Search Results (469)

Methane (CH₄) is a potent greenhouse gas, with livestock rumination being a significant contributor to global emissions. This study developed a real-time monitoring system utilizing Off-Axis Integrated Cavity Output Spectroscopy (OA-ICOS) to simultaneously track rumination behavior and CH₄ concentrations in cattle breath. By optimizing the off-axis integrated cavity structure and implementing a specialized environmental control system, we enhanced stability and detection accuracy, achieving a rapid 3 s response time to dynamic concentration changes. Laboratory stability tests and Allan deviation analysis demonstrated a minimum detection limit of 0.07 ppm. Continuous field monitoring of Simmental cattle revealed a daily methane production of approximately 311.83 L. The emission rates exhibited a distinct double-peak pattern heavily influenced by feeding schedules. Furthermore, a positive correlation was observed between the time elapsed post feeding and both the frequency and intensity of methane emission peaks. This method enables highly dynamic, stable, long-term monitoring of greenhouse gas emissions from ruminants, providing a robust tool for quantifying emissions and informing scientific feeding practices. Full article

Circulant follicular helper T cells (cTfh) are a specialized subset of CD4⁺ T cells that induce immunoglobulin class switching and antibody secretion in plasma cells through the production of IL-21. To investigate the role of cTfh-like cells in the development of Sjögren’s disease (SjD), we analyzed the circulating Tfh-like cells, their production of IL-21 and IL-4, and the co-expression of ICOS, CXCR5, and CCR9 by flow cytometry, and evaluated their association with clinical characteristics of the disease. Percentages of CD4⁺ IL-21⁺ CXCR5⁺ ICOS⁺ CCR9⁺ IL-4⁺ T cells were analyzed in peripheral blood samples from 20 healthy controls (HCs) and 19 patients with SjD. Serum levels of IL-1β, IL-4, IL-6, IL-21, and sCD40L were assessed using a Luminex assay. Laboratory data included anti-Ro/La antibodies, immunoglobulin levels (IgA and IgG), focus score, disease duration, and ESDDAI/SSDDI scores. Decreased frequencies of CXCR5⁺ IL-21⁺ T cells and CCR9⁺ IL-4⁺ T cells were observed in the peripheral blood of patients with SjD. Heatmap analysis was used to identify correlations between cTfh-like cells and clinical parameters. Elevated proportions of cTfh-like cells were positively correlated with disease severity, inflammatory markers, and autoantibody production. High-dimensional analysis identified distinct subpopulations with differential expression of ICOS, CXCR5, CCR9 and IL-21, suggesting heterogeneity of these cells in SjD and their involvement in disease pathogenesis. Full article

This study evaluates temporal variability and algorithm differences in soil moisture estimates over Europe using the European Center for Medium-range Weather Forecasts (ECMWF) operational analysis and the passive Soil Moisture Active Passive (SMAP) soil moisture product. While models and satellite retrievals have improved in capturing the timing of soil moisture dynamics, absolute accuracy and temporal variability magnitudes still diverge. This study compares the representation of short-term and seasonal variability of soil moisture in absolute and normalized terms over two different hydrometeorological growing periods (2021 and 2022). Both datasets exhibit intermediate to high temporal correlations with in situ measurements at selected stations (median Pearson correlation coefficients of all stations range between 0.65 and 0.79), confirming previous studies. However, they overestimate the magnitude of absolute soil moisture variability at most stations (median interquartile range of all stations at 0.085 (0.10) m³m⁻³ for ECMWF and 0.072 (0.079) m³m⁻³ for SMAP opposed to 0.063 (0.072) m³m⁻³ for in situ in 2021 (2022)) due to an overestimation of short-term fluctuations, especially at dry stations in southern France and Eastern Europe. The soil wetness index is underestimated, particularly within SMAP estimates. The performance of both is sensitive to hydrometeorological conditions, with the 2022 European drought causing strong seasonal and weak short-term fluctuations. This is easier to capture than conditions with pronounced short-term and weaker seasonal fluctuations, as in 2021. Overall, SMAP and ECMWF time series show considerable coincident timing, whereas the magnitude of temporal variability and accuracy depend on site-specific characteristics and the pre-processing of the data. Full article

Inducible costimulator (ICOS) is a costimulatory immune checkpoint receptor expressed on activated T-cells, while the ICOS ligand (ICOSL) is expressed on antigen-presenting cells. The ICOS–ICOSL axis promotes the survival of memory and effector T-cells and induces several immune responses. In addition, the ICOS–ICOSL interaction induces cell proliferation, cell survival, and cytokine production. The roles of ICOS and ICOSL in cutaneous T-cell lymphoma (CTCL) are unclear. In this study, we examined the roles of ICOS and ICOSL in CTCL. The tumor cells co-expressed ICOS and ICOSL, and the upregulated expression of ICOS and ICOSL reflected disease severity. Anti-ICOS and anti-ICOSL neutralizing antibodies inhibited both the in vitro and in vivo proliferation of CTCL cell lines. The anti-ICOSL neutralizing antibodies induced apoptosis and suppressed CCR4 expression on tumor cells, inhibiting CCR4–CCL17-mediated migration. These results suggest that the ICOS–ICOSL axis plays an essential role in CTCL pathogenesis, and targeting the ICOS–ICOSL axis could be a viable strategy for treating CTCL. Full article

Introduction: The metabolic complications and poor biocompatibility of conventional glucose-based (GLU) peritoneal dialysis fluid (PDF) have driven the need for improved alternatives. To address this, we developed and evaluated a novel PDF utilizing succinylated gelatin (GEL) as osmotic agent and citrate as buffer, designed to provide effective solute clearance while offering enhanced biocompatibility. Methods: Physicochemical parameters (pH and osmolality) of the novel GEL-PDF were measured. Its performance was assessed in rats with chronic kidney disease. A total of 20 rats were randomized into short-term experiments to evaluate 4 h creatinine clearance and ultrafiltration (UF). A 12-week long-term experiment (n = 35) compared the GEL-PDF against normal saline (NS), GLU, and icodextrin-based (ICO) PDFs, monitoring survival, biochemical parameters, peritoneal membrane histology, and kidney histology. Results: The GEL-PDF demonstrated a neutral pH (7.30) and lower osmolality (317 mOsm/L) compared to GLU-PDF. In the short-term experiment, GEL-PDF achieved effective creatinine clearance by 4 h and provided higher 4 h UF than NS and GLU, comparable to ICO. However, during prolonged dwells (6–16 h), its UF was inferior to ICO. In the long-term experiment, GEL-PDF preserved peritoneal membrane structure, showing the least thickness and collagen deposition. Furthermore, the GEL-PDF demonstrated superior preservation of serum albumin compared to the GLU-PDF. It also exhibited a more favorable lipid profile, as evidenced by significantly lower total cholesterol levels than the ICO group at 12 weeks (p = 0.035), with no adverse effects on electrolytes, liver function, or glucose metabolism. Conclusions: The novel GEL and citrate-based PDF provide effective short-dwell UF and solute removal while exhibiting superior biocompatibility, as evidenced by significant protection against peritoneal membrane injury and favorable metabolic profiles. Although its long-duration UF was lower than that of ICO, it substantially outperformed GLU-PDF. These properties position the GEL-PDF as a promising candidate for short- to medium-dwell exchanges, particularly for daytime use, where it could fill an important clinical gap by providing enhanced UF without the high GLU exposure associated with conventional PDF. Full article

Background: Follicular lymphoma (FL) is the second most common B-cell lymphoma in Western countries, typically presenting as an indolent disease with prolonged overall survival. Despite favorable initial responses to therapy, most patients experience relapse, and early progression is associated with poor outcomes. Methods: This guideline provides evidence-based recommendations from the Spanish GELTAMO group on the diagnosis, staging, treatment, and follow-up of FL. A systematic literature review was conducted, and recommendations were graded according to the GRADE system. Results: Histopathological diagnosis should be based on excisional biopsy. PET-CT is recommended for staging and response evaluation. For localized disease, involved-site radiotherapy (ISRT) remains the treatment of choice. In asymptomatic patients with advanced-stage disease and low tumor burden, a watch-and-wait approach is appropriate, although rituximab monotherapy is also acceptable. For advanced-stage disease with high tumor burden, immunochemotherapy with anti-CD20 antibodies (rituximab or obinutuzumab) combined with CHOP, CVP, or bendamustine is recommended, followed by maintenance therapy. Management of relapsed disease is tailored based on tumor burden, treatment history, and timing of relapse. Although novel immunotherapies (CAR-T therapy and bispecific antibodies) are emerging as promising options, autologous stem cell therapies may still be a valid option in young patients with early relapse who are sensitive to immunochemotherapy. Conclusions: FL is a heterogeneous disease requiring individualized management strategies. Recent advances in immunotherapy and molecular diagnostics are reshaping the therapeutic landscape. These updated GELTAMO recommendations aim to provide practical guidance for optimal FL management in clinical practice. Full article

Background/Objectives: This study aimed to analyze the relationship between various anthropometric measurements (Body Mass Index (BMI), Clínica Universidad de Navarra-Body Adiposity Estimator (CUNBAE), hip and waist circumference (WC), weight, and height) and Triple-Negative Breast Cancer (TNBC) according to menopausal status. Methods: A total of 113 TNBC cases and 226 matched controls from the MCC-Spain study were included. Controls were matched by age, educational level, family history, and province. Conditional logistic regression models, stratified by menopausal status, were used to estimate adjusted Odds Ratios (aORs) and their 95% Confidence Intervals (95% CIs) for the association between anthropometric measures and TNBC risk. Results: A divergent non-significant trend was observed: compared to their respective controls, premenopausal cases tended to have lower mean anthropometric measurements (except height), while postmenopausal cases showed higher means. No statistically significant associations were observed for individual measures derived from logistic regressions. However, when comparing women with normal BMI and normal WC (the reference group), a non-significant association of risk was found in those premenopausal women who were centrally obese (normal weight/high WC) (aOR = 1.79; 95% CI = 0.17–18.29), but the combination of overweight and a large WC showed an aOR of 0.22 (95% CI = 0.03–1.68) before menopause. In contrast, the combination of overweight and a high WC showed a statistically significant adjusted OR of 3.28 in postmenopausal women (95% CI = 1.10–9.81). Conclusions: Our findings suggest that the relationship between adiposity and TNBC is inverse in premenopausal women and direct in postmenopausal women, highlighting the importance of considering both body fat distribution and menopausal status when evaluating TNBC. However, our findings are limited by low statistical power, which may have led to a lack of statistical significance, and there is a need for larger, collaborative studies. Full article

Bioactive compounds in food contribute to reducing the risk of developing colon cancer by modulating the gut microbiota. We have recently demonstrated that garambullo (Myrtillocactus geometrizans), an endemic fruit of Mexico rich in bioactive compounds, attenuates aberrant crypt foci in an animal model. However, its potential to modulate the gut microbiota is unknown. The main objective of this study was to evaluate whether its consumption modulates colon carcinogenesis by altering the microbiota in an in vivo model induced by azoxymethane and dextran sulfate sodium (AOM/DSS). Fecal samples were collected from twelve male Sprague-Dawley rats and analyzed for microbiota composition after 0, 8, and 16 weeks of treatment with saline (control), AOM/DSS, garambullo (G), or residue of garambullo (RG) with AOM/DSS (G+AOM/DSS and RG+AOM/DSS, respectively). Characterization of the microbiome was based on the conserved region of the 16S rRNA V3-V4 gene, and analyzed by the ZymoBIOMICS’ Targeted Metagenomics Sequencing (Zymo Research) service. In an animal model induced with AOM/DSS for 8 weeks, consumption of G and its residue increased the bacterial genera Shuttleworthiia, Subdoligranulum, Lactobacillus, Faecalibacterium, and Alloprevotella (p < 0.05). Consumption of G and its residue allowed the proliferation of bacteria that produce short-chain fatty acids and are associated with protective mechanisms of the colon. Full article

Background/Objectives: Brain metastases (BM) are a major challenge in the treatment of non-small cell lung cancer (NSCLC), particularly among patients with anaplastic lymphoma kinase rearrangements (ALK+ NSCLC), where incidence can reach up to 60% during the course of the disease. This study used in silico systems biology and artificial intelligence-based modeling to investigate the mechanistic effects of brigatinib, a second-generation ALK inhibitor, on metastatic processes in both primary tumors (PT) and established BM. Methods: We applied the Therapeutic Performance Mapping System (TPMS) technology, which integrates systems biology and artificial intelligence, to simulate the impact of brigatinib on metastasis-associated pathways in PT and BM of ALK+ NSCLC patients. Results: In these simulations, brigatinib was predicted to modulate a broad set of proteins implicated in metastasis in both PT and BM, acting mainly through IGF1R, EGFR, FLT3, and ROS1, in addition to its known target ALK. Conclusions: These results suggest brigatinib’s potential to impact key pathways involved in metastatic progression and intracranial disease control. Overall, this study provides insights into brigatinib’s multifaceted role in targeting metastatic processes in ALK+ NSCLC, underscoring its potential benefits in both PT and BM. Nonetheless, further experimental and clinical studies would confirm our results and the potential of in silico models reported here. Full article

Racial and ethnic disparities in acute myeloid leukemia (AML) survival persist despite advances in treatment, with non-Hispanic black (NHB) patients and Hispanic patients often experiencing worse outcomes than Non-Hispanic White (NHW) patients due to a combination of clinical, socioeconomic, and biological factors. This review focuses on these disparities and emphasizes potential contributions of biology, as illustrated by the effects of the nucleophosmin 1 (NPM1) mutation. Mutation landscapes and chromosomal abnormalities strongly influence AML patient outcomes. While AML cases with NPM1 mutations are associated with favorable prognoses for NHW patients, NHB patients with NPM1-mutated AML have adverse outcomes. Thus, treatment algorithms and prognostic systems based on outcomes from a single racial ancestry group are inadequate. Beyond the more traditional socioeconomic determinants of health, addressing disparities in AML to achieve equity in care requires exploring biological factors linked to ancestry that shape treatment response. Full article

Primary urethral cancer is an extremely rare malignancy, accounting for less than 1% of all cancers. Due to its rarity, evidence-based treatment recommendations are lacking. We report the case of a 44-year-old woman with metastatic squamous cell urethral carcinoma and paraneoplastic Sweet syndrome. The tumor was p16-positive with strong PD-L1 expression (CPS > 50%). Following surgery and adjuvant chemoradiotherapy, the patient developed hepatic and lymph node metastases. Pembrolizumab was initiated as first-line systemic therapy because of prior hematologic toxicity with cisplatin. After four cycles, complete radiologic remission of metastases and full resolution of the Sweet syndrome were achieved. This case highlights the potential benefit of immune checkpoint inhibitors in metastatic urethral SCC, particularly in p16-positive and PD-L1-high tumors, suggesting an inflamed and immunogenic microenvironment. To our knowledge, this is the first reported case of paraneoplastic Sweet syndrome successfully treated with pembrolizumab. These findings underscore the need for further investigation of immunotherapy in this rare and challenging malignancy. Full article

Background: Paclitaxel (PTX) is an anti-neoplastic drug that inhibits not only melanoma cell proliferation but also migration and angiogenesis. ICOS-Fc is a recombinant molecule that triggers ICOS ligand (ICOSL) on tumor cells and cells of the tumor microenvironment and inhibits tumor growth, angiogenesis, and metastasis. This study investigated the effects of chitosan nanobubbles loaded with low doses of PTX and surface decorated with ICOS-Fc (ICOS-Fc-NB-PTX) in inhibiting in vitro and in vivo melanoma cell growth and invasiveness. Methods: Preparation and characterization of nanoformulations, as well as in vitro drug release studies, were carried out. Nanoformulations were studied both in vitro and in vivo. In melanoma cells, viability, migration, and invasion assays were analyzed. For the in vivo experiments, C57BL/6 Wild-type (WT) male mice were injected subcutaneously with D4M-3A cells, a murine melanoma cell line engineered to carry the BRAF^V600E mutation. After treatments, in vivo tumor growth, proliferation, and angiogenesis markers were studied. Results: In vitro tests showed the great ability of ICOS-Fc-NB-PTX to inhibit cell viability, migration, and invasion. These results were confirmed in vivo, where the tumors of mice treated with ICOS-Fc-NB-PTX displayed decreased growth accompanied by downregulation of the proliferation marker Ki-67 and reduced development of CD31⁺ blood vessels. Conclusions: In conclusion, the ICOS-Fc-NB-PTX formulation deserves to be further analyzed as a highly effective combination for melanoma, exerting multifaceted anti-tumor activities. Full article

Background/Objectives: Metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge due to its aggressive behavior and resistance to therapy. Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in various cancers and associated with poor prognosis. YM155 (Sepantronium bromide) suppresses survivin expression and has demonstrated antitumor activity in preclinical models. We investigated the association between survivin expression and clinical outcomes in mCRPC patients and evaluated the antitumor activity of YM155, alone and in combination with carboplatin, in mCRPC cell lines. Methods: Analysis of publicly available RNA-seq datasets from mCRPC patients was performed to assess correlations between survivin expression and clinical outcomes. Radiographic progression-free survival (rPFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared via log-rank or Fisher’s exact tests. In vitro assays were conducted on mCRPC cell lines treated with YM155, carboplatin, or both, to evaluate cell viability, clonogenicity, and apoptosis. Results: Survivin was significantly overexpressed in mCRPC compared with localized prostate cancer and was even higher in castration-resistant neuroendocrine disease. High survivin levels were associated with shorter OS (p = 0.006). In patients treated with platinum-based therapies, high survivin was also linked to shorter rPFS (p = 0.01), reduced OS (p = 0.006), and a smaller PSA decline (p = 0.006). In vitro, YM155 reduced survivin expression, impaired cell viability and colony formation, induced apoptosis, and synergistically enhanced the cytotoxicity of carboplatin. Conclusions: Our findings suggest that survivin may serve as a prognostic biomarker and potential therapeutic target in platinum-treated, AR-independent mCRPC. The integration of clinical and functional data provides translational support for combining the survivin inhibitor YM155 with platinum-based therapy. These results warrant further validation in larger patient cohorts and in vivo models. Full article

Geographic isolation can shape genetic variation and structure, leading to divergence between island and mainland populations. The Oriental Garden lizard (Calotes versicolor Daudin, 1802) is a widespread agamid reptile in Asia, occurring across diverse habitats from continental Southeast Asia to offshore islands. We examined mitochondrial cytochrome c oxidase subunit I (CO1) sequence variation in 143 individuals from 23 localities across the Andaman Sea and Gulf of Thailand to assess genetic diversity and structure between insular and mainland populations. Forty-six haplotypes (Cve1–Cve46) were identified, with haplotype diversity (Hd) ranging from 0.500 to 1.000 and nucleotide diversity (π) from 0.0057 to 0.0265. AMOVA revealed low to moderate differentiation between island and mainland groups in the Andaman Sea (F_CT = 0.075, p > 0.05) and negligible differentiation in the Gulf of Thailand (F_CT = 0.009, p > 0.05). Haplotype networks and PCoA showed clustering of most island and mainland populations within regions, with some localized divergence. Divergence-time analysis indicated that lineages split within the last 0.5 million years ago (Ma), coinciding with late Pleistocene climatic oscillations and sea-level changes. Species delimitation analyses supported three major lineages, including a geographically restricted clade confined to Trat Province and Phuket Island. These results suggest that C. versicolor populations are structured more by regional geography than strict island–mainland separation, reflecting historical connectivity and contemporary gene flow. The findings contribute to understanding reptile biogeography in Southeast Asia and highlight populations of conservation value. Full article

People with HIV (PWH) are at an increased risk for AIDS-associated non-Hodgkin lymphoma (AIDS-NHL); however, the immune signatures underlying this risk are not well understood. In this study, we utilized mass cytometry by time-of-flight (CyTOF) to analyze T-cells and monocytes in the PBMCs of treatment-naïve PWH, including those 3 to 36 months before an AIDS-NHL diagnosis (HIV-positive pre-NHL), as well as people without HIV (PWoH). Mass cytometry is an advanced single-cell analysis platform that combines flow cytometry principles with mass spectrometry. Unlike conventional flow cytometry, this technology employs antibodies conjugated to unique metal isotopes instead of fluorescent markers, enabling simultaneous measurement of over 40 distinct cellular markers per individual cell without spectral overlap limitations. Participants were enrolled at the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Unsupervised clustering and Uniform Manifold Approximation and Projection (UMAP) analysis identified CD3⁺ T-cell and CD14⁺ monocyte metaclusters, and Spearman’s rank correlation assessed their relationships with B-cell subsets exhibiting aberrant phenotypes. We observed elevated levels of CD8⁺CD20⁺ T-cells, CD8⁺CD14⁺ T-cells, and M2-like CD14⁺CD163⁺ monocytes in HIV-positive pre-NHL individuals compared to HIV-negative controls. Positive correlations were found between CD19⁺ AICDA⁺ cMYC⁺ B-cells and M1-like CD14⁺cMYC⁺ monocytes (metacluster, MC02), and between metaclusters of CD8⁺PD-1⁺CD27⁺CXCR4⁻ T-cells (MC05) and CD4⁺FoxP3⁺PD-1⁺CD27⁺CD28⁺CXCR4⁻ ICOS⁺ T-cells (MC08). In addition, a different CD19⁺ B-cell metacluster (FoxP3⁺AICDA⁺cMYC⁺) was positively associated with a metacluster of CD8⁺PD-1⁺CD27⁺CD28⁺CXCR4⁺ T-cells (MC03). Moreover, the metacluster of CD8⁺PD-1⁺CD27⁺CXCR4⁻ T-cells (MC05) negatively correlated with M2-like CD14⁺CD163⁺ monocytes (MC06), while CD8⁺CD14⁺ T-cells positively correlated with AICDA⁺ Bregs and IL-10⁺ B-regs in HIV-positive pre-NHL individuals. Unsupervised analysis revealed increased frequencies of CD8⁺CD20⁺ T-cells in HIV-positive individuals compared to HIV-negative controls. These immune alterations provide valuable insights into potential biomarkers for early detection, monitoring, and therapeutic strategies for AIDS-NHL. Full article