration platform that unites consumers and producers into a single system through end-to-end sales channels, a single financial infrastructure and communication standards. As the best practices of interaction between ecosystems and the state, the experience of implementing complex projects of the largest national ecosystems was used: Sber, MTS, Rostelecom, Yandex.&#x0D; The paper proposes the current scheme of interaction between the ecosystem and the government in the framework of the realization strategic transformation programs. The scheme is formed on the basis of a sophisticated business model (B2G2B2C), involving the participation of all macroeconomic agents. The scheme presents several functional contours: the formation and execution of a complex regional order (the essential contour of agent interaction), financial interaction between participants.&#x0D; The second part of the study examines scenarios for the development of the relationship between the ecosystem and the state from the position of influence on society, taking into account two variables: the willingness of the state to play an active role in regulating the activities of ecosystems within the national contour; the level of favorability of external rejection for ecosystems. As a result, 4 scenarios were considered that answer the questions of ecosystem development, their contribution to public welfare, and work with innovations.

The Residue Theorem: Applications in Complex Integrals

The Residue Theorem: Applications in Complex Integrals

Abstract 5446: The role of snoRNAs in GBM cells, GSCs, neuronal precursor cells (NPCs), astrocytes, and normal brain tissues

Abstract rRNA modification are a crucial step in ribosome assembly and function. Small nucleolar RNAs select which nucleotides in rRNAs get modified. Typically, C/D box snoRNAs are implicated in 2’-O-ribose methylation (2’Omet) while H/ACA box snoRNAs are responsible for pseudo-uridylations. Alterations in snoRNA expression have been described in multiple tumor types while distinct snoRNAs have been linked to cancer-relevant phenotypes. Our initial study on snoRNA expression using a dedicated Ampliseq platform revealed a specific glioma stem cell (GSC) signature. We propose this snoRNA signature creates a unique rRNA modification pattern that shapes the ribosome, favoring the translation of genes in pathways critical for GSC growth and survival. We will expand our study and characterize the expression profile of snoRNAs and 2’Omethylation in a large panel of GBM cells, GSCs, neuronal precursor cells (NPCs), astrocytes, and normal brain tissues. Next, we will select snoRNAs displaying differential expression in GSCs and determine if changes in their levels affect proliferation, viability, response to temozolomide and radiation, and translation. We and others have observed that the integrity of protein complexes that regulate ribosomal biogenesis depends on PolyADP-ribosylation (PARylation)and PAR-binding. In agreement, genomic screenings determined that multiple genes regulating ribosome biogenesis confer sensitivity to PARP inhibitors. These findings offer a therapeutic opportunity. We will investigate the functional impact of PARylation on rRNA modification by determining the effect of PARP inhibitors on snoRNP assembly and 2’Omethylation. Finally, we will test the hypothesis that PARP and ribosome biogenesis inhibitor combinations would be more effective than PARP inhibition alone in treating GBM. Citation Format: Sujash Chatterjee, Scott Kuersten, Christina Middle, Morgan Roos, Pedro A. Galante, Gabriela Guardia, Luiz Penalva. The role of snoRNAs in GBM cells, GSCs, neuronal precursor cells (NPCs), astrocytes, and normal brain tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5446.

Hydroxychloroquine interaction with phosphoinositide 3-kinase modulates prostate cancer growth in bone microenvironment: In vitro and molecular dynamics based approach

Patients with advanced prostate cancer (PCa) are more likely to develop bone metastases. Tumor cells thrive in the bone microenvironment, interacting with osteoblasts and osteoclasts. Given the PI3K/AKT pathway's metastatic potential and signal integration's ability to modulate cell fates in PCa development, drugs targeting this system have great therapeutic promise. Hydroxychloroquine (HCQ) is an anti-malarial medication commonly used to treat clinical conditions such as rheumatology and infectious disorders. We explored the anti-neoplastic effect of HCQ on PC3 and C4-2B cell lines in the bone microenvironment. Interestingly, HCQ treatment substantially decreases the viability, proliferation, and migration potential of PCa cells in the bone microenvironment. HCQ induces apoptosis and cell cycle arrest, even in the presence of osteoblast-secreted factors. Mechanistically, HCQ inhibited the activity of the PI3K/AKT signaling pathway, which ultimately regulates the proliferation and migration of PCa cells in the bone. The binding energy for docking HCQ with PI3K was −6.7 kcal/mol, and the complex was stabilized by hydrogen bonds, hydrophobic forces, and van der Waals forces. Molecular simulations further validated the structural integrity of the HCQ-PI3K complex without altering PI3K's secondary structure. Our findings underscore the efficacy of HCQ as a potential therapeutic agent in treating PCa.

Validation of spectrophotometric and colorimetric methods for determination of efavirenz in various biological matrices: Application to the development of dissolvable microneedle-based efavirenz complex inclusion for vaginal delivery

One of the antiretroviral treatments (ART) used to treat Human Immunodeficiency Virus (HIV) disease is efavirenz (EFV). EFV itself has bioavailability issues during oral therapy due to its poor solubility. When injected, administration issues arise. Hence, creating medication delivery methods was crucial to creating EFV delivery. HIV therapy benefits from the vaginal medication delivery system's ease of use, higher bioavailability, and quick systemic absorption in the surface folds. In this study, an inclusion complex (IC) was added to the EFV formulation to increase solubility, and dissolving microneedles (DMN) was used for delivery to increase penetration. Here, in support of this formulation creation process, we carried out validation utilizing spectrophotometric and colorimetric techniques. The amount of EFV was determined by validating ethanol and artificial vaginal fluid (AVF) using UV–Vis spectrophotometry. Vaginal tissue and plasma were also validated using colorimetric with the β-naphthol reagent. The International Council for Harmonization (ICH) and US Food and Drug Administration (FDA) requirements were adhered to in verifying the creation of analytical procedures. The outcomes demonstrated a linear correlation value of ≥0.9998. The LLOQ levels were 0.99 g/mL, 0.97 g/mL, 0.66 g/mL, 0.74 g/mL, and 0.74 g/mL in ethanol, AVF, porcine vaginal tissue, rat vaginal tissue, and vaginal plasma, respectively. The developed precision and accuracy were confirmed. The approach was successfully used to determine the amount of EFV in inclusion complex integration and DMN platform. The outcomes demonstrated high IC-EFV incorporation release and penetration profiles, permeation and high drug retention andex vivokinetics in the vagina and enhanced bioavailability fromin vivostudy pharmacokinetic profiles of DMN-IC-EFV.

A Comparative performance evaluation of a complex-order PI controller for DC–DC converters

Switched-mode DC–DC converters are required to maintain constant output under uncertainties and variations in input voltage and load. The controller’s robustness is crucial in such systems, and hence various controllers have been proposed in the past few decades for DC–DC converter control. Fractional order PID controllers have attracted the attention of researchers due to their robustness and flexibility in control of power converters. Such controllers use fractional orders of integration and differentiation. Complex order controllers are the generalized form of the fractional order PID controllers and have complex orders of integration and differentiation. These controllers are very robust in the control of nonlinear systems with time-varying parameters. But complex order controllers have been very sparingly used in power electronic control. This paper proposes a complex order PI controller with a complex order integrator for controlling DC–DC buck and boost converters. The complex PID controller has four parameters to be tuned. The complex order PI controller is designed by optimization using the metaheuristic Cohort Intelligence algorithm. The results are compared with that of a fractional-order PID controller. It was observed that the complex PI controller gave a better response than the FOPID controller and was more robust to parameter variations.

Complex deformable calculus

In this paper, we give a new complex deformable derivative and integral of order λ which coincides with the classical derivative and integral for the special values of the parameters. We examine the basic properties of this derivative and integral. We also investigate the basic concepts of complex analysis for the λ-complex deformable derivative. Finally, we give some applications.

Looking beyond the hype: The challenges of blockchain adoption in accounting

Blockchain has been hyped and considered a potential game-changer for the recording of accounting transactions as it enables triple-entry accounting and real-time reporting. However, there is very little knowledge of the uptake of blockchain in accounting, and most blockchain accounting research is conceptual, lacking empirical evidence. This study addresses this gap and examines the organisational factors that drive and hinder the adoption of blockchain in accounting, as well as the perceived benefits. Using the technology-organisation-environment (TOE) framework, we analyse interview data collected from blockchain experts and accountants (N = 19). The findings confirm the influence of nine context-specific factors, highlighting the challenges and lack of knowledge in understanding the usage and benefits of blockchain in accounting, its complex integration with existing accounting systems, and the increased costs associated with the adoption intention. This study provides novel empirical evidence of the factors by adequately contextualising an established theoretical framework in the context of accounting. The findings are useful for practitioners and the broader accounting information systems research community as they provide empirical insights into how context-specific factors influence blockchain adoption in accounting.

Role of Cytoskeletal Elements in Regulation of Synaptic Functions: Implications Toward Alzheimer's Disease and Phytochemicals-Based Interventions.

Alzheimer's disease (AD), a multifactorial disease, is characterized by the accumulation of neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques. AD is triggered via several factors like alteration in cytoskeletal proteins, a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), amyloid precursor protein (APP), and post-translational modifications (PTMs) in the cytoskeletal elements. Owing to the major structural and functional role of cytoskeletal elements, like the organization of axon initial segmentation, dendritic spines, synaptic regulation, and delivery of cargo at the synapse; modulation of these elements plays an important role in AD pathogenesis; like Tau is a microtubule-associated protein that stabilizes the microtubules, and it also causes inhibition of nucleo-cytoplasmic transportation by disrupting the integrity of nuclear pore complex. One of the major cytoskeletal elements, actin and its dynamics, regulate the dendritic spine structure and functions; impairments have been documented towards learning and memory defects. The second major constituent of these cytoskeletal elements, microtubules, are necessary for the delivery of the cargo, like ion channels and receptors at the synaptic membranes, whereas actin-binding protein, i.e., Cofilin's activation form rod-like structures, is involved in the formation of paired helical filaments (PHFs) observed in AD. Also, the glial cells rely on their cytoskeleton to maintain synaptic functionality. Thus, making cytoskeletal elements and their regulation in synaptic structure and function as an important aspect to be focused for better management and targeting AD pathology. This review advocates exploring phytochemicals and Ayurvedic plant extracts against AD by elucidating their neuroprotective mechanisms involving cytoskeletal modulation and enhancing synaptic plasticity. However, challenges include their limited bioavailability due to the poor solubility and the limited potential to cross the blood-brain barrier (BBB), emphasizing the need for targeted strategies to improve therapeuticefficacy.