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11 pages, 2066 KiB  
Article
Force Profile Characteristics of Gravitational and Pneumatic Resistances in Pull and Push Exercises
by Manuel Barba-Ruiz, Juan Ramón Heredia-Elvar, Adrián Martín-Castellanos, Javier Iglesias-García and Francisco Hermosilla-Perona
Sports 2025, 13(8), 239; https://doi.org/10.3390/sports13080239 - 22 Jul 2025
Viewed by 184
Abstract
Introduction: Strength training, essential for health and performance, often uses free weights for greater stabilization demands and pulleys for easier load adjustment and progression. Methods: The aim of the study was to analyze the differences in force application using gravitational and pneumatic resistances. [...] Read more.
Introduction: Strength training, essential for health and performance, often uses free weights for greater stabilization demands and pulleys for easier load adjustment and progression. Methods: The aim of the study was to analyze the differences in force application using gravitational and pneumatic resistances. Twenty experienced subjects participated in the study (age: 21.9 ± 3.8 years; body mass: 76.3 ± 9.4 kg; height: 177.4 ± 7.5 cm), performing four exercises with each type of resistance: bench press, lat pulldown, chest fly, and single-arm row. The participants performed 8 repetitions per exercise. Peak and mean force were measured with a 100 Hz load cell (SUIFF S2 Pro) during the concentric phase of the lifts. Differences between resistance types were analyzed using one-way ANOVA and paired t-tests. Results: Peak force was higher with gravitational resistance across all exercises (p < 0.001; d = 2.1–4.7). Average force with gravitational resistance was also higher in the bench press and lat pulldown (p < 0.05; d = 0.7–1.4), but not in the chest fly or single-arm row. Conclusions: Gravitational resistance may better enhance peak strength, while pneumatic resistance supports consistent force and neuromuscular control. These results allow us to select the resistance type based on specific mechanical characteristics. Full article
(This article belongs to the Special Issue Biomechanics and Sports Performances (2nd Edition))
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20 pages, 1106 KiB  
Article
Synchrotron-Based Structural Analysis of Nanosized Gd2(Ti1−xZrx)2O7 for Radioactive Waste Management
by Marco Pinna, Andrea Trapletti, Claudio Minelli, Armando di Biase, Federico Bianconi, Michele Clemente, Alessandro Minguzzi, Carlo Castellano and Marco Scavini
Nanomaterials 2025, 15(14), 1134; https://doi.org/10.3390/nano15141134 - 21 Jul 2025
Viewed by 222
Abstract
Complex oxides with the general formula Gd2(Ti1−xZrx)2O7 are promising candidates for radioactive waste immobilization due to their capacity to withstand radiation by dissipating part of the free energy driving defect creation and phase transitions. [...] Read more.
Complex oxides with the general formula Gd2(Ti1−xZrx)2O7 are promising candidates for radioactive waste immobilization due to their capacity to withstand radiation by dissipating part of the free energy driving defect creation and phase transitions. In this study, samples with varying zirconium content (xZr = 0.00, 0.15, 0.25, 0.375, 0.56, 0.75, 0.85, 1.00) were synthesized via the sol–gel method and thermally treated at 500 °C to obtain nanosized powders mimicking the defective structure of irradiated materials. Synchrotron-based techniques were employed to investigate their structural properties: High-Resolution X-ray Powder Diffraction (HR-XRPD) was used to assess long-range structure, while Pair Distribution Function (PDF) analysis and Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy provided insights into the local structure. HR-XRPD data revealed that samples with low Zr content (xZr ≤ 0.25) are amorphous. Increasing Zr concentration led to the emergence of a crystalline phase identified as defective fluorite (xZr = 0.375, 0.56). Samples with the highest Zr content (xZr ≥ 0.75) were fully crystalline and exhibited only the fluorite phase. The experimental G(r) functions of the fully crystalline samples in the low r range are suitably fitted by the Weberite structure, mapping the relaxations induced by structural disorder in defective fluorite. These structural insights informed the subsequent EXAFS analysis at the Zr-K and Gd-L3 edges, confirming the splitting of the cation–cation distances associated with different metal species. Moreover, EXAFS provided a local structural description of the amorphous phases, identifying a consistent Gd-O distance across all compositions. Full article
(This article belongs to the Section Physical Chemistry at Nanoscale)
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12 pages, 1344 KiB  
Article
Transcriptomic Profiling of Paired Primary Tumors and CNS Metastases in Breast Cancer Reveals Immune Modulation Signatures
by Ana Julia Aguiar de Freitas, Muriele Bertagna Varuzza, Stéphanie Calfa, Rhafaela Lima Causin, Vinicius Duval da Silva, Cristiano de Pádua Souza and Márcia Maria Chiquitelli Marques
Int. J. Mol. Sci. 2025, 26(14), 6944; https://doi.org/10.3390/ijms26146944 - 19 Jul 2025
Viewed by 247
Abstract
Breast cancer is a leading cause of central nervous system (CNS) metastases in women, often associated with poor prognosis and limited therapeutic options. However, molecular differences between primary tumors and CNS metastases remain underexplored. We aimed to characterize transcriptomic differences between primary breast [...] Read more.
Breast cancer is a leading cause of central nervous system (CNS) metastases in women, often associated with poor prognosis and limited therapeutic options. However, molecular differences between primary tumors and CNS metastases remain underexplored. We aimed to characterize transcriptomic differences between primary breast tumors and matched CNS metastases and identify immune-related biomarkers associated with metastatic progression and patient outcomes. Transcriptomic profiling was based on 11 matched FFPE sample pairs (primary tumor and CNS metastasis). Paired formalin-fixed paraffin-embedded (FFPE) samples from primary tumors (T1) and CNS metastases (T2) were analyzed using the NanoString nCounter® platform and the PanCancer IO 360™ Gene Expression Panel. Differential gene expression, Z-score transformation, and heatmap visualization were performed in R. In silico survival analyses for overall survival (OS) and recurrence-free survival (RFS) were conducted using publicly available TCGA and GEO datasets. Forty-five genes were significantly differentially expressed between the T1 and T2 samples. Immune-related genes such as CXCL9, IL7R, CD79A, and CTSW showed consistent downregulation in CNS metastases. High expression of CXCL9 and CD79A was associated with improved OS and RFS, whereas high IL7R and CTSW expression correlated with worse outcomes. These findings indicate immune suppression as a hallmark of CNS colonization. Comparative transcriptomic analysis further underscored the distinct molecular landscapes between primary and metastatic tumors. This study highlights transcriptional signatures associated with breast cancer CNS metastases, emphasizing the role of immune modulation in metastatic progression. The identified genes have potential as prognostic biomarkers and therapeutic targets, supporting the need for site-specific molecular profiling in metastatic breast cancer management. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Brazil, 3rd Edition)
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16 pages, 4588 KiB  
Article
CTC-537E7.3 as a Liver-Specific Biomarker for Hepatocellular Carcinoma: Diagnostic and Prognostic Implications
by Hyung Seok Kim, Se Ha Jang, Geum Ok Baek, Moon Gyeong Yoon, Jaewon Shim, Ji Eun Han, Soon Sun Kim, Jae Youn Cheong and Jung Woo Eun
Curr. Issues Mol. Biol. 2025, 47(7), 563; https://doi.org/10.3390/cimb47070563 - 18 Jul 2025
Viewed by 266
Abstract
Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with [...] Read more.
Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with CTC-537E7.3 expression lost in 95% of cases (*** p < 0.0001). It demonstrated excellent diagnostic performance in discriminating tumor from non-tumor tissue (AUC = 0.95), which was maintained in early-stage (I/II) disease. Low CTC-537E7.3 expression correlated with shorter overall and disease-free survival and was inversely associated with serum α-fetoprotein (AFP) levels, highlighting its complementary clinical value. Mechanistic investigation revealed a potential competing endogenous RNA (ceRNA) axis. The microRNA miR-190b-5p was highly expressed in tumors and predicted to bind CTC-537E7.3, while its target, PLGLB1, was significantly suppressed. Survival analysis confirmed that concurrent high expression of CTC-537E7.3 and PLGLB1 conferred superior outcomes. These findings establish CTC-537E7.3 as a liver-specific, ceRNA-mediated tumor suppressor with robust diagnostic and prognostic potential. It represents a promising adjunct to existing HCC surveillance strategies, such as ultrasound and AFP measurement, for high-risk populations. Full article
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31 pages, 4652 KiB  
Article
A Delayed Malware Propagation Model Under a Distributed Patching Mechanism: Stability Analysis
by Wei Zhang, Xiaofan Yang and Luxing Yang
Mathematics 2025, 13(14), 2266; https://doi.org/10.3390/math13142266 - 14 Jul 2025
Viewed by 147
Abstract
Antivirus (patch) is one of the most powerful tools for defending against malware spread. Distributed patching is superior to its centralized counterpart in terms of significantly lower bandwidth requirement. Under the distributed patching mechanism, a novel malware propagation model with double delays and [...] Read more.
Antivirus (patch) is one of the most powerful tools for defending against malware spread. Distributed patching is superior to its centralized counterpart in terms of significantly lower bandwidth requirement. Under the distributed patching mechanism, a novel malware propagation model with double delays and double saturation effects is proposed. The basic properties of the model are discussed. A pair of thresholds, i.e., the first threshold R0 and the second threshold R1, are determined. It is shown that (a) the model admits no malware-endemic equilibrium if R01, (b) the model admits a unique patch-free malware-endemic equilibrium and admits no patch-endemic malware-endemic equilibrium if 1<R0R1, and (c) the model admits a unique patch-free malware-endemic equilibrium and a unique patch-endemic malware-endemic equilibrium if R0>R1. A criterion for the global asymptotic stability of the malware-free equilibrium is given. A pair of criteria for the local asymptotic stability of the patch-free malware-endemic equilibrium are presented. A pair of criteria for the local asymptotic stability of the patch-endemic malware-endemic equilibrium are derived. Using cybersecurity terms, these theoretical outcomes have the following explanations: (a) In the case where the first threshold can be kept below unity, the malware can be eradicated through distributed patching. (b) In the case where the first threshold can only be kept between unity and the second threshold, the patches may fail completely, and the malware cannot be eradicated through distributed patching. (c) In the case where the first threshold cannot be kept below the second threshold, the patches may work permanently, but the malware cannot be eradicated through distributed patching. The influence of the delays and the saturation effects on malware propagation is examined experimentally. The relevant conclusions reveal the way the delays and saturation effects modulate these outcomes. Full article
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16 pages, 2487 KiB  
Article
Overexpression of Circular PRMT1 Transcripts in Colorectal Adenocarcinoma Predicts Recurrence and Poor Overall Survival
by Panagiotis Kokoropoulos, Spyridon Christodoulou, Panagiotis Tsiakanikas, Panteleimon Vassiliu, Christos K. Kontos and Nikolaos Arkadopoulos
Int. J. Mol. Sci. 2025, 26(14), 6683; https://doi.org/10.3390/ijms26146683 - 11 Jul 2025
Viewed by 205
Abstract
Colorectal cancer (CRC) is one of the most prevalent and deadly neoplasms globally; this fact puts emphasis on the need for accurate molecular biomarkers for early detection and accurate prognosis. Circular RNAs (circRNAs) have recently emerged as very promising cancer biomarkers. In this [...] Read more.
Colorectal cancer (CRC) is one of the most prevalent and deadly neoplasms globally; this fact puts emphasis on the need for accurate molecular biomarkers for early detection and accurate prognosis. Circular RNAs (circRNAs) have recently emerged as very promising cancer biomarkers. In this study, we thoroughly examined whether the expression levels of circular transcripts of the protein arginine methyltransferase 1 (PRMT1) gene can predict the prognosis of patients diagnosed with colorectal adenocarcinoma, the most frequent type of CRC. Hence, a highly sensitive quantitative PCR (qPCR) assay was developed and applied to quantify circ-PRMT1 expression in cDNAs from 210 primary colorectal adenocarcinoma tissue specimens and 86 paired normal colorectal mucosae. Extensive biostatistical analysis was then performed to assess the potential prognostic power of circ-PRMT1. Significant overexpression of this molecule was observed in colorectal adenocarcinoma tissue samples in contrast to their non-cancerous counterparts. Moreover, higher circ-PRMT1 expression was correlated with poorer disease-free survival (DFS) and worse overall survival (OS) in colorectal adenocarcinoma patients. Interestingly, multivariate Cox regression analysis revealed that the prognostic value of the expression of this circRNA does not depend on other established prognostic factors included in the prognostic model. Furthermore, the stratification of patients based on TNM staging revealed that higher circ-PRMT1 levels were significantly related to shorter DFS and OS intervals, particularly in patients with colorectal adenocarcinoma of TNM stage II or III. In summary, this original research study provides evidence that circ-PRMT1 overexpression represents a promising molecular biomarker of poor prognosis in colorectal adenocarcinoma, not depending on other established prognostic factors such as TNM staging. Full article
(This article belongs to the Special Issue New Molecular Aspects of Colorectal Cancer)
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13 pages, 2944 KiB  
Article
Milking the Orchil: How the Presence of Goat Milk in the Orchil Dyebath May Affect the Color of Dyed Wool
by Isabella Whitworth, Victor J. Chen and Gregory D. Smith
Heritage 2025, 8(7), 272; https://doi.org/10.3390/heritage8070272 - 9 Jul 2025
Viewed by 286
Abstract
Among the craft recipes for artisans collected in the 4th-century Egyptian documents the Leyden and Stockholm papyri, there is one calling for adding animal milk to orchil for wool dyeing. To understand the rationale for this practice, wool yarns were dyed with and [...] Read more.
Among the craft recipes for artisans collected in the 4th-century Egyptian documents the Leyden and Stockholm papyri, there is one calling for adding animal milk to orchil for wool dyeing. To understand the rationale for this practice, wool yarns were dyed with and without goat milk added to orchil dyebaths, each made using lichens from three different sources. The results showed orchil containing milk dyed yarns a noticeably deeper red hue. The colorants extracted from the dyed yarns were analyzed by liquid chromatography-diode-array-detector-mass spectrometry to assess the relative amounts of nine identifiable orceins. The data showed that the yarns dyed with milk gave extracts exhibiting several fold more α-aminoorcein and α-hydroxyorcein, with only small differences in the other seven. Scanning electron microscopic analysis of a representative pair of dyed yarns showed that milk promoted surface changes in the fiber that may indicate increased cutaneous damage. Hypotheses for the milk’s effects on orchil dyeing were proposed that included the formation of milk–protein complexes with the two enriched orceins that possibly enhanced wool binding and/or better wool uptake of free and/or complexed orceins due to biodegradation of the wool’s surface cuticle caused by microbial growth promoted by the addition of milk. Full article
(This article belongs to the Special Issue Dyes in History and Archaeology 43)
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33 pages, 5024 KiB  
Article
An Enhanced Dynamic Model of a Spatial Parallel Mechanism Receiving Direct Constraints from the Base at Two Point-Contact Higher Kinematic Pairs
by Chen Cheng, Xiaojing Yuan and Yenan Li
Biomimetics 2025, 10(7), 437; https://doi.org/10.3390/biomimetics10070437 - 3 Jul 2025
Viewed by 326
Abstract
In this paper, a biologically congruent parallel mechanism (PM) inspired by the masticatory system of human beings has been proposed to recreate complete chewing behaviours in three-dimensional space. The mechanism is featured by direct constraints from the base (DCFB) to its end effector [...] Read more.
In this paper, a biologically congruent parallel mechanism (PM) inspired by the masticatory system of human beings has been proposed to recreate complete chewing behaviours in three-dimensional space. The mechanism is featured by direct constraints from the base (DCFB) to its end effector at two higher kinematic pairs (HKPs), which greatly raise its topological complexity. Meanwhile, friction effects occur at HKPs and actuators, causing wear and then reducing motion accuracy. Regarding these, an inverse dynamic model that can raise the computational efficiency and the modelling fidelity is proposed, being prepared to be applied to realise accurate real-time motion and/or force control. In it, Euler parameters are employed to express the motions of the constrained end effector, and Newton–Euler’s law is applied, which can conveniently incorporate friction effects at both HKPs and actuators into the dynamic model. Numerical results show that the time consumption of the model using Euler parameters is only approximately 23% of that of the model using Euler angles, and friction effects significantly increase the model’s nonlinearity. Further, from the comparison between the models of the target PM and its counterpart free of DCFB, these constraints sharply raise the modelling complexity in terms of the transformation between Euler parameters and Euler angles in the end effector and the computational cost of inverse dynamics. Full article
(This article belongs to the Special Issue Recent Advances in Bioinspired Robot and Intelligent Systems)
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12 pages, 839 KiB  
Article
Iterative Solver of the Wet-Bed Step Riemann Problem
by Renyi Xu and Alistair G. L. Borthwick
Water 2025, 17(13), 1994; https://doi.org/10.3390/w17131994 - 2 Jul 2025
Viewed by 182
Abstract
This study presents a one-dimensional solver of the shallow water equations designed for the wet-bed step Riemann problem. Nonlinear mass and momentum equations incorporating shock and rarefaction waves in a straight one-dimensional channel are expressed as a pair of equations that depend solely [...] Read more.
This study presents a one-dimensional solver of the shallow water equations designed for the wet-bed step Riemann problem. Nonlinear mass and momentum equations incorporating shock and rarefaction waves in a straight one-dimensional channel are expressed as a pair of equations that depend solely on local depth values either side of the step. These unified equations are uniquely designed for the four conditions involving shock and rarefaction waves that can occur in the Step Riemann Problem. The Levenberg–Marquardt method is used to solve these simplified nonlinear equations. Four verification tests are considered for shallow free surface flow in a wet-bed channel with a step. These cases involve two rarefactions, opposing shock-like hydraulic bores, and a rarefaction and shock-like bore. The numerical predictions are in close agreement with existing theory, demonstrating that the method is very effective at solving the wet-bed step Riemann problem. Full article
(This article belongs to the Special Issue Hydraulics and Hydrodynamics in Fluid Machinery, 2nd Edition)
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26 pages, 11861 KiB  
Article
Convection in a Rapidly Rotating Spherical Shell: Newton’s Method Using Implicit Coriolis Integration
by Juan Cruz Gonzalez Sembla, Camille Rambert, Fred Feudel and Laurette S. Tuckerman
Mathematics 2025, 13(13), 2113; https://doi.org/10.3390/math13132113 - 27 Jun 2025
Viewed by 386
Abstract
Geophysical flows are characterized by rapid rotation. Simulating these flows requires small timesteps to achieve stability and accuracy. Numerical stability can be greatly improved by the implicit integration of the terms that are most responsible for destabilizing the numerical scheme. We have implemented [...] Read more.
Geophysical flows are characterized by rapid rotation. Simulating these flows requires small timesteps to achieve stability and accuracy. Numerical stability can be greatly improved by the implicit integration of the terms that are most responsible for destabilizing the numerical scheme. We have implemented an implicit treatment of the Coriolis force in a rotating spherical shell driven by a radial thermal gradient. We modified the resulting timestepping code to carry out steady-state solving via Newton’s method, which has no timestepping error. The implicit terms have the effect of preconditioning the linear systems, which can then be rapidly solved by a matrix-free Krylov method. We computed the branches of rotating waves with azimuthal wavenumbers ranging from 4 to 12. As the Ekman number (the non-dimensionalized inverse rotation rate) decreases, the flows are increasingly axially independent and localized near the inner cylinder, in keeping with well-known theoretical predictions and previous experimental and numerical results. The advantage of the implicit over the explicit treatment also increases dramatically with decreasing Ek, reducing the cost of computation by as much as a factor of 20 for Ekman numbers of order of 105. We carried out continuation for both the Rayleigh and Ekman numbers and obtained interesting branches in which the drift velocity remained unchanged between pairs of saddle–node bifurcations. Full article
(This article belongs to the Special Issue Numerical Simulation and Methods in Computational Fluid Dynamics)
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12 pages, 1739 KiB  
Article
Local T-Cell Dysregulation and Immune Checkpoint Expression in Human Papillomavirus-Mediated Recurrent Respiratory Papillomatosis
by Hans N. C. Eckel, Su Ir Lyu, Frederik Faste, Shachi J. Sharma, Anne Nobis, Nora Wuerdemann, Maria Ziogas, Marcel Mayer, Malte C. Suchan, Kerstin Wennhold, Maria A. Garcia-Marquez, Martin Thelen, Elena Hagen, Julia Eßer, Charlotte Klasen, Oliver Siefer, Martin Otte, Hans A. Schloesser, Jens P. Klussmann, Alexander Quaas and Kevin K. Hansenadd Show full author list remove Hide full author list
Cells 2025, 14(13), 985; https://doi.org/10.3390/cells14130985 - 27 Jun 2025
Viewed by 411
Abstract
Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition [...] Read more.
Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition and expression of the immune checkpoints programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in RRP. We analyzed tissue samples from 30 patients treated at a tertiary care center between 2009 and 2021, including paired samples from individual patients collected at different time points. Immunohistochemical staining was performed for CD4, CD8, CTLA-4, FoxP3, and PD-L1 and correlated with disease severity and previous adjuvant therapies. Overall disease burden and intervention-free survival were not associated with the abundance of CD4+, CD8+, or FoxP3+ T cells, nor with immune checkpoint expression. However, patients with aggressive disease exhibited a higher intralesional FoxP3/CD4 T-cell ratio. Prior intralesional cidofovir treatment was associated with reduced CD4+ T-cell infiltration. These findings suggest that a locally immunosuppressive microenvironment, reflected by an elevated FoxP3/CD4 ratio, contributes to disease severity in RRP. Consistent CTLA-4 expression across all evaluated samples supports further investigation of anti-CTLA-4 therapy, either alone or in combination with other checkpoint inhibitors. Full article
(This article belongs to the Section Cellular Immunology)
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20 pages, 1210 KiB  
Article
Generative AI for Bayesian Computation
by Nick Polson and Vadim Sokolov
Entropy 2025, 27(7), 683; https://doi.org/10.3390/e27070683 - 26 Jun 2025
Viewed by 481
Abstract
Generative Bayesian Computation (GBC) provides a simulation-based approach to Bayesian inference. A Quantile Neural Network (QNN) is trained to map samples from a base distribution to the posterior distribution. Our method applies equally to parametric and likelihood-free models. By generating a large training [...] Read more.
Generative Bayesian Computation (GBC) provides a simulation-based approach to Bayesian inference. A Quantile Neural Network (QNN) is trained to map samples from a base distribution to the posterior distribution. Our method applies equally to parametric and likelihood-free models. By generating a large training dataset of parameter–output pairs inference is recast as a supervised learning problem of non-parametric regression. Generative quantile methods have a number of advantages over traditional approaches such as approximate Bayesian computation (ABC) or GANs. Primarily, quantile architectures are density-free and exploit feature selection using dimensionality reducing summary statistics. To illustrate our methodology, we analyze the classic normal–normal learning model and apply it to two real data problems, modeling traffic speed and building a surrogate model for a satellite drag dataset. We compare our methodology to state-of-the-art approaches. Finally, we conclude with directions for future research. Full article
(This article belongs to the Section Information Theory, Probability and Statistics)
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17 pages, 932 KiB  
Article
A Lymphocyte Subset-Based Prediction Model for Refractory Community-Acquired Pneumonia in Immunocompetent Patients
by Jingyuan Zhang, Xinyu Hu, Ailifeila Aili, Lei Pan, Xinying Xue and Xiaolan Chen
Diagnostics 2025, 15(13), 1627; https://doi.org/10.3390/diagnostics15131627 - 26 Jun 2025
Viewed by 353
Abstract
Background/Objectives: Refractory community-acquired pneumonia (r-CAP) has become a thorny issue in clinical practice, especially after the COVID-19 pandemic, even in immunocompetent patients, as conventionally defined. In this study, we aimed to identify the risk factors for immunocompetent patients with r-CAP. Methods: This [...] Read more.
Background/Objectives: Refractory community-acquired pneumonia (r-CAP) has become a thorny issue in clinical practice, especially after the COVID-19 pandemic, even in immunocompetent patients, as conventionally defined. In this study, we aimed to identify the risk factors for immunocompetent patients with r-CAP. Methods: This was a single-center retrospective study. In total, we collected clinical data from 82 patients with r-CAP in whom the first-line antibiotic therapy failed and 82 patients with general CAP (g-CAP) who recovered with first-line antibiotics, matched at a ratio of 1:1, admitted to Beijing Shijitan Hospital, Capital Medical University, from 1 January 2022, to 31 December 2023. The differences between the two groups (clinical characteristics, peripheral blood cell count, lymphocyte subsets, and regular laboratory indicators) were analyzed using paired t, paired Wilcoxon, Chi-square, or Fisher’s exact tests, and univariate and multivariate logistics regression analyses were conducted to identify the independent risk factors. A model for predicting indicators with statistical significance was established and proved with the receiver operating characteristic (ROC) curve. Results: Warm season, a history of chronic obstructive pulmonary disease, longer time from onset to admission (TO-A), higher percentages of CD4+ T, CD8+ T, and double-negative T (DNT) lymphocytes, as well as higher levels of C-reactive protein (CRP), low-density lipoprotein cholesterin (LDL-C), serum sodium ion (Na+), and free-calcium ion (FCa2+) were regarded as independent risk factors, while T lymphocyte percentage (T%) and total cholesterol (TC) were identified as protective factors. The combined multivariate model using all the above factors proved to be sensitive and specific (AUC = 0.8711, p < 0.0001, R2 = 0.4235), and thus better than the respective univariate models. Conclusions: Increased CD4+ T%Lym, CD8+ T%Lym, and DNT%Lym, warm season, a history of COPD, longer TO-A, and increased levers of CRP, LDL-C, Na+, and FCa2+ potentially cause CAP to be refractory, while the T lymphocyte count, namely, the overall cellular immunity, was impaired in r-CAP patients, and increased TC levels could be beneficial to pneumonia recovery. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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21 pages, 3245 KiB  
Article
Interactions of Nedaplatin with Nucleobases and Purine Alkaloids: Their Role in Cancer Therapy
by Kamil Szupryczyński and Beata Szefler
Biomedicines 2025, 13(7), 1551; https://doi.org/10.3390/biomedicines13071551 - 25 Jun 2025
Viewed by 369
Abstract
Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, [...] Read more.
Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, it is important to consider how the presence of other chemical compounds with structural similarities to Adenine or Guanine, such as aromatic, purine, or pyrimidine compounds containing a nitrogen atom with a free electron pair, might influence its activity at the cellular level. Alkaloids with structures similar to DNA nucleobases are common, and their influence on Nedaplatin’s activity requires investigation. Methods: In this study, the interactions between Nedaplatin (including its hydrolyzed forms, such as [Pt(NH3)2(H2O)2]2+ and [Pt(NH3)2(H2O)(OH)]+) and nucleobases (Adenine and Guanine) and purine alkaloids (Caffeine, Theobromine and Theophylline) were thoroughly investigated using theoretical (density functional theory, DFT) and experimental (UV-Vis spectroscopy) methods. DFT calculations were performed at the B3LYP/6-31G(d,p)/LANL2DZ and MN15/def2-TZVP levels, with structure optimization and harmonic analysis in the gas phase and aqueous solution (modeled using IEF-PCM). UV-Vis spectroscopy was used to verify theoretical findings by examining changes in absorption spectra. Results: Both theoretical and experimental studies confirmed that Nedaplatin forms complexes with both nucleobases and purine alkaloids. Nedaplatin was found to exhibit a higher affinity for nucleobases than for purine alkaloids. Furthermore, this affinity was dependent on the computational method used and on the hydrolyzed form of Nedaplatin. Theoretical calculations showed the formation of stable complexes through bonding with nitrogen atoms in the ligand molecules, which was confirmed by changes in UV-Vis spectra, indicating adduct formation. Conclusions: The results indicate that Nedaplatin readily forms complexes with both nucleobases and purine alkaloids, showing a stronger affinity for nucleobases. This finding highlights the potential importance of Nedaplatin’s interactions with other compounds present in the body, which may influence its effectiveness and mechanism of action in cancer therapy. These studies provide new insights into the molecular mechanisms of Nedaplatin’s action and may contribute to a better understanding of its pharmacological interactions. However, research requires confirmation not only in in vivo studies but also in clinical trials. Full article
(This article belongs to the Special Issue Chemoprevention to Dwindle Tumor Development)
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22 pages, 27201 KiB  
Article
Spatiotemporal Interactive Learning for Cloud Removal Based on Multi-Temporal SAR–Optical Images
by Chenrui Xu, Zhenfei Wang, Liang Chen and Xiangchao Meng
Remote Sens. 2025, 17(13), 2169; https://doi.org/10.3390/rs17132169 - 24 Jun 2025
Viewed by 407
Abstract
Optical remote sensing images suffer from information loss due to cloud interference, while Synthetic Aperture Radar (SAR), capable of all-weather and day–night imaging capabilities, provides crucial auxiliary data for cloud removal and reconstruction. However, existing cloud removal methods face the following key challenges: [...] Read more.
Optical remote sensing images suffer from information loss due to cloud interference, while Synthetic Aperture Radar (SAR), capable of all-weather and day–night imaging capabilities, provides crucial auxiliary data for cloud removal and reconstruction. However, existing cloud removal methods face the following key challenges: insufficient utilization of spatiotemporal information in multi-temporal data, and fusion challenges arising from fundamentally different imaging mechanisms between optical and SAR images. To address these challenges, a spatiotemporal feature interaction-based cloud removal method is proposed to effectively fuse SAR and optical images. Built upon a conditional generative adversarial network framework, the method incorporates three key modules: a multi-temporal spatiotemporal feature joint extraction module, a spatiotemporal information interaction module, and a spatiotemporal discriminator module. These components jointly establish a many-to-many spatiotemporal interactive learning network, which separately extracts and fuses spatiotemporal features from multi-temporal SAR–optical image pairs to generate temporally consistent, cloud-free image sequences. Experiments on both simulated and real datasets demonstrate the superior performance of the proposed method. Full article
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