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Search Results (485)

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18 pages, 816 KiB  
Review
Traumatic Brain Injury as a Public Health Issue: Epidemiology, Prognostic Factors and Useful Data from Forensic Practice
by Michele Ahmed Antonio Karaboue, Federica Ministeri, Francesco Sessa, Chiara Nannola, Mario Giuseppe Chisari, Giuseppe Cocimano, Lucio Di Mauro, Monica Salerno and Massimiliano Esposito
Healthcare 2024, 12(22), 2266; https://doi.org/10.3390/healthcare12222266 - 13 Nov 2024
Viewed by 455
Abstract
Traumatic brain injury (TBI) represents a major public health problem, being a leading cause of disability and mortality among young people in developed countries. Head trauma occurs across all age groups, each experiencing consistently high rates of mortality and disability. This review aims [...] Read more.
Traumatic brain injury (TBI) represents a major public health problem, being a leading cause of disability and mortality among young people in developed countries. Head trauma occurs across all age groups, each experiencing consistently high rates of mortality and disability. This review aims to present an overview of TBI epidemiology and its socioeconomic impact, alongside data valuable for prevention, clinical management, and research efforts. Methods: A narrative review of TBI was performed with a particular focus on forensic pathology and public health. In fact, this review highlighted the economic and epidemiological aspects of TBI, as well as autopsy, histology, immunohistochemistry, and miRNA. Results: These data, together with immunohistochemical markers, are crucial for histopathological diagnosis and to determine the timing of injury onset, a fundamental aspect in forensic pathology practice. There is compelling evidence that brain injury biomarkers may enhance predictive models for clinical and prognostic outcomes. By clarifying the cause of death and providing details on survival time after trauma, forensic tools offer valuable information to improve the clinical management of TBI and guide preventive interventions. Conclusions: TBI is one of the most common causes of death today, with high costs for health care spending. Knowing the different mechanisms of TBI, reduces health care costs and helps improve prognosis. Full article
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<p>Summary of the metabolic and cascades pathways involved in TBI.</p>
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17 pages, 833 KiB  
Review
Utilization of Single-Pulse Transcranial-Evoked Potentials in Neurological and Psychiatric Clinical Practice: A Narrative Review
by Hilla Fogel, Noa Zifman and Mark Hallett
Neurol. Int. 2024, 16(6), 1421-1437; https://doi.org/10.3390/neurolint16060106 - 11 Nov 2024
Viewed by 237
Abstract
Background: The utility of single-pulse TMS (transcranial magnetic stimulation)-evoked EEG (electroencephalograph) potentials (TEPs) has been extensively studied in the past three decades. TEPs have been shown to provide insights into features of cortical excitability and connectivity, reflecting mechanisms of excitatory/inhibitory balance, in various [...] Read more.
Background: The utility of single-pulse TMS (transcranial magnetic stimulation)-evoked EEG (electroencephalograph) potentials (TEPs) has been extensively studied in the past three decades. TEPs have been shown to provide insights into features of cortical excitability and connectivity, reflecting mechanisms of excitatory/inhibitory balance, in various neurological and psychiatric conditions. In the present study, we sought to review and summarize the most studied neurological and psychiatric clinical indications utilizing single-pulse TEP and describe its promise as an informative novel tool for the evaluation of brain physiology. Methods: A thorough search of PubMed, Embase, and Google Scholar for original research utilizing single-pulse TMS-EEG and the measurement of TEP was conducted. Our review focused on the indications and outcomes most clinically relevant, commonly studied, and well-supported scientifically. Results: We included a total of 55 publications and summarized them by clinical application. We categorized these publications into seven sub-sections: healthy aging, Alzheimer’s disease (AD), disorders of consciousness (DOCs), stroke rehabilitation and recovery, major depressive disorder (MDD), Parkinson’s disease (PD), as well as prediction and monitoring of treatment response. Conclusions: TEP is a useful measurement of mechanisms underlying neuronal networks. It may be utilized in several clinical applications. Its most prominent uses include monitoring of consciousness levels in DOCs, monitoring and prediction of treatment response in MDD, and diagnosis of AD. Additional applications including the monitoring of stroke rehabilitation and recovery, as well as a diagnostic aid for PD, have also shown encouraging results but require further evidence from randomized controlled trials (RCTs). Full article
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<p>Illustrative examples of the changes in TEP across clinical conditions/interventions. <a href="#neurolint-16-00106-f001" class="html-fig">Figure 1</a>—illustrative simulated TEP waveforms showing voltage (μV, y-axis) over time (ms, x-axis). (<b>A</b>) Age-related changes showing decreased amplitudes and delayed latency of TEP components. (<b>B</b>) Illustration of a typical AD TEP with increased P30. (<b>C</b>) Illustration of an MDD TEP waveform with increased baseline P60-N100 amplitude. (<b>D</b>) Illustration of the changes in TEP peaks in response to pharmacological interventions.</p>
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<p>Rise in TMS-EEG publications from 1993 to 2023. Bars represent the number of publications on TMS-EEG each year.</p>
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11 pages, 436 KiB  
Brief Report
Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2)
by Ilaria Ammendolia, Maria Sframeli, Emanuela Esposito, Luigi Cardia, Alberto Noto, Mariaconcetta Currò, Gioacchino Calapai, Maria De Pasquale, Carmen Mannucci and Fabrizio Calapai
Pharmaceuticals 2024, 17(11), 1513; https://doi.org/10.3390/ph17111513 - 11 Nov 2024
Viewed by 450
Abstract
Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of [...] Read more.
Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3–11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth. Full article
(This article belongs to the Section Pharmacology)
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<p>Flowchart of methodology. ICSRs (Individual Cases Safety Reports).</p>
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15 pages, 1793 KiB  
Article
Machine Learning Analysis of Factors Influencing Pediatric Telehealth Visits During COVID-19: A State-Level Comparison Using 2021–22 National Survey of Children’s Health Data
by Yu-Sheng Lee, Junu Shrestha, Matthew Evan Sprong, Xueli Huang, Sushil Tuladhar and Michael Y. Chuang
Healthcare 2024, 12(21), 2170; https://doi.org/10.3390/healthcare12212170 - 31 Oct 2024
Viewed by 528
Abstract
Background/Objectives: The COVID-19 pandemic reduced in-person pediatric visits in the United States by over 50%, while telehealth visits increased significantly. The national use of telehealth for children and the factors influencing their use have been rarely studied. This study aimed to investigate [...] Read more.
Background/Objectives: The COVID-19 pandemic reduced in-person pediatric visits in the United States by over 50%, while telehealth visits increased significantly. The national use of telehealth for children and the factors influencing their use have been rarely studied. This study aimed to investigate the prevalence of telehealth use during the COVID-19 pandemic and explore the potential factors linked to its use at the state level. Methods: A cross-sectional study of the National Survey of Children’s Health (2021–22) sponsored by the federal Maternal and Child Health Bureau was performed. We used the least absolute shrinkage and selection operator (LASSO) regression to predict telehealth use during the pandemic. A bar map showing the significant factors from the multivariable regression was created. Results: Of the 101,136 children, 15.25% reported using telehealth visits due to COVID-19, and 3.67% reported using telehealth visits due to other health reasons. The Northeast states showed the highest telehealth use due to COVID-19. In the Midwest and Southern states, children had a lower prevalence of telehealth visits due to other health reasons. The LASSO regressions demonstrated that telehealth visits were associated with age, insurance type, household income, usual source of pediatric preventive care, perceived child health, blood disorders, allergy, brain injury, seizure, ADHD, anxiety, depression, and special needs. Conclusions: This study demonstrated significant variability in the use of telehealth among states during the COVID-19 pandemic. Understanding who uses telehealth and why, as well as identifying access barriers, helps maximize telehealth potential and improve healthcare outcomes for all. Full article
(This article belongs to the Section TeleHealth and Digital Healthcare)
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<p>Prevalence map of telehealth use during COVID-19 pandemic. (<b>A</b>) Telehealth visits due to COVID-19. (<b>B</b>) Telehealth visits due to other health reasons.</p>
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12 pages, 1017 KiB  
Article
A Predictive Model for Perinatal Brain Injury Using Machine Learning Based on Early Birth Data
by Ga Won Jeon, Yeong Seok Lee, Won-Ho Hahn and Yong Hoon Jun
Children 2024, 11(11), 1313; https://doi.org/10.3390/children11111313 - 29 Oct 2024
Viewed by 414
Abstract
Background/Objective: It is difficult to predict perinatal brain injury, and performing brain magnetic resonance imaging (MRI) based on suspected injury remains a clinical challenge. Therefore, we aimed to develop a reliable method for predicting perinatal brain injury using a machine learning model with [...] Read more.
Background/Objective: It is difficult to predict perinatal brain injury, and performing brain magnetic resonance imaging (MRI) based on suspected injury remains a clinical challenge. Therefore, we aimed to develop a reliable method for predicting perinatal brain injury using a machine learning model with early birth data. Methods: Neonates admitted to our institution from January 2017 to June 2024 with a gestational age of ≥36 weeks, a birth weight of ≥1800 g, admission within 6 h of birth, and who underwent brain MRI to confirm perinatal brain injury were included. Various machine learning models, including gradient boosting, were trained using early birth data to predict perinatal brain injury. Synthetic minority over-sampling and adaptive synthetic sampling (ADASYN) were applied to address class imbalance. Model performance was evaluated using accuracy, F1 score, and ROC curves. Feature importance scores and Shapley additive explanations (SHAP) values were also calculated. Results: Among 179 neonates, 39 had perinatal brain injury. There were significant differences between the injury and non-injury groups in mode of delivery, Apgar scores, capillary pH, lactate dehydrogenase (LDH) levels, and whether therapeutic hypothermia was performed. The gradient boosting model with the ADASYN method achieved the best performance. In terms of feature importance scores, the 1 min Apgar score was the most influential predictor. Additionally, SHAP analysis showed that LDH levels had the highest SHAP values. Conclusion: the gradient boosting model with ADASYN oversampling effectively predicts perinatal brain injury, potentially improving early detection for predicting long-term outcomes, reducing unnecessary MRI scans, and lowering healthcare costs. Full article
(This article belongs to the Section Pediatric Neurology & Neurodevelopmental Disorders)
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<p>ROC curves for each model and technique. The gradient boosting model using the ADASYN technique showed the highest ROC AUC at 0.82. SVC, support vector classifier; KNN, K-nearest neighbors; SMOTE, synthetic minority over-sampling technique; and ADASYN, adaptive synthetic sampling method.</p>
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<p>Top 15 features selected using gradient boosting. (<b>A</b>) Feature importance. The X-axis indicates the feature importance score. This score reflects how much each feature contributes to the model’s predictive accuracy. A higher score suggests that the feature plays a more significant role in making accurate predictions. (<b>B</b>) SHAP values. The X-axis indicates the mean |SHAP value|. This value represents the average magnitude of each feature’s impact on the model’s predictions across all samples. Higher SHAP values signify that the feature has a greater influence on the model’s output. Hb, hemoglobin; LDH, lactate dehydrogenase; Plt, platelet; MAS, meconium aspiration syndrome; PPHN, persistent pulmonary hypertension of the newborn; GA, gestational age; TTN, transient tachypnea of the newborn; RDS, respiratory distress syndrome; and SHAP, Shapley additive explanations.</p>
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17 pages, 3100 KiB  
Article
New Insights on the Effects of Krill Oil Supplementation, a High-Fat Diet, and Aging on Hippocampal-Dependent Memory, Neuroinflammation, Synaptic Density, and Neurogenesis
by John M. Andraka, Naveen Sharma and Yannick Marchalant
Int. J. Mol. Sci. 2024, 25(21), 11554; https://doi.org/10.3390/ijms252111554 - 28 Oct 2024
Viewed by 545
Abstract
Krill oil (KO) has been described as having the potential to ameliorate the detrimental consequences of a high-fat diet (HFD) on the aging brain, though the magnitude and mechanism of this benefit is unclear. We thus hypothesized that dietary KO supplementation could counteract [...] Read more.
Krill oil (KO) has been described as having the potential to ameliorate the detrimental consequences of a high-fat diet (HFD) on the aging brain, though the magnitude and mechanism of this benefit is unclear. We thus hypothesized that dietary KO supplementation could counteract the effects of cognitive aging and an HFD on spatial learning, neuroinflammation, neurogenesis, and synaptic density in the cortex and hippocampus of aged rats. Sixteen-month-old Sprague Dawley rats were fed for 12 weeks while being divided into four groups: control (CON); control with KO supplementation (CONKO); high-fat diet (HF); and high-fat diet with KO supplementation (HFKO). We measured food consumption, body mass, spatial memory (Morris water maze), microglia, neurogenesis, cytokine concentrations, and synaptic markers (post-synaptic density-95 and synaptophysin). Predictably, an HFD did induce significant differences in body weights, with the high-fat groups gaining more weight than the low-fat controls. However, KO supplementation did not produce significant changes in the other quantified parameters. Our results demonstrate that the dietary KO dose provided in the current study does not benefit hippocampal or cortical functions in an aging model. Our results provide a benchmark for future dosing protocols that may eventually prove to be beneficial. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: “Neuroinflammation”)
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<p>Comparison of weekly mean food consumption between dietary groups. Statistically significant between-subject effects were identified with lower food intake in the HF group when compared to both CON and HFKO groups (one-way repeated measures ANOVA, <span class="html-italic">p</span> &lt; 0.05). Error bars represent SEM. n = 7–8 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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<p>Comparison of weekly mean body mass between dietary groups. Statistically significant between-subject effects identified with greater mass noted in the HFKO group when compared to the CON group (One-way repeated measures ANOVA, <span class="html-italic">p</span> &lt; 0.05). Error bars represent SEM. n = 7–8 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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<p>Morris water maze testing. (<b>A</b>) Time-to-platform for each dietary group on testing days 1–4. Although each group demonstrated learning with overall decreases in time-to-platform over the four testing days, diet did not induce statistically significant differences. (<b>B</b>) Morris water maze probe trial. No statistically significant differences were identified between groups when comparing the percentage of time spent in the removed platform quadrant. All groups showed a preference for the target quadrant with time spent greater than 25%. The dashed line indicates platform choice equivalent to random chance (25%). Error bars represent SEM. n = 7–8 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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<p>Pro-inflammatory and anti-inflammatory cytokine concentrations in the hippocampus and cortex. Error bars represent SEM. n = 7–8 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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<p>Comparison of stereological analysis of microglia between dietary groups in the hippocampus and cortex. (<b>A</b>) Quantification of microglia counts in the rat cortex, dentate gyrus and total combined. Error bars represent SEM. n = 4–6 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation. (<b>B</b>) Representative image of microglia at 6300× magnification. Ionized calcium-binding adaptor molecule 1 (Iba-1) antibody, DAB substrate, and cresyl violet staining. StereoInvestigator dissector box and markers shown.</p>
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<p>Comparison of average doublecortin markers per section in the dentate gyrus. Circle symbols are individual data points. Error bars represent SEM. n = 4–6 per group. CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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<p>Synaptophysin (SYP) and post-synaptic density-95 (PSD-95) in the cortex and hippocampus. Western immunoblotting was utilized to measure relative concentrations of SYP (38 kDa) and PSD-95 (100 kDa) with β-tubulin loading control (55 kDa) in the cortex (<b>A</b>) and hippocampus (<b>C</b>). Errors bars represent SEM. n = 7–8 per group. Representative blots for cortex (<b>B</b>) and hippocampus (<b>D</b>). CON: control diet; CONKO: control diet with krill oil supplementation; HF: high-fat diet; HFKO: high-fat diet with krill oil supplementation.</p>
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14 pages, 676 KiB  
Review
Predictive and Explainable Artificial Intelligence for Neuroimaging Applications
by Sekwang Lee and Kwang-Sig Lee
Diagnostics 2024, 14(21), 2394; https://doi.org/10.3390/diagnostics14212394 - 27 Oct 2024
Viewed by 678
Abstract
Background: The aim of this review is to highlight the new advance of predictive and explainable artificial intelligence for neuroimaging applications. Methods: Data came from 30 original studies in PubMed with the following search terms: “neuroimaging” (title) together with “machine learning” (title) or [...] Read more.
Background: The aim of this review is to highlight the new advance of predictive and explainable artificial intelligence for neuroimaging applications. Methods: Data came from 30 original studies in PubMed with the following search terms: “neuroimaging” (title) together with “machine learning” (title) or ”deep learning” (title). The 30 original studies were eligible according to the following criteria: the participants with the dependent variable of brain image or associated disease; the interventions/comparisons of artificial intelligence; the outcomes of accuracy, the area under the curve (AUC), and/or variable importance; the publication year of 2019 or later; and the publication language of English. Results: The performance outcomes reported were within 58–96 for accuracy (%), 66–97 for sensitivity (%), 76–98 for specificity (%), and 70–98 for the AUC (%). The support vector machine and the convolutional neural network registered the best performance (AUC 98%) for the classifications of low- vs. high-grade glioma and brain conditions, respectively. Likewise, the random forest delivered the best performance (root mean square error 1) for the regression of brain conditions. The following factors were discovered to be major predictors of brain image or associated disease: (demographic) age, education, sex; (health-related) alpha desynchronization, Alzheimer’s disease stage, CD4, depression, distress, mild behavioral impairment, RNA sequencing; (neuroimaging) abnormal amyloid-β, amplitude of low-frequency fluctuation, cortical thickness, functional connectivity, fractal dimension measure, gray matter volume, left amygdala activity, left hippocampal volume, plasma neurofilament light, right cerebellum, regional homogeneity, right middle occipital gyrus, surface area, sub-cortical volume. Conclusion: Predictive and explainable artificial intelligence provide an effective, non-invasive decision support system for neuroimaging applications. Full article
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<p>Flow diagram.</p>
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11 pages, 1640 KiB  
Article
Association Between Derivatives of Reactive Oxygen Metabolites and Hemodynamics in Children with Left-to-Right Shunt Congenital Heart Disease
by Takamichi Ishikawa, Daisuke Masui and Hiroki Uchiyama
Antioxidants 2024, 13(11), 1294; https://doi.org/10.3390/antiox13111294 - 25 Oct 2024
Viewed by 406
Abstract
Existing reports on the association between oxidative stress and pulmonary hemodynamics in congenital heart disease (CHD) are limited, and the relationship remains inadequately understood. To address this, we evaluated the link between oxidative stress and hemodynamics in children with left-to-right shunt CHD. We [...] Read more.
Existing reports on the association between oxidative stress and pulmonary hemodynamics in congenital heart disease (CHD) are limited, and the relationship remains inadequately understood. To address this, we evaluated the link between oxidative stress and hemodynamics in children with left-to-right shunt CHD. We analyzed the derivatives of reactive oxygen metabolites (d-ROMs) in a cohort of 60 children with left-to-right shunt CHD and compared them to 60 healthy, age- and sex-matched controls. In the CHD group, hemodynamics measured by cardiac catheterization were evaluated in relation to d-ROMs. We also assessed the diagnostic performance of the d-ROMs for a pulmonary-to-systemic blood flow ratio (Qp/Qs) of >1.5. We found that the blood d-ROM levels in the CHD group were significantly higher than those in the control group (p < 0.001). A significant positive correlation was observed between d-ROMs and Qp/Qs (p < 0.001), d-ROMs and the ratio of the right ventricular end-diastolic volume (p < 0.001), d-ROMs and the mean pulmonary arterial pressure (p < 0.001), and d-ROMs and the ratio of the left ventricular end-diastolic volume (p = 0.007). In the receiver operating characteristic curve analysis, the area under the curve for d-ROMs in predicting Qp/Qs > 1.5 was 0.806 (p < 0.001), which, although not statistically significant, was higher than that of the plasma N-terminal pro-brain natriuretic peptide (0.716). These findings indicate that d-ROM levels are closely associated with hemodynamics and the disease severity in patients with left-to-right shunt CHD and may serve as a valuable marker for determining the need for surgical intervention. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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<p>Box plots showing the distribution of d-ROMs in the two groups. The upper boundary of the box represents the 75th percentile, and the lower boundary of the box represents the 25th percentile. The line through each box represents the median value in each group. d-ROMs, derivatives of reactive oxygen metabolites; CHD, congenital heart disease.</p>
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<p>A scatter plot and correlation between d-ROM and (<b>A</b>) Qp/Qs, (<b>B</b>) %RVEDV, (<b>C</b>) mean PAP, and (<b>D</b>) %LVEDV. The solid line represents the regression line. The dotted lines show the 95% confidence interval. d-ROMs, derivatives of reactive oxygen metabolites; Qp/Qs, pulmonary-to-systemic blood flow ratio; %RVEDV, ratio of right ventricular end-diastolic volume; PAP, pulmonary arterial pressure; %LVEDV, ratio of left ventricular end-diastolic volume.</p>
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<p>A scatter plot and the correlation between d-ROMs and pulmonary arterial SO<sub>2</sub> (<b>A</b>), Qp/Qs and %RVEDV (<b>B</b>), Qp/Qs and the mean PAP (<b>C</b>), and Qp/Qs and %LVEDV (<b>D</b>). The solid line represents the regression line. The dotted lines show the 95% confidence interval. d-ROMs, derivatives of reactive oxygen metabolites; SO<sub>2</sub>, oxygen saturation; Qp/Qs, pulmonary-to-systemic blood flow ratio; %RVEDV, ratio of right ventricular end-diastolic volume; PAP, pulmonary arterial pressure; %LVEDV, ratio of left ventricular end-diastolic volume.</p>
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<p>Receiver operator curves analysis used to determine the diagnostic performance of d-ROMs for Qp/Qs &gt; 1.5. d-ROMs, derivatives of reactive oxygen metabolites; NT-proBNP, plasma N-terminal pro-brain natriuretic peptide.</p>
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16 pages, 596 KiB  
Review
The Role of Natriuretic Peptides in the Management of Heart Failure with a Focus on the Patient with Diabetes
by Michela Vergani, Rosa Cannistraci, Gianluca Perseghin and Stefano Ciardullo
J. Clin. Med. 2024, 13(20), 6225; https://doi.org/10.3390/jcm13206225 - 18 Oct 2024
Viewed by 966
Abstract
Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines [...] Read more.
Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting. Full article
(This article belongs to the Section Cardiology)
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<p>The diagnostic algorithm for heart failure. BNP: B-type natriuretic peptide; ECG: electrocardiogram; HFmrEF: heart failure with mildly reduced ejection fraction; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; LVEF: left ventricular ejection fraction; NT-proBNP: N-terminal pro-B type natriuretic peptide.</p>
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11 pages, 2385 KiB  
Article
Mechanical Mapping of the Common Carotid Artery in Healthy Individuals Aged 2 to 40 Years
by Roch Listz Maurice and Nagib Dahdah
J. Clin. Med. 2024, 13(20), 6220; https://doi.org/10.3390/jcm13206220 - 18 Oct 2024
Viewed by 531
Abstract
(1) Background: In 2022, the World Stroke Organization said there were more than 12.2 million new cases of stroke each year, between all ages and sexes. Six and a half million people die each year from stroke. Ischemic stroke accounts for 7.6 [...] Read more.
(1) Background: In 2022, the World Stroke Organization said there were more than 12.2 million new cases of stroke each year, between all ages and sexes. Six and a half million people die each year from stroke. Ischemic stroke accounts for 7.6 million (62%) cases, with 3.3 million (51%) deaths. Stroke is mainly linked to the atherosclerosis of a large artery. (2) Objective: Since the carotid artery directly supplies the brain, we used age-dependent mechanical mapping on the healthy common carotid artery (CCA) with the aim of being able to predict and thus potentially prevent ischemic stroke. (3) Methods: We assessed the CCA stiffness of 95 healthy control (CTL) females (2.23–39.46 years) and 107 healthy CTL males (2.85–40 years). Cine-loops of B-mode CCA data were digitally recorded with conventional medical ultrasound devices. Arterial wall elastic moduli were estimated offline using a proprietary non-invasive imaging-based biomarker algorithm (ImBioMark). Statistical analyzes were carried out with Excel software. (4) Results: Females showed a linear regression profile of CCA elastic moduli ranging from 41 ± 2 kPa to 54 ± 17 kPa (R2 = 0.88), while males showed one ranging from 38 ± 5 kPa to 63 ± 22 kPa (R2 = 0.83). For qualitative and quantitative illustrations, the elastic modulus data of CTLs were compared with those of subjects with Kawasaki disease and subjects born prematurely, respectively. (5) Conclusions: This study introduced some fundamental features of the mechanical evolution of the CCA as a function of age (2–40 years). Since atherosclerotic arteriopathy starts early in life, this gives the ability to predict risks of stroke and other cardiovascular diseases with the possibility of applying a more comprehensive range of potential preventive measures early in life. This is consistent with preventive medicine objectives which aim to be more predictive to implement pre-emptive measures as opposed to diagnostic and curative approaches. Full article
(This article belongs to the Section Vascular Medicine)
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<p>Reminder of the main steps of ImBioMark. (<b>a</b>,<b>b</b>) B-mode CCA ultrasound data sequences <math display="inline"><semantics> <mrow> <mi mathvariant="normal">I</mi> <mfenced separators="|"> <mrow> <mi mathvariant="normal">t</mi> </mrow> </mfenced> </mrow> </semantics></math> recorded non-invasively; (<b>c</b>) ImBioMark processing algorithm computes axial strain elastograms; (<b>d</b>) Illustration of an axial strain elastogram <math display="inline"><semantics> <mrow> <msub> <mrow> <mi mathvariant="normal">D</mi> </mrow> <mrow> <mi mathvariant="normal">n</mi> </mrow> </msub> <mfenced separators="|"> <mrow> <mi mathvariant="normal">t</mi> </mrow> </mfenced> </mrow> </semantics></math>; (<b>e</b>) Illustration of a CCA deformation curve; (<b>f</b>) Calculation of ImBioMark elastic modulus (E). The colorbar in (<b>d</b>) quantifies the deformation in (%). E, the elastic modulus in (<b>f</b>), is expressed in kPa.</p>
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<p>(<b>a</b>) Quadratic polynomial regressions showing weight stability at 61 ± 8 kg (R<sup>2</sup> = 0.95) and 80 ± 11 kg (R<sup>2</sup> = 0.96) for females and males, respectively; (<b>b</b>) height stability is observed at 165 ± 8 cm (R<sup>2</sup> = 0.93) and 179 ± 8 cm (R<sup>2</sup> = 0.96) for females and males, respectively. For both genders, somatic stability is reached around the age of 25.</p>
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<p>Contrasting females’ and males’ physiological data. Males’ SBP (<span class="html-italic">p</span> = 0.0007) and PP (<span class="html-italic">p</span> = 0.0006) were observed higher than those for females for each age group, although no statistically significant difference was observed for DBP (<span class="html-italic">p</span> = 0.0580).</p>
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<p>Elastic moduli (E) for female and male CTL subjects as a function of age groups. Males’ CCA plot has a slope (0.9307) almost twice as steep as females’ slope (0.4995), indicating that males’ CCA increases more rapidly with age than females.</p>
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<p>Contrasting mechanical and somatic data, with respect to gender. (<b>a</b>) Elastic modulus (E) vs. age, for females; (<b>b</b>) elastic modulus (E) vs. age, for males; (<b>c</b>) elastic modulus (E) vs. weight, for females; (<b>d</b>) elastic modulus (E) vs. weight, for males; (<b>e</b>) elastic modulus (E) vs. height, for females; (<b>f</b>) elastic modulus (E) vs. height, for males; (<b>g</b>) elastic modulus (E) vs. BMI, for females; (<b>h</b>) elastic modulus (E) vs. BMI, for males.</p>
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<p>Comparing the reference (CTL) CCA elastic moduli (E) with those obtained in KD and PMB for female (<b>a</b>,<b>c</b>) and male (<b>b</b>,<b>d</b>) subjects.</p>
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16 pages, 9204 KiB  
Article
Neuroimaging-Based Brain Morphometry in Alzheimer’s Disease
by Nonyelum Aniebo and Tarun Goswami
BioMed 2024, 4(4), 430-445; https://doi.org/10.3390/biomed4040034 - 17 Oct 2024
Viewed by 476
Abstract
Background/Objectives: Alzheimer’s disease (AD) is a leading cause of death worldwide, affecting millions of older Americans and resulting in a substantial economic burden. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) aims to investigate and develop treatments for AD. Methods: This study included 60 participants, [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is a leading cause of death worldwide, affecting millions of older Americans and resulting in a substantial economic burden. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) aims to investigate and develop treatments for AD. Methods: This study included 60 participants, divided equally into AD and control cohorts, and utilized magnetic resonance imaging (MRI) scans to detect gray matter volumetric alterations, a key biomarker of AD. The participants’ cortical volume and surface area were quantified using an automated pipeline in MIMICS (Materialise Interactive Medical Imaging Control System). Results: A multivariate regression analysis was conducted to explore the relationship between cortical measurements and potential factors influencing AD susceptibility. The study found that both cortical volume and surface area were statistically significant predictors of AD (p = 0.0004 and p = 0.011, respectively). Age was also a significant factor, with the 65–70 age group showing the strongest association (p < 0.001). The model achieved an accuracy of 0.68 in predicting AD. Conclusions: While voxel-based morphometry (VBM) using MIMICS showed promise, further development of the automated pipeline could enhance accuracy and correlation indices. These findings contribute to our understanding of brain atrophy in AD pathophysiology and highlight the potential of MRI morphometry as a tool for AD biomarker development. Full article
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<p>Workflow pipeline developed in MIMICS: a comprehensive overview of the design and implementation process.</p>
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<p>Transformation matrix applied during image cropping illustrating geometric adjustments and spatial alignment.</p>
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<p>Noise reduction and blurring of non-target areas for enhanced average weighting in desired regions using gaussian filter.</p>
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<p>Image segmentation demonstrating voxel value segmentation to distinguish bone, white matter, and gray matter regions.</p>
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<p>Global thresholding for image segmentation: binary image of white matter and corresponding 3D model representation [<a href="#B16-biomed-04-00034" class="html-bibr">16</a>].</p>
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<p>Segmented gray matter image with the corresponding 3D model.</p>
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<p>Process workflow for dynamic region—-growing segmentation of gray matter in brain imaging demonstrating 3D histogram analysis and 3D model reconstruction, in a control subject.</p>
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<p>Process workflow for dynamic region—-growing segmentation of gray matter in brain imaging demonstrating 3D histogram analysis and 3D model reconstruction, in an AD subject.</p>
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<p>Surface area and volume measurements of brain regions for Alzheimer’s disease (AD) and cognitively normal (CN) cohorts.</p>
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<p>Part volume comparison between research groups.</p>
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<p>Summary of the generalized model for the research group.</p>
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<p>A generic regression model of part volume measurements in Alzheimer’s disease (AD) and control groups.</p>
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<p>A generic regression model for part surface area measurements in Alzheimer’s disease (AD) and control groups.</p>
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<p>Bivariate analysis of part volume probability for the female Alzheimer’s disease (AD) subgroup [<a href="#B16-biomed-04-00034" class="html-bibr">16</a>].</p>
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11 pages, 978 KiB  
Article
Estimating Progression-Free Survival in Patients with Primary High-Grade Glioma Using Machine Learning
by Agnieszka Kwiatkowska-Miernik, Piotr Gustaw Wasilewski, Bartosz Mruk, Katarzyna Sklinda, Maciej Bujko and Jerzy Walecki
J. Clin. Med. 2024, 13(20), 6172; https://doi.org/10.3390/jcm13206172 - 16 Oct 2024
Viewed by 846
Abstract
Background/Objectives: High-grade gliomas are the most common primary malignant brain tumors in adults. These neoplasms remain predominantly incurable due to the genetic diversity within each tumor, leading to varied responses to specific drug therapies. With the advent of new targeted and immune [...] Read more.
Background/Objectives: High-grade gliomas are the most common primary malignant brain tumors in adults. These neoplasms remain predominantly incurable due to the genetic diversity within each tumor, leading to varied responses to specific drug therapies. With the advent of new targeted and immune therapies, which have demonstrated promising outcomes in clinical trials, there is a growing need for image-based techniques to enable early prediction of treatment response. This study aimed to evaluate the potential of radiomics and artificial intelligence implementation in predicting progression-free survival (PFS) in patients with highest-grade glioma (CNS WHO 4) undergoing a standard treatment plan. Methods: In this retrospective study, prediction models were developed in a cohort of 51 patients with pathologically confirmed highest-grade glioma (CNS WHO 4) from the authors’ institution and the repository of the Cancer Imaging Archive (TCIA). Only patients with confirmed recurrence after complete tumor resection with adjuvant radiotherapy and chemotherapy with temozolomide were included. For each patient, 109 radiomic features of the tumor were obtained from a preoperative magnetic resonance imaging (MRI) examination. Four clinical features were added manually—sex, weight, age at the time of diagnosis, and the lobe of the brain where the tumor was located. The data label was the time to recurrence, which was determined based on follow-up MRI scans. Artificial intelligence algorithms were built to predict PFS in the training set (n = 75%) and then validate it in the test set (n = 25%). The performance of each model in both the training and test datasets was assessed using mean absolute percentage error (MAPE). Results: In the test set, the random forest model showed the highest predictive performance with 1-MAPE = 92.27% and a C-index of 0.9544. The decision tree, gradient booster, and artificial neural network models showed slightly lower effectiveness with 1-MAPE of 88.31%, 80.21%, and 91.29%, respectively. Conclusions: Four of the six models built gave satisfactory results. These results show that artificial intelligence models combined with radiomic features could be useful for predicting the progression-free survival of high-grade glioma patients. This could be beneficial for risk stratification of patients, enhancing the potential for personalized treatment plans and improving overall survival. Further investigation is necessary with an expanded sample size and external multicenter validation. Full article
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<p>Assuming that each small square represents a pixel, the morphological and first-order features of images (<b>A</b>,<b>B</b>) would be the same, but the images differ in texture.</p>
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<p>Study flowchart. (<b>a</b>) Magnetic resonance (MR) imaging; the study is based on contrast-enhanced T1—w images. (<b>b</b>) Identification of a region of interest (ROI) and semi-automatic image segmentation. (<b>c</b>) Normalization and radiomic feature extraction from the defined ROI; 109 radiomic features were obtained in the study. (<b>d</b>) Data preprocessing and analysis; five different machine learning (ML) models were trained on the received data (AI—artificial intelligence, DL—deep learning). (<b>e</b>) Results.</p>
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<p>Flowchart of the patient selection process.</p>
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<p>Glioma CNS WHO 4 in the left parietal lobe. T1-weighted image after administration of contrast agent; the blue color was used to mark the tumor segmented by the semi-automated method.</p>
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<p>Kaplan–Meier curve of PFS for patients in the study group.</p>
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<p>Performance of the five models for predicting the PFS presented using 1-MAPE.</p>
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<p>Kaplan–Meier curve of predicted PFS for the test set by the random forest model marked in blue and Kaplan–Meier curve of PFS for patients in the study group marked in orange.</p>
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24 pages, 3265 KiB  
Article
A Map of Transcriptomic Signatures of Different Brain Areas in Alzheimer’s Disease
by Riccardo Rocco Ferrari, Valentina Fantini, Maria Garofalo, Rosalinda Di Gerlando, Francesca Dragoni, Bartolo Rizzo, Erica Spina, Michele Rossi, Chiara Calatozzolo, Xhulja Profka, Mauro Ceroni, Antonio Guaita, Annalisa Davin, Stella Gagliardi and Tino Emanuele Poloni
Int. J. Mol. Sci. 2024, 25(20), 11117; https://doi.org/10.3390/ijms252011117 - 16 Oct 2024
Viewed by 670
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In this study, a whole-transcriptome analysis was carried out on brain samples from the hippocampus (HI), temporal and parietal cortices (TC and PC, respectively), cingulate cortex (CG), and substantia nigra (SN) of six subjects with a definite AD diagnosis and three healthy age-matched controls in duplicate. The transcriptomic results showed a greater number of differentially expressed genes (DEGs) in the TC (1571) and CG (1210) and a smaller number of DEGs in the HI (206), PC (109), and SN (60). Furthermore, the GSEA showed a difference between the group of brain areas affected early (HI and TC) and the group of areas that were subsequently involved (PC, CG, and SN). Notably, in the HI and TC, there was a significant downregulation of shared DEGs primarily involved in synaptic transmission, while in the PC, CG, and SN, there was a significant downregulation of genes primarily involved in protein folding and trafficking. The course of AD could follow a definite time- and severity-related pattern that arises from protein misfolding, as observed in the PC, CG, and SN, and leads to synaptic impairment, as observed in the HI and TC. Therefore, a map of the molecular and biological processes involved in AD pathogenesis may be traced. This could aid in the discovery of novel biological targets in order to develop effective and well-timed therapeutic approaches. Full article
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<p>Hippocampus. (<b>A</b>) PCA of DEGs in the HI of AD subjects in comparison with those of the CTRL subjects; AD subjects and CTRL subjects were separated into two distinct groups, suggesting a substantial difference between the two groups from a statistical point of view. (<b>B</b>) Volcano plot of DEGs between AD and CTRL subjects. Genes were plotted in order to emphasize both statistical significance (<span class="html-italic">p</span>-value) and magnitude of change (Log<sub>2</sub> fold change). Genes whose deregulation was the most statistically significant and that had a large fold change are represented with red dots. (<b>C</b>) GO-enriched terms in the HI of AD vs. CTRL for biological processes, molecular functions (<b>D</b>), and cellular components (<b>E</b>). The dots in each category may vary in color and dimension; a color that tends toward red indicates a higher statistical significance, while large dots indicate a higher number of genes of that specific enrichment term that were deregulated in the analyzed sample in comparison with the original GO classification.</p>
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<p>Temporal cortex. (<b>A</b>) PCA of DEGs in the TC of AD subjects in comparison with CTRL subjects. AD subjects and CTRL subjects were separated into two distinct groups, suggesting a substantial difference between the two groups from a statistical point of view. (<b>B</b>) Volcano plot of DEGs between AD and CTRL subjects. Genes were plotted in order to emphasize both statistical significance (<span class="html-italic">p</span>-value) and magnitude of change (Log<sub>2</sub> fold change). Genes whose deregulation was most statistically significant and that had a large fold change are represented by red dots; (<b>C</b>) GO-enriched terms in the TC of AD vs. CTRL for biological processes, molecular functions (<b>D</b>), and cellular components (<b>E</b>). The dots in each category may vary in color and dimension; a color that tends toward red indicates greater statistical significance, while large dots indicate a higher number of genes of that specific enrichment term that were deregulated in the analyzed sample in comparison with the original GO classification.</p>
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<p>Parietal cortex. (<b>A</b>) PCA of DEGs in the PC of AD subjects in comparison with CTRL subjects. In this case, the separation between AD subjects and CTRL subjects was less defined, suggesting a minor difference between the two groups from a statistical point of view. (<b>B</b>) Volcano plot of DEGs between AD and CTRL subjects. Genes were plotted in order to emphasize both statistical significance (<span class="html-italic">p</span>-value) and the magnitude of change (Log<sub>2</sub> fold change). Genes whose deregulation was most statistically significant and those with a large fold change are represented by red dots. (<b>C</b>) Interaction network for the PC obtained through STRING. The two nodes are represented by <span class="html-italic">HSPH1</span> and <span class="html-italic">DNAJB1</span>. Interactions between the two nodes were determined using curated datasets and experimental determinations. (<b>D</b>) GO-enriched terms in the PC of AD vs. CTRL for biological processes, molecular functions (<b>E</b>), and cellular components (<b>F</b>). The dots in each category may vary in color and dimension; a color that tends toward red indicates a greater statistical significance, while large dots indicate a higher number of genes of that specific enrichment term that were deregulated in the analyzed sample in comparison with the original GO classification. In this case, the reduced number of DEGs observed in the PC resulted in a less defined enrichment analysis with a minor degree of statistical significance.</p>
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<p>Cingulate gyrus. (<b>A</b>) PCA of DEGs in the CG of AD subjects compared with the CTRL subjects. In this case, the separation between AD subjects and CTRL subjects was less defined, suggesting a minor difference between the two groups from a statistical point of view. (<b>B</b>) Volcano plot of DEGs between the AD and CTRL subjects. Genes were plotted in order to emphasize both statistical significance (<span class="html-italic">p</span>-value) and the magnitude of change (Log<sub>2</sub> fold change). Genes whose deregulation was most statistically significant and those that had a large fold change are represented by red dots. (<b>C</b>) GO-enriched terms in the CG of AD vs. CTRL for biological processes, molecular functions (<b>D</b>), and cellular components (<b>E</b>). Dots in each category may vary in color and dimension; a color that tends toward red indicates a higher statistical significance, while large dots indicate a higher number of genes of that specific enrichment term that were deregulated in the analyzed sample in comparison with the original GO classification.</p>
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<p>Substantia nigra. (<b>A</b>) PCA of DEGs in the SN of AD subjects in comparison with CTRL subjects. AD subjects and CTRL subjects were separated into two distinct groups, suggesting a substantial difference between the two groups from a statistical point of view. (<b>B</b>) Volcano plot of DEGs between the AD and CTRL subjects. Genes were plotted in order to emphasize both statistical significance (<span class="html-italic">p</span>-value) and the magnitude of change (Log<sub>2</sub> fold change). Genes whose deregulation was most statistically significant and those that had a large fold change are represented by red dots. (<b>C</b>) GO-enriched terms in the SN of AD vs. CTRL for biological processes, molecular functions (<b>D</b>), and cellular components (<b>E</b>). Dots in each category may vary in color and dimension; a color that tends toward red indicates a higher statistical significance, while large dots indicate a higher number of genes of that specific enrichment term that were deregulated in the analyzed sample in comparison with the original GO classification.</p>
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<p>Brain areas of AD subjects were clustered according to the deregulation of the same class of enrichment terms. (<b>A</b>) Venn diagram of DEGs across the analyzed brain areas in AD subjects. The selection of DEGs was made by considering protein-coding genes with an adjusted <span class="html-italic">p</span> value of ≤0.05. The Venn diagrams referring to the overlapping of GO enrichment terms resulted from the STRING functional enrichment analysis: (<b>B</b>) GO biological process terms; (<b>C</b>) GO molecular function terms; and (<b>D</b>) GO cellular component terms.</p>
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17 pages, 1018 KiB  
Article
Resting-State Functional Connectivity Predicts Attention Problems in Children: Evidence from the ABCD Study
by Kelly A. Duffy and Nathaniel E. Helwig
NeuroSci 2024, 5(4), 445-461; https://doi.org/10.3390/neurosci5040033 - 12 Oct 2024
Viewed by 922
Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, and numerous functional and structural differences have been identified in the brains of individuals with ADHD compared to controls. This study uses data from the baseline sample of the large, epidemiologically informed Adolescent Brain [...] Read more.
Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, and numerous functional and structural differences have been identified in the brains of individuals with ADHD compared to controls. This study uses data from the baseline sample of the large, epidemiologically informed Adolescent Brain Cognitive Development Study of children aged 9–10 years old (N = 7979). Cross-validated Poisson elastic net regression models were used to predict a dimensional measure of ADHD symptomatology from within- and between-network resting-state correlations and several known risk factors, such as biological sex, socioeconomic status, and parental history of problematic alcohol and drug use. We found parental history of drug use and biological sex to be the most important predictors of attention problems. The connection between the default mode network and the dorsal attention network was the only brain network identified as important for predicting attention problems. Specifically, we found that reduced magnitudes of the anticorrelation between the default mode and dorsal attention networks relate to increased attention problems in children. Our findings complement and extend recent studies that have connected individual differences in structural and task-based fMRI to ADHD symptomatology and individual differences in resting-state fMRI to ADHD diagnoses. Full article
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<p>The 12 functional brain networks considered in this study. The brain networks were defined using regions of interest (ROIs) from the Gordon parcellation [<a href="#B42-neurosci-05-00033" class="html-bibr">42</a>] and were plotted using the BrainNet Viewer software, version 1.7 [<a href="#B43-neurosci-05-00033" class="html-bibr">43</a>]. The brain network abbreviations used in the ABCD Study<sup>®</sup> include AD = auditory network, CA = cinguo-parietal network, CGC = cinguo-opercular network, DLA = dorsal attention network, DT = default network, FO = frontoparietal network, RSPLTP = restrosplenial temporal network, SA = salience network, SMH = somatomotor hand network, SMM = somatomotor mouth network, VIS = visual network, and VTA = ventral attention network.</p>
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<p>Histogram of the Attention Problems subscale of the Child Behavior Checklist (CBCL).</p>
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<p>Prediction error curves for the three examined penalty functions. The <span class="html-italic">x</span>-axis represents the logarithm of each of the 100 <math display="inline"><semantics> <mi>λ</mi> </semantics></math> values tested in cross-validation as part of the solution path. Red points show the average prediction error (operationalized as mean absolute error, and averaged across the 10 folds), whereas the gray lines display +/− one standard error. The two vertical (dotted) lines denote the solutions that minimize the prediction error (left) and the solution that is within one standard error of the minimum (right).</p>
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<p>Variable importance indices for the demographic and parental history variables (<b>top</b>) and the active brain connectivity variables (<b>bottom</b>).</p>
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<p>Predicted Child Behavior Checklist (CBCL) Attention Problems on the link scale (i.e., additive effect <math display="inline"><semantics> <msub> <mi>f</mi> <mi>j</mi> </msub> </semantics></math>) as a function of the resting-state functional connectivity between the default mode (DT) and the dorsal attention (DLA) networks.</p>
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<p>Predicted Child Behavior Checklist (CBCL) Attention Problems on the response scale (i.e., multiplicative effect <math display="inline"><semantics> <mrow> <mo form="prefix">exp</mo> <mo>(</mo> <msub> <mi>f</mi> <mi>j</mi> </msub> <mo>)</mo> </mrow> </semantics></math>) as a function of the resting-state functional connectivity between the default mode (DT) and the dorsal attention (DLA) networks.</p>
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13 pages, 1475 KiB  
Article
Nongenetic and Genetic Factors Associated with White Matter Brain Aging: Exposome-Wide and Genome-Wide Association Study
by Li Feng, Halley S. Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L. Elliot Hong, Peter Kochunov, David K. Y. Lei and Tianzhou Ma
Genes 2024, 15(10), 1285; https://doi.org/10.3390/genes15101285 - 30 Sep 2024
Viewed by 1071
Abstract
Background/Objectives: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying [...] Read more.
Background/Objectives: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals. Methods: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor imaging data to predict the white matter brain age gap (BAG) and treated it as the marker of brain aging. For XWAS, we included 107 variables encompassing five major categories of modifiable exposures that potentially impact brain aging and performed both univariate and multivariate analysis to select the final set of nongenetic risk factors. Results: We found current tobacco smoking, dietary habits including oily fish, beef, lamb, cereal, and coffee intake, length of mobile phone use, use of UV protection, and frequency of solarium/sunlamp use were associated with the BAG. In genetic analysis, we identified several SNPs on chromosome 3 mapped to genes IP6K1, GMNC, OSTN, and SLC25A20 significantly associated with the BAG, showing the high heritability and polygenic architecture of human brain aging. Conclusions: The critical nongenetic and genetic risk factors identified in our study provide insights into the causal relationship between white matter brain aging and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Advances in Bioinformatics and Environmental Health)
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<p>Overview of the analytical steps in this study.</p>
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<p>Coefficients and 95% CIs of the 17 exposure variables selected in the univariate analysis of XWAS. Variables are ordered by categories. Dots represents coefficients, and lines represent the 95% CIs.</p>
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<p>Manhattan plot of association results from GWAS on BAGs. Chromosome numbers are shown on the <span class="html-italic">x</span>-axis, and −log10 association <span class="html-italic">p</span>-values on the <span class="html-italic">y</span>-axis.</p>
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