Search Results (1,192)

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/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

This essay examines two hybrid poetic texts that emerged from a period of feminist activism in U.S. and global poetry communities from 2014 to 2017: the collaboratively, anonymously authored “No Manifesto” (2015) and the radically revised second edition of the book of poetry and visual art YOU DA ONE by Jennif(f)er Tamayo. “No Manifesto” and YOU DA ONE embrace the hybrid tactics of collectivity, incongruity, and nonresolution as ways of protesting sexism and sexual violence in poetry communities. Synthesizing theories of hybridity from poetry criticism as well as immigrant and borderlands studies, the essay defines hybridity as a literary representation of cultural positions forcefully imposed upon subjects. Born out of the domination of sexual and state violence, hybridity marks the wound that remakes the subject, who develops strategies for resistance. By refusing to play by the rules of poetic or social discourse—the logics of domination that would have them be singular, cohesive, and compliant—Tamayo and the authors of “No Manifesto” insist on alternative ways of performing activism, composing literature, and entering the public sphere. These socially engaged, hybrid poetic texts demonstrate the power of the collective to disrupt the social and literary status quo. Full article

Background and Objectives: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. Preclinical studies have explored drugs targeting YAP1–TEAD interactions, but therapeutic application is limited. Materials and Methods: This study included 50 patients with locally advanced breast cancer, who were assessed by a multidisciplinary tumor board and underwent neoadjuvant treatment per tumor subtype and clinical guidelines. Eligibility required both pre-treatment core biopsy and post-treatment surgical resection samples. Due to the absence of residual tumor in some patients achieving complete pathological response, post-treatment tissue was available and analyzable in 30 patients. YAP1 expression was evaluated immunohistochemically for nuclear and cytoplasmic staining patterns. ROC analysis identified a cutoff for YAP1 expression, defining tumors with ≥70% nuclear and ≥80% cytoplasmic staining. Results: YAP1 expression had a significant relationship with tumor subtype (p = 0.001), being most frequent in HER-2-positive tumors (55.6%) and least frequent in luminal tumors (11.1%). YAP1 positivity significantly predicted axillary pathological complete response (pCR) (p = 0.01). In YAP1-positive patients, 77.8% achieved axillary pCR compared to 31.7% in YAP1-negative patients, though the YAP1 status and breast pCR association were insignificant (p = 0.07). The Mann–Whitney U test indicated that higher Ki-67 values were significantly associated with positive YAP1 expression (p = 0.028). In contrast, there was no association between ER, PR status, age, and tumor size. Following treatment, there was a statistically significant change in YAP1 expression, with nuclear staining decreasing (p = 0.004) while cytoplasmic staining increased (p = 0.002). YAP1 was significantly linked to axillary pCR, HER-2 status, and Ki-67. Conclusions: Post treatment, nuclear YAP1 decreased, whereas cytoplasmic expression increased, showing a localization shift. These results suggest that YAP1 may predict treatment response and become a future therapeutic target. Full article

The effects of a methanol extract of Nymphaea odorata (MeNO) rhizomes, its fractions and the active compound (methyl gallate, MeG) were investigated in estrogen receptor-positive (ER+) breast cancer cell lines MCF-7 and T47-D:A18, as well as ER-negative line SKBr3. Cell viability and cytotoxicity were determined using CellTiter-Glo^® 2.0 assays at concentrations ranging from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo^® 3/7, Caspase-Glo^® 8, and ApoTox-Glo™ triplex assays, as well as qPCR. Total RNA was isolated from MCF-7 cells treated with MeG. RNA-seq libraries were prepared using a Universal Plus mRNASeq kit, and sequencing was performed on a NovaSeq 6000. MeNO inhibited the growth of MCF-7 cells with an IC₅₀ of 14.1 μg/mL, as well as T47-D:A18 (IC₅₀ of 25.6 μg/mL) and SKBr3 cells (IC₅₀ of 35.5 μg/mL). Bioassay-guided fractionation of MeNO in MCF-7 cells identified the active fraction containing one compound, namely methyl gallate (MeG). MeG had an IC₅₀ of 8.6 μg/mL in MCF-7 cells. Transcriptomic analysis of MeG-treated MCF-7 cells showed differential expression of 10,634 genes, with 5643 upregulated and 4991 downregulated (FDR < 0.05). Ingenuity pathway analysis revealed the involvement of 43 canonical pathways, with the top upregulated pathways including apoptosis, autophagy, and the unfolded protein response pathways. Full article

Background/Objectives: HIF-1α and ERRα are both implicated in breast cancer progression, yet their functional interplay remains poorly understood. This study investigates their molecular crosstalk in the context of hypoxia-induced drug resistance. Methods: MCF-7 (estrogen receptor, ER-positive) spheroids and CoCl₂-treated SK-BR-3 (ER-negative) cells were used to model tumor hypoxia. Protein expression, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), pharmacological inhibition, and siRNA-mediated gene silencing were employed to assess physical and functional interactions. Immunohistochemistry (IHC) on a tissue microarray (TMA) of 168 invasive breast carcinomas was performed to evaluate clinical relevance. Results: ERRα levels remained unchanged under hypoxia, while its coactivator, Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 α (PGC-1α), was upregulated. ERRα physically interacted with HIF-1α and was required for HIF-1 transcriptional activity under hypoxic conditions. ChIP assays showed that ERRα-driven overexpression of Permeability glycoprotein 1 (P-gp) and Vascular Endothelial Growth Factor (VEGF) was mediated by HIF-1α binding to the MDR1 and VEGF promoters. Inhibition or silencing of ERRα reversed P-gp overexpression and restored intracellular doxorubicin. TMA analysis confirmed the clinical correlation between ERRα, HIF-1α, and P-gp expression, highlighting the role of ERRα in hypoxia-induced drug resistance. ERRα expression was independent of ER status, suggesting an estrogen-independent function. Conclusions: This study identifies a novel physical and functional interaction between ERRα and HIF-1α that promotes chemoresistance in hypoxic breast tumors. Targeting ERRα may represent a promising therapeutic strategy to overcome drug resistance in aggressive, ER-independent breast cancer subtypes. Full article

Background: Male breast cancer (MBC) is extremely rare, representing less than 1% of breast cancer (BC). Owing to the rarity, there is a substantial knowledge gap regarding the survival trends of MBC compared with female breast cancer (FBC). Methods: We queried the National Cancer Database for BC patients diagnosed during 2004–2018 and utilized an inverse propensity weighted cox regression model assessed the association between sex and overall survival (OS) and survival trends over time by sex. Results: We identified 24,055 MBC and 2,532,470 FBC patients. Patients with MBC were older (mean age: 65.6 vs. 61.4 years), and more likely to have stage IV at diagnosis (7% vs. 4.7%), larger tumors (cT4: 6% vs. 3.7%), and node-positive disease (18.5% vs. 15.5%) (p < 0.001) compared with FBC. MBC were more likely to be estrogen (ER) (88.5% vs. 78.5%) and progesterone receptor (PR) (79.6% vs. 68%) positive and less likely to be HER2 receptor positive (7.9% vs. 9.3%) or triple negative (2.8% vs. 7.6%) compared with FBC (all p < 0.001). The OS rates were lower in MBC compared with FBC (5-year: 73% vs. 83%; 10-year: 54% vs. 70%, p < 0.001). In the propensity weighted cox-regression model, males had higher mortality than females with BC (HR 2.8, 95% CI 2.88–2.9, p < 0.001). The 5-year OS rates increased steadily for FBC from 2004–2015; however, the survival rates did not improve for MBC over the last decade. Conclusions: Our study shows that MBC patients continue to have poor OS compared with patients with FBC and no significant improvement in survival of MBC patients over the past decade. These results underscore the need to investigate personalized treatment interventions for patients with MBC to improve outcomes. Full article

Background and Objective: We aim to determine the efficacy and the factors associated with the effectiveness of first-line CDK4/6i (ribociclib or palbociclib) treatment in HR-positive, HER2-negative MBC patients. Materials and Methods: This is a retrospective, cross-sectional, and descriptive study. Ninety patients with metastatic breast cancer receiving CDK 4/6i treatment from three different oncology clinics were included in this study. Results: Of the patients, 56 (62.2%) received ribociclib, and 34 (37.8%) were administered palbociclib. There was no significant difference between the groups regarding age, gender, comorbidities, ECOG performance status, or menopausal status (p > 0.05). The cut-off values for ER, PR, and Ki-67 levels were determined via ROC curve analysis. These values were found to be 80% for ER levels, 50% for PR levels, and 30% for Ki-67 levels. PFS was significantly longer for patients with ER levels greater than 80% and Ki-67 expression levels less than 30% according to multivariate analysis. Among the patients included in our study, the median PFS was 22.41 months for the patients with Ki-67 levels of 30% and above, while the median PFS was 17.24 months for the patients with ER levels of 80% and below. Among the patients with a combined ER of 80% or less and a Ki-67 of 30% or more, the median PFS was 12.42 months (p < 0.001). Conclusions: This study demonstrates that CDK4/6i therapies led to longer PFS among patients with ER levels greater than 80% and Ki-67 expression levels less than 30%. It is essential to determine which patient group benefits more from first-line CDK4/6is therapy. Full article

Employees’ green voice behavior (GVB), as a specific category of extra-role green behavior, plays a vital role in promoting a firm’s sustainable development. However, its underlying mechanism has not been sufficiently explored. Drawing on social learning theory (SLT), this study proposes a research model that examines the indirect influence of environmentally-specific transformational leadership (ESTFL) on GVB via psychological empowerment (PE) and ecological reflexivity (ER) as well as the moderating role of person-supervisor value congruence (PSVC). To achieve the research goals, we conducted a two-wave online survey via the convenience sampling method to collect data from 530 employees and 106 direct supervisors working in the manufacturing, hospitality and service, energy production, construction, transportation, information and communication, and finance industries in China. Regression analyses and CFA based on SPSS and Mplus were employed to test and validate the research model. Our findings show that PE and ER both partially mediated the positive association between ESTFL and GVB. Moreover, PSVC moderated the mediating effects of ESTFL on GVB via PE and ER. This study advances empirical research regarding how leadership impacts GVB by revealing dual cognitive mechanisms and identifying its boundary condition. It also offers managerial implications for leaders and enterprises in China to promote employees’ GVB and improve sustainable management. Full article

Mammary tumors are the most common neoplasms diagnosed in female dogs and have been considered excellent models for studying human breast cancer. Establishing cell lines from primary cultures of canine mammary tumors provides an in vitro model to better understand the disease and develop new treatments. This study aimed to establish and characterize canine mammary tumor cell lines. Ten cell cultures were generated from tumor tissue obtained from affected dogs, including seven from primary mammary tumors and three from metastatic sites. Characterization included molecular marker expression (ER, PR, HER2, cytokeratin 5/6 (CK5/6), vimentin, and the marker of cell proliferation Ki67) and in vitro tumorigenic capacity assessment. Additionally, the susceptibility of five cell lines to DOX, 5-FU, paclitaxel, colchicine, and carboplatin was evaluated using the MTT assay. ICC analysis revealed negative expression of hormonal receptors (ER and PR) in five cell lines, while only one cell line was positive for both. Six cell lines were HER2-negative and positive for vimentin. Five cell lines exhibited in vitro tumorigenic capacity, forming colonies in soft agar. DOX showed the highest growth-inhibitory effect (DOX > Paclitaxel > Colchicine > 5-FU > Carboplatin). Two cell lines had a minimal concentration for 50% inhibition in vitro (IC₅₀) < 0.63 µM and 4.37 ± 0.40 µM for DOX, while one was sensitive to colchicine and paclitaxel (IC₅₀ 0.19 µM and 0.04 µM, respectively). All tested cell lines were resistant to carboplatin and 5-FU. These cell lines provide a valuable model for studying breast cancer in humans and dogs and evaluating new potential therapeutic strategies. 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

The increasing sophistication of cyberattacks on smart grid infrastructure demands advanced anomaly detection and recovery systems that balance high recall rates with acceptable precision while providing reliable data restoration capabilities. This study presents an optimized two-stage anomaly detection and recovery system combining an enhanced TimerXL detector with a DeBERTa-v3-based verification and recovery mechanism. The first stage employs an optimized increment-based detection algorithm achieving 95.0% for recall and 54.8% for precision through multidimensional analysis. The second stage leverages a modified DeBERTa-v3 architecture with comprehensive 25-dimensional feature engineering per variable to verify potential anomalies, improving the precision to 95.1% while maintaining 84.1% for recall. Key innovations include (1) a balanced loss function combining focal loss ($\alpha$ = 0.65, $\gamma$ = 1.2), Dice loss (weight = 0.5), and contrastive learning (weight = 0.03) to reduce over-rejection by 73.4%; (2) an ensemble verification strategy using multithreshold voting, achieving 91.2% accuracy; (3) optimized sample weighting prioritizing missed positives (weight = 10.0); (4) comprehensive feature extraction, including frequency domain and entropy features; and (5) integration of a generative time series model (TimER) for high-precision recovery of tampered data points. Experimental results on 2000 hourly smart grid measurements demonstrate an F1-score of 0.873 ± 0.114 for detection, representing a 51.4% improvement over ARIMA (0.576), 621% over LSTM-AE (0.121), 791% over standard Anomaly Transformer (0.098), and 904% over TimesNet (0.087). The recovery mechanism achieves remarkably precise restoration with a mean absolute error (MAE) of only 0.0055 kWh, representing a 99.91% improvement compared to traditional ARIMA models and 98.46% compared to standard Anomaly Transformer models. We also explore an alternative implementation using the Lag-LLaMA architecture, which achieves an MAE of 0.2598 kWh. The system maintains real-time capability with a 66.6 ± 7.2 ms inference time, making it suitable for operational deployment. Sensitivity analysis reveals robust performance across anomaly magnitudes (5–100 kWh), with the detection accuracy remaining above 88%. Full article

Background: Breast cancer is the most prevalent women’s cancer, representing about a third of all cancers diagnosed in women. Estrogen receptor (ER) is an important transcription factor expressed in 70% to 75% of all breast cancers. Of these breast cancers, the majority express ER robustly in 91–100% of tumor cells. However, a minority of breast cancers express ER in intermediate levels between 11% and 90% of tumor cells. The characteristics and outcomes of this intermediate subset of ER-positive breast cancers are not well studied. Methods: We retrospectively reviewed the medical records of all breast cancer patients treated in our Cancer Center over a period of 8 years. Patients were grouped according to the level of ER expression in tumors with negative/low ER expression, intermediate ER expression, and high ER expression, and the groups were compared for tumor characteristics and outcomes. Results: Patients with high ER levels (91% to 100%) represented 75.6% (600 of 794 patients), patients with intermediate ER expression represented 11.5% of the entire group (91 of 794 patients), and patients with negative/low ER expression (ER expression 0–10%) represented 12.9% of the entire cohort (103 of 794 patients). Patients with intermediate ER expression presented at a younger age than patients with high-ER cancers, as well as a more advanced stage and higher grade. These characteristics were more akin to patients with negative/low ER levels. Mastectomy was the surgical method of resection more commonly in ER-intermediate tumors than in ER-high tumors. The relapse-free survival (RFS) of patients with ER-intermediate cancers was worse than the RFS of patients that expressed ER robustly. Conclusion: The level of expression of ER defines groups of patients with varying characteristics and prognoses. Patients in the intermediate ER expression group had notable differences from patients in the high ER expression group including younger age, (more often) a higher grade, and low PR positivity. Differences observed between the group of patients with intermediate ER expression and that with high ER expression may help to prioritize therapeutic algorithms. Full article

During the past decades, agricultural soil heavy metal pollution has been becoming increasingly severe due to urbanization and industrialization. However, the impact of externally input heavy metals on deep soils remains unclear because most previous relevant research only focused on surface soils. In the present study, Concentrations of eight heavy metals (Cu, Zn, Ni, Pb, Cr, Cd, As, and Hg) were determined for 72 pairs of surface and deep soil samples collected from an agricultural region close to the Pearl River estuary. Subsequently, heavy metal pollution and potential health risks were assessed using the Geo-accumulation Index and Potential Ecological Risk Index, a dose response model and Monte Carlo simulation, respectively. Principal component analysis (PCA) and the positive matrix factorization (PMF) receptor model were combined to analyze heavy metal sources. The results indicated that average concentrations of all heavy metals exceeded their corresponding background values. Cd was identified as the main pollutant due to its extremely high values of I_geo and Er. Unacceptable potential heavy metal non-carcinogenic and carcinogenic risks indicated by respectively calculated HI and TCR, higher than thresholds 1.0 and 1.0 × 10⁻⁴, mainly arose from heavy metals As, Cd, Cr, and Ni through food ingestion and dermal absorption. Anthropogenic sources respectively contributed 19.7% and 38.9% for soil As and accounted for the main contributions to Cd, Cu, and Hg (Surface: 90.2%, 65.4%, 67.3%; Deep: 53.8%, 54.6%, 56.2%) within surface and deep layers. These results indicate that soil heavy metal contents with deep layers were also significantly influenced by anthropogenic input. Therefore, we suggest that both surface and deep soils should be investigated simultaneously to gain relatively accurate results for soil heavy metal pollution and source apportionments. Full article

Background: Traumatic brain injury (TBI) is a major cause of morbimortality in the world, and it can cause potential intracranial hemorrhage (ICH), a life-threatening condition that requires rapid diagnosis with computed tomography (CT). Artificial intelligence tools for ICH detection are now commercially available. Objectives: Investigate the real-world performance of qER.ai, an artificial intelligence-based CT hemorrhage detection tool, in a post-traumatic population. Methods: Retrospective monocentric observational study of a dataset of consecutively acquired head CT scans at the emergency radiology unit to explore brain trauma. AI performance was compared to ground truth determined by expert consensus. A subset of night shift cases with the radiological report of a junior resident was compared to the AI results and ground truth. Results: A total of 682 head CT scans were analyzed. AI demonstrated a sensitivity of 88.8% and a specificity of 92.1% overall, with a positive predictive value of 65.4% and a negative predictive value of 98%. AI’s performance was comparable to that of junior residents in detecting ICH, with the latter showing a sensitivity of 85.7% and a high specificity of 99.3%. Interestingly, the AI detected two out of three ICH cases missed by the junior residents. When AI assistance was integrated, the combined sensitivity improved to 95.2%, and the overall accuracy reached 98.8%. Conclusions: This study shows better performance from AI and radiologist residents working together than each one alone. These results are encouraging for rethinking the radiological workflow and the future of triage of this large population of brain traumatized patients in the emergency unit. Full article