Search Results (670)

Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human papillomavirus (HPV), CDKN2A (p16) status, and aberrant p53 expression. Methods: A tissue microarray (TMA) was constructed with three cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry, and H-scores for membrane and cytoplasm staining were assessed (range 0–300). The percentage of cores and patient tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. The association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence-free survival (RFS), and cancer-specific survival (CSS) was assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data were determined in a similar manner. Results: TF staining was evident in 26 (81.3%) of the cohort and was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs. 18.8; p = 0.003) and cytoplasm (H-score 59.2 vs. 17.7, p = 0.007). Cytoplasmic (H-score 61.7 vs. 11.7, p < 0.001) and membrane TF staining (H-score 71.7 vs. 15.0, p < 0.001) favored p16-negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs. 18.3, p = 0.012; membrane H-score 67.5 vs. 20.3, p = 0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p = 0.052; cytoplasmic H-score 135 vs. 107.5, p = 0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p = 0.014; cytoplasmic H-score 110 vs. 93.3, p = 0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this was due to our small sample size. Conclusions: Our results indicate that TF was expressed in the majority of advanced PSCC with enhanced expression among HPV-independent, p53-aberrant tumors and may represent a novel therapy target in advanced PSCC. Full article

The cause of nephrotic–nephritic syndrome and elevated blood pressure values was investigated by renal biopsy in a 72-year-old Caucasian male with B-cell chronic lymphocytic leukemia (B-CLL) and a low level of IgG/lambda paraprotein. Double-contoured glomerular capillaries, glomerular thrombi, interstitial B-CLL infiltrates, and normal-looking arteries and arterioles were observed histologically. The glomerular capillaries displayed nonspecific entrapment of IgM and C3 and pseudolinear C4d positivity immunohistochemically. With electron microscopy, diffusely effaced foot processes, widened and duplicated glomerular basement membrane (BM), mesangial cell interposition, and thickened, non-fenestrated, and serrated endothelial cells located on subendothelial BM layer(s) were seen. The peritubular capillaries lacked any significant BM multilayering. Chronic glomerular thrombotic microangiopathy (TMA) was diagnosed; the C4d positivity result indicated structural remodeling of glomerular capillary walls. Laboratory features of microangiopathic hemolytic anemia were absent. The functional complement assay found selective classical pathway activation and the consumption of early complement components. The components of the alternative pathway were not consumed. A disease-causing variant in the coding region of the complement C2 gene was screened, with negative results. The kidney function gradually deteriorated to stage 4 chronic kidney disease over a period of six months. Second-line treatment with ibrutinib markedly decreased the leukemic symptoms, stopped the production of paraprotein, and eliminated the nephrotic syndrome; the kidney function improved. The decreased activity of the classical pathway remained unchanged. The culprit of glomerular anomalies seemed to be the paraprotein, which acted as a nephrotoxic mediator and triggered glomerular TMA. A hypothetical pathophysiologic explanation of TMA is presented. The paraneoplastic classical pathway activation of complement did not play any role in the development of glomerular TMA. Full article

A multimode magneto-optical fiber based on Tb³⁺-containing borogermanate glass was designed, fabricated, and characterized, aiming at potential sensing applications. There are continuing challenges in the development of single-mode (SMF) or multimode (MMF) optical fibers doped with rare-earth (RE) ions and exhibiting high Verdet constants, related to devitrification of the precursor glass. Most RE-doped glass compositions are not suitable as precursors for core-cladding fiber production due to devitrification processes and consequent poor optical quality. Application as Faraday rotators is limited by the intrinsically low Verdet constant of silica (~0.589 rad T⁻¹ m⁻¹ at 1550 nm and 0.876 rad T⁻¹ m⁻¹ at 1310 nm). Borogermanate glasses are good candidates for manufacturing optical fibers due to their excellent potential to solubilize high concentrations of Tb³⁺ ions as well as satisfactory thermal stability. In this work, a magneto-optical core-cladding borogermanate fiber with a 227 μm diameter was fabricated, with characterization using differential scanning calorimetry (DSC), thermomechanical analysis (TMA), viscosity measurements, M-lines spectroscopy, UV-Vis-NIR absorption spectroscopy, the cut-back technique, and magneto-optical measurements. The measured numerical aperture (NA) was 0.183, with minimum attenuation of 13 dB m⁻¹ at 1270 nm. The Verdet constant (V_B) reached −6.74 rad T⁻¹ m⁻¹ at 1330 nm. Full article

Introduction: Allogeneic hematopoietic cell transplantation (allo-HSCT)-associated thrombotic microangiopathy (TA-TMA) and pre-transplant renal dysfunction are recognized risk factors for mortality after allo-HSCT. Utilizing the data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we investigated the association between onset of TA-TMA and pre-HSCT renal dysfunction on renal failure requiring dialysis (RFD). Methods: We evaluated TA-TMA as a time-dependent covariate in a multivariate Cox regression model for RFD in Allo-HSCT recipients aged ≥ 40 years between 2008 and 2016. Pre-HSCT patients were divided into two groups, estimated GFR (eGFR) < 60 mL/min/1.73 m² group and eGFR ≥ 60 mL/min/1.73 m². Cumulative hazards of RFD in patients with and without onset of TA-TMA were estimated. Results: TA-TMA was significantly associated with increased risk (6.6-fold compared to No TA-TMA) for RFD, the highest of all the significant risk factors. The estimated cumulative hazard for patients with TA-TMA in the two pre-HSCT renal function groups was significantly elevated when compared to similar patients with no TA-TMA (80% vs. 12% for eGFR < 60 mL/min and 50% vs. 5% for eGFR ≥ 60 mL/min group, respectively) at 12 months post-HSCT. Conclusions: Our results demonstrate that the adjusted HR of renal failure requiring dialysis and cumulative hazard was much higher in patients with onset of TA-TMA, especially among patients with pre-existing renal dysfunction, underscoring the importance of early recognition and risk-adapted management. Full article

The seafood industry is increasingly adopting intelligent packaging to preserve product quality and improve freshness transparency. This study developed and evaluated a pH-sensitive freshness indicator (FI) for skate sashimi (Zearaja chilensis). This product is consumed at varying stages of fermentation. The FI incorporated bromothymol blue (BTB) and bromocresol purple (BCP) in a polymer matrix. It targeted volatile basic nitrogen (VBN) compounds, with trimethylamine (TMA) as the primary marker. As freshness declined, VBN compounds accumulated in the package headspace and caused a gradual FI color change from yellow to blue through pH variation. ΔE increased from 7.72 on day 2 to 23.52 on day 3. This marked the onset of visible color change and the FI reached full blue by day 7. Headspace solid-phase microextraction (HS-SPME) and gas chromatography–flame ionization detection (GC-FID) quantified monomethylamine (MMA), dimethylamine (DMA) and TMA throughout storage. ΔE correlated strongly with total bacterial count (TBC, r = 0.978), pH (r = 0.901) and TMA (r = 0.888). These results indicate that microbial growth, alkalinity increase and amine production were closely associated with color transitions. The FI reliably tracked freshness loss in skate sashimi. It has potential to enhance consumer transparency and strengthen quality control in the seafood supply chain. Full article

Gut microbiota has increasingly been shown to exert effects beyond the gastrointestinal tract, some of which are mediated through its metabolites, such as trimethylamine N-oxide (TMAO)—a compound converted by gut bacteria from dietary choline found predominantly in animal products that is associated with cardiovascular disease (CVD). However, a significant gap persists in human clinical trials assessing its potential causal role. This narrative review aims to present the current understanding of the gut microbiome, TMAO, and their relationship with CVD, while proposing future directions that may support the use of TMAO as a biomarker and guide potential interventions to reduce its harmful impact. Both animal and human studies have demonstrated a link between TMAO and CVD, with animal studies also indicating a causal effect—showing increased cardiovascular risk following TMAO administration and reduced risk when TMAO is eliminated. While direct extrapolation from animal models to humans is limited due to biological differences, these findings offer a foundation for the development of well-designed clinical trials in human populations. Although direct approaches to target TMAO—such as trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide (ASO) therapy—have shown promising results in animal studies, they have yet to be investigated in human trials, leaving indirect strategies such as dietary changes and probiotics as the only currently available options. Full article

Precise trajectory prediction in the airspace of a high-density terminal area (TMA) is crucial for Trajectory Based Operations (TBO), but frequent aircraft interactions and maneuvering behaviors can introduce significant uncertainties. Most existing approaches use deterministic deep learning models that lack uncertainty quantification and explicit spatial awareness. To address this gap, we propose the BST-Transformer, a Bayesian spatio-temporal deep learning framework that produces probabilistic multi-step trajectory forecasts and supports probabilistic conflict alerting. The framework first extracts temporal and spatial interaction features via spatio-temporal attention encoders and then uses a Bayesian decoder with variational inference to yield trajectory distributions. Potential conflicts are evaluated by Monte Carlo sampling of the predictive distributions to produce conflict probabilities and alarm decisions. Experiments based on real SSR data from the Guangzhou TMA show that this model performs exceptionally well in improving prediction accuracy by reducing MADE 60.3% relative to a deterministic ST-Transformer with analogous reductions in horizontal and vertical errors (MADHE and MADVE), quantifying uncertainty and significantly enhancing the system’s ability to identify safety risks, and providing strong support for intelligent air traffic management with uncertainty perception capabilities. Full article

The persistent issue of odor nuisance poses significant challenges to the sustainable development of livestock farming. While previous studies have primarily focused on individual gas concentrations, a comprehensive understanding of overall odor impact based on human perception remains limited. This study introduces a novel perspective by employing the odor activity value (OAV)—calculated from the ratio of gas concentration to its olfactory threshold—to evaluate the actual odor contribution of various compounds. Through a meta-analysis of data from 123 papers, we systematically assessed odor emission characteristics and mitigation strategies across different manure management stages. The results indicated that ammonia (NH₃) (with maximum concentration of 8056 ppm) and hydrogen sulfide (H₂S) (with maximum concentration of 20,057 ppm) were the most concentrated odor components in the whole manure management links. However, considering the olfactory threshold, trimethylamine (TMA) (with OAVmax 380800), H₂S (with OAVmax 48919512), butyric acid (with OAVmax 801684), and aldehydes (with OAVmax 11707) played major odor-causing roles. Notably, biological methods (83%), covering (77%), and additives (39%) were the most efficient odor mitigation strategies in the barn, manure storage, and manure treatment link, respectively. Therefore, employing the OAV-based approach is crucial for identifying priority pollutants and developing targeted control strategies across different livestock species and management stages, ultimately guiding more effective odor mitigation and healthier cohabitation. Full article

Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common tumours worldwide. This study investigated the suitability of visible and near-infrared hyperspectral imaging compared to visual assessment and conventional digital image analysis for quantifying immunohistochemical staining on the example of Dickkopf-3 (DKK-3) in OSCC. Materials and methods: A retrospective analysis of TMAs containing DKK-3 stained OSCC of 50 patients was retrieved from the archives at the Institute of Pathology, Medical University of Innsbruck. TMAs were first evaluated visually, followed by digital image analysis using QuPath (version 0.3.2, open-source software). For hyperspectral imaging, six exemplary cases were selected (three cases with strong expression and three cases with weak expression) and evaluated. The collected hyperspectral images were visualised using TIVITA (Tissue Imaging System). The resulting true-colour images and the classified HSI images were then assessed using the QuPath software. The Allred score and the H-score were used for all analyses. Results: 97 tissue cores were used for visual and digital image analysis. No significant difference was found between the evaluations of visual and digital image analysis using the H-score (pWilcoxon = 0.278), and both H-scores correlated significantly with each other (p^Spearman < 0.001). Similar results were also found using the Allred score. The kappa value was 0.67, which represents a “substantial” correlation. Finally, the H-scores and Allred scores were compared for visual, digital, and HSI imaging. No significant differences were found between the three groups concerning the H-score (pWilcoxon > 0.1). Using Cohen’s Kappa, a “fair” to “moderate” correlation was observed between the three evaluations. Conclusion: Visible and near-infrared hyperspectral imaging (VIS-NIR-HSI) is a promising complementary tool for digital pathology workflows. This proof-of-concept study suggests that HSI offers the potential for more objective quantification of DKK-3 expression in oropharyngeal squamous cell carcinoma, particularly in cases with weak staining. However, given the small sample size and exploratory design, the findings should be regarded as hypothesis-generating. Future studies with larger, clinically annotated cohorts and standardised workflows are needed before any consideration of routine clinical application. Full article

Yin Yang 1 (YY1) is a multifunctional transcription factor implicated in gene regulation, cell proliferation, and survival. While its role in breast cancer (BC) has been explored, its prognostic significance remains controversial. In this study, we evaluated nuclear YY1 expression in 276 BC tissue samples using immunohistochemistry (IHC), tissue microarrays (TMAs), and digital pathology (DP). Nuclear staining was quantified using Aperio ImageScope software, focusing on tumor regions to avoid confounding from stromal or non-tumor tissues. This selective and standardized approach enabled precise quantification of YY1 expression. Our results show elevated median YY1 expression in tumor vs. normal matched tissues (p < 0.001). The optimal cutoff for medium-intensity nuclear YY1 expression in tumor areas for overall survival (OS) was established by a receiver operating characteristic (ROC) curve (AUC = 0.718, 95% CI: 0.587–0.849, p = 0.008). In contrast, ROC curves showed no prognostic impact (AUC and p-value) for YY1 quantification in whole spots (tumor + normal). As a categorical variable, high YY1 expression was correlated with more aggressive BC features, including tumor size > 3 cm (57.7% vs. 44.2% p = 0.037), the triple-negative breast cancer (TNBC) molecular subtype (27.3% vs. 13.9% p = 0.026), and advanced prognostic stage (III) (31.8% vs. 16.7% p = 0.003), while as a continuous variable, YY1 was associated with higher histological (p = 0.003) and nuclear grades (p = 0.022). High YY1 expression was significantly associated with a reduced OS of BC patients, as shown by Kaplan–Meier curves (HR = 2.227, p = 0.002). Since YY1 was significantly enriched in TNBC, we evaluated its prognostic resolution in this subgroup. But, probably due to the small number of patients within this subset, our results were not statistically significant (HR = 1.317, 95% CI: 0.510–3.405, p = 0.566). Next, we performed multivariate Cox regression, confirming YY1 as an independent prognostic factor for overall survival (HR = 1.927, 95% CI: 1.144–3.247, p = 0.014). In order to improve prognostic value, we constructed a mathematical model derived from the multivariate Cox regression results, including YYI, AJCC prognostic stage (STA), and axillary lymph node dissection (ALN), with the following equation: h(t) = h₀(t) × exp (0.695 × YY1 + 1.103 × STA − 0.503 × ALN). ROC analysis of this model showed a better AUC of 0.915, similar sensitivity (83.3%), and much higher specificity (92%). Bioinformatic analysis of public datasets supported these findings in BC, showing YY1 overexpression in multiple cancer types and its association with poor outcomes in BC. These results suggest that YY1 may play a role in tumor progression and serve as a valuable prognostic biomarker in BC. DP combined with molecular data enhanced biomarker accuracy, supporting clinical applications of YY1 in routine diagnostics and personalized therapy. Additionally, developing a combined score based on the modeling of multiple prognostic factors significantly enhanced survival predictions, representing a practical tool for risk stratification and the guidance of therapeutic decisions. Full article

Ectopic expression of human leukocyte antigen class II (HLA-II) on tumor cells correlates with anti-tumor immunity and prognosis in various cancers, but its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods: HLA-II expression was evaluated in 34 ESCC tissue sections and a 102-sample tissue microarray (TMA) using immunohistochemistry (IHC) and in 10 ESCC cell lines via flow cytometry. Transcriptome sequencing of KYSE270, KYSE180, KYSE450, and KYSE510 was performed to investigate HLA-II regulatory mechanisms, while tumor samples from 104 ESCC patients were analyzed for neoantigen load. The prognostic significance of neoantigen burden was assessed using Cox regression. Results: HLA-II was ectopically expressed in ESCC, with positivity rates of 20.59% (34 tissues) and 25.49% (TMA). Among 10 ESCC cell lines, only KYSE270 exhibited spontaneous HLA-II expression. Transcriptome analysis revealed 1278 KYSE270-specific genes enriched in immune-related pathways (e.g., “Cytokine–cytokine receptor interaction”), suggesting immune-mediated HLA-II regulation. IFN-γ stimulation induced HLA-II expression in KYSE180, KYSE450, and KYSE510, indicating broader inducible HLA-II potential. In 104 patients, MHC-II-restricted neoantigen burden varied widely (0–75) and lacked direct correlation with HLA-II expression. Additionally, MHC-II-restricted neoantigen load was not significantly associated with overall survival (p > 0.05). Conclusion: Ectopic HLA-II expression in ESCC may influence the tumor immune microenvironment, while the prognostic value of MHC-II-restricted neoantigen burden in ESCC remains unclear, providing potential implications for immunotherapy strategies. Full article

The growing demand for natural and sustainable food preservatives has drawn interest in carbon dots (CDs) derived from plant sources. This study aimed to synthesize CDs from dried German chamomile flowers (DF) and residual biomass (RB) obtained after essential oil extraction using a hydrothermal process. Their characteristics, bioactivities and cytotoxicity were examined. Both DF-CDs and RB-CDs were spherical (7–10 nm), exhibited strong UV blocking properties and tunable fluorescence and were rich in polyphenolic functional groups, especially the –OH group. DF-CDs generally showed higher antioxidant capacity than RB-CDs as assayed by DPPH, ABTS radical scavenging activities, FRAP and metal chelation activity. Both CDs showed antibacterial effects toward pathogenic bacterial strains (Escherichia coli and Listeria monocytogenes) and spoilage bacteria (Shewanella putrefaciens and Pseudomonas aeruginosa) in a dose-dependent manner. Cytotoxicity was assessed in BJ human fibroblasts, and both CDs exhibited high biocompatibility (>88% viability at 1000 µg/mL). When both CDs at 300 and 600 ppm were applied in a precooked baby clam edible portion (PBC-EP) stored at 4 °C, microbial growth, TVB and TMA contents were lower than those of the control. The total viable count was still under the limit (5.8 log CFU/mL) for the sample treated with CDs at 600 ppm up to 9 days, while the control was kept for only 3 days. Furthermore, the lipid oxidation level (PV and TBARS value) of PBC-EP decreased with CD treatment, especially at higher concentrations (600 ppm). Therefore, chamomile-derived CDs could serve as a promising alternative for perishable seafood preservation. Full article

The thermal, thermomechanical, and viscoelastic properties of continuous unidirectional (UD) glass fiber/high-density polyethylene (GF/HDPE) and ultra-high-molecular-weight polyethylene/high-density polyethylene (UHMWPE/HDPE) tapes are characterized in this paper in order to support their use in extreme environments. Unlike prior studies that focus on short-fiber composites or limited thermal conditions, this work examines continuous fiber architectures under five operational environments derived from Army Regulation 70-38, reflecting realistic defense-relevant extremes. Differential scanning calorimetry (DSC) was used to identify melting transitions for GF/HDPE and UHMWPE/HDPE, which guided the selection of test conditions for thermomechanical analysis (TMA) and dynamic mechanical analysis (DMA). TMA revealed anisotropic thermal expansion consistent with fiber orientation, while DMA, via strain sweep, temperature ramp, frequency sweep, and stress relaxation, quantified their temperature- and time-dependent viscoelastic behavior. The frequency-dependent storage modulus highlighted multiple resonant modes, and stress relaxation data were fitted with high accuracy (R² > 0.99) to viscoelastic models, yielding model parameters that can be used for predictive simulations of time-dependent material behavior. A comparative analysis between the two material systems showed that UHMWPE/HDPE offers enhanced unidirectional stiffness and better low-temperature performance. At the same time, GF/HDPE exhibits lower thermal expansion, better transverse stiffness, and greater stability at elevated temperatures. These differences highlight the impact of fiber type on thermal and mechanical responses, informing material selection for applications that require directional load-bearing or dimensional control under thermal cycling. By integrating thermal and viscoelastic characterization across realistic operational profiles, this study provides a foundational dataset for the application of continuous fiber thermoplastic tapes in structural components exposed to harsh thermal and mechanical conditions. Full article

Trimethylamine (TMA) is a common malodorous pollutant known for its detrimental effects on both the natural environment and human health. In this study, strain PM-1 was successfully isolated from activated sludge in a sewage treatment plant and identified as the first Microbacterium lacticum capable of degrading TMA. Strain PM-1 is characterized as a mesophilic and mild halotolerant bacterium, thriving within a temperature range of 20–40 °C and a salinity range of 10–80 g/L NaCl. The optimal initial TMA concentrations for strain PM-1 were determined to be 0.1 wt% under aerobic conditions and 0.05 wt% under anaerobic conditions. The strain demonstrated efficient TMA degradation rates of 98.02 mg/L/h aerobically and 4.44 mg/L/h anaerobically. Additionally, beef extract and peptone significantly enhanced TMA degradation and bacterial growth by 293% and 688%, respectively, under aerobic conditions. Microbacterium lacticum strain PM-1 is the first isolated Microbacterium lacticum with the ability to convert TMA. Further research will focus on its TMA degradation pathway through the identification of key enzymes and application in TMA-containing wastewater and exhaust gas. Full article

Background/Objectives: Gut microbial metabolism of choline and related quaternary amines to trimethylamine (TMA) is the first step in the production of trimethylamine N-oxide (TMAO), a circulating metabolite that contributes to the development of atherosclerosis and other forms of cardiovascular disease (CVD). No data exist on regional differences in TMA production within the colon due to difficulties studying gut regions in vivo. A better understanding of TMA production by gut microbiota is needed to develop strategies to limit TMA production in the gut and TMAO levels in circulation with the goal of reducing CVD risk. Methods: We employed our novel three-compartment MiGut in vitro model, which establishes three distinct microbial ecologies mimicking the proximal, mid, and distal colon, to study conversion of choline to TMA by human gut microbiota using isotopically labelled substrate. Results: Choline-d₉ was almost completely converted to TMA-d₉ in vessels 2–3 (mimicking the mid and distal colon) within 6–8 h, but little conversion occurred in vessel 1 (mimicking the proximal colon). Abundance of cutC, part of the cutC/D gene cluster responsible for choline conversion to TMA, was highest in vessel 1 vs. 2–3, suggesting that its expression or activity may be suppressed in the proximal colon. Another possibility is that the viability/activity of bacteria expressing cutC could be suppressed in the same region. Conclusions: This novel finding suggests that while bacteria capable of converting choline to TMA exist throughout the colon, their activity may be different in distinct colon regions. The regional specificity of TMA production, if confirmed in vivo, has implications for both basic microbial ecology related to CVD and the development of strategies to control TMA and TMAO production, with the goal of lowering CVD risk. These findings warrant further study in vitro and in vivo. Full article