QSAR: Using the Past to Study the Present.

Quantitative structure-activity relationships (QSAR) is a method for predicting the physical and biological properties of small molecules; it is in use in industry and public services. However, as any scientific method, it is challenged by more and more requests, especially considering its possible role in assessing the safety of new chemicals. To answer the question whether QSAR, by exploiting available knowledge, can build new knowledge, the chapter reviews QSAR methods in search of a QSAR epistemology. QSAR stands on tree pillars, i.e., biological data, chemical knowledge, and modeling algorithms. Usually the biological data, resulting from good experimental practice, are taken as a true picture of the world; chemical knowledge has scientific bases; so if a QSAR model is not working, blame modeling. The role of modeling in developing scientific theories, and in producing knowledge, is so analyzed. QSAR is a mature technology and is part of a large body of in silico methods and other computational methods. The active debate about the acceptability of the QSAR models, about the way to communicate them, and the explanation to provide accompanies the development of today QSAR models. An example about predicting possible endocrine-disrupting chemicals (EDC) shows the many faces of modern QSAR methods.

Drone and ground-truth data collection, image annotation and machine learning: A protocol for coastal habitat mapping and classification.

Aerial drone imaging is an efficient tool for mapping and monitoring of coastal habitats at high spatial and temporal resolution. Specifically, drone imaging allows for time- and cost-efficient mapping covering larger areas than traditional mapping and monitoring techniques, while also providing more detailed information than those from airplanes and satellites, enabling for example to differentiate various types of coastal vegetation. Here, we present a systematic method for shallow water habitat classification based on drone imagery. The method includes:•Collection of drone images and creation of orthomosaics.•Gathering ground-truth data in the field to guide the image annotation and to validate the final map product.•Annotation of drone images into - potentially hierarchical - habitat classes and training of machine learning algorithms for habitat classification.As a case study, we present a field campaign that employed these methods to map a coastal site dominated by seagrass, seaweed and kelp, in addition to sediments and rock. Such detailed but efficient mapping and classification can aid to understand and sustainably manage ecologically and valuable marine ecosystems.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

BACKGROUND: Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE: This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS: This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS: Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. CONCLUSIONS: The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.

Exploring metabolic anomalies in COVID-19 and post-COVID-19: a machine learning approach with explainable artificial intelligence.

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant challenges worldwide, including diverse clinical outcomes and prolonged post-recovery symptoms known as Long COVID or Post-COVID-19 syndrome. Emerging evidence suggests a crucial role of metabolic reprogramming in the infection's long-term consequences. This study employs a novel approach utilizing machine learning (ML) and explainable artificial intelligence (XAI) to analyze metabolic alterations in COVID-19 and Post-COVID-19 patients. Samples were taken from a cohort of 142 COVID-19, 48 Post-COVID-19, and 38 control patients, comprising 111 identified metabolites. Traditional analysis methods, like PCA and PLS-DA, were compared with ML techniques, particularly eXtreme Gradient Boosting (XGBoost) enhanced by SHAP (SHapley Additive exPlanations) values for explainability. XGBoost, combined with SHAP, outperformed traditional methods, demonstrating superior predictive performance and providing new insights into the metabolic basis of the disease's progression and aftermath. The analysis revealed metabolomic subgroups within the COVID-19 and Post-COVID-19 conditions, suggesting heterogeneous metabolic responses to the infection and its long-term impacts. Key metabolic signatures in Post-COVID-19 include taurine, glutamine, alpha-Ketoglutaric acid, and LysoPC a C16:0. This study highlights the potential of integrating ML and XAI for a fine-grained description in metabolomics research, offering a more detailed understanding of metabolic anomalies in COVID-19 and Post-COVID-19 conditions.

Impact of a Digital Scribe System on Clinical Documentation Time and Quality: Usability Study.

BACKGROUND: Physicians spend approximately half of their time on administrative tasks, which is one of the leading causes of physician burnout and decreased work satisfaction. The implementation of natural language processing-assisted clinical documentation tools may provide a solution. OBJECTIVE: This study investigates the impact of a commercially available Dutch digital scribe system on clinical documentation efficiency and quality. METHODS: Medical students with experience in clinical practice and documentation (n=22) created a total of 430 summaries of mock consultations and recorded the time they spent on this task. The consultations were summarized using 3 methods: manual summaries, fully automated summaries, and automated summaries with manual editing. We then randomly reassigned the summaries and evaluated their quality using a modified version of the Physician Documentation Quality Instrument (PDQI-9). We compared the differences between the 3 methods in descriptive statistics, quantitative text metrics (word count and lexical diversity), the PDQI-9, Recall-Oriented Understudy for Gisting Evaluation scores, and BERTScore. RESULTS: The median time for manual summarization was 202 seconds against 186 seconds for editing an automatic summary. Without editing, the automatic summaries attained a poorer PDQI-9 score than manual summaries (median PDQI-9 score 25 vs 31, P<.001, ANOVA test). Automatic summaries were found to have higher word counts but lower lexical diversity than manual summaries (P<.001, independent t test). The study revealed variable impacts on PDQI-9 scores and summarization time across individuals. Generally, students viewed the digital scribe system as a potentially useful tool, noting its ease of use and time-saving potential, though some criticized the summaries for their greater length and rigid structure. CONCLUSIONS: This study highlights the potential of digital scribes in improving clinical documentation processes by offering a first summary draft for physicians to edit, thereby reducing documentation time without compromising the quality of patient records. Furthermore, digital scribes may be more beneficial to some physicians than to others and could play a role in improving the reusability of clinical documentation. Future studies should focus on the impact and quality of such a system when used by physicians in clinical practice.

AI-Enhanced ECG Applications in Cardiology: Comprehensive Insights from the Current Literature with a Focus on COVID-19 and Multiple Cardiovascular Conditions.

The application of artificial intelligence (AI) in electrocardiography is revolutionizing cardiology and providing essential insights into the consequences of the COVID-19 pandemic. This comprehensive review explores AI-enhanced ECG (AI-ECG) applications in risk prediction and diagnosis of heart diseases, with a dedicated chapter on COVID-19-related complications. Introductory concepts on AI and machine learning (ML) are explained to provide a foundational understanding for those seeking knowledge, supported by examples from the literature and current practices. We analyze AI and ML methods for arrhythmias, heart failure, pulmonary hypertension, mortality prediction, cardiomyopathy, mitral regurgitation, hypertension, pulmonary embolism, and myocardial infarction, comparing their effectiveness from both medical and AI perspectives. Special emphasis is placed on AI applications in COVID-19 and cardiology, including detailed comparisons of different methods, identifying the most suitable AI approaches for specific medical applications and analyzing their strengths, weaknesses, accuracy, clinical relevance, and key findings. Additionally, we explore AI's role in the emerging field of cardio-oncology, particularly in managing chemotherapy-induced cardiotoxicity and detecting cardiac masses. This comprehensive review serves as both an insightful guide and a call to action for further research and collaboration in the integration of AI in cardiology, aiming to enhance precision medicine and optimize clinical decision-making.

Development of Lung Cancer Risk Prediction Machine Learning Models for Equitable Learning Health System: Retrospective Study.

BACKGROUND: A significant proportion of young at-risk patients and nonsmokers are excluded by the current guidelines for lung cancer (LC) screening, resulting in low-screening adoption. The vision of the US National Academy of Medicine to transform health systems into learning health systems (LHS) holds promise for bringing necessary structural changes to health care, thereby addressing the exclusivity and adoption issues of LC screening. OBJECTIVE: This study aims to realize the LHS vision by designing an equitable, machine learning (ML)-enabled LHS unit for LC screening. It focuses on developing an inclusive and practical LC risk prediction model, suitable for initializing the ML-enabled LHS (ML-LHS) unit. This model aims to empower primary physicians in a clinical research network, linking central hospitals and rural clinics, to routinely deliver risk-based screening for enhancing LC early detection in broader populations. METHODS: We created a standardized data set of health factors from 1397 patients with LC and 1448 control patients, all aged 30 years and older, including both smokers and nonsmokers, from a hospital's electronic medical record system. Initially, a data-centric ML approach was used to create inclusive ML models for risk prediction from all available health factors. Subsequently, a quantitative distribution of LC health factors was used in feature engineering to refine the models into a more practical model with fewer variables. RESULTS: The initial inclusive 250-variable XGBoost model for LC risk prediction achieved performance metrics of 0.86 recall, 0.90 precision, and 0.89 accuracy. Post feature refinement, a practical 29-variable XGBoost model was developed, displaying performance metrics of 0.80 recall, 0.82 precision, and 0.82 accuracy. This model met the criteria for initializing the ML-LHS unit for risk-based, inclusive LC screening within clinical research networks. CONCLUSIONS: This study designed an innovative ML-LHS unit for a clinical research network, aiming to sustainably provide inclusive LC screening to all at-risk populations. It developed an inclusive and practical XGBoost model from hospital electronic medical record data, capable of initializing such an ML-LHS unit for community and rural clinics. The anticipated deployment of this ML-LHS unit is expected to significantly improve LC-screening rates and early detection among broader populations, including those typically overlooked by existing screening guidelines.

Unlocking Hidden Risks: Harnessing Artificial Intelligence (AI) to Detect Subclinical Conditions from an Electrocardiogram (ECG).

Recent artificial intelligence (AI) advancements in cardiovascular medicine offer potential enhancements in diagnosis, prediction, treatment, and outcomes. This article aims to provide a basic understanding of AI enabled ECG technology. Specific conditions and findings will be discussed, followed by reviewing associated terminology and methodology. In the appendix, definitions of AUC versus accuracy are explained. The application of deep learning models enables detecting diseases from normal electrocardiograms at accuracy not previously achieved by technology or human experts. Results with AI enabled ECG are encouraging as they considerably exceeded current screening models for specific conditions (i.e., atrial fibrillation, left ventricular dysfunction, aortic stenosis, and hypertrophic cardiomyopathy). This could potentially lead to a revitalization of the utilization of the ECG in the insurance domain. While we are embracing the findings with this rapidly evolving technology, but cautious optimism is still necessary at this point.

Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning.

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

Automated System to Capture Patient Symptoms From Multitype Japanese Clinical Texts: Retrospective Study.

BACKGROUND: Natural language processing (NLP) techniques can be used to analyze large amounts of electronic health record texts, which encompasses various types of patient information such as quality of life, effectiveness of treatments, and adverse drug event (ADE) signals. As different aspects of a patient's status are stored in different types of documents, we propose an NLP system capable of processing 6 types of documents: physician progress notes, discharge summaries, radiology reports, radioisotope reports, nursing records, and pharmacist progress notes. OBJECTIVE: This study aimed to investigate the system's performance in detecting ADEs by evaluating the results from multitype texts. The main objective is to detect adverse events accurately using an NLP system. METHODS: We used data written in Japanese from 2289 patients with breast cancer, including medication data, physician progress notes, discharge summaries, radiology reports, radioisotope reports, nursing records, and pharmacist progress notes. Our system performs 3 processes: named entity recognition, normalization of symptoms, and aggregation of multiple types of documents from multiple patients. Among all patients with breast cancer, 103 and 112 with peripheral neuropathy (PN) received paclitaxel or docetaxel, respectively. We evaluate the utility of using multiple types of documents by correlation coefficient and regression analysis to compare their performance with each single type of document. All evaluations of detection rates with our system are performed 30 days after drug administration. RESULTS: Our system underestimates by 13.3 percentage points (74.0%-60.7%), as the incidence of paclitaxel-induced PN was 60.7%, compared with 74.0% in the previous research based on manual extraction. The Pearson correlation coefficient between the manual extraction and system results was 0.87 Although the pharmacist progress notes had the highest detection rate among each type of document, the rate did not match the performance using all documents. The estimated median duration of PN with paclitaxel was 92 days, whereas the previously reported median duration of PN with paclitaxel was 727 days. The number of events detected in each document was highest in the physician's progress notes, followed by the pharmacist's and nursing records. CONCLUSIONS: Considering the inherent cost that requires constant monitoring of the patient's condition, such as the treatment of PN, our system has a significant advantage in that it can immediately estimate the treatment duration without fine-tuning a new NLP model. Leveraging multitype documents is better than using single-type documents to improve detection performance. Although the onset time estimation was relatively accurate, the duration might have been influenced by the length of the data follow-up period. The results suggest that our method using various types of data can detect more ADEs from clinical documents.

Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients.

BACKGROUND: Chronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized. METHODS: Blood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm. RESULTS: Five serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59). CONCLUSION: Using state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions. FUNDING: Supported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).

Enhancing Vaxign-DL for Vaccine Candidate Prediction with added ESM-Generated Features.

Many vaccine design programs have been developed, including our own machine learning approaches Vaxign-ML and Vaxign-DL. Using deep learning techniques, Vaxign-DL predicts bacterial protective antigens by calculating 509 biological and biomedical features from protein sequences. In this study, we first used the protein folding ESM program to calculate a set of 1,280 features from individual protein sequences, and then utilized the new set of features separately or in combination with the traditional set of 509 features to predict protective antigens. Our result showed that the usage of ESM-derived features alone was able to accurately predict vaccine antigens with a performance similar to the orginal Vaxign-DL prediction method, and the usage of the combined ESM-derived and orginal Vaxign-DL features significantly improved the prediction performance according to a set of seven scores including specificity, sensitivity, and AUROC. To further evaluate the updated methods, we conducted a Leave-One-Pathogen-Out Validation (LOPOV) study, and found that the usage of ESM-derived features significantly improved the the prediction of vaccine antigens from 10 bacterial pathogens. This research is the first reported study demonstrating the added value of protein folding features for vaccine antigen prediction.

Investigating Acoustic and Psycholinguistic Predictors of Cognitive Impairment in Older Adults: Modeling Study.

BACKGROUND: About one-third of older adults aged 65 years and older often have mild cognitive impairment or dementia. Acoustic and psycho-linguistic features derived from conversation may be of great diagnostic value because speech involves verbal memory and cognitive and neuromuscular processes. The relative decline in these processes, however, may not be linear and remains understudied. OBJECTIVE: This study aims to establish associations between cognitive abilities and various attributes of speech and natural language production. To date, the majority of research has been cross-sectional, relying mostly on data from structured interactions and restricted to textual versus acoustic analyses. METHODS: In a sample of 71 older (mean age 83.3, SD 7.0 years) community-dwelling adults who completed qualitative interviews and cognitive testing, we investigated the performance of both acoustic and psycholinguistic features associated with cognitive deficits contemporaneously and at a 1-2 years follow up (mean follow-up time 512.3, SD 84.5 days). RESULTS: Combined acoustic and psycholinguistic features achieved high performance (F1-scores 0.73-0.86) and sensitivity (up to 0.90) in estimating cognitive deficits across multiple domains. Performance remained high when acoustic and psycholinguistic features were used to predict follow-up cognitive performance. The psycholinguistic features that were most successful at classifying high cognitive impairment reflected vocabulary richness, the quantity of speech produced, and the fragmentation of speech, whereas the analogous top-ranked acoustic features reflected breathing and nonverbal vocalizations such as giggles or laughter. CONCLUSIONS: These results suggest that both acoustic and psycholinguistic features extracted from qualitative interviews may be reliable markers of cognitive deficits in late life.

Diagnostic value of an interpretable machine learning model based on clinical ultrasound features for follicular thyroid carcinoma.

Background: Follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) present diagnostic challenges due to overlapping clinical and ultrasound features. Improving the diagnosis of FTC can enhance patient prognosis and effectiveness in clinical management. This study seeks to develop a predictive model for FTC based on ultrasound features using machine learning (ML) algorithms and assess its diagnostic effectiveness. Methods: Patients diagnosed with FTA or FTC based on surgical pathology between January 2009 and February 2023 at Zhejiang Provincial Cancer Hospital and Zhejiang Provincial People's Hospital were retrospectively included. A total of 562 patients from Zhejiang Provincial Cancer Hospital comprised the training set, and 218 patients from Zhejiang Provincial People's Hospital constituted the validation set. Subsequently, clinical parameters and ultrasound characteristics of the patients were collected. The diagnostic parameters were analyzed using the least absolute shrinkage and selection operator and multivariate logistic regression screening methods. Next, a comparative analysis was performed using seven ML models. The area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), precision, recall, and comprehensive evaluation index (F-score) were calculated to compare the diagnostic efficacy among the seven models and determine the optimal model. Further, the optimal model was validated, and the SHapley Additive ExPlanations (SHAP) approach was applied to explain the significance of the model variables. Finally, an individualized risk assessment was conducted. Results: Age, echogenicity, thyroglobulin antibody (TGAb), echotexture, composition, triiodothyronine (T3), thyroglobulin (TG), margin, thyroid-stimulating hormone (TSH), calcification, and halo thickness >2 mm were influential factors for diagnosing FTC. The XGBoost model was identified as the optimal model after a comprehensive evaluation. The AUC of this model in the validation set was 0.969 [95% confidence interval (CI), 0.946-0.992], while its precision sensitivity, specificity, and accuracy were 0.791, 0.930, 0.913 and 0.917, respectively. Conclusions: XGBoost model based on ultrasound features was constructed and interpreted using the SHAP method, providing evidence for the diagnosis of FTC and guidance for the personalized treatment of patients.

A Chronicle Review of In-Silico Approaches for Discovering Novel Antimicrobial Agents to Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) poses a foremost threat to global health, necessitating innovative strategies for discovering antimicrobial agents. This review explores the role and recent advances of in-silico techniques in identifying novel antimicrobial agents and combating AMR giving few briefings of recent case studies of AMR. In-silico techniques, such as homology modeling, virtual screening, molecular docking, pharmacophore modeling, molecular dynamics simulation, density functional theory, integrated machine learning, and artificial intelligence, are systematically reviewed for their utility in discovering antimicrobial agents. These computational methods enable the rapid screening of large compound libraries, prediction of drug-target interactions, and optimization of drug candidates. The review discusses integrating in-silico approaches with traditional experimental methods and highlights their potential to accelerate the discovery of new antimicrobial agents. Furthermore, it emphasizes the significance of interdisciplinary collaboration and data-sharing initiatives in advancing antimicrobial research. Through a comprehensive discussion of the latest developments in in-silico techniques, this review provides valuable insights into the future of antimicrobial research and the fight against AMR. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01355-x.

Effect of urban environment on cardiovascular health: a feasibility pilot study using machine learning to predict heart rate variability in patients with heart failure.

Aims: Urbanization is related to non-communicable diseases such as congestive heart failure (CHF). Understanding the influence of diverse living environments on physiological variables such as heart rate variability (HRV) in patients with chronic cardiac disease may contribute to more effective lifestyle advice and telerehabilitation strategies. This study explores how machine learning (ML) models can predict HRV metrics, which measure autonomic nervous system responses to environmental attributes in uncontrolled real-world settings. The goal is to validate whether this approach can ascertain and quantify the connection between environmental attributes and cardiac autonomic response in patients with CHF. Methods and results: A total of 20 participants (10 healthy individuals and 10 patients with CHF) wore smartwatches for 3 weeks, recording activities, locations, and heart rate (HR). Environmental attributes were extracted from Google Street View images. Machine learning models were trained and tested on the data to predict HRV metrics. The models were evaluated using Spearman's correlation, root mean square error, prediction intervals, and Bland-Altman analysis. Machine learning models predicted HRV metrics related to vagal activity well (R > 0.8 for HR; 0.8 > R > 0.5 for the root mean square of successive interbeat interval differences and the Poincaré plot standard deviation perpendicular to the line of identity; 0.5 > R > 0.4 for the high frequency power and the ratio of the absolute low- and high frequency power induced by environmental attributes. However, they struggled with metrics related to overall autonomic activity, due to the complex balance between sympathetic and parasympathetic modulation. Conclusion: This study highlights the potential of ML-based models to discern vagal dynamics influenced by living environments in healthy individuals and patients diagnosed with CHF. Ultimately, this strategy could offer rehabilitation and tailored lifestyle advice, leading to improved prognosis and enhanced overall patient well-being in CHF.

Identification and functional characterization of the npc-2-like domain containing rust effector protein that suppresses cell death in plants.

The MD-2-related lipid-recognition (ML/Md-2) domain is a lipid/sterol-binding domain that are involved in sterol transfer and innate immunity in eukaryotes. Here we report a genome-wide survey of this family, identifying 84 genes in 30 fungi including plant pathogens. All the studied species were found to have varied ML numbers, and expansion of the family was observed in Rhizophagus irregularis (RI) with 33 genes. The molecular docking studies of these proteins with cholesterol derivatives indicate lipid-binding functional conservation across the animal and fungi kingdom. The phylogenetic studies among eukaryotic ML proteins showed that Puccinia ML members are more closely associated with animal (insect) npc2 proteins than other fungal ML members. One of the candidates from leaf rust fungus Puccinia triticina, Pt5643 was PCR amplified and further characterized using various studies such as qRT-PCR, subcellular localization studies, yeast functional complementation, signal peptide validation, and expression studies. The Pt5643 exhibits the highest expression on the 5th day post-infection (dpi). The confocal microscopy of Pt5643 in onion epidermal cells and N. benthamiana shows its location in the cytoplasm and nucleus. The functional complementation studies of Pt5643 in npc2 mutant yeast showed its functional similarity to the eukaryotic/yeast npc2 gene. Furthermore, the overexpression of Pt5643 also suppressed the BAX, NEP1, and H2O2-induced program cell death in Nicotiana species and yeast. Altogether the present study reports the novel function of ML domain proteins in plant fungal pathogens and their possible role as effector molecules in host defense manipulation.

A robust deep learning attack immune MRAM-based physical unclonable function.

The ubiquitous presence of electronic devices demands robust hardware security mechanisms to safeguard sensitive information from threats. This paper presents a physical unclonable function (PUF) circuit based on magnetoresistive random access memory (MRAM). The circuit utilizes inherent characteristics arising from fabrication variations, specifically magnetic tunnel junction (MTJ) cell resistance, to produce corresponding outputs for applied challenges. In contrast to Arbiter PUF, the proposed effectively satisfies the strict avalanche criterion (SAC). Additionally, the grid-like structure of the proposed circuit preserves its resistance against machine learning-based modeling attacks. Various machine learning (ML) attacks employing multilayer perceptron (MLP), linear regression (LR), and support vector machine (SVM) networks are simulated for two-array and four-array architectures. The MLP-attack prediction accuracy was 53.61% for a two-array circuit and 49.87% for a four-array circuit, showcasing robust performance even under the worst-case process variations. In addition, deep learning-based modeling attacks in considerable high dimensions utilizing multiple networks such as convolutional neural network (CNN), recurrent neural network (RNN), MLP, and Larq are used with the accuracy of 50.31%, 50.25%, 50.31%, and 50.31%, respectively. The efficiency of the proposed circuit at the layout level is also investigated for simplified two-array architecture. The simulation results indicate that the proposed circuit offers intra and inter-hamming distance (HD) with a mean of 0.98% and 49.96%, respectively, and a mean diffuseness of 49.09%.

Machine learning prediction of no reflow in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background: No-reflow (NRF) phenomenon is a significant challenge in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Accurate prediction of NRF may help improve clinical outcomes of patients. This retrospective study aimed at creating an optimal model based on machine learning (ML) to predict NRF in these patients, with the additional objective of guiding pre- and intra-operative decision-making to reduce NRF incidence. Methods: Data were collected from 321 STEMI patients undergoing pPCI between January 2022 and May 2023, with the dataset being randomly divided into training and internal validation sets in a 7:3 ratio. Selected features included pre- and intra-operative demographic data, laboratory parameters, electrocardiogram, comorbidities, patients' clinical status, coronary angiographic data, and intraoperative interventions. Post comprehensive feature cleaning and engineering, three logistic regression (LR) models [LR-classic, LR-random forest (LR-RF), and LR-eXtreme Gradient Boosting (LR-XGB)], a RF model and an eXtreme Gradient Boosting (XGBoost) model were developed within the training set, followed by performance evaluation on the internal validation sets. Results: Among the 261 patients who met the inclusion criteria, 212 were allocated to the normal flow group and 49 to the NRF group. The training group consisted of 183 patients, while the internal validation group included 78 patients. The LR-XGB model, with an area under the curve (AUC) of 0.829 [95% confidence interval (CI): 0.779-0.880], was selected as the representative model for logistic regression analyses. The LR model had an AUC slightly lower than XGBoost model (AUC 0.835, 95% CI: 0.781-0.889) but significantly higher than RF model (AUC 0.731, 95% CI: 0.660-0.802). Internal validation underscored the unique advantages of each model, with the LR model demonstrating the highest clinical net benefit at relevant thresholds, as determined by decision curve analysis. The LR model encompassed seven meaningful features, and notably, thrombolysis in myocardial infarction flow after initial balloon dilation (TFAID) was the most impactful predictor in all models. A web-based application based on the LR model, hosting these predictive models, is available at https://l7173o-wang-lyn.shinyapps.io/shiny-1/. Conclusions: A LR model was successfully developed through ML to forecast NRF phenomena in STEMI patients undergoing pPCI. A web-based application derived from the LR model facilitates clinical implementation.

The Global Evolution and Impact of Systems Biology and Artificial Intelligence in Stem Cell Research and Therapeutics Development: A Scoping Review.

Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024. We identified an 8-10-fold increase in research output related to all three search terms between 2000 and 2021, with a 10-fold increase in AI-related production since 2010. Use of SysBio and AI still predominates in preclinical basic research with increasing use in clinically oriented translational medicine since 2010. SysBio- and AI-related research was found all over the globe, with SysBio output led by the United States (US, n=1487), United Kingdom (UK, n=1094), Germany (n=355), The Netherlands (n=339), Russia (n=215), and France (n=149), while for AI-related research the US (n=853) and UK (n=258) take a strong lead, followed by Switzerland (n=69), The Netherlands (n=37), and Germany (n=19). The US and UK are most active in SCs publications related to AI/ML and AI/DL. The prominent use of SysBio in ESC research was recently overtaken by prominent use of AI in iPSC and MSC research. This study reveals the global evolution and growing intersection between AI, SysBio, and SC research over the past two decades, with substantial growth in all three fields and exponential increases in AI-related research in the past decade.