Search Results (305)

Background/Objectives: Patients with suspicious prostate mpMRI but negative baseline biopsy remain challenging to manage, as some are later diagnosed with clinically significant prostate cancer (csPCa). This study evaluated whether baseline whole-gland radiomic features from T2-weighted imaging and apparent diffusion coefficient (ADC) maps could predict subsequent csPCa detection. Methods: This retrospective radiomics sub-analysis of the MULTIPROS trial included men with suspicious baseline mpMRI findings (PI-RADS v2.0 categories 3–5) and no csPCa detected at baseline biopsy. The primary outcome was subsequent csPCa detection during follow-up, defined as ISUP Grade Group ≥2. Whole-gland prostate segmentation was performed on baseline T2-weighted images using a semi-automated approach with manual refinement, and the resulting T2-derived masks were applied to the spatially corresponding ADC maps. Radiomic features were extracted using PyRadiomics version 3.1.0a2 after standardised preprocessing. Feature robustness was assessed in a 20-patient reproducibility subset using intra- and inter-reader intraclass correlation coefficients, followed by correlation filtering and LASSO-based feature prioritisation. Radiomics-only, clinicoradiological-only, and clinicoradiological–radiomic logistic regression models were evaluated using stratified five-fold cross-validation. Results: T2-based modelling included 151 patients, of whom 36/151 (23.8%) had subsequent csPCa detected; the median time to csPCa detection or last follow-up was 64 months. ADC analyses included 144 patients, of whom 34/144 (23.6%) had subsequent csPCa detected. The T2 clinicoradiological–radiomic model achieved a mean AUC of 0.696 ± 0.060, compared with 0.713 ± 0.072 for the T2 clinicoradiological-only model and 0.456 ± 0.091 for the T2 radiomics-only model. In the ADC-available cohort, ADC radiomics-only, ADC clinicoradiological–radiomic, and combined T2 + ADC clinicoradiological–radiomic models achieved mean AUCs of 0.684 ± 0.052, 0.635 ± 0.157, and 0.663 ± 0.106, respectively. Calibration was imperfect, with deviations at higher predicted probabilities and overprediction in the highest predicted-risk bin. Conclusions: Baseline whole-gland MRI radiomics showed limited and inconsistent predictive value for subsequent csPCa detection after negative biopsy and did not demonstrate consistent incremental improvement over clinicoradiological predictors. These findings are exploratory and hypothesis-generating, and external validation is required before clinical use. Full article

Background: Recent studies have reported associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer (CRC). However, the findings thus far are inconsistent. This study aims to clarify the association of vitamin D intake, VDR levels, and relevant polymorphisms in early stages of CRC in Thai patients following vitamin D₃ supplementation. Methods: Total RNA and genomic DNA were isolated from the buffy coats of CRC patients (n = 27). The levels of VDR, RXR, CYP27B1, and CYP24A1 were measured using quantitative real-time PCR. Associations of nine single-nucleotide polymorphisms (SNPs) of VDR, CYP27B1, CYP24A1 and serum vitamin D levels were investigated. Results: The expression levels of VDR, RXR and CYP27B1 were significantly elevated in the vitamin D₃-treated group. However, no significant associations were observed between vitamin D intake and the specific VDR SNPs, including FokI, BsmI, ApaI, TaqI, and Tru9I. Furthermore, none of the SNPs or haplotypes within the VDR, CYP27B1 (rs10877012), or CYP24A1 (rs6013897, rs158552, rs17217119) were linked to colorectal cancer susceptibility. Conclusions: This finding demonstrated that vitamin D intake enhances the expression of VDR and related genes in early-stage CRC patients; these effects are independent of VDR, CYP27B1, and CYP24A1 genetic polymorphisms. This suggests that gene expression changes may be driven more by vitamin D status than by underlying genetic variation. Full article

Sodium-cooled fast reactors (SFRs) are being developed with various fuel cycle strategies, including once-through and recycling options. Initial U.S. deployments are expected to use compact SFR cores fueled with high-assay low-enriched uranium (HALEU). As SFR technology advances, higher fuel burnups and lower enrichments are anticipated. This study provides an economic assessment of utilizing HALEU in SFRs with a once-through fuel cycle (OTC) compared to recycling used nuclear fuel (UNF) across a range of advanced fuel and reactor designs. As an alternative to current once-through options (FC #1), three recycling alternatives are evaluated: (FC #2) recovered uranium (RU) downblended for pressurized water reactor (PWR) fuel, (FC #3) RU re-enriched for SFR fuel, and (FC #4) RU co-recycled with transuranics (RU/TRU) for SFR fuel. Results indicate that recycling RU from SFR UNF in both fresh PWR and SFR fuel can be economically advantageous compared to the OTC approach, provided the U-235 content remains sufficiently high—a condition met by current and near-term SFR designs. Increased burnup and in situ plutonium production in SFRs reduce overall OTC costs and natural uranium requirements. However, the economic viability of recycling SFR RU depends strongly on the specific UNF composition and the recycling pathway chosen. Recycling both RU and TRU consistently offers the lowest fuel cycle costs across all scenarios, even as fuel and reactor designs advance. These findings provide a framework for identifying when recycling offers economic benefits over direct disposal, informing future fuel cycle decisions for advanced reactors. Full article

Breast cancer (BC) is a heterogeneous disease influenced by genetic and regulatory mechanisms. Despite this, X-linked non-coding variants remain underexplored, particularly in admixed Latin American populations. Therefore, this study aimed to characterize the non-coding variant rs5945619 at Xp11.22 in Ecuadorian mestizo women with BC and to assess its potential regulatory effects on nearby genes through in silico cis-eQTL analysis. A prospective observational case series was conducted in 21 Ecuadorian mestizo women with histologically confirmed BC. Tumor DNA was extracted and analyzed using the Illumina TruSight Cancer Sequencing Panel. The rs5945619 variant was identified from sequencing data and compared with reference allele frequencies from dbSNP, ALFA, and the 1000 Genomes Project. Regulatory potential was assessed using RegulomeDB v2.2, and tissue-specific cis-eQTL associations were explored using GTEx. All 21 patients carried the genetic variant rs5945619 in a heterozygous state. The mean age at diagnosis was 54.5 ± 12.2 years, and invasive breast carcinoma of no special type was the predominant histological subtype. The T-allele frequency in the study cohort was 0.50, whereas Latin American reference populations showed higher frequencies ranging from 0.69 to 0.83. RegulomeDB assigned rs5945619 a rank of 1f and a functional score of 0.22, supporting its regulatory potential. GTEx analysis identified tissue-specific cis-eQTL signals, including LINC01496 upregulation in testis, NUDT11 and LINC01496 downregulation in prostate, and modest GSPT2 downregulation in mammary tissue. This study provides the first characterization of rs5945619 in Ecuadorian mestizo women with BC and suggests its role as a potential X-linked regulatory variant, requiring further validation. Although universal heterozygosity was observed, the small sample size, tumor-only design, and absence of a healthy control cohort prevent any causal, risk-factor, or tumor-driven selection inference. The in silico evidence supports a tissue-dependent regulatory model involving LINC01496 and NUDT11, mainly in prostate/testis, and a modest GSPT2 signal in mammary tissue. Therefore, breast cancer-specific eQTL analyses, functional validation, and larger ancestry-informed case–control studies are required to determine the biological and clinical relevance of this locus. Full article

This study presents an integrated computational framework combining Computational Fluid Dynamics (CFD), experimental validation, and surrogate modelling to analyse and optimise the thermal performance, thermodynamic stability, and energy efficiency of a refrigerated truck compartment. CFD simulations were conducted to investigate airflow distribution and temperature uniformity under operating temperatures ranging from 0 to 5 °C. The results showed that airflow circulation was primarily governed by the evaporator outlet, while recirculation zones enhanced air mixing but were insufficient to completely eliminate localised hotspots. Increasing the operating temperature from 0 to 5 °C resulted in a rise in the maximum compartment temperature from 6.26 to 10.01 °C. Thermodynamic stability analysis revealed that operation within the 3–5 °C range provided more stable thermal conditions due to reduced refrigeration load and improved temperature uniformity. Experimental measurements of airflow velocity and evaporator surface temperature demonstrated good agreement with CFD predictions, confirming the reliability of the numerical model. Furthermore, CFD-based optimisation reduced the electrical energy consumption of the eTRU system by 10.0%, decreasing the energy intensity from 0.117 to 0.105 kWh km⁻¹, while maintaining improved thermal stability throughout the refrigerated compartment. The surrogate model achieved excellent predictive performance with R² = 0.9576 and RMSE = 0.0386, demonstrating its suitability for rapid optimisation of refrigerated transport systems. The proposed framework offers an effective tool for improving thermal management, enhancing energy efficiency, and supporting the development of sustainable refrigerated transport systems. Full article

The continuous expansion of digital tourism has increased the need to understand tourists’ intentions to book hotels online in competitive digital marketplaces. Previous studies have generally relied on symmetric analytical approaches, which have limited the understanding of the complex causal mechanisms underlying online hotel booking intention, especially in emerging tourism markets such as Thailand. This study aimed to investigate the determinants of online hotel booking intention (OBI) among Thai tourists by integrating partial least squares structural equation modeling (PLS-SEM) and fuzzy-set Qualitative Comparative Analysis (fsQCA). The study collected data from 1884 Thai tourists who had prior experience with online hotel booking. Furthermore, PLS-SEM was used to examine the linear relationships among the study constructs, whereas fsQCA was employed to identify multiple causal configurations leading to OBI. The findings indicate that electronic word of mouth (E-WOM) was the strongest direct driver of OBI, while customer experience (CEX) significantly enhanced perceived value (PCV). Trust (TRU) emerged as a key relational mechanism that strengthened perceived usefulness (PU) and facilitated the development of E-WOM, while electronic promotion (EPM) indirectly influenced OBI. In addition, fsQCA identified multiple sufficient configurational pathways leading to high OBI, supporting the principle of equifinality. Collectively, these findings advance the theoretical understanding of OBI by demonstrating that the integration of symmetric and asymmetric analytical approaches provides complementary insights into tourists’ decision-making processes. Full article

This document outlines the quality standards, experimental configurations, and precise workflows utilized to execute a metallic powder bed fusion process for creating aerospace test pieces. Using AlSi10Mg alloy, validation specimens were produced on a TRUMPF TruPrint 2000 machine according to a dedicated commissioning strategy. Metallographic evaluations targeted grain dimensions, morphology, boundaries, and phase compositions like precipitates or carbides. Findings showed scattered precipitates averaging 4 µm across the cross-sections. Subsequent X-ray microtomography (XCT) assessed porosity levels plus defect geometry and placement, offering comprehensive data on specific inclusions alongside broader statistics. XCT detected internal pore sizes ranging from 0.02 to 0.9 mm and rare clusters of high-density particles with a diameter of approximately 0.03 mm. Tensile evaluations of two batches showed a 72 GPa longitudinal elasticity modulus, 240 MPa offset yield strength, 350 MPa ultimate tensile strength, and 7% failure elongation. These positive results finalized a successful commissioning phase, enabling the subsequent design of lightweight aerospace mechanical assemblies. Full article

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline pathogenic or likely pathogenic variants (PV/LPV) in mismatch repair (MMR) genes. Data on the spectrum of LS-associated variants in Slavic populations, including Serbia, remain limited. Given the high burden of CRC and endometrial cancer and the limited implementation of hereditary CRC screening, characterizing the spectrum of germline variants in clinically selected high-risk individuals is important for improving genetic testing strategies, risk assessment, and clinical management. Between 2018 and 2025, 176 individuals underwent germline testing for hereditary CRC syndrome based on the Amsterdam/Bethesda criteria, validated LS risk prediction models, and/or family history (FH). Next-generation sequencing (NGS) was performed using the Illumina TruSight Hereditary Cancer Panel, and variants were classified according to American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) guidelines. PV/LPVs in MMR genes were identified in 27/176 (15.3%) and were associated with positive FH of LS-related tumors (p = 0.0001). Most PV/LPVs were identified in MLH1 (10.2%), followed by MSH2 (4.0%) and MSH6 (1.1%), with no PV/LPVs identified in PMS2. Additionally, no pathogenic sequence-level EPCAM variants detectable by the applied panel-based NGS approach were identified. Recurrent MLH1 variants were observed in multiple families, and two previously unreported MLH1 variants were identified. This first systematic analysis of a clinically selected high-risk Serbian cohort provides novel data on the spectrum of LS-associated variants in this referral population, demonstrates the predominance of MLH1 variants, and supports broader implementation of genetic testing, tumor screening, and genetic counseling. Full article

This study examined the extent to which corporate social responsibility (CSR) dimensions shaped hotel reputation (REP) through customer trust (TRU), and whether customer engagement (ENG) moderated this relationship in the Mekong Delta context. Although prior studies had acknowledged the importance of CSR in shaping customer perceptions, they had paid limited attention to the distinct effects of multidimensional CSR and the conditions under which TRU was transformed into REP. A structured questionnaire survey was administered to 874 hotel guests in the Mekong Delta, Vietnam. The measurement scales were adapted from previous studies and refined through a pilot test. Partial least squares structural equation modeling (PLS-SEM), together with bootstrapping, was used to test the direct, mediating, and moderating effects. CSR dimensions exhibited heterogeneous effects. Customer-oriented responsibility had the strongest impact on both TRU and REP, followed by environmental and economic responsibilities. Legal responsibility directly enhanced REP but did not significantly affect TRU, whereas community responsibility strengthened TRU without directly influencing REP. TRU significantly improved REP and mediated most CSR–REP relationships. ENG positively moderated the TRU–REP link, amplifying reputational outcomes. The study contributed to CSR and hospitality research by modeling CSR as a multidimensional construct and by identifying ENG as a boundary condition that strengthened the TRU–REP mechanism. Managers should prioritize customer-focused CSR and enhance engagement to maximize reputational gains. Full article

Unbalanced input voltage can significantly affect the electrical behavior of transformer rectifier units (TRUs), especially when a diode open-circuit (OC) fault breaks the original diode conduction symmetry. However, the effect of unbalanced input voltage on the diode OC fault has not been sufficiently clarified from the perspective of a conduction mechanism. This paper analyzes the effect of unbalanced input voltage on diode OC faults in TRUs by establishing a conduction-oriented mechanism. Unbalanced input voltage is divided into two forms, namely, unequal magnitude and phase-shift deviation. The effects on diode conduction boundaries, conduction angles, and conduction intervals are first derived theoretically. Then, using a 12-pulse TRU with $D_{11}$ and $D_{21}$ OC faults as representative cases, current and voltage responses are investigated in both time and frequency domains. The experimental results show that the two forms change diode conduction intervals in different ways. In particular, an unequal magnitude changes the relative driving voltage dominance near the conduction boundaries, resulting in the stretching or compression of diode conduction intervals; phase-shift deviation shifts the angular positions of the driving voltages and modifies the commutation timing. Two forms further aggravate waveform asymmetry and enhance low-order and non-characteristic harmonics under diode OC fault conditions. This effect analysis provides a more comprehensive basis for understanding diode OC fault responses in 12-pulse TRUs and supports the development of more robust diode OC fault diagnosis methods under non-ideal input voltage conditions. Full article

Background/Objectives: Given rising lung cancer incidence and limited data on pulmonologist-performed ultrasound-guided transthoracic core biopsy (US-TTCB), in this study, we evaluated diagnostic yield and safety for pleural or pulmonary lung masses, using Clavien–Dindo classification to standardize complication reporting. Methods: We retrospectively reviewed single-center pulmonologist-performed US-TTCB using a MEDONE biopsy gun with a 16 G/18 G Tru-Cut needle between January 2019 and December 2025. The primary endpoints were diagnostic yield, defined as specific malignant or benign histology, and complication rate. Non-diagnostic results were assessed using available clinical/imaging follow-up. Univariate analyses screened candidate correlates, and a prespecified computer tomography (CT)-completed subanalysis (n = 67) used multivariable logistic regression and receiver operating characteristic (ROC) analysis to assess CT lesion size discrimination. Results: Diagnostic yield was 84.2% (202/240); complications occurred in 12.1% (29/240), including one Clavien–Dindo Grade III event (0.4%). In the CT-completed subset (n = 67), diagnostic yield was independently associated with CT lesion size (aOR 1.03/mm, 95% CI 1.00–1.05; p = 0.022) and Chronic Obstructive Pulmonary Disease (COPD) (aOR 2.30, 95% CI 1.06–4.96; p = 0.034); CT lesion size showed an area under the curve (AUC) of 0.717 for predicting yield. Diagnostic yield remained stable over time (84.2% in first vs. second half; p = 1.00), with no association between case order and yield (OR 0.999; p = 0.64). Conclusions: US-TTCB of pleural/pulmonary masses achieved a high diagnostic yield with minimal major complications. Large CT dimension and COPD were associated with higher diagnostic success, and CT size provided fair discrimination for predicting yield; findings should be interpreted in the context of the retrospective single-center design and the restricted CT-completed subset. Full article

Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score ≥42, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation. Full article

Introduction: Lung cancer, the leading cause of cancer-related mortality worldwide, is a heterogeneous malignancy comprising distinct histological and molecular subtypes, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases and adenocarcinoma (ADC) representing the most prevalent histotype. An emerging pathological feature of NSCLC, spread through air spaces (STAS)—defined as the extension of tumor cells into the lung parenchyma beyond the main tumor margin—has been associated with worse disease-free and overall survival and has been proposed as a possible predictor of recurrence to guide surgical extent. Concurrently, recent comprehensive genomic profiling of early-stage NSCLC has highlighted the need to interpret multi-omics data and their relationship with pathological variables, including IASLC histological subtypes, to better personalize treatment strategies. In this context, we investigated the overall distribution of STAS and its association with tumor mutational profiles and IASLC histological subtypes in a large real-world cohort of lung adenocarcinoma patients from the LANTERN project. Materials and Methods: In a prospective, multicenter observational study (March 2023–December 2024), 271 NSCLC patients were enrolled, and clinicopathological, immunohistochemical, and genomic data were collected; comprehensive genomic profiling was performed using the TruSight Oncology 500 assay to analyze 523 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability; and STAS was assessed according to IASLC criteria. Adenocarcinoma accounted for roughly 90% of the cases, with a median age of 69 years and a predominance of stage IV disease (49.5%). STAS was evaluable in 162 cases and was detected in 17.9% of tumors. Results: STAS-positive tumors showed a higher trend towards locally advanced and advanced disease; no differences were observed in sex, age, smoking status, tumor mutational burden, or PD-L1 expression. Additionally, STAS-positive tumors showed a higher association with micropapillary, mucinous, and papillary patterns, whereas the acinar pattern was more frequent in STAS-negative tumors. The most frequently mutated genes were TP53, KRAS, EGFR, and STK11, with no significant differences between groups; ROS1 alterations were absent in STAS-negative tumors but detected more frequently in STAS-positive cases. Conclusions: Overall, these findings indicate that STAS positivity is associated with high-risk histological subtypes and advanced disease, suggesting its importance as a marker of tumor aggressiveness and emphasizing the need for its systematic evaluation in lung adenocarcinoma to better guide surgical planning and patient risk assessment. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Prostate cancer (PCa) is predominantly an acinar adenocarcinoma arising from the prostatic glandular epithelium, with tumor grade assessed using the International Society of Urological Pathology (ISUP) Grade Group classification, reflecting the degree of glandular differentiation and underlying molecular heterogeneity. PCa exhibits wide clinical behavior heterogeneity, ranging from indolent disease to aggressive forms with poor outcomes. Accurate prognostic assessment is, therefore, essential for guiding treatment selection and monitoring disease progression. This review examines recent advances in imaging and non-imaging biomarkers that contribute to improved risk stratification, treatment planning, and disease monitoring. Particular attention is given to multiparametric magnetic resonance imaging (mpMRI), whole-body magnetic resonance imaging (WB-MRI), positron emission tomography/computed tomography (PET/CT), positron emission tomography/magnetic resonance imaging (PET/MRI), computed tomography (CT), and transrectal ultrasound (TRUS), evaluated for their capacity not only to detect disease but also to predict recurrence, progression, and survival outcomes. In parallel, the prognostic role of non-imaging biomarkers is discussed, including the prostate-specific antigen (PSA), histopathological grading, biochemical and inflammatory biomarkers, as well as genomic classifiers and circulating tumor DNA (ctDNA). Emerging approaches such as radiomics, liquid-biopsy-derived molecular profiles, and artificial intelligence (AI)-based multimodal integration are highlighted for their potential to enhance individualized decision making. This review underscores the importance of combining imaging and molecular information to refine prognostic models and accelerate the translation of precision medicine in PCa. Full article