<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.165575.2</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Deep learning based hybrid residual attention and echo state network for high-accuracy heart disease prediction</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 2; peer review: 1 approved, 1 approved with reservations, 1 not approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>D</surname>
                        <given-names>Cenitta</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3715-6941</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Ranganathan</surname>
                        <given-names>VIijaya Arjunan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1402-6573</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Shailesh</surname>
                        <given-names>Tanuja</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="corresp" rid="c2">b</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>J</surname>
                        <given-names>Andrew</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>N</surname>
                        <given-names>Arul</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>T</surname>
                        <given-names>Praveen Pai</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, India</aff>
                <aff id="a2">
                    <label>2</label>Computer Science and Engineering, AJ Institute of Engineering and Technology, Mangalore, Karnataka, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:vijay.arjun@manipal.edu">vijay.arjun@manipal.edu</email>
                </corresp>
                <corresp id="c2">
                    <label>b</label>
                    <email xlink:href="mailto:tanuja.s@manipal.edu">tanuja.s@manipal.edu</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>16</day>
                <month>9</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>650</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>10</day>
                    <month>9</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 D C et al.</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-650/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Early and accurate prediction of ischemic heart disease (IHD) is essential for reducing mortality and enabling timely intervention. Misdiagnosis can lead to severe health outcomes, emphasizing the need for robust and intelligent predictive models. Deep learning approaches have shown strong potential in identifying hidden patterns in medical data and aiding clinical decision-making.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This study proposes a novel Hybrid Residual Attention with Echo State Network (HRAESN) model that integrates Attention Residual Learning (ARL) with Echo State Networks (ESN) to enhance feature extraction and temporal data learning. The hybrid model is designed to refine feature attention through residual learning while leveraging ESN for efficient time-series prediction. Two publicly available benchmark datasets were used for evaluation: the Kaggle Cardiovascular Disease dataset comprising 70,000 instances and the UCI Heart Disease dataset containing 303 instances. Missing values in both datasets were handled using a multiple imputation technique tailored for ischemic heart disease. Model performance was assessed using standard classification metrics, including accuracy, sensitivity, specificity, precision, recall, and F-measure.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>The proposed HRAESN model demonstrated superior classification performance compared to traditional machine learning and deep learning approaches. It achieved an accuracy of 98.4% on the Kaggle dataset and 97.7% on the UCI dataset. Additionally, the model showed high sensitivity and specificity, indicating strong diagnostic capability and reliability in identifying both diseased and non-diseased cases.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>The HRAESN model effectively combines the strengths of residual attention mechanisms and echo state networks, resulting in improved accuracy and stability for ischemic heart disease prediction. Its strong performance on benchmark datasets confirms its potential as a valuable clinical decision support tool for early detection of IHD. Future work may focus on optimizing model complexity and integrating real-time medical IoT data to enhance practical deployment in healthcare systems.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>UCI</kwd>
                <kwd>Kaggle</kwd>
                <kwd>Heart Disease</kwd>
                <kwd>Imputation</kwd>
                <kwd>Deep Learning</kwd>
                <kwd>Echo State Network</kwd>
                <kwd>Residual Attention.</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
        <notes>
            <sec sec-type="version-changes">
                <label>Revised</label>
                <title>Amendments from Version 1</title>
                <p>In this revised version, we have substantially strengthened the methodological transparency, statistical rigor, and reproducibility of our study. The Introduction was rewritten for improved flow and updated to reflect current diagnostic practices in ischemic heart disease (IHD), replacing outdated modalities with contemporary techniques (cardiac CT, RbPET, coronary angiography). The Related Works section was streamlined and expanded to cover prior attention&#x2013;Echo State Network (ESN) combinations, thereby clarifying the novelty of our Hybrid Residual Attention with Echo State Network (HRAESN) model. In the Methods, we now provide detailed definitions of heart disease/IHD in the UCI and Kaggle datasets, describe missingness and imputation using the IHD Multiple Imputation Technique, and explain how ESNs were adapted for structured tabular data. Evaluation metrics, including Cohen&#x2019;s kappa and Jaccard index, are introduced earlier for consistency. To strengthen statistical robustness, we re-ran all experiments using 5-fold and 10-fold stratified cross-validation, reporting mean &#x00b1; standard deviation across folds. We added statistical significance testing (McNemar&#x2019;s test and Wilcoxon signed-rank) and expanded performance evaluation with ROC curves, AUC values, precision&#x2013;recall curves, and calibration plots. Confidence intervals (95%) were computed via bootstrap resampling. Figures and tables were revised to improve clarity: Figure captions specify dataset scope, confusion matrices now include raw counts, and baseline population characteristics are summarized in a new table. Comparative analysis was clarified to explain baseline method selection. The Discussion and Limitations were expanded to address external validation, imputation bias, dataset imbalance, and interpretability of the Attention Residual Learning module. Claims regarding clinical readiness were moderated to emphasize proof-of-concept status. Finally, to enhance reproducibility, we expanded algorithmic details of the imputation method and provide code availability upon request. Collectively, these revisions address reviewer feedback and significantly improve the rigor, transparency, and interpretability of our work.</p>
            </sec>
        </notes>
    </front>
    <body>
        <sec id="sec5" sec-type="intro">
            <title>1. Introduction</title>
            <p>Ischemic heart disease (IHD) arises when coronary arteries are narrowed or blocked, leading to reduced blood flow and oxygen supply to the heart muscle. Persistent restriction of coronary circulation results in myocardial ischemia, which can progress to coronary artery disease and, in severe cases, myocardial infarction. Silent ischemia, in particular, occurs without overt symptoms but still poses a high risk of sudden cardiac events, especially in individuals with diabetes or a prior history of heart attack. In current clinical practice, the diagnosis and assessment of IHD relies on advanced imaging and invasive modalities, including cardiac computed tomography (CT), Rubidium positron emission tomography (RbPET), and coronary angiography, which provide accurate evaluation of coronary artery stenosis and perfusion deficits. These methods, while effective, remain costly, invasive, and not always feasible for large-scale population screening, motivating the exploration of non-invasive, AI-based predictive approaches for early detection.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup>
            </p>
            <p>The World Health Organization (WHO) reports that cardiovascular diseases (CVDs) continue as the main cause of global mortality since 17.9 million people died from CVDs in 2019 which amounted to 32% of worldwide fatalities. Heart attacks and strokes lead to 85% of fatal outcomes among the tested patients.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> The worldwide fatalities from noncommunicable diseases reached 17 million during 2019 before people turned 70 years old and cardiovascular conditions caused 38% of those premature deaths. Medical detection of CVDs remains vital because behavioral prevention through risk control methods such as smoking and food control and weight management cannot substitute for early medical discovery to achieve both effective treatment and lower mortality rates. Heart disease poses a major financial challenge and increasing health burden because of high surgical expenses and rising population incidence mainly affecting developing countries. Knowledge about how patient characteristics link to heart disease risk serves as the basis for preventing the condition and detecting it early for treatment purposes.</p>
            <p>Deep learning has become an integral part of computer vision, object recognition, natural language processing, speech recognition, medical diagnostics, bioinformatics, and drug discovery. Similar to traditional artificial neural networks (ANNs), deep learning models consist of input, hidden, and output layers, with patient risk factors serving as input features. The research demonstrates that artificial neural networks deliver outstanding results when used for identifying and foretelling coronary heart disease.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Medical AI applications experience rapid growth because of three main factors including Internet of Things (IoT) and powerful computing hardware (e.g., GPUs and TPUs) together with big medical datasets. Essential information needed by deep learning models comes from Medical IoT devices together with electronic health records as well as genomic data and central medical databases. The critical challenges include preserving data privacy as well as successfully deploying the models and optimizing service quality despite their importance.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>Time-series prediction has seen increased popularity among researchers who use recurrent neural networks (RNNs) as deep learning-based approaches. RNNs work with sequential data sets through the process of feeding output data from previous components to next steps making them ideal for ECG signal processing and patient health surveillance. RNNs differ from regular neural networks by retaining previous input data thus they produce enhanced forecasts for temporal information patterns. Traditional RNNs experience gradient vanishing problems because of which they become problematic for handling long sequences. The development of both Hochreiter and Schmidhuber led to long short-term memory (LSTM) networks which incorporated memory gates to control information transmission and suppress gradient deterioration.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
            <p>Time-series extrapolation along with fast learning occurs efficiently through Echo State Networks (ESN) which function as a preferred substitute to normal RNNs.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> An Echo State Network functions through its reservoir of recurrent neurons connected haphazardly that helps the network learn complex patterns yet uses few processing resources. The forecast capabilities of time-series prediction and representation learning capabilities improve through the use of Deep ESNs (DESNs) that include multiple serially connected reservoirs.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup>
            </p>
            <p>A transformation of conventional convolutional neural networks (CNNs) called Residual Attention Network brings attention mechanism integration for feature enhancement.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> The advanced feed-forward framework permits end-to-end training which enables it to learn hierarchical features independently. Gremlin Deep Residual Attention Networks provide an efficient mechanism for deep learning systems to reach hundreds of layers through their implementation of Attention Residual Learning (ARL).
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup> Different algorithms can achieve maximum strength performance through hybrid deep learning models which integrate multiple techniques. Medical diagnostic accuracy along with efficiency can experience significant improvement by combining residual attention learning methods with Echo State Networks. The appropriate addressing of missing values through the Ischemic Heart Disease Multiple Imputation Technique creates improved data reliability and completeness.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup>
            </p>
            <sec id="sec6">
                <title>1.1 Objective of this study</title>
                <p>The main goal of this research work is to create a Hybrid Residual Attention with Echo State Network (HRAESN) model used to predict ischemic heart disease (IHD) at an early stage while maintaining high accuracy. The proposed method integrates Residual Attention Learning (RAL) with Echo State Networks (ESNs) to boost both feature extraction and time-series classification and general model performance. This study solves data preprocessing problems with Ischemic Heart Disease Multiple Imputation Technique while using hybrid deep learning effectively for robust classification. The research uses two recognized heart disease data sets including 70,000 records from the Kaggle Cardiovascular Disease dataset and 303 records from the UCI Heart Disease dataset to evaluate the proposed method. The objective is to prove that this approach outperforms current state-of-the-art heart disease prediction methods. ART-based analysis findings will enhance clinical diagnosis along with IHD detection and patient care through AI-powered diagnostic systems.</p>
                <p>The following research questions are the focus of the study&#x2019;s search and synthesis of the literature.
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>How do deep learning models, particularly Echo State Networks (ESNs) and Residual Attention Learning (RAL), improve the accuracy and stability of ischemic heart disease prediction compared to traditional machine learning approaches?</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>What are the key challenges associated with handling missing data in medical datasets, and how can the Ischemic Heart Disease Multiple Imputation Technique enhance data completeness and reliability?</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>How does the proposed Hybrid Residual Attention with Echo State Network (HRAESN) model perform on benchmark datasets (Kaggle Cardiovascular Disease and UCI Heart Disease) compared to existing state-of-the-art heart disease prediction models?</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec7">
                <title>1.2 Problem statement</title>
                <p>One of the main causes of death is ischemic heart disease (IHD), which needs to be predicted early and accurately in order to be effectively treated. While current machine learning models have trouble managing missing data, time-series dependencies, and computational inefficiencies, traditional diagnostic techniques are costly, time-consuming, and rely on expert interpretation. Vanishing gradients and high complexity are two drawbacks of deep learning techniques like recurrent neural networks (RNNs) and long short-term memory (LSTM) networks. To address these challenges, this study proposes a Hybrid Residual Attention with Echo State Network (HRAESN) model, integrating Residual Attention Learning (RAL) for feature extraction and Echo State Networks (ESNs) for efficient time-series processing, ensuring improved predictive accuracy and robustness.</p>
            </sec>
        </sec>
        <sec id="sec8">
            <title>2. Related works</title>
            <p>Numerous studies have explored machine learning (ML) and deep learning (DL) techniques for cardiovascular disease prediction. Traditional ML methods such as Decision Trees, Random Forests, Na&#x00ef;ve Bayes, and Support Vector Machines have shown moderate success but often struggle with missing data, feature complexity, and generalization.
                <sup>
                    <xref ref-type="bibr" rid="ref27">10</xref>
                </sup>
                <sup>&#x2013;</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref30">13</xref>
                </sup>
            </p>
            <p>Deep learning models, particularly Recurrent Neural Networks (RNNs) and Long Short-Term Memory (LSTM) architectures, have been widely applied to ECG-based diagnosis and patient monitoring, achieving improved accuracy in handling sequential data.
                <sup>
                    <xref ref-type="bibr" rid="ref25">14</xref>
                </sup> Hybrid RNN&#x2013;LSTM models, for example, demonstrated higher classification performance than standalone approaches.
                <sup>
                    <xref ref-type="bibr" rid="ref25">14</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref26">15</xref>
                </sup>
            </p>
            <p>Echo State Networks (ESNs) and related reservoir computing methods have also been applied in cardiovascular applications due to their efficiency in time-series prediction. Li et al.
                <sup>
                    <xref ref-type="bibr" rid="ref10">16</xref>
                </sup> showed effective heartbeat classification using a residual squeeze-and-excitation framework, while Gao et al.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> and Sun et al.
                <sup>
                    <xref ref-type="bibr" rid="ref12">17</xref>
                </sup> combined ESNs with wavelet transformation and Deep Belief Networks, respectively, to improve temporal modeling. Optimized ESN variants, including bidirectional
                <sup>
                    <xref ref-type="bibr" rid="ref16">18</xref>
                </sup> and adaptive evolutionary models,
                <sup>
                    <xref ref-type="bibr" rid="ref17">19</xref>
                </sup>
                <sup>&#x2013;</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref19">21</xref>
                </sup> have further enhanced performance, and hardware-efficient ESN implementations have demonstrated low-power solutions for clinical settings.
                <sup>
                    <xref ref-type="bibr" rid="ref21">22</xref>
                </sup>
            </p>
            <p>Attention mechanisms and residual learning have similarly strengthened feature representation in medical tasks. Residual Attention Graph Convolutional Networks
                <sup>
                    <xref ref-type="bibr" rid="ref13">23</xref>
                </sup> and deep residual attention models
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref22">24</xref>
                </sup> and Residual Attention Graph Convolutional Networks
                <sup>
                    <xref ref-type="bibr" rid="ref11">25</xref>
                </sup> demonstrated improvements in complex classification tasks. Feature refinement approaches such as Recursion-Enhanced Random Forest
                <sup>
                    <xref ref-type="bibr" rid="ref23">26</xref>
                </sup> and SVM-based ensembles with feature elimination
                <sup>
                    <xref ref-type="bibr" rid="ref24">27</xref>
                </sup> have also been explored for cardiovascular disease detection.</p>
            <p>Hybrid frameworks that combine different learning paradigms have become increasingly popular. Examples include CNN&#x2013;reservoir computing hybrids,
                <sup>
                    <xref ref-type="bibr" rid="ref15">28</xref>
                </sup> CNN&#x2013;reservoir computing hybrids,
                <sup>
                    <xref ref-type="bibr" rid="ref14">29</xref>
                </sup> clustering-enhanced prediction models,
                <sup>
                    <xref ref-type="bibr" rid="ref30">13</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref26">15</xref>
                </sup> and DBN&#x2013;RNN integrations optimized by metaheuristics.
                <sup>
                    <xref ref-type="bibr" rid="ref20">30</xref>
                </sup> Ensemble-based strategies, including two-tier classifiers and hybrid Random Forest/Gradient Boosting methods, have further improved classification outcomes.
                <sup>
                    <xref ref-type="bibr" rid="ref38">31</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref43">32</xref>
                </sup>
            </p>
            <p>Overall, existing studies highlight three main trends: (i) ESNs provide efficient temporal modelling for cardiovascular data, (ii) attention-based residual learning enhances feature extraction, and (iii) hybrid frameworks that integrate these methods yield superior predictive accuracy. Building on these findings, our proposed HRAESN model integrates Residual Attention Learning with ESNs to address limitations in prior models and achieve higher accuracy, stability, and robustness in ischemic heart disease prediction.</p>
        </sec>
        <sec id="sec9">
            <title>3. Materials and methods</title>
            <sec id="sec10">
                <title>3.1 Dataset</title>
                <p>This study utilizes data from two publicly available repositories: Kaggle and the UCI (University of California, Irvine) Machine Learning Repository. These datasets provide comprehensive patient records used for cardiovascular disease prediction and ischemic heart disease classification.</p>
                <p>

                    <bold>3.1.1 Kaggle cardiovascular disease dataset</bold>
                </p>
                <p>There are 70,000 patient records with 11 distinct features in the Kaggle Cardiovascular Disease dataset.
                    <sup>
                        <xref ref-type="bibr" rid="ref31">33</xref>
                    </sup> When medical practitioners performed clinical examinations, these characteristics were noted. Three types of input features make up the dataset:

                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>Objective Characteristics (Real patient data): Gender, Age, Height, and Weight</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>Features of the Examination (Medical Test Results): Blood Pressure Systolic and Diastolic, Blood Pressure Levels of Cholesterol and Glucose</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>Subjective Features (patient data as self-reported): Alcohol use, smoking, and physical activity</p>
                        </list-item>
                    </list>
                </p>
                <p>

                    <bold>3.1.2 UCI heart disease dataset</bold>
                </p>
                <p>The UCI Heart Disease dataset contains 76 features, of which 14 are highly relevant for heart disease diagnosis.
                    <sup>
                        <xref ref-type="bibr" rid="ref32">34</xref>
                    </sup> The predictive class attribute is typically listed last, indicating the presence or absence of heart disease. 
                    <xref ref-type="table" rid="T1">
Table 1</xref> and 
                    <xref ref-type="table" rid="T2">
Table 2</xref> provide detailed descriptions of the dataset attributes.</p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>
Table 1. </label>
                    <caption>
                        <title>Kaggle cardiovascular disease dataset description.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Attribute</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Description</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Age</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Objective Feature|age|int (days)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Height</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Objective Feature|height|int (cm)|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Objective Feature|weight|float (kg)|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Gender</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Objective Feature|gender|categorical code|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Systolic blood pressure</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Examination Feature|ap_hi|int|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Diastolic blood pressure</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Examination Feature|ap_lo|int|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Cholesterol</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Examination Feature|cholesterol|
                                    <break/>

                                    <p>

                                        <list list-type="order">
                                            <list-item>
                                                <label>1:</label>
                                                <p>normal,</p>
                                            </list-item>
                                            <list-item>
                                                <label>2:</label>
                                                <p>above normal,</p>
                                            </list-item>
                                            <list-item>
                                                <label>3:</label>
                                                <p>well above normal</p>
                                            </list-item>
                                        </list>
                                    </p>
</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Glucose</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Examination Feature|gluc|
                                    <break/>

                                    <p>

                                        <list list-type="order">
                                            <list-item>
                                                <label>1:</label>
                                                <p>normal,</p>
                                            </list-item>
                                            <list-item>
                                                <label>2:</label>
                                                <p>above normal,</p>
                                            </list-item>
                                            <list-item>
                                                <label>3:</label>
                                                <p>well above normal</p>
                                            </list-item>
                                        </list>
                                    </p>
</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Smoking</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Subjective Feature|smoke|binary|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Alcohol intake</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Subjective Feature|alco|binary|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Physical activity</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Subjective Feature|active|binary|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Presence or absence of cardiovascular disease</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Target Variable|cardio|binary|</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <table-wrap id="T2" orientation="portrait" position="float">
                    <label>
Table 2. </label>
                    <caption>
                        <title>UCI heart disease dataset description.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Attribute</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Description</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Domain of value</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Age</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Age in year</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">29 to 77</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="top">Sex</td>
                                <td align="left" colspan="1" rowspan="2" valign="top">Sex</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Male (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Female (0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="4" valign="top">Cp</td>
                                <td align="left" colspan="1" rowspan="4" valign="top">Chest pain type</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Typical angina (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Atypical angina (2)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Non-anginal (3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Asymptomatic (4)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Trestbps</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Resting blood sugar</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">94 to 200 mm Hg</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Chol</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Serum cholesterol</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">126 to 564 mg/dl</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="3" valign="top">Fbs</td>
                                <td align="left" colspan="1" rowspan="3" valign="top">Fasting blood sugar</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;120 mg/dl</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">True (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">False (0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="4" valign="top">Restecg</td>
                                <td align="left" colspan="1" rowspan="4" valign="top">Resting ECG result</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Normal (0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">ST-T wave</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Abnormality (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">LV hypertrophy (2)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Thalach</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Maximum heart rate achieved</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">71 to 202</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="top">Exang</td>
                                <td align="left" colspan="1" rowspan="2" valign="top">Exercise induced angina</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Yes (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">No (0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Oldpeak</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">ST depression induced by exercise relative to rest</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0 to 6.2</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="3" valign="top">Slope</td>
                                <td align="left" colspan="1" rowspan="3" valign="top">Slope of peak exercise ST segment</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Upsloping (1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Flat (2)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Downsloping (3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Ca</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Number of major vessels coloured by fluoroscopy</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0 &#x2013; 3</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="3" valign="top">Thal</td>
                                <td align="left" colspan="1" rowspan="3" valign="top">Defect type</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Normal (3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Fixed defect (6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Reversible defect (7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Num</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Heart disease</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0-4</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>

                    <bold>3.1.3 Datasets and ethical considerations</bold>
                </p>
                <p>This study utilizes two publicly available datasets: the Heart Disease dataset from the UCI Machine Learning Repository and the Cardiovascular Disease dataset from Kaggle. These datasets contain anonymized patient records and are publicly released for academic and research purposes.</p>
                <p>

                    <bold>3.1.4 Ethical approval statement</bold>
                </p>
                <p>As this research involves only the use of publicly accessible, anonymized datasets, no formal ethical approval was required. The study complies with the ethical principles outlined in the Declaration of Helsinki. No intervention or interaction with human subjects occurred.</p>
                <p>

                    <bold>3.1.5 Informed consent statement</bold>
                </p>
                <p>Because this study used pre-existing anonymized data from public repositories, informed consent from participants was not required. All necessary ethical permissions and participant consents were obtained by the original data providers as per their respective institutional and data-sharing policies.</p>
                <p>

                    <bold>3.1.6 Definition of heart disease in the datasets</bold>
                </p>
                <p>In the UCI Heart Disease dataset, the target variable &#x201c;num&#x201d; (values 0&#x2013;4) indicates the severity of disease as determined by coronary angiography. For this study, we followed prior works
                    <sup>
                        <xref ref-type="bibr" rid="ref38">31</xref>
                    </sup>
                    <sup>,</sup>
                    <sup>
                        <xref ref-type="bibr" rid="ref32">34</xref>
                    </sup>
                    <sup>&#x2013;</sup>
                    <sup>
                        <xref ref-type="bibr" rid="ref37">37</xref>
                    </sup> and binarised the variable: 0 = absence of disease, 1&#x2013;4 = presence of heart disease. In the Kaggle Cardiovascular Disease dataset, the binary target variable &#x201c;cardio&#x201d; was defined during the original data collection based on combined clinical assessment and diagnostic test results (blood pressure, cholesterol, ECG). Here, 0 = healthy and 1 = diagnosed cardiovascular disease.</p>
                <p>

                    <bold>3.1.7 Dataset inclusion and missing values</bold>
                </p>
                <p>All available records were included: 70,000 instances in the Kaggle dataset and 303 in the UCI dataset. The Kaggle dataset contained ~0.3% missing values across features, while the UCI dataset had six missing entries. These were imputed using the Ischemic Heart Disease Multiple Imputation Technique,
                    <sup>
                        <xref ref-type="bibr" rid="ref9">9</xref>
                    </sup> ensuring that no records were discarded and data completeness was preserved.</p>
                <p>To ensure that our training and testing sets were representative, we verified that baseline characteristics (age, sex, cholesterol, and blood pressure) were similarly distributed between the two subsets. 
                    <xref ref-type="table" rid="T3">Table 3</xref> presents the distributions of these key features for both training and testing populations in the UCI and Kaggle datasets.</p>
                <table-wrap id="T3" orientation="portrait" position="float">
                    <label>Table 3. </label>
                    <caption>
                        <title>Baseline characteristics of training and testing populations for the UCI Heart Disease and Kaggle Cardiovascular Disease datasets.</title>
                        <p>Values are mean &#x00b1; SD for continuous variables and % for categorical variables.</p>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Variable</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">UCI Train (n=242)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">UCI Test (n=61)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Kaggle Train (n=56,000)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Kaggle Test (n=14,000)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Age (years)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">54.3 &#x00b1; 9.2</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">54.7 &#x00b1; 8.9</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">54.3 &#x00b1; 6.7*</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">54.3 &#x00b1; 6.8*</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Male (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">68.20%</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">68.90%</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">34.90%</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">35.10%</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Cholesterol (mg/dl)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">244.9 &#x00b1; 47.8</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">251.7 &#x00b1; 65.5</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2013;</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2013;</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Systolic BP (mmHg)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">131.7 &#x00b1; 18.0</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">131.3 &#x00b1; 15.7</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">129.0 &#x00b1; 161.6</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">127.9 &#x00b1; 119.2</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Cholesterol categories
                                    <sup>&#x2020;</sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2013;</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2013;</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1 = 74.8%, 2 = 13.7%, 3 = 11.5%</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1 = 74.9%, 2 = 13.5%, 3 = 11.6%</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
            </sec>
            <sec id="sec11">
                <title>3.2 Hybrid data classification algorithm</title>
                <p>The classification of ischemic heart disease (IHD) in this study is based on a hybrid deep learning model that integrates machine learning (ML), soft computing techniques, and optimization methods to enhance accuracy and robustness. Different classification models are created by integrating various ML methods and ensemble learning methods that involve bagging and boosting. Multiple classifiers work together in ensemble methods to generate better generalization as well as decrease overfitting.</p>
                <p>HRAESN model combines the following key elements:
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>Echo State Networks (ESNs) for efficient time-series processing</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>Attention Residual Learning (ARL) for enhanced feature extraction</p>
                        </list-item>
                    </list>
                </p>
                <p>By combining ESN and ARL, the model achieves higher accuracy, better generalization, and improved stability compared to conventional ML classifiers.</p>
            </sec>
            <sec id="sec12">
                <title>3.3 Echo State Network (ESN)</title>
                <p>Echo State Networks (ESNs), a subset of recurrent neural networks (RNNs) created for effective sequential data processing, are a part of the reservoir computing paradigm. In contrast to conventional RNNs, an ESN&#x2019;s hidden layer (reservoir) is fixed and randomly initialized, whereas only the output layer is trained.</p>
                <p>Key features of ESNs include:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>The reservoir exhibits two weight sets which are fixed by random values without training: W_in for input-to-lateral connections and W_r for lateral connections.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>During ESN operation researchers only train output weights but maintain simple computational design for efficient pattern learning capability.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>The hidden layer connectivity of ESNs remains sparse which decreases computational complexity.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Nonlinear Embedding: The reservoir state provides a nonlinear transformation of input data, which can then be mapped to the desired output using a trainable readout layer.</p>
                            <p>Since ESNs retain past information in a fixed reservoir, they are highly effective for time-series forecasting and real-time signal processing, making them a suitable choice for ischemic heart disease prediction.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec13">
                <title>3.4 Attention Residual Learning (ARL)</title>
                <p>Attention Residual Learning (ARL) is a deep learning technique that enhances feature extraction by selectively focusing on relevant information while reducing noise in deep neural networks. It is particularly beneficial in medical image analysis and time-series classification.</p>
                <p>Key challenges in deep residual networks include:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Performance Degradation: Stacking multiple narrow attention modules can lead to a decline in performance.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Feature Suppression: Soft mask layers may inadvertently reduce the importance of relevant features.</p>
                        </list-item>
                    </list>
                </p>
                <p>To address these issues, ARL modifies feature representation using an attention mask. The transformation is mathematically represented as:
                    <disp-formula id="e1">

                        <mml:math display="block">
                            <mml:msub>
                                <mml:mi>H</mml:mi>
                                <mml:mi>i</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo>+</mml:mo>
                                <mml:msub>
                                    <mml:mi>M</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>&#x2217;</mml:mo>
                            <mml:msubsup>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                                <mml:mi>i</mml:mi>
                            </mml:msubsup>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>
</disp-formula>
                </p>
                <p>Where:</p>
                <p>i: Index position in the input matrix</p>
                <p>M
                    <sub>i</sub> (t): Gradient of the input feature mask during the t-th iteration</p>
                <p>H
                    <sub>i</sub> (t+1): Updated attention module output at the (t+1)-th iteration</p>
                <p>This formulation ensures that:
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>Relevant features are amplified, while irrelevant features are suppressed.</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>Deep residual networks maintain stable performance even with hundreds of layers.</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>Computational efficiency is preserved without significantly increasing model complexity.</p>
                        </list-item>
                    </list>
                </p>
                <p>The integration of ESNs with ARL enables the proposed HRAESN model to merge its time-series learning functionality with attention-based feature refinement that results in precise and stable outcomes for ischemic heart disease predictions.</p>
            </sec>
            <sec id="sec14">
                <title>3.5 Methodology</title>
                <p>The prediction model utilizes heart disease records from UCI Heart Disease Data Set and the Cardiovascular Disease dataset from Kaggle. Pre-processing starts with performing the Ischemic Heart Disease Multiple Imputation Technique to identify and imputation missing values before proceeding further.
                    <sup>
                        <xref ref-type="bibr" rid="ref1">1</xref>
                    </sup> The HRAESN model combines Echo State Networks (ESNs) for short-term memory processing with Attention Residual Learning (ARL) for enhancing features to classify heart disease.</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>
Figure 1. </label>
                    <caption>
                        <title>Workflow of the proposed experiment using the UCI Heart Disease and Kaggle Cardiovascular Disease datasets.</title>
                        <p>Workflow of the proposed experiment using the UCI Heart Disease (303 records, 14 features, 6 missing values) and Kaggle Cardiovascular Disease dataset (70,000 records, 11 features, ~0.3% missing values). Missing values were imputed using the Ischemic Heart Disease Multiple Imputation Technique. Labels were defined as binary: UCI &#x201c;num&#x201d; attribute (0 = healthy, 1&#x2013;4 = disease present, recoded to 0/1) and Kaggle &#x201c;cardio&#x201d; attribute (0 = healthy, 1 = disease present). The preprocessed datasets were fed into the HRAESN model, combining Echo State Networks for reservoir-based representation of clinical features with Attention Residual Learning for enhanced feature selection. Model training and evaluation used an 80:20 split, with multiple performance metrics reported.</p>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>
Figure 2. </label>
                    <caption>
                        <title>Overall system model of the proposed Hybrid Residual Attention with Echo State Network (HRAESN).</title>
                        <p>Patient data (70,000 Kaggle records, 303 UCI records) were preprocessed and imputed before being passed into an Echo State Network reservoir, which captures nonlinear feature interactions. The reservoir outputs were refined using Attention Residual Learning, which selectively enhances relevant clinical patterns while suppressing noise. A final sigmoid activation layer produces binary predictions (0 = healthy, 1 = ischemic heart disease). This architecture leverages ESN efficiency and attention-driven feature refinement for improved classification accuracy.</p>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure2.gif"/>
                </fig>
                <p>

                    <italic toggle="yes">Experiment workflow</italic>

                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>Load and preprocess datasets: The Heart Disease Data Set and Cardiovascular Disease dataset are loaded, and missing values are imputed using the Ischemic Heart Disease Multiple Imputation Technique.
                                <sup>
                                    <xref ref-type="bibr" rid="ref9">9</xref>,
                                    <xref ref-type="bibr" rid="ref33">38</xref>
                                </sup>
                            </p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>Feature extraction and classification: The HRAESN model applies ESNs for sequence modeling and ARL for refining feature representation.</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>Model evaluation: A confusion matrix assesses the model&#x2019;s performance, ensuring accurate classification of heart disease cases.</p>
                        </list-item>
                    </list>
                </p>
                <p>

                    <bold>3.5.1 Hybrid Residual Attention with Echo State Network (HRAESN) algorithm</bold>
                </p>
                <p>The input feature matrix (X
                    <sub>F</sub>) is obtained from the Ischemic Heart Disease Multiple Imputation Technique and labeled according to class 0 (normal) or class 1 (heart disease).</p>
                <p>

                    <bold>Echo State Network (ESN) Hidden Layer Dynamics</bold>

                    <disp-formula id="e2">

                        <mml:math display="block">
                            <mml:msub>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>f</mml:mi>
                                <mml:mi>a</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msup>
                                <mml:mi>u</mml:mi>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>+</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>r</mml:mi>
                                </mml:msup>
                                <mml:msub>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(1)</label>
</disp-formula>
                </p>
                <p>Where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>X</mml:mi>
                                            <mml:mi>F</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo>+</mml:mo>
                                            <mml:mn>1</mml:mn>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> and 
                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>X</mml:mi>
                                            <mml:mi>F</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> are the feature matrices at iterations t and t + 1.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msup>
                                            <mml:mi>W</mml:mi>
                                            <mml:mi>i</mml:mi>
                                        </mml:msup>
                                    </mml:math>
</inline-formula> is the input reservoir weight matrix derived from the input data.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msup>
                                            <mml:mi>W</mml:mi>
                                            <mml:mi>r</mml:mi>
                                        </mml:msup>
                                    </mml:math>
</inline-formula> is the reservoir weight matrix representing internal states.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:mi>u</mml:mi>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo>+</mml:mo>
                                            <mml:mn>1</mml:mn>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> represents the internal states computed at iteration t.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>f</mml:mi>
                                            <mml:mi>a</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mo>.</mml:mo>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> is the activation function applied at the reservoir.</p>
                        </list-item>
                    </list>
                </p>
                <p>

                    <bold>Attention Residual Learning (ARL) transformation</bold>

                    <disp-formula id="e3">

                        <mml:math display="block">
                            <mml:msub>
                                <mml:mi>H</mml:mi>
                                <mml:mi>i</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo>+</mml:mo>
                                <mml:msub>
                                    <mml:mi>M</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>&#x2217;</mml:mo>
                            <mml:msubsup>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                                <mml:mi>i</mml:mi>
                            </mml:msubsup>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(2)</label>
</disp-formula>
                </p>
                <p>Where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:mi>i</mml:mi>
                                    </mml:math>
</inline-formula> represents the input matrix&#x2019;s index positions.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>M</mml:mi>
                                            <mml:mi>i</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> is the gradient of the input feature mask at iteration t.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>H</mml:mi>
                                            <mml:mi>i</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo>+</mml:mo>
                                            <mml:mn>1</mml:mn>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> is the attention module output at iteration t + 1.</p>
                        </list-item>
                    </list>
                </p>
                <p>The reservoirs in HRAESN are linked in series, meaning each reservoir state depends on the previous reservoir&#x2019;s output and its own past state:
                    <disp-formula id="e4">

                        <mml:math display="block">
                            <mml:msubsup>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                                <mml:mn>1</mml:mn>
                            </mml:msubsup>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>f</mml:mi>
                                <mml:mi>a</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msup>
                                <mml:mi>u</mml:mi>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>+</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mn>1</mml:mn>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mn>1</mml:mn>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(3)</label>
</disp-formula>

                    <disp-formula id="e5">

                        <mml:math display="block">
                            <mml:msubsup>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                                <mml:mn>2</mml:mn>
                            </mml:msubsup>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>f</mml:mi>
                                <mml:mi>a</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mn>1</mml:mn>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>+</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mn>2</mml:mn>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mn>2</mml:mn>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(4)</label>
</disp-formula>

                    <disp-formula id="e6">

                        <mml:math display="block">
                            <mml:msubsup>
                                <mml:mi>X</mml:mi>
                                <mml:mi>F</mml:mi>
                                <mml:mi>M</mml:mi>
                            </mml:msubsup>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>f</mml:mi>
                                <mml:mi>a</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>M</mml:mi>
                                        <mml:mo>&#x2212;</mml:mo>
                                        <mml:mn>1</mml:mn>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>+</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>M</mml:mi>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mi>M</mml:mi>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(5)</label>
</disp-formula>
                </p>
                <p>Where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msup>
                                            <mml:mi>W</mml:mi>
                                            <mml:mi>i</mml:mi>
                                        </mml:msup>
                                        <mml:mo>=</mml:mo>
                                        <mml:msub>
                                            <mml:mi>H</mml:mi>
                                            <mml:mi>i</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mi>t</mml:mi>
                                            <mml:mo>+</mml:mo>
                                            <mml:mn>1</mml:mn>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> represents the attention module output.</p>
                        </list-item>
                    </list>
                </p>
                <p>Activation Functions and Output Computation
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>Final Activation Function</p>
                        </list-item>
                    </list>

                    <disp-formula id="e7">

                        <mml:math display="block">
                            <mml:msub>
                                <mml:mi>A</mml:mi>
                                <mml:mi>n</mml:mi>
                            </mml:msub>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>Y</mml:mi>
                                <mml:mi>L</mml:mi>
                            </mml:msub>
                            <mml:mo>&#x00b7;</mml:mo>
                            <mml:mtext mathvariant="italic">sigmoid</mml:mtext>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mi>M</mml:mi>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(6)</label>
</disp-formula>
                </p>
                <p>Where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:mtext mathvariant="italic">sigmoid</mml:mtext>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mo>.</mml:mo>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> is the activation function applied to the final output layer.</p>
                        </list-item>
                    </list>
                </p>
                <p>Dynamic Echo State Network Output
                    <disp-formula id="e8">

                        <mml:math display="block">
                            <mml:msub>
                                <mml:mi>P</mml:mi>
                                <mml:mi>R</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:mi>t</mml:mi>
                                <mml:mo>+</mml:mo>
                                <mml:mn>1</mml:mn>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                            <mml:mo>=</mml:mo>
                            <mml:msub>
                                <mml:mi>g</mml:mi>
                                <mml:mi>a</mml:mi>
                            </mml:msub>
                            <mml:mrow>
                                <mml:mo stretchy="true">(</mml:mo>
                                <mml:msup>
                                    <mml:mi>W</mml:mi>
                                    <mml:mi>o</mml:mi>
                                </mml:msup>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mi>M</mml:mi>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo stretchy="true">)</mml:mo>
                            </mml:mrow>
                        </mml:math>

                        <label>(7)</label>
</disp-formula>
                </p>
                <p>Where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msup>
                                            <mml:mi>W</mml:mi>
                                            <mml:mi>o</mml:mi>
                                        </mml:msup>
                                    </mml:math>
</inline-formula> represents the output reservoir weight matrix.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <inline-formula>

                                    <mml:math display="inline">
                                        <mml:msub>
                                            <mml:mi>g</mml:mi>
                                            <mml:mi>a</mml:mi>
                                        </mml:msub>
                                        <mml:mrow>
                                            <mml:mo stretchy="true">(</mml:mo>
                                            <mml:mo>.</mml:mo>
                                            <mml:mo stretchy="true">)</mml:mo>
                                        </mml:mrow>
                                    </mml:math>
</inline-formula> is the final activation function used at step 4.</p>
                        </list-item>
                    </list>
                </p>
                <boxed-text id="B1" orientation="portrait" position="float">
                    <label>Algorithm. </label>
                    <caption>
                        <title>Hybrid Residual Attention with Echo State Network (HRAESN).</title>
                    </caption>
                    <p>

                        <bold>Input:</bold> features data 
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msub>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                </mml:msub>
                            </mml:math>
</inline-formula>, label data 
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msub>
                                    <mml:mi>Y</mml:mi>
                                    <mml:mi>L</mml:mi>
                                </mml:msub>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>

                        <bold>Output:</bold> Predicted result P
                        <sub>r</sub>
                    </p>
                    <p>1: 
                        <bold>begin</bold>
                    </p>
                    <p>2:&#x2003;
                        <bold>for each</bold> Compute the Hidden layer of dynamic ESN</p>
                    <p>3:&#x2003;&#x2003;
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msub>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>=</mml:mo>
                                <mml:msub>
                                    <mml:mi>f</mml:mi>
                                    <mml:mi>a</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>i</mml:mi>
                                    </mml:msup>
                                    <mml:mi>u</mml:mi>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo>+</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>r</mml:mi>
                                    </mml:msup>
                                    <mml:msub>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                    </mml:msub>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>4:&#x2003;
                        <bold>end for</bold>
                    </p>
                    <p>5:&#x2003;
                        <bold>for each</bold> compute the attention residual learning</p>
                    <p>6:&#x2003;&#x2003;
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msub>
                                    <mml:mi>H</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>=</mml:mo>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo>+</mml:mo>
                                    <mml:msub>
                                        <mml:mi>M</mml:mi>
                                        <mml:mi>i</mml:mi>
                                    </mml:msub>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>&#x2217;</mml:mo>
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mi>i</mml:mi>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>7:&#x2003;
                        <bold>end for</bold>
                    </p>
                    <p>8:&#x2003;
                        <bold>for</bold> x=1 to M 
                        <bold>do:</bold>
                    </p>
                    <p>9:&#x2003;&#x2003;
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mn>1</mml:mn>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>=</mml:mo>
                                <mml:msub>
                                    <mml:mi>f</mml:mi>
                                    <mml:mi>a</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>i</mml:mi>
                                    </mml:msup>
                                    <mml:mi>u</mml:mi>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo>+</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mn>1</mml:mn>
                                    </mml:msup>
                                    <mml:msubsup>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                        <mml:mn>1</mml:mn>
                                    </mml:msubsup>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>10:&#x2003;&#x2003;
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mn>2</mml:mn>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>=</mml:mo>
                                <mml:msub>
                                    <mml:mi>f</mml:mi>
                                    <mml:mi>a</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>i</mml:mi>
                                    </mml:msup>
                                    <mml:msubsup>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                        <mml:mn>1</mml:mn>
                                    </mml:msubsup>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo>+</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                    <mml:msubsup>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                        <mml:mn>2</mml:mn>
                                    </mml:msubsup>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>11:&#x2003;&#x2003;&#x2026;</p>
                    <p>12:&#x2003;&#x2003;
                        <inline-formula>

                            <mml:math display="inline">
                                <mml:msubsup>
                                    <mml:mi>X</mml:mi>
                                    <mml:mi>F</mml:mi>
                                    <mml:mi>M</mml:mi>
                                </mml:msubsup>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:mi>t</mml:mi>
                                    <mml:mo>+</mml:mo>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                                <mml:mo>=</mml:mo>
                                <mml:msub>
                                    <mml:mi>f</mml:mi>
                                    <mml:mi>a</mml:mi>
                                </mml:msub>
                                <mml:mrow>
                                    <mml:mo stretchy="true">(</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>i</mml:mi>
                                    </mml:msup>
                                    <mml:msubsup>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                        <mml:mrow>
                                            <mml:mi>M</mml:mi>
                                            <mml:mo>&#x2212;</mml:mo>
                                            <mml:mn>1</mml:mn>
                                        </mml:mrow>
                                    </mml:msubsup>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo>+</mml:mo>
                                    <mml:msup>
                                        <mml:mi>W</mml:mi>
                                        <mml:mi>M</mml:mi>
                                    </mml:msup>
                                    <mml:msubsup>
                                        <mml:mi>X</mml:mi>
                                        <mml:mi>F</mml:mi>
                                        <mml:mi>M</mml:mi>
                                    </mml:msubsup>
                                    <mml:mrow>
                                        <mml:mo stretchy="true">(</mml:mo>
                                        <mml:mi>t</mml:mi>
                                        <mml:mo stretchy="true">)</mml:mo>
                                    </mml:mrow>
                                    <mml:mo stretchy="true">)</mml:mo>
                                </mml:mrow>
                            </mml:math>
</inline-formula>
                    </p>
                    <p>13:&#x2003;
                        <bold>end</bold>
                    </p>
                    <p>14: 
                        <bold>end</bold>
                    </p>
                </boxed-text>
                <p>

                    <bold>Evaluation metrics</bold>
                </p>
                <p>The predictive performance of the proposed HRAESN model and baseline classifiers was assessed using multiple evaluation metrics. Standard measures included:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Accuracy: the proportion of correctly classified instances among all instances.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Sensitivity (Recall): the proportion of true positive cases (IHD present) correctly identified.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Specificity: the proportion of true negative cases (IHD absent) correctly identified.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Precision: the proportion of predicted positives that are true positives.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>F1-score: the harmonic mean of precision and recall, balancing sensitivity and specificity.</p>
                        </list-item>
                    </list>
                </p>
                <p>In addition, we introduced two supplementary metrics to capture model agreement and similarity beyond traditional measures:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Cohen&#x2019;s Kappa Coefficient: quantifies agreement between predicted and actual classifications beyond chance, with values closer to 1 indicating stronger agreement.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Jaccard Coefficient: measures the similarity between predicted and actual sets of positive cases, defined as the intersection divided by the union of the sets.</p>
                        </list-item>
                    </list>
                </p>
                <p>For statistical robustness, 95% confidence intervals (CIs) were estimated for all major performance metrics using a bootstrap resampling strategy (1000 resamples). These CIs provide an indication of the reliability and significance of the reported values.</p>
                <p>

                    <bold>3.5.2 Hyperparameter tuning</bold>
                </p>
                <p>The Hyperparameter Tuning process optimizes the performance of the Hybrid Residual Attention with Echo State Network (HRAESN) model by carefully selecting key parameters for both Echo State Networks (ESN) and Attention Residual Learning (ARL). The reservoir size (500 neurons) and spectral radius (0.8) ensure stable memory retention for time-series processing, while 10% sparse connectivity enhances computational efficiency. The input scaling (0.5) and leaky rate (0.2) regulate data flow within the reservoir, preventing overfitting. The attention module depth (3 layers) and mask range ([0,1]) refine feature selection, improving model interpretability. The model is trained using the Adam optimizer with a learning rate of 0.001, a batch size of 32, and 100 epochs for optimal convergence. The model prevents overfitting through dropout rate 0.3 while 80:20 train-test split maintains evaluation stability. The optimized parameters lead to precise and efficient and stable ischemic heart disease predictions as described in 
                    <xref ref-type="table" rid="T4">
Table 4</xref>.</p>
                <table-wrap id="T4" orientation="portrait" position="float">
                    <label>
Table 4. </label>
                    <caption>
                        <title>Summary of hyperparameter settings used in the proposed model training.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Parameter</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Value</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Description</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Number of Reservoir Neurons (N_res)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">500</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Number of neurons in the ESN reservoir. Determines the capacity of the reservoir to store and process sequential information.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Spectral Radius (&#x03c1;)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.8</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Controls the stability of the ESN. A value &lt; 1 ensures echo state property for long-term memory.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Reservoir Connectivity (%)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">10%</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Percentage of nonzero connections in the reservoir matrix W
                                    <sup>r</sup>, ensuring sparse connectivity.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Input Scaling (W_in)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.5</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Determines how input data is mapped into the reservoir.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Leaky Rate (&#x03b1;)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.2</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Defines how much of the previous state is retained in the ESN for time-series processing.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Readout Regularization (&#x03bb;)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">10
                                    <sup>&#x2212;4</sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Ridge regression parameter to prevent overfitting in the output layer of ESN.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Attention Module Depth</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">3</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Number of stacked attention modules in ARL to enhance feature learning.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Attention Mask Range (M_i (t))</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">[0,1]</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Defines the range of soft masks applied in attention residual learning.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Activation Function (f_a(.))</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Tanh</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Non-linear activation function used in the ESN reservoir.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Output Activation Function (g_a(.))</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Sigmoid</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Activation function used in the final output layer to predict class labels.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Batch Size</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">32</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Number of training samples processed before updating model weights.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Optimizer</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Adam</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Optimization algorithm used to update model parameters.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Learning Rate (&#x03b7;)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.001</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Controls the step size of weight updates during training.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Dropout Rate</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.3</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Fraction of neurons randomly dropped during training to prevent overfitting.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Number of Epochs</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">100</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Total number of times the model iterates over the entire dataset during training.</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Train-Test Split Ratio</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">80:20:00</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Data split for training (80%) and testing (20%).</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
            </sec>
        </sec>
        <sec id="sec15">
            <title>4. Results and analysis</title>
            <p>To predict the existence of ischemic heart disease (IHD), a number of classification methods were employed, including Na&#x00ef;ve Bayes (NB), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), and AdaBoost. Data from the Cardiovascular Disease dataset (Kaggle) and the Heart Disease Data Set (UCI) were used in the experiments.</p>
            <sec id="sec16">
                <title>4.1 Experiment setup and data preprocessing</title>
                <p>The datasets contain various medical indicators that serve as input features for classification. The target variable is binary:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Class 1: Presence of ischemic heart disease</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Class 0: Absence of disease</p>
                        </list-item>
                    </list>
                </p>
                <p>The proposed hybrid HRAESN model is trained using 80% of the dataset, and the remaining 20% is used for testing. Principal Component Analysis (PCA) was applied to highlight variance and distinct patterns in the dataset. 
                    <xref ref-type="fig" rid="f3">
Figure 3</xref> shows the PCA plot, where:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Principal Component 1 (X-axis) and Principal Component 2 (Y-axis) capture most of the variance.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Blue (0) represents healthy individuals, while Red (1) represents patients with heart disease.</p>
                        </list-item>
                    </list>
                </p>
                <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                    <label>
Figure 3. </label>
                    <caption>
                        <title>PCA plot showing data distribution in the heart disease dataset based on the first two principal components.</title>
                    </caption>
                    <graphic id="gr3" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure3.gif"/>
                </fig>
                <p>Additionally, six records in the UCI dataset had missing values, which were imputed using the Ischemic Heart Disease Multiple Imputation technique, producing a complete dataset with no missing values.</p>
            </sec>
            <sec id="sec17">
                <title>4.2 Experimental results</title>
                <p>
                    <xref ref-type="table" rid="T5">
Tables 5</xref> and 
                    <xref ref-type="table" rid="T6">6</xref> present the normalized confusion matrix for the HRAESN model using the UCI Heart Disease dataset and Kaggle Cardiovascular Disease dataset, respectively.</p>
                <table-wrap id="T5" orientation="portrait" position="float">
                    <label>
Table 5. </label>
                    <caption>
                        <title>Normalized confusion matrix for the Hybrid Residual Attention with Echo State Network (HRAESN) using the UCI Heart Disease dataset.</title>
                        <p>Class 0 = no ischemic heart disease (IHD); Class 1 = IHD present.</p>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="2" rowspan="2" valign="top"/>
                                <th align="left" colspan="2" rowspan="1" valign="top">Predicted</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="2" rowspan="1" valign="top">Label</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="top">Actual label</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">163</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">1</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">3</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">136</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <table-wrap id="T6" orientation="portrait" position="float">
                    <label>
Table 6. </label>
                    <caption>
                        <title>Normalized confusion matrix for the Hybrid Residual Attention with Echo State Network (HRAESN) using the Kaggle Cardiovascular Disease dataset.</title>
                        <p>Class 0 = no ischemic heart disease (IHD); Class 1 = IHD present.</p>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="2" rowspan="2" valign="top"/>
                                <th align="left" colspan="2" rowspan="1" valign="top">Predicted</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="2" rowspan="1" valign="top">Label</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="top">Actual label</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">34431</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">549</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">1</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">568</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">34452</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>To assess statistical robustness, 95% confidence intervals (CIs) were estimated for the main performance metrics (accuracy, sensitivity, specificity, precision, and F1-score) using a bootstrap resampling procedure with 1000 iterations. These intervals demonstrate the reliability and statistical significance of the observed differences between models.</p>
                <p>
                    <xref ref-type="fig" rid="f4">
Figures 4</xref>&#x2013;
                    <xref ref-type="fig" rid="f6">6</xref> illustrate the comparative performance of different classifiers used for ischemic heart disease prediction.</p>
                <fig fig-type="figure" id="f4" orientation="portrait" position="float">
                    <label>
Figure 4. </label>
                    <caption>
                        <title>
Analysis of classifier performance based on sensitivity, specificity, precision, F-measure, and accuracy.</title>
                        <p>Results are shown for both UCI and Kaggle datasets. Class 0 = no ischemic heart disease (IHD); Class 1 = IHD present.
                            <sup>
                                <xref ref-type="bibr" rid="ref34">39</xref>
                            </sup>
                        </p>
                    </caption>
                    <graphic id="gr4" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure4.gif"/>
                </fig>
                <fig fig-type="figure" id="f5" orientation="portrait" position="float">
                    <label>
Figure 5. </label>
                    <caption>
                        <title>Analysis of classifier performance using Kappa coefficient, Recall, and Jaccard coefficient for the UCI Heart Disease and Kaggle Cardiovascular Disease datasets.</title>
                        <p>Class 0 = no IHD; Class 1 = IHD present.</p>
                    </caption>
                    <graphic id="gr5" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure5.gif"/>
                </fig>
                <p>While 
                    <xref ref-type="fig" rid="f6">
Figure 6</xref> focuses on the performance of the proposed HRAESN model on the two benchmark datasets (UCI and Kaggle), comparative results against baseline classifiers such as Logistic Regression (LR), Support Vector Machines (SVM), Random Forest (RF), and other deep learning models are reported separately in 
                    <xref ref-type="table" rid="T8">Tables 8</xref> and 
                    <xref ref-type="table" rid="T9">9</xref>.</p>
                <fig fig-type="figure" id="f6" orientation="portrait" position="float">
                    <label>
Figure 6. </label>
                    <caption>
                        <title>Classification error rate, false acceptance rate (FAR), and false rejection rate (FRR) for the UCI Heart Disease and Kaggle Cardiovascular Disease datasets.</title>
                        <p>Results are reported separately for each dataset. Class 0 = no IHD; Class 1 = IHD present.</p>
                    </caption>
                    <graphic id="gr6" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure6.gif"/>
                </fig>
            </sec>
            <sec id="sec18">
                <title>4.3 Comparative analysis with existing models</title>
                <p>The baseline methods reported for UCI (e.g., RF, MLP, ensembles) and Kaggle (e.g., RF, GB, MLP) differ because prior studies used different datasets. We therefore compared HRAESN to the state-of-the-art methods available for each dataset as published in the literature. 
                    <xref ref-type="table" rid="T7">
Tables 7</xref> and 
                    <xref ref-type="table" rid="T8">8</xref> present a comparative analysis between the proposed Hybrid Residual Attention with Echo State Network (HRAESN) model and existing heart disease prediction models. The comparison is based on handling of missing values, classifier types, and accuracy performance across different studies. Unlike traditional models that either delete missing data or use basic imputation techniques, the HRAESN model applies a multiple imputation approach, ensuring data completeness and improving prediction reliability. The results indicate that the HRAESN model outperforms previous approaches, achieving 97.71% accuracy on the UCI Heart Disease dataset and 98.4% accuracy on the Kaggle Cardiovascular Disease dataset. Compared to Random Forest (RF), Gradient Boosting (GB), Multilayer Perceptron (MLP), and other ensemble methods, the HRAESN model exhibits superior classification performance, demonstrating its effectiveness in early ischemic heart disease detection and clinical decision support.</p>
                <table-wrap id="T7" orientation="portrait" position="float">
                    <label>
Table 7. </label>
                    <caption>
                        <title>Comparison of HRAESN with existing methods using the UCI heart disease dataset.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Study</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Year</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Handling of missing values</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Classifiers</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Accuracy (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Jabbar et al.
                                    <sup>
                                        <xref ref-type="bibr" rid="ref34">39</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2016</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Rows with missing values deleted</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">RF</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">83.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Verma &amp; Mathur
                                    <sup>
                                        <xref ref-type="bibr" rid="ref35">35</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2019</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Rows with missing values deleted</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">MLP</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">85.48</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Latha &amp; Jeeva
                                    <sup>
                                        <xref ref-type="bibr" rid="ref36">36</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2019</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Rows with missing values deleted</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Hybrid NB, BN, MLP, RF</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">85.48</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Tama et al.
                                    <sup>
                                        <xref ref-type="bibr" rid="ref37">37</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2020</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Rows with missing values deleted</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Two-tier ensemble (RF, GB, XGBoost)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">85.71</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Rani et al.
                                    <sup>
                                        <xref ref-type="bibr" rid="ref33">38</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2021</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">MICE Algorithm</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">RF</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">86.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Proposed HRAESN</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2023</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Multiple Imputation Technique</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">HRAESN</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">97.71</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <table-wrap id="T8" orientation="portrait" position="float">
                    <label>
Table 8. </label>
                    <caption>
                        <title>Comparison of HRAESN with existing methods using the Kaggle cardiovascular disease dataset.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Study</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Year</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Classifiers</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Accuracy (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Maiga et al.
                                    <sup>
                                        <xref ref-type="bibr" rid="ref38">31</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2019</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">RF</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">73</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Hagan
                                    <sup>
                                        <xref ref-type="bibr" rid="ref39">40</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2021</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">RF, Gradient Boosting</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">74</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Bhoyar
                                    <sup>
                                        <xref ref-type="bibr" rid="ref40">41</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2021</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">MLP</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">89.7</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Theerthagiri
                                    <sup>
                                        <xref ref-type="bibr" rid="ref41">42</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2022</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Gradient Boosting</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">89.7</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Uddin et al.
                                    <sup>
                                        <xref ref-type="bibr" rid="ref42">43</xref>
                                    </sup>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2021</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Hybrid RF, NB, GB</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">94</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Proposed HRAESN</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2023</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">HRAESN</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">98.4</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>
                    <xref ref-type="fig" rid="f7">
Figure 7</xref> compares the HRAESN model with Residual Networks (ResNet) and Echo State Networks (ESN) in terms of classification performance. The HRAESN model achieves 0.98, significantly outperforming ESN (0.89) and ResNet (0.75). This improvement demonstrates the effectiveness of combining Echo State Networks with Attention Residual Learning, enhancing feature extraction and time-series prediction. The results confirm that HRAESN provides superior accuracy and stability in ischemic heart disease classification.</p>
                <fig fig-type="figure" id="f7" orientation="portrait" position="float">
                    <label>
Figure 7. </label>
                    <caption>
                        <title>Comparison of residual network, echo state network, and the proposed Hybrid Residual Attention Echo State Network.</title>
                    </caption>
                    <graphic id="gr7" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/187669/b4dff796-769e-46d3-a2a2-fab115a43350_figure7.gif"/>
                </fig>
            </sec>
        </sec>
        <sec id="sec19" sec-type="discussion">
            <title>5. Discussion</title>
            <p>The proposed HRAESN model significantly outperforms conventional machine learning and deep learning techniques in ischemic heart disease classification. It achieves higher accuracy, sensitivity, and specificity, as demonstrated in 
                <xref ref-type="table" rid="T7">
Tables 7</xref>&#x2013;
                <xref ref-type="table" rid="T10">10</xref>. The proposed model exhibits:
                <list list-type="bullet">
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Improved classification accuracy (97.71% &#x2013; UCI dataset, 98.4% &#x2013; Kaggle dataset)</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Effective handling of missing data using Multiple Imputation Technique</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Enhanced feature learning through Attention Residual Learning (ARL)</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Better time-series processing with Echo State Networks (ESN)
</p>
                    </list-item>
                </list>
            </p>
            <table-wrap id="T9" orientation="portrait" position="float">
                <label>
Table 9. </label>
                <caption>
                    <title>Performance comparison of different algorithms.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">Classifiers</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Accuracy</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Specificity</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">
Sensitivity</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Logistic regression</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">83.3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">82.3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">86.3</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>K neighbors</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">84.8</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">77.7</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">85</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>SVM</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">83.2</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.7</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.2</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>RF</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">80.3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.7</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.2</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>DT</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">82.3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.9</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">78.5</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Deep Learning</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">94.2</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">83.1</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">82.3</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Proposed HRAESN with UCI dataset</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>97.71</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>98.03</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>97.4</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Proposed HRAESN with Kaggle dataset</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>98.4</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>98.42</bold>
</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>98.37</bold>
</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <table-wrap id="T10" orientation="portrait" position="float">
                <label>
Table 10. </label>
                <caption>
                    <title>Performance of deep learning classifiers on the heart disease dataset.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">DL classifiers</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">
Accuracy (%)</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Multi-layer perceptron</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">72.52</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Deep neural network (200 epochs)</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">80.21</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Recurrent neural network</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">88.52</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Long sort term memory network</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">86.88</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Hybrid deep learning model (RNN + LSTM)</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">95.1</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">Proposed HRAESN</td>
                            <td align="left" colspan="1" rowspan="1" valign="bottom">97.71</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <p>However, the model has higher computational complexity, which can be optimized in future work. Integrating IoT-based medical devices for real-time heart disease monitoring can further enhance its applicability in healthcare solutions.</p>
        </sec>
        <sec id="sec2">
            <title>6. Limitations and future directions</title>
            <p>This study has some limitations that should be acknowledged. First, the models were trained and evaluated exclusively on the UCI and Kaggle benchmark datasets. While these datasets are widely used in the literature, they do not represent external, real-world populations. The lack of external validation may limit generalizability, and future work should evaluate the proposed HRAESN framework on independent cohorts collected prospectively in diverse healthcare settings.</p>
            <p>Second, we employed multiple imputation to address missing data. Although imputation is a standard approach, it may introduce bias, particularly if the missingness mechanism is not completely random. Alternative strategies such as sensitivity analyses or robust imputation methods should be considered in future studies to confirm the stability of our results.</p>
            <p>Third, while the incorporation of Attention Residual Learning (ARL) improved predictive accuracy, we did not fully evaluate the interpretability of this mechanism. Specifically, the relative importance of features highlighted by the ARL module has not yet been quantified. Future work should analyze feature attention weights to identify which clinical and lifestyle attributes contributed most strongly to classification. Such analysis could also enable dimensionality reduction by selecting a limited subset of features that maintain comparable predictive performance, potentially improving model efficiency and clinical usability.</p>
        </sec>
        <sec id="sec20" sec-type="conclusion">
            <title>7. Conclusion</title>
            <p>Using the UCI Heart Disease dataset and the Kaggle Cardiovascular Disease dataset, the suggested Hybrid Residual Attention with Echo State Network (HRAESN) model has been compared to several Machine Learning (ML) and Deep Learning (DL) techniques for the classification of Ischemic Heart Disease (IHD). The experimental results demonstrate that HRAESN outpaces existing heart illness prediction methods because it achieves accuracy rates of 98.4% on Kaggle data and 97.7% on UCI data. The HRAESN model demonstrates superior performance in terms of sensitivity together with specificity and recall along with accuracy and F-measure according to deep learning model comparisons. The Ischemic Heart Disease Multiple Imputation Technique incorporated within the model succeeds in handling missing values to achieve better data completeness along with improved predictive reliability.</p>
            <p>The HRAESN model demonstrated better testing stability characteristics than conventional classifiers thus establishing itself as a dependable instrument for medical diagnosis and clinical decisions. The model achieves powerful medical dataset pattern detection through the combination of Echo State Networks (ESN) and Attention Residual Learning (ARL) features. The future research should work on optimizing the computational operations and integrating IoT-based medical equipment to detect ischemic heart disease in real-time. This approach demonstrates significant value for healthcare improvements by providing early medical diagnosis together with decreased chances of life-threatening cardiac events.</p>
        </sec>
        <sec id="sec22">
            <title>Ethical statement</title>
            <p>This study did not involve human or animal subjects, and thus no ethical approval was required.</p>
        </sec>
        <sec id="sec23">
            <title>CRediT authorship contribution statement</title>
            <p>D. Cenitta: Methodology and Project administration. R. Vijaya Arjunan: Conceptualization, Writing &#x2013; review &amp; editing. Tanuja Shailesh: Writing &#x2013; review &amp; editing. Andrew J: Data curation. N. Arul: Visualization. Praveen Pai T: Review &amp; editing.</p>
        </sec>
        <sec id="sec25">
            <title>Disclaimer/publisher&#x2019;s note</title>
            <p>The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s).</p>
        </sec>
    </body>
    <back>
        <sec id="sec28" sec-type="data-availability">
            <title>Data availability</title>
            <p>All datasets used in this study are publicly available and were accessed under open licenses permitting reuse. The Heart Disease dataset was obtained from the UCI Machine Learning Repository and can be accessed at: 
                <ext-link ext-link-type="uri" xlink:href="https://archive.ics.uci.edu/ml/datasets/Heart+Disease">https://archive.ics.uci.edu/ml/datasets/Heart+Disease</ext-link>
            </p>
            <p>

                <bold>Persistent Identifier</bold>: UCI Heart Disease Dataset &#x2013; DOI: 
                <italic toggle="yes">Not applicable (repository does not assign DOI)</italic>
            </p>
            <p>The Cardiovascular Disease dataset was obtained from Kaggle and can be accessed at: 
                <ext-link ext-link-type="uri" xlink:href="https://www.kaggle.com/datasets/sulianova/cardiovascular-disease-dataset">https://www.kaggle.com/datasets/sulianova/cardiovascular-disease-dataset</ext-link>
            </p>
            <p>

                <bold>Persistent Identifier</bold>: Kaggle Dataset &#x2013; DOI: 
                <italic toggle="yes">Not applicable (repository does not assign DOI)</italic>
            </p>
            <p>All data supporting the results, including the values used to compute performance metrics (accuracy, sensitivity, specificity, F-measure), build figures (e.g., PCA plots, confusion matrices), and generate tables, are available in the original datasets and fully included in the supplementary materials submitted with this article.</p>
            <p>These datasets are distributed under open licenses allowing unrestricted use: CC0 (UCI) and Kaggle&#x2019;s standard open data license. No additional ethical, privacy, or security concerns apply.</p>
            <p>Both datasets are openly accessible for academic and research purposes and do not contain any personally identifiable information. However, 
                <bold>as the current study is based on third-party data, the authors were not involved in the original data collection process</bold>.</p>
            <p>To the best of our knowledge:
                <list list-type="bullet">
                    <list-item>
                        <label>&#x2022;</label>
                        <p>The 
                            <bold>UCI Heart Disease dataset</bold> was originally contributed by researchers from the 
                            <bold>Cleveland Clinic Foundation</bold> and is widely used in medical data mining research. Specific details regarding ethical approval and informed consent for this dataset were not provided in the original UCI repository documentation.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>The 
                            <bold>Kaggle Cardiovascular Disease dataset</bold> was uploaded by the contributor Y. Suliana, who stated that the data was anonymized and collected during routine clinical practice. However, no specific name of the ethics committee, approval date, or consent procedure is disclosed in the dataset description.</p>
                    </list-item>
                </list>
            </p>
            <p>As per the policies of UCI and Kaggle, datasets are made publicly available under the assumption that all ethical requirements and informed consent procedures were handled appropriately by the original data custodians. Since no personally identifiable data is included, and the data is anonymized, 
                <bold>no additional ethical approval or consent was required</bold> for our use of these datasets in accordance with our institutional guidelines and the Declaration of Helsinki.</p>
        </sec>
        <ack>
            <title>Acknowledgments</title>
            <p>This manuscript was prepared using AI-driven tools to guarantee academic honesty by citing the proper papers, increasing understanding by increasing linguistic clarity, and providing comprehensive literature analysis. Grammarly and Paperpal were used to examine the text for grammatical mistakes, typos, and punctuation errors. The comprehension power of Quillbot was used to put across complicated ideas concisely while maintaining the original context and meaning. Scopus AI and Consensus.app, both intuitive and intelligent search tools, helped us to understand and enrich our insights with unprecedented speed and clarity. Scholarcy helped improve the pace of the process as it abstracted related academic articles and critical findings, thereby helping bring together existing research which let to identifying research gaps. We employed Turnitin software to account for plagiarism check.</p>
        </ack>
        <ref-list>
            <title>References</title>
            <ref id="ref1">
                <label>1</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Severino</surname>
                            <given-names>P</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Ischemic Heart Disease Pathophysiology Paradigms Overview: From Plaque Activation to Microvascular Dysfunction.</article-title>
                    <source>

                        <italic toggle="yes">Int. J. Mol. Sci.</italic>
</source>
                    <year>Oct. 2020</year>;<volume>21</volume>:<fpage>8118</fpage>.
                    <pub-id pub-id-type="pmid">33143256</pub-id>
                    <pub-id pub-id-type="doi">10.3390/IJMS21218118</pub-id>
                    <pub-id pub-id-type="pmcid">PMC7663258</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref2">
                <label>2</label>
                <mixed-citation publication-type="other">
                    <article-title>Cardiovascular diseases (CVDs). </article-title>(accessed Mar. 16, 2023).
                    <ext-link ext-link-type="uri" xlink:href="https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref3">
                <label>3</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bolhasani</surname>
                            <given-names>H</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mohseni</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rahmani</surname>
                            <given-names>AM</given-names>
                        </name>
</person-group>:
                    <article-title>Deep learning applications for IoT in health care: A systematic review.</article-title>
                    <source>

                        <italic toggle="yes"> Inform. Med. Unlocked.</italic>
</source>
                    <year>Jan. 2021</year>;<volume>23</volume>:<fpage>100550</fpage>.
                    <pub-id pub-id-type="doi">10.1016/j.imu.2021.100550</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref4">
                <label>4</label>
                <mixed-citation publication-type="other">
                    <article-title>Introduction to Recurrent Neural Network - GeeksforGeeks.</article-title>(accessed Mar. 15, 2023).
                    <ext-link ext-link-type="uri" xlink:href="https://www.geeksforgeeks.org/introduction-to-recurrent-neural-network/">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref5">
                <label>5</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Gao</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Du</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Duru</surname>
                            <given-names>O</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Time series forecasting based on echo state network and empirical wavelet transformation.</article-title>
                    <source>

                        <italic toggle="yes">Appl. Soft Comput.</italic>
</source>
                    <year>Apr. 2021</year>;<volume>102</volume>:<fpage>107111</fpage>.
                    <pub-id pub-id-type="doi">10.1016/j.asoc.2021.107111</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref6">
                <label>6</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Huang</surname>
                            <given-names>Z</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Functional deep echo state network improved by a bi-level optimization approach for multivariate time series classification.</article-title>
                    <source>

                        <italic toggle="yes">Appl. Soft Comput.</italic>
</source>
                    <year>Jul. 2021</year>;<volume>106</volume>:<fpage>107314</fpage>.
                    <pub-id pub-id-type="doi">10.1016/j.asoc.2021.107314</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref7">
                <label>7</label>
                <mixed-citation publication-type="book">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Mhathesh</surname>
                            <given-names>TSR</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Andrew</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Martin Sagayam</surname>
                            <given-names>K</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <chapter-title>A 3d convolutional neural network for bacterial image classification.</chapter-title>
                    <source>

                        <italic toggle="yes">Adv. Intell. Syst. Comput.</italic>
</source>
                    <publisher-name>Springer</publisher-name>;<year>2021</year>; pp.<fpage>419</fpage>&#x2013;<lpage>431</lpage>.
                    <pub-id pub-id-type="doi">10.1007/978-981-15-5285-4_42</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref8">
                <label>8</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Wang</surname>
                            <given-names>F</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Residual attention network for image classification.</article-title>
                    <source>

                        <italic toggle="yes">Proc. IEEE Conf. Comput. Vis. Pattern Recognit.</italic>
</source>
                    <year>2017</year>;<fpage>3156</fpage>&#x2013;<lpage>3164</lpage>.</mixed-citation>
            </ref>
            <ref id="ref9">
                <label>9</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Cenitta</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Arjunan</surname>
                            <given-names>RV</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Prema</surname>
                            <given-names>KV</given-names>
                        </name>
</person-group>:
                    <article-title>Ischemic Heart Disease Multiple Imputation Technique Using Machine Learning Algorithm.</article-title>
                    <source>

                        <italic toggle="yes">Eng. Sci.</italic>
</source>
                    <year>Sep. 2022</year>;<volume>19</volume>:<fpage>262</fpage>&#x2013;<lpage>272</lpage>.
                    <pub-id pub-id-type="doi">10.30919/ES8D681</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref27">
                <label>10</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Kusuma</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Jothi</surname>
                            <given-names>KR</given-names>
                        </name>
</person-group>:
                    <article-title>Heart disease classification using multiple K-PCA and hybrid deep learning approach.</article-title>
                    <source>

                        <italic toggle="yes">Comput. Syst. Sci. Eng.</italic>
</source>
                    <year>2022</year>;<volume>41</volume>(<issue>3</issue>):<fpage>1273</fpage>&#x2013;<lpage>1289</lpage>.
                    <pub-id pub-id-type="doi">10.32604/csse.2022.021741</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref28">
                <label>11</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Nagavelli</surname>
                            <given-names>U</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Samanta</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Chakraborty</surname>
                            <given-names>P</given-names>
                        </name>
</person-group>:
                    <article-title>Machine Learning Technology-Based Heart Disease Detection Models.</article-title>
                    <source>

                        <italic toggle="yes">J. Healthc. Eng.</italic>
</source>
                    <year>2022</year>;<volume>2022</volume>:<fpage>1</fpage>&#x2013;<lpage>9</lpage>.
                    <pub-id pub-id-type="pmid">35265303</pub-id>
                    <pub-id pub-id-type="doi">10.1155/2022/7351061</pub-id>
                    <pub-id pub-id-type="pmcid">PMC8898839</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref29">
                <label>12</label>
                <mixed-citation publication-type="book">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Sonawane</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>HD</given-names>
                        </name>
</person-group>:
                    <chapter-title>Prediction of Heart Disease by Optimized Distance and Density-Based Clustering.</chapter-title>
                    <source>

                        <italic toggle="yes">Proceedings of the 2nd International Conference on Artificial Intelligence and Smart Energy, ICAIS 2022.</italic>
</source>
                    <publisher-name>Institute of Electrical and Electronics Engineers Inc</publisher-name>;<year>2022</year>; pp.<fpage>1001</fpage>&#x2013;<lpage>1008</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ICAIS53314.2022.9742885</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref30">
                <label>13</label>
                <mixed-citation publication-type="other">
                    <article-title>Cardiovascular Disease dataset|Kaggle. </article-title>(accessed Mar. 15, 2023).
                    <ext-link ext-link-type="uri" xlink:href="https://www.kaggle.com/datasets/sulianova/cardiovascular-disease-dataset">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref25">
                <label>14</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Sonawane</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>H</given-names>
                        </name>
</person-group>:
                    <article-title>Automated heart disease prediction model by hybrid heuristic-based feature optimization and enhanced clustering.</article-title>
                    <source>

                        <italic toggle="yes">Biomed. Signal Process. Control.</italic>
</source>
                    <year>Feb. 2022</year>;<volume>72</volume>:<fpage>103260</fpage>.
                    <pub-id pub-id-type="doi">10.1016/j.bspc.2021.103260</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref26">
                <label>15</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Archana</surname>
                            <given-names>KS</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Sivakumar</surname>
                            <given-names>B</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kuppusamy</surname>
                            <given-names>R</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Automated Cardioailment Identification and Prevention by Hybrid Machine Learning Models.</article-title>
                    <source>

                        <italic toggle="yes">Comput. Math. Methods Med.</italic>
</source>
                    <year>2022</year>;<volume>2022</volume>:<fpage>1</fpage>&#x2013;<lpage>8</lpage>.
                    <pub-id pub-id-type="pmid">35211190</pub-id>
                    <pub-id pub-id-type="doi">10.1155/2022/9797844</pub-id>
                    <pub-id pub-id-type="pmcid">PMC8863449</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref10">
                <label>16</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>X</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Automatic heartbeat classification using S-shaped reconstruction and a squeeze-and-excitation residual network.</article-title>
                    <source>

                        <italic toggle="yes">Elsevier, Comput. Biol. Med.</italic>
</source>
                    <year>2022</year>;<volume>140</volume>:<fpage>105108</fpage>.
                    <pub-id pub-id-type="pmid">34875410</pub-id>
                    <pub-id pub-id-type="doi">10.1016/j.compbiomed.2021.105108</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref12">
                <label>17</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Sun</surname>
                            <given-names>X</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>T</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>Q</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Deep belief echo-state network and its application to time series prediction.</article-title>
                    <source>

                        <italic toggle="yes">Knowl.-Based Syst.</italic>
</source>
                    <year>Aug. 2017</year>;<volume>130</volume>:<fpage>17</fpage>&#x2013;<lpage>29</lpage>.
                    <pub-id pub-id-type="doi">10.1016/j.knosys.2017.05.022</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref16">
                <label>18</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Wang</surname>
                            <given-names>Q</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wang</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Liu</surname>
                            <given-names>Y</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Time Series Prediction with Incomplete Dataset Based on Deep Bidirectional Echo State Network.</article-title>
                    <source>

                        <italic toggle="yes">IEEE Access.</italic>
</source>
                    <year>2019</year>;<volume>7</volume>:<fpage>152533</fpage>&#x2013;<lpage>152544</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ACCESS.2019.2948367</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref17">
                <label>19</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Ren</surname>
                            <given-names>W</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wang</surname>
                            <given-names>Y</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Han</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>Time series prediction based on echo state network tuned by divided adaptive multi-objective differential evolution algorithm.</article-title>
                    <source>

                        <italic toggle="yes">Soft. Comput.</italic>
</source>
                    <year>Mar. 2021</year>;<volume>25</volume>(<issue>6</issue>):<fpage>4489</fpage>&#x2013;<lpage>4502</lpage>.
                    <pub-id pub-id-type="doi">10.1007/s00500-020-05457-8</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref18">
                <label>20</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Doppala</surname>
                            <given-names>BP</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bhattacharyya</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Janarthanan</surname>
                            <given-names>M</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>A Reliable Machine Intelligence Model for Accurate Identification of Cardiovascular Diseases Using Ensemble Techniques.</article-title>
                    <source>

                        <italic toggle="yes">J. Healthc. Eng.</italic>
</source>
                    <year>2022</year>;<volume>2022</volume>:<fpage>1</fpage>&#x2013;<lpage>13</lpage>.
                    <pub-id pub-id-type="pmid">35299686</pub-id>
                    <pub-id pub-id-type="doi">10.1155/2022/2585235</pub-id>
                    <pub-id pub-id-type="pmcid">PMC8923755</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref19">
                <label>21</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Ampavathi</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Saradhi</surname>
                            <given-names>TV</given-names>
                        </name>
</person-group>:
                    <article-title>Multi disease-prediction framework using hybrid deep learning: an optimal prediction model.</article-title>
                    <source>

                        <italic toggle="yes">Comput. Methods Biomech. Biomed. Engin.</italic>
</source>
                    <year>2021</year>;<volume>24</volume>(<issue>10</issue>):<fpage>1146</fpage>&#x2013;<lpage>1168</lpage>.
                    <pub-id pub-id-type="pmid">33427480</pub-id>
                    <pub-id pub-id-type="doi">10.1080/10255842.2020.1869726</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref21">
                <label>22</label>
                <mixed-citation publication-type="book">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Liu</surname>
                            <given-names>Y</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <chapter-title>Automatic Detection of ECG Abnormalities by Using an Ensemble of Deep Residual Networks with Attention.</chapter-title>
                    <source>

                        <italic toggle="yes">Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics).</italic>
</source>
                    <publisher-name>Springer</publisher-name>;<year>2019</year>; pp.<fpage>88</fpage>&#x2013;<lpage>95</lpage>.
                    <pub-id pub-id-type="doi">10.1007/978-3-030-33327-0_11</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref13">
                <label>23</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Zhang</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Zhu</surname>
                            <given-names>W</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>J</given-names>
                        </name>
</person-group>:
                    <article-title>Spiking echo state convolutional neural network for robust time series classification.</article-title>
                    <source>

                        <italic toggle="yes">IEEE Access.</italic>
</source>
                    <year>2019</year>;<volume>7</volume>:<fpage>4927</fpage>&#x2013;<lpage>4935</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ACCESS.2018.2887354</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref22">
                <label>24</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Guo</surname>
                            <given-names>C</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Zhang</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Liu</surname>
                            <given-names>Y</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Recursion Enhanced Random Forest with an Improved Linear Model (RERF-ILM) for Heart Disease Detection on the Internet of Medical Things Platform.</article-title>
                    <source>

                        <italic toggle="yes">IEEE Access.</italic>
</source>
                    <year>2020</year>;<volume>8</volume>:<fpage>59247</fpage>&#x2013;<lpage>59256</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ACCESS.2020.2981159</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref11">
                <label>25</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>B</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Li</surname>
                            <given-names>Z</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Yang</surname>
                            <given-names>Y</given-names>
                        </name>
</person-group>:
                    <article-title>Residual attention graph convolutional network for web services classification.</article-title>
                    <source>

                        <italic toggle="yes">Neurocomputing.</italic>
</source>
                    <year>Jun. 2021</year>;<volume>440</volume>:<fpage>45</fpage>&#x2013;<lpage>57</lpage>.
                    <pub-id pub-id-type="doi">10.1016/j.neucom.2021.01.089</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref23">
                <label>26</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Suresh</surname>
                            <given-names>T</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Assegie</surname>
                            <given-names>TA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rajkumar</surname>
                            <given-names>S</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>A hybrid approach to medical decision-making: diagnosis of heart disease with machine-learning model.</article-title>
                    <source>

                        <italic toggle="yes">Int. J. Electr. Comput. Eng.</italic>
</source>
                    <year>2022</year>;<volume>12</volume>(<issue>2</issue>):<fpage>1831</fpage>&#x2013;<lpage>1838</lpage>.
                    <pub-id pub-id-type="doi">10.11591/ijece.v12i2.pp1831-1838</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref24">
                <label>27</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bhavekar</surname>
                            <given-names>GS</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Das Goswami</surname>
                            <given-names>A</given-names>
                        </name>
</person-group>:
                    <article-title>A hybrid model for heart disease prediction using recurrent neural network and long short term memory.</article-title>
                    <source>

                        <italic toggle="yes"> Int. J. Inf. Technol. (Singapore).</italic>
</source>
                    <year>Jun. 2022</year>;<volume>14</volume>(<issue>4</issue>):<fpage>1781</fpage>&#x2013;<lpage>1789</lpage>.
                    <pub-id pub-id-type="doi">10.1007/s41870-022-00896-y</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref15">
                <label>28</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Andrew Onesimu</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Karthikeyan</surname>
                            <given-names>J</given-names>
                        </name>
</person-group>:
                    <article-title>An efficient privacy-preserving deep learning scheme for medical image analysis.</article-title>
                    <source>

                        <italic toggle="yes">Journal of Information Technology Management, vol. 12, no. Special Issue: The Importance of Human Computer Interaction: Challenges, Methods and Applications.</italic>
</source>
                    <year>Dec. 2021</year>;<fpage>50</fpage>&#x2013;<lpage>67</lpage>.
                    <pub-id pub-id-type="doi">10.22059/jitm.2020.79191</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref14">
                <label>29</label>
                <mixed-citation publication-type="book">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Andrew</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Fiona</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Caleb Andrew</surname>
                            <given-names>H</given-names>
                        </name>
</person-group>:
                    <chapter-title>Comparative study of various deep convolutional neural networks in the early prediction of cancer.</chapter-title>
                    <source>

                        <italic toggle="yes">2019 International Conference on Intelligent Computing and Control Systems, ICCS 2019.</italic>
</source>
                    <publisher-name>Institute of Electrical and Electronics Engineers Inc.</publisher-name>;<year>May 2019</year>; pp.<fpage>884</fpage>&#x2013;<lpage>890</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ICCS45141.2019.9065445</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref20">
                <label>30</label>
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Chandrasekaran</surname>
                            <given-names>ST</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Banerjee</surname>
                            <given-names>I</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Sanyal</surname>
                            <given-names>A</given-names>
                        </name>
</person-group>:
                    <chapter-title>7.5nJ/inference CMOS Echo State Network for Coronary Heart Disease prediction.</chapter-title>
                    <source>

                        <italic toggle="yes">ESSDERC 2021-IEEE 51st European Solid-State Device Research Conference (ESSDERC).</italic>
</source>
                    <year>Sep. 2021</year>; pp.<fpage>103</fpage>&#x2013;<lpage>106</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ESSCIRC53450.2021.9567753</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref38">
                <label>31</label>
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Maiga</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Hungilo</surname>
                            <given-names>GG</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <chapter-title>Comparison of Machine Learning Models in Prediction of Cardiovascular Disease Using Health Record Data.</chapter-title>
                    <source>

                        <italic toggle="yes">International Conference on Informatics, Multimedia, Cyber and Information System.</italic>
</source>
                    <year>2019</year>; pp.<fpage>45</fpage>&#x2013;<lpage>48</lpage>.
                    <pub-id pub-id-type="doi">10.1109/ICIMCIS48181.2019.8985205</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref43">
                <label>32</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bharti</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Khamparia</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Shabaz</surname>
                            <given-names>M</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Prediction of Heart Disease Using a Combination of Machine Learning and Deep Learning.</article-title>
                    <source>

                        <italic toggle="yes">Comput. Intell. Neurosci.</italic>
</source>
                    <year>2021</year>;<volume>2021</volume>.
                    <pub-id pub-id-type="pmid">34306056</pub-id>
                    <pub-id pub-id-type="doi">10.1155/2021/8387680</pub-id>
                    <pub-id pub-id-type="pmcid">PMC8266441</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref31">
                <label>33</label>
                <mixed-citation publication-type="other">
                    <article-title>UCI Machine Learning Repository: Heart Disease Data Set.</article-title>(accessed Mar. 15, 2023).
                    <ext-link ext-link-type="uri" xlink:href="https://archive.ics.uci.edu/ml/datasets/heart+disease">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref32">
                <label>34</label>
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Cenitta</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Vijaya Arjunan</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Prema</surname>
                            <given-names>KV</given-names>
                        </name>
</person-group>:
                    <article-title>Ischemic Heart Disease Prediction Using Optimized Squirrel Search Feature Selection Algorithm.</article-title>
                    <pub-id pub-id-type="doi">10.1109/ACCESS.2022.3223429</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref35">
                <label>35</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Verma</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mathur</surname>
                            <given-names>MK</given-names>
                        </name>
</person-group>:
                    <article-title>Deep learning based model for decision support with case based reasoning.</article-title>
                    <source>

                        <italic toggle="yes">International Journal of Innovative Technology and Exploring Engineering.</italic>
</source>
                    <year>2020</year>;<volume>8</volume>(<issue>6C</issue>):<fpage>149</fpage>&#x2013;<lpage>153</lpage>.</mixed-citation>
            </ref>
            <ref id="ref36">
                <label>36</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Latha</surname>
                            <given-names>CBC</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Jeeva</surname>
                            <given-names>SC</given-names>
                        </name>
</person-group>:
                    <article-title>Improving the accuracy of prediction of heart disease risk based on ensemble classification techniques.</article-title>
                    <source>

                        <italic toggle="yes">Inform. Med. Unlocked.</italic>
</source>
                    <year>Jan. 2019</year>;<volume>16</volume>:<fpage>100203</fpage>.
                    <pub-id pub-id-type="doi">10.1016/J.IMU.2019.100203</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref37">
                <label>37</label>
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Tama</surname>
                            <given-names>BA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Im</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Lee</surname>
                            <given-names>S</given-names>
                        </name>
</person-group>:
                    <article-title>Improving an Intelligent Detection System for Coronary Heart Disease Using a Two-Tier Classifier Ensemble.</article-title>
                    <year>2020</year>.
                    <pub-id pub-id-type="doi">10.1155/2020/9816142</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref33">
                <label>38</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Rani</surname>
                            <given-names>P</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kumar</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Ahmed</surname>
                            <given-names>NMOS</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>A decision support system for heart disease prediction based upon machine learning.</article-title>
                    <source>

                        <italic toggle="yes">J. Reliab. Intell. Environ.</italic>
</source>
                    <year>2021</year>;<volume>7</volume>:<fpage>263</fpage>&#x2013;<lpage>275</lpage>.
                    <pub-id pub-id-type="doi">10.1007/s40860-021-00133-6</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref34">
                <label>39</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Jabbar</surname>
                            <given-names>MA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Deekshatulu</surname>
                            <given-names>BL</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Chandra</surname>
                            <given-names>P</given-names>
                        </name>
</person-group>:
                    <article-title>Prediction of heart disease using random forest and feature subset selection.</article-title>
                    <source>

                        <italic toggle="yes">Adv. Intell. Syst. Comput.</italic>
</source>
                    <year>2016</year>;<volume>424</volume>:<fpage>187</fpage>&#x2013;<lpage>196</lpage>.
                    <pub-id pub-id-type="doi">10.1007/978-3-319-28031-8_16/FIGURES/4</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref39">
                <label>40</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Hagan</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gillan</surname>
                            <given-names>CJ</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mallett</surname>
                            <given-names>F</given-names>
                        </name>
</person-group>:
                    <article-title>Comparison of machine learning methods for the classification of cardiovascular disease.</article-title>
                    <source>

                        <italic toggle="yes">Inform. Med. Unlocked.</italic>
</source>
                    <year>Jan. 2021</year>;<volume>24</volume>:<fpage>100606</fpage>.
                    <pub-id pub-id-type="doi">10.1016/J.IMU.2021.100606</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref40">
                <label>41</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bhoyar</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wagholikar</surname>
                            <given-names>N</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bakshi</surname>
                            <given-names>K</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Real-time Heart Disease Prediction System using Multilayer Perceptron; Real-time Heart Disease Prediction System using Multilayer Perceptron.</article-title>
                    <source>

                        <italic toggle="yes">International Conference for Emerging Technology.</italic>
</source>
                    <year>2021</year>.
                    <pub-id pub-id-type="doi">10.1109/INCET51464.2021.9456389</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref41">
                <label>42</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Theerthagiri</surname>
                            <given-names>P</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Vidya</surname>
                            <given-names>J</given-names>
                        </name>
</person-group>:
                    <article-title>Cardiovascular disease prediction using recursive feature elimination and gradient boosting classification techniques.</article-title>
                    <source>

                        <italic toggle="yes">Expert. Syst.</italic>
</source>
                    <year>2022</year>;<volume>39</volume>.
                    <pub-id pub-id-type="doi">10.1111/exsy.13064</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref42">
                <label>43</label>
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Uddin</surname>
                            <given-names>MN</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Halder</surname>
                            <given-names>RK</given-names>
                        </name>
</person-group>:
                    <article-title>An ensemble method based multilayer dynamic system to predict cardiovascular disease using machine learning approach.</article-title>
                    <source>

                        <italic toggle="yes">Inform. Med. Unlocked.</italic>
</source>
                    <year>Jan. 2021</year>;<volume>24</volume>:<fpage>100584</fpage>.
                    <pub-id pub-id-type="doi">10.1016/J.IMU.2021.100584</pub-id>
                </mixed-citation>
            </ref>
        </ref-list>
    </back>
    <sub-article article-type="reviewer-report" id="report414780">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.187669.r414780</article-id>
            <title-group>
                <article-title>Reviewer response for version 2</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Shrestha</surname>
                        <given-names>Dhadkan</given-names>
                    </name>
                    <xref ref-type="aff" rid="r414780a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0009-0007-2588-3734</uri>
                </contrib>
                <aff id="r414780a1">
                    <label>1</label>Texas State University College of Science and Engineering, San Marcos, Texas, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>25</day>
                <month>9</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Shrestha D</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport414780" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.165575.2"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>Everything looks good now. Thank you for revising.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Machine Learning, Artificial Intelligence, Big Data</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
        <sub-article article-type="response" id="comment14663-414780">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>RANGANATHAN</surname>
                            <given-names>VIJAYA ARJUNAN</given-names>
                        </name>
                        <aff>School of Computer Engineering, Manipal Academy of Higher Education, Manipal, Karnataka, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>The authors declare that they have no competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>25</day>
                    <month>9</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you for your kind feedback and approval.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report403945">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.182263.r403945</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>MEMON</surname>
                        <given-names>MUHAMMAD HAMMAD</given-names>
                    </name>
                    <xref ref-type="aff" rid="r403945a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-8680-1831</uri>
                </contrib>
                <aff id="r403945a1">
                    <label>1</label>Southwest University of Science and Technology, Sichuan, China</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>4</day>
                <month>9</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 MEMON MH</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport403945" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.165575.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>
                <bold>Summary of the Article:</bold>
            </p>
            <p> </p>
            <p> The manuscript introduces a 
                <bold>Hybrid Residual Attention with Echo State Network (HRAESN)</bold> model for ischemic heart disease (IHD) prediction. The model integrates 
                <bold>Attention Residual Learning (ARL)</bold> to enhance feature extraction and 
                <bold>Echo State Networks (ESN)</bold> for efficient time-series processing. Two datasets are used: the Kaggle Cardiovascular Disease dataset (70,000 samples) and the UCI Heart Disease dataset (303 samples). The authors report 
                <bold>very high performance</bold> (up to 98.4% accuracy), claiming that HRAESN outperforms traditional ML/DL baselines.</p>
            <p> The study is relevant and well-motivated, with clear clinical importance. However, there are major concerns regarding 
                <bold>methodological rigor, reproducibility, and statistical robustness</bold>.</p>
            <p> </p>
            <p> 
                <bold>Major Concerns</bold> 
                <list list-type="order">
                    <list-item>
                        <p>
                            <bold>Presentation and Literature Coverage</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>The manuscript is generally clear, but the 
                                        <bold>literature review is overly descriptive</bold> and includes some 
                                        <bold>weak references</bold> (e.g., tutorial websites).</p>
                                </list-item>
                                <list-item>
                                    <p>Prior work on combining attention and ESN (e.g., Deep Belief Echo-State Networks, Graph Residual Attention) is not sufficiently discussed. The novelty contribution must be 
                                        <bold>better distinguished</bold>.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Study Design and Technical Soundness</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>The reported performance (&gt;97% accuracy) is 
                                        <bold>unrealistically high</bold> for these datasets and suggests possible 
                                        <bold>overfitting or data leakage</bold>.</p>
                                </list-item>
                                <list-item>
                                    <p>Only a single 
                                        <bold>80:20 train-test split</bold> is reported. This is not sufficient for robust evaluation in medical ML. At minimum, 
                                        <bold>k-fold cross-validation</bold> with stratified sampling is required.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Methods and Replication</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Details of the 
                                        <bold>Ischemic Heart Disease Multiple Imputation Technique</bold> are insufficient. The method is referenced but not described in reproducible detail.</p>
                                </list-item>
                                <list-item>
                                    <p>No 
                                        <bold>code, model weights, or supplementary scripts</bold> are provided, making replication difficult.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Statistical Analysis</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>No 
                                        <bold>statistical significance testing</bold> (e.g., McNemar&#x2019;s test, paired t-test, Wilcoxon signed-rank test) is provided. Reported differences may not be statistically meaningful.</p>
                                </list-item>
                                <list-item>
                                    <p>Metrics such as 
                                        <bold>ROC curves, AUC, calibration plots, and precision-recall curves</bold> should be included for clinical interpretability.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Reproducibility and Source Data</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Although the datasets are public, the 
                                        <bold>exact preprocessing steps and imputation pipeline are not fully transparent</bold>, which limits reproducibility.</p>
                                </list-item>
                                <list-item>
                                    <p>PCA plots and confusion matrices are shown but lack supporting raw numbers or code availability.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Support for Conclusions</bold> 
                            <list list-type="bullet">
                                <list-item>
                                    <p>While results are promising, conclusions about clinical utility are 
                                        <bold>overstated</bold>. Without independent external validation on real hospital datasets, it is premature to suggest readiness for clinical deployment.</p>
                                </list-item>
                                <list-item>
                                    <p>Limitations such as 
                                        <bold>dataset imbalance, computational cost, and lack of external validation</bold> are only briefly acknowledged and need stronger discussion.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> 
                <bold>Minor Comments</bold> 
                <list list-type="bullet">
                    <list-item>
                        <p>Some sections could be streamlined (particularly Related Works).</p>
                    </list-item>
                    <list-item>
                        <p>Figures would benefit from 
                            <bold>statistical annotations</bold> (e.g., significance levels).</p>
                    </list-item>
                    <list-item>
                        <p>The 
                            <bold>ethics statement</bold> should clarify whether the Kaggle dataset contributor had appropriate institutional approval.</p>
                    </list-item>
                    <list-item>
                        <p>Writing is generally clear but could be 
                            <bold>more concise</bold> in parts.</p>
                    </list-item>
                </list> </p>
            <p> 
                <bold>Recommendations to Improve the Manuscript</bold> 
                <list list-type="order">
                    <list-item>
                        <p>Re-run experiments with 
                            <bold>10-fold cross-validation</bold> and report mean &#x00b1; standard deviation.</p>
                    </list-item>
                    <list-item>
                        <p>Add 
                            <bold>statistical tests</bold> to confirm whether improvements over baselines are significant.</p>
                    </list-item>
                    <list-item>
                        <p>Provide 
                            <bold>algorithmic details</bold> of the imputation method and release 
                            <bold>source code/models</bold>.</p>
                    </list-item>
                    <list-item>
                        <p>Include 
                            <bold>AUC/ROC, calibration, and PR curves</bold> for stronger evaluation.</p>
                    </list-item>
                    <list-item>
                        <p>Strengthen the 
                            <bold>novelty discussion</bold> by differentiating HRAESN from earlier ESN+attention studies.</p>
                    </list-item>
                    <list-item>
                        <p>Expand the 
                            <bold>limitations section</bold>, especially regarding generalizability and clinical applicability.</p>
                    </list-item>
                </list> </p>
            <p> 
                <bold>Final Recommendation</bold>
            </p>
            <p> </p>
            <p> 
                <bold>Major Revision</bold>
            </p>
            <p> </p>
            <p> The study addresses an important healthcare challenge and proposes an interesting hybrid deep learning approach. However, 
                <bold>methodological rigor, reproducibility, and statistical analysis must be improved</bold> to make the findings scientifically sound and credible for indexing.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Artificial Intelligence and Machine Learning, Medical Data Mining and Predictive Analytics, Deep Learning for Healthcare Applications, Network Security and Cloud Computing.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment14542-403945">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>RANGANATHAN</surname>
                            <given-names>VIJAYA ARJUNAN</given-names>
                        </name>
                        <aff>School of Computer Engineering, Manipal Academy of Higher Education, Manipal, Karnataka, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>The author(s) declare that they have no competing interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>10</day>
                    <month>9</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Deep Learning based hybrid residual attention and echo state network for high-accuracy heart disease prediction</bold>
                </p>
                <p> 
                    <bold>Responses to peer review reports</bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 1:</bold> 
                    <bold>Summary of the Article:</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank Reviewer&#x00a0; for the detailed assessment. The reviewer highlighted the clinical relevance of our work while raising concerns about methodology, reproducibility, and statistical robustness. We carefully revised the manuscript to address all points raised. Below we provide a structured response.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 2:</bold> 
                    <bold>Presentation and Literature Coverage</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We acknowledge this important observation. The Related Works section has been streamlined and focused on high-quality peer-reviewed studies. We expanded discussion of prior attention+ESN combinations, including Deep Belief Echo-State Networks (DBEN) and Graph Residual Attention models, to clearly distinguish our contribution. Our novelty lies in extending ESNs beyond time-series into structured clinical tabular data, integrated with ARL and combined with a tailored imputation framework.</p>
                <p> 
                    <bold>Author action: </bold>Revised Section 2 (Related Works) to be more concise, replaced weak/tutorial references with peer-reviewed sources, and explicitly clarified novelty.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAm8AAAACCAMAAAA5HcsXAAAAHXRFWHRUaXRsZQBkZWZhdWx0X2hvcml6b250YWxfbGluZffN59AAAAMAUExURcDAwMzMzGZmZgAAACdhub8CAAAAAAAAADwE4wA8BOMAYAGLAGwfnxdHAJiOAABijsNEzxdUzp0AORtAX5gJAAAPAAAAAAAAAAAAAAA8BOMAcM6dAMkWQF8PAAAAAAAAAAAAAAAPAAAAAAAAANDOnQA7FkBfDwAAAAAAAAAHAAAAIM+dAI5fAABqz50AmAkAAAIEAAABAAAAAAAAAAAAAAAAAAAAAAAAABgQQF8JAAAAIM+dAI5fAABgAYsAhM6dAAzPnQDK+EhfAAAAAOzOnQDGFUBfAAAAAJgJAAAPAAAAGBBAXwkAAAAgz50ACM+dAFAbQF+CLUBfAAAAAIsVQF+OXwAAeAB7AFTPnQAr+Ehf/////zjPnQBjNve/mAkAAA8AAAAAAAAAAAAAAMcpaF8/AQAATM+dACMZ978AAAAAlBRdgZko+b95Gve/iF8AAKDRnQAuGfe/xyloXwAAAABoX28pAAAAAEYCAADGXwIALjsCAOcWAAA/JycBAABvKT8nJwHMX/o7BxcEAAAAAAAAAEQVQF8AAAAAAAAAAA8AAAD6OxAAAAAAAAAAuF80ev//bynMX0E8Bxf//28pAAAAAG8prADsTQ5gAAADAEQVQF/ngs8XAAAAAAAAAAAPAJgJrAACAOxNAAAAAAAA8D9/AgFAFQoDeP8AAAAAAAAAfw5/AgAAAAB4AgFm4LP0AJCz9AAAAAAAAAEAAHBlAQDsTQIAAAA/AQAAowAsAmkBOQIAAJQUXYGZKKwAVGBOZLcXAREBAOxNAgA/AUcTAQBoYA0NtxcBAQAAAAAAAOxNAgASDcBgIABvAQEBAAAAAD8r978/JycB3GD6OwcXBAAAAJkQsggAALwMtxcBAQAAoNGdAMgn97/HIva/AHCdAFADXYEAAAAAAAAAAA0QAAAAAAAA1Bh7AAAAAADk0J0AamK5vw6AAACQEQBmpHHjAIYfAGakceMAAAAAAOoAAABI0Z0A8+cAZqRx4wDqAAAArB4AZqRx4wDqAAAA4LP0AHxzF6YAAAABYktHRACIBR1IAAAACXBIWXMAAABAAAAAQABiQ2NbAAAADGNtUFBKQ21wMDcxMgAAAANIAHO8AAAAGklEQVQ4T2NgGgWjIUC/EGBgHAWjIUC/EAAAyQQHTjPuGOgAAAAASUVORK5CYII="/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 3:</bold> 
                    <bold>Study Design and Technical Soundness</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We appreciate this concern. To strengthen robustness, we re-ran experiments with 5-fold and 10-fold stratified cross-validation in addition to the 80:20 split. Results are now reported as mean &#x00b1; standard deviation. Performance remained consistently high, though slightly lower than single-split values, confirming stability without evidence of leakage.</p>
                <p> 
                    <bold>Author action: </bold>Added cross-validation experiments and updated Tables 7&#x2013;10 with mean &#x00b1; SD. Reproducibility pipeline clarified in Section 3.5 Methodology.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 4:</bold> 
                    <bold>Methods and Replication</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree. The Ischemic Heart Disease Multiple Imputation Technique (IHD-MIT) is now described in step-by-step detail (predictor selection, iterative regression, variance preservation). For transparency, we have expanded the methodological description of the IHD-MIT imputation pipeline and model implementation in detail.</p>
                <p> 
                    <bold>Author action: </bold>Expanded Section 3.5.1 (IHD-MIT) with algorithmic details.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 5:</bold> 
                    <bold>Statistical Analysis</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We fully agree. We added statistical significance testing (McNemar&#x2019;s test for paired predictions, Wilcoxon signed-rank across folds) to confirm differences. Additionally, we now report ROC curves, AUC values, and calibration plots for clinical interpretability. Results demonstrate that HRAESN improvements are statistically significant (p &lt; 0.05).</p>
                <p> 
                    <bold>Author action: </bold>Added Figure 7 for ROC/AUC; included calibration analysis. Expanded Results Section 4.2&#x2013;4.3 to include statistical testing.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 6:</bold> 
                    <bold>Reproducibility and Source Data</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We clarified all preprocessing steps, including normalization, imputation, train-test stratification, and cross-validation.</p>
                <p> 
                    <bold>Author action: </bold>Updated Figures 3&#x2013;6 captions with supporting details.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 7:</bold> 
                    <bold>Support for Conclusions</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree and have moderated claims. We now clearly state that this work is a proof-of-concept and not clinically deployable yet. We expanded Limitations to address external validation needs, potential bias from imputation, dataset imbalance, computational cost, and the need for interpretability studies.</p>
                <p> 
                    <bold>Author action: </bold>Expanded Section 6 Limitations and Future Directions, emphasizing generalizability and next steps toward real-world validation.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAm8AAAACCAMAAAA5HcsXAAAAHXRFWHRUaXRsZQBkZWZhdWx0X2hvcml6b250YWxfbGluZffN59AAAAMAUExURcDAwMzMzGZmZgAAACdhub8CAAAAAAAAADwE4wA8BOMAYAGLAGwfnxdHAJiOAABijsNEzxdUzp0AORtAX5gJAAAPAAAAAAAAAAAAAAA8BOMAcM6dAMkWQF8PAAAAAAAAAAAAAAAPAAAAAAAAANDOnQA7FkBfDwAAAAAAAAAHAAAAIM+dAI5fAABqz50AmAkAAAIEAAABAAAAAAAAAAAAAAAAAAAAAAAAABgQQF8JAAAAIM+dAI5fAABgAYsAhM6dAAzPnQDK+EhfAAAAAOzOnQDGFUBfAAAAAJgJAAAPAAAAGBBAXwkAAAAgz50ACM+dAFAbQF+CLUBfAAAAAIsVQF+OXwAAeAB7AFTPnQAr+Ehf/////zjPnQBjNve/mAkAAA8AAAAAAAAAAAAAAMcpaF8/AQAATM+dACMZ978AAAAAlBRdgZko+b95Gve/iF8AAKDRnQAuGfe/xyloXwAAAABoX28pAAAAAEYCAADGXwIALjsCAOcWAAA/JycBAABvKT8nJwHMX/o7BxcEAAAAAAAAAEQVQF8AAAAAAAAAAA8AAAD6OxAAAAAAAAAAuF80ev//bynMX0E8Bxf//28pAAAAAG8prADsTQ5gAAADAEQVQF/ngs8XAAAAAAAAAAAPAJgJrAACAOxNAAAAAAAA8D9/AgFAFQoDeP8AAAAAAAAAfw5/AgAAAAB4AgFm4LP0AJCz9AAAAAAAAAEAAHBlAQDsTQIAAAA/AQAAowAsAmkBOQIAAJQUXYGZKKwAVGBOZLcXAREBAOxNAgA/AUcTAQBoYA0NtxcBAQAAAAAAAOxNAgASDcBgIABvAQEBAAAAAD8r978/JycB3GD6OwcXBAAAAJkQsggAALwMtxcBAQAAoNGdAMgn97/HIva/AHCdAFADXYEAAAAAAAAAAA0QAAAAAAAA1Bh7AAAAAADk0J0AamK5vw6AAACQEQBmpHHjAIYfAGakceMAAAAAAOoAAABI0Z0A8+cAZqRx4wDqAAAArB4AZqRx4wDqAAAA4LP0AHxzF6YAAAABYktHRACIBR1IAAAACXBIWXMAAABAAAAAQABiQ2NbAAAADGNtUFBKQ21wMDcxMgAAAANIAHO8AAAAGklEQVQ4T2NgGgWjIUC/EGBgHAWjIUC/EAAAyQQHTjPuGOgAAAAASUVORK5CYII="/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 8:</bold> 
                    <bold>Minor Comments</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer. Related Works was condensed (as above). Figures now include statistical annotations (significance levels). We clarified that Kaggle data are anonymized and released under open license, with ethical approvals obtained by original curators. The manuscript was carefully edited for conciseness.</p>
                <p> 
                    <bold>Author action: </bold>Revised Section 2, updated figure annotations, clarified Ethics Statement, and streamlined prose throughout.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#3, Concern # 1:</bold> 
                    <bold>Reviewer Recommendations Implemented</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; 
                    <list list-type="bullet">
                        <list-item>
                            <p>Re-ran experiments with 10-fold cross-validation.</p>
                        </list-item>
                        <list-item>
                            <p>Reported mean &#x00b1; SD for all metrics.</p>
                        </list-item>
                        <list-item>
                            <p>Added statistical tests (McNemar, Wilcoxon).</p>
                        </list-item>
                        <list-item>
                            <p>Included ROC curves.</p>
                        </list-item>
                        <list-item>
                            <p>Provided algorithmic details of IHD-MIT.</p>
                        </list-item>
                        <list-item>
                            <p>Strengthened novelty discussion and limitations.</p>
                        </list-item>
                    </list> &#x00b7;
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> We sincerely thank Reviewer&#x00a0; for the constructive and rigorous feedback. All major concerns regarding methodology, reproducibility, and statistical robustness have been addressed with substantial new analyses, expanded methodological detail, and clearer discussion of novelty and limitations. We believe these revisions significantly improve the scientific soundness and transparency of the manuscript.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report406539">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.182263.r406539</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Shrestha</surname>
                        <given-names>Dhadkan</given-names>
                    </name>
                    <xref ref-type="aff" rid="r406539a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0009-0007-2588-3734</uri>
                </contrib>
                <aff id="r406539a1">
                    <label>1</label>Texas State University College of Science and Engineering, San Marcos, Texas, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>4</day>
                <month>9</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Shrestha D</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport406539" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.165575.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>
                <bold>1. Summary of the Article</bold>
            </p>
            <p> The manuscript presents a 
                <bold>Hybrid Residual Attention with Echo State Network (HRAESN)</bold> model for predicting ischemic heart disease (IHD). The approach integrates 
                <bold>Attention Residual Learning (ARL)</bold> for feature extraction with 
                <bold>Echo State Networks (ESNs)</bold> for efficient time-series learning. The study evaluates performance on two publicly available datasets: the 
                <bold>Kaggle Cardiovascular Disease dataset (70,000 records)</bold> and the 
                <bold>UCI Heart Disease dataset (303 records)</bold>. Missing values were handled using a tailored 
                <bold>Multiple Imputation Technique</bold>. The proposed model achieved high classification performance, with accuracies of 
                <bold>98.4% (Kaggle)</bold> and 
                <bold>97.7% (UCI)</bold>, surpassing traditional ML and DL baselines. The authors conclude that the model offers strong potential as a clinical decision-support tool for early IHD detection.</p>
            <p> </p>
            <p> 
                <bold>2. Evaluation of Key Criteria</bold>
            </p>
            <p> (a) Clarity, Accuracy, and Literature Coverage 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>Yes (with minor improvements suggested)</bold>
                        </p>
                        <p> The manuscript is clearly written, structured logically, and cites a broad range of recent literature. The background is thorough and informative. A few parts (e.g., the objectives and problem statement) overlap slightly and could be streamlined for conciseness.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Constructive suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Condense repetitive sections to make the narrative flow smoother.</p>
                                </list-item>
                                <list-item>
                                    <p>More explicitly highlight how this approach differs from other recent hybrid deep learning works to strengthen the novelty claim.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> (b) Study Design and Technical Soundness 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>&#x00a0;Yes</bold>
                        </p>
                        <p> The study design is technically sound, and the proposed model is innovative. The integration of ARL and ESN is well motivated. The results are very strong, though the extremely high accuracy on the small UCI dataset raises the possibility of overfitting. Still, the use of dropout and a robust hyperparameter setup is a positive point.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>For added robustness, apply 
                                        <bold>k-fold cross-validation</bold> (especially for UCI dataset).</p>
                                </list-item>
                                <list-item>
                                    <p>Briefly discuss class balance and whether any balancing strategy (e.g., weighting) was needed.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> (c) Methods and Replicability 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>Partly</bold>
                        </p>
                        <p> The mathematical formulation is clear, and hyperparameters are well documented. This is very helpful. However, replication would be easier if code or pseudo-code for preprocessing and training were made available.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Consider providing 
                                        <bold>code, pseudocode, or a detailed pipeline</bold> in supplementary materials.</p>
                                </list-item>
                                <list-item>
                                    <p>Clarify how hyperparameters were tuned (manual search, grid search, etc.).</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> (d) Statistical Analysis and Interpretation 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>&#x00a0;Yes</bold>
                        </p>
                        <p> The authors present a comprehensive set of performance metrics (accuracy, sensitivity, specificity, F1, Kappa, FAR/FRR), which is commendable. Interpretation is generally appropriate. One minor limitation is the absence of variance/confidence intervals across multiple runs.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Indicate whether results are from a single run or averaged across runs.</p>
                                </list-item>
                                <list-item>
                                    <p>If possible, include confidence intervals or standard deviations.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> (e) Availability of Source Data 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>Yes</bold>
                        </p>
                        <p> The datasets (UCI and Kaggle) are publicly available and properly cited. Ethical considerations are addressed. This ensures reproducibility of the raw data.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>It would be helpful to share the 
                                        <bold>preprocessed datasets or preprocessing scripts</bold> used before training.</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> </p>
            <p> (f) Conclusions and Support from Results 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Assessment</bold>: 
                            <bold>Yes</bold>
                        </p>
                        <p> The conclusions are well supported by the reported results. The performance improvement over baselines is clear. That said, claims about clinical applicability should be framed as 
                            <bold>potential future applications</bold> rather than immediate readiness.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Suggestions</bold>: 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Add a brief &#x201c;Limitations&#x201d; section noting that real-world hospital validation is pending.</p>
                                </list-item>
                                <list-item>
                                    <p>Slightly temper statements on clinical deployment to emphasize this is a proof-of-concept</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list> 
                <bold>3. Key Points to Address</bold>
            </p>
            <p> To make the manuscript even stronger, the authors should consider: 
                <list list-type="order">
                    <list-item>
                        <p>Adding 
                            <bold>cross-validation results</bold> (especially for the UCI dataset).</p>
                    </list-item>
                    <list-item>
                        <p>Reporting 
                            <bold>variance or confidence intervals</bold> for performance metrics.</p>
                    </list-item>
                    <list-item>
                        <p>Providing 
                            <bold>code/pseudocode or preprocessing details</bold> for easier replication.</p>
                    </list-item>
                    <list-item>
                        <p>Including a short 
                            <bold>limitations section</bold> (dataset size, clinical validation, computational cost).</p>
                    </list-item>
                </list>
            </p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Machine Learning, Artificial Intelligence, Big Data</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment14541-406539">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>RANGANATHAN</surname>
                            <given-names>VIJAYA ARJUNAN</given-names>
                        </name>
                        <aff>School of Computer Engineering, Manipal Academy of Higher Education, Manipal, Karnataka, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>The author(s) declare that they have no competing interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>10</day>
                    <month>9</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Deep Learning based hybrid residual attention and echo state network for high-accuracy heart disease prediction</bold>
                </p>
                <p> 
                    <bold>Responses to peer review reports</bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 1:</bold> Summary of the Article</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer for the accurate and concise summary of our work. We appreciate the recognition of our proposed Hybrid Residual Attention with Echo State Network (HRAESN) model, our methodological contributions (Attention Residual Learning combined with Echo State Networks), and our evaluation using the Kaggle and UCI datasets. We also thank the reviewer for noting our strategy for handling missing values and the strong performance achieved by the model.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 2:</bold> Clarity, Accuracy, and Literature Coverage</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree with this suggestion. We revised the Introduction to remove overlap between the problem statement and objectives, improving narrative flow. Additionally, we added a new paragraph at the end of the Introduction to explicitly highlight novelty: (i) integration of ARL with ESNs, (ii) extending ESNs to structured/tabular clinical data, and (iii) introducing an IHD-specific multiple imputation method.</p>
                <p> 
                    <bold>Author action: </bold>Revised Introduction: merged problem statement + objectives into a concise paragraph. Added final paragraph in Introduction to emphasize novelty.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,/9j/4AAQSkZJRgABAQEAkACQAAD/2wBDAAgGBgcGBQgHBwcJCQgKDBQNDAsLDBkSEw8UHRofHh0aHBwgJC4nICIsIxwcKDcpLDAxNDQ0Hyc5PTgyPC4zNDL/wAALCAADAqYBAREA/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAAAF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RFRkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/9oACAEBAAA/AO9/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Rr/9k="/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 3:</bold> Study Design and Technical Soundness</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer for this important point. To address robustness, we added text in Methods clarifying that k-fold cross-validation (k=5) was performed on the UCI dataset, confirming stable results across folds. We also report class balance: UCI dataset (~54% IHD, ~46% healthy) and Kaggle dataset (~50% each), showing no major imbalance. No resampling or weighting was needed. We further acknowledge the potential risk of overfitting in the Discussion as a limitation.</p>
                <p> 
                    <bold>Author action: </bold>Added in Section 3.5: description of k-fold cross-validation on UCI dataset. Added in Section 3.1.4: class balance description. Expanded Discussion: limitation noting overfitting risk in small datasets.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,/9j/4AAQSkZJRgABAQEAkACQAAD/2wBDAAgGBgcGBQgHBwcJCQgKDBQNDAsLDBkSEw8UHRofHh0aHBwgJC4nICIsIxwcKDcpLDAxNDQ0Hyc5PTgyPC4zNDL/wAALCAADAqYBAREA/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAAAF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RFRkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/9oACAEBAAA/AO9/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Rr/9k="/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 4:</bold> Methods and Replicability</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We appreciate this suggestion. To enhance replicability, we included a pseudo-code style Algorithm (Algorithm 1) in the Methods section, summarizing the preprocessing, model training, and evaluation pipeline. We also clarified that hyperparameters were tuned via grid search, selecting the configuration with the highest validation F1-score.</p>
                <p> 
                    <bold>Author action: </bold>Added Algorithm 1 (pipeline) in Section 3.5. Clarified hyperparameter tuning strategy (grid search).</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 5:</bold> Statistical Analysis and Interpretation</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree. Results now explicitly state they are averaged across multiple runs. We also computed 95% confidence intervals for all primary metrics using bootstrap resampling (1000 iterations).</p>
                <p> 
                    <bold>Author action: </bold>Updated Results to note averaged results across runs.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 6:</bold> Availability of Source Data</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer for this comment. While raw datasets are already public, we recognize that preprocessing adds value for replication. We now provide a detailed preprocessing description in Methods (Section 3.1.4) and make scripts available upon request.</p>
                <p> 
                    <bold>Author action: </bold>Expanded Section 3.1.4 with detailed preprocessing description.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,/9j/4AAQSkZJRgABAQEAkACQAAD/2wBDAAgGBgcGBQgHBwcJCQgKDBQNDAsLDBkSEw8UHRofHh0aHBwgJC4nICIsIxwcKDcpLDAxNDQ0Hyc5PTgyPC4zNDL/wAALCAADAqYBAREA/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAAAF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RFRkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/9oACAEBAAA/AO9/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/wCEZ0X/AKB0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/hGdF/6B0P5Gj/AIRnRf8AoHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP+EZ0X/oHQ/kaP8AhGdF/wCgdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Ro/4RnRf+gdD+Rr/9k="/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 7:</bold> Conclusions and Support from Results</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree with this suggestion. The Discussion has been expanded with a new Limitations subsection addressing dataset size, lack of external clinical validation, potential imputation bias, and computational cost. Statements on clinical application have been revised to emphasize that this is a proof-of-concept with potential future clinical use.</p>
                <p> 
                    <bold>Author action: </bold>Expanded Discussion with Limitations subsection. Rephrased Conclusion to emphasize proof-of-concept, not immediate deployment.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/>
                    </bold>
                </p>
                <p> 
                    <bold>Reviewer#2, Concern # 8:</bold> Key Points to Address</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; All these points have been addressed in the revision: 
                    <list list-type="bullet">
                        <list-item>
                            <p>Cross-validation results for UCI dataset included.</p>
                        </list-item>
                        <list-item>
                            <p>95% confidence intervals.</p>
                        </list-item>
                        <list-item>
                            <p>Algorithm 1 (pseudo-code pipeline) added in Methods.</p>
                        </list-item>
                        <list-item>
                            <p>Expanded Discussion with a Limitations section.</p>
                        </list-item>
                    </list> 
                    <bold>Author action: </bold>Revisions made in Sections 3.1.4, 3.5, Results, and Discussion.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/>
                    </bold>
                </p>
                <p> We sincerely thank Reviewer&#x00a0; for the constructive and rigorous feedback. All major concerns regarding methodology, reproducibility, and statistical robustness have been addressed with substantial new analyses, expanded methodological detail, and clearer discussion of novelty and limitations. We believe these revisions significantly improve the scientific soundness and transparency of the manuscript.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report401540">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.182263.r401540</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Haue</surname>
                        <given-names>Amalie Dahl</given-names>
                    </name>
                    <xref ref-type="aff" rid="r401540a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-7656-7976</uri>
                </contrib>
                <aff id="r401540a1">
                    <label>1</label>University of Copenhagen, Copenhagen, Denmark</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>25</day>
                <month>8</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Haue AD</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport401540" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.165575.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The research article by Ranganathan et al. presents a deep learning based hybrid residual attention and echo state network for high-accuracy heart disease prediction derived from analysis of the Kaggle Cardiovascular Disease dataset and the UCI Heart Disease dataset. Their model (HRAEN) demonstrates superior perfomance with accuracy rating between 97.7% and 98.4%.</p>
            <p> </p>
            <p> Introduction</p>
            <p> The very first paragraph is could benefit from being rewritten to ensure a better flow and updated to align with current practise. For example, neither stress test, nor Holter monitoring are used routinely to detect ischemic heart disease (IHD). Rather cardiac CT, RbPET and invasive examinations such as coronary arteriography are being used to assess degree of IHD</p>
            <p> </p>
            <p> Related works</p>
            <p> This section would benefit greatly from a more condensed presentation of the literature.</p>
            <p> </p>
            <p> Materials and methods</p>
            <p> It is not clear how heart disease (presence or absence) was defined in the two cohorts, i.e. which diagnostic tests were used.</p>
            <p> Figure 1 and 2 are not detailed enough, i.e. were all entries (observations) in the two datasets included in the study, what was the degree of missingness, and (again) how was IHD assessed?</p>
            <p> It is not clear how the Echo State Networkds (ESNs) were applied to the data at hand since not time-series data is introduced.</p>
            <p> </p>
            <p> Results and analysis</p>
            <p> The different classes are not annotated consistently. That is, is "Class 1" "heart disease" (as listed in Materials and methods) or "ischemic heart disease" (as listed in Results and analysis)?</p>
            <p> New metrics, such as Kappa score/coefficient and Jaccard coefficient are introduced in this section. They ought to be introduced in Materials and methods.&#x00a0;</p>
            <p> Figure 4: Does the figure display the performance of the models on a particular dataset or a combined version?</p>
            <p> For the performance metrics, it would be beneficial to include confidence intervals for assessment of statistical significance.</p>
            <p> Figure 6: The authors state that it converts that the proposed HRAESN model outperforms traditional classifiers in multiple performance aspects. However, only the HRAESN evaluated on the UCI and Kaggle dataset are reported in this figure.</p>
            <p> Were the test and training sets similar? It would be nice with a table that provides an overview of the baseline characteristics in the different populations.</p>
            <p> Table 6 and 7: The authors ought to argue that the HRAESN is comparable to the existing methods. For example, it is not clear why HRAESN on the UCI Heart Disease Dataset and the Kaggle Cardiovascular Disease dataset are being compared to different existing methods. Further, were the existing methods trained to perform a similar classification task as HRAESN. Again the definition of heart disease/IHD as how it was diagnosed is crucial here, but unfortunately lacking from this version of the manuscript.</p>
            <p> </p>
            <p> Discussion</p>
            <p> This section appears to be incomplete. For example, the lack of external validation is not addressed. Further, the use of imputation and the potential bias of the results is not discussed. Finally, there is not evaluation of the impact of the Attention Residual Learning (ARL), i.e., which features were most important in the classification when ARL was performed? And, could this strategy be used to identify a limited set of features that could obtain similar performance metrics?</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>I cannot comment. A qualified statistician is required.</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Yes</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Cardiology resident</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment14540-401540">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>RANGANATHAN</surname>
                            <given-names>VIJAYA ARJUNAN</given-names>
                        </name>
                        <aff>School of Computer Engineering, Manipal Academy of Higher Education, Manipal, Karnataka, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>The author(s) declare that they have no competing interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>10</day>
                    <month>9</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Deep Learning based hybrid residual attention and echo state network for high-accuracy heart disease prediction</bold>
                </p>
                <p> 
                    <bold>Responses to peer review reports</bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 1:</bold> Introduction</p>
                <p> The very first paragraph is could benefit from being rewritten to ensure a better flow and updated to align with current practise. For example, neither stress test, nor Holter monitoring are used routinely to detect ischemic heart disease (IHD). Rather cardiac CT, RbPET and invasive examinations such as coronary arteriography are being used to assess degree of IHD</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer for this valuable suggestion. We have revised the introductory paragraph to better reflect current clinical practices, replacing outdated references (stress test, Holter monitoring) with contemporary modalities such as cardiac CT, RbPET, and coronary angiography.</p>
                <p> 
                    <bold>Author action: </bold>The Introduction now begins with a discussion of ischemic heart disease pathophysiology and updated diagnostic modalities.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 2: Related works</bold>
                </p>
                <p> 
                    <bold>This section would benefit greatly from a more condensed presentation of the literature.</bold>
                </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We appreciate this suggestion. We revised the Related Works section to streamline the narrative, grouping studies under thematic categories (traditional ML, deep learning, hybrid models, ESN-based, and attention-based methods).</p>
                <p> 
                    <bold>Author action: </bold>Section 2 was restructured for conciseness while retaining comprehensiveness.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 3:</bold> Materials and methods</p>
                <p> It is not clear how heart disease (presence or absence) was defined in the two cohorts, i.e. which diagnostic tests were used.</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We acknowledge this concern. We now clearly define the target variables in both datasets: 
                    <list list-type="bullet">
                        <list-item>
                            <p>UCI: angiography-based &#x201c;num&#x201d; variable, binarized (0 = absence, 1&#x2013;4 = presence of disease).</p>
                        </list-item>
                        <list-item>
                            <p>Kaggle: &#x201c;cardio&#x201d; variable defined by combined clinical assessments (blood pressure, cholesterol, ECG).</p>
                        </list-item>
                    </list> 
                    <bold>Author action: </bold>Added Section 3.1.4 Definition of Heart Disease in the Datasets.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 4: </bold>Figure 1 and 2 are not detailed enough, i.e. were all entries (observations) in the two datasets included in the study, what was the degree of missingness, and (again) how was IHD assessed?</p>
                <p> &#x00a0;
                    <bold>Author response:</bold>&#x00a0; We appreciate this important comment. We have clarified in Section 3.1.4 how IHD was defined in each dataset (Kaggle: cardio; UCI: num attribute binarized). Missing data handling using the IHD Multiple Imputation Technique is now described. We also added clarification on how Echo State Networks were applied to structured tabular data (not time-series). Figures 1 and 2 were redesigned to show dataset composition, preprocessing, and architecture in greater detail.</p>
                <p> 
                    <bold>Author action: </bold>Section 3.1.4 updated with disease definition, missingness handling, and ESN applicability.</p>
                <p> Redesigned Figure 1 (workflow with dataset size, missing values, preprocessing, labels, metrics).</p>
                <p> Redesigned Figure 2 (detailed HRAESN architecture with ESN + ARL modules).</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 5:</bold> It is not clear how the Echo State Networkds (ESNs) were applied to the data at hand since not time-series data is introduced.</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree this required clarification. While raw ECG series were not used, we adapted ESNs by treating patient feature vectors as structured sequences, mapping them into reservoir states to capture nonlinear feature dependencies.</p>
                <p> 
                    <bold>Author action: </bold>Added explanation in Section 3.5 Methodology &#x2013; Application of ESNs to Tabular Data.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 6:</bold> Results and analysis</p>
                <p> The different classes are not annotated consistently. That is, is "Class 1" "heart disease" (as listed in Materials and methods) or "ischemic heart disease" (as listed in Results and analysis)?</p>
                <p> </p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We standardized terminology throughout: Class 0 = no IHD, Class 1 = IHD present.</p>
                <p> 
                    <bold>Author action: </bold>Updated class definitions consistently across Materials &amp; Methods, Results, and figures.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 7:</bold> New metrics, such as Kappa score/coefficient and Jaccard coefficient are introduced in this section. They ought to be introduced in Materials and methods.&#x00a0;</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We thank the reviewer. These metrics are now introduced in Evaluation Metrics subsection of Materials and Methods.</p>
                <p> 
                    <bold>Author action: </bold>Section 3.5 includes definitions of Kappa coefficient and Jaccard index.</p>
                <p> 
                    <inline-graphic xlink:href="data:image/png;base64,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"/>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 8:</bold> Figure 4: Does the figure display the performance of the models on a particular dataset or a combined version?</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We have clarified the figure captions to indicate that Figure 4 reports performance metrics separately for both UCI and Kaggle datasets.</p>
                <p> 
                    <bold>Author action: </bold>Updated
                    <bold> </bold>Figure 4 caption as suggested</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 9:</bold> For the performance metrics, it would be beneficial to include confidence intervals for assessment of statistical significance.</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We have now reported 95% confidence intervals using bootstrap resampling (1000 iterations) for all major performance metrics.</p>
                <p> 
                    <bold>Author action: </bold>Confidence intervals are included in tables as suggested.</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 10:</bold> Figure 6: The authors state that it converts that the proposed HRAESN model outperforms traditional classifiers in multiple performance aspects. However, only the HRAESN evaluated on the UCI and Kaggle dataset are reported in this figure.</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree this was ambiguous. Figure 6 is intended to illustrate HRAESN error rates across datasets, while comparative results with baselines are in Tables 8&#x2013;9.</p>
                <p> 
                    <bold>Author action: </bold>Figure 6 caption updated to clarify scope</p>
                <p> 
                    <bold>
                        <inline-graphic xlink:href="data:image/png;base64,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"/> </bold>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 11:</bold> Were the test and training sets similar? It would be nice with a table that provides an overview of the baseline characteristics in the different populations.</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We now provide a table of baseline characteristics (age, sex, cholesterol, blood pressure) for training and test subsets.</p>
                <p> 
                    <bold>Author action: </bold>Added Table 3: Baseline Characteristics.</p>
                <p> 
                    <inline-graphic xlink:href="data:image/png;base64,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"/>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 12:</bold> Table 6 and 7: The authors ought to argue that the HRAESN is comparable to the existing methods. For example, it is not clear why HRAESN on the UCI Heart Disease Dataset and the Kaggle Cardiovascular Disease dataset are being compared to different existing methods. Further, were the existing methods trained to perform a similar classification task as HRAESN. Again the definition of heart disease/IHD as how it was diagnosed is crucial here, but unfortunately lacking from this version of the manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Author response:</bold> We appreciate this comment. Tables 6 and 7 were updated/clarified with consistent captions and explanations of dataset comparisons.&#x00a0; We expanded the Discussion to address: 
                    <list list-type="bullet">
                        <list-item>
                            <p>Lack of external validation and need for future hospital-based datasets.</p>
                        </list-item>
                        <list-item>
                            <p>Potential imputation bias and future use of sensitivity analyses.</p>
                        </list-item>
                        <list-item>
                            <p>Importance of ARL interpretability and plans to evaluate feature contributions.</p>
                        </list-item>
                    </list> 
                    <bold>Author action: </bold>Tables 6&#x2013;7 revised with rationale for comparing UCI vs Kaggle against different baselines. Expanded Section 6 Limitations and Future Directions.</p>
                <p> 
                    <inline-graphic xlink:href="data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAm8AAAACCAMAAAA5HcsXAAAAHXRFWHRUaXRsZQBkZWZhdWx0X2hvcml6b250YWxfbGluZffN59AAAAMAUExURcDAwMzMzGZmZgAAACdhub8CAAAAAAAAADwE4wA8BOMAYAGLAGwfnxdHAJiOAABijsNEzxdUzp0AORtAX5gJAAAPAAAAAAAAAAAAAAA8BOMAcM6dAMkWQF8PAAAAAAAAAAAAAAAPAAAAAAAAANDOnQA7FkBfDwAAAAAAAAAHAAAAIM+dAI5fAABqz50AmAkAAAIEAAABAAAAAAAAAAAAAAAAAAAAAAAAABgQQF8JAAAAIM+dAI5fAABgAYsAhM6dAAzPnQDK+EhfAAAAAOzOnQDGFUBfAAAAAJgJAAAPAAAAGBBAXwkAAAAgz50ACM+dAFAbQF+CLUBfAAAAAIsVQF+OXwAAeAB7AFTPnQAr+Ehf/////zjPnQBjNve/mAkAAA8AAAAAAAAAAAAAAMcpaF8/AQAATM+dACMZ978AAAAAlBRdgZko+b95Gve/iF8AAKDRnQAuGfe/xyloXwAAAABoX28pAAAAAEYCAADGXwIALjsCAOcWAAA/JycBAABvKT8nJwHMX/o7BxcEAAAAAAAAAEQVQF8AAAAAAAAAAA8AAAD6OxAAAAAAAAAAuF80ev//bynMX0E8Bxf//28pAAAAAG8prADsTQ5gAAADAEQVQF/ngs8XAAAAAAAAAAAPAJgJrAACAOxNAAAAAAAA8D9/AgFAFQoDeP8AAAAAAAAAfw5/AgAAAAB4AgFm4LP0AJCz9AAAAAAAAAEAAHBlAQDsTQIAAAA/AQAAowAsAmkBOQIAAJQUXYGZKKwAVGBOZLcXAREBAOxNAgA/AUcTAQBoYA0NtxcBAQAAAAAAAOxNAgASDcBgIABvAQEBAAAAAD8r978/JycB3GD6OwcXBAAAAJkQsggAALwMtxcBAQAAoNGdAMgn97/HIva/AHCdAFADXYEAAAAAAAAAAA0QAAAAAAAA1Bh7AAAAAADk0J0AamK5vw6AAACQEQBmpHHjAIYfAGakceMAAAAAAOoAAABI0Z0A8+cAZqRx4wDqAAAArB4AZqRx4wDqAAAA4LP0AHxzF6YAAAABYktHRACIBR1IAAAACXBIWXMAAABAAAAAQABiQ2NbAAAADGNtUFBKQ21wMDcxMgAAAANIAHO8AAAAGklEQVQ4T2NgGgWjIUC/EGBgHAWjIUC/EAAAyQQHTjPuGOgAAAAASUVORK5CYII="/>
                </p>
                <p> 
                    <bold>Reviewer#1, Concern # 13:</bold> Discussion</p>
                <p> This section appears to be incomplete. For example, the lack of external validation is not addressed. Further, the use of imputation and the potential bias of the results is not discussed. Finally, there is not evaluation of the impact of the Attention Residual Learning (ARL), i.e., which features were most important in the classification when ARL was performed? And, could this strategy be used to identify a limited set of features that could obtain similar performance metrics?</p>
                <p> 
                    <bold>Author response:</bold>&#x00a0; We agree with this comment and have expanded the Discussion to address these limitations. We now discuss the absence of external validation, the potential bias introduced by imputation, and the interpretability of ARL. We also comment on future work to explore feature importance and whether a smaller subset of features could achieve comparable accuracy.</p>
                <p> 
                    <bold>Author action: </bold>Discussion section expanded with subsections on limitations, imputation bias, and ARL interpretability.</p>
                <p> 
                    <inline-graphic xlink:href="data:image/png;base64,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"/>
                </p>
                <p> We sincerely thank Reviewer&#x00a0; for the constructive and rigorous feedback. All major concerns regarding methodology, reproducibility, and statistical robustness have been addressed with substantial new analyses, expanded methodological detail, and clearer discussion of novelty and limitations. We believe these revisions significantly improve the scientific soundness and transparency of the manuscript.</p>
            </body>
        </sub-article>
    </sub-article>
</article>
