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Keywords = Discriminant Function Analysis

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16 pages, 643 KB  
Article
Profiling the Kidney Before the Incision: CT-Derived Signatures Steering Reconstructive Strategy After Off-Clamp Minimally Invasive Partial Nephrectomy
by Umberto Anceschi, Antonio Tufano, Davide Vitale, Francesco Prata, Rocco Simone Flammia, Federico Cappelli, Leonardo Teodoli, Claudio Trobiani, Giulio Eugenio Vallati, Antonio Minore, Salvatore Basile, Riccardo Mastroianni, Aldo Brassetti, Gabriele Tuderti, Maddalena Iori, Giuseppe Spadaro, Mariaconsiglia Ferriero, Alfredo Maria Bove, Elva Vergantino, Eliodoro Faiella, Aldo Di Blasi, Rocco Papalia and Giuseppe Simoneadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3236; https://doi.org/10.3390/cancers17193236 - 5 Oct 2025
Abstract
Introduction: In minimally invasive, off-clamp partial nephrectomy (ocMIPN), the reconstructive strategy profoundly influences functional outcomes. Traditional nephrometry scores aid preoperative planning but do not directly inform the choice of closure technique. This dual-institutional study aimed primarily to identify preoperative CT-derived parameters predictive of [...] Read more.
Introduction: In minimally invasive, off-clamp partial nephrectomy (ocMIPN), the reconstructive strategy profoundly influences functional outcomes. Traditional nephrometry scores aid preoperative planning but do not directly inform the choice of closure technique. This dual-institutional study aimed primarily to identify preoperative CT-derived parameters predictive of renorrhaphy versus a sutureless approach, and secondarily to compare perioperative and functional outcomes between these techniques. Methods: We retrospectively analyzed 201 consecutive ocMIPN cases performed using a standardized off-clamp technique by two experienced surgical teams across robotic platforms and conventional laparoscopy. Preoperative CT scans were centrally reviewed to quantify morphometric features, including contact surface area (CSA), tumor radius, and Gerota’s fascia thickness. Univariable and multivariable logistic regression models—one restricted to radiologic variables and one expanded with RENAL score terms—were generated to identify independent predictors. Perioperative outcomes, renal functional metrics, and Trifecta rates were compared between cohorts. Results: Among the 201 patients, 101 (50.2%) underwent sutureless reconstruction and 100 (49.8%) renorrhaphy. Cohorts were comparable at baseline except for tumor size (3.1 vs. 3.6 cm; p = 0.04). In multivariable analysis, CSA > 15 cm2 (OR 3.93; 95% CI 1.26–12.26; p = 0.02) and tumor radius (OR 1.14 per mm; 95% CI 1.01–1.29; p = 0.04) consistently predicted renorrhaphy, while Gerota’s fascia < 10 mm emerged as significant only in the expanded specification (OR 0.08; 95% CI 0.01–0.70; p = 0.02). Integration with RENAL improved predictive performance (ΔAUC 0.06; NRI 0.14; IDI 0.07), and the final model demonstrated strong discrimination (AUC 0.81) with satisfactory calibration. Perioperative outcomes, postoperative renal function, and Trifecta achievement were similar between groups (all p ≥ 0.21). Conclusions: A concise set of CT-derived morphologic markers—CSA, tumor radius, and perinephric fascia thickness—anticipated reconstructive strategy in ocMIPN and augmented the discriminatory power of RENAL nephrometry. When anatomy was favorable, sutureless repair was not associated with statistically significant differences in perioperative safety or renal function, although the study was not powered for formal equivalence testing. These findings support the integration of radiologic markers into preoperative planning frameworks for nephron-sparing surgery. Full article
(This article belongs to the Section Methods and Technologies Development)
25 pages, 3625 KB  
Article
Checkpoint Imbalance in Primary Glomerulopathies: Comparative Insights into IgA Nephropathy and Membranoproliferative Glomerulonephritis
by Sebastian Mertowski, Paulina Mertowska, Milena Czosnek, Iwona Smarz-Widelska, Wojciech Załuska and Ewelina Grywalska
Cells 2025, 14(19), 1551; https://doi.org/10.3390/cells14191551 - 3 Oct 2025
Abstract
Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also [...] Read more.
Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also exist in soluble forms, reflecting systemic immune balance. Objective: To compare immune checkpoint profiles in IgAN and MPGN versus healthy volunteers (HV) through surface expression, soluble serum levels, and PBMC transcripts, with attention to sex-related differences and diagnostic value assessed by ROC curves. Materials and Methods: Ninety age-matched subjects were studied: IgAN (n = 30), MPGN (n = 30), HV (n = 30). Flow cytometry evaluated checkpoint expression on CD4+/CD8+ T cells, CD19+ B cells, and NK cells. ELISA quantified sPD-1, sPD-L1, sCTLA-4, sCD86, sCD200, sCD200R; PBMC transcript levels were assessed. Group comparisons, sex stratification, and ROC analyses were performed. Results: Lymphocyte distributions were preserved, but IgAN patients showed anemia and impaired renal function, while MPGN patients had greater proteinuria and dyslipidemia. GN patients displayed increased PD-1/PD-L1 and CD200R/CD200, with reduced CTLA-4/CD86, compared to HV. Serum analysis revealed elevated sPD-1, sPD-L1, sCD200, sCD200R and decreased sCTLA-4, sCD86. PBMC transcripts paralleled these trends, with PD-1/PD-L1 mainly increased in MPGN. Sex had minimal impact. ROC analyses showed strong GN vs. HV discrimination by CD19+CTLA-4+, PD-1/PD-L1, and CD200/CD200R, but limited ability to separate IgAN from MPGN. Conclusions: IgAN and MPGN share a sex-independent checkpoint signature: PD-1/PD-L1 and CD200R/CD200 upregulation with CTLA-4/CD86 downregulation. CD19+, CTLA-4+, and soluble PD-1/PD-L1/CD200(R) emerge as promising biomarkers requiring further validation. Full article
(This article belongs to the Special Issue Kidney Disease: The Role of Cellular Mechanisms in Renal Pathology)
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23 pages, 2159 KB  
Article
Single-Locus, Interaction, and Functional Pathway Analyses of Acne Severity in a 60-SNP Panel
by Valentina Russo, Laura Vila-Vecilla, Albert Sanchez Guerrero, Laura Gascón Madrigal, Caroline Brandão Chiovatto and Gustavo Torres de Souza
Cosmetics 2025, 12(5), 217; https://doi.org/10.3390/cosmetics12050217 - 2 Oct 2025
Abstract
Acne vulgaris is a multifactorial disease with high heritability, but the genetic determinants of severity remain incompletely defined. This study evaluated 650 individuals genotyped with a 60-single-nucleotide polymorphism (SNP) panel covering immune, lipid, endocrine, and barrier pathways. Acne severity was graded as 1 [...] Read more.
Acne vulgaris is a multifactorial disease with high heritability, but the genetic determinants of severity remain incompletely defined. This study evaluated 650 individuals genotyped with a 60-single-nucleotide polymorphism (SNP) panel covering immune, lipid, endocrine, and barrier pathways. Acne severity was graded as 1 (n = 193), 2–3 (n = 383), or 4 (n = 74). Single-SNP analysis highlighted associations in loci such as LHCGR (rs13405728), TGF-β2 (rs1159268), FST (rs38055), WNT10A (rs74333950), PIK3R1 (rs10515088), and THADA (rs13429458) and barrier-related variants (FLG, FLG-AS1). Epistasis analysis of 44 quality-controlled SNPs revealed 190 significant interactions (false discovery rate, FDR ≤ 0.10), with TLR4 as the main hub (degree = 22), bridging immune (IL10, TNF), lipid (PNPLA3, APOE), and barrier (FLG-AS1, OVOL1) genes. Polygenic risk scoring (PRS) showed a monotonic increase across severity grades, with Grade 4 displaying higher median scores (0.319) compared to Grade 1 (−0.129) and Grades 2–3 (0.034). Discrimination was modest but consistent (AUC: 0.661 for Grade 4 vs. 1; 0.662 vs. 2–3; 0.679 vs. all others). These results support a framework where microbial sensing, lipid metabolism, and barrier function converge to drive severe acne, underscoring the potential of genetic profiling for risk stratification and precision therapy. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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20 pages, 2230 KB  
Article
Relationship Between Parapapillary Microvasculature Dropout and Visual Field Defect in Glaucoma: A Cross-Sectional OCTA Analysis
by Fiorella Cuba Sullucucho and Carmen Mendez-Hernandez
J. Clin. Med. 2025, 14(19), 6936; https://doi.org/10.3390/jcm14196936 - 30 Sep 2025
Abstract
Background: Glaucoma is a multifactorial optic neuropathy and the leading cause of irreversible blindness worldwide. Vascular mechanisms, including impaired perfusion of the optic nerve head, are increasingly recognized as contributors to disease progression. Optical coherence tomography angiography (OCTA) enables non-invasive assessment of retinal [...] Read more.
Background: Glaucoma is a multifactorial optic neuropathy and the leading cause of irreversible blindness worldwide. Vascular mechanisms, including impaired perfusion of the optic nerve head, are increasingly recognized as contributors to disease progression. Optical coherence tomography angiography (OCTA) enables non-invasive assessment of retinal and choroidal microvasculature, including peripapillary microvasculature dropout (MvD), which may serve as a marker of glaucomatous damage. Methods: A cross-sectional case–control study was conducted, including patients with primary open-angle glaucoma (OAG) and healthy controls. All participants underwent a comprehensive ophthalmic evaluation and OCTA imaging using the PLEX Elite 9000 system. Peripapillary vessel density (pVD), flow index (pFI), peripapillary choroidal thickness (PCT), β-zone parapapillary atrophy (β-PPA), and choroidal vascular indices were measured. MvD was defined as the complete absence of microvasculature within the β-PPA boundary. Statistical analyses included univariate and multivariate regression models to examine variables associated with PCT and to assess the association between MvD and visual field mean defect (MD), as well as other glaucoma characteristics. ROC curve analysis was performed to evaluate the ability of MvD to discriminate between different levels of visual field defects. Results: A total of 87 eyes (41 glaucomatous, 46 controls) were analyzed. Glaucoma patients exhibited significantly lower pVD, pFI, PCT, and choroidal vascular indices compared to the controls. MvD was detected in 10 glaucomatous eyes and was associated with a larger β-PPA area, smaller choroidal luminal and stromal areas, and worse mean deviation (MD) values. Multivariate regression showed that the number of ocular hypotensive treatments and StructureIndex variables were significantly associated with PCT (adjusted R2 = 0.14). Logistic regression analysis identified MD, MD slope, and β-PPA area as variables significantly associated with the presence of MvD. ROC analysis showed that the presence of MvD had good discriminatory ability for visual field mean defects (MDs) (AUC = 0.77, 95% CI: 0.69–0.87; p = 0.005). Conclusions: Peripapillary MvD detected by OCTA is associated with reduced choroidal vascularity, increased β-PPA, and greater visual field deterioration in glaucoma patients. MvD may serve as a structural marker associated with functional deterioration in glaucoma patients. Full article
(This article belongs to the Special Issue Clinical Advances in Glaucoma: Current Status and Prospects)
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20 pages, 1372 KB  
Article
A Novel Multi-Scale Entropy Approach for EEG-Based Lie Detection with Channel Selection
by Jiawen Li, Guanyuan Feng, Chen Ling, Ximing Ren, Shuang Zhang, Xin Liu, Leijun Wang, Mang I. Vai, Jujian Lv and Rongjun Chen
Entropy 2025, 27(10), 1026; https://doi.org/10.3390/e27101026 - 29 Sep 2025
Abstract
Entropy-based analyses have emerged as a powerful tool for quantifying the complexity, regularity, and information content of complex biological signals, such as electroencephalography (EEG). In this regard, EEG-based lie detection offers the advantage of directly providing more objective and less susceptible-to-manipulation results compared [...] Read more.
Entropy-based analyses have emerged as a powerful tool for quantifying the complexity, regularity, and information content of complex biological signals, such as electroencephalography (EEG). In this regard, EEG-based lie detection offers the advantage of directly providing more objective and less susceptible-to-manipulation results compared to traditional polygraph methods. To this end, this study proposes a novel multi-scale entropy approach by fusing fuzzy entropy (FE), time-shifted multi-scale fuzzy entropy (TSMFE), and hierarchical multi-band fuzzy entropy (HMFE), which enables the multidimensional characterization of EEG signals. Subsequently, using machine learning classifiers, the fused feature vector is applied to lie detection, with a focus on channel selection to investigate distinguished neural signatures across brain regions. Experiments utilize a publicly benchmarked LieWaves dataset, and two parts are performed. One is a subject-dependent experiment to identify representative channels for lie detection. Another is a cross-subject experiment to assess the generalizability of the proposed approach. In the subject-dependent experiment, linear discriminant analysis (LDA) achieves impressive accuracies of 82.74% under leave-one-out cross-validation (LOOCV) and 82.00% under 10-fold cross-validation. The cross-subject experiment yields an accuracy of 64.07% using a radial basis function (RBF) kernel support vector machine (SVM) under leave-one-subject-out cross-validation (LOSOCV). Furthermore, regarding the channel selection results, PZ (parietal midline) and T7 (left temporal) are considered the representative channels for lie detection, as they exhibit the most prominent occurrences among subjects. These findings demonstrate that the PZ and T7 play vital roles in the cognitive processes associated with lying, offering a solution for designing portable EEG-based lie detection devices with fewer channels, which also provides insights into neural dynamics by analyzing variations in multi-scale entropy. Full article
(This article belongs to the Special Issue Entropy Analysis of Electrophysiological Signals)
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12 pages, 7146 KB  
Article
Host Phylogeny Shapes Gut Microbiota and Predicted Functions in Captive Artiodactyls
by Guolei Sun, Tian Xia, Qinguo Wei, Xibao Wang, Yuehuan Dong, Xiufeng Yang, Lei Zhang, Weilai Sha and Honghai Zhang
Microorganisms 2025, 13(10), 2250; https://doi.org/10.3390/microorganisms13102250 - 25 Sep 2025
Abstract
Host phylogeny can imprint the gut microbiota, but it is often masked by diet and environment. Leveraging the standardized husbandry of a zoological collection, we profiled fecal microbiota from 55 captive artiodactyls representing 12 species in Bovidae, Cervidae, and Camelidae using 16S rRNA [...] Read more.
Host phylogeny can imprint the gut microbiota, but it is often masked by diet and environment. Leveraging the standardized husbandry of a zoological collection, we profiled fecal microbiota from 55 captive artiodactyls representing 12 species in Bovidae, Cervidae, and Camelidae using 16S rRNA amplicon sequencing targeting the V3–V4 region on the Illumina MiSeq platform. Community composition differed significantly among host families (Bray–Curtis PERMANOVA, R2 = 0.1075, p = 0.001). A host–microbiota tanglegram, which juxtaposes the host phylogeny with a dendrogram of microbiota similarity, recovered a topology congruent with the host phylogeny, with camelids forming a distinct branch separate from true ruminants in both trees. The linear discriminant analysis effect size (LEfSe; LDA ≥ 3.5) identified family-specific biomarkers, including enrichment of Acinetobacter/Moraxellaceae in Bovidae, Rikenellaceae (the Rikenellaceae_RC9_gut_group) in Cervidae, and Rummeliibacillus together with the Christensenellaceae_R-7_group in Camelidae. Functional inference with PICRUSt2 revealed significant differences in KEGG level-2 pathways (e.g., carbohydrate metabolism and xenobiotics biodegradation), consistent with taxonomic shifts. Altogether, these findings show that—even under uniform captive conditions—host evolutionary history remains a primary determinant of both the structure and the predicted functions of the artiodactyl gut microbiota, refining the scope of phylosymbiosis and providing actionable baselines for veterinary monitoring and conservation management in zoo settings. Full article
(This article belongs to the Section Gut Microbiota)
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22 pages, 7309 KB  
Article
Population Genomics and Genetic Diversity of Prosopis cineraria in the United Arab Emirates: Insights for Conservation in Arid Ecosystems
by Anestis Gkanogiannis, Salama Rashed Almansoori, Maher Kabshawi, Mohammad Shahid, Saif Almansoori, Hifzur Rahman and Augusto Becerra Lopez-Lavalle
Plants 2025, 14(19), 2970; https://doi.org/10.3390/plants14192970 - 25 Sep 2025
Abstract
Prosopis cineraria (L.) Druce is a keystone tree species in the arid and semi-arid regions of West and South Asia, with critical ecological, cultural, and conservation significance. In the United Arab Emirates (UAE) and other regions of the Arabian Peninsula, this beneficial tree [...] Read more.
Prosopis cineraria (L.) Druce is a keystone tree species in the arid and semi-arid regions of West and South Asia, with critical ecological, cultural, and conservation significance. In the United Arab Emirates (UAE) and other regions of the Arabian Peninsula, this beneficial tree is called Ghaf. Despite its importance, genomic resources and population-level diversity data for the tree remain limited. Here, we present the first comprehensive population genomics study of Ghaf based on whole-genome resequencing of 204 individual trees collected across the UAE. Following Single-Nucleotide Polymorphism (SNP) discovery and stringent filtering, we analyzed 57,183 high-quality LD-pruned SNPs to assess population structure, diversity, and gene flow. Principal component analysis (PCA), sparse non-negative matrix factorization (sNMF), and discriminant analysis of principal components (DAPC) revealed four well-defined genetic clusters, broadly corresponding to geographic origins. The genetic diversity varied significantly among the groups, with observed heterozygosity (Ho), inbreeding coefficients (F), and nucleotide diversity (π) showing strong population-specific trends. Genome-wide fixation index FST scans identified multiple highly differentiated genomic regions, enriched for genes involved in stress response, transport, and signaling. Functional enrichment using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Pfam annotations indicated overrepresentation of protein kinase activity, ATP binding, and hormone signaling pathways. TreeMix analysis revealed gene flow into one of the genetic clusters from both others, suggesting historical admixture and geographic connectivity. This work provides foundational insights into the population genomic profile of P. cineraria, supporting conservation planning, restoration strategies, and long-term genetic monitoring in arid ecosystems. Full article
(This article belongs to the Special Issue Genetic Diversity and Population Structure of Plants)
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18 pages, 636 KB  
Article
The Body, Gender, and Religious Practices: A Comparative Study of Daoist Inner Alchemy for Women and Buddhist Thoughts on the Female-to-Male Transformation
by Qiongke Geng
Religions 2025, 16(10), 1222; https://doi.org/10.3390/rel16101222 - 24 Sep 2025
Viewed by 140
Abstract
This article examines the concept of female-to-male transformation in Daoism inner alchemy for women (nüdan 女丹) and Buddhism, both of which have records of female practitioners and nuns being required to transform their bodies into men, such as “women change their bodies [...] Read more.
This article examines the concept of female-to-male transformation in Daoism inner alchemy for women (nüdan 女丹) and Buddhism, both of which have records of female practitioners and nuns being required to transform their bodies into men, such as “women change their bodies to become men” (nühuan nanti 女換男體) in nüdan and “transform a woman into a man”(nüzhuan nanshen 女轉男身) in Buddhism. When considering these literal meanings in isolation, this can be interpreted as suggesting that these religions uphold the superiority of the male body with its physical attributes over the female body. Women who practice religious meditation must be transgender to have the possibility of becoming a Daoist immortal or an enlightened Buddhist. But is this the case? This article employs an analytical approach to examine the interpretations of the transgender concept of “female-to-male transformation” in Daoist nüdan and Buddhism. The analysis reveals the metaphorical expressive function of this concept and thereby refutes the simplistic view that equates it with gender discrimination. The present paper reveals the profound differences and commonalities between nüdan and the Buddhist concept of “female-to-male transformation” through comparative analysis of their fundamental concepts, gender metaphors, and cultivation paths. The study demonstrates that while these two traditional systems address gender and transcendence differently, both provide women with diverse paths to spiritual liberation through their unique methods of cultivation. Full article
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12 pages, 1247 KB  
Review
Imaging Flow Cytometry as a Molecular Biology Tool: From Cell Morphology to Molecular Mechanisms
by Yoshikazu Matsuoka
Int. J. Mol. Sci. 2025, 26(19), 9261; https://doi.org/10.3390/ijms26199261 - 23 Sep 2025
Viewed by 149
Abstract
Insights into the state of individual cells within a living organism are essential for identifying diseases and abnormalities. The internal state of a cell is reflected in its morphological features and changes in the localization of intracellular molecules. Using this information, it is [...] Read more.
Insights into the state of individual cells within a living organism are essential for identifying diseases and abnormalities. The internal state of a cell is reflected in its morphological features and changes in the localization of intracellular molecules. Using this information, it is possible to infer the state of the cells with high precision. In recent years, technological advancements and improvements in instrument specifications have made large-scale analyses, such as single-cell analysis, more widely accessible. Among these technologies, imaging flow cytometry (IFC) is a high-throughput imaging platform that can simultaneously acquire information from flow cytometry (FCM) and cellular images. While conventional FCM can only obtain fluorescence intensity information corresponding to each detector, IFC can acquire multidimensional information, including cellular morphology and the spatial arrangement of proteins, nucleic acids, and organelles for each imaging channel. This enables the discrimination of cell types and states based on the localization of proteins and organelles, which is difficult to assess accurately using conventional FCM. Because IFC can acquire a large number of single-cell morphological images in a short time, it is well suited for automated classification using machine learning. Furthermore, commercial instruments that combine integrated imaging and cell sorting capabilities have recently become available, enabling the sorting of cells based on their image information. In this review, we specifically highlight practical applications of IFC in four representative areas: cell cycle analysis, protein localization analysis, immunological synapse formation, and the detection of leukemic cells. In addition, particular emphasis is placed on applications that directly contribute to elucidating molecular mechanisms, thereby distinguishing this review from previous general overviews of IFC. IFC enables the estimation of cell cycle phases from large numbers of acquired cellular images using machine learning, thereby allowing more precise cell cycle analysis. Moreover, IFC has been applied to investigate intracellular survival and differentiation signals triggered by external stimuli, to monitor DNA damage responses such as γH2AX foci formation, and more recently, to detect immune synapse formation among interacting cells within large populations and to analyze these interactions at the molecular level. In hematological malignancies, IFC combined with fluorescence in situ hybridization (FISH) enables high-throughput detection of chromosomal abnormalities, such as BCR-ABL1 translocations. These advances demonstrate that IFC provides not only morphological and functional insights but also clinically relevant genomic information at the single-cell level. By summarizing these unique applications, this review aims to complement existing publications and provide researchers with practical insights into how IFC can be implemented in both basic and translational research. Full article
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11 pages, 376 KB  
Article
Clinical Characteristics and Risk Factors for Severe Exacerbation in Never-Smokers with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study
by Josep Montserrat-Capdevila, Pilar Vaqué Castilla, Yoseba Cánovas Zaldúa, Francesc Alòs, Joan Deniel-Rosanas, Pere Simonet, Pau Olivares-Sanzo, Jennyfer Jiménez Díaz, Sandra Moreno Garcia, Araceli Fuentes, Eugeni Paredes and Pere Godoy
Healthcare 2025, 13(18), 2374; https://doi.org/10.3390/healthcare13182374 - 22 Sep 2025
Viewed by 252
Abstract
Background: Chronic obstructive pulmonary disease (COPD) in nonsmokers is increasingly recognized, yet its clinical profile and outcomes remain less well defined compared to smoking-related COPD. The aim of this study was to compare the clinical characteristics, comorbidities, and risk factors associated with severe [...] Read more.
Background: Chronic obstructive pulmonary disease (COPD) in nonsmokers is increasingly recognized, yet its clinical profile and outcomes remain less well defined compared to smoking-related COPD. The aim of this study was to compare the clinical characteristics, comorbidities, and risk factors associated with severe exacerbations in nonsmoking COPD patients versus smokers. Methods: We conducted a prospective cohort study including 2376 patients with a diagnosis of COPD from the Lleida Health Region (Catalonia, Spain). Patients were followed for 2 years (2021–2022). Severe exacerbation was defined as hospital admission due to worsening COPD symptoms. Clinical variables were collected at baseline, and logistic regression analysis was performed to identify risk factors for severe exacerbation in the COPD-NS subgroup. Results: A total of 2376 COPD patients were included, of whom 966 (40.7%) were never-smokers. During the two-year follow-up, 165 patients (6.9%) required hospitalization for a severe exacerbation, nearly half of whom were never-smokers (48.5%). In multivariate analysis restricted to COPD never-smokers, the following independent predictors of hospitalization were identified: atrial fibrillation (OR: 2.35; 95% CI: 1.37–3.93), bronchiectasis (OR: 1.91; 95% CI: 1.08–3.28), and lower lung function measured by FVC (OR: 0.64; 95% CI: 0.45–0.89) and FEV1/FVC ratio (OR: 0.64; 95% CI: 0.45–0.89). Female gender was associated with a lower risk (OR: 0.44; 95% CI: 0.21–0.88). The predictive model demonstrated moderate discrimination (AUC = 0.71). Conclusions: COPD-NS patients represent a large proportion of the COPD population and present distinct clinical features. Although the incidence of severe exacerbation is similar to that of smokers/ex-smokers, risk factors such as atrial fibrillation and bronchiectasis have a stronger impact in this subgroup. Early identification of these factors may help guide more targeted clinical management strategies. Full article
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21 pages, 874 KB  
Article
Genetic Variants in Cytokines IL-10 and IL-17A Are Associated with the Risk and Severity of Sporadic Parkinson’s Disease in Mexican Patients
by Nancy Monroy-Jaramillo, Alberto Ortega-Vázquez, Marisol López-López and Laura Virginia Adalid-Peralta
Life 2025, 15(9), 1480; https://doi.org/10.3390/life15091480 - 20 Sep 2025
Viewed by 273
Abstract
Background/Objective: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, in which the inflammatory hypothesis posits that dysregulation of the immune system is an important factor in its etiology. Based on our previous findings, we aimed to explore if promoter functional genetic [...] Read more.
Background/Objective: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, in which the inflammatory hypothesis posits that dysregulation of the immune system is an important factor in its etiology. Based on our previous findings, we aimed to explore if promoter functional genetic variants in cytokines encoded by IL-10 and IL-17A, and a coding variant in the IL-13 gene, confer risk to the inflammatory profile of PD patients. Methods: For population genetic purposes, DNA samples from 239 patients with sporadic PD and 84 healthy controls were included and genotyped for IL-10_rs1800896, IL-10_rs1800872, IL-13_rs20541, IL-17A_rs2275913, and IL-17_rs8193036 variants by allelic discrimination in real-time PCR. All participants were Mexican Mestizos (MMs). Gene frequencies and haplotype association analyses were assessed. Then, a subgroup of 26 untreated PD patients and 21 controls were selected from this cohort for detailed biochemical and clinical data and evaluated by multivariate correlation analysis at the baseline and one year post-dopaminergic replacement treatment. Results and Conclusions: IL-17A_rs8193036 was found to be associated with increased PD risk (p < 0.010, OR = 1.91, CI95% = 1.22–2.98). The genetic variants IL-10_rs1800896, IL-10_rs1800872, and IL_17A_rs8193036 were related to the inflammatory process in sporadic MM PD patients, suggesting that they may play potential roles in the development and severity of the disease. Full article
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16 pages, 4747 KB  
Article
Divergent Morphologies and Common Signaling Features of Active and Inactive Oncogenic RHOA Mutants in Yeast
by Chenwei Wang, Shinsuke Ohnuki, Anna Savchenko, Hiroyuki Aburatani, Satoshi Yoshida, Riko Hatakeyama and Yoshikazu Ohya
Cells 2025, 14(18), 1439; https://doi.org/10.3390/cells14181439 - 15 Sep 2025
Viewed by 242
Abstract
RHOA, a member of the Rho family of small GTPases, harbors recurrent mutations in diverse cancers, but how these mutations cause their cellular effects remains poorly understood. To investigate their cellular consequences, we expressed oncogenic RHOA variants (R5Q, G17V, C16R, and A161P) [...] Read more.
RHOA, a member of the Rho family of small GTPases, harbors recurrent mutations in diverse cancers, but how these mutations cause their cellular effects remains poorly understood. To investigate their cellular consequences, we expressed oncogenic RHOA variants (R5Q, G17V, C16R, and A161P) in Saccharomyces cerevisiae, substituting for the essential yeast homologue RHO1. While the E40Q variant failed to complement RHO1 deletion, other mutants supported viability and enabled phenotypic characterization. All four variants conferred myriocin resistance, suggesting activation of the membrane stress response pathway, but induced no major changes in growth or caspofungin sensitivity. Using high-dimensional image analysis, we quantified 501 morphological parameters and applied principal component analysis and linear discriminant analysis to determine distinct phenotypic profiles. Gain-of-function (C16R and A161P) and loss-of-function (R5Q and G17V) mutants formed separate morphological clusters, indicating functional divergence. Our yeast model enabled systematic dissection of the functions of RHOA mutants and highlighted the utility of morphology-based approaches to characterize context-dependent mechanisms of oncogenesis. Full article
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18 pages, 1265 KB  
Article
Genomic Variants, Transcriptomic Profile, Ultrasonographic Findings, and Antioxidant and Immunological Biomarkers Linked to Pregnancy Toxemia Susceptibility in Goats
by Ahmed El-Sayed, Mohamed Marzok, Huda A. Alqahtani, Amin Tahoun, Adel I. Almubarak, Rasha Yassin Elkhidr, Zakriya Al Mohamed, Elshymaa A. Abdelnaby, Hussein Babiker, Hanan M. Alharbi, Khairiah M. Alwutayd and Ahmed Ateya
Vet. Sci. 2025, 12(9), 891; https://doi.org/10.3390/vetsci12090891 - 15 Sep 2025
Viewed by 419
Abstract
Pregnancy toxemia (PT) represents a significant metabolic disorder affecting small ruminants that causes substantial economic losses due to reduced productivity, reproductive failure, and high mortality. This study investigated the clinical, ultrasonographic, hematobiochemical, oxidative stress, and immunological profiles, as well as the gene expression [...] Read more.
Pregnancy toxemia (PT) represents a significant metabolic disorder affecting small ruminants that causes substantial economic losses due to reduced productivity, reproductive failure, and high mortality. This study investigated the clinical, ultrasonographic, hematobiochemical, oxidative stress, and immunological profiles, as well as the gene expression and nucleotide sequence variations, associated with PT susceptibility in Shami goats. Fifty late-pregnant does (33 healthy and 17 PT-affected) were examined. Clinical evaluation, complete blood count, biochemical analysis, cytokine profiling, antioxidant assays, hepatic ultrasonography, quantitative real-time PCR of immune (IL6, IL8), antioxidant (SOD3, HMOX1), and lipogenic (ACACA, FASN) genes, and PCR-DNA sequencing were performed. PT does exhibit significant hypoglycemia, hyperketonemia, elevated liver and kidney function biomarkers, dyslipidemia, oxidative stress (↑ MDA, ↓ GSH, GPx, SOD, CAT), increased pro-inflammatory cytokines (IL1α, IL1β, IL6, TNFα), and reduced IL10. Gene expression analysis revealed upregulation of IL6 and IL8 and downregulation of SOD3, HMOX1, ACACA, and FASN in PT does. Sequencing identified multiple synonymous and non-synonymous SNPs significantly associated with PT. Ultrasonography indicated hepatic fatty infiltration. Discriminant analysis using SNPs achieved 100% classification accuracy between healthy and PT does. These findings suggested that combined clinical, biochemical, oxidative, immunological, and genetic markers could enhance early PT diagnosis and may provide a basis for future studies aimed at selective breeding for improved resistance. Full article
(This article belongs to the Special Issue Molecular Markers in Ruminant Reproduction)
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21 pages, 1391 KB  
Article
Global Longitudinal Strain as a Sensitive Marker of Left Ventricular Dysfunction in Pediatric Dilated Cardiomyopathy: A Case–Control Study
by Iolanda Muntean, Beatrix-Jullia Hack and Asmaa Carla Hagau
J. Cardiovasc. Dev. Dis. 2025, 12(9), 351; https://doi.org/10.3390/jcdd12090351 - 12 Sep 2025
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Abstract
Pediatric dilated cardiomyopathy (DCM) is a rare but important cause of heart failure (HF) and a major indication for cardiac transplantation. Early detection of subclinical myocardial dysfunction is essential for risk stratification and management. This study aimed to evaluate left ventricular (LV) systolic [...] Read more.
Pediatric dilated cardiomyopathy (DCM) is a rare but important cause of heart failure (HF) and a major indication for cardiac transplantation. Early detection of subclinical myocardial dysfunction is essential for risk stratification and management. This study aimed to evaluate left ventricular (LV) systolic function in children with DCM using conventional echocardiographic parameters and speckle-tracking echocardiography (STE) and to explore the relationship between deformation indices, clinical severity and biomarkers. Methods: We conducted a case–control study including 29 children diagnosed with DCM and 27 healthy controls matched by age and sex. All participants underwent clinical evaluation, NT-proBNP measurement, and transthoracic echocardiography. LV systolic function was assessed using conventional echocardiographic parameters, while STE was used to measure LV global longitudinal strain (GLS) and strain rate (SR) from all apical views. Results: GLS and SR were significantly reduced in the DCM group across all apical views (Global GLS: −11.13 ± 6.79% vs. −19.98 ± 3.25%, Global SR: −0.74 ± 0.39 s−1 vs. −1.12 ± 0.16 s−1; p < 0.01). GLS strongly correlated with functional indices (LV ejection fraction, shortening fraction, S′ lateral wave), LV end-diastolic diameter Z-score and NT-proBNP (p < 0.05), but not with MAPSE. In the primary model, GLS was associated with NYHA/Ross III–IV (OR 1.54 per 1% increase; 95% CI 1.14–2.07; p = 0.005); adding systolic blood pressure (p = 0.798) or heart rate (p = 0.973) did not materially change the GLS estimate (Δ ≤ 2%). In separate collinearity-avoiding models, LVEF (OR 1.12 per 1% decrease; 95% CI 1.03–1.22; p = 0.009), LVSF (OR 1.19 per 1% decrease; 95% CI 1.04–1.36; p = 0.011), and NT-proBNP (≈OR 1.11 per 100 units; p = 0.013) were also associated with advanced class. ROC analysis showed excellent discrimination for NT-proBNP (AUC 0.948) and GLS (AUC 0.906), and good–excellent performance for LVEF (AUC 0.869) and LVSF (AUC 0.875). Conclusions: Speckle-tracking derived parameters such as GLS and SR are sensitive and clinically relevant markers of LV dysfunction in pediatric DCM. Global longitudinal strain demonstrated a strong association with both clinical and biochemical markers of disease severity, after accounting for heart rate and blood pressure, supporting its integration into routine evaluation and risk stratification in pediatric DCM. Full article
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26 pages, 3019 KB  
Article
Energy Analysis, Soliton Dynamics, Chaos, and Sensitivity Analysis for a Forced Damped Gardner Model
by Syed T. R. Rizvi, Atef F. Hashem, Aiman Shahbaz, Zunaira Iqbal, Ijaz Ali, A. S. Al-Moisheer and Aly R. Seadawy
Symmetry 2025, 17(9), 1529; https://doi.org/10.3390/sym17091529 - 12 Sep 2025
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Abstract
In this study, the complete discrimination system for the polynomial method (CDSPM) is employed to analyze the integrable Gardner Equation (IGE). Through a traveling wave transformation, the model is reduced to a nonlinear ordinary differential equation, enabling the derivation of a wide class [...] Read more.
In this study, the complete discrimination system for the polynomial method (CDSPM) is employed to analyze the integrable Gardner Equation (IGE). Through a traveling wave transformation, the model is reduced to a nonlinear ordinary differential equation, enabling the derivation of a wide class of exact solutions, including trigonometric, hyperbolic, rational, and Jacobi elliptic functions. For example, a bright soliton solution is obtained for parameters A=1.3, β=0.1, and γ=0.8. Qualitative analysis reveals diverse phase portraits, indicating the presence of saddle points, centers, and cuspidal points depending on parameter values. Chaos and quasi-periodic dynamics are investigated via Poincaré maps and time-series analysis, where chaotic patterns emerge for values like ν1=1.45, ν2=2.18, Ξ0=4, and λ=2π. Sensitivity analysis confirms the model’s sensitivity to initial conditions χ=2.2,2.4,2.6, reflecting real-world unpredictability. Additionally, the energy balance method (EBM) is applied to approximate periodic solutions by conserving kinetic and potential energies. These results highlight the IGE’s ability to capture complex nonlinear behaviors relevant to fluid dynamics, plasma waves, and nonlinear optics. Full article
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