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12 pages, 1009 KiB  
Article
The Systemic Inflammation Response Index Efficiently Discriminates between the Failure Patterns of Patients with Isocitrate Dehydrogenase Wild-Type Glioblastoma Following Radiochemotherapy with FLAIR-Based Gross Tumor Volume Delineation
by Sukran Senyurek, Murat Serhat Aygun, Nulifer Kilic Durankus, Eyub Yasar Akdemir, Duygu Sezen, Erkan Topkan, Yasemin Bolukbasi and Ugur Selek
Brain Sci. 2024, 14(9), 922; https://doi.org/10.3390/brainsci14090922 (registering DOI) - 15 Sep 2024
Abstract
Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients [...] Read more.
Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients who received RT at a dose of 60 Gy to the GTV and 50 Gy to the clinical target volume (CTV) and had documented recurrence were retrospectively analyzed. Each patient’s maximum distance of recurrence (MDR) from the GTV was documented in whichever plane it extended the farthest. The failure patterns were described as intra-GTV, in-CTV/out-GTV, distant, and intra-GTV and distant. For analytical purposes, the failure pattern was categorized into two groups, namely Group 1, intra-GTV or in-CTV/out-GTV, and Group 2, distant or intra-GTV and distant. The SIRI was calculated before surgery and corticosteroid administration. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal SIRI cut-off that distinguishes between the different failure patterns. Results: Failure occurred as follows: intra-GTV in 40 (56.3%), in-CTV/out-GTV in 4 (5.6%), distant in 18 (25.4%), and intra-GTV + distant in 9 (12.7%) patients. The mean MDR was 13.5 mm, and recurrent lesions extended beyond 15 mm in only seven patients. Patients with an SIRI score ≥ 3 demonstrated a significantly higher incidence of Group 1 failure patterns than their counterparts with an SIRI score < 3 (74.3% vs. 50.0%; p = 0.035). Conclusions: The present results show that using the SIRI with a cut-off value of ≥3 significantly predicts failure patterns. Additionally, the margin for the GTV can be safely reduced to 15 mm when using FLAIR-based target delineation in patients with GB. Full article
(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy)
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<p>Examples of failure pattern definition. Intra-GTV (<b>a</b>,<b>b</b>), in-CTV/out-GTV (<b>c</b>), and distant (<b>d</b>). Red line: gross tumor volume (prescribed dose: 60 Gy/30 fr), blue line: clinical target volume (prescribed dose: 50 Gy/30 fr), cyan line: recurrent lesion.</p>
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<p>Receiver operating characteristic curve analyses outcomes. Area under curve: 71.8%; sensitivity: 71.8%; specificity: 70.3%; J-index: 0.421.</p>
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14 pages, 1182 KiB  
Article
High-Density Lipoprotein-Associated Paraoxonase-1 (PON-1) and Scavenger Receptor Class B Type 1 (SRB-1) in Coronary Artery Disease: Correlation with Disease Severity
by Manish Kumar, Wahid Ali, Kusum Yadav, Swati Kaumri, Sridhar Mishra, Paolo Nardi, Ferdinando Iellamo, Sergio Bernardini, Akshyaya Pradhan and Marco Alfonso Perrone
J. Clin. Med. 2024, 13(18), 5480; https://doi.org/10.3390/jcm13185480 (registering DOI) - 15 Sep 2024
Abstract
Background: Coronary artery disease (CAD) is the leading cause of death worldwide. High-Density lipoprotein (HDL) is a well-established marker associated with CAD. The current research goes beyond the conventional HDL-C measurement in previous studies and dives into the functional intricacies of HDL. By [...] Read more.
Background: Coronary artery disease (CAD) is the leading cause of death worldwide. High-Density lipoprotein (HDL) is a well-established marker associated with CAD. The current research goes beyond the conventional HDL-C measurement in previous studies and dives into the functional intricacies of HDL. By understanding how HDL works, rather than just how much of it exists, we can better tailor diagnostic and therapeutic strategies for CAD and related conditions. Hence, the current study quantifies the serum levels of two novel HDL-associated markers, Paraoxonase-1 (PON-1) and Scavenger Receptor Class B Type 1 (SRB-1), in CAD cases vs. controls. Methods: A total of 92 subjects, including 69 CAD and 23 healthy controls, were included, based on the prevalence of the disease. Further, based on the severity of the disease, CAD cases were subcategorized as CAD-I, -II, and -III. Serum PON-1 and SRB-1 levels were measured and compared between patient and control groups. Results: The levels of PON-1 and SRB-1 (32.6 ng/mL and 12.49 ng/mL) were significantly lower in CAD patients vs. the healthy control, at 60.36 ng/mL and 15.85 ng/mL, respectively (p < 0.000). A further intergroup comparison showed a statistically significant difference between the CAT-I and -III for PON-1 (p < 0.025), the CAT-I and -III, and CAT-II and -III for SRB-1 (p < 0.000). The receiver operating characteristics (ROC) curve showed cutoff values of 48.20 ng/mL and 14.90 ng/mL for PON-1 and SRB-1. Conclusions: The current study found that serum levels of HDL-associated PON-1 and SRB-1 are significantly lower in CAD cases, and were also inversely related to the increasing severity of coronary artery disease. This inference implies that serum PON-1 and SRB-1 could be used as non-invasive tools for the identification of coronary atherosclerosis and risk assessment in CAD cases. Full article
(This article belongs to the Special Issue Cardiovascular Medicine and Cardiac Surgery)
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<p>Scatter plot showing the level of PON-1 in cases and controls, as well as different categories of the CAD severity.</p>
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<p>Scatter plot showing the level of SRB-1 in cases and controls, as well as different categories of the CAD severity.</p>
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<p>ROC curve showing the sensitivity and specificity of PON-1 and SRB-1 in cases and controls and with different categories of CAD severity.</p>
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14 pages, 1870 KiB  
Article
Optimization of Basophil Activation Test in the Diagnosis and Qualification for Allergen-Specific Immunotherapy in Children with Respiratory Allergy to the House Dust Mite Dermatophagoides pteronyssinus
by Radoslaw Spiewak, Aleksandra Gregorius, Grzegorz Ostrowski and Ewa Czarnobilska
Int. J. Mol. Sci. 2024, 25(18), 9959; https://doi.org/10.3390/ijms25189959 (registering DOI) - 15 Sep 2024
Abstract
The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4–17 years, [...] Read more.
The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4–17 years, with perennial asthma or allergic rhinitis caused by D. pteronyssinus. The control group consisted of 13 girls and 19 boys aged 4–17 years with seasonal allergic asthma or rhinitis provoked by Timothy or birch pollen. House dust mite (HDM) allergy was excluded in the controls based on their medical history, skin prick test (SPT) results and sIgE determination. In all patients, a basophil activation test (BAT) was performed with five dilutions of D. pteronyssinus allergen (the dilution series ranged from 22.5 to 0.00225 ng/mL). The results were analyzed by using the receiver operating characteristics (ROC) to determine the optimal allergen concentrations, outcome measures and cut-off points that would differentiate most accurately between HDM-allergic and non-allergic patients. As a “gold standard”, criteria for allergen-specific immunotherapy with D. pteronyssinus or respective pollens were applied by an experienced pediatric allergist following the guidelines of the European Academy of Allergy and Clinical Immunology. The highest diagnostic efficiency was yielded by the protocol assuming a cut-off value of 9.76% activated basophils after activation with a single allergen concentration of 2.25 ng/mL (sensitivity 90.6%, specificity 100%). This protocol yielded 3 (4.7%) misclassifications, all false negative, when compared with the “gold standard”. There was a strong correlation with the BAT results at 22.5, 2.25 and 0.225 ng/mL (respectively r = 0.90 and r = 0.78, p < 0.001), as well as between the BAT at 2.25 ng/mL and SPT (r = 0.82, p < 0.001) and between the SPT and sIgE levels (r = 0.78, p < 0.001). High cross-reactivity between D. pteronyssinus and D. farinae was confirmed based on the BAT at 22.5 ng/mL (r = 0.82, p < 0.001). In conclusion, the BAT showed very good concordance with the result of a meticulous process of decision-making that combined validated allergy tests (SPT, sIgE) with expert guidelines, specialist knowledge and experience. Facing the risk of the incorrect qualification of patients for costly, long-lasting and potentially risky allergen-specific immunotherapy, the inclusion of a basophil activation test into diagnostic process seems fully justified. Full article
(This article belongs to the Collection Feature Papers in Molecular Immunology)
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<p>Results of the BAT expressed as the percent of stimulated (CD63+) basophils with different concentrations of <span class="html-italic">D. pteronyssinus</span> allergen in cases (red) and controls (blue). Numerical data for the graphs are listed in the <a href="#app1-ijms-25-09959" class="html-app">Supplementary Materials</a> (<a href="#app1-ijms-25-09959" class="html-app">Table S1</a>).</p>
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<p>Cumulative results of the BAT (area under the curve—AUC) in cases (red) and controls (blue). Numerical data for the graphs are listed in the <a href="#app1-ijms-25-09959" class="html-app">Supplementary Materials</a> (<a href="#app1-ijms-25-09959" class="html-app">Table S2</a>).</p>
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<p>Graphs representing the receiver operating characteristics (ROC) analyses of the diagnostic accuracy of the compared BAT outcomes. The arrows indicate the computed cut-off values. Letters (<b>a</b>–<b>h</b>) assigned to individual graphs refer to detailed data presented in <a href="#ijms-25-09959-t001" class="html-table">Table 1</a>.</p>
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<p>Gating strategy for basophils (<b>left</b>) and exemplary graphs showing basophil reactivity to controls and response to the allergen of <span class="html-italic">D. pteronyssinus</span> (<b>right</b>).</p>
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22 pages, 4048 KiB  
Article
An Improved Driving Safety Field Model Based on Vehicle Movement Uncertainty for Highway Ramp Influence Areas
by Yueru Xu, Wei Ye, Yalin Luan and Bingbo Cui
Systems 2024, 12(9), 370; https://doi.org/10.3390/systems12090370 (registering DOI) - 14 Sep 2024
Viewed by 249
Abstract
Road traffic accidents result in numerous fatalities and injuries annually. Advanced driving assistance systems (ADASs) have garnered significant attention to mitigate these harms. An accurate safety assessment can significantly improve the effectiveness and credibility of ADASs. However, a real-time safety assessment remains a [...] Read more.
Road traffic accidents result in numerous fatalities and injuries annually. Advanced driving assistance systems (ADASs) have garnered significant attention to mitigate these harms. An accurate safety assessment can significantly improve the effectiveness and credibility of ADASs. However, a real-time safety assessment remains a key challenge due to the complex interactions among humans, vehicles, and the road environment. Traditional safety assessment methods, relying on crash data and surrogate safety measures (SSMs), face limitations in real-time applicability and scenario coverage, especially in freeway ramp areas with frequent merging and lane changing. To address these gaps, this paper develops a driving safety field based on the uncertainty of vehicle movements, which integrates the characteristics of driving behaviors, vehicles, and the road environment. The proposed method is validated with a simulation of driving scenarios and ROC curves obtained from the NGSIM dataset. The results demonstrate that our proposed driving safety field effectively quantifies the real-time risk in ramp influence areas and outperforms Time to Collision (TTC), making it suitable for integration into collision warning systems of ADASs. Full article
13 pages, 3015 KiB  
Article
Evaluating the Clinical Utility of Left Ventricular Strains in Severe AS: A Pilot Study with Feature-Tracking Cardiac Magnetic Resonance
by Carmen Cionca, Alexandru Zlibut, Renata Agoston, Lucia Agoston-Coldea, Rares Ilie Orzan and Teodora Mocan
Biomedicines 2024, 12(9), 2104; https://doi.org/10.3390/biomedicines12092104 (registering DOI) - 14 Sep 2024
Viewed by 212
Abstract
Background: Aortic valve stenosis (AS) is the most common degenerative valvular heart disease, significantly impacting the outcome. Current guidelines recommend valve replacement only for symptomatic patients, but advanced cardiovascular imaging, particularly cardiac magnetic resonance (CMR), may refine these recommendations. Feature-tracking CMR (FT-CMR) effectively [...] Read more.
Background: Aortic valve stenosis (AS) is the most common degenerative valvular heart disease, significantly impacting the outcome. Current guidelines recommend valve replacement only for symptomatic patients, but advanced cardiovascular imaging, particularly cardiac magnetic resonance (CMR), may refine these recommendations. Feature-tracking CMR (FT-CMR) effectively assesses left ventricular (LV) strain and shows promise in predicting major adverse cardiovascular events (MACEs), though data on AS are limited. This study explored the role of CMR-derived LV strain in predicting MACEs occurrence in patients with severe AS. Method: We prospectively assessed 84 patients with severe AS and 84 matched controls. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were evaluated using FT-CMR. A composite endpoint—cardiac death, ventricular tachyarrhythmias, and heart failure hospitalization—was analyzed over a median follow-up of 31 months. Results: GLS was considerably reduced in AS patients (−15.8% vs. −19.7%, p < 0.001) and significantly predicted MACEs (HR = 1.24, p = 0.002) after adjusting for LVEF, 6 min walk distance, native T1, and late gadolinium enhancement. This underscores GLS’s unique and robust predictive capability for MACEs in severe AS patients. Kaplan–Meier curves and ROC analysis both showed that GLS had the highest predictive performance for MACEs, with an AUC of 0.857. Conclusions: GLS provided independent incremental predictive value for outcome. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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<p>Flow-chart of the study design.</p>
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<p>Example of post-processing feature-tracking technique using standard bSSF-CMR Images. The epicardial und endocardial contours are correspondingly drawn and LV strain metrics are graphically reported using the AHA 17-Segment model: GLS (<b>A</b>,<b>B</b>), GRS (<b>C</b>,<b>D</b>), and GCS (<b>E</b>,<b>F</b>). Usually, GLS and GCS show as negative percentage (<b>B</b>,<b>D</b>), whereas GRS show as positive one (<b>F</b>). Abbreviations: AHA, American Heart Association; GLS, global longitudinal strain; GCS, global circumferential strain; GRS, global radial strain; bSSF-CMR, balanced steady-state free precession cardiac magnetic resonance.</p>
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<p>ROC analysis demonstrating the ability of GLS, T1 native, ECV, and LGE. Abbreviations: GLS, global longitudinal strain; LGE, late gadolinium enhancement; ECV, extracellular volume.</p>
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<p>Kaplan–Meier curves for time-to-event analysis of GLS (<b>A</b>,<b>B</b>), GCS (<b>C</b>), and GRS (<b>D</b>). Abbreviations: GLS, global longitudinal strain; GCS, global circumferential strain; GRS, global radial strain.</p>
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<p>Incremental predictive value of GLS added to LVEF, LGE, and ECV. The <span class="html-italic">y</span>-axis represents the Chi-square values of the stepwise Cox proportional hazards models. Abbreviations: GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; LGE, late gadolinium enhancement; ECV, extracellular volume.</p>
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10 pages, 1212 KiB  
Article
Prognostic Significance of Lactate Clearance in Cardiogenic Pulmonary Edema in the Emergency Department
by Mehmet Göktuğ Efgan, Ejder Saylav Bora, Ahmet Kayalı, Umut Payza, Tutku Duman Şahan and Zeynep Karakaya
Medicina 2024, 60(9), 1502; https://doi.org/10.3390/medicina60091502 (registering DOI) - 14 Sep 2024
Viewed by 139
Abstract
Background and Objectives: Acute cardiorespiratory failure disrupts the delicate balance of energy supply, demand, and consumption, with elevated lactate levels and decreased blood pH serving as crucial indicators. Acute cardiogenic pulmonary edema (ACPO), a common cause of acute respiratory failure, poses a [...] Read more.
Background and Objectives: Acute cardiorespiratory failure disrupts the delicate balance of energy supply, demand, and consumption, with elevated lactate levels and decreased blood pH serving as crucial indicators. Acute cardiogenic pulmonary edema (ACPO), a common cause of acute respiratory failure, poses a substantial mortality risk. Lactate, a byproduct of pyruvate reduction, is a pertinent marker in perfusion assessment. Lactate clearance (LC) has proven prognostic efficacy in various conditions but lacks consensus on its predictive power in acute cardiogenic pulmonary edema. Materials and Methods: This prospective observational study, conducted in a metropolitan area’s third-level emergency department, involved patients with cardiogenic pulmonary edema from May 2021 to August 2023. The inclusion criteria specified acute cardiogenic pulmonary edema, excluding patients with incomplete data or other respiratory conditions. Lactate clearance, calculated at presentation and after 6 h, served as the primary outcome predictor. Our data analysis employed logistic regression, the ROC curve, and statistical tests. Results: The cohort of 106 patients revealed that a lactate clearance below 14.29% was significantly associated with mortality. While 51.6% of survivors were discharged, LC’s predictive success for discharge was inconclusive. Logistic regression underscored the significance of lactate clearance, with a one-unit increase yielding a 5.55-fold probability of survival. The AUC for LC was 0.759. Conclusions: This study pioneers the exploration of lactate clearance in patients with acute cardiogenic pulmonary edema. LC below 14.29% signifies a poor prognosis, emphasizing its potential as an early treatment initiation marker. While acknowledging this study’s limitations, we advocate for further multicenter research to refine the understanding of lactate clearance in this context. Full article
(This article belongs to the Section Emergency Medicine)
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<p>Consultation diagram.</p>
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<p>ROC curve for LC measurement performance in predicting outcome.</p>
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<p>ROC analysis for LC success in predicting discharge.</p>
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23 pages, 1172 KiB  
Article
Prevention of Cardiometabolic Syndrome in Children and Adolescents Using Machine Learning and Noninvasive Factors: The CASPIAN-V Study
by Hamid Reza Marateb, Mahsa Mansourian, Amirhossein Koochekian, Mehdi Shirzadi, Shadi Zamani, Marjan Mansourian, Miquel Angel Mañanas and Roya Kelishadi
Information 2024, 15(9), 564; https://doi.org/10.3390/info15090564 - 13 Sep 2024
Viewed by 251
Abstract
Cardiometabolic syndrome (CMS) is a growing concern in children and adolescents, marked by obesity, hypertension, insulin resistance, and dyslipidemia. This study aimed to predict CMS using machine learning based on data from the CASPIAN-V study, which involved 14,226 participants aged 7–18 years, with [...] Read more.
Cardiometabolic syndrome (CMS) is a growing concern in children and adolescents, marked by obesity, hypertension, insulin resistance, and dyslipidemia. This study aimed to predict CMS using machine learning based on data from the CASPIAN-V study, which involved 14,226 participants aged 7–18 years, with a CMS prevalence of 82.9%. We applied the XGBoost algorithm to analyze key noninvasive variables, including self-rated health, sunlight exposure, screen time, consanguinity, healthy and unhealthy dietary habits, discretionary salt and sugar consumption, birthweight, and birth order, father and mother education, oral hygiene behavior, and family history of dyslipidemia, obesity, hypertension, and diabetes using five-fold cross-validation. The model achieved high sensitivity (94.7% ± 4.8) and specificity (78.8% ± 13.7), with an area under the ROC curve (AUC) of 0.867 ± 0.087, indicating strong predictive performance and significantly outperformed triponderal mass index (TMI) (adjusted paired t-test; p < 0.05). The most critical selected modifiable factors were sunlight exposure, screen time, consanguinity, healthy and unhealthy diet, dietary fat type, and discretionary salt consumption. This study emphasizes the clinical importance of early identification of at-risk individuals to implement timely interventions. It offers a promising tool for CMS risk screening. These findings support using predictive analytics in clinical settings to address the rising CMS epidemic in children and adolescents. Full article
(This article belongs to the Section Artificial Intelligence)
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Graphical abstract
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<p>Flow chart of the Prevalence and Dissemination of Non-Communicable Diseases in Children and Adolescents (CASPIAN-V) study design.</p>
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<p>Comparison of ROC curves between our method and the TMI index. The ROC curve for “our method” (blue, solid line) shows an AUC of 0.87. The ROC curve for the TMI index (red, dashed-dot line) is also compared, illustrating its discriminative performance (AUC = 0.75). The diagonal grey dashed line represents the line of no discrimination (AUC = 0.50).</p>
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27 pages, 23025 KiB  
Article
Disulfidptosis: A New Target for Parkinson’s Disease and Cancer
by Tingting Liu, Xiangrui Kong and Jianshe Wei
Curr. Issues Mol. Biol. 2024, 46(9), 10038-10064; https://doi.org/10.3390/cimb46090600 - 12 Sep 2024
Viewed by 259
Abstract
Recent studies have uncovered intriguing connections between Parkinson’s disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves [...] Read more.
Recent studies have uncovered intriguing connections between Parkinson’s disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise. This has sparked our interest in exploring common molecular mechanisms and genetic factors that may be involved in the relationship between neurodegenerative diseases and tumorigenesis. The Gene4PD database was used to retrieve PD differentially expressed genes (DEGs), the biological functions of differential expression disulfidptosis-related genes (DEDRGs) were analyzed, the ROCs of DEDRGs were analyzed using the GEO database, and the expression of DEDRGs was verified by an MPTP-induced PD mouse model in vivo. Then, the DEDRGs in more than 9000 samples of more than 30 cancers were comprehensively and systematically characterized by using multi-omics analysis data. In PD, we obtained a total of four DEDRGs, including ACTB, ACTN4, INF2, and MYL6. The enriched biological functions include the regulation of the NF-κB signaling pathway, mitochondrial function, apoptosis, and tumor necrosis factor, and these genes are rich in different brain regions. In the MPTP-induced PD mouse model, the expression of ACTB was decreased, while the expression of ACTN4, INF2, and MYL6 was increased. In pan-cancer, the high expression of ACTB, ACTN4, and MYL6 in GBMLGG, LGG, MESO, and LAML had a poor prognosis, and the high expression of INF2 in LIHC, LUAD, UVM, HNSC, GBM, LAML, and KIPAN had a poor prognosis. Our study showed that these genes were more highly infiltrated in Macrophages, NK cells, Neutrophils, Eosinophils, CD8 T cells, T cells, T helper cells, B cells, dendritic cells, and mast cells in pan-cancer patients. Most substitution mutations were G-to-A transitions and C-to-T transitions. We also found that miR-4298, miR-296-3p, miR-150-3p, miR-493-5p, and miR-6742-5p play important roles in cancer and PD. Cyclophosphamide and ethinyl estradiol may be potential drugs affected by DEDRGs for future research. This study found that ACTB, ACTN4, INF2, and MYL6 are closely related to PD and pan-cancer and can be used as candidate genes for the diagnosis, prognosis, and therapeutic biomarkers of neurodegenerative diseases and cancers. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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<p>The DEDRG-enriched GO terms and KEGG pathways. (<b>A</b>) GOBP, GOCC, and GOMF analysis. (<b>B</b>) Signaling pathway enrichment analysis. Red represents DEDRGs, green represents biological process, purple represents molecular function, orange represents cellular component, and blue represents signaling pathways.</p>
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<p>Spatio-temporal expression profiles of (<b>A</b>) ACTB, (<b>B</b>) ACTN4, (<b>C</b>) INF2, and (<b>D</b>) MYL6 retrieved from BrainSpan. The darker the blue color, the higher the protein expression level in the brain region.</p>
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<p>Diagnostic value of DEDRGs in (<b>A</b>) 16 PD and 9 control subjects from the substantia nigra postmortem brain from the GSE7621 dataset; (<b>B</b>) 8 PD and 9 control subjects from the substantia nigra of postmortem brains from the GSE20163 dataset; (<b>C</b>) 6 PD and 5 control subjects from substantia nigra samples from the GSE20164 dataset; (<b>D</b>) control Braak α-synuclein Stage 0: 8 samples; Braak α-synuclein stages 1–2: 5 samples; Braak α-synuclein stages 3–4: 7 samples; Braak α-synuclein stages 5–6: 8 samples from the GSE49036 dataset; (<b>E</b>) 8 PD and 8 control subjects from peripheral mononuclear blood cells from the GSE22491 dataset; (<b>F</b>) 233 healthy controls and 205 idiopathic PD patients from whole blood from the GSE99039 dataset. (<b>G</b>) The expression of DEDRGs from the GSE49036 dataset at different stages. Gene ID: 200801_x_at, 213867_x_at, 224594_x_at, AFFX-HSAC07/X00351_3_at, AFFX-HSAC07/X00351_5_at, AFFX-HSAC07/X00351_M_at, 200601_at, 218144_s_at, 222534_s_at, 222535_at, 224469_s_at, 212082_s_at, 214002_at.</p>
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<p>Validity verification of DEDRGs. (<b>A</b>) Validation of DEDRGs by Western blotting. (<b>B</b>) Statistical plots of SLC7A11, ACTB, ACTN4, INF2, and MYL6. Compared with the saline group, ns = no significance, * <span class="html-italic">p &lt;</span> 0.05, ** <span class="html-italic">p</span> &lt; 0.01. <span class="html-italic">n</span> = 3. (<b>C</b>) Location of ACTN4 and INF2 proteins in cells from the HPA database: green represents the target protein, red represents microtubules, yellow represents the endoplasmic reticulum, and blue represents the nucleus (scale bar, 20 µm).</p>
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<p>Box plot of differential expression of DEDRGs between normal and tumor samples. (<b>A</b>) The differential expression of ACTB in pan-cancer. (<b>B</b>) The differential expression of ACTN4 in pan-cancer. (<b>C</b>) The differential expression of INF2 in pan-cancer. (<b>D</b>) The differential expression of MYL6 in pan-cancer. Compared with the normal samples, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Pan-cancer prognostic analysis of DEDRGs using univariate Cox regression, including (<b>A</b>) ACTB, (<b>B</b>) ACTN4, (<b>C</b>) INF2, and (<b>D</b>) MYL6.</p>
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<p>Survival analysis of DEDRG expression in pan-cancer. (<b>A</b>–<b>H</b>) Survival curves of ACTB in GBMLGG, LGG, MESO, KIRC, UVM, HNSC, LIHC, LUAD. (<b>I</b>–<b>N</b>) Survival curves of ACTN4 in GBMLGG, LGG, MESO, PAAD, LUAD, KIRC. (<b>O</b>–<b>R</b>) Survival curves of INF2 in LIHC, HNSC, GBM, LAML. (<b>S</b>–<b>X</b>) Survival curves of MYL6 in GBMLGG, LGG, ACC, UVM, LAML, SARC.</p>
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<p>Pan-cancer immune infiltration analysis: (<b>A</b>) Immunoinfiltration analysis of ACTB in GBMLGG, LGG, MESO, KIRC, UVM, HNSC, LIHC, LUAD, and GBM. (<b>B</b>) Immunoinfiltration analysis of ACTN4 in GBMLGG, LGG, MESO, PAAD, LUAD, and KIRC. (<b>C</b>) Immunoinfiltration analysis of INF2 in LIHC, HNSC, GBM, and LAML. (<b>D</b>) Immunoinfiltration analysis of MYL6 in GBMLGG, ACC, LGG, UVM, LAML, and SARC. The correlation coefficient being positive indicates a positive correlation between two variables; a negative correlation coefficient indicates a negative correlation between two variables. The absolute value of the correlation coefficient represents the degree of correlation: 0–0.3 indicates weak or no correlation; 0.3–0.5 indicates weak correlation; 0.5–0.8 indicates moderate correlation; 0.8–1 indicates strong correlation. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Single-cell type analysis of DEDRGs, including ACTB, ACTN4, INF2, and MYL6, mainly from glandular epithelial cells, squamous epithelial cells, specialized epithelial cells, endocrine cells, neuronal cells, glial cells, germ cells, trophoblast cells, endothelial cells, muscle cells, adipocytes, pigment cells, mesenchymal cells, undifferentiated cells, and blood and immune cells.</p>
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<p>Gene mutation analysis of DEDRGs. (<b>A</b>) The pan-cancer mutation status of ACTB was determined using the cBioPortal tool. (<b>B</b>) ACTB base mutation frequency. (<b>C</b>) The pan-cancer mutation status of ACTN4 was determined using the cBioPortal tool. (<b>D</b>) ACTN4 base mutation frequency. (<b>E</b>) The pan-cancer mutation status of INF2 was determined using the cBioPortal tool. (<b>F</b>) INF2 base mutation frequency. (<b>G</b>) The pan-cancer mutation status of MYL6 was determined using the cBioPortal tool. (<b>H</b>) MYL6 base mutation frequency.</p>
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<p>Tumor pathological staining of ACTB in glioma, renal cancer, head and neck cancer, liver cancer, and lung cancer; ACTN4 in glioma, pancreatic cancer, lung cancer, and renal cancer; INF2 in liver cancer, head and neck cancer, and glioma; MYL6 in glioma (scale bar, 20 µm).</p>
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<p>Coexpression network of DEDRGs and target miRNAs.</p>
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<p>Binding mode of screened drugs to their targets by molecular docking. (<b>A</b>) The structure of cyclophosphamide. (<b>B</b>) The structure of ethinyl estradiol. (<b>C</b>) The structure of ACTB (3byh). (<b>D</b>) Molecular docking results of ACTB and cyclophosphamide. (<b>E</b>) Molecular docking results of ACTB and ethinyl estradiol.</p>
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16 pages, 2706 KiB  
Article
Classification of Moral Decision Making in Autonomous Driving: Efficacy of Boosting Procedures
by Amandeep Singh, Yovela Murzello, Sushil Pokhrel and Siby Samuel
Information 2024, 15(9), 562; https://doi.org/10.3390/info15090562 - 11 Sep 2024
Viewed by 327
Abstract
Autonomous vehicles (AVs) face critical decisions in pedestrian interactions, necessitating ethical considerations such as minimizing harm and prioritizing human life. This study investigates machine learning models to predict human decision making in simulated driving scenarios under varying pedestrian configurations and time constraints. Data [...] Read more.
Autonomous vehicles (AVs) face critical decisions in pedestrian interactions, necessitating ethical considerations such as minimizing harm and prioritizing human life. This study investigates machine learning models to predict human decision making in simulated driving scenarios under varying pedestrian configurations and time constraints. Data were collected from 204 participants across 12 unique simulated driving scenarios, categorized into young (24.7 ± 3.5 years, 38 males, 64 females) and older (71.0 ± 5.7 years, 59 males, 43 females) age groups. Participants’ binary decisions to maintain or change lanes were recorded. Traditional logistic regression models exhibited high precision but consistently low recall, struggling to identify true positive instances requiring intervention. In contrast, the AdaBoost algorithm demonstrated superior accuracy and discriminatory power. Confusion matrix analysis revealed AdaBoost’s ability to achieve high true positive rates (up to 96%) while effectively managing false positives and negatives, even under 1 s time constraints. Learning curve analysis confirmed robust learning without overfitting. AdaBoost consistently outperformed logistic regression, with AUC-ROC values ranging from 0.82 to 0.96. It exhibited strong generalization, with validation accuracy approaching 0.8, underscoring its potential for reliable real-world AV deployment. By consistently identifying critical instances while minimizing errors, AdaBoost can prioritize human safety and align with ethical frameworks essential for responsible AV adoption. Full article
(This article belongs to the Special Issue Machine Learning and Artificial Intelligence with Applications)
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<p>Examples of four different pedestrian configurations used in the simulated driving scenarios: (<b>a</b>) 5 pedestrians in the driving lane, 0 pedestrians in the alternate lane; (<b>b</b>) 1 pedestrian in the driving lane, 5 pedestrians in the alternate lane; (<b>c</b>) 0 pedestrians in the driving lane, 5 pedestrians in the alternate lane; and (<b>d</b>) 5 pedestrians in the driving lane, 1 pedestrian in the alternate lane [<a href="#B34-information-15-00562" class="html-bibr">34</a>].</p>
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<p>AUC-ROC curve of the logistic regression model.</p>
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<p>AUC-ROC curve of the AdaBoost model.</p>
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<p>Confusion matrix analysis of the logistic regression model.</p>
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<p>Confusion matrix analysis of the AdaBoost model.</p>
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<p>Learning curve analysis: (<b>a</b>) loss vs epoch and (<b>b</b>) accuracy vs epoch of AdaBoost Model.</p>
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14 pages, 1089 KiB  
Article
The Value of Systemic Inflammatory Indices for Predicting Early Postoperative Complications in Colorectal Cancer
by Irina Shevchenko, Catalin Cicerone Grigorescu, Dragos Serban, Bogdan Mihai Cristea, Laurentiu Simion, Florentina Gherghiceanu, Andreea Cristina Costea, Dan Dumitrescu, Catalin Alius, Corneliu Tudor, Minodora Onisai, Sebastian Gradinaru and Ana Maria Dascalu
Medicina 2024, 60(9), 1481; https://doi.org/10.3390/medicina60091481 - 11 Sep 2024
Viewed by 449
Abstract
Background and Objectives: Systemic inflammatory indices have been largely investigated for their potential predictive value in multiple inflammatory, infectious, and oncological diseases; however, their value in colorectal cancer is still a subject of research. This study investigates the dynamics of pre- and [...] Read more.
Background and Objectives: Systemic inflammatory indices have been largely investigated for their potential predictive value in multiple inflammatory, infectious, and oncological diseases; however, their value in colorectal cancer is still a subject of research. This study investigates the dynamics of pre- and postoperative values of NLR, PLR, SII, and MLR in patients with colorectal cancer and their predictive value for early postoperative outcomes. Materials and Methods: A 2-year retrospective cohort study was performed on 200 patients operated for colorectal adenocarcinoma. Systemic inflammatory indices were calculated based on complete blood count preoperatively and on the first and sixth postoperative days. The patients were divided into two groups based on their emergency or elective presentation. The pre- and postoperative values of serum inflammatory biomarkers and their correlations with postoperative outcomes were separately analyzed for the two study subgroups. Results: There were no significant differences in sex distribution, addressability, associated comorbidities, or types of surgery between the two groups. Patients in the emergency group presented higher preoperative and postoperative values of WBC, neutrophils, NLR, and SII compared to elective patients. The postsurgery hospital stays correlated well with pre- and postoperative day one and day six values of NLR (p = 0.001; 0.02; and <0.001), PLR (p < 0.001), SII (p = 0.037; <0.001; <0.001), and MLR (p = 0.002; p = 0.002; <0.001). In a multivariate analysis, reintervention risk was higher for emergency presentation and anemia, and lower in right colon cancer. In the emergency group, a multivariate model including age, MLR PO1, and pTNM stage was predictive for severe postoperative complications (AUC ROC 0.818). First-day postoperative inflammatory indices correlated well with sepsis, with the best predictive value being observed for the first postoperative day NLR (AUC 0.836; sensibility 88.8%; specificity 66.7%) and SII (AUC 0.796; sensitivity 66.6%; specificity 90%). For elective patients, the first postoperative day PLR and anemia were included in a multivariate model to predict Clavien–Dindo complications graded 3 or more (AUC ROC 0.818) and reintervention (AUC ROC 0.796). Conclusions: Easy-to-calculate and inexpensive systemic inflammatory biomarkers could be useful in predicting early postoperative outcomes in colorectal cancer for both elective and emergency surgery. Full article
(This article belongs to the Special Issue Recent Advances and Future Challenges in Colorectal Surgery)
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<p>ROC curve (blue color) describing the prediction of severe complications in the emergency group by the multivariate model.</p>
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<p>Comparative ROC curve for the described model of sepsis in emergency subgroup.</p>
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<p>ROC curves (blue color) to describe the predictive power of the multivariate model for severe postoperative complications (<b>left</b>) and reinterventions (<b>right</b>).</p>
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13 pages, 1074 KiB  
Article
Assessing the Utility of Prediction Scores PAINT, ISARIC4C, CHIS, and COVID-GRAM at Admission and Seven Days after Symptom Onset for COVID-19 Mortality
by Alina Doina Tanase, Oktrian FNU, Dan-Mihai Cristescu, Paula Irina Barata, Dana David, Emanuela-Lidia Petrescu, Daliana-Emanuela Bojoga, Teodora Hoinoiu and Alexandru Blidisel
J. Pers. Med. 2024, 14(9), 966; https://doi.org/10.3390/jpm14090966 - 11 Sep 2024
Viewed by 268
Abstract
The COVID-19 pandemic underscores the need for accurate prognostic tools to predict patient outcomes. This study evaluates the effectiveness of four prominent COVID-19 prediction scores—PAINT, ISARIC4C, CHIS, and COVID-GRAM—at two critical time points: at admission and seven days post-symptom onset, to assess their [...] Read more.
The COVID-19 pandemic underscores the need for accurate prognostic tools to predict patient outcomes. This study evaluates the effectiveness of four prominent COVID-19 prediction scores—PAINT, ISARIC4C, CHIS, and COVID-GRAM—at two critical time points: at admission and seven days post-symptom onset, to assess their utility in predicting mortality among hospitalized patients. Conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, this retrospective analysis included adult patients hospitalized with confirmed SARS-CoV-2 infection. Eligible patients had complete data for the scores at both time points. Statistical analysis involved ROC curves and logistic regression to assess the scores’ predictive accuracy for mortality. The study included 215 patients, split into 139 survivors and 76 non-survivors. At admission, the PAINT, ISARIC4C, CHIS, and COVID-GRAM scores significantly differentiated between the survival outcomes (p < 0.0001). The best cutoff values at admission were 6.26 for PAINT, 7.95 for ISARIC4C, 5.58 for CHIS, and 0.63 for COVID-GRAM, corresponding to sensitivities of 85.47%, 80.56%, 88.89%, and 83.33% and specificities of 77.34%, 82.12%, 75.01%, and 78.45%, respectively. By day seven, the cutoff values increased, indicating deteriorating conditions in patients who eventually succumbed to the virus. The hazard ratios at admission for exceeding these cutoffs were significant: PAINT (HR = 3.45), ISARIC4C (HR = 2.89), CHIS (HR = 4.02), and COVID-GRAM (HR = 3.15), highlighting the scores’ abilities to predict severe outcomes. One week post symptom onset, these scores’ predictive values and corresponding hazard ratios increased, further validating their prognostic significance over time. The evaluated COVID-19 prediction scores robustly predict mortality at admission and become more predictive by the seventh day of symptom onset. These findings support the use of these scores in clinical settings to facilitate early identification and intervention for high-risk patients, potentially improving patient outcomes during the ongoing global health crisis. Full article
(This article belongs to the Special Issue Novel Diagnostics and Therapies for Infectious Disease)
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<p>AUROC analysis of clinical prediction scores for COVID-19 mortality at initial measurement.</p>
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<p>AUROC analysis of clinical prediction scores for COVID-19 mortality at one week post symptom onset.</p>
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11 pages, 1547 KiB  
Article
Non-Conventional Prognostic Markers in Life-Threatening COVID-19 Cases—When Less Is More
by Martin Rozanovic, Kata Várady-Szabó, Kamilla Domokos, Tamás Kiss, Csaba Loibl, Gergely Márovics, Szilárd Rendeki and Csaba Csontos
J. Clin. Med. 2024, 13(18), 5369; https://doi.org/10.3390/jcm13185369 - 11 Sep 2024
Viewed by 395
Abstract
Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio—NLR; platelet/lymphocyte ratio—PLR) and conventional markers (C-reactive protein—CRP; procalcitonin—PCT; interleukin-6—IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, [...] Read more.
Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio—NLR; platelet/lymphocyte ratio—PLR) and conventional markers (C-reactive protein—CRP; procalcitonin—PCT; interleukin-6—IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR’s accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes. Full article
(This article belongs to the Special Issue Critical Care during COVID-19 Pandemic)
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<p>The kinetics of the median NLR (<b>A</b>) and PCT (<b>B</b>) levels between survivor and non-survivor patients. Green columns: surviving patients; red columns: non-surviving patients. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.005 between the NSU and SU groups. Data are presented as medians in 25–75% interquartile ranges and 5–95% confidence intervals.</p>
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<p>The kinetics of the median NLR (<b>A</b>) and PCT (<b>B</b>) levels between survivor and non-survivor patients. Green columns: surviving patients; red columns: non-surviving patients. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.005 between the NSU and SU groups. Data are presented as medians in 25–75% interquartile ranges and 5–95% confidence intervals.</p>
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<p>The kinetics of the NLR (<b>A</b>) and PCT (<b>B</b>) levels between patients with or without the need for renal replacement therapy. Yellow columns: patients without the need for RRT; blue columns: patients with the need for RRT. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.005 between the “non-RRT” and “RRT” groups. Data are presented as medians in 25–75% interquartile ranges and 5–95% confidence intervals.</p>
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<p>The ROC curve for predicting mortality. The NLR and PCT (highlighted lines) exhibit higher discriminatory power than CRP, IL-6, and the PLR. The reference line (green line) represents a model with no discriminative ability.</p>
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20 pages, 1836 KiB  
Article
Advanced Detection of Abnormal ECG Patterns Using an Optimized LADTree Model with Enhanced Predictive Feature: Potential Application in CKD
by Muhammad Binsawad and Bilal Khan
Algorithms 2024, 17(9), 406; https://doi.org/10.3390/a17090406 - 11 Sep 2024
Viewed by 375
Abstract
Detecting abnormal ECG patterns is a crucial area of study aimed at enhancing diagnostic accuracy and enabling early identification of Chronic Kidney Disease (CKD)-related abnormalities. This study compares a unique strategy for abnormal ECG patterns using the LADTree model to standard machine learning [...] Read more.
Detecting abnormal ECG patterns is a crucial area of study aimed at enhancing diagnostic accuracy and enabling early identification of Chronic Kidney Disease (CKD)-related abnormalities. This study compares a unique strategy for abnormal ECG patterns using the LADTree model to standard machine learning (ML) models. The study design includes data collection from the MIT-BIH Arrhythmia dataset, preprocessing to address missing values, and feature selection using the CfsSubsetEval method using Best First Search, Harmony Search, and Particle Swarm Optimization Search approaches. The performance assessment consists of two scenarios: percentage splitting and K-fold cross-validation, with several evaluation measures such as Kappa statistic (KS), Best First Search, recall, precision-recall curve (PRC) area, receiver operating characteristic (ROC) area, and accuracy. In scenario 1, LADTree outperforms other ML models in terms of mean absolute error (MAE), KS, recall, ROC area, and PRC. Notably, the Naïve Bayes (NB) model has the lowest MAE, but the Support Vector Machine (SVM) performs badly. In scenario 2, NB has the lowest MAE but the highest KS, recall, ROC area, and PRC area, closely followed by LADTree. Overall, the findings indicate that the LADTree model, when optimized for ECG signal data, delivers promising results in detecting abnormal ECG patterns potentially related with CKD. This study advances predictive modeling tools for identifying abnormal ECG patterns, which could enhance early detection and management of CKD, potentially leading to improved patient outcomes and healthcare practices. Full article
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<p>Overview of the study’s methodology for abnormal ECG patterns using the LADTree model and ECG signal data, highlighting the comparison with various machine learning models and assessment measures.</p>
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<p>Comparison of Mean Absolute Error (MAE) Values for Machine Learning Models in Predicting Chronic Kidney Disease (CKD) from Electrocardiogram (ECG) Signal Data Using Percentage Splitting Criteria.</p>
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<p>Comparison of Kappa Statistic (KS) Values for Employed Models in Predicting Abnormal ECG Patterns Using the Percentage Splitting Criteria.</p>
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<p>Comparison of Performance Metrics Across Employed Machine Learning Models for Abnormal ECG Patterns Prediction using the Percentage Splitting Criteria.</p>
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<p>Comparison of Machine Learning Model Accuracy in abnormal ECG patterns Using the Percentage Splitting Criteria.</p>
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<p>Mean Absolute Error Analysis of Abnormal ECG Patterns on Employed Machine Learning Models Using ECG Signal Data with K-fold Cross-Validation.</p>
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<p>Kappa Statistic (KS) Values for Employed Machine Learning Models Used in Predicting Abnormal ECG Patterns Using K-Fold Cross-Validation.</p>
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<p>Performance Measures (Recall, ROCA, PRCA) of Machine Learning Models for Predicting Abnormal ECG Patterns using K-Fold Cross-Validation.</p>
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<p>Accuracy Values of Employed Machine Learning Models for Predicting Abnormal ECG Patterns Using Electrocardiogram (ECG) Signal Data Based on the K-Fold Cross-Validation Criteria.</p>
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12 pages, 3121 KiB  
Article
Application of Eight Machine Learning Algorithms in the Establishment of Infertility and Pregnancy Diagnostic Models: A Comprehensive Analysis of Amino Acid and Carnitine Metabolism
by Rui Zhang, Lei Zhou, Xiaoyan Hao, Liu Yang, Li Ding, Ruiqing Xing, Juanjuan Hu, Fengjuan Wang, Xiaonan Zhai, Yuanbing Guo, Zheng Cai, Jiawei Gao, Jun Yang and Jiayun Liu
Metabolites 2024, 14(9), 492; https://doi.org/10.3390/metabo14090492 - 10 Sep 2024
Viewed by 297
Abstract
To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis [...] Read more.
To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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<p>Patient information. Flowchart of inclusion and exclusion criteria for the female study groups.</p>
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<p>Flowchart of data processing.</p>
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<p>Multivariate data analysis. (<b>a</b>) Score plots of the supervised orthogonal partial least squares discriminant analyses (OPLS−DA) model. Control (yellow) and non-pregnant women with infertility (NPWI, red) groups. (<b>b</b>) Score plots of the supervised OPLS−DA model. Control (yellow) and pregnant women without infertility (PWI, green) groups. (<b>c</b>) Score plots of the supervised OPLS−DA model. infertility-treated pregnant women (ITPW, blue) and PWI (green) groups. (<b>d</b>) Venn diagram of the indicators (<span class="html-italic">p</span> &lt; 0.05) between ITPW vs. PWI (pink) and NPWI vs. control women (gray). (<b>e</b>) Pathway analysis of significant metabolite changes between control group and NPWI group. (<b>f</b>) Pathway analysis of significant metabolite changes between control group and PWI group. (<b>g</b>) Pathway analysis of significant metabolite changes between control group and ITPW group. (<b>h</b>) Venn diagram of the pathways with significant changes between ITPW vs. control women and PWI (gray) vs. control women (pink).</p>
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<p>(<b>a</b>) C8:1, AMH, Pip, Gln, C4/C3, Gln/Cit, and Arg/Orn levels in NPWI and control women. (<b>b</b>) NEUT#, LYMPH%, NEUT%, C0, ALB, BU, CRE, Orn/Cit, Glu/Cit, and C8:1 levels in PWI and control groups. (<b>c</b>) Ala, Gly, C3/C16, and UA levels in the PWI and ITPW groups. (<b>d</b>) Receiver operating characteristic (ROC) curves of the model obtained from the training set of the seven different indices selected for NPWI and control women. (<b>e</b>) ROC curves of the model obtained from the verified set of the seven different indices selected for NPWI and control women. (<b>f</b>) ROC curves of the model obtained from the training set of the 10 different indices selected for the PWI and control women. (<b>g</b>) ROC curves of the model obtained from the verified set of the 10 different indices selected for the PWI and control women. (<b>h</b>) ROC curves of the model obtained from the training set of the four different indices selected for the PWI and ITPW. (<b>i</b>) ROC curves of the model obtained from the verified set of the four different indices selected for the PWI and ITPW. Abbreviations: C8:1, octenoyl carnitine; AMH, anti-Müllerian hormone; Pip, piperidine, Gln, glutamine; C4, butyryl carnitine; C3, propionyl carnitine; Cit, citrulline; Arg, arginine, Orn, ornithine; NEUT#, number of neutrophils; LYMPH%, lymphocyte percentage; NEUT%, neutrophil percentage; C0, free carnitine; ALB, albumin; BU, urea; CRE, creatinine; Glu, glutamic acid; Ala, alanine; Gly, glycine; C16, hexadecanoyl carnitine; UA, uric acid. ****, <span class="html-italic">p</span> &lt; 0.0001.</p>
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12 pages, 2195 KiB  
Article
Platelet and Lymphocyte-Related Parameters as Potential Markers of Osteoarthritis Severity: A Cross-Sectional Study
by Francesca Salamanna, Stefania Pagani, Giuseppe Filardo, Deyanira Contartese, Angelo Boffa, Lucia Angelelli, Melania Maglio, Milena Fini, Stefano Zaffagnini and Gianluca Giavaresi
Biomedicines 2024, 12(9), 2052; https://doi.org/10.3390/biomedicines12092052 - 10 Sep 2024
Viewed by 278
Abstract
Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering [...] Read more.
Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI). Methods: Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren–Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves. Results: The study involved 245 OA patients (51.4% female, 48.6% male) aged 40–90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m2 in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model’s accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805]). Conclusions: Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations. Full article
(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)
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<p>Schematic representation of the biomarkers in osteoarthritis. IL: interleukin; TNF-α: tumor necrosis factor-α; PLT: platelet; LINF: lymphocyte; CTX I and II: C-terminal telopeptides of type I and II collagen; MMP: matrix metalloproteinase; COMP: cartilage oligometric matrix protein; IF-γ IP-10: interferon-γ inducible protein 10.</p>
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<p>Boxplot of hematologic parameters by KL grade of OA. The data show significant variations in PLT levels and differences in the distribution of MPV and LINF between KL grades.</p>
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<p>ROC curve analysis.</p>
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