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20 pages, 1692 KiB  
Article
Serum hsa-miR-22-3p, hsa-miR-885-5p, Lipase-to-Amylase Ratio, C-Reactive Protein, CA19-9, and Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Advanced Pancreatic Ductal Adenocarcinoma
by Jakub Wnuk, Dorota Hudy, Joanna Katarzyna Strzelczyk, Łukasz Michalecki, Kamil Dybek and Iwona Gisterek-Grocholska
Curr. Issues Mol. Biol. 2025, 47(1), 27; https://doi.org/10.3390/cimb47010027 - 3 Jan 2025
Abstract
Pancreatic cancer (PC) is the seventh most common cause of cancer-related death worldwide. The low survival rate may be due to late diagnosis and asymptomatic early-stage disease. Most patients are diagnosed at an advanced stage of the disease. The search for novel prognostic [...] Read more.
Pancreatic cancer (PC) is the seventh most common cause of cancer-related death worldwide. The low survival rate may be due to late diagnosis and asymptomatic early-stage disease. Most patients are diagnosed at an advanced stage of the disease. The search for novel prognostic factors is still needed. Two miRNAs, miR-22-3p and miR-885-5p, which show increased expression in PC, were selected for this study. The aim of this study was to evaluate the utility of these miRNAs in the prognosis of PC. Other prognostic factors such as lipase-to-amylase ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), and carbohydrate antigen 19-9 (CA19-9) were also evaluated in this study. This study was conducted in 50 patients previously diagnosed with pancreatic ductal adenocarcinoma in clinical stage (CS) III and IV. All patients underwent a complete medical history, physical examination, and routine laboratory tests including a complete blood count, C-reactive protein (CRP), CA19-9, lipase, and amylase. Two additional blood samples were taken from each patient to separate plasma and serum. Isolation of miRNA was performed using TRI reagent with cel-miR-39-3p as a spike-in control. Reverse transcription of miRNA was performed using a TaqMan Advanced miRNA cDNA Synthesis Kit. The relative expression levels of miR-22-3p and miR-885-5p were measured using RT-qPCR. Serum hsa-miR-22-3p was detected in 22 cases (44%), while hsa-miR-885-5p was detected in 33 cases (66%). There were no statistically significant differences in serum or plasma miRNA expression levels between patient groups based on clinical stage, gender, or BMI. There were no statistically significant differences in LAR between patients with different CS. For NLR, CRP and CA19-9 thresholds were determined using ROC analysis (6.63, 24.7 mg/L and 4691 U/mL, respectively). Cox’s F test for overall survival showed statistically significant differences between groups (p = 0.002 for NLR, p = 0.007 for CRP and p = 0.007 for CA19-9). Utility as prognostic biomarkers was confirmed in univariate and multivariate analysis for CA19-9, CRP, and NLR. The selected miRNAs and LAR were not confirmed as reliable prognostic markers in PC. Full article
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<p>Probability of survival according to clinical stage (Cox’s F test <span class="html-italic">p</span> = 0.043). CS—clinical stage.</p>
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<p>Probability of survival based on an age threshold of 72 years (Cox’s F test <span class="html-italic">p</span> &gt; 0.05; 0.07).</p>
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<p>Probability of survival based on CA19-9 levels (threshold: 4619 U/mL).</p>
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<p>Probability of survival based on C-reactive protein (CRP) level (threshold 24.7 mg/L).</p>
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<p>Probability of survival based on NLR values (threshold: 6.63).</p>
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16 pages, 293 KiB  
Article
Modeling Anomalous Transport of Cosmic Rays in the Heliosphere Using a Fractional Fokker–Planck Equation
by José Luis Díaz Palencia
Fractal Fract. 2025, 9(1), 24; https://doi.org/10.3390/fractalfract9010024 - 2 Jan 2025
Viewed by 230
Abstract
Cosmic rays exhibit anomalous diffusion behaviors in the heliospheric environment that cannot be adequately described by classical diffusion models. In this paper, we develop a theoretical framework employing a fractional Fokker–Planck equation to model the anomalous transport of cosmic rays. This approach accounts [...] Read more.
Cosmic rays exhibit anomalous diffusion behaviors in the heliospheric environment that cannot be adequately described by classical diffusion models. In this paper, we develop a theoretical framework employing a fractional Fokker–Planck equation to model the anomalous transport of cosmic rays. This approach accounts for the observed non-Gaussian distributions, long-range correlations and memory effects in cosmic ray fluxes. We derive analytical solutions using the Adomian Decomposition Method and express them in terms of Mittag-Leffler functions and Lévy stable distributions. The model parameters, including the fractional orders α and μ and the entropic index q, are estimated by a short comparison between theoretical predictions and observational data from cosmic ray experiments. Our findings suggest that the integration of fractional calculus and non-extensive statistics can be employed for describing the cosmic ray propagation and the anomalous diffusion observed in the heliosphere. Full article
12 pages, 888 KiB  
Article
Practicing Meta-Analytics with Rectification
by Ramalingam Shanmugam and Karan P. Singh
Publications 2025, 13(1), 2; https://doi.org/10.3390/publications13010002 - 2 Jan 2025
Viewed by 196
Abstract
This article demonstrates the necessity of assessing homogeneity in meta-analyses using the Higgins method. The researchers realize the importance of assessing homogeneity in meta-analytic work. However, a significant issue with the Higgins method has been identified. In this article, we explain the nature [...] Read more.
This article demonstrates the necessity of assessing homogeneity in meta-analyses using the Higgins method. The researchers realize the importance of assessing homogeneity in meta-analytic work. However, a significant issue with the Higgins method has been identified. In this article, we explain the nature of this problem and propose solutions to address it. Our narrative in this article is to point out the problem, analyze it, and present it well. A prerequisite to check the consistency of findings in comparable studies in meta-analyses is that the studies should be homogeneous, not heterogeneous. The Higgins I2 score, a version of the Cochran Q value, is commonly used to assess heterogeneity. The Higgins score is an improvement in the Q value. However, there is a problem with Higgins score statistically. The Higgins score is supposed to follow a Chi-squared distribution, but it does not do so because the Chi-squared distribution becomes invalid once the Q score is less than the degrees of freedom. This problem was recently rectified using an alternative method (S2 score). Using this method, we examined 14 published articles representing 133 datasets and observed that many studies declared homogeneous by the Higgins method were, in fact, heterogeneous. This article urges the research community to be cautious in making inferences using the Higgins method. Full article
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<p>Comparison of the Higgins <math display="inline"><semantics> <mrow> <msup> <mrow> <mi>I</mi> </mrow> <mrow> <mn>2</mn> </mrow> </msup> </mrow> </semantics></math> score and the <math display="inline"><semantics> <mrow> <msup> <mrow> <mi>S</mi> </mrow> <mrow> <mn>2</mn> </mrow> </msup> </mrow> </semantics></math> score in terms of Box plots.</p>
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27 pages, 6354 KiB  
Article
Potential Clinical Application of Analysis of Bisphenols in Pericardial Fluid from Patients with Coronary Artery Disease with the Use of Liquid Chromatography Combined with Fluorescence Detection and Triple Quadrupole Mass Spectrometry
by Tomasz Tuzimski, Szymon Szubartowski, Janusz Stążka, Kamil Baczewski, Daria Janiszewska, Viorica Railean, Bogusław Buszewski and Małgorzata Szultka-Młyńska
Molecules 2025, 30(1), 140; https://doi.org/10.3390/molecules30010140 - 1 Jan 2025
Viewed by 314
Abstract
Bisphenols may negatively impact human health. In this study, we propose the use of HPLC–FLD for the simultaneous determination of bisphenols in pericardial fluid samples collected from patients with coronary artery disease undergoing coronary artery bypass surgery. For sample preparation, a fast, simple, [...] Read more.
Bisphenols may negatively impact human health. In this study, we propose the use of HPLC–FLD for the simultaneous determination of bisphenols in pericardial fluid samples collected from patients with coronary artery disease undergoing coronary artery bypass surgery. For sample preparation, a fast, simple, and ”green” DLLME method was used, achieving mean recovery values in the range of 62%–98% with relative standard deviations between 2% and 6% for all analytes. Quantitative analysis of bisphenols in the samples was then performed by LC–MS/MS on a triple quadrupole (QqQ) mass spectrometer and electrospray ionization (ESI-/ESI+) was applied in the negative and positive ion modes, respectively. The LODs and LOQs ranged from 0.04 ng/mL to 0.37 ng/mL and 0.12 ng/mL to 1.11 ng/mL, respectively. Pericardial fluid was collected from patients with coronary artery disease during coronary artery bypass surgery. Bisphenol residues were identified and quantified in samples from 19 patients. The procedure was successfully applied to the biomonitoring of free forms of 14 bisphenols in pericardial fluid. After statistical examination of the relationships between the selected variables, a strongly positive correlation was found between creatinine kinase and troponin I, as well as the number of venous anastomoses, circulation time, and clamp cap time. Full article
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<p>The diagram shows the recovery values for the analyzed bisphenols with relative standard deviations between 2% and 6% for all analytes.</p>
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<p>Example chromatograms obtained during the HPLC–FLD analysis: mixture of bisphenol standards (25 ng/mL) and three spiked samples at 10 ng/mL, 20 ng/mL, and 30 ng/mL. 1—BADGE∙2H<sub>2</sub>O, 2—BPF, 3—BPE, 4—BPA, 5—BADGE∙2HCl, 6—BADGE, 7—BPP.</p>
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<p>QqQ–ESI–MS and MS/MS spectra of following bisphenols residues detected in pericardial fluid samples: (<b>a</b>) BPS (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 249), (<b>b</b>) BPF (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 199), (<b>c</b>) BPE (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 213), (<b>d</b>) BPA (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 227), (<b>e</b>) BPB (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 241), (<b>f</b>) BPP (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 345), (<b>g</b>) BPZ (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 267), (<b>h</b>) BPAF (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 335), (<b>i</b>) BPAP (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 335), (<b>j</b>) BADGE•2H<sub>2</sub>O (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 394), (<b>k</b>) BADGE•H<sub>2</sub>O (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 376), (<b>l</b>) BADGE•H<sub>2</sub>O•HCl (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 412), (<b>m</b>) BADGE•2HCl (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 430), and (<b>n</b>) BADGE (<span class="html-italic">m</span>/<span class="html-italic">z</span> = 358).</p>
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<p>Selected clinical data of 19 patients with coronary artery diseases and undergoing coronary artery bypass surgery.</p>
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<p>Heatmap showing the distribution and concentration (ng/mL) of quantified bisphenols in pericardial fluids collected from 19 patients with coronary artery diseases and undergoing coronary artery bypass surgery. The samples numbers (1–19) indicate the name of samples analyzed by LC–ESI–QqQ. Hierarchical cluster analysis shows the correlations between the analyzed bisphenols. #a, #b, #c—indicates the main formed clusters.</p>
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<p>PCA score plots for bisphenols concentration (<b>A</b>) in pericardial fluids determined by LC–ESI–QqQ and patients (<b>B</b>) with coronary artery diseases.</p>
Full article ">Figure 7
<p>Heat map showing pairwise correlation matrix of the input variables (clinical data of 19 patients with coronary artery diseases) and quantified bisphenols. CCS/central cord syndrome; CCTime/circulation time (min); CLCTime/clamp cap time (min); NTAA/no of thoracic artery anastomoses; NVA/no of venous anastomoses; NRAA/no of radial artery anastomoses; CK24h/creatinine kinase (U/L), 24 h after the surgency; CK48h/creatinine kinase (U/L), 48 h after the surgency; Tr/I_24h/Troponin I (ng/L), 24 h after the surgency; Tr/I_48h/Troponin I (ng/L), 48 h after the surgency; Tr/I_HD/Troponin I (ng/L), Hospital discharge data.</p>
Full article ">Figure 8
<p>PCA score plots for clinical data and quantified bisphenols referred to 19 patients (<b>A</b>) and the scatter plot for patients (<b>B</b>) with coronary artery diseases. The numbers plotted in (<b>A</b>) represent the <span class="html-italic">m</span>/<span class="html-italic">z</span> of bisphenols while the numbers plotted in (B) represent the patients name. 227—BPA, 249—BPS, 241—BPB, 199—BPF, 345—BPP, 213—BPE, 267—BPZ, 335—BPAP, BPAF—335, 358—BADGE, 376—BADGE•H<sub>2</sub>O, 394—BADGE•2H<sub>2</sub>O, 412—BADGE•H<sub>2</sub>O•HCl, and 430—BADGE•2HCl. CCS/central cord syndrome; CCTime/circulation time (min); CLCTime/clamp cap time (min); NTAA/No. of thoracic artery anastomoses; NVA/No. of venous anastomoses; NRAA/No. of radial artery anastomoses; CK24h/creatinine kinase (U/L), 24 h after the surgency; CK48h/creatinine kinase (U/L), 48 h after the surgency; Tr/I_24h/Troponin I (ng/L), 24 h after the surgency; Tr/I_48h/Troponin I (ng/L), 48 h after the surgency; Tr/I_HD/Troponin I (ng/L), Hospital discharge data.</p>
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<p>The flowchart of DLLME procedure.</p>
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13 pages, 1398 KiB  
Article
Do Salivary Cullin7 Gene Expression and Protein Levels Provide Advantages over Plasma Levels in Diagnosing Breast Cancer?
by Ceren Tilgen Yasasever, Derya Duranyıldız, Süleyman Bademler and Hilal Oğuz Soydinç
Curr. Issues Mol. Biol. 2025, 47(1), 19; https://doi.org/10.3390/cimb47010019 - 31 Dec 2024
Viewed by 305
Abstract
In addition to the tumor suppressor role of Cullin 7 (Cul7), one of the proteins belonging to the Cullin (Cul) family, studies have also suggested that Cul7 may act as an oncogene under certain conditions. The role of the Cul7 molecule in breast [...] Read more.
In addition to the tumor suppressor role of Cullin 7 (Cul7), one of the proteins belonging to the Cullin (Cul) family, studies have also suggested that Cul7 may act as an oncogene under certain conditions. The role of the Cul7 molecule in breast cancer is still unclear, and understanding its function could have significant implications for identifying novel therapeutic targets or improving diagnostic strategies in breast cancer management. In this study, the levels of the Cul7 molecule in plasma and noninvasive material saliva were investigated, and its possibility as a marker for breast cancer was discussed. Protein levels of blood and saliva samples taken from breast cancer patients and a healthy control group were measured by the ELISA (Enzyme-Linked Immunosorbent Assay) method. Gene expression levels between the two groups were analyzed by the qPCR (quantitative Polymerase Chain Reaction) method. In our study, Cul7 mRNA and protein expression levels were examined in 60 breast cancer patients and 20 healthy female controls, and a statistically insignificant difference was found between the patient and control groups in both plasma and saliva samples (p > 0.05). No correlation was found between the clinical characteristics of the patients and plasma and saliva Cul7 gene expression and protein levels (p > 0.05). Considering the possibility of Cul7 being a biomarker at the protein and mRNA levels, plasma is thought to be a better study material for Cul7. Our findings suggest that in the context of a study on salivary material, the expression of Cul7 at the mRNA level may have better potential utility as a biomarker. Full article
(This article belongs to the Section Molecular Medicine)
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<p>Gene expression of plasma (<b>a</b>) and saliva (<b>b</b>) <span class="html-italic">Cul7</span> median levels of breast cancer patients and healthy controls.</p>
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<p>ROC analysis of gene expression tests.</p>
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<p>Box plots of Cul7 protein in plasma (<b>a</b>) and saliva (<b>b</b>) samples of breast cancer patients and healthy controls.</p>
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<p>ROC analysis of plasma and saliva Cul7 protein tests.</p>
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27 pages, 1362 KiB  
Article
Modeling the Phylogenetic Rates of Continuous Trait Evolution: An Autoregressive–Moving-Average Model Approach
by Dwueng-Chwuan Jhwueng
Mathematics 2025, 13(1), 111; https://doi.org/10.3390/math13010111 - 30 Dec 2024
Viewed by 274
Abstract
The rates of continuous evolution plays a crucial role in understanding the pace at which species evolve. Various statistical models have been developed to estimate the rates of continuous trait evolution for a group of related species evolving along a phylogenetic tree. Existing [...] Read more.
The rates of continuous evolution plays a crucial role in understanding the pace at which species evolve. Various statistical models have been developed to estimate the rates of continuous trait evolution for a group of related species evolving along a phylogenetic tree. Existing models often assume the independence of the rate parameters; however, this assumption may not account for scenarios where the rate of continuous trait evolution correlates with its evolutionary history. We propose using the autoregressive–moving-average (ARMA) model for modeling the rate of continuous trait evolution along the tree, hypothesizing that rates between two successive generations (ancestor–descendant) are time-dependent and correlated along the tree. We denote PhyRateARMA(p,q) as a phylogenetic rate-of-continuous-trait-evolution ARMA(p,q) model in our framework. Our algorithm begins by utilizing the tree and trait data to estimate the rates on each branch, followed by implementing the ARMA process to infer the relationships between successive rates. We apply our innovation to analyze the primate body mass dataset and plant genome size dataset and test for the autoregressive effect of the rates of continuous evolution along the tree. Full article
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<p>Trait values under Brownian motion dynamics with two different rates (<b>left</b>: <math display="inline"><semantics> <mrow> <mi>σ</mi> <mo>=</mo> <mn>1</mn> </mrow> </semantics></math>, <b>right</b>: <math display="inline"><semantics> <mrow> <mi>σ</mi> <mo>=</mo> <mn>4</mn> </mrow> </semantics></math>). Histograms in the top row represent the distribution of final positions, showing greater spread with higher <math display="inline"><semantics> <mi>σ</mi> </semantics></math>. The bottom row illustrates 100 trajectories in red over time and the mean trajectory in blue, with higher <math display="inline"><semantics> <mi>σ</mi> </semantics></math> resulting in more dispersed paths. The time span is set to 100.</p>
Full article ">Figure 2
<p>Trajectories of trait evolution for 4 species <math display="inline"><semantics> <mrow> <mi>A</mi> <mo>,</mo> <mi>B</mi> <mo>,</mo> <mi>C</mi> <mo>,</mo> <mi>D</mi> </mrow> </semantics></math> along a rooted phylogenetic tree. <b>Middle panel</b>: A rooted phylogenetic tree with four taxa <math display="inline"><semantics> <mrow> <mi>A</mi> <mo>,</mo> <mi>B</mi> <mo>,</mo> <mi>C</mi> <mo>,</mo> <mi>D</mi> </mrow> </semantics></math>. <b>Left panel</b>: A set of four dependent trajectories along the tree using a single rate (<math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mi>t</mi> </msub> <mo>=</mo> <mi>σ</mi> </mrow> </semantics></math> on all branches). <b>Right panel</b>: A set of four dependent trajectories along the tree using two rates (<math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mi>t</mi> </msub> <mo>=</mo> <msub> <mi>σ</mi> <mn>1</mn> </msub> </mrow> </semantics></math> on the blue branches, and <math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mi>t</mi> </msub> <mo>=</mo> <msub> <mi>σ</mi> <mn>2</mn> </msub> </mrow> </semantics></math> on the red branches). <math display="inline"><semantics> <mi>μ</mi> </semantics></math> is the root status denoted as a parameter of interest (analogous to <math display="inline"><semantics> <msub> <mi>y</mi> <mn>0</mn> </msub> </semantics></math>).</p>
Full article ">Figure 3
<p>A rooted phylogenetic tree of three taxa with tip nodes <span class="html-italic">A</span>, <span class="html-italic">B</span>, and <span class="html-italic">C</span>; internal nodes <span class="html-italic">D</span> and <span class="html-italic">E</span>; and root node <span class="html-italic">O</span>, where the branch lengths are <math display="inline"><semantics> <msub> <mi>l</mi> <mi>A</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>l</mi> <mi>B</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>l</mi> <mi>C</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>l</mi> <mi>D</mi> </msub> </semantics></math>, and <math display="inline"><semantics> <msub> <mi>l</mi> <mi>E</mi> </msub> </semantics></math>, and the rate variables are <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>A</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>B</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>C</mi> </msub> </semantics></math>, <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>D</mi> </msub> </semantics></math>, and <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>E</mi> </msub> </semantics></math>.</p>
Full article ">Figure 4
<p>The phylogenetic ARMA<math display="inline"><semantics> <mrow> <mo>(</mo> <mn>1</mn> <mo>,</mo> <mn>1</mn> <mo>)</mo> </mrow> </semantics></math> rate model for the rates of continuous evolution along the studied tree. The root status <span class="html-italic">O</span> starts with <math display="inline"><semantics> <msub> <mi>σ</mi> <mn>0</mn> </msub> </semantics></math>, and along the tree is the error of the rate estimate. The ARMA rates are bound to the tree topology’s ancestral–descendant relationship. For instance, the rate <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>A</mi> </msub> </semantics></math> at tip node <span class="html-italic">A</span> has the relationship with the ancestor node <span class="html-italic">D</span> of <math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mi>A</mi> </msub> <mo>=</mo> <mi>ϕ</mi> <msub> <mi>σ</mi> <mi>A</mi> </msub> <mo>+</mo> <mi>θ</mi> <msub> <mi>σ</mi> <mi>D</mi> </msub> <mo>+</mo> <msub> <mi>ϵ</mi> <mi>A</mi> </msub> </mrow> </semantics></math>, where <math display="inline"><semantics> <mrow> <msub> <mi>ϵ</mi> <mi>A</mi> </msub> <mo>∼</mo> <mi mathvariant="script">N</mi> <mrow> <mo>(</mo> <mn>0</mn> <mo>,</mo> <msup> <mi>τ</mi> <mn>2</mn> </msup> <msub> <mi>l</mi> <mi>A</mi> </msub> <mo>)</mo> </mrow> </mrow> </semantics></math>, while the rate <math display="inline"><semantics> <msub> <mi>σ</mi> <mi>D</mi> </msub> </semantics></math> at internal node <span class="html-italic">D</span> has the relationship with the ancestor node <span class="html-italic">E</span> of <math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mi>E</mi> </msub> <mo>=</mo> <mi>ϕ</mi> <msub> <mi>σ</mi> <mi>E</mi> </msub> <mo>+</mo> <mi>θ</mi> <msub> <mi>σ</mi> <mn>0</mn> </msub> <mo>+</mo> <msub> <mi>ϵ</mi> <mi>D</mi> </msub> </mrow> </semantics></math>, where <math display="inline"><semantics> <mrow> <msub> <mi>ϵ</mi> <mi>D</mi> </msub> <mo>∼</mo> <mi mathvariant="script">N</mi> <mrow> <mo>(</mo> <mn>0</mn> <mo>,</mo> <msup> <mi>τ</mi> <mn>2</mn> </msup> <msub> <mi>l</mi> <mi>D</mi> </msub> <mo>)</mo> </mrow> </mrow> </semantics></math>.</p>
Full article ">Figure 5
<p>Test heterogeneity rates for trait evolution on the two subclades of the tree with tips <math display="inline"><semantics> <mrow> <mi>A</mi> <mo>,</mo> <mi>B</mi> <mo>,</mo> <mi>C</mi> <mo>,</mo> <mi>D</mi> <mo>,</mo> <mi>E</mi> <mo>,</mo> <mi>F</mi> </mrow> </semantics></math>. Evaluate the model with two <math display="inline"><semantics> <mi>ϕ</mi> </semantics></math>’s (<math display="inline"><semantics> <mrow> <msub> <mi>ϕ</mi> <mn>1</mn> </msub> <mo>,</mo> <msub> <mi>ϕ</mi> <mn>2</mn> </msub> </mrow> </semantics></math>) vs. a single <math display="inline"><semantics> <mi>ϕ</mi> </semantics></math>.</p>
Full article ">Figure 6
<p>Power curve for varying taxon levels (using balanced tree and birth–death tree cases as demonstration). The horizontal axis represents an adjusted value of a parameter called <math display="inline"><semantics> <msub> <mi>ϕ</mi> <mi>a</mi> </msub> </semantics></math>, ranging from 0 to near 1. The vertical axis depicts the statistical power, indicating the probability of rejecting a null hypothesis when an alternative is true; a range from 0 suggests no detection ability, while 1 signifies certain detection. The four curves represent different taxon counts <math display="inline"><semantics> <mrow> <mo>(</mo> <mn>16</mn> <mo>,</mo> <mn>32</mn> <mo>,</mo> <mn>64</mn> <mo>,</mo> <mn>128</mn> <mo>)</mo> </mrow> </semantics></math>, which could indicate distinct sample sizes or biological classifications. The horizontal lines present the type I error rate using level <math display="inline"><semantics> <mrow> <mn>0.05</mn> </mrow> </semantics></math>.</p>
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<p><b>Left</b>: Herbaticus tree. <b>Right</b>: Woody species <b>Middle</b>: Combined herbaticus and woody species. The herbaticus and woody trees were obtained using <tt>TimeTree</tt> [<a href="#B36-mathematics-13-00111" class="html-bibr">36</a>], where species names are entered and the system generates the tree in Newick format. The combined tree was obtained using R <tt>ape</tt> package (version 5.8-1) function <tt>bind.tree</tt> by applying the molecular dating with a penalized likelihood approach [<a href="#B29-mathematics-13-00111" class="html-bibr">29</a>] for branch-length estimation. This was performed using the R <tt>ape</tt> package (version 5.8-1) function <tt>chronopl</tt>, taking the herbaticus tree and woody tree as input.</p>
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<p><b>Left</b>: Tree with 54 nocturnal primates. <b>Right</b>: Tree with 28 diurnal primates. <b>Middle</b>: Combined phylogenetic tree of 88 primate species.</p>
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<p>A rooted phylogenetic tree <math display="inline"><semantics> <mi mathvariant="script">T</mi> </semantics></math> of 8 taxa.</p>
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25 pages, 4111 KiB  
Article
Development of Speech and Communication in Polish Children with 22q11.2 Deletion Syndrome: A Cross-Sectional Study
by Natalia Moćko, Marcin Rudzki, Zuzanna Miodońska, Julia Olesiak, Katarzyna Jochymczyk-Woźniak and Michał Kręcichwost
Brain Sci. 2025, 15(1), 24; https://doi.org/10.3390/brainsci15010024 (registering DOI) - 29 Dec 2024
Viewed by 493
Abstract
Background/Objectives: 22q11.2 microdeletion syndrome (22q11DS) is a genetic disease caused by aberration of chromosome 22 that results in some phenotypic features and developmental disorders. This paper presents a cross-sectional study on speech and communication of Polish children with 22q11DS. Methods: Individuals affected with [...] Read more.
Background/Objectives: 22q11.2 microdeletion syndrome (22q11DS) is a genetic disease caused by aberration of chromosome 22 that results in some phenotypic features and developmental disorders. This paper presents a cross-sectional study on speech and communication of Polish children with 22q11DS. Methods: Individuals affected with 22q11DS may show difficulties in functioning, including speech and hearing. Therefore, we prepared a speech development questionnaire and employed it to obtain data from parents (or legal guardians) of 54 children with 22q11DS. The questionnaire covered the following speech and communication development stages: babbling, using first words, first sentences, verbal and non-verbal communication, speech disfluencies, hearing loss, speech intelligibility, difficulties in interpersonal contact, and participation in speech therapy. The obtained answers underwent statistical analysis to verify relationships between the stages of personal development and selected dysfunctions and disorders. Results: In the study group we observed delays in achieving subsequent speech developmental stages and that hearing loss was associated with delays in producing first words. Hearing loss was reported in about a quarter of cases, but a significant proportion of children (55.56%) reported speech disfluencies, which had not been emphasized in previous works, where hearing loss is considered a common co-occurring disorder. Conclusions: Our findings suggest that this may represent a phenomenon associated with 22q11DS that warrants further investigation using standardized tests for assessing disfluencies. Additionally, we observed that speech therapists and caregivers were perceived as not fully aware of the speech development impairments caused by 22q11DS. These preliminary observations point to the need for future studies and increased awareness efforts in this area. Full article
(This article belongs to the Section Neurolinguistics)
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<p>(<b>a</b>) Age (years) of the participants; (<b>b</b>) age (years) at diagnosis of 22q11DS.</p>
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<p>Age (years) of the study group: dispersion within individual age groups.</p>
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<p>Time of babbling onset (year; month age groups) and age dispersion (years).</p>
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<p>Time of the appearance of the first words (year; month age groups) and age dispersion (years).</p>
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<p>Time of the appearance of the first sentences (year; month age groups) and age dispersion (years).</p>
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<p>Ability to diversify verbal and non-verbal signals in children and age dispersion (years).</p>
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<p>Speech disfluencies: age dispersion (years) in the groups of children with and without disfluencies.</p>
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<p>Types of observed disfluencies and age dispersion (years).</p>
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<p>Reported hearing loss in the study group and age dispersion (years).</p>
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<p>The age (years) of participants: (<b>a</b>) when starting speech therapy; (<b>b</b>) the duration of speech therapy (years).</p>
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<p>The respondents’ opinions on the question whether speech therapists had sufficient knowledge of 22q11DS.</p>
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17 pages, 1179 KiB  
Article
Magnetocaloric Effect for a Q-Clock-Type System
by Michel Aguilera, Sergio Pino-Alarcón, Francisco J. Peña, Eugenio E. Vogel, Natalia Cortés and Patricio Vargas
Entropy 2025, 27(1), 11; https://doi.org/10.3390/e27010011 - 27 Dec 2024
Viewed by 260
Abstract
In this work, we study the magnetocaloric effect (MCE) in a working substance corresponding to a square lattice of spins with Q possible orientations, known as the “Q-state clock model”. When the Q-state clock model has Q5 possible [...] Read more.
In this work, we study the magnetocaloric effect (MCE) in a working substance corresponding to a square lattice of spins with Q possible orientations, known as the “Q-state clock model”. When the Q-state clock model has Q5 possible configurations, it presents the famous Berezinskii–Kosterlitz–Thouless (BKT) phase associated with vortex states. We calculate the thermodynamic quantities using Monte Carlo simulations for even Q numbers, ranging from Q=2 to Q=8 spin orientations per site in a lattice. We use lattices of different sizes with N=L×L=82,162,322,642,and1282 sites, considering free boundary conditions and an external magnetic field varying between B=0 and B=1.0 in natural units of the system. By obtaining the entropy, it is possible to quantify the MCE through an isothermal process in which the external magnetic field on the spin system is varied. In particular, we find the values of Q that maximize the MCE depending on the lattice size and the magnetic phase transitions linked with the process. Given the broader relevance of the Q-state clock model in areas such as percolation theory, neural networks, and biological systems, where multi-state interactions are essential, our study provides a robust framework in applied quantum mechanics, statistical physics, and related fields. Full article
(This article belongs to the Section Statistical Physics)
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<p>(<b>a</b>) Schematic representation for a square lattice of size <math display="inline"><semantics> <mrow> <mn>6</mn> <mo>×</mo> <mn>6</mn> </mrow> </semantics></math> with spin orientations corresponding to <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math>. (<b>b</b>) <span class="html-italic">Q</span>-clock model for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> <mo>,</mo> <mn>4</mn> <mo>,</mo> <mn>6</mn> </mrow> </semantics></math>, and 8 states. Orange dots indicate sites, and blue arrows are the possible spin orientation at each site with spin vector <math display="inline"><semantics> <mover accent="true"> <msub> <mi>S</mi> <mi>i</mi> </msub> <mo stretchy="false">→</mo> </mover> </semantics></math>.</p>
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<p>Normalized internal energy <math display="inline"><semantics> <mrow> <mi>U</mi> <mo>/</mo> <mi>N</mi> </mrow> </semantics></math> as a function of temperature for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> and lattice sizes <math display="inline"><semantics> <mrow> <mn>8</mn> <mo>×</mo> <mn>8</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>16</mn> <mo>×</mo> <mn>16</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>32</mn> <mo>×</mo> <mn>32</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>64</mn> <mo>×</mo> <mn>64</mn> </mrow> </semantics></math>, and <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> for an external magnetic field of (<b>a</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.0</mn> </mrow> </semantics></math> and (<b>b</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math>.</p>
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<p>Normalized internal energy <math display="inline"><semantics> <mrow> <mi>U</mi> <mo>/</mo> <mi>N</mi> </mrow> </semantics></math> as a function of the inverse of the lattice size <math display="inline"><semantics> <mrow> <mn>1</mn> <mo>/</mo> <mi>L</mi> </mrow> </semantics></math>, for different <span class="html-italic">Q</span> values, namely, 4, 6, and 8, and two values of the magnetic field <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.0</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math>. The left panel (<b>a</b>) corresponds to a low-temperature value, <math display="inline"><semantics> <mrow> <mi>T</mi> <mo>=</mo> <mn>0.5</mn> </mrow> </semantics></math>, while the right panel (<b>b</b>) corresponds to a high-temperature value of <math display="inline"><semantics> <mrow> <mn>3.5</mn> </mrow> </semantics></math>.</p>
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<p>Normalized specific heat <math display="inline"><semantics> <mrow> <mi>C</mi> <mo>/</mo> <mi>N</mi> </mrow> </semantics></math> as a function of temperature for even <span class="html-italic">Q</span> values between <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math> and a <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> lattice. (<b>a</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.0</mn> </mrow> </semantics></math>; (<b>b</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math>. The shift of the peaks to the right at <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math> is clearly seen for all <span class="html-italic">Q</span>.</p>
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<p>Normalized (<b>a</b>) internal energy, (<b>b</b>) magnetization, and (<b>c</b>) entropy as a function of temperature for even values of <span class="html-italic">Q</span> between <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math> and a <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> lattice. <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.0</mn> </mrow> </semantics></math> (purple curves); <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math> (blue curves).</p>
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<p>Normalized entropy difference <math display="inline"><semantics> <mrow> <mo>−</mo> <mo>Δ</mo> <mi>S</mi> <mo>=</mo> <mi>S</mi> <mrow> <mo>(</mo> <mi>T</mi> <mo>,</mo> <msub> <mi>B</mi> <mn>0</mn> </msub> <mo>=</mo> <mn>0</mn> <mo>)</mo> </mrow> <mo>−</mo> <mi>S</mi> <mrow> <mo>(</mo> <mi>T</mi> <mo>,</mo> <mi>B</mi> <mo>)</mo> </mrow> </mrow> </semantics></math> as a function of temperature for lattices sizes from <math display="inline"><semantics> <mrow> <mn>8</mn> <mo>×</mo> <mn>8</mn> </mrow> </semantics></math> to <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> sites, and <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.2</mn> </mrow> </semantics></math> (lower curves) and <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math> (upper curves). (<b>a</b>) <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math>; (<b>b</b>) <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math>.</p>
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<p>Normalized magnetocaloric effect for a <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> lattice using Monte Carlo simulations for the case of <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> up to <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math> and external <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math>.</p>
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<p>Caloric response for a <math display="inline"><semantics> <mrow> <mn>3</mn> <mo>×</mo> <mn>3</mn> </mrow> </semantics></math> lattice with an initial field of B = 0.05 and a final field of (<b>a</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.1</mn> </mrow> </semantics></math> and (<b>b</b>) <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>1.0</mn> </mrow> </semantics></math> for the exact and mean-field cases for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> <mo>,</mo> <mn>4</mn> <mo>,</mo> <mn>6</mn> </mrow> </semantics></math>, and 8.</p>
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<p>Maximum caloric response (<math display="inline"><semantics> <mrow> <mo>−</mo> <mo>Δ</mo> <msub> <mi>S</mi> <mrow> <mi>m</mi> <mi>a</mi> <mi>x</mi> </mrow> </msub> </mrow> </semantics></math>) as a function of the applied external field between <math display="inline"><semantics> <mrow> <mn>0.1</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mn>1.0</mn> </mrow> </semantics></math> for a <math display="inline"><semantics> <mrow> <mn>3</mn> <mo>×</mo> <mn>3</mn> </mrow> </semantics></math> lattice with an initial magnetic field <math display="inline"><semantics> <mrow> <mi>B</mi> <mo>=</mo> <mn>0.05</mn> </mrow> </semantics></math> for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> <mo>,</mo> <mn>4</mn> <mo>,</mo> <mn>6</mn> </mrow> </semantics></math>, and 8 employing exact calculations (solid lines) and mean-field calculations (dashed lines).</p>
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<p><span class="html-italic">T</span> vs. <span class="html-italic">B</span> phase diagram for (<b>a</b>) <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>4</mn> </mrow> </semantics></math> and for (<b>b</b>) <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>6</mn> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math>. The solid lines for (<b>a</b>) represent the critical temperatures of the FP-PP-type transition of the final state of the spin system <math display="inline"><semantics> <mrow> <mi>S</mi> <mo>(</mo> <mi>T</mi> <mo>,</mo> <mi>B</mi> <mo>)</mo> </mrow> </semantics></math>, while for (<b>b</b>), the solid lines represent the critical temperatures of the FP-BKT-type transition of the final state of the spin system <math display="inline"><semantics> <mrow> <mi>S</mi> <mo>(</mo> <mi>T</mi> <mo>,</mo> <mi>B</mi> <mo>)</mo> </mrow> </semantics></math>. For (<b>a</b>), the light blue triangles indicate the maximum obtained from <math display="inline"><semantics> <mrow> <mo>−</mo> <mo>Δ</mo> <mi>S</mi> <mo>=</mo> <mi>S</mi> <mrow> <mo>(</mo> <mi>T</mi> <mo>,</mo> <msub> <mi>B</mi> <mn>0</mn> </msub> <mo>=</mo> <mn>0.05</mn> <mo>)</mo> </mrow> <mo>−</mo> <mi>S</mi> <mrow> <mo>(</mo> <mi>T</mi> <mo>,</mo> <mi>B</mi> <mo>)</mo> </mrow> </mrow> </semantics></math> with <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> and the green squares indicate the same but for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>4</mn> </mrow> </semantics></math>. The same applies to <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>6</mn> </mrow> </semantics></math> represented by magenta circles and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math> with blue circles. The horizontal dotted lines indicate the critical temperature of the <math display="inline"><semantics> <mrow> <mi>S</mi> <mo>(</mo> <mi>T</mi> <mo>,</mo> <msub> <mi>B</mi> <mn>0</mn> </msub> <mo>=</mo> <mn>0.05</mn> <mo>)</mo> </mrow> </semantics></math> state for <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>2</mn> </mrow> </semantics></math> (light blue), <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>4</mn> </mrow> </semantics></math> (green), <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>6</mn> </mrow> </semantics></math> (magenta), and <math display="inline"><semantics> <mrow> <mi>Q</mi> <mo>=</mo> <mn>8</mn> </mrow> </semantics></math> (blue). The black vertical dotted lines (for panels (<b>a</b>,<b>b</b>)) represent the location where the systems maximize <math display="inline"><semantics> <mrow> <mo>−</mo> <mo>Δ</mo> <mi>S</mi> </mrow> </semantics></math> passing through an effective phase change.</p>
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19 pages, 3428 KiB  
Article
Vitamin E Intake Attenuated the Association Between Elevated Blood Heavy Metal (Pb, Cd, and Hg) Concentrations and Diabetes Risk in Adults Aged 18–65 Years: Findings from 2007–2018 NHANES
by Chenggang Yang, Shimiao Dai, Yutian Luo, Qingqing Lv, Junying Zhu, Aolin Yang, Zhan Shi, Ziyu Han, Ruirui Yu, Jialei Yang, Longjian Liu and Ji-Chang Zhou
Toxics 2025, 13(1), 9; https://doi.org/10.3390/toxics13010009 - 25 Dec 2024
Viewed by 379
Abstract
The association between heavy metal exposure and diabetes is controversial and vitamin E (VE) may reduce diabetes risk. We aimed to examine the associations between blood heavy metals (BHMs) and diabetes risk and VE’s role in the relationship. From the 2007–2018 NHANES, 10,721 [...] Read more.
The association between heavy metal exposure and diabetes is controversial and vitamin E (VE) may reduce diabetes risk. We aimed to examine the associations between blood heavy metals (BHMs) and diabetes risk and VE’s role in the relationship. From the 2007–2018 NHANES, 10,721 participants aged ≥ 18 were included for multiple statistical analyses, which revealed that BHMs and dietary VE intake were negatively associated with diabetes and fasting plasma glucose (FPG). The diabetes prevalence in each quartile (Q) of heavy metal exposure increased with age, but within age Q4, it generally decreased with exposure quartiles. Moreover, BHMs were positively associated with all-cause and diabetes-related mortalities with aging, which induced an age breakpoint of 65 years for age-stratified analyses on the associations between BHMs and diabetes risk. In those aged > 65, BHMs were negatively correlated with diabetes risk and its biomarkers; however, in adults aged 18–65, the correlation was positive. At higher VE intake levels, blood lead was associated with a lower diabetes risk and all three BHMs demonstrated lower FPG levels than those at lower VE intake levels. In conclusion, consuming sufficient VE and avoiding heavy metal exposure are highly recommended to reduce diabetes risk. Full article
(This article belongs to the Special Issue Dietary Exposure to Heavy Metals and Health Risks)
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<p>Flow chart of participant recruitment, NHANES 2007–2018.</p>
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<p>Kaplan–Meier survival curves depicting the unadjusted relationships of heavy metal exposure levels with all-cause (<b>A</b>–<b>D</b>) and diabetes-related mortalities (<b>E</b>–<b>H</b>). Data are population survival at specific time points. <span class="html-italic">N</span> = 10,721 in heavy metals analysis; <span class="html-italic">N</span> = 6464 in WQS analysis. Cd, cadmium; Hg, mercury; Pb, lead; WQS, weighted quantile sum.</p>
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<p>Cox regression analysis of heavy metals with overall (<b>A</b>–<b>D</b>) and diabetes-related mortalities (<b>E</b>–<b>H</b>). Data are hazard ratios and 95% confidence intervals. Model 1, adjusted for age, gender, and race. Model 2, adjusted for factors in Model 1 plus education, cotinine, body mass index, ratio of family income to poverty, and physical activity. Model 3, adjusted for factors in Model 2 plus hypertension and hypercholesteremia. Model 4, adjusted for factors in Model 3 plus medication histories of antidiabetic drugs and insulin. <span class="html-italic">N</span> = 10,721 in heavy metals analysis; <span class="html-italic">N</span> = 6464 in WQS analysis. Cd, cadmium; Hg, mercury; HR, hazard ratio; Pb, lead; WQS, weighted quantile sum.</p>
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<p>The odds ratio of diabetes associated with heavy metals (<b>A</b>–<b>C</b>) and the non-linear relationships of glucose metabolic biomarkers with heavy metals (<b>D</b>–<b>O</b>) in participants aged 18–65. Data are ORs (<b>A</b>–<b>C</b>) or estimated values (<b>D</b>–<b>O</b>) and 95% CIs. The model was adjusted for age, gender, race, education, cotinine, body mass index, ratio of family income to poverty, physical activity, hypertension, and hypercholesteremia. <span class="html-italic">N</span> = 7601. Cd, cadmium; CI, confidence interval; Hg, mercury; OR, odds ratio; Pb, lead.</p>
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<p>Estimated risk and weighted values of heavy metals for diabetes and glucose by WQS models in participants aged 18–65. (<b>A</b>) associations of blood heavy metals (BHMs) with diabetes risk (ORs and 95% CIs) in participants aged 18–65 years; (<b>B</b>) weighted values of BHMs for diabetes; (<b>C</b>) associations of BHMs with glucose (βs and 95% CIs) in participants aged 18–65 years; (<b>D</b>) weighted values of BHMs for glucose. Model 1, adjusted for age, gender, and race. Model 2, adjusted for factors in Model 1 plus education, cotinine, body mass index, ratio of family income to poverty, and physical activity. Model 3, adjusted for factors in Model 2 plus hypertension and hypercholesteremia. <span class="html-italic">N</span> = 7601. Cd, cadmium; CI, confidence interval; Hg, mercury; OR, odds ratio; Pb, lead; WQS, weighted quantile sum.</p>
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<p>The associations of diabetes risk (<b>A</b>) and blood glucose levels (<b>B</b>–<b>D</b>) with heavy metals at different vitamin E (VE) levels. Data are ORs (<b>A</b>) or estimated values (<b>B</b>–<b>D</b>) and 95% CIs. The model was adjusted for age, gender, race, education, cotinine, body mass index, ratio of family income to poverty, physical activity, hypertension, and hypercholesteremia. <span class="html-italic">N</span> = 7601. Level 1, Quantile 1 of VE intake; Level 2, Quantiles 2–3 of VE intake; Level 3, Quantile 4 of VE intake. Cd, cadmium; CI, confidence interval; Hg, mercury; OR, odds ratio; Pb, lead.</p>
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Article
The Frequency of DPYD c.557A>G in the Dominican Population and Its Association with African Ancestry
by Mariela Guevara, Carla González de la Cruz, Fernanda Rodrigues-Soares, Ernesto Rodríguez, Caíque Manóchio, Eva Peñas-Lledó, Pedro Dorado and Adrián LLerena
Pharmaceutics 2025, 17(1), 8; https://doi.org/10.3390/pharmaceutics17010008 - 24 Dec 2024
Viewed by 350
Abstract
Background/Objectives: Genetic polymorphism of the dihydropyrimidine dehydrogenase gene (DPYD) is responsible for the variability found in the metabolism of fluoropyrimidines such as 5-fluorouracil (5-FU), capecitabine, or tegafur. The DPYD genotype is linked to variability in enzyme activity, 5-FU elimination, and toxicity. [...] Read more.
Background/Objectives: Genetic polymorphism of the dihydropyrimidine dehydrogenase gene (DPYD) is responsible for the variability found in the metabolism of fluoropyrimidines such as 5-fluorouracil (5-FU), capecitabine, or tegafur. The DPYD genotype is linked to variability in enzyme activity, 5-FU elimination, and toxicity. Approximately 10–40% of patients treated with fluoropyrimidines develop severe toxicity. The interethnic variability of DPYD gene variants in Afro-Latin Americans is poorly studied, thereby establishing a barrier to the implementation of personalized medicine in these populations. Therefore, the present study aims to analyze the frequency of DPYD variants with clinical relevance in the Dominican population and their association with genomic ancestry components. Methods: For this study, 196 healthy volunteers from the Dominican Republic were genotyped for DPYD variants by qPCR, and individual genomic ancestry analysis was performed in 178 individuals using 90 informative ancestry markers. Data from the 1000 Genomes project were also retrieved for comparison and increased statistical power. Results and Conclusions: The c.557A>G variant (decreased dihydropyrimidine dehydrogenase function) presented a frequency of 2.6% in the Dominican population. Moreover, the frequency of this variant is positively associated with African ancestry (r2 = 0.67, p = 1 × 10−7), which implies that individuals with high levels of African ancestry are more likely to present this variant. HapB3 is completely absent in Dominican, Mexican, Peruvian, Bangladeshi, and all East Asian and African populations, which probably makes its analysis dispensable in these populations. The implementation of pharmacogenetics in oncology, specifically DPYD, in populations of Afro-Latin American ancestry should include c.557A>G, to be able to carry out the safe and effective treatment of patients treated with fluoropyrimidines. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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<p><span class="html-italic">DPYD</span> c.557A&gt;G allele frequencies as a function of African ancestry proportions in the 1000 Genomes project populations, plus the Dominican Republic population. East Asian: CDX: Dai Chinese from Xishuangbanna, CHS: Han Chinese from the south, CHB: Han Chinese from Beijing, JPT: Japanese from Tokyo; European: TSI: Italians from Tuscany, IBS: Iberians from Spain, GBR: British from England and Scotland, CEU: European descendants from Utah, FIN: Finns from Finland; South Asian: PJL: Pakistanis, GIH: Gujarati Indians in Houston USA, ITU: Telugu Indians in the UK, STU: Sri Lankan Tamils in the UK, BEB: Bengalis from Bangladesh, and KHV: Kinh Vietnamese from Ho Chi Minh City.</p>
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<p>World map presenting the frequency of c.557A&gt;G in 1000 Genomes project populations and in the Dominican Republic. EAS: Dai Chinese from Xishuangbanna, Han Chinese from the South, Han Chinese from Beijing, Japanese from Tokyo; EUR: Italians from Tuscany, Iberians from Spain, British from England and Scotland, European descendants from Utah, Finns from Finland; ESN: Esan from Nigeria, LWK: Luhya from Kenya, YRI: Yoruba from Nigeria, MSL: Mande from Sierra Leone, GWD: Mandinka from Gambia, ASW: African-Americans from the southwestern United States, MXL: Mexican descent from Los Angeles, ACB: Afro-Caribbeans from Barbados, CLM: Colombians from Medellín, PEL: Peruvians from Lima, DR: Dominican Republic (present study).</p>
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10 pages, 2540 KiB  
Systematic Review
Relationship Between Rheumatoid Arthritis and Periodontal Disease—Systematic Review and Meta-Analysis
by Sabino Dolcezza, Javier Flores-Fraile, Ana Belén Lobo-Galindo, José María Montiel-Company and Álvaro Zubizarreta-Macho
J. Clin. Med. 2025, 14(1), 10; https://doi.org/10.3390/jcm14010010 - 24 Dec 2024
Viewed by 216
Abstract
Background/Objectives: The aim of this systematic review and meta-analysis was to determine the association between rheumatoid arthritis and periodontal disease. Methods: This systematic review and meta-analysis of the scientific literature was carried out based on the recommendations of Preferred Reporting Items for Systematic [...] Read more.
Background/Objectives: The aim of this systematic review and meta-analysis was to determine the association between rheumatoid arthritis and periodontal disease. Methods: This systematic review and meta-analysis of the scientific literature was carried out based on the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We analyzed all studies that evaluated the relationship between the chronic inflammatory diseases through the response to non-surgical periodontal treatment, comparing the values of CAL (Clinical Attachment Level) for PD (periodontal disease) and DAS28 for RA. A total of three databases were searched in the literature search: Pubmed, Scopus, and Web of Science. After eliminating duplicate articles and applying certain inclusion criteria, of the 29 articles found, a total of 6 were included in the present study. Results: A statistically significant difference in mean reduction of −0.56 mm was obtained for CAL, with a 95% confidence interval of the difference between −0.82 and −0.31 (z-test = −4.33; p-value = 0.001) in favor of the periodontal treatment group. The heterogeneity of the meta-analysis was slight (I2 = 39% and Q = 8.19; p-value = 0.146). For DAS28, treatment showed a mean reduction of −0.39 DAS points, with a 95% CI between −0.46 and −0.31 (z-test = −10.3; p-value < 0.001) among patients with PD and RA. Conclusions: The present study shows how the control of periodontal disease through non-surgical periodontal treatment can reduce the severity of RA. This finding consistently supports the idea that there is a pathogenic association between these two chronic inflammatory diseases. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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<p>PRISMA flow diagram showing the preferred reporting items for systematic reviews and meta-analyses approach. The diagram illustrates the process of selecting studies for inclusion, starting from the identification of records through database searches, followed by screening for eligibility, and concludes with the final number of studies included in the review. The flowchart highlights the various stages of the review process, including exclusions and reasons for exclusion at each stage.</p>
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<p>Forest plot of the meta-analysis of the difference in means (CAL in mm) [<a href="#B53-jcm-14-00010" class="html-bibr">53</a>,<a href="#B55-jcm-14-00010" class="html-bibr">55</a>,<a href="#B57-jcm-14-00010" class="html-bibr">57</a>,<a href="#B58-jcm-14-00010" class="html-bibr">58</a>,<a href="#B60-jcm-14-00010" class="html-bibr">60</a>,<a href="#B61-jcm-14-00010" class="html-bibr">61</a>].</p>
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<p>Funnel plots of the meta-analysis of the mean difference in CAL in mm with the trim-and-fill method, showing the initial estimate (<b>left funnel plot</b>) and the estimate with the 3 studies added as white points (<b>right funnel plot</b>).</p>
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<p>Forest plot of the meta-analysis of mean difference (DAS28 score) [<a href="#B53-jcm-14-00010" class="html-bibr">53</a>,<a href="#B55-jcm-14-00010" class="html-bibr">55</a>,<a href="#B57-jcm-14-00010" class="html-bibr">57</a>,<a href="#B58-jcm-14-00010" class="html-bibr">58</a>,<a href="#B60-jcm-14-00010" class="html-bibr">60</a>,<a href="#B61-jcm-14-00010" class="html-bibr">61</a>].</p>
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<p>Funnel plots of the meta-analysis of the mean difference in DAS28 score with the trim-and-fill method, showing the initial estimate (<b>left funnel plot</b>) and the estimate with the 3 studies added as white points (<b>right funnel plot</b>).</p>
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21 pages, 4117 KiB  
Article
One-Week Maternal Separation Caused Sex-Specific Changes in Behavior and Hippocampal Metabolomics of Offspring Rats
by Meng-Chen Dong, Yu-Xin Chen, Xin-Ran Sun, Ning Jiang, Qi Chang, Xin-Min Liu and Rui-Le Pan
Brain Sci. 2024, 14(12), 1275; https://doi.org/10.3390/brainsci14121275 - 18 Dec 2024
Viewed by 854
Abstract
To investigate the effects of one-week maternal separation (MS) on anxiety- and depression-like behaviors in adolescent and adulthood as well as adult hippocampal metabolomics simultaneously in offspring female and male rats. In the MS group, newborn SD rats were separated from their mothers [...] Read more.
To investigate the effects of one-week maternal separation (MS) on anxiety- and depression-like behaviors in adolescent and adulthood as well as adult hippocampal metabolomics simultaneously in offspring female and male rats. In the MS group, newborn SD rats were separated from their mothers for 3 h per day from postnatal days (PND) 2 to 8. The open field test (OFT), elevated plus mazes (EPM), novelty suppressed feeding test (NSFT), and forced swimming test (FST) were conducted during adolescence and adulthood. Serum corticosterone, mRNA expression of hippocampal inflammatory cytokines, and hippocampal untargeted metabolomics of offspring adult rats were examined using an assay kit, qRT-PCR, and UPLC-Q-TOF/MS. Both MS female and male rats showed similar behaviors in OFT, EPM, NSFT, and SPT, except for the latency to feeding during adolescence and the open arm entries during adulthood, showed statistical significance only in MS female rats. Serum corticosterone and hippocampal pro-inflammatory cytokines IFN-γ were significantly elevated in both female and male rats, and IL-1β and TNF-α were significantly increased only in female rats. In hippocampal metabolism, the identification of differential metabolites displayed 53 and 37 in female rats and male rats, respectively (with 35 common metabolites), which were involved in 33 and 30 metabolic pathways with 28 common pathways. One-week MS induced sex-specific anxiety- and depression-like behaviors in female and male offspring rats during adolescence and adulthood, as well as sex-differentiated characteristics in the hippocampus inflammatory cytokines and metabolomics of adult MS rats. From the experimental data, the effects of MS on the female offspring rats were more severe than those of the male offspring rats. Full article
(This article belongs to the Section Behavioral Neuroscience)
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<p>Animal experiment process. OFT: Open Field Test; EPM: Elevated Plus Maze; NSFT: Novelty Suppressed Feeding Test; FST: Forced Swimming Test.</p>
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<p>Curve plot of body weight changes in one-week MS rats. The data represented mean ± SEM, CON: control group, MS: maternal separation group; compared with control group, *** <span class="html-italic">p</span> &lt; 0.001; (<b>A</b>), curve plot of body weight change in all rats (<span class="html-italic">n</span> = 20); (<b>B</b>), curve plot of body weight change in female rats (<span class="html-italic">n</span> = 8–12); (<b>C</b>), curve plot of body weight change in male rats (<span class="html-italic">n</span> = 8–12).</p>
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<p>Effect of one-week MS on adolescent behavior of offspring rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 8–12. CON: control group, MS: maternal separation group; compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01; (<b>A</b>), OFT: open field test, (1) movement distance (2) movement time (3) percent of distance moved in center area (%) (4) percent of time moved in center area (%), (<b>B</b>), EPM: elevated plus mazes, (1) open arm entries (%) (2) open arm duration (%), (<b>C</b>), NSFT: novelty suppressed feeding test.</p>
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<p>Effect of one-week MS on adulthood behavior of offspring rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 8–12. CON: control group, MS: maternal separation group; compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01; (<b>A</b>), OFT: open field test, (1) movement distance (2) movement time (3) percent of distance moved in center area (%) (4) percent of time moved in center area (%), (<b>B</b>), EPM: elevated plus mazes, (1) open arm entries (%) (2) open arm duration (%), (<b>C</b>), NSFT: novelty suppressed feeding test, (<b>D</b>), FST: forced swimming test.</p>
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<p>Effect of one-week MS on serum CORT of offspring rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 6–8. CON: control group, MS: maternal separation group; Compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Effect of one-week MS on hippocampal inflammatory cytokines of offspring rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 6–8. CON: control group, MS: maternal separation group; compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. (<b>A</b>), Effect of MS on pro-inflammatory cytokine expression in offspring rats, (1) IL-1β mRNA expression (2) IFN-γ mRNA expression (3) TNF-α mRNA expression, (<b>B</b>), Effect of MS on anti-inflammatory cytokine expression in offspring rats, (1) IL-10 mRNA expression (2) TGF-β mRNA expression.</p>
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<p>Untargeted metabolomic profile analysis of hippocampus in MS female and male rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 8–12, (<b>A</b>), Scatterplot of PCA, CON (control group, blue dots); MS (maternal separation group, red dots) (1) PCA scatterplot of positive ion metabolomic profiles in female rats (R2Y = 0.996, Q2 = 0.92), (2) PCA scatterplot of negative ion metabolomic profiles in females (R2Y = 0.994, Q2 = 0.864), (3) PCA scatterplot of positive ion metabolomic profiles in male rats (R2Y = 0.996, Q2 = 0.918), (4) PCA scatterplot of negative ion metabolomic profiles in male rats (R2Y = 1, Q2 = 0.856); (<b>B</b>), OPLS-DA analysis scatterplot, CON (blue dots); MS (red dots), (1) female rat positive mode OPLS-DA scatterplot (R2Y = 0.996, Q2 (cum) = 0.92), (2) female rat negative mode OPLS-DA scatterplot (R2Y = 0.994, Q2 (cum) = 0.864), (3) male rat positive mode OPLS-DA scatterplot (R2Y = 0.996, Q2 (cum) = 0.918), (4) male rat negative mode OPLS-DA scatterplot (R2Y = 1, Q2 (cum) = 0.856); (<b>C</b>), OPLS-DA permutation test plot, R2 (green dots) Q2 (blue squares), (1) female rat positive OPLS-DA permutation test plot (R2Y = 0.957, Q2 = −0.143), (2) female rat negative OPLS-DA permutation test plot (R2Y = 0.948, Q2 = −0.142), (3) male rat positive OPLS-DA permutation test plot (R2Y = 0.891, Q2 = −0.229), and (4) male rat negative OPLS-DA permutation test plot (R2Y = 0.997, Q2 = −0.00434).</p>
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<p>Heat map of differential metabolite changes in male and female rats. (<b>A</b>), Heat map of differential metabolite changes in female rats; (<b>B</b>), Heat map of differential metabolite changes in male rats.</p>
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<p>Pathway analysis of differential metabolites of hippocampus in female and male rats. The redder the color, the larger the -LOG(p) value, and the larger the bubble, the larger the Pathway Impact value. (<b>A</b>), Pathway analysis of differential metabolites of hippocampus in female rats; (<b>B</b>), Pathway analysis of differential metabolites of hippocampus in male rats.</p>
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<p>The main correlation of behavior and hippocampal differential metabolites in MS female and male rats. The horizontal coordinate is the behavior data, the vertical coordinate is the metabolite intensity, the blue line shows the correlation in males and the red line shows females.</p>
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<p>Effect of one-week MS on hippocampal NAD+ and NADH of offspring rats. The data represented mean ± SEM, <span class="html-italic">n</span> = 6–8. CON: control group, MS: maternal separation group; compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. (<b>A</b>), NAD+; (<b>B</b>), NADH; (<b>C</b>), ratio of NAD+/NADH.</p>
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17 pages, 7699 KiB  
Systematic Review
Long Non-Coding RNAs as Diagnostic Biomarkers for Ischemic Stroke: A Systematic Review and Meta-Analysis
by Jianwei Pan, Weijian Fan, Chenjie Gu, Yongmei Xi, Yu Wang and Peter Wang
Genes 2024, 15(12), 1620; https://doi.org/10.3390/genes15121620 - 18 Dec 2024
Viewed by 381
Abstract
Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of [...] Read more.
Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of lncRNAs for ischemic stroke by analyzing existing research. A comprehensive literature search was conducted across the PubMed, ScienceDirect, Wiley Online Library, and Web of Science databases for articles published up to July 10, 2024. Statistical analyses were performed using Stata 17.0 software to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), diagnostic odds ratio (DOR), negative likelihood ratio (NLR), and area under the curve (AUC). Heterogeneity was explored with the Cochran-Q test and the I2 statistical test, and publication bias was assessed with Deeks’ funnel plot. A total of 44 articles were included, involving 4302 ischemic stroke patients and 3725 healthy controls. Results demonstrated that lncRNAs H19, GAS5, PVT1, TUG1, and MALAT1 exhibited consistent trends across multiple studies. The pooled sensitivity of lncRNAs in the diagnosis of ischemic stroke was 79% (95% CI: 73–84%), specificity was 88% (95% CI: 77–94%), PLR was 6.63 (95% CI: 3.11–14.15), NLR was 0.23 (95% CI: 0.16–0.33), DOR was 28.5 (95% CI: 9.88–82.21), and AUC was 0.88 (95% CI: 0.85–0.90). Furthermore, the results of subgroup analysis indicated that lncRNA H19 had superior diagnostic performance. LncRNAs demonstrated strong diagnostic accuracy in distinguishing ischemic stroke patients from healthy controls, underscoring their potential as reliable biomarkers. Because most of the articles included in this study originate from China, large-scale, high-quality, multi-country prospective studies are required to further validate the reliability of lncRNAs as biomarkers for ischemic stroke. Full article
(This article belongs to the Special Issue The Epigenetic Roles of lncRNAs)
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<p>Flow diagram of study search and selection.</p>
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<p>Risk of bias assessment of eligible studies using QUADAS-2. (<b>A</b>) Summary of bias risk items in the QUADAS-2 quality assessment. (<b>B</b>) Percentile of risk of bias in the QUADAS-2 quality assessment [<a href="#B18-genes-15-01620" class="html-bibr">18</a>,<a href="#B19-genes-15-01620" class="html-bibr">19</a>,<a href="#B21-genes-15-01620" class="html-bibr">21</a>,<a href="#B25-genes-15-01620" class="html-bibr">25</a>,<a href="#B28-genes-15-01620" class="html-bibr">28</a>,<a href="#B30-genes-15-01620" class="html-bibr">30</a>,<a href="#B32-genes-15-01620" class="html-bibr">32</a>,<a href="#B38-genes-15-01620" class="html-bibr">38</a>,<a href="#B41-genes-15-01620" class="html-bibr">41</a>,<a href="#B43-genes-15-01620" class="html-bibr">43</a>,<a href="#B51-genes-15-01620" class="html-bibr">51</a>,<a href="#B52-genes-15-01620" class="html-bibr">52</a>,<a href="#B53-genes-15-01620" class="html-bibr">53</a>,<a href="#B56-genes-15-01620" class="html-bibr">56</a>,<a href="#B57-genes-15-01620" class="html-bibr">57</a>,<a href="#B58-genes-15-01620" class="html-bibr">58</a>,<a href="#B59-genes-15-01620" class="html-bibr">59</a>].</p>
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<p>(<b>A</b>) Forest plot showing the pooled sensitivity and specificity of lncRNAs in diagnosing ischemic stroke. Squares represent individual studies, while line segments indicate the 95% confidence interval (CI) for each study. The center of the diamond and the red dashed line represent the pooled effect size, and the width of the diamond corresponds to the 95% CI of the pooled results. (<b>B</b>) Summary receiver operating characteristic (SROC) curve with the 95% confidence and prediction contours. The <span class="html-italic">Y</span>-axis represents sensitivity, and the <span class="html-italic">X</span>-axis represents specificity. Numbers represent individual studies, and the curves depict combined diagnostic performance.</p>
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<p>Fagan nomogram (<b>A</b>) and likelihood ratio scattergram (<b>B</b>) are illustrated. (<b>A</b>) If two values are known, the nomogram can be used to calculate a third value. (<b>B</b>) The ordinate represents the positive likelihood ratio, indicating the likelihood of a positive result in a patient compared to a non-patient. The abscissa represents the negative likelihood ratio, indicating the likelihood of a negative result in a patient compared to a non-patient.</p>
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<p>Deeks’ funnel plot for publication bias analysis. A <span class="html-italic">p</span>-value &gt; 0.05 indicates no significant publication bias.</p>
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<p>LncRNAs as diagnostic markers for ischemic stroke. Created using <a href="https://BioRender.com" target="_blank">https://BioRender.com</a> (accessed on 3 December 2024).</p>
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12 pages, 1852 KiB  
Article
Nondestructive Determination of Tocopherol and Tocotrienol in Vitamin E Powder Using Near- and Mid-Infrared Spectroscopy
by Saowaluk Rungchang, Sila Kittiwachana, Sujitra Funsueb, Chitsiri Rachtanapun, Juthamas Tantala, Phumon Sookwong, Laichheang Yort, Chayanid Sringarm and Sudarat Jiamyangyuen
Foods 2024, 13(24), 4079; https://doi.org/10.3390/foods13244079 - 17 Dec 2024
Viewed by 651
Abstract
Vitamin E is an essential nutrient, but its poor water solubility limits food and pharmaceutical applications. The usability of vitamin E can be enhanced via modification methods such as encapsulation, which transforms the physical state of vitamin E from a liquid to a [...] Read more.
Vitamin E is an essential nutrient, but its poor water solubility limits food and pharmaceutical applications. The usability of vitamin E can be enhanced via modification methods such as encapsulation, which transforms the physical state of vitamin E from a liquid to a powder. This study examined the efficacy of near-infrared (NIR) and mid-infrared (MIR) spectroscopy in identifying and predicting various vitamin E derivatives in vitamin E-encapsulated powder (VEP). An MIR analysis revealed the fundamental C–H vibrations of vitamin E in the range of 2700–3250 cm−1, whereas an NIR analysis provided information about the corresponding combination, first, and second overtones in the range of 4000–9000 cm−1. The MIR and NIR data were analyzed using a principal component analysis to characterize the VEP. Partial least squares (PLS) regression was applied to predict the content of individual vitamin E derivatives. PLS cross-validation revealed that NIR analysis provides more reliable predictive accuracy and precision for the contents of vitamin E derivatives, achieving a higher coefficient of determination for prediction (Q2) (0.92–0.99) than MIR analysis (0.20–0.85). For test set validation, the NIR predictions exhibited a significant level of accuracy, as indicated by a high ratio of prediction to deviation (RPD) and Q2. Furthermore, the PLS models developed using the NIR data had statistically significant predictive performance, with a high RPD (1.54–3.92) and Q2 (0.66–0.94). Thus, NIR spectroscopy is a valuable nondestructive technique for analyzing vitamin E samples, while MIR spectroscopy serves as a useful method for confirming its presence. Full article
(This article belongs to the Section Food Analytical Methods)
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<p>(<b>a</b>) NIR and (<b>b</b>) MIR spectra of encapsulated vitamin E.</p>
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<p>PCA score and loading plots of (<b>a</b>) NIR and (<b>b</b>) MIR data for encapsulated vitamin E.</p>
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<p>Scatter plots of the actual and predicted quality parameters for the NIR spectra of encapsulated vitamin E.</p>
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<p>PLS coefficients for the NIR spectra of encapsulated vitamin E.</p>
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15 pages, 2093 KiB  
Article
Exploring the In Vitro Effects of Zingerone on Differentiation and Signalling Pathways in Bone Cell Lines
by Brunhildé De Vos, Abe E. Kasonga, Anna M. Joubert and Trevor T. Nyakudya
Metabolites 2024, 14(12), 693; https://doi.org/10.3390/metabo14120693 - 9 Dec 2024
Viewed by 656
Abstract
Objective: Ensuring adequate bone health is crucial for preventing conditions such as osteoporosis and fractures. Zingerone, a phytonutrient isolated from cooked ginger, has gained attention for its potential benefits in bone health. This study evaluated the osteoprotective potential of zingerone and its effects [...] Read more.
Objective: Ensuring adequate bone health is crucial for preventing conditions such as osteoporosis and fractures. Zingerone, a phytonutrient isolated from cooked ginger, has gained attention for its potential benefits in bone health. This study evaluated the osteoprotective potential of zingerone and its effects on differentiation and signalling pathways in vitro using SAOS-2 osteosarcoma and RAW264.7 macrophage cell lines, aiming to elucidate its mechanism of action in bone remodelling. Methods: SAOS-2 osteosarcoma and RAW264.7 macrophage cells were treated with zingerone at concentrations of 200 µM. Osteoblast differentiation was assessed by alkaline phosphatase (ALP) activity, bone mineralisation via Alizarin Red S stain, and gene expression markers (ALP, runt-related transcription factor 2 (Runx2), and osteocalcin) via quantitative polymerase chain reaction (q-PCR). Osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity, and mitogen-activated protein kinase (MAPK) pathways. Results: Treatment with zingerone was non-toxic at 200 µM. Zingerone (200 µM) significantly stimulated the gene expression of ALP and Runx2 in SAOS-2 cells (p < 0.05) without statistically significantly enhancing SAOS-2 mineralisation via calcium deposits. Moreover, zingerone significantly inhibited osteoclast differentiation in RAW264.7 cells as evidenced by reduced TRAP staining and activity (p < 0.05). Conclusions: Zingerone shows promise in reducing osteoclast activity and supporting early osteoblast differentiation, suggesting its potential as a dietary supplement for bone health. Further in vivo and clinical studies are needed to confirm its role in managing osteoporosis. Full article
(This article belongs to the Special Issue Advances in Phytomedicine Intervention on Metabolic Disorders)
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<p>Synthesis of zingerone during ginger processing. In the process, 6-Gingerol is formed by cooking or drying ginger root which then produces zingerone through a retro-aldol reaction. Zingerone is not present in fresh ginger. Chemical structures were sketched with PubChem Sketcher V2.4 (<a href="https://pubchem.ncbi.nlm.nih.gov//edit3/index.html" target="_blank">https://pubchem.ncbi.nlm.nih.gov//edit3/index.html</a> accessed on 27 October 2024). MW: molecular weight.</p>
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<p>Effect of zingerone on cell viability, mineralisation, and ALP activity in SAOS-2 cells. (<b>A</b>) Zingerone (0.1–200 µM) effects on cell viability (%) of undifferentiated SAOS-2 cells following 48 h treatment. Triton X-100 (0.2%) served as the positive control for cytotoxicity. (<b>B</b>) Mineralisation of SAOS-2 cells treated with zingerone (5–200 µM) for 7–21 days, evaluated using Alizarin Red S staining and measured at 540 nm. (<b>C</b>) SAOS-2 cells treated with osMcCoy media with or without zingerone for 21 days. (<b>D</b>) Zingerone’s effect on ALP activity as a marker of osteoblast-like differentiation measured over three stages of differentiation: 7, 14, and 21 days. Resazurin assay was used to evaluate cell viability. Data presented as mean ± SD (n = 3) (<b>A</b>) or mean ± SEM (<b>C</b>,<b>D</b>) containing at least three independent experiments. **** <span class="html-italic">p</span> &lt; 0.001 (vs. DMSO). Zing: zingerone; DMSO ODM–: undifferentiated media; DMSO ODM+: osteogenic media.</p>
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<p>The gene expression of <span class="html-italic">ALP</span> (<b>i</b>), <span class="html-italic">Runx2</span> (<b>ii</b>), and <span class="html-italic">OC</span> (<b>iii</b>) in SAOS-2 cells treated with 200 µM zingerone for 7 and 14 days of differentiation was assessed by q-PCR. Evaluation of the effects of zingerone on the expression of genes involved in the early and intermediate stages of osteoblast differentiation was conducted by exposing cells to osteogenic media for 7 days (<b>A</b>) and 14 days (<b>B</b>). Data presented as mean ± SD (n = 3), normalised to DMSO ODM–. *<sup>/</sup>** <span class="html-italic">p</span> &lt; 0.05 compared to control (DMSO ODM–). Zing: zingerone; DMSO ODM–: undifferentiated media; DMSO ODM+: osteogenic media.</p>
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<p>Effect of zingerone on cell viability and osteoclast differentiation in RAW264.7 cells. (<b>A</b>) Zingerone’s (0.1–200 µM) effects on cell viability (%) were evaluated by resazurin assay in undifferentiated RAW264.7 cells after 48 h treatment. Triton X-100 (0.2%) served as the positive control for cytotoxicity. (<b>B</b>) Microscopic images of TRAP-stained RAW264.7 cells (scale bar = 2 mm) treated with zingerone (100–200 µM) and RANKL (5 ng/mL). (<b>C</b>) Quantification of osteoclasts, identified as large multinucleated cells with three or more nuclei, stained pink. (<b>D</b>) TRAP activity measured in conditioned media via <span class="html-italic">p</span>-NPP substrate and displayed relative to the R+ cells. Data presented as mean ± SD (n = 3). (<b>A</b>): **** <span class="html-italic">p</span> &lt; 0.05 vs. DMSO. (<b>C</b>): * <span class="html-italic">p</span> &lt; 0.05 vs. R+. (<b>D</b>): **** <span class="html-italic">p</span> &lt; 0.05 V+ vs. R+. ** <span class="html-italic">p</span> &lt; 0.05 200 µM Zing vs. R+. V+: vehicle control (no RANKL added); R+: RANKL-stimulated cells; Zing: zingerone.</p>
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<p>The effects of zingerone (200 µM) on osteoclast-specific protein expression via RANKL-stimulated (15 ng/mL) MAPK (JNK, p38, ERK) signalling pathway. (<b>A</b>) Evaluating the effects of 200 µM zingerone on RANKL-stimulated MAPK signalling as represented by membrane images. GAPDH was used as the control (<b>B</b>–<b>D</b>) The expression levels of MAPKs (JNK, p38, and ERK) in RAW264.7s were treated with 200 µM zingerone and quantified by western blot via cytoplasmic extraction protocol. Data presented as mean ± SD of 3 independent repetitions (n = 3). ** <span class="html-italic">p</span> &lt; 0.05 compared to vehicle control (V+). RANKL: receptor activator of nuclear factor kappa beta; JNK: Jun N-terminal kinase; ERK: extracellular signal-regulated kinase; MAPKs: mitogen-activated protein kinases; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; V+: vehicle control (RANKL not present); R+: RANKL-only stimulated control; Zing: zingerone.</p>
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