Search Results (242)

The study investigates the contribution of technology (TECH), quantified by Internet penetration, in influencing tourism performance (TP) among the top ten touristic nations in Europe: France, Spain, Italy, Turkey, the United Kingdom, Germany, Greece, Austria, Portugal, and the Netherlands. Using panel data from 2000–2022, the study includes additional structural controls like environment quality, gross domestic production (GDP) per capita, exchange rate (ER), and safety index (SI). The Method of Moments Quantile Regression (MMQR) is employed to capture heterogeneous effects at different levels of TP, and Driscoll–Kraay standard error (DKSE) correction is employed to make the analysis robust against autocorrelation as well as cross-sectional dependence. Spectral–Granger causality tests are also conducted to check short- and long-run dynamics in the relationships. Empirical results are that TECH and SI are important in TP at all quantiles, but with stronger effects for lower-performing countries. Environmental quality (EQ) and GDP per capita (GDPPC) exert increasing impacts at upper quantiles, suggesting their importance in sustaining high-level tourism economies. ER effects are limited and primarily short-term. The findings highlight the need for integrated digital, environmental, and economic policies to achieve sustainable tourism development. The paper contributes to tourism research by providing a comprehensive, frequency-sensitive, and distributional analysis of macroeconomic determinants of tourism in highly developed European tourist destinations. Full article

Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article

Background: Gastric cancer (GC) is a highly heterogeneous disease and remains one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including diffuse and intestinal GC that may differ in their incidence between Asian and non-Asian cohorts. The intestinal-subtype GC has declined over the past 50 years. In contrast to the intestinal-subtype adenocarcinoma, the incidence of diffuse-subtype GC, often associated with poor overall survival, has constantly increased in the USA and Europe. The aim of this study was to analyze the expression and clinical significance of steroid hormone receptors, two membrane-bound receptors (ERRγ and GPER), and several genes involved in epigenetic alterations. The findings may contribute to revealing events driving tumorigenesis and may aid prognosis. Methods: Using mRNA from diffuse and intestinal GC tumor samples, the expression level of 11 genes, including those coding for sex hormone receptors (estrogen receptors ERα and ERβ), progesterone receptor (PR) and androgen receptor (AR), and the putative relevant ERRγ and GPER receptor were determined by RT-qPCR. Results: In diffuse GC, the expression of ERα, ERβ, PR and AR differed from their expression in the intestinal subtype. The expression of ERα and ERβ was strongly increased in the diffuse subtype compared to the intestinal subtype (×1.90, p = 0.001 and ×2.68, p = 0.002, respectively). Overexpression of ERα and ERβ was observed in diffuse GC (15 and 42%, respectively). The expression levels of PR and AR were strongly decreased in the intestinal subtype as compared to diffuse GC (×0.48, p = 0.005 and ×0.25, p = 0.003, respectively; 37.5% and 56% underexpression). ERα, ERβ, PR and AR showed notable differences for clinicopathological correlation in the diffuse and intestinal GC. A significant decrease of ERα, ERβ, PR and AR in intestinal GC correlated with the absence of lymphatic invasion and lower TNM (I-II). In diffuse GC, among the hormone receptors, increases of ERs and PR mainly correlated with expression of growth factors and receptors (IGF1, FGF7 and FGFR1), and with genes involved in epithelial-mesenchymal transition (VIM and ZEB2) or cell migration (MMP2). Our results also report the strong decreased expression of ERRγ and GPER (two receptors that bind estrogen or xenoestrogens) in diffuse and intestinal subtypes. Conclusions: Our study identified new target genes, namely hormone receptors and membrane receptors (ERRγ and GPER), whose expression is associated with an aggressive phenotype of diffuse GC, and revealed the importance of epigenetic factors (EZH2, HOTAIR, H19 and DNMT1) in gastric cancers. Full article

Soil quality assessment plays a critical role in promoting sustainable land management, particularly in fragile steppe ecosystems. This study provides a comprehensive geoecological evaluation of heavy metal contamination (Pb, Cd, Zn, Cu, Co, Ni, Fe, and Mn) in soils across five districts of the Akmola region, Kazakhstan. The assessment incorporates multiple integrated pollution indices, including the geochemical pollution index (Igeo), pollution coefficient (CF), ecological risk index (Er), pollution load index (PLI), and integrated pollution index (Zc). Spatial analysis combined with multivariate statistical techniques (PCA and clustering analysis) was used to identify pollutant distribution patterns and differentiate areas by risk levels. The findings reveal generally low to moderate contamination, with cadmium (Cd) posing the highest environmental risk due to its elevated toxic response coefficient, despite its low concentration. The study also explores the connection between current soil conditions and historical land-use changes, particularly those associated with the Virgin Lands Campaign of the mid-20th century. The highest PLI values were recorded in the Yesil and Atbasar districts (7.88 and 7.54, respectively), likely driven by intensive agricultural activity and lithological factors. PCA and cluster analysis revealed distinct spatial groupings, reflecting heterogeneity in both the sources and distribution of soil pollutants. Full article

New urbanization (NU) is an urban development strategy proposed by China that takes into account both urban development and ecological protection. It aims to improve the resistance and resilience of ecosystems, that is, to improve ecological resilience (ER). Whether NU has a sustained positive effect on ER is the focus of scholars, but they mostly ignore the fact that different scales and geographical conditions may lead to non-linear or threshold effects on ER. This study used a variety of spatial analysis models to construct a multi-scale heterogeneity analysis framework to explore this impact. The results show that (1) The impact of NU on ER has a threshold effect, which is affected by population agglomeration and innovation diffusion. (2) At the whole basin scale, the impact of NU on ER changed from negative to positive, while at the urban scale, it showed coordinated development in the south and an antagonism in the north. (3) The urban population density, education and technology expenditure, and urban greening rate are the dominant factors affecting ER. Their spatial differentiation rules verify the synergy mechanism between human capital and green infrastructure. This research has important guiding value for the ecological protection of rapid urbanization areas. Full article

Breast cancer is the leading threat to the health of women, with a rising global incidence linked to social and psychological factors. Among its subtypes, triple-negative breast cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is highly heterogeneous with early metastasis and a poor prognosis, making it the most challenging subtype. Mounting evidence shows that the mitochondrial quality control (MQC) system is vital for maintaining cellular homeostasis. Dysfunction of the MQC is tied to tumor cell invasiveness, metastasis, and chemoresistance. This paper comprehensively reviews the molecular link between MQC and TNBC development. We focused on how abnormal MQC affects TNBC progression by influencing chemoresistance, immune evasion, metastasis, and cancer stemness. On the basis of current studies, new TNBC treatment strategies targeting key MQC nodes have been proposed. These findings increase the understanding of TNBC pathogenesis and offer a theoretical basis for overcoming treatment challenges, providing new research angles and intervention targets for effective precision therapy for TNBC. Full article

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), remains a therapeutic challenge due to its aggressive nature, limited treatment options, and high recurrence rates. Current therapies, including chemotherapy and immune checkpoint inhibitors, face resistance driven by tumor heterogeneity, immunosuppressive signaling, and dysregulated redox pathways. This review explores silibinin’s potential to modulate the tumor immune microenvironment (TIME) and overcome therapeutic resistance in TNBC. Silibinin exerts multifaceted anticancer effects by suppressing PD-L1 expression through the inhibition of JAK/STAT3 signaling and MUC1-C interaction, attenuating NF-κB-driven inflammation, and downregulating CCL2-mediated recruitment of tumor-associated macrophages (TAMs). Additionally, silibinin disrupts redox adaptation by targeting the Nrf2-EGFR-MYC-TXNIP axis, enhancing oxidative stress and chemosensitivity. Preclinical studies highlight its ability to inhibit epithelial–mesenchymal transition (EMT), reduce cancer stem cell (CSC) populations, and synergize with existing therapies like PD-1 inhibitors. Despite its low bioavailability, advanced formulations such as liposomes and nanoparticles show promise in improving delivery and efficacy. By reshaping TIME through dual antioxidant and immunomodulatory mechanisms, silibinin emerges as a viable adjunct therapy to reverse immunosuppression and chemoresistance in TNBC. Full article

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of outer dynein arms (ODA), with chaperones like Glucose-regulated protein 78 (GRP78) facilitating protein folding. This study investigates ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) mutations in individuals with PCD. Methods: Eight individuals aged 14–22 with clinical PCD symptoms and confirmed DNAH5 mutations were included. We analyzed the correlation between DNAH5 abnormalities and preassembly/chaperone proteins using immunofluorescence labeling. Nasal swabs were double-labeled (DNAH5–β-tubulin, β-tubulin–ZMYND10, β-tubulin–GRP78) and examined via fluorescence microscopy. Serum metabolomics and proteomics were also assessed. Results: The corrected total cell fluorescence (CTCF) levels of DNAH5, ZMYND10, and GRP78 were significantly different between PCD individuals and controls. Metabolomic analysis showed reduced valine, leucine, and isoleucine biosynthesis, with increased malate and triacylglycerol biosynthesis, malate-aspartate and glycerol phosphate shuttles, and arginine/proline metabolism, suggesting mitochondrial and ER stress. Conclusions: The altered expression of DNAH5, ZMYND10, and GRP78, along with metabolic shifts, points to a complex link between ciliary dysfunction and cellular stress in PCD. Further studies are needed to clarify the underlying mechanisms. Full article

Background/Objectives: This study aims to distinguish radiological differences between primary idiopathic Usual Interstitial Pneumonia (UIP) and secondary UIP patterns Methods: This retrospective study included patients with HRCT findings consistent with a UIP pattern. Final diagnoses were established via multidisciplinary discussion and classified as primary UIP/IPF or secondary UIP, following the 2022 ATS/ERS/JRS/ALAT guidelines. An expert thoracic radiologist (>10 years of experience), blinded to clinical data, reviewed the earliest available HRCT assessing key imaging features: honeycombing (micro-, macro- or exuberant), fibrosis distribution (symmetry, anterior-upper lobe sign, etc.), ground-glass opacities (GGO), dilatation of esophagus. Additionally, AI software AVIEW Build 1.1.46.28-win Coreline (©Coreline Soft Co., Ltd. All Rights Reserved). performed lung texture analysis, quantifying total lung volume and radiological patterns. Statistical analysis was performed to reveal results. Results: Among 53 cases, 31 were classified as IPF and 22 as secondary UIP cases. The expert radiologist achieved a diagnostic sensitivity of 82.9%, specificity of 889%, with a positive predictive value of 93.5%—in distinguishing between primary and secondary UIP. Primary UIP cases exhibited typical hallmark radiological features, including uniform honeycombing with cranio-caudal distribution (90.3%). Reticulations contributed significantly to the fibrotic texture, maintaining a consistent cranio-caudal gradient and axial symmetry (84.8%). Secondary UIP displayed more significant radiological heterogeneity, including patchy fibrosis with irregular GGO distribution (84.5% versus 53.33%); other findings—such as exuberant honeycombing, four corner sign and wedge-shaped fibrosis—were mainly observed in secondary pattern with respective percentages of 31.8%, 9% and 49%. Conclusions: Experienced thoracic radiologists, leveraging hallmark imaging features, play a critical role in improving diagnostic accuracy between primary and secondary UIP patterns. Full article

Surface mining activities cause severe disruption to ecosystems, resulting in the substantial destruction of surface vegetation, the loss of soil organic carbon stocks, and a decrease in the ecosystem’s ability to sequester carbon. The ecological restoration of mining areas has been found to significantly enhance the carbon storage capacity of ecosystems. This study evaluated ecological restoration strategies in Chongqing’s Tongluo Mountain mining area by integrating GF-6 satellite multispectral data (2 m panchromatic/8 m multispectral resolution) with ground surveys across 45 quadrats to develop a quadratic regression model based on vegetation indices and the field-measured biomass. The methodology quantified carbon storage variations among engineered restoration (ER), natural recovery (NR), and unmanaged sites (CWR) while identifying optimal vegetation configurations for karst ecosystems. The methodology combined the high-spatial-resolution satellite imagery for large-scale vegetation mapping with field-measured biomass calibration to enhance the quantitative accuracy, enabling an efficient carbon storage assessment across heterogeneous landscapes. This hybrid approach overcame the limitations of traditional plot-based methods by providing spatially explicit, cost-effective monitoring solutions for mining ecosystems. The results demonstrate that engineered restoration significantly enhances carbon sequestration, with the aboveground vegetation biomass reaching 5.07 ± 1.05 tC/ha, a value 21% higher than in natural recovery areas (4.18 ± 0.23 tC/ha) and 189% greater than at unmanaged sites (1.75 ± 1.03 tC/ha). In areas subjected to engineered restoration, both the vegetation and soil carbon storage showed an upward trend, with soil carbon sequestration being the primary form, contributing to 81% of the total carbon storage, and with engineered restoration areas exceeding natural recovery and unmanaged zones by 17.6% and 106%, respectively, in terms of their soil carbon density (40.41 ± 9.99 tC/ha). Significant variations in the carbon sequestration capacity were observed across vegetation types. Bamboo forests exhibited the highest carbon density (25.8 tC/ha), followed by tree forests (2.54 ± 0.53 tC/ha), while grasslands showed the lowest values (0.88 ± 0.52 tC/ha). For future restoration initiatives, it is advisable to select suitable vegetation types based on the local dominant species for a comprehensive approach. Full article

Background: Idiopathic duodenal hematoma is a rare clinical condition, typically associated with trauma, anticoagulation therapy, gastrointestinal procedures, or coagulopathies. We present a unique case of spontaneous duodenal hematoma in a patient without identifiable risk factors. Case presentation: We present the case of a 60-year-old Asian woman who presented to the emergency room (ER) with a 10-day history of progressive abdominal pain, early satiety, nausea, and vomiting. She had no history of trauma, anticoagulant use, or underlying predisposing conditions. On clinical evaluation, she was hemodynamically stable, and the initial laboratory results were unremarkable except for signs of dehydration and inflammation. A computed tomography (CT) scan revealed a heterogeneous lesion in the second portion of the duodenum, initially raising suspicion of a duodenal tumor. Further evaluation with magnetic resonance imaging (MRI) confirmed a duodenal hematoma with compression of the adjacent pancreas. Management and Outcome: The patient was managed conservatively with bowel rest, nasogastric decompression, intravenous (IV) fluid, and a proton pump inhibitor (PPI). Serial imaging demonstrated gradual hematoma resolution, with progressive improvement in her symptoms. She was discharged in stable condition and returned to normal activity after three weeks with complete hematoma resolution as seen on follow-up imaging. Conclusions: This case highlights the importance of considering spontaneous hematoma in the differential diagnosis of abdominal pain, even without risk factors. Early diagnosis and conservative treatment remain the mainstay of management and can lead to full recovery in uncomplicated cases. Full article

The evidential reasoning (ER) rule has been widely adopted in engineering fault diagnosis, yet its conventional implementations inherently neglect evidence correlations due to the foundational independence assumption required for Bayesian inference. This limitation becomes particularly critical in practical scenarios where heterogeneous evidence collected from diverse sensor types exhibits significant correlations. Existing correlation processing methods fail to comprehensively address both linear and nonlinear correlations inherent in such heterogeneous evidence systems. To resolve these theoretical and practical constraints, this study develops MICER—a novel ER framework that incorporates correlation analysis based on the maximum mutual information coefficient (MIC). The proposed methodology advances ER theory by systematically integrating evidence interdependencies, thereby expanding both the theoretical boundaries of ER rules and their applicability in real-world fault diagnosis. Flange ring loosening fault diagnosis and flywheel system fault diagnosis cases are experimentally verified and the effectiveness of the method is demonstrated. Full article

Low-carbon steels, such as ER70S-6, are typically considered resistant to phase transformations due to their high critical cooling rate. However, this study investigates how the manufacturing process and specimen geometry influence heat dissipation, potentially leading to localized grain size variations that impact mechanical properties. To analyze these effects, samples were fabricated using Laser Wire-Feed Additive Manufacturing (LWAM) with different geometries, and their hardness and microstructural characteristics were evaluated. Vickers microhardness tests were performed along the specimens to assess local variations, while dilatometry measurements were conducted to determine thermal expansion coefficients for future integration into finite element models (FEMs) of residual stress distribution. The results reveal that differences in heat dissipation during fabrication lead to grain size heterogeneity, affecting hardness at a microscopic scale and overall mechanical performance. These findings highlight the importance of considering thermal history and geometry in LWAM-fabricated components to ensure consistent material properties. Full article

Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 TNBC patients from two large regional cancer programs in Canada. Patients seen between 1 January 2004 and 31 December 2022 were included. Patients with grade 1 tumors and stage IV disease were excluded from analysis. Demographic information regarding the patient, tumor, and treatment were collected. The primary outcomes, relapse-free survival (RFS) and overall survival (OS), were analyzed using the Cox proportional hazards model and max-combo test. Results: For patients with grade 2 TNBC, median RFS was 14.1 years (95% CI, 9.48 to not reached (NR)) while it was not reached for patients with grade 3 tumors. No difference for relapse was identified in the first five years. Beyond 5 years, 4.9% of the patients with grade 2 tumors and 1.6% of those with grade 3 tumors relapsed (p = 0.006). In that same study period, 10.4% of patients with grade 2 tumors and 5.7% of those with grade 3 tumors died (p = 0.03). Conclusion: Grade 2 TNBC was associated with a higher risk of relapse and death after the 5-year mark compared to grade 3 TNBC. This distinct pattern of relapse and survival in grade 2 TNBC, characterized by an increased risk of relapse and mortality after 5 years, warrants confirmatory investigations. Full article

Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I–III breast cancer patients across 90 institutions in the United States and stratified risk groups based on a 70-gene signature (MammaPrint^®-MP) and molecular subtype based on an 80-gene signature (BluePrint^®-BP). This study aimed to identify the gene expression patterns and biomarkers associated with breast cancer risk and progression by integrating transcriptomic and clinical data. Methods: Targeted 111 unique gene expression and clinical data points from 978 breast cancer samples, representing each BP subtype (26% Luminal A, 26% Luminal B, 25% Basal, 23% HER2), obtained from Agendia Inc. These genes were selected based on their involvement in the mercapturic acid pathway, white and brown adipose tissue markers, inflammation markers, tumor-associated genes, apoptosis, autophagy, and ER stress markers. All statistical analyses, including principal component analysis (PCA), were performed using R version [4.4.0]. Prognostic values and genetic alterations were investigated using various web-based programs as described in the Methods section. Results: PCA of gene expression data revealed distinct clustering patterns associated with risk categories and molecular subtypes, particularly with principal component 4 (PC4). Genes related to oxidative stress, autophagy, apoptosis, and histone modification showed altered expression across risk categories and molecular subtypes. Key differentially expressed genes included SOD2, KLK5, KLK7, IL8, GSTM1/2, GLI1, CBS, and IGF1. Pathway analysis highlighted the enrichment of processes related to autophagy, cellular stress response, apoptosis, glutathione metabolism, deacetylation, and oxidative stress in high-risk and basal-like tumors compared with Ultralow and Luminal A tumors, respectively. Conclusions: This study identified gene expression signatures associated with breast cancer risk and molecular subtypes. These findings provide insights into the biological processes that may drive breast cancer progression and could inform the development of prognostic biomarkers and personalized therapeutic strategies. Full article