Search Results (4,190)

Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation remain the cornerstone treatments for those with resectable disease, endoscopic techniques have emerged as versatile tools for diagnosis, therapy, and palliation. In recent years, there have been major advancements in endoscopic therapies, including radiofrequency ablation (RFA), intraluminal brachytherapy (ILBT), and photodynamic therapy (PDT). The current narrative review serves to provide an overview of current and emerging endoscopic strategies for CCA, emphasizing diagnostic capabilities, therapeutic approaches, palliative interventions, and future directions. Full article

Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article

Objectives: This study investigates the nonlinear association between myeloperoxidase (MPO) levels and Helicobacter pylori (H. pylori) infection risk in Chinese adults, evaluating potential modifiers and clinical implications for infection prevention. Methods: An analysis was conducted on cross-sectional data from 15,180 adults who underwent routine health examinations between January and December 2021. H. pylori infection was diagnosed using the 14C-urea breath test with a threshold of disintegrations per minute (DPM) ≥ 100. ELISA was used to measure plasma MPO levels. Nonlinear associations were assessed through logistic regression, restricted cubic splines, threshold effect analysis, and subgroup interactions. Results: The study identified a U-shaped correlation between MPO levels and the risk of H. pylori infection. Compared to the middle tertile (T2: 20.6–31 ng/mL), participants in the lowest (T1: ≤20.6 ng/mL; OR = 1.36, 95% CI: 1.24–1.49) and highest tertiles (T3: ≥31 ng/mL; OR = 1.12, 1.02–1.22) exhibited elevated infection risk after full adjustment (p < 0.001). DPM levels were notably elevated in T1 (β = 37.1, 26.66–47.57) and T3 (β = 19.27, 8.81–29.72) relative to T2 (p < 0.0001). RCS-based threshold analysis identified a nonlinear inflection at 24.0 ng/mL of MPO, where each additional 1 ng/mL of MPO below this threshold was associated with a reduced infection risk (OR = 0.959, 95% CI: 0.947–0.971), whereas levels above increased the risk (OR = 1.004, 95% CI: 1.002–1.007). This pattern aligned with H. pylori breath test values, which mirrored the U-shaped trend across MPO tertiles. Subgroup analyses revealed uniform associations between MPO and H. pylori infection risk/DPM across various factors such as age, sex, BMI, and metabolic comorbidities, with all interaction p-values exceeding 0.05. Conclusions: MPO levels exhibit a robust U-shaped association with H. pylori infection risk, independent of anthropometric and metabolic confounders. Monitoring MPO may aid in identifying individuals at bidirectional infection risk, suggesting novel insights into the inflammation–infection interplay. The study’s cross-sectional design limits the ability to establish causal relationships, necessitating further longitudinal research to validate these findings and elucidate their clinical implications. Full article

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article

Background and Objectives: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. Materials and Methods: We retrospectively reviewed 302 adults (mean age 60.7 ± 13.4 years; 80.8% men) with stage IV NSCLC managed at OncoHelp Medical Center, Timișoara, between January 2022 and December 2024. Eligibility demanded a single radiologically confirmed distant site at diagnosis and pre-treatment CBC. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) ratios were compared across pleural (n = 52), bone (n = 86), liver (n = 66), and brain (n = 98) metastases using Kruskal–Wallis tests with Bonferroni adjustment; z-standardized logistic models identified independent predictors. Results: Metastases clustered most often in brain (32.5%), followed by bone (28.5%), liver (21.9%), and pleura (17.2%). Median PLR rose selectively in pleural disease (274 vs. 217–253 in other sites; p = 0.006). LMR fell to 2.0 in bone but climbed to 2.8 in brain lesions (p = 0.032 and 0.008, respectively). NLR was globally elevated (6.7–7.6), yet differed significantly only for bone and liver deposits. Logistic modeling showed that each standard-deviation rise in absolute neutrophil count quadrupled the odds of hepatic involvement (Odd Ratio (OR) 4.26; 99% Confidence inerval (CI) 2.20–6.25), monocytosis nearly doubled bone risk (OR 1.83; 1.01–3.33), while higher erythrocytes, eosinophils, and lymphocytes independently protected against pleural seeding (all p < 0.01). Age-stratified analysis revealed that osseous and cerebral metastases predominated in patients ≤ 50 years, whereas inflammatory indices were age-invariant. Conclusions: Routine CBC ratios encode distinct “inflammatory fingerprints” that mirror the first metastatic destination in NSCLC: platelets herald pleural spread, neutrophils favor liver and bone, and divergent lymphocyte–monocyte balances separate bone from brain. Although no substitute for cross-sectional imaging, these low-cost markers could refine clinical suspicion, guide targeted work-up, and illuminate the biology of organ-selective dissemination, particularly in resource-limited settings. Full article

Background: For the first time, humanity is facing the worldwide challenge of global population aging over 80 years. As individuals age, energy acquisition and metabolism undergo significant changes, leading to a progressive decline in energy intake, absorption, and utilization. These changes contribute to malnutrition, loss of muscle mass, frailty, hormonal decline, mineral depletion, and impaired hydration, all of which increase the risk of morbidity and decrease quality of life. In addition, as life expectancy increases, advanced age often brings a gradual loss of autonomy, mirroring early-life dependency. Objectives: Addressing this age shift requires targeted interventions to support the wellness of the growing very elderly population. This review provides an overview of healthy aging through an integrated approach that includes nutritional intervention, lifestyle modifications, and targeted supplementation to support functional independence and overall well-being in older adults. The guiding principle is that longevity matters less than aging well. Full article

Rapid full-field surface topography measurement for large-scale wafers remains challenging due to limitations in speed, system complexity, and scalability. This work presents a interferometric system based on thin-film interference for high-precision wafer profiling. An optical flat serves as the reference surface, forming a parallel air-gap structure with the wafer under test. A large-aperture collimated beam is introduced via an off-axis parabolic mirror to generate high-contrast interference fringes across the entire field of view. Once the wafer is fully illuminated, topographic information is directly extracted from the fringe pattern. Comparative measurements with a commercial interferometer show relative deviations below $3\%$ in bow and warp, confirming the system’s accuracy and stability. With its simple optical layout, low cost, and robust performance, the proposed method shows strong potential for industrial applications in wafer inspection and online surface monitoring. Full article

Urban green spaces are important nature-based solutions to mitigate climate change. While the distribution of green spaces within cities is well documented, few studies assess whether inequities in green space quantity (i.e., percent cover) are mirrored by inequities in green space quality (i.e., vegetation health or sensitivity to stressors). Green space quality is important to measure alongside green space quantity because vegetation that is healthier and less sensitive to stressors such as climatic fluctuations sustain critical ecosystem services through stressful environmental conditions, especially as the climate changes. We use a 40-year remote sensing dataset to examine the spatial patterns and underlying drivers of vegetation sensitivity to short-term (monthly) climate fluctuations in Chicago. Our results show that although vegetation cover was not equitably distributed between racially and ethnically segregated census tracts, socio-demographic composition was not a key driver of spatial variation in short-term vegetation sensitivity to climate. Instead, we found that vegetation growth form was a strong predictor of differences in vegetation sensitivity among communities. At the census tract level, higher herbaceous/shrub cover was associated with increased sensitivity to climate, while higher tree cover was associated with decreased sensitivity. These results suggest that urban green spaces comprising trees will be less sensitive (i.e., more resistant) to short-term climate fluctuations than those comprising predominately herbaceous or shrub cover. Our findings highlight that urban green space quality can vary spatially within cities; however, more work is needed to understand how the drivers of vegetation sensitivity vary among cities, especially those experiencing different climatic regimes. This work is key to planning and planting high-quality, climate change-resilient and equitable urban green spaces. Full article

Vitiligo is a chronic autoimmune dermatosis defined by selective melanocyte depletion and patchy depigmentation. IFN–γ-driven recruitment of autoreactive CD8⁺ T cells and induction of melanocyte apoptosis are central to its pathogenesis. Current therapies—including UVB phototherapy, tacrolimus, vitamin D3 analogs, and surgical methods—show limited and inconsistent efficacy. Emerging treatments like JAK inhibitors and WNT activators offer potential but require further validation. Translational progress is hindered by a lack of scalable human models. Here, we describe a tunable in vitro vitiligo platform in which human iPSC-derived melanocytes (iMc) are co-cultured with keratinocytes on Matrigel and exposed to precise graded IFN-γ concentrations. Our data revealed dose-dependent decreases in iMc survival and dendritic structure, faithfully mirroring derived melanocyte pathology. Leveraging this platform, we first evaluated the short-term efficacy of the ROCK inhibitor Y27632 under early-stage patient IFN-γ concentrations representative of patient lesional thresholds. At three days, Y27632 significantly upregulated adhesion molecules E-cadherin and DDR1, and two central factors—ET1 and bFGF. Importantly, ROCK inhibition reversed dendritic retraction and improved overall viability of iMc-keratinocytes. These findings position ROCK blockade as a promising adjunctive strategy and establish a pre-clinical platform for evaluating combination therapies for durable pigment restoration. Full article

This paper explores the integration of digital twin technologies and big data in the metaverse to improve urban traffic management. It highlights the importance of technology in mirroring and augmenting our physical and virtual worlds. This study examines how big data and digital twin technologies merge in the metaverse to improve traffic management. Our work applies artificial intelligence (AI) and blockchain technologies to address concerns about privacy, scalability, and interoperability. In a literature review and case study on traffic management, we outline how big data analytics and digital twins can increase operational and decision-making efficiency. This study aims to elucidate the transformative potential of such technologies for urban transport and postulates future areas of social, regulatory, and environmental research gaps. Full article

In Australasian countries such as New Zealand, algae consumption is gaining in popularity within consumer markets. Beverages containing macro-algae, like kelp, and those containing micro-algae, such as spirulina, are considered novel products. While consumer preferences for algae-based products are well explored, less attention has been given to beverages, despite their importance for consumers, specifically those interested in health and well-being. The present study is dedicated to this research gap and investigates the key factors driving and hindering New Zealand consumers’ willingness to drink, pay a price premium, and spread word of mouth about micro-algae-based beverages, such as tea, smoothies, and cuppa soups. Theoretically, the present study is grounded in a seminal Australasian driver and barrier model of seaweed consumption. The current research design both confirms and extends the consumer behaviours previously examined. An online consumer study was distributed and collected via an opt-in panel provider, resulting in 437 responses. Consumers mirroring the NZ population in age, gender, and household income were the target sample, and descriptive statistics and a quantitative analysis via a partial least squares structural analysis served as the methodological foundation for the study. Food neophilia and involvement with algae were significant drivers for all three behavioural intentions investigated. Food neophobia was a significant inhibitor to the willingness to drink but not significantly related to the willingness to pay a price premium or spread word of mouth. Consumer perceptions of product attributes were a significant driver of New Zealand consumers’ willingness to spread word of mouth. The study provides best practice recommendations for marketers in Australasian beverage industries. In terms of its theoretical merit, two aspects stand out. Micro-algae beverages are an emerging beverage product category in Australasian markets, requiring wider exploration and complementary consumer research dedicated to algae-based food items. The focus on food neophobia and neophilia is original, as it helps to understand the barriers and drivers essential to beverages. In contrast to food items, beverages cannot hide novel ingredients such as micro-algae, making them simultaneously more appealing to food neophilic consumers and extremely challenging to food neophobic consumers. Full article

Using multiple species in native plant communities may improve control efficiency compared with single-species use. We conducted field investigations to assess the effects of Artemisia argyi, Portulaca oleracea, and their mixtures on the growth and reproduction of Mikania micrantha, followed by a greenhouse de Wit replacement series to compare different combinations of M. micrantha, A. argyi, and P. oleracea in terms of multispecies competition, phytoallelopathy, and photosynthesis. Field investigation showed that compared with M. micrantha monoculture (Group D), aboveground biomass, total stem length, flower biomass, inflorescence biomass, seed biomass, and seed number of M. micrantha increased in the P. oleracea community (Group B), though only seed number was significantly higher (p < 0.05). In contrast, in the A. argyi community (Group A) and the mixed community of A. argyi and P. oleracea (Group C), all these indicators decreased significantly (p < 0.05), in the order: Group C < Group A < Group D < Group B. This indicates that the mixed community (Group C) most strongly suppressed M. micrantha growth and reproduction. The effects of A. argyi, P. oleracea, and their mixture on the growth of M. micrantha in the greenhouse experiments mirrored the trends observed in field investigations. Calculated indices (relative yield, relative yield total, competitive balance index, and change in contribution) of A. argyi, P. oleracea, and their mixed population on M. micrantha demonstrated a higher competitive ability and higher influence of the combination of the two species compared with either A. argyi or P. oleracea alone. The interspecific phytoallelopathy experiment demonstrated strong allelopathic potential of A. argyi versus M. micrantha (p < 0.05) but showed no significant effect on P. oleracea. The net photosynthetic rate (Pn) of M. micrantha was generally lower in communities with both competitors compared with single-species communities. Our results suggest that, compared with a single plant population, the mixed population of A. argyi and P. oleracea exhibited a markedly enhanced ecological control capability through increased relative competitive ability, strengthened allelopathic inhibition, and markedly reduced photosynthetic efficiency of M. micrantha. Full article

The adhesion G protein-coupled receptor ADGRE5/CD97 is upregulated in many cancers, representing a potential drug target in oncology/immuno-oncology. Yet, ADGRE5′s activation and signaling mechanisms remain poorly understood. Here, we used enhanced bystander bioluminescence resonance energy transfer (ebBRET)-based biosensors and three strategies to characterize human (h) ADGRE5 signaling. First, a synthetic tobacco etch virus (TEV) protease-cleavable receptor chimera enabling controlled tethered agonist (TA) exposure at the GPCR proteolysis site (GPS) revealed signaling through Gα12 and Gα13, along with the recruitment of β-Arrestins 1/2 (β-Arrs). Second, we investigated WT hADGRE5 signaling elicited by Gingipain K (Kgp), an endopeptidase that cleaves hADGRE5 upstream of the GAIN domain. Kgp mirrored TEV-induced signaling but also promoted Gαz and Gα11 activity. The abolition of hADGRE5′s GPS did not block Kgp-induced receptor activation, revealing a GPS cleavage-independent mechanism of action. Finally, we developed an assay to study hADGRE5 mechanical stimulation (MS) using β-Arr2 as a readout. MS promoted β-Arr2 recruitment in hADGRE5-expressing cells, and this response was lost upon abolition of the GPS. A neutralizing antibody to the hADGRE5 ligand CD55 significantly dampened MS-induced β-Arr2 engagement. Overall, this study advances our understanding of hADGRE5′s signaling and highlights the receptor’s plasticity in activating pathways via both GPS cleavage-dependent and -independent mechanisms. Full article

Laser beam scanning (LBS) projection systems based on MEMS micromirrors offer advantages such as compact size, low power consumption, and vivid color performance, making them well suited for applications like AR glasses and portable projectors. Among various scanning methods, raster scanning is widely adopted; however, it suffers from artifacts such as dark bands between adjacent scanning lines and non-uniform distribution of the scanning trajectory relative to the original image. These issues degrade the overall viewing experience. In this study, we address these problems by introducing random variations to the slow-axis driving signal to alter the vertical offset of the scanning trajectories between different scan cycles. The variation is defined as an integer multiple of 1/8 of the fast-axis scanning period ($1/{\mathrm{f}}_{\mathrm{h}}$) Due to the temporal integration effect of human vision, trajectories from different cycles overlap, thereby enhancing the scanning fill factor relative to the target image area. The simulation and experimental results demonstrate that the maximum ratio of non-uniform line spacing is reduced from 7:1 to 1:1, and the modulation of the scanned display image is reduced to 0.0006—below the human eye’s contrast threshold of 0.0039 under the given experimental conditions. This method effectively addresses scanning display artifacts without requiring additional hardware modifications. Full article