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Keywords = tremor modelling

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20 pages, 8922 KiB  
Article
Prediction and Elimination of Physiological Tremor During Control of Teleoperated Robot Based on Deep Learning
by Juntao Chen, Zhiqing Zhang, Wei Guan, Xinxin Cao and Ke Liang
Sensors 2024, 24(22), 7359; https://doi.org/10.3390/s24227359 - 18 Nov 2024
Viewed by 371
Abstract
Currently, teleoperated robots, with the operator’s input, can fully perceive unknown factors in a complex environment and have strong environmental interaction and perception abilities. However, physiological tremors in the human hand can seriously affect the accuracy of processes that require high-precision control. Therefore, [...] Read more.
Currently, teleoperated robots, with the operator’s input, can fully perceive unknown factors in a complex environment and have strong environmental interaction and perception abilities. However, physiological tremors in the human hand can seriously affect the accuracy of processes that require high-precision control. Therefore, this paper proposes an EEMD-IWOA-LSTM model, which can decompose the physiological tremor of the hand into several intrinsic modal components (IMF) by using the EEMD decomposition strategy and convert the complex nonlinear and non-stationary physiological tremor curve of the human hand into multiple simple sequences. An LSTM neural network is used to build a prediction model for each (IMF) component, and an IWOA is proposed to optimize the model, thereby improving the prediction accuracy of the physiological tremor and eliminating it. At the same time, the prediction results of this model are compared with those of different models, and the results of EEMD-IWOA-LSTM presented in this study show obvious superior performance. In the two examples, the MSE of the prediction model proposed are 0.1148 and 0.00623, respectively. The defibrillation model proposed in this study can effectively eliminate the physiological tremor of the human hand during teleoperation and improve the control accuracy of the robot during teleoperation. Full article
(This article belongs to the Special Issue Advanced Robotic Manipulators and Control Applications)
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Figure 1
<p>Control flow chart of teleoperation system.</p>
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<p>Tremor Suppression Model.</p>
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<p>LSTM structure diagram.</p>
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<p>Decomposition process of EEMD.</p>
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<p>EEMD-LSTM model structure diagram.</p>
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<p>IWOA flow chart.</p>
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<p>Decomposition results of EEMD.</p>
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<p>Modeling process in Example 1.</p>
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<p>Prediction results of tremor signal.</p>
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<p>Prediction results of tremor signal.</p>
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<p>Fitness curve of each IMF component.</p>
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<p>Box diagram of different axes. (<b>a</b>) is the <span class="html-italic">x</span> axis, (<b>b</b>) is the <span class="html-italic">y</span> axis, and (<b>c</b>) is the <span class="html-italic">z</span> axis.</p>
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<p>Comparison of the effects of different activation functions.</p>
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<p>Prediction results of tremor signal.</p>
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<p>Error box diagram; (<b>a</b>) is the <span class="html-italic">x</span> axis, (<b>b</b>) is the <span class="html-italic">y</span> axis, and (<b>c</b>) is the <span class="html-italic">z</span> axis.</p>
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<p>Tremor data <math display="inline"><semantics> <mrow> <msup> <mrow> <mi mathvariant="normal">R</mi> </mrow> <mrow> <mn>2</mn> </mrow> </msup> </mrow> </semantics></math> for three axes in two cases; (<b>a</b>) Case 1; (<b>b</b>) Case 2.</p>
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18 pages, 1030 KiB  
Review
Biomechanics of Parkinson’s Disease with Systems Based on Expert Knowledge and Machine Learning: A Scoping Review
by Luis Pastor Sánchez-Fernández
Computation 2024, 12(11), 230; https://doi.org/10.3390/computation12110230 - 17 Nov 2024
Viewed by 606
Abstract
Patients with Parkinson’s disease (PD) can present several biomechanical alterations, such as tremors, rigidity, bradykinesia, postural instability, and gait alterations. The Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has a good reputation for uniformly evaluating motor and non-motor aspects of PD. However, [...] Read more.
Patients with Parkinson’s disease (PD) can present several biomechanical alterations, such as tremors, rigidity, bradykinesia, postural instability, and gait alterations. The Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has a good reputation for uniformly evaluating motor and non-motor aspects of PD. However, motor clinical assessment depends on visual observations, which are mostly qualitative, with subtle differences not recognized. Many works have examined evaluations and analyses of these biomechanical alterations. However, there are no reviews on this topic. This paper presents a scoping review of computer models based on expert knowledge and machine learning (ML). The eligibility criteria and sources of evidence are represented by papers in journals indexed in the Journal Citation Report (JCR), and this paper analyzes the data, methods, results, and application opportunities in clinical environments or as support for new research. Finally, we analyze the results’ explainability and the acceptance of such systems as tools to help physicians, both now and in future contributions. Many researchers have addressed PD biomechanics by using explainable artificial intelligence or combining several analysis models to provide explainable and transparent results, considering possible biases and precision and creating trust and security when using the models. Full article
(This article belongs to the Special Issue Application of Biomechanical Modeling and Simulation)
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Figure 1
<p>Six sensors (IMU) are distributed on the trunk and upper and lower extremities.</p>
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<p>Overview of the computer method (modified graphical abstract of [<a href="#B59-computation-12-00230" class="html-bibr">59</a>]).</p>
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28 pages, 5036 KiB  
Article
Optimal Feature Selection and Classification for Parkinson’s Disease Using Deep Learning and Dynamic Bag of Features Optimization
by Aarti, Swathi Gowroju, Mst Ismat Ara Begum and A. S. M. Sanwar Hosen
BioMedInformatics 2024, 4(4), 2223-2250; https://doi.org/10.3390/biomedinformatics4040120 - 12 Nov 2024
Viewed by 502
Abstract
Parkinson’s Disease (PD) is a neurological condition that worsens with time and is characterized bysymptoms such as cognitive impairment andbradykinesia, stiffness, and tremors. Parkinson’s is attributed to the interference of brain cells responsible for dopamine production, a substance regulating communication between brain cells. [...] Read more.
Parkinson’s Disease (PD) is a neurological condition that worsens with time and is characterized bysymptoms such as cognitive impairment andbradykinesia, stiffness, and tremors. Parkinson’s is attributed to the interference of brain cells responsible for dopamine production, a substance regulating communication between brain cells. The brain cells involved in dopamine generation handle adaptation and control, and smooth movement. Convolutional Neural Networks are used to extract distinctive visual characteristics from numerous graphomotor sample representations generated by both PD and control participants. The proposed method presents an optimal feature selection technique based on Deep Learning (DL) and the Dynamic Bag of Features Optimization Technique (DBOFOT). Our method combines neural network-based feature extraction with a strong optimization technique to dynamically choose the most relevant characteristics from biological data. Advanced DL architectures are then used to classify the chosen features, guaranteeing excellent computational efficiency and accuracy. The framework’s adaptability to different datasets further highlights its versatility and potential for further medical applications. With a high accuracy of 0.93, the model accurately identifies 93% of the cases that are categorized as Parkinson’s. Additionally, it has a recall of 0.89, which means that 89% of real Parkinson’s patients are accurately identified. While the recall for Class 0 (Healthy) is 0.75, meaning that 75% of the real healthy cases are properly categorized, the precision decreases to 0.64 for this class, indicating a larger false positive rate. Full article
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Graphical abstract

Graphical abstract
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<p>The proposed system architecture.</p>
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<p>Proposed fine-tuned LSTM-BoF model for PD classification.</p>
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<p>The clinical data with updrs_1, updrs_2, updrs_3, updrs_4 labels.</p>
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<p>Patients and their NPX values against their visit month. (<b>a</b>) NPX values at the baseline (month 0). (<b>b</b>) NPX values at the 24-month visit. (<b>c</b>) NPX values at 36 months. (<b>d</b>) NPX values at the 60-month visit.</p>
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<p>Patients and their NPX values against their visit month. (<b>a</b>) NPX values at the baseline (month 0). (<b>b</b>) NPX values at the 24-month visit. (<b>c</b>) NPX values at 36 months. (<b>d</b>) NPX values at the 60-month visit.</p>
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<p>Patients and their NPX values against their visit month. (<b>a</b>) NPX values at the baseline (month 0). (<b>b</b>) NPX values at the 24-month visit. (<b>c</b>) NPX values at 36 months. (<b>d</b>) NPX values at the 60-month visit.</p>
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<p>Mean Squared Error during Out of Bag results.</p>
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<p>Preprocessed hand-written PD patient’s spiral drawing images. (<b>a</b>) There are three separate loops in this spiral, which begin with a small, tight centre and grow outward. The spiral’s breadth seems to be rather constant, although there are a few tiny abnormalities are the signs of mild motor control problems. (<b>b</b>) In comparison to the first image, the loops are a little bit more enlarged. With fewer line deviations and a smoother appearance, the spiral may indicate improved motor control or less tremor. (<b>c</b>) The spiral is uniformly wide throughout, but it seems less accurate with a more noticeable outward curvature, which might suggest more severe motor problems. (<b>d</b>) This spiral has been enlarged to reveal more information on a selected section of the spiral. This line exhibits increased jaggedness and abnormalities, indicating a more serious problem with motor control. It may be associated with the tremor or another Parkinson’s Disease symptom.</p>
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<p>Model predictions on spiral drawings for PD detection.</p>
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<p>Predictions on spiral images: predicted probabilities of spiral drawings for PD detection.</p>
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<p>ROC curve representing the accuracy of models.</p>
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<p>Confusion matrix of proposed system.</p>
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<p>Comparison of model performance using two different datasets: (<b>a</b>) classification accuracy of model’s performance using PTD dataset and (<b>b</b>) classification accuracy of handwriting analysis.</p>
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<p>Comparison of model performance using two different datasets: (<b>a</b>) classification accuracy of model’s performance using PTD dataset and (<b>b</b>) classification accuracy of handwriting analysis.</p>
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27 pages, 6449 KiB  
Article
In Vivo Insights: Near-Infrared Photon Sampling of Reflectance Spectra from Cranial and Extracranial Sites in Healthy Individuals and Patients with Essential Tremor
by Antonio Currà, Riccardo Gasbarrone, Davide Gattabria, Giuseppe Bonifazi, Silvia Serranti, Daniela Greco, Paolo Missori, Francesco Fattapposta, Alessandra Picciano, Andrea Maffucci and Carlo Trompetto
Photonics 2024, 11(11), 1025; https://doi.org/10.3390/photonics11111025 - 30 Oct 2024
Viewed by 459
Abstract
Near-infrared (NIR) spectroscopy is a powerful non-invasive technique for assessing the optical properties of human tissues, capturing spectral signatures that reflect their biochemical and structural characteristics. In this study, we investigated the use of NIR reflectance spectroscopy combined with chemometric analysis to distinguish [...] Read more.
Near-infrared (NIR) spectroscopy is a powerful non-invasive technique for assessing the optical properties of human tissues, capturing spectral signatures that reflect their biochemical and structural characteristics. In this study, we investigated the use of NIR reflectance spectroscopy combined with chemometric analysis to distinguish between patients with Essential Tremor (ET) and healthy individuals. ET is a common movement disorder characterized by involuntary tremors, often making it difficult to clinically differentiate from other neurological conditions. We hypothesized that NIR spectroscopy could reveal unique optical fingerprints that differentiate ET patients from healthy controls, potentially providing an additional diagnostic tool for ET. We collected NIR reflectance spectra from both extracranial (biceps and triceps) and cranial (cerebral cortex and brainstem) sites in ET patients and healthy subjects. Using Partial Least Squares Discriminant Analysis (PLS-DA) and Partial Least Squares (PLS) regression models, we analyzed the optical properties of the tissues and identified significant wavelength peaks associated with spectral differences between the two groups. The chemometric analysis successfully classified subjects based on their spectral profiles, revealing distinct differences in optical properties between cranial and extracranial sites in ET patients compared to healthy controls. Our results suggest that NIR spectroscopy, combined with machine learning algorithms, offers a promising non-invasive method for the in vivo characterization and differentiation of tissues in ET patients. Full article
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<p>Average reflectance spectra collected from extracranial and cranial sites: (<b>a</b>) ET biceps vs. Normal biceps, (<b>b</b>) ET triceps vs. Normal triceps, (<b>c</b>) ET cortical vs. Normal cortical, and (<b>d</b>) ET brainstem vs. Normal brainstem.</p>
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<p>Principal Component Analysis (PCA) scores plot for the first two principal components, based on spectra collected at the extracranial/biceps site in both ET patients and healthy subjects (Normal) (<b>a</b>). The loadings plot for the first principal component (PC1) is shown in (<b>b</b>).</p>
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<p>Panel (<b>a</b>): scores plot of Principal Component Analysis (PCA) for the first two principal components, based on spectra collected from the extracranial/triceps site in both patients (ET) and healthy subjects (Normal). Panel (<b>b</b>): loadings plot for the first principal component.</p>
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<p>Panel (<b>a</b>): scores plot of Principal Component Analysis (PCA) for the first two components, based on spectra collected from the cranial/cortical site in both patients (ET) and healthy subjects (Normal). Panel (<b>b</b>): loadings plot for the first principal component.</p>
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<p>Panel (<b>a</b>): scores plot of Principal Component Analysis (PCA) for the first two components, based on spectra collected from the cranial/brainstem site in both patients (ET) and healthy subjects (Normal)<b>.</b> Panel (<b>b</b>): loadings plot for the first principal component.</p>
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<p>VIP scores plot for “ET biceps/Normal biceps” (<b>a</b>) and “ET triceps/Normal triceps” (<b>b</b>).</p>
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<p>Panel (<b>a</b>) VIP scores plot for “ET cortical/Normal cortical”; panel (<b>b</b>) “ET brainstem/Normal brainstem”.</p>
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<p>Regression models for “ET biceps/Normal biceps” data based on age panel (<b>a</b>) and BMI panel (<b>c</b>), along with the corresponding VIP score plots for the age-based model panel (<b>b</b>) and the BMI-based model panel (<b>d</b>). Biceps (B) = ET biceps; Biceps (N) = Normal biceps.</p>
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<p>Regression models for “ET triceps/Normal triceps” data based on age panel (<b>a</b>) and BMI panel (<b>c</b>), including the VIP score plots for the age-based model panel (<b>b</b>) and the BMI-based model panel (<b>d</b>). Triceps (B) = ET triceps; Triceps (N) = Normal triceps.</p>
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<p>Regression models for “ET cortical/Normal cortical” data based on age panel (<b>a</b>) and BMI panel (<b>c</b>), along with VIP score plots for the age-based model panel (<b>b</b>) and the BMI-based model panel (<b>d</b>). Cerebral cortex (B) = ET cortical; Cerebral cortex (N) = Normal cortical.</p>
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<p>Regression models for “ET cortical/Normal cortical” data based on age panel (<b>a</b>) and BMI panel (<b>c</b>), along with VIP score plots for the age-based model panel (<b>b</b>) and the BMI-based model panel (<b>d</b>). Cerebral cortex (B) = ET cortical; Cerebral cortex (N) = Normal cortical.</p>
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<p>Regression models for “ET brainstem/Normal brainstem” data based on age panel (<b>a</b>) and BMI panel (<b>c</b>), featuring the VIP score plots for the age-based model panel (<b>b</b>) and the BMI-based model panel (<b>d</b>). Mid-brain (B) = ET brainstem; Mid-brain (N) = Normal brainstem.</p>
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25 pages, 6142 KiB  
Article
Targeting the Sirtuin–1/PPAR–Gamma Axis, RAGE/HMGB1/NF-κB Signaling, and the Mitochondrial Functions by Canagliflozin Augments the Protective Effects of Levodopa/Carbidopa in Rotenone-Induced Parkinson’s Disease
by Mennatallah A. Elkady, Ahmed M. Kabel, Lamees M. Dawood, Azza I. Helal, Hany M. Borg, Hanan Abdelmawgoud Atia, Nesreen M. Sabry, Nouran M. Moustafa, El-Shaimaa A. Arafa, Shuruq E. Alsufyani and Hany H. Arab
Medicina 2024, 60(10), 1682; https://doi.org/10.3390/medicina60101682 - 14 Oct 2024
Viewed by 945
Abstract
Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no [...] Read more.
Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD. Full article
(This article belongs to the Section Pharmacology)
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<p>An illustrative representation of the experimental protocol of the study.</p>
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<p>The open field test apparatus.</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the pole test (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the open field test (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the rotarod test (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the striatal dopamine levels (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the levels of Nrf2 and the redox state of the striatal tissues (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the levels of toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and nuclear factor kappa B (NF-kB) p65 in the striatal tissues (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the striatal tissue levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)-gamma (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the striatal tissue levels of HMGB1 and receptors of advanced glycation end products (RAGE) (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the mitochondrial functions (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the striatal tissue levels of AMPK and mTOR (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Effect of levodopa/carbidopa with or without canagliflozin on rotenone-induced changes in the autophagy markers in the striatal tissues (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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<p>Hematoxylin- and eosin-stained sections from the hippocampus of: (<b>A</b>) the control group demonstrating multiple compact layers of pyramidal cells with polygonal cell bodies and vesicular nuclei (thin arrows); (<b>B</b>) rotenone-injected group showing significant diminution of the thickness of the pyramidal cell layer, with many cells showing apoptotic changes (thin arrows), diffuse inflammatory cellular infiltration (thick arrow), and marked vascular congestion (arrow head); (<b>C</b>) rotenone-injected group treated with levodopa/carbidopa and (<b>D</b>) rotenone-injected group treated with canagliflozin exhibiting moderate decline in the number of cells that showed apoptotic changes (thick arrows) with a significantly increased number of normal cells with vesicular nuclei and prominent nucleoli (thin arrows); (<b>E</b>) rotenone-injected group treated with levodopa/carbidopa concomitantly with canagliflozin exhibiting marked increase in the number of normal neurons with vesicular nuclei (thin arrows), with scanty dystrophic apoptotic neurons in between (thick arrow); (<b>F</b>) the average thickness of the different areas of the hippocampus (Mean ± SD). ROT (rotenone); CNG (canagliflozin); DG (dentate gyrus).</p>
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<p>Hematoxylin- and eosin-stained sections from the substantia nigra of (<b>A</b>) the control group demonstrating the dopaminergic neurons with vesicular nuclei and basophilic cytoplasm (thin arrows); (<b>B</b>) rotenone-injected group showing massive neurodegeneration. The neurons appear small and shrunken (thick arrows) with many neurons showing irregular outlines, cytoplasmic shrinkage, and pyknotic darkly stained nuclei (arrow heads) with perineuronal vacuolations (thin arrows); (<b>C</b>) rotenone-injected group treated with levodopa/carbidopa; and (<b>D</b>) rotenone-injected group treated with canagliflozin exhibiting a moderate decline in the number of the degenerated shrunken cells (thick arrows) and the nuclei showing pyknotic changes (arrow head) with significantly increased number of the normal dopaminergic neurons with vesicular nuclei (thin arrows); (<b>E</b>) rotenone-injected group treated with levodopa/carbidopa concomitantly with canagliflozin exhibiting significant increase in the number of the normal dopaminergic neurons with vesicular nuclei (thin arrows) associated with scanty small shrunken neurons in-between (thick arrow).</p>
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<p>The immunohistochemical staining of tyrosine hydroxylase (TH) (×40) in the tissue sections of the substantia nigra of: (<b>A</b>) the control group exhibiting strong positive TH immunostaining; (<b>B</b>) rotenone-injected group showing minimal positive TH immunostaining; (<b>C</b>) rotenone-injected group treated with levodopa/carbidopa; and (<b>D</b>) rotenone-injected group treated with canagliflozin demonstrating moderately positive TH immunostaining; (<b>E</b>) rotenone-injected group treated with levodopa/carbidopa concomitantly with canagliflozin revealing strong positive TH immunostaining; (<b>F</b>) the percentage of positive immunostaining of TH in the substantia nigra (Mean ± SD). <sup>a</sup> Significant compared to the control group (<span class="html-italic">p</span>-value less than 0.05); <sup>b</sup> significant relative to rotenone group (<span class="html-italic">p</span>-value less than 0.05); <sup>c</sup> significant relative to rotenone + levodopa/carbidopa group (<span class="html-italic">p</span>-value less than 0.05); <sup>d</sup> significant relative to rotenone + canagliflozin group (<span class="html-italic">p</span>-value less than 0.05). ROT (rotenone); CNG (canagliflozin).</p>
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17 pages, 2351 KiB  
Article
Deep Learning for Parkinson’s Disease Diagnosis: A Graph Neural Network (GNN) Based Classification Approach with Graph Wavelet Transform (GWT) Using Protein–Peptide Datasets
by Prabhavathy Mohanraj, Valliappan Raman and Saveeth Ramanathan
Diagnostics 2024, 14(19), 2181; https://doi.org/10.3390/diagnostics14192181 - 29 Sep 2024
Viewed by 701
Abstract
Abstract: Background: An important neurological disorder of Parkinson’s Disease (PD) is characterized by motor and non-motor activity of the patients. Empirical condition of the patient: PD assessment uses the Movement Disorder Society Unified Parkinson’s Rating Scale part III (MDS-UPDRS-III) measures for identifying [...] Read more.
Abstract: Background: An important neurological disorder of Parkinson’s Disease (PD) is characterized by motor and non-motor activity of the patients. Empirical condition of the patient: PD assessment uses the Movement Disorder Society Unified Parkinson’s Rating Scale part III (MDS-UPDRS-III) measures for identifying the prediction of PD. Due to the unstable value of the measurement, the PD prediction and tracking lead to a lower prediction rate. Methods: To overcome this limitation, this paper proposed the Graph Wavelet Transform (GWT) based weighted feature extraction along with the Graph Neutral Network (GNN) classification. The main contribution of this research is (i) The weighted correlation between the data is calculated by GWT for effective prediction of PD. (ii) Machine learning algorithms were trained to predict Parkinson’s disease based on these patterns. In this research, we developed a new model called Graph Neural Network (GNN) to predict PD tremors’ MDS-UPDRS-III score using input data. To strengthen PD research and enable the construction of individualized treatment plans, these linked networks work together to methodically examine the data and find significant discoveries. Results: The proposed approach for predicting PD severity (motor- and MDS_UPDRS) has a mean squared error of 0.1796 and a root mean squared error of 0.2845, according to the experimental data. The prediction accuracy is increased by 27.66%, 54.11%, and 0.71%, correspondingly, when compared with the most effective State-of-the-Art methods of DNN, ANFIS + SVR, and Mixed MLP models. Conclusion: In conclusion, this proves that the proposed strategy is more effective at making predictions. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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<p>Flow Diagram of Protein–Peptide (PP) Data Based on PD Prediction.</p>
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<p>GWT–GNN-based PD Prediction Model.</p>
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<p>Feature Vector Extraction using Graph Wavelet Transform.</p>
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<p>Monitoring PD patients’ Health Report for Severity Prediction.</p>
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<p>Average accuracy comparison of the proposed model.</p>
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<p>Performance Comparison with State-of-the-Art Methods.</p>
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<p>Regression Comparison of Various Architecture of the Proposed Model.</p>
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16 pages, 12495 KiB  
Article
Design and Analysis of a Hand-Held Surgical Forceps with a Force-Holding Function
by Yang Bai, Yang Yu and Zhenbang Xu
Sensors 2024, 24(18), 5895; https://doi.org/10.3390/s24185895 - 11 Sep 2024
Viewed by 803
Abstract
Physiological hand tremors, twitching, and the nonlinear characteristics of the relationship between surgical forceps clamping force and operating force seriously affect the clamping accuracy of surgical instruments. To address this problem, a new type of surgical forceps with a force-holding function was developed [...] Read more.
Physiological hand tremors, twitching, and the nonlinear characteristics of the relationship between surgical forceps clamping force and operating force seriously affect the clamping accuracy of surgical instruments. To address this problem, a new type of surgical forceps with a force-holding function was developed to replace traditional forceps, which was studied in terms of structural design, statics, and dynamics. The overall structure of the surgical forceps was designed based on the lever principle, the kinematic model of the clamping part of the surgical forceps was established by the geometrical method, and the correctness of the kinematic model was verified by ADAMS. To address the clamping accuracy of the surgical forceps, a stress analysis was performed, its dynamics model was established, a finite element simulation was performed, the modal of the forceps was optimized using the Box–Behnken method, and, finally, an experimental platform was built to perform the accuracy test. The results demonstrate that the designed surgical forceps exhibit high clamping accuracy and fulfill the design specifications for surgical operations. Full article
(This article belongs to the Section Biomedical Sensors)
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<p>Overall structure of the surgical forceps.</p>
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<p>Pseudo-rigid body model of the surgical forceps.</p>
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<p>Comparison of the kinematic modeling and simulation of the clamping action.</p>
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<p>Comparison of the kinematic modeling and simulation of release action.</p>
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<p>Simplified model of the arm under the forceps.</p>
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<p>Force clouds for two limit states of the forceps.</p>
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<p>Three-dimensional response surface of the fundamental frequency.</p>
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<p>Optimal values of hinge parameters.</p>
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<p>Fundamental frequency in two limit states of the forceps.</p>
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<p>Fundamental frequency of the forceps.</p>
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<p>Experimental test platform.</p>
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<p>Variation in the gripping force of the forceps.</p>
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<p>Variation of clamping force with time for long clamping times.</p>
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18 pages, 10927 KiB  
Article
Transient Increases in Neural Oscillations and Motor Deficits in a Mouse Model of Parkinson’s Disease
by Yue Wu, Lidi Lu, Tao Qing, Suxin Shi and Guangzhan Fang
Int. J. Mol. Sci. 2024, 25(17), 9545; https://doi.org/10.3390/ijms25179545 - 2 Sep 2024
Viewed by 933
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD’s pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD’s pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between the motor symptoms of PD and transient changes in brain oscillations before and after motor tasks in different brain regions remain unclear. This study aimed to investigate neural oscillations in both healthy and PD model mice using local field potential (LFP) recordings from multiple brain regions during rest and locomotion. The histological evaluation confirmed the significant dopaminergic neuron loss in the injection side in 6-OHDA lesioned mice. Behavioral tests showed motor deficits in these mice, including impaired coordination and increased forelimb asymmetry. The LFP analysis revealed increased delta, theta, alpha, beta, and gamma band activity in 6-OHDA lesioned mice during movement, with significant increases in multiple brain regions, including the primary motor cortex (M1), caudate–putamen (CPu), subthalamic nucleus (STN), substantia nigra pars compacta (SNc), and pedunculopontine nucleus (PPN). Taken together, these results show that the motor symptoms of PD are accompanied by significant transient increases in brain oscillations, especially in the gamma band. This study provides potential biomarkers for early diagnosis and therapeutic evaluation by elucidating the relationship between specific neural oscillations and motor deficits in PD. Full article
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<p>Dopaminergic cell loss in the SNc after 6-OHDA injection. (<b>A</b>) Schematic representation of injection sites in the SNc, and the subplots C-H show enlarged pictures of the boxed area. (<b>B</b>) The number of TH+ neurons in the SNc for the sham group (n = 10) and the lesion group (n = 10). (<b>C</b>–<b>H</b>) Immunofluorescence staining of TH+ neurons (green, <b>C</b>,<b>F</b>), DAPI (blue, <b>D</b>,<b>G</b>), and a merged image (<b>E</b>,<b>H</b>) of the injection side of the SNc. The white arrows indicate TH+ neurons in the pictures. The scale bar represents 100 μm. All data are expressed as the mean ± SD. *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Behavioral performance of mice after 6-OHDA injection. (<b>A</b>–<b>C</b>) Latency to fall, speed at fall, and total distance traveled in the rotarod test. (<b>D</b>–<b>E</b>) Total time for traversal and number of hindlimb lapses for the balance beam traversal test. (<b>F</b>) Time to descend from top to base in the pole test. n = 16 for the lesion group and n = 15 for the sham group. All data are expressed as the mean ± SD. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Limb symmetry, gait impairment, and spontaneous locomotion after 6-OHDA injection. (<b>A</b>) Percentage of forelimb use on the injection side in the rearing cylinder test. n = 16 for the lesion group and n = 12 for the sham group. (<b>B</b>,<b>C</b>) Percentage of diagonal support and three-limb support during locomotion. (<b>D</b>–<b>F</b>) Average distance moved, number of entries into the central area, and percentage of time spent in the central area in the open field test. For pictures (<b>B</b>–<b>F</b>), n = 16 for the lesion group and n = 15 for the sham group. All data are expressed as the mean ± SD. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Verification of electrode placement. (<b>A</b>) Primary motor cortex (M1). (<b>B</b>) Corpus striatum (CPu). (<b>C</b>) Substantia nigra pars compacta (SNc). (<b>D</b>) Subthalamic nucleus (STN). (<b>E</b>) Pedunculopontine tegmental nucleus (PPN). Arrows indicate electrode sites. The scale bar represents 500 μm.</p>
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<p>Typical LFP waveforms recorded from the M1, CPu, STN, SNc, and PPN during resting and walking states for both sham and lesion mice.</p>
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<p>Power spectral density of LFPs recorded for the M1 (<b>A</b>), CPu (<b>B</b>), STN (<b>C</b>), PPN (<b>D</b>), and SNc (<b>E</b>). Left column shows average power spectral density of sham group during resting (red) and walking (blue) states for each brain region; middle column indicates average power spectral density of lesion group during resting (red) and walking (blue) states for each brain region; right column illustrates differences in power spectral density between walking and resting states in sham group (green) and lesion group (orange). All data are expressed as mean ± SEM. The dotted lines divide the frequency range into the delta (1–4 Hz), theta (4–8 Hz), alpha (8–21 Hz), beta (21–32 Hz), and gamma (32–100 Hz) bands.</p>
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<p>Difference in power spectra of various bands of LFP, including delta (1–4 Hz) (<b>A</b>), theta (4–8 Hz) (<b>B</b>), alpha (8–21 Hz) (<b>C</b>), beta (21–32 Hz) (<b>D</b>), and gamma (32–100 Hz) (<b>E</b>) bands. n = 10 for each group. All data are expressed as the mean ± SD. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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18 pages, 4318 KiB  
Article
Prognostic Properties of Instantaneous Amplitudes Maxima of Earth Surface Tremor
by Alexey Lyubushin and Eugeny Rodionov
Entropy 2024, 26(8), 710; https://doi.org/10.3390/e26080710 - 21 Aug 2024
Viewed by 957
Abstract
A method is proposed for analyzing the tremor of the earth’s surface, measured by GPS, in order to highlight prognostic effects. The method is applied to the analysis of daily time series of vertical displacements in Japan. The network of 1047 stations is [...] Read more.
A method is proposed for analyzing the tremor of the earth’s surface, measured by GPS, in order to highlight prognostic effects. The method is applied to the analysis of daily time series of vertical displacements in Japan. The network of 1047 stations is divided into 15 clusters. The Huang Empirical Mode Decomposition (EMD) is applied to the time series of the principal components from the clusters, with subsequent calculation of instantaneous amplitudes using the Hilbert transform. To ensure the stability of estimates of the waveforms of the EMD decomposition, 1000 independent additive realizations of white noise of limited amplitude were averaged before the Hilbert transform. Using a parametric model of the intensities of point processes, we analyze the connections between the instants of sequences of times of the largest local maxima of instantaneous amplitudes, averaged over the number of clusters and the times of earthquakes in the vicinity of Japan with minimum magnitude thresholds of 5.5 for the time interval 2012–2023. It is shown that the sequence of the largest local maxima of instantaneous amplitudes significantly more often precedes the moments of time of earthquakes (roughly speaking, has an “influence”) than the reverse “influence” of earthquakes on the maxima of amplitudes. Full article
(This article belongs to the Special Issue Time Series Analysis in Earthquake Complex Networks)
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<p>(<b>a</b>) shows the positions of 1047 GPS stations and their division into 15 clusters. The numbered circles indicate the centers of gravity of the clusters, and the blue lines indicate the boundaries between Voronoi cells. The blue star shows the position of the center of mass of all cluster centers. (<b>b</b>) shows a plot of the pseudo-F-statistic that allowed us to select 15 as the number of clusters.</p>
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<p>Graphs of weighted average vertical displacements of the earth’s surface in each of the selected 15 clusters in a sliding time window of 365 days. The Y axes represent displacement increments in mm.</p>
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<p>EEMD waveform plots for the first 6 decomposition levels for 3 clusters (numbers 1, 9 and 15). Decomposition level numbers are indicated on the left.</p>
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<p>Plots of mean EEMD waveforms and mean instantaneous amplitudes averaged over all 15 station clusters for the first 6 decomposition levels. The left side of the figure, separated by a vertical blue line, shows pairs of graphs (waveforms—their amplitudes) for levels 1–3, and the right side shows graphs for levels 4–6. The decomposition level numbers are indicated between the waveform and amplitude graphs.</p>
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<p>Time sequence of earthquakes with a magnitude of at least 5.5 in the vicinity of the Japanese Islands: (<b>a</b>) in the time period 2009–2023; (<b>b</b>) in the period of time 2012–2023.</p>
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<p>Distribution of epicenters of 349 earthquakes with a magnitude of at least 5.5 in the vicinity of the Japanese Islands in the time period 2012–2023. The red asterisk marks the center of gravity of the centers of 15 clusters of GPS stations (<a href="#entropy-26-00710-f001" class="html-fig">Figure 1</a>a), which is chosen as the center of a circle with a radius of 1500 km.</p>
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<p>Average instantaneous amplitudes of the second level of EEMD decomposition and the 349 largest local maxima (red dots).</p>
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<p>Graphs of changes in the components of the influence matrix between sequences of seismic events with a magnitude of at least 5.5 and the sequence of moments in time of 349 of the largest local maxima of the average amplitudes at the second level of EEMD decomposition. The estimates were made in a sliding time window of length 2 years with a shift of 0.01 year for a relaxation time <math display="inline"><semantics> <mi>τ</mi> </semantics></math> of the model (24, 25) of 0.1 year. The graphs (<b>a1</b>–<b>c1</b>) refer to the components of the influence matrix (35), which refers to the intensity fractions of the sequence of the largest local amplitude maxima, while the graphs (<b>a2</b>–<b>c2</b>) refer to the intensity fractions of the sequence of seismic events. Plots (<b>d1</b>) and (<b>d2</b>) present the numbers of local maxima of amplitudes (<b>d1</b>) and the number of seismic events (<b>d2</b>) within moving time window. Other explanations are in the text.</p>
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<p>Maximum values of the elements of the influence matrices in a sequence of 100 time windows of length from 1 to 3 years, taken with an offset of 0.01 year: (<b>a</b>) for the “direct” influence of the time points of seismic events on the positions of the largest local maxima of average amplitudes on the second EEMD level of decomposition; (<b>b</b>) for the “reverse” influence of the positions of amplitude maxima on earthquakes. The relaxation time of the model is 0.1 year.</p>
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23 pages, 2271 KiB  
Perspective
Chronic Cocaine Use and Parkinson’s Disease: An Interpretative Model
by Manuel Glauco Carbone and Icro Maremmani
Int. J. Environ. Res. Public Health 2024, 21(8), 1105; https://doi.org/10.3390/ijerph21081105 - 21 Aug 2024
Cited by 2 | Viewed by 1242
Abstract
Over the years, the growing “epidemic” spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world’s population aged 15 to 64 report using cocaine; this number corresponds to approximately [...] Read more.
Over the years, the growing “epidemic” spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world’s population aged 15 to 64 report using cocaine; this number corresponds to approximately 24.6 million cocaine users worldwide and approximately 1 million subjects with cocaine use disorder (CUD). While we specifically know the short-term side effects induced by cocaine, unfortunately, we currently do not have exhaustive information about the medium/long-term side effects of the substance on the body. The scientific literature progressively highlights that the chronic use of cocaine is related to an increase in cardio- and cerebrovascular risk and probably to a greater incidence of psychomotor symptoms and neurodegenerative processes. Several studies have highlighted an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant abuse. EPSs include movement dysfunction such as dystonia, akathisia, tardive dyskinesia, and characteristic symptoms of Parkinsonism such as rigidity, bradykinesia, and tremor. In the present paper, we propose a model of interpretation of the neurobiological mechanisms underlying the hypothesized increased vulnerability in chronic cocaine abusers to neurodegenerative disorders with psychomotor symptoms. Specifically, we supposed that the chronic administration of cocaine produces significant neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic pathways. We believe that a better understanding of these cellular and molecular mechanisms involved in cocaine-induced neuropsychotoxicity may have helpful clinical implications and provide targets for therapeutic intervention. Full article
(This article belongs to the Section Behavioral and Mental Health)
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<p>Direct and indirect pathways.</p>
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<p>Pre-synaptic and post-synaptic effects of cocaine (from <a href="https://doi.org/10.3390/toxins14040278" target="_blank">https://doi.org/10.3390/toxins14040278</a>, (accessed on 3 May 2024) modified).</p>
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<p>Cocaine effects on serotoninergic system (from <a href="https://doi.org/10.3390/ijms242216416" target="_blank">https://doi.org/10.3390/ijms242216416</a>, (3 May 2024) modified).</p>
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<p>(<b>a</b>). Chronic cocaine use depletion of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Legend: dopamine transporter (DAT), norepinephrine transporter (NET), serotonin transporter (SERT), monoamine oxidase (MAO), reactive oxygen species (ROS), Vesicular Monoamine Transporter 2 (VMAT-2), dopamine receptor D<sub>2</sub> (D<sub>2</sub> receptors). (<b>b</b>). Chronic cocaine use neurotoxicity and neurodegeneration. Legend: myocyte enhancer factor-2 (MEF-2).</p>
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<p>(<b>a</b>). Chronic cocaine use depletion of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Legend: dopamine transporter (DAT), norepinephrine transporter (NET), serotonin transporter (SERT), monoamine oxidase (MAO), reactive oxygen species (ROS), Vesicular Monoamine Transporter 2 (VMAT-2), dopamine receptor D<sub>2</sub> (D<sub>2</sub> receptors). (<b>b</b>). Chronic cocaine use neurotoxicity and neurodegeneration. Legend: myocyte enhancer factor-2 (MEF-2).</p>
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12 pages, 2114 KiB  
Article
Regulation of TIR-1/SARM-1 by miR-71 Protects Dopaminergic Neurons in a C. elegans Model of LRRK2-Induced Parkinson’s Disease
by Devin Naidoo and Alexandre de Lencastre
Int. J. Mol. Sci. 2024, 25(16), 8795; https://doi.org/10.3390/ijms25168795 - 13 Aug 2024
Cited by 1 | Viewed by 1000
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by symptoms such as bradykinesia, resting tremor, and rigidity, primarily driven by the degradation of dopaminergic (DA) neurons in the substantia nigra. A significant contributor to familial autosomal dominant PD cases is mutations in [...] Read more.
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by symptoms such as bradykinesia, resting tremor, and rigidity, primarily driven by the degradation of dopaminergic (DA) neurons in the substantia nigra. A significant contributor to familial autosomal dominant PD cases is mutations in the LRRK2 gene, making it a primary therapeutic target. This study explores the role of microRNAs (miRNAs) in regulating the proteomic stress responses associated with neurodegeneration in PD using C. elegans models. Our focus is on miR-71, a miRNA known to affect stress resistance and act as a pro-longevity factor in C. elegans. We investigated miR-71’s function in C. elegans models of PD, where mutant LRRK2 expression correlates with dopaminergic neuronal death. Our findings reveal that miR-71 overexpression rescues motility defects and slows dopaminergic neurodegeneration in these models, suggesting its critical role in mitigating the proteotoxic effects of mutant LRRK2. Conversely, miR-71 knockout exacerbates neuronal death caused by mutant LRRK2. Additionally, our data indicate that miR-71’s neuroprotective effect involves downregulating the toll receptor domain protein tir-1, implicating miR-71 repression of tir-1 as vital in the response to LRRK2-induced proteotoxicity. These insights into miR-71’s role in C. elegans models of PD not only enhance our understanding of molecular mechanisms in neurodegeneration but also pave the way for potential research into human neurodegenerative diseases, leveraging the conservation of miRNAs and their targets across species. Full article
(This article belongs to the Special Issue Role of MicroRNAs in Human Diseases)
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<p>miR-71 preserves dopaminergic neurons in LRRK2 worms. (<b>A</b>) Results from the dopaminergic neurodegeneration assay at different time points of adulthood (<span class="html-italic">n</span> = 10 worms). Error bars indicate SEM. One-way ANOVA: * <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 versus GFP control worms at each time point. † <span class="html-italic">p</span> &lt; 0.05 and †† <span class="html-italic">p</span> &lt; 0.01 versus G2019S worms at each time point. (<b>B</b>) Z-stack images from data shown in (<b>B</b>) were merged to identify DA neuronal cell bodies. Circles denote DA neurons and white arrows indicate abnormal or absent cephalic dopaminergic neurons. (<b>C</b>) Results from the basal slowing assay at different time points of adulthood (<span class="html-italic">n</span> = 20 worms). Error bars indicate SEM. One-way ANOVA: ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.005 versus GFP control worms at each time point. † <span class="html-italic">p</span> &lt; 0.05 versus G2019S worms at each time point. (<b>D</b>) Kaplan–Meier survival analysis comparing LRRK2 expressing worms crossed with miR-71 mutants to GFP Control models. (E) Mean lifespan from data shown in (<b>D</b>). Bars represent mean ± SEM. One-way ANOVA: **** <span class="html-italic">p</span> &lt; 0.0005 versus GFP Control. <sup>####</sup> <span class="html-italic">p</span> &lt; 0.0005 versus G2019S.</p>
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<p>Loss of the toll-like receptor <span class="html-italic">tir</span>-1 is neuroprotective in LRRK2 expressing <span class="html-italic">C. elegans.</span> (<b>A</b>) The putative binding site between miR-71 and the toll-like receptor <span class="html-italic">tir</span>-1 3′ untranslated region (UTR). The minimum free energy of binding is −27.0 kcal/mol. (<b>B</b>) Results from qRT-PCR looking at relative expression of <span class="html-italic">tir</span>-1 at different time points of adulthood (<span class="html-italic">n</span> = 3 biological replicates). Error bars indicate SEM. One-way ANOVA: ns (not statistically significant), * <span class="html-italic">p</span> &lt; 0.05, and *** <span class="html-italic">p</span> &lt; 0.005. (<b>C</b>) Results from the dopaminergic neurodegeneration assay at different time points of adulthood (<span class="html-italic">n</span> = 10 worms). Error bars indicate SEM. One-way ANOVA: * <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 versus G2019S worms at each time point. † <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; 0.005 versus G2019S; miR-71 KO at each time point. # <span class="html-italic">p</span> &lt; 0.05 and ## <span class="html-italic">p</span> &lt; 0.01 versus GFP control at each time point. (<b>D</b>) Z-stack images from data shown in C were merged to identify DA neuronal cell bodies. Circles denote DA neurons and white arrows indicate abnormal or absent cephalic dopaminergic neurons. (<b>E</b>) Results from the basal slowing assay at different time points of adulthood (<span class="html-italic">n</span> = 20 worms). Error bars indicate SEM. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 versus G2019S at each time point. † <span class="html-italic">p</span> &lt; 0.05 and ††† <span class="html-italic">p</span> &lt; 0.005 versus G2019S; miR-71 KO at each time point. # <span class="html-italic">p</span> &lt; 0.05 versus GFP control at each time point.</p>
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<p>miR-71 directly regulates the toll-like receptor <span class="html-italic">tir</span>-1 in LRRK2 expressing <span class="html-italic">C. elegans.</span> (<b>A</b>) Three miR-71 binding sites on the 3′ UTR of <span class="html-italic">tir-1</span> were mutated to remove miR-71 regulation capability (tir-1 3′UTR(mut)). (<b>B</b>,<b>C</b>) Results from qRT-PCR looking at relative expression of <span class="html-italic">tir</span>-1 at different time points of adulthood (<span class="html-italic">n</span> = 3 biological replicates). Experiments for qRT-PCR were done in triplicate with about 50 worms per strain per experiment. Error bars indicate SEM. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01. (<b>D</b>) Z-stack images from data shown in B were merged into a singular image to identify DA neuronal cell bodies. Circles denote DA neurons and white arrows indicate abnormal or absent cephalic dopaminergic neurons. (<b>E</b>) Results from the basal slowing assay at different time points of adulthood (<span class="html-italic">n</span> = 20 worms). Error bars indicate SEM. One-way ANOVA: * <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 versus GFP control worms at each time point. † <span class="html-italic">p</span> &lt; 0.05 and †† <span class="html-italic">p</span> &lt; 0.01 versus G2019S at each time point. # <span class="html-italic">p</span> &lt; 0.05 versus G2019S;m71 OE at each time point.</p>
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25 pages, 10266 KiB  
Article
Random Forest—Based Identification of Factors Influencing Ground Deformation Due to Mining Seismicity
by Karolina Owczarz and Jan Blachowski
Remote Sens. 2024, 16(15), 2742; https://doi.org/10.3390/rs16152742 - 26 Jul 2024
Viewed by 901
Abstract
The goal of this study was to develop a model describing the relationship between the ground-displacement-caused tremors induced by underground mining, and mining and geological factors using the Random Forest Regression machine learning method. The Rudna mine (Poland) was selected as the research [...] Read more.
The goal of this study was to develop a model describing the relationship between the ground-displacement-caused tremors induced by underground mining, and mining and geological factors using the Random Forest Regression machine learning method. The Rudna mine (Poland) was selected as the research area, which is one of the largest deep copper ore mines in the world. The SAR Interferometry methods, Differential Interferometric Synthetic Aperture Radar (DInSAR) and Small Baseline Subset (SBAS), were used in the first case to detect line-of-sight (LOS) displacements, and in the second case to detect cumulative LOS displacements caused by mining tremors. The best-prediction LOS displacement model was characterized by R2 = 0.93 and RMSE = 5 mm, which proved the high effectiveness and a high degree of explanation of the variation of the dependent variable. The identified statistically significant driving variables included duration of exploitation, the area of the exploitation field, energy, goaf area, and the average depth of field exploitation. The results of the research indicate the great potential of the proposed solutions due to the availability of data (found in the resources of each mine), and the effectiveness of the methods used. Full article
(This article belongs to the Special Issue Machine Learning and Remote Sensing for Geohazards)
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<p>(<b>A</b>) Location of the area of interest in Poland. (<b>B</b>) Rudna mining area of the Legnica-Głogów Copper District. (<b>C</b>) Number of tremors registered in the Rudna mining area in 2016–2020.</p>
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<p>Research methodology.</p>
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<p>Residuals for the observed values in the LOS displacement model, the training, and the test datasets with the outliers.</p>
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<p>Residuals for the observed values in the LOS displacement model, the training, and the test datasets without the two outliers.</p>
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<p>Residuals for the predicted values in the LOS displacement model, training, and test datasets without the two outliers.</p>
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<p>Residual values for the LOS displacement model, training, and test datasets without the two outliers.</p>
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<p>Statistical significance of independent variables for the LOS displacement model based on the MDI approach. The higher the value, the more important the variable (for explanations of the variables’ acronyms, please refer to <a href="#remotesensing-16-02742-t0A1" class="html-table">Table A1</a> in <a href="#app1-remotesensing-16-02742" class="html-app">Appendix A</a>).</p>
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<p>Importance of the independent variables for the RFR model based on the MDA approach implemented in the eli5 library (for explanations of the variables’ acronyms, please refer to <a href="#remotesensing-16-02742-t0A1" class="html-table">Table A1</a> in <a href="#app1-remotesensing-16-02742" class="html-app">Appendix A</a>).</p>
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<p>Global variable importance graph on the basis of absolute mean SHAP values (for explanations of the variables’ acronyms, please refer to <a href="#remotesensing-16-02742-t0A1" class="html-table">Table A1</a> in <a href="#app1-remotesensing-16-02742" class="html-app">Appendix A</a>).</p>
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<p>Map of the location of high-energy tremors (energy ≥ 10<sup>6</sup> J) that occurred from January 2016 to 11 October 2020. Map based on data from the Rudna O/ZG, Rock Burst Department.</p>
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<p>LOS displacements determined based on the DInSAR and SBAS methods.</p>
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<p>The matrix of Pearson’s (r) correlation coefficients for the 20 variables of the dataset without taking into account the dummy variables.</p>
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<p>The matrix of the scatter plots of the variables (20) in the dataset without taking into account the dummy variables.</p>
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16 pages, 1650 KiB  
Review
Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson’s Disease: A Review of Inflammatory Markers and Potential Effects
by Karol Sadowski, Weronika Zając, Łukasz Milanowski, Dariusz Koziorowski and Monika Figura
Int. J. Mol. Sci. 2024, 25(14), 7741; https://doi.org/10.3390/ijms25147741 - 15 Jul 2024
Cited by 1 | Viewed by 1404
Abstract
Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, [...] Read more.
Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut–brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers. Full article
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<p>The schematic diagram of the fecal microbiota transplantation process.</p>
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<p>The crucial pathways representing the interplay between gut microbiota and inflammation. Due to increased intestinal permeability, LPS can translocate to blood circulation. LPS increases levels of IL-1β, IL-6, and TNF-α. TNF-α activates cells to release IL-1β. To control this response, TNF-α stimulates the X nerve’s afferent branch, which conveys this signal to the CNS. Interleukin-6 (IL-6) stimulates the production of acute-phase proteins, such as CRP and fibrinogen. IL-6 promotes the migration of neutrophils and monocytes to the inflamed tissue. IL-6 also regulates activity of T and B lymphocytes and promotes the development of regulatory T cells, which help to dampen the immune response and prevent excessive inflammation. IL-1β promotes the synthesis of acetylcholinesterase, which decreases acetylcholine and promotes inflammation. In the periphery, IL-1β production leads to TNF-α production (and vice versa). In the brain, IL-6 stimulates T and B lymphocytes, leading to the activation of microglia and astrocytes. Monocytes can cross the blood–brain barrier, which also promotes inflammation. The motor branch of the X nerve releases acetylcholine in the periphery, which interacts with macrophages and other cytokine-releasing cells. It inhibits the release of proinflammatory cytokines, particularly TNF-α.</p>
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<p>The functions of IL-1β and IL-6 in peripheral tissues and central nervous system. Monocytes, IL-1β, LPS, and TNF-α promote the synthesis of IL–6, which increase the blood–brain barrier’s permeability. It stimulates the division of microglia and the differentiation of B lymphocytes. IL-6 production also leads to T lymphocytes production (and vice-versa). These pathways promote inflammation. LPS increase the level of IL-1β, and thus, IL-1β activates microglia and increases the level of IL-6 via stimulating astrocytes to release this cytokine.</p>
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17 pages, 11808 KiB  
Article
Geomechanical Analysis of the Main Roof Deformation in Room-and-Pillar Ore Mining Systems in Relation to Real Induced Seismicity
by Dariusz Chlebowski and Zbigniew Burtan
Appl. Sci. 2024, 14(13), 5710; https://doi.org/10.3390/app14135710 - 29 Jun 2024
Viewed by 741
Abstract
Rockbursts represent one of the most serious and severe natural hazards emerging in underground copper mines within the Legnica–Glogow Copper District (LGCD) in Poland. The contributing factor determining the scale of this event is mining-induced seismicity of the rock strata. Extensive expertise of [...] Read more.
Rockbursts represent one of the most serious and severe natural hazards emerging in underground copper mines within the Legnica–Glogow Copper District (LGCD) in Poland. The contributing factor determining the scale of this event is mining-induced seismicity of the rock strata. Extensive expertise of the copper mining practitioners clearly indicates that high-energy tremors are the consequence of tectonic disturbances or can be attributed to stress/strain behaviour within the burst-prone roof strata. Apparently, seismic activity is a triggering factor; hence, attempts are made by mine operators to mitigate and control that risk. Underlying the effective rockburst control strategy is a reliable seismicity forecast, taking into account the causes of the registered phenomena. The paper summarises the geomechanics analyses aimed to verify the actual seismic and rockburst hazard levels in one of the panels within the copper mine Rudna (LGCD). Two traverses were designated at the face range and comparative analyses were conducted to establish correlations between the locations of epicentres of registered tremors and anomaly zones obtained via analytical modelling of changes in stress/strain behaviours within the rock strata. The main objective of this study was to evaluate the likelihood of activating carbonate/anhydrite layers within the main roof over the excavation being mined, with an aim to verify the potential causes and conditions which might have triggered the registered high-energy events. Special attention is given to two seismic events giving rise to rockbursts in mine workings. Results seem to confirm the adequacy and effectiveness of solutions provided by mechanics of deformable bodies in the context of forecasting the scale and risk of dynamic phenomena and selecting the appropriate mitigation and control measures in copper mines employing the room-and-pillar mining system. Full article
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<p>A part of lithological profile in the vicinity of the ore deposit (XVII/1 site).</p>
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<p>Status of mining operations in panel XVII/1 at the end of Year 3.</p>
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<p>Status of mining operations in panel XVII/1 at the end of Year 6.</p>
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<p>Number of seismic events in the energy class (≥10<sup>3</sup> J).</p>
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<p>Foci locations during tremors in the energy class ≥10<sup>5</sup> J.</p>
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<p>Shear strain energy density (end of Year 3).</p>
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<p>Effort factor (end of Year 3).</p>
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<p>Shear strain energy density (end of Year 6).</p>
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<p>Effort factor (end of Year 6).</p>
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<p>Shear strain energy density along the+ cross-profile A–B.</p>
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24 pages, 4391 KiB  
Article
A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia
by Sandeep Sathyanandan Nair and Srinivasa Chakravarthy
Brain Sci. 2024, 14(6), 620; https://doi.org/10.3390/brainsci14060620 - 20 Jun 2024
Viewed by 1911
Abstract
Parkinson’s disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) [...] Read more.
Parkinson’s disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents. Full article
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<p>Block diagram of the proposed cortico-basal ganglia model. The model consists of a 2-link arm model, the proprioceptive cortex (PC), the prefrontal cortex (PFC), the motor cortex (MC), and the basal ganglia (BG). Here, the input nucleus striatum, the output nucleus globus pallidus internus (GPi), the globus pallidus externus (GPe), the subthalamic nucleus (STN), and the thalamus (THAL) constitute the BG. MC integrates the inputs received from the prefrontal cortex (PFC) and the proprioceptive cortex (PC) along with the feedback signal from BG and sends the signal to the arm via the spinal motor neurons.</p>
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<p>Comparison of performance of the proposed model with experimental data adapted from [<a href="#B61-brainsci-14-00620" class="html-bibr">61</a>]. (<b>A</b>) Movement time, (<b>B</b>) time-to-peak velocity, (<b>C</b>) peak velocity; sec, second; m/s, meter per second. The dark blue bar represents the healthy control (HC) group, and the green bar represents the PD condition.</p>
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<p>Firing rates and synchrony. (<b>A</b>) The firing rates of STN and GPe neurons for various values of DA levels are shown. The blue line represents the GPe, and the orange line represents the STN neurons. (<b>B</b>) Synchrony within STN and GPe nuclei. Again, blue and orange lines represent the GPe and STN neurons, respectively. Synchrony keeps decreasing with increasing DA levels. The mean and variance values for the above plots were calculated over five epochs.</p>
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<p>The firing of single STN and GPe neurons in the HC group is shown in (<b>a</b>,<b>d</b>). Under HC conditions, both the STN and GPe neurons exhibit regular firings. The firing of single STN and GPe neurons under PD conditions is shown in (<b>g</b>,<b>j</b>). (<b>b</b>,<b>e</b>) The raster plot of the STN, and (<b>h</b>,<b>k</b>) the GPe neurons in PD. (<b>c</b>,<b>f</b>) the synchrony of STN and GPe neurons under healthy conditions, and (<b>i</b>,<b>l</b>) the synchrony of STN and GPe neurons under PD condition. The orange lines in (<b>a</b>,<b>d</b>,<b>g</b>,<b>j</b>) indicate the reference line corresponding to the theoretical resting membrane potential (-60 mV) and the blue line represents the spike data.</p>
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<p>(<b>A</b>) The frequency spectrum of the acceleration of the arm movements. The blue line represents the healthy control (HC) condition, and the orange line represents the PD tremor condition in all (<b>A</b>–<b>C</b>). (<b>B</b>) This plot shows the distance to the target as the time progresses. (<b>C</b>) The velocity of the arm movement, where the curve follows a bell curve under HC conditions and keeps oscillating under PD tremor conditions.</p>
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<p>The trajectory of the arm movements is given. The blue line (for the arm) represents the healthy control (HC) condition, the yellow line (for the arm) represents the tremor condition, and the green line (for the arm) represents the rigidity condition. In the case of HCs, the reaching is successful, whereas in the case of tremor and rigidity, it is not.</p>
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<p>(<b>A</b>) This plot shows the distance to the target as the time progresses. (<b>B</b>) This plot shows the velocity of the arm movement, where the curve follows a bell curve for the HCs, has multiple lesser-magnitude peaks under the bradykinesia condition, and keeps oscillating under the PD tremor condition. The arm hardly moves, and the velocity curve quickly decreases down under rigidity conditions. The blue line represents the healthy controls (HCs), the purple line represents the rigidity condition, the orange line represents the tremor condition, and the black line represents the bradykinesia condition.</p>
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<p>The potential of the STN neuronal population in the local field is shown. The violet curve indicates the HC condition, the green line indicates the PD condition, and the blue line represents the DBS-treated condition.</p>
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<p>(<b>A</b>) DBS is currently applied to the center of most neurons in the STN population. (<b>B</b>) The spread of the current in nearby neurons. (<b>C</b>) The FFT of the local field potential of the STN population. (<b>D</b>) The mean relative power of the LFP of the STN was redrawn as recorded in the experimental studies (Kuhn et al., 2008) [<a href="#B68-brainsci-14-00620" class="html-bibr">68</a>].</p>
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<p>The movement trajectory of the arm movements is given in (<b>A</b>), where the blue line represents the trajectory and the red dot represents the target position. The distance to target over time is shown in (<b>B</b>), where as the frequency spectrum of the acceleration of arm movements is shown in (<b>C</b>) and the velocity of arm movements is shown in (<b>D</b>).</p>
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<p>(<b>A</b>) The frequency spectra of STN LFP for PD and DBS-applied conditions are shown. (<b>B</b>) The peak velocities during a reaching task for varying DBS frequencies are shown.</p>
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<p>Hypothetical block diagram with the integrated cortico-basal ganglia and the corticocerebellar loops. PPC, posterior parietal cortex; STR, striatum; PN, pontine nuclei, DN, dentate nuclei; PFC, prefrontal cortex; GPe/GPi globus pallidus externus and globus pallidus interna.</p>
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