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16 pages, 1176 KB  
Article
Sensorless Speed Control of PMSM in the Low-Speed Region Using a Runge–Kutta Model-Based Nonlinear Gradient Observer
by Adile Akpunar Bozkurt
Machines 2026, 14(4), 369; https://doi.org/10.3390/machines14040369 - 27 Mar 2026
Abstract
High-performance operation of permanent magnet synchronous motors (PMSMs) strongly depends on the reliable availability of rotor position and speed information. Although this information is commonly obtained using physical position sensors, such sensors increase system cost and structural complexity and may reduce long-term reliability, [...] Read more.
High-performance operation of permanent magnet synchronous motors (PMSMs) strongly depends on the reliable availability of rotor position and speed information. Although this information is commonly obtained using physical position sensors, such sensors increase system cost and structural complexity and may reduce long-term reliability, particularly in demanding operating environments. In this study, a model-based, discrete-time, nonlinear gradient observer is adapted for the sensorless estimation of rotor speed and position in PMSMs. The developed Runge–Kutta model-based gradient observer (RKGO) utilizes stator voltage inputs and measured stator currents within a mathematical motor model to estimate the system states. In contrast to conventional sensorless estimation approaches, the adopted observer framework exploits discretization-based gradient dynamics to enhance numerical robustness and convergence behavior under nonlinear operating conditions. The observer design specifically targets stable and accurate state estimation in discrete-time implementations, with a particular focus on low-speed operating conditions. The performance of the adapted method is experimentally evaluated under low-speed operating conditions, including transient and steady-state operation. Real-time implementation is carried out on a dSPACE DS1104 control platform, including loaded acceleration scenarios to assess practical robustness. In addition, a comparative analysis with the Extended Kalman Filter (EKF) and the Runge–Kutta Extended Kalman Filter (RKEKF) is conducted at 60 rad/s under identical experimental conditions. Experimental results show that the RKGO method achieves accurate steady-state speed and position estimation with acceptable transient performance. The findings demonstrate that RKGO can be considered a viable alternative for low-speed sensorless PMSM drive applications. Full article
24 pages, 6235 KB  
Review
Coronary Plaque Vulnerability and Pericoronary Adipose Tissue Inflammation: Emerging Insights from Advanced CT Imaging
by Botond Barna Mátyás, Imre Benedek, Nóra Rat, Renáta Gerculy and Theodora Benedek
Medicina 2026, 62(4), 630; https://doi.org/10.3390/medicina62040630 - 26 Mar 2026
Abstract
Cardiovascular emergencies most frequently arise from the sudden destabilization of atherosclerotic plaques. Conventional diagnostic strategies predominantly focus on luminal stenosis, despite the fact that most acute coronary events originate from non-obstructive lesions with high inflammatory activity. Recent advances in cardiac computed tomography (CCT) [...] Read more.
Cardiovascular emergencies most frequently arise from the sudden destabilization of atherosclerotic plaques. Conventional diagnostic strategies predominantly focus on luminal stenosis, despite the fact that most acute coronary events originate from non-obstructive lesions with high inflammatory activity. Recent advances in cardiac computed tomography (CCT) enable visualization of plaque morphology and surrounding perivascular fat, offering a unique window into coronary inflammation. The fat attenuation index (FAI), derived from pericoronary adipose tissue (PCAT) radiodensity, has emerged as a dynamic imaging biomarker capable of detecting vascular inflammation before clinical events occur. This review summarizes current evidence on the role of PCAT inflammation in plaque vulnerability, its implications for acute cardiovascular presentations, and recent technological innovations—including AI-enhanced analysis and photon-counting CT—that advance risk prediction. Inflammation-based imaging derived from CCT, including PCAT-FAI, has emerged as a promising research tool that may enhance risk stratification in patients presenting with chest pain. These developments signify a shift from purely anatomical assessment toward biological characterization of CAD, potentially transforming prevention and acute care. Full article
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22 pages, 2938 KB  
Article
Design and Analytical Modeling of a Unidirectional Series Elastic Actuator with Tension-Spring-Based Rotational Stiffness Mechanism
by Deokgyu Kim, Jiho Lee and Chan Lee
Actuators 2026, 15(4), 180; https://doi.org/10.3390/act15040180 - 25 Mar 2026
Abstract
This study proposes a tension-spring-based unidirectional rotational stiffness mechanism (TS-URM) and its implementation in a Unidirectional Series Elastic Actuator (USEA). Unlike conventional bidirectional rotary SEAs, the proposed design is structurally optimized for unidirectional torque transmission, improving deformation utilization efficiency in pulling-type applications. An [...] Read more.
This study proposes a tension-spring-based unidirectional rotational stiffness mechanism (TS-URM) and its implementation in a Unidirectional Series Elastic Actuator (USEA). Unlike conventional bidirectional rotary SEAs, the proposed design is structurally optimized for unidirectional torque transmission, improving deformation utilization efficiency in pulling-type applications. An analytical model was derived to establish the geometric relationship between spring elongation and rotational deformation, enabling explicit formulation of the torque–angle relationship. The influence of the installation angle on stiffness linearity was systematically analyzed, and a multilayer spring configuration was optimized to achieve a target rotational stiffness of approximately 42 Nm/rad. A preload adjustment mechanism was incorporated to eliminate nonlinear behavior in the initial operating region. Experimental results validated the analytical model and demonstrated stable unidirectional force control up to 130 N with steady-state errors within 1 N. The proposed mechanism provides predictable stiffness characteristics and an efficient structural solution for compact USEA systems. Full article
(This article belongs to the Special Issue Actuators in Robotic Control—3rd Edition)
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16 pages, 1895 KB  
Article
The Value of Multimodal Ultrasound in Differentiating Benign from Malignant Cytologically Indeterminate Thyroid Nodules
by Rong Yang, Yanfang Wang, Guo Chen, Xiaorong Lv, Yuanqing Zhang and Fang Nie
Cancers 2026, 18(7), 1071; https://doi.org/10.3390/cancers18071071 - 25 Mar 2026
Abstract
Aim: To evaluate the diagnostic value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in differentiating benign from malignant Bethesda III/IV thyroid nodules, and to identify independent predictors of malignancy. Methods: We retrospectively analyzed 164 surgically confirmed Bethesda III/IV thyroid nodules. CUS [...] Read more.
Aim: To evaluate the diagnostic value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in differentiating benign from malignant Bethesda III/IV thyroid nodules, and to identify independent predictors of malignancy. Methods: We retrospectively analyzed 164 surgically confirmed Bethesda III/IV thyroid nodules. CUS and CEUS features were evaluated by two experienced radiologists blinded to pathological outcomes. Univariate analysis compared features between benign and malignant groups. Multivariate logistic regression was used to identify independent predictors. Diagnostic models were constructed based on CUS alone, CEUS alone, and their combination, with performance evaluated using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each model. Results: The malignancy rate was 48.8% (80/164). Multivariate analysis identified microcalcifications (OR = 4.815, p < 0.001), aspect ratio >1 (OR = 2.499, p = 0.028), and irregular shape (OR = 2.465, p = 0.035) as independent risk factors, while older age (OR = 0.926 per year, p < 0.001) was protective. The CUS model achieved an AUC of 0.815 with high sensitivity (91.3%) and NPV (87.7%). The CEUS model performed poorly (AUC = 0.609). The combined model (AUC = 0.823) showed no significant improvement over CUS alone (p > 0.05). Physician subjective diagnosis based on CEUS TI-RADS yielded an AUC of 0.775. Conclusions: Conventional ultrasound features provide good diagnostic value for Bethesda III/IV nodules, with high sensitivity and NPV suitable for clinical screening. The addition of CEUS offered limited incremental benefit in this specific population, suggesting that the diagnostic value of CEUS for differentiating benign from malignant cytologically indeterminate thyroid nodules (ITNs) may be limited. Full article
(This article belongs to the Special Issue Application of Ultrasound in Cancer Diagnosis and Treatment)
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11 pages, 10037 KB  
Article
EFA-RadNet: Efficient Feature Aggregation with Balanced Attention for Raw Radar Multi-Task Learning
by Chengliang Zhong, Xiuping Li, Jingjing Li, Juan Liu and Xiyan Sun
Sensors 2026, 26(7), 2050; https://doi.org/10.3390/s26072050 - 25 Mar 2026
Abstract
Original high-definition radar data contains rich environmental information, including distance, Doppler velocity, and azimuth. However, extracting robust features from such sparse and noisy frequency-domain data remains a challenge. To address this issue, this paper proposes an improved multi-task network, the Efficient Feature Aggregation [...] Read more.
Original high-definition radar data contains rich environmental information, including distance, Doppler velocity, and azimuth. However, extracting robust features from such sparse and noisy frequency-domain data remains a challenge. To address this issue, this paper proposes an improved multi-task network, the Efficient Feature Aggregation with Balanced Attention Radar Network (EFA-RadNet). This network introduces the VoVNetV2 architecture into the field of raw radar perception and effectively preserves feature diversity across different receptive fields through a One-Shot Aggregation (OSA) module, avoiding signal aliasing. In addition, we propose an attention mechanism module, Balanced effective Squeeze–Excitation (B-eSE), which is better suited for sparse radar processing and effectively addresses the problem of weak target loss in the radar spectrum. Experiments on the RADIal dataset show that our EFA-RadNet achieves excellent target detection performance while also attaining optimal accuracy in free space segmentation. Full article
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13 pages, 664 KB  
Article
Performance of a Screening Mammography AI Algorithm Repurposed for Symptomatic Mammography in a Tertiary Outpatient Clinic
by Helen Ngo, Eric Niller, Eric Schmitz, Elmar Kotter, Marisa Windfuhr-Blum, Claudia Neubauer, Ana-Luisa Palacios, Fabian Bamberg, Jakob Neubauer, Jakob Weiss and Caroline Wilpert
Diagnostics 2026, 16(7), 984; https://doi.org/10.3390/diagnostics16070984 - 25 Mar 2026
Abstract
Background/Objectives: The aim of the study was to evaluate the diagnostic accuracy of a commercial artificial intelligence (AI) algorithm originally developed for screening mammography when applied to symptomatic women presenting to a tertiary outpatient clinic. Methods: This single-center, retrospective diagnostic accuracy [...] Read more.
Background/Objectives: The aim of the study was to evaluate the diagnostic accuracy of a commercial artificial intelligence (AI) algorithm originally developed for screening mammography when applied to symptomatic women presenting to a tertiary outpatient clinic. Methods: This single-center, retrospective diagnostic accuracy study included women who presented with breast symptoms to a tertiary outpatient clinic between January and June 2013 and underwent digital mammography. An AI algorithm cleared by the U.S. Food and Drug Administration (FDA)-cleared AI algorithm was applied to all mammograms and generated continuous malignancy scores ranging from 1 to 100. Mammographic breast density was classified according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) by two experienced radiologists. Histopathology, when available, or otherwise a minimum of 2 years of clinical and imaging follow-up served as the reference standard. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis with calculation of the area under the curve (AUC) and 95% confidence intervals (CI) derived by patient level bootstrap resampling (n = 2000). Analyses were performed for the overall cohort and stratified by breast density (non-dense [BI-RADS A–B] vs. dense [BI-RADS C–D]). Results: A total of 78 women (mean age, 55 ± 11 years) were included, of whom 16 had histopathological verification of suspicious lesions with proven breast cancer in 14 patients and 62 were classified based on follow-up alone. In the overall cohort (156 breasts, including 15 breasts with malignancies), the AI algorithm achieved an AUC of 0.96 (95% CI: 0.86–1.00). Performance remained high in non-dense breasts (AUC = 0.96; 95% CI: 0.88–1.00) and dense breasts (AUC = 0.99; 95% CI: 0.93–1.00), with no statistically significant difference observed between density subgroups (DeLong test, p = 0.36), although subgroup comparisons were underpowered. Decision curve analysis suggested a consistent positive net benefit across a wide range of threshold probabilities in both density groups. Conclusions: In this preliminary, single-center retrospective cohort, a screening-trained AI algorithm showed promising diagnostic accuracy when applied to symptomatic mammograms. These findings require validation in larger, contemporary, multicenter cohorts before clinical implementation. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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21 pages, 26584 KB  
Article
Connecting Meteorite Spectra to Lunar Surface Composition Using Hyperspectral Imaging and Machine Learning
by Fatemeh Fazel Hesar, Mojtaba Raouf, Amirmohammad Chegeni, Peyman Soltani, Bernard Foing, Elias Chatzitheodoridis, Michiel J. A. de Dood and Fons J. Verbeek
Universe 2026, 12(4), 93; https://doi.org/10.3390/universe12040093 - 24 Mar 2026
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Abstract
We present an innovative, cost-effective framework integrating laboratory Hyperspectral Imaging (HSI) of the Bechar 010 Lunar meteorite with ground-based lunar HSI and supervised Machine Learning (ML) to generate high-fidelity mineralogical maps. A 3 mm thin section of Bechar 010 was imaged under a [...] Read more.
We present an innovative, cost-effective framework integrating laboratory Hyperspectral Imaging (HSI) of the Bechar 010 Lunar meteorite with ground-based lunar HSI and supervised Machine Learning (ML) to generate high-fidelity mineralogical maps. A 3 mm thin section of Bechar 010 was imaged under a microscope with a 30 mm focal length lens at 150 mm working distance, using 6x binning to increase the signal-to-noise ratio, producing a data cube (X × Y × λ = 791×1024×224, 0.24 mm × 0.2 mm resolution) across 400 nm to 1000 nm (224 bands, 2.7 nm spectral sampling, 5.5 nm full width at half maximum spectral resolution) using a Specim FX10 camera. Ground-based lunar HSI was captured with a Celestron 8SE telescope (3 km/pixel), yielded a data cube (371×1024×224). Solar calibration was performed using a Spectralon reference (99% reflectance < 2% error) ensured accurate reflectance spectra. A Support Vector Machine (SVM) with a radial basis function kernel, trained on expert-labeled spectra, achieved 93.7% classification accuracy (5-fold cross-validation) for olivine (92% precision, 90% recall) and pyroxene (88% precision, 86% recall) in Bechar 010. LIME analysis identified key wavelengths (e.g., 485 nm, 22.4% for M3; 715 nm, 20.6% for M6) across 10 pre-selected regions (M1 to M10), indicating olivine-rich (Highland-like) and pyroxene-rich (Mare-like) compositions. SAM analysis revealed angles from 0.26 rad to 0.66 rad, linking M3 and M9 to Highlands and M6 and M10 to Mares. K-means clustering of Lunar data identified 10 mineralogical clusters (88% accuracy), validated against Chandrayaan-1 Moon mineralogy Mapper (M3) data (140 m/pixel, 10 nm spectral resolution). A novel push-broom HSI approach with a telescope achieves 0.8 arcsec resolution for lunar spectroscopy, inspiring full-sky multi-object spectral mapping. Full article
(This article belongs to the Section Planetary Sciences)
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13 pages, 1084 KB  
Article
Circulating Plasma Cells as a Minimally Invasive Adjunct to Bone Marrow Aspirates for Genetic Analysis of ER Stress and Autophagy in Multiple Myeloma: A Feasibility Study
by A.-M. Joëlle Marivel, Therese M. Becker, Alexander James, Yafeng Ma, Nirupama D. Verma, Tara L. Roberts and Silvia Ling
Biomedicines 2026, 14(4), 737; https://doi.org/10.3390/biomedicines14040737 (registering DOI) - 24 Mar 2026
Viewed by 124
Abstract
Background: Multiple myeloma (MM) is characterised by clonal expansion of plasma cells (PCs) in the bone marrow (BM). Disease assessment and monitoring typically rely on invasive, single-site procedures, such as BM biopsies (BMBs), which may inadequately capture intra- and extra-medullary spatial heterogeneity. Circulating [...] Read more.
Background: Multiple myeloma (MM) is characterised by clonal expansion of plasma cells (PCs) in the bone marrow (BM). Disease assessment and monitoring typically rely on invasive, single-site procedures, such as BM biopsies (BMBs), which may inadequately capture intra- and extra-medullary spatial heterogeneity. Circulating plasma cells (CPCs), enriched from peripheral blood (PB), may represent a minimally invasive alternative or adjunct for molecular profiling. Objectives: This study aimed to evaluate the feasibility of using CPCs, enriched from PB, for mRNA analysis in plasma cell dyscrasia, including MM. A secondary objective was to assess whether mRNA expression levels of the endoplasmic reticulum (ER) stress sensors X-box-binding protein 1 (uXBP1) and activating transcription factor 6 (ATF6), and the chaperone-mediated autophagy marker Lysosomal-Associated Membrane Protein 2 (LAMP2A) by droplet digital PCR (ddPCR), were associated with resistance to the second-generation proteasome inhibitor (PI) carfilzomib (Cfz). Methods: Multiple myeloma (MM) cell lines (H929 and U266) and their carfilzomib-adapted derivatives were used to establish and validate droplet digital PCR (ddPCR) assays targeting ER stress (uXBP1, ATF6) and autophagy-related (LAMP2A) transcripts. Solid tumour cell lines, including serum-starved HeLa cells, served as biological controls to support assay specificity and sensitivity. Total RNA was extracted and reverse-transcribed to complementary DNA prior to analysis. Transcript levels were normalised to those of β-actin or GAPDH, as appropriate. ddPCR was performed using the BioRad QX200 system, with results reported as the normalised transcript copy number per microlitre of reaction. Matched bone marrow aspirate (BMA) and peripheral blood (PB) samples were collected at a single clinical time point from adults undergoing investigation for plasma cell dyscrasia between January 2021 and December 2023. Samples were obtained as part of standard clinical care and/or during treatment with Bortezomib (Btz) or Cfz. Mononuclear cells were isolated by density gradient centrifugation, and CD138+ plasma cells were enriched by fluorescence-activated cell sorting. Enrichment purity was assessed qualitatively by immunofluorescence microscopy using CD138 and CD117 markers. Samples yielding fewer than 1000 CD138+ plasma cells were excluded, resulting in 10 evaluable matched patient pairs. Results: Carfilzomib-adapted MM cell lines demonstrated reduced levels of uXBP1, ATF6, and LAMP2A mRNA compared to treatment-naïve cells. In matched BM and PB samples, uXBP1 mRNA levels were consistently lower in circulating PCs than in BM-derived PCs, whereas ATF6 mRNA levels were concordant between compartments. LAMP2A mRNA levels exhibited marked inter-patient heterogeneity. Conclusions: This study demonstrates the feasibility of using CPCs as a minimally invasive source for mRNA-based biomarker assessment and highlights ddPCR as a sensitive platform for quantifying ER stress and chaperone-mediated autophagy related transcripts in CPCs. Cfz adaptation was associated with reduced levels of uXBP1 and LAMP2A mRNA in MM cell lines. Future prospective studies evaluating the clinical utility of ER stress and chaperone-mediated autophagy associated transcripts in CPCs as predictors of resistance to PI are warranted. Full article
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17 pages, 2064 KB  
Article
Particulate Hexavalent Chromium Inhibits RAD51 Paralogs Necessary for RAD51 Filament Formation and Stabilization During Homologous Recombination Repair
by Aggie R. Williams, Idoia Meaza, Haiyan Lu, James T. F. Wise, Sandra S. Diven, Jennifer H. Toyoda, J. Calvin Kouokam and John Pierce Wise
Occup. Health 2026, 1(1), 13; https://doi.org/10.3390/occuphealth1010013 - 23 Mar 2026
Viewed by 89
Abstract
Hexavalent chromium [Cr(VI)] is a lung carcinogen. Central to its carcinogenic mechanism are Cr(VI)-induced DNA double strand breaks and chromosome instability. While breaks are usually repaired in healthy cells, Cr(VI) inhibits homologous recombination repair by targeting RAD51. RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, [...] Read more.
Hexavalent chromium [Cr(VI)] is a lung carcinogen. Central to its carcinogenic mechanism are Cr(VI)-induced DNA double strand breaks and chromosome instability. While breaks are usually repaired in healthy cells, Cr(VI) inhibits homologous recombination repair by targeting RAD51. RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are responsible for RAD51 loading and the stabilization of nucleoprotein filaments necessary for DNA strand exchange and repair. This study aimed to investigate the effects of Cr(VI) exposure on RAD51 paralogs. WTHBF-6 cells, a human lung cell line, were exposed to various environmentally and occupationally relevant concentrations of zinc chromate for acute (24 h) and prolonged (120 h) exposure times. After exposure to Cr(VI), we collected RNA for sequencing and assessed the ability of DNA repair proteins to form foci using immunofluorescence. Protein levels were measured with western blotting, RNA-Seq was validated with RT-qPCR, and protein–protein interactions were assessed with the Proximity Ligation Assay (PLA) assay. Cr(VI) transcriptionally repressed all RAD51 paralogs. Further functional analyses showed that Cr(VI) inhibited the foci formation of RAD51D after acute and prolonged exposures and of XRCC2 and XRCC3 after prolonged exposure. Cr(VI) also inhibited overall RAD51D protein expression, as well as its interaction with RAD51. These findings suggest that Cr(VI) inhibits all RAD51 paralogs, but RAD51D might be an early target of Cr(VI), leading to the loss of RAD51 filament formation and function and the overall inhibition of homologous recombination repair. Full article
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26 pages, 2197 KB  
Review
Next-Generation Genotyping: Innovations Driving Plant Genomic Improvement
by Valeriya Kostyukova, Roza Kenzhebekova, Egor Protsenko, Bakyt Dulat, Marina Khusnitdinova and Dilyara Gritsenko
Life 2026, 16(3), 521; https://doi.org/10.3390/life16030521 - 21 Mar 2026
Viewed by 226
Abstract
In recent years, plant genotyping has been shifting from the accumulation of whole-genome data toward their effective use in breeding programs This review examines key genotyping platforms, including single-nucleotide polymorphism (SNP) arrays, reduced-representation sequencing methods such as genotyping-by-sequencing (GBS) and restriction site-associated DNA [...] Read more.
In recent years, plant genotyping has been shifting from the accumulation of whole-genome data toward their effective use in breeding programs This review examines key genotyping platforms, including single-nucleotide polymorphism (SNP) arrays, reduced-representation sequencing methods such as genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), targeted genotyping approaches, and whole-genome sequencing (WGS), analyzing their informativeness, cost, and computational limitations. The transition to pangenome-based genotyping and graph genomes is discussed, as these approaches reduce reference bias and increase sensitivity for detecting structural variants, introgressions, and rare alleles that are important for adaptation and breeding. The growing role of AI/ML is highlighted in modeling complex genotype–phenotype relationships, integrating genomic and phenotypic data, and improving the accuracy and interpretability of genomic predictions. Full article
(This article belongs to the Special Issue Advances in Plant Biotechnology and Molecular Breeding)
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21 pages, 4268 KB  
Article
Epacadostat and Olaparib Synergistically Inhibit the Growth of BRCA-Proficient Triple-Negative Breast Cancer by Suppressing the Expression of BRCA1 and RAD51
by Lei Huang, Ye Yang, Dongxia Duan, Li Dai, Bingxin Zhai and Bingjun Qian
Molecules 2026, 31(6), 1039; https://doi.org/10.3390/molecules31061039 - 20 Mar 2026
Viewed by 210
Abstract
Triple-negative breast cancer (TNBC) cells with intact homologous recombination (HR) repair mechanism can survive treatment with Olaparib, which further limits the clinical application of PARP1/2 inhibitors. Previous studies have demonstrated that inhibition of indoleamine 2,3-dioxygenase (IDO) can enhance the sensitivity of human tumor [...] Read more.
Triple-negative breast cancer (TNBC) cells with intact homologous recombination (HR) repair mechanism can survive treatment with Olaparib, which further limits the clinical application of PARP1/2 inhibitors. Previous studies have demonstrated that inhibition of indoleamine 2,3-dioxygenase (IDO) can enhance the sensitivity of human tumor cells to PARP1/2 inhibitors. However, the mechanisms underlying their synergistic effects in the treatment of TNBC remain unclear. Herein, we demonstrate that the combination of Olaparib and Epacadostat significantly reduces the proliferation of BRCA-proficient MDA-MB-231 and MDA-MB-468 cells compared to either monotherapy. Mechanistically, Epacadostat reduces intracellular kynurenine and NAD+ levels, thereby sensitizing TNBCs to PARP1/2 inhibition and significantly amplifying Olaparib-induced DNA damage. Furthermore, Epacadostat and Olaparib synergistically increase cellular reactive oxygen species (ROS), leading to DNA oxidative damage and apoptosis. In vivo, Epacadostat and Olaparib significantly suppressed MDA-MB-468 tumor growth compared to the monotherapy groups, while promoting an increase in phosphorylated H2AX. Notably, the dual inhibition of IDO1 and PARP1/2 specifically reduced the expression of HR core genes and proteins, such as BRCA1 and RAD51, which may contribute to impaired DNA-damage repair and increased sensitivity to Olaparib. In summary, targeting both IDO1 and PARP1/2 represents a promising combination therapy for BRCA-proficient TNBC. Full article
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20 pages, 2202 KB  
Review
MRI and Endometrial Cancer After FIGO 2023—What’s New? A Narrative Review
by Marco Gennarini, Roberta Valerieva Ninkova, Valentina Miceli, Federica Curti, Sandrine Riccardi, Benedetta Gui, Stefania Rizzo, Aradhana M. Venkatesan, Stephanie Nougaret and Lucia Manganaro
Cancers 2026, 18(6), 1005; https://doi.org/10.3390/cancers18061005 - 20 Mar 2026
Viewed by 170
Abstract
Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries, and its diagnostic and prognostic framework has evolved substantially following the introduction of the 2023 FIGO staging system, which integrates molecular classification with clinicopathologic features. Both histopathologic features, such as lymphovascular [...] Read more.
Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries, and its diagnostic and prognostic framework has evolved substantially following the introduction of the 2023 FIGO staging system, which integrates molecular classification with clinicopathologic features. Both histopathologic features, such as lymphovascular space invasion (LVSI) and molecular subtype, including POLE mutation status, mismatch-repair deficiency, and p53-abnormal phenotype, are incorporated into the updated staging system, highlighting the importance of tumour biology in risk stratification. Accordingly, the value and contribution of MRI to patient management must extend beyond macroscopic assessment to support a more biologically driven approach. This narrative review synthesizes recent advances in MRI for EC, highlighting developments that improve diagnostic accuracy and align imaging with the molecular paradigm. Multiparametric MRI remains the reference standard for local staging, while emerging quantitative diffusion techniques provide microstructural biomarkers associated with tumor aggressiveness and prognostic features. The consistency of nodal staging has been enhanced by Node-RADS, a structured reporting system that integrates nodal morphology and configuration, with the goal of improving reproducibility and diagnostic performance over size-based assessment alone. Radiomics and artificial intelligence (AI) represent the most transformative frontier, enabling MRI to infer biological behaviours previously accessible only via histopathologic assessment. Radiomics and deep-learning models have demonstrated high accuracy in predicting LVSI, DMI, nodal metastasis, and molecular subtypes, offering non-invasive biomarkers aligned with FIGO 2023 prognostic categories. Together, these advances position MRI as a quantitatively enriched, biologically relevant tool that supports precision oncology in endometrial cancer. Full article
(This article belongs to the Special Issue Updates on Imaging of Common Urogenital Neoplasms—2nd Edition)
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21 pages, 30483 KB  
Article
Preliminary Assessment of ICON-LAM Performance in Romania: Sensitivity Studies
by Amalia Iriza-Burcă, Ioan-Ştefan Gabrian, Ştefan Dinicilă, Mihaela Silvana Neacşu and Rodica Claudia Dumitrache
Atmosphere 2026, 17(3), 315; https://doi.org/10.3390/atmos17030315 - 19 Mar 2026
Viewed by 177
Abstract
The Earth system model ICON (ICOsahedral Nonhydrostatic general circulation) is a flexible framework that can be configured and tuned for various applications such as weather forecasting, simulations of aerosols and trace gases, and climate modelling. The numerical weather prediction component ICON is used [...] Read more.
The Earth system model ICON (ICOsahedral Nonhydrostatic general circulation) is a flexible framework that can be configured and tuned for various applications such as weather forecasting, simulations of aerosols and trace gases, and climate modelling. The numerical weather prediction component ICON is used in limited area mode (ICON-LAM) in Romania to obtain realistic weather simulations that support operational forecasting activities. The sensitivity of ICON-LAM is preliminarily evaluated for the geographical area of Romania. Numerical simulations using two parameterization schemes for radiation processes, two convection settings and different values for the laminar resistance of heat transfer from the surface to the air are evaluated against a control run employed for operational forecasts at the National Meteorological Administration. The validation is performed focusing on the precipitation field and surface continuous parameters. All configurations were integrated for a short period in summer when forecasted precipitation was strongly overestimated. Further on, selected configurations were evaluated for winter cases. The experiment with the shallow convection only, the ecRad radiation parameterization, and the laminar heat value 10 emerged as the best fit for Romania. This configuration (considered optimal) was evaluated alongside the operational control run for August 2022. Overall results indicate the selected optimal configuration generally outperforms the control run both with regard to precipitation and in forecasting surface parameters. This experiment has been adapted and implemented in operational workflow. Full article
(This article belongs to the Section Meteorology)
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21 pages, 14401 KB  
Article
Biparametric Versus Multiparametric MRI for VI-RADS Assessment: Reproducibility Relative to Routine mpMRI Reporting and Impact of Radiologist Experience in a Single-Center Study
by Fabrizio Urraro, Nicoletta Giordano, Vittorio Patanè, Maria Chiara Brunese, Claudia Rossi, Antonio Cioffi, Anna Russo, Carlo Varelli, Fiammetta Cappabianca and Alfonso Reginelli
Cancers 2026, 18(6), 999; https://doi.org/10.3390/cancers18060999 - 19 Mar 2026
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Abstract
Background: We tested whether a contrast-free protocol can reproduce contrast-enhanced VI-RADS scoring and whether reader expertise influences results. Methods: In this retrospective single-center study (January–December 2024), 65 patients (69 lesions) underwent bladder multiparametric MRI. Two blinded radiologists assigned VI-RADS scores using [...] Read more.
Background: We tested whether a contrast-free protocol can reproduce contrast-enhanced VI-RADS scoring and whether reader expertise influences results. Methods: In this retrospective single-center study (January–December 2024), 65 patients (69 lesions) underwent bladder multiparametric MRI. Two blinded radiologists assigned VI-RADS scores using only T2-weighted and diffusion-weighted imaging (biparametric, non-contrast MRI): an expert (>15 years in urogenital radiology) in genitourinary MRI and a non-expert (5 years of experience in genitorurinary radiology). Two complementary reference standards were used. For reproducibility analysis, the reference standard was the VI-RADS score from the original clinical report based on the full multiparametric examination including contrast-enhanced imaging. For diagnostic accuracy analysis, histopathology was used as the reference standard for muscle-invasive versus non-muscle-invasive disease. Agreement was evaluated with confusion matrices, overall agreement, and weighted Cohen’s kappa. Discrimination for high likelihood of muscle invasion (VI-RADS ≥ 4) was assessed with receiver operating characteristic analysis. Results: Reference scores were VI-RADS 2 (34.8%), 3 (14.5%), 4 (20.3%), and 5 (30.4%). Agreement was higher for the expert than the non-expert (73.9% vs. 56.5%; weighted kappa 0.74 [95% confidence interval 0.56–0.89] vs. 0.58 [0.37–0.75]). The area under the curve for VI-RADS ≥ 4 was 0.87 (0.78–0.95) for the expert and 0.81 (0.69–0.91) for the non-expert. Sensitivity at a biparametric threshold of VI-RADS ≥ 4 was 88.6% for both readers; specificity was 85.3% vs. 73.5%. Post-resection cases showed more discrepancies, mainly overstaging. Conclusions: Contrast-free biparametric MRI may approximate multiparametric VI-RADS scoring only in treatment-naïve pre-TURBT cases with clearly low-risk, non-equivocal imaging features, but performance is reader-dependent and less reliable in equivocal, higher-risk, and post-resection examinations. Contrast-enhanced multiparametric MRI remains preferred for staging. Full article
(This article belongs to the Special Issue Clinical Applications of Advanced MRI Technologies for Cancers)
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Article
Development of Stearic Acid Nanoemulsion for Therapeutic Delivery of Talazoparib Against Breast Cancer
by Jingjing Zhang, Zhongkun Zhang, Xiaohan Xia, Kaixin Feng, Siyu Yao, Yufei Wang and Min Wu
Pharmaceutics 2026, 18(3), 378; https://doi.org/10.3390/pharmaceutics18030378 - 19 Mar 2026
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Abstract
Objectives: Talazoparib (TZL) is a potent PARP inhibitor but suffers from poor aqueous solubility, dissolution-limited absorption, and dose-limiting systemic toxicities, which together restrict its antitumor efficacy in some breast cancer settings. This study aimed to develop a stearic acid-based nanoemulsion (SANE) to [...] Read more.
Objectives: Talazoparib (TZL) is a potent PARP inhibitor but suffers from poor aqueous solubility, dissolution-limited absorption, and dose-limiting systemic toxicities, which together restrict its antitumor efficacy in some breast cancer settings. This study aimed to develop a stearic acid-based nanoemulsion (SANE) to improve the delivery of TZL and enhance its antitumor activity and preliminarily explore its impact on DNA damage response-related pathways. Methods: SANE-TZL was prepared using a high-pressure homogenization method, and its physicochemical properties were characterized. MCF-7 and MDA-MB-231 breast cancer cells were used to evaluate cellular uptake, cytotoxicity, and changes in key DNA damage response markers. In vivo therapeutic efficacy and safety were assessed in an MDA-MB-231 xenograft mouse model. Results: SANE-TZL exhibited a uniform particle size of approximately 118 nm with excellent stability. In MCF-7 cells, SANE-TZL significantly enhanced drug internalization, resulting in an 8.4-fold reduction in IC50 compared to free TZL. Consistently, in MDA-MB-231 cells, SANE-TZL also showed markedly increased antiproliferative activity. At the molecular level, SANE-TZL modulated the expression of several DNA damage response-related genes, including BRCA1, RAD51, and SLFN11, in a manner consistent with impaired DNA repair capacity. In vivo, high-dose SANE-TZL achieved a tumor growth inhibition (TGI) rate of 58.55%, which was higher than that of the free TZL group (41.86%) and the blank eSANE group (17.59%). No evident hematological or organ toxicities were observed in the SANE-TZL-treated groups. Conclusions: SANE-TZL markedly improves the delivery efficiency and antitumor activity of TZL in breast cancer models while maintaining a favorable safety profile. By combining a functional stearic acid carrier with TZL, this nanoemulsion formulation represents a safe and potent strategy to enhance PARP inhibitor-based chemotherapy in breast cancer, and it may provide a basis for further mechanistic studies on DNA damage response modulation. Full article
(This article belongs to the Special Issue Advanced Nano-Formulations for Drug Delivery and Cancer Immunotherapy)
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