In-silico approaches to assessing multiple high-level drug-drug and drug-disease adverse drug effects.

INTRODUCTION: Pharmacovigilance plays a pivotal role in monitoring adverse events (AEs) related to chemical substances in human/animal populations. With increasing spontaneous-reporting systems, researchers turned to in-silico approaches to efficiently analyze drug safety profiles. Here, we review in-silico methods employed for assessing multiple drug-drug/drug-disease AEs covered by comparative analyses and visualization strategies. AREAS COVERED: Disproportionality, involving multi-stage statistical methodologies and data processing, identifies safety signals among drug-AE pairs. By stratifying data based on disease indications/demographics, researchers address confounders and assess drug safety. Comparative analyses, including clustering techniques and visualization techniques, assess drug similarities, patterns, and trends, calculate correlations, and identify distinct toxicities. Furthermore, we conducted a thorough Scopus search on 'pharmacovigilance,' yielding 5,836 publications spanning 2003 to 2023. EXPERT OPINION: Pharmacovigilance relies on diverse data sources, presenting challenges in the integration of in-silico approaches and requiring compliance with regulations and AI adoption. Systematic use of statistical analyses enables identifications of potential risks with drugs. Frequentist and Bayesian methods are used in disproportionalities, each with its strengths and weaknesses. Integration of pharmacogenomics with pharmacovigilance enables personalized medicine, with AI further enhancing patient engagement. This multidisciplinary approach holds promise, improving drug efficacy and safety, and should be a core mission of One-Health studies.

Machine learning model to predict the width of maxillary central incisor from anthropological measurements.

PURPOSE: To improve smile esthetics, clinicians should comprehensively analyze the face and ensure that the sizes selected for the maxillary anterior teeth are compatible with the available anthropological measurements. The inter commissural (ICW), interalar (IAW), intermedial-canthus (MCW), interlateral-canthus (LCW), and interpupillary (IPW) widths are used to determine the width of maxillary central incisors (CW). The aim of this study was to develop an automated approach using machine learning (ML) algorithms to predict central incisor width in a young Turkish population using anthropological measurements. This automation can contribute to digital dentistry and clinical decision-making. METHODS: In the initial phase of this cross-sectional study, several ML regression models-including multiple linear regression (MLR), multi-layer-perceptron (MLP), decision-tree (DT), and random forest (RF) models-were validated to confirm the central width prediction accuracy. Datasets containing only male and female measurements, as well as combined were considered for ML model implementation, and the performance of each model was evaluated for an unbiased population dataset. RESULTS: Compared with the other algorithms, the RF algorithm showed improved performance for all cases, with an accuracy of 96%, which represents the percentage of correct predictions. The plot reveals the applicability of the RF model in predicting the CW from anthropological measurements irrespective of the candidate's sex. CONCLUSIONS: These results demonstrated the possibility of predicting central incisor widths based on anthropometric measurements using ML models. The accurate central incisor width prediction from these trials also indicates the applicability of the proposed model to be deployed for enhanced clinical decision-making.

Development of machine learning algorithms to estimate maximum residue limits for veterinary medicines.

Establishing maximum-residue limits (MRLs) for veterinary medicine helps to protect the human food supply. Guidelines for establishing MRLs are outlined by regulatory authorities that drug sponsors follow in each country. During the drug approval process, residue limits are targeted for specific animal species and matrices. Therefore, MRLs are commonly not established for other species. This study demonstrates unestablished MRLs can be reliably predicted for under-represented food commodity groups using machine learning (ML). Classification methods with imbalanced data were used to analyze MRL data from multiple countries by implementing resampling techniques in different ML classifiers. Afterward, we developed and evaluated a data-mining method for predicting unestablished MRLs. Seven different ML classifiers such as support vector classifier, multi-layer perceptron (MLP), random forest, decision tree, k-neighbors, Gaussian NB, and AdaBoost have been selected in this baseline study. Among these, the neural network MLP classifier reliably scored the highest average-weighted F1 score (accuracy >99% with markers and ≈88% without markets) in predicting unestablished MRLs. This provides the first study to apply ML algorithms in regulatory food animal medicine. By predicting and estimating MRLs, we can potentially decrease the use and cost of live animals and the overall research burden of determining new MRLs.

A Review on Saliva-Based Health Diagnostics: Biomarker Selection and Future Directions.

The human body has a unique way of saying when something is wrong with it. The molecules in the body fluids can be helpful in the early detection of diseases by enabling health and preventing disease progression. These biomarkers enabling better healthcare are becoming an extensive area of research interest. Biosensors that detect these biomarkers are becoming the future, especially Point Of Care (POC) biosensors that remove the need to be physically present in the hospital. Detection of complex and systemic diseases using biosensors has a long way to go. Saliva-based biosensors are gaining attention among body fluids due to their non-invasive collection and ability to detect periodontal disease and identify systemic diseases. The possibility of saliva-based diagnostic biosensors has gained much publicity, with companies sending home kits for ancestry prediction. Saliva-based testing for covid 19 has revealed effective clinical use and relevance of the economic collection. Based on universal biomarkers, the detection of systemic diseases is a booming research arena. Lots of research on saliva-based biosensors is available, but it still poses challenges and limitations as POC devices. This review paper talks about the relevance of saliva and its usefulness as a biosensor. Also, it has recommendations that need to be considered to enable it as a possible diagnostic tool.

An Automated Customizable Live Web Crawler for Curation of Comparative Pharmacokinetic Data: An Intelligent Compilation of Research-Based Comprehensive Article Repository.

Data curation has significant research implications irrespective of application areas. As most curated studies rely on databases for data extraction, the availability of data resources is extremely important. Taking a perspective from pharmacology, extracted data contribute to improved drug treatment outcomes and well-being but with some challenges. Considering available pharmacology literature, it is necessary to review articles and other scientific documents carefully. A typical method of accessing articles on journal websites is through long-established searches. In addition to being labor-intensive, this conventional approach often leads to incomplete-content downloads. This paper presents a new methodology with user-friendly models to accept search keywords according to the investigators' research fields for metadata and full-text articles. To accomplish this, scientifically published records on the pharmacokinetics of drugs were extracted from several sources using our navigating tool called the Web Crawler for Pharmacokinetics (WCPK). The results of metadata extraction provided 74,867 publications for four drug classes. Full-text extractions performed with WCPK revealed that the system is highly competent, extracting over 97% of records. This model helps establish keyword-based article repositories, contributing to comprehensive databases for article curation projects. This paper also explains the procedures adopted to build the proposed customizable-live WCPK, from system design and development to deployment phases.

Artificial intelligence and machine learning as a viable solution for hip implant failure diagnosis-Review of literature and in vitro case study.

The digital health industry is experiencing fast-paced research which can provide digital care programs and technologies to enhance the competence of healthcare delivery. Orthopedic literature also confirms the applicability of artificial intelligence (AI) and machine learning (ML) models to medical diagnosis and clinical decision-making. However, implant monitoring after primary surgery often happens with a wellness visit or when a patient complains about it. Neglecting implant design and other technical errors in this scenario, unmonitored circumstances, and lack of post-surgery monitoring may ultimately lead to the implant system's failure and leave us with the only option of high-risk revision surgery. Preventive maintenance seems to be a good choice to identify the onset of an irreversible prosthesis failure. Considering all these aspects for hip implant monitoring, this paper explores existing studies linking ML models and intelligent systems for hip implant diagnosis. This paper explores the feasibility of an alternative continuous monitoring technique for post-surgery implant monitoring backed by an in vitro ML case study. Tribocorrosion and acoustic emission (AE) data are considered based on their efficacy in determining irreversible alteration of implant material to prevent total failures. This study also facilitates the relevance of developing an artificially intelligent implant monitoring methodology that can function with daily patient activities and how it can influence the digital orthopedic diagnosis. AI-based non-invasive hip implant monitoring system enabling point-of-care testing.

Total hip replacement monitoring: numerical models for the acoustic emission technique.

Any mechanical instability associated with total hip replacement (THR) excites elastic waves with different frequencies and propagates through the surrounding biological layers. Using the acoustic emission (AE) technique as a THR monitoring tool provides valuable information on structural degradations associated with these implants. However, several factors can compromise the reliability of the signals detected by AE sensors, such as attenuation of the detected signal due to the presence of biological layers in the human body between prosthesis (THR) and AE sensor. The main objective of this study is to develop a numerical model of THR that evaluates the impact of biological layer thicknesses on AE signal propagation. Adipose tissue thickness, which varies the most between patients, was modeled at two different thicknesses 40 mm and 70 mm, while the muscle and skin thicknesses were kept to a constant value. The proposed models were tested at different micromotions of 2 µm, 15-20 µm at modular junctions, and different frequencies of 10-60 kHz. Attenuation of signal is observed to be more with an increase in the selected boundary conditions along with an increase in distance the signals propagate through. Thereby, the numerical observations drawn on each interface helped to simulate the effect of tissue thicknesses and their impact on the attenuation of elastic wave propagation to the AE receiver sensor.