Search Results (420)

In the tradition of Irish traditional music, ownership of music is vague and sometimes contested. Tunes are not generally associated with a “composer”, but, if identified with anyone at all, are generally associated with the person most well-known for performing them, or a person identified with a tune, or a particular version thereof. This article will examine some of the songs and performances/singers in the collection of the late Tom Munnelly (1944–2007), collector of the most extensive collection of English-language songs in Ireland and not only an avid collector but also a very talented singer. Of primary concern will be Tom Munnelly’s attitude to song and its ownership, shedding light on a field long contested and much debated. Drawing on Tom Munnelly’s field recordings of specific songs, the article will endeavour to shed fresh light on how traditional music in Ireland is viewed. Full article

Background: Anti-dsDNA is an important biomarker for the diagnosis, prognosis, and monitoring of systemic lupus erythematosus (SLE). Although several assays for anti-dsDNA antibody detection are routinely used, standardization remains limited, and differences have been reported. This study aimed to compare five methods for anti-dsDNA antibody detection and to estimate their association with complement consumption. Methods: A total of 149 samples submitted for routine laboratory testing were collected and tested on five platforms: Crithidia luciliae indirect immunofluorescence test (CLIFT), addressable laser bead immunoassay (ALBIA), a high-avidity (HA) enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CIA), and a novel particle-based multi-analyte technology (PMAT). Complements C3 and C4 were available for a subset of the total samples. Results: Correlation between anti-dsDNA assays ranged from 0.94 (CIA and PMAT) to 0.65 (ALBIA and CLIFT). The AUC from the ROC analysis using CLIFT as a reference was 0.95 for PMAT, 0.94 for CIA, 0.93 for ELISA, and 0.86 for ALBIA. The highest sensitivity relative to CLIFT at a fixed specificity of 94.4% was 84.7% for CIA and ELISA, 76.3% for PMAT, and 42.4% for ALBIA. Correlation between anti-dsDNA and C3 ranged from −0.81 for ELISA to −0.51 for ALBIA. Conclusions: Different anti-dsDNA detection methods showed varying diagnostic performance and correlation and varying agreement with CLIFT and complement consumption. ELISA, CIA, and PMAT showed high correlation to each other and to CLIFT and were in strong concordance with low C3 levels. In contrast, ALBIA revealed lower clinical performance and correlation with CLIFT and complement consumption. Full article

The purpose was to determine the ability of 18-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET-CT) scans performed within 24 h of percutaneous image-guided ablation of primary and metastatic malignancies to predict ablation effectiveness and local tumor progression (LTP). This single-center retrospective review included patients who underwent image guided ablation (microwave ablation (MWA), cryoablation, or irreversible electroporation (IRE)) between August 2018 and February 2024 for primary and metastatic malignancies. The primary outcome measure encompassed correlating post-ablation 18F-FDG PET-CT findings with LTP development per tumor, assessed using the chi-square test. The secondary outcome measure was local tumor progression-free survival (LTPFS) per tumor, evaluated using the Kaplan–Meier survival curves, and potential confounders were identified in multivariable analysis utilizing Cox proportional hazards regression models. A total of 132 patients, who underwent 159 procedures for 224 tumors, were included. During follow-up, LTP developed in 120 out of 224 tumors (53.6%). The presence of residual nodular 18F-FDG avidity on PET-CT within 24 h after the ablation significantly correlated with the development of LTP at follow-up imaging (p < 0.001). The positive predictive value of nodular 18F-FDG avidity was 86.7%. In multivariable analysis, the hazard ratio (HR) for 18F-FDG avidity was 2.355 (95% CI 1.614–2.647; p < 0.001). The presence of 18F-FDG avidity on PET-CT within 24 h after the ablation was highly correlated with development of LTP and decreased LTPFS. The detection of residual tumor tissue may allow early re-treatments, especially in tumors with nodular uptake, contributing to increased LTPFS. Full article

Genetic fusion of a tag sequence to a target protein, or protein of interest (POI), is one of the most widely used technologies for recombinant expression. Tag-fusion proteins can enhance soluble expression, prolong half-life, increase binding avidity, and facilitate protein purification or refolding. In addition, tag-fusion proteins can be used to identify POI-binding partners through pull-down or immunoprecipitation assays. Beyond these classical applications, tags have evolved to serve as multifunctional tools, enabling real-time imaging, spatial localization, targeted delivery, and regulation of protein activity in living systems. Some engineered tags also allow conditional control, such as pH or ligand-dependent stabilization, thus expanding their utility in synthetic biology and therapeutic design. Here, we summarize protein-based and peptide-based tags, as well as methods for tag removal. While not fully comprehensive, this review aims to help researchers design suitable tag formats for specific goals. Full article

Due to possible congenital infections, cytomegalovirus (CMV) remains a significant public health concern in childbearing-aged and pregnant women. We analyzed the spatial, temporal, and age-related trends in CMV seroepidemiology in Croatia over 10 years. A total of 2838 childbearing-aged and pregnant women, aged 16–45 years, tested between 2015 and 2024 were included in the study. CMV IgM/IgG antibodies were detected using a commercial ELISA. IgM/IgG-positive samples were tested for IgG avidity. CMV IgG antibodies were detected in 2006 (70.6%) of participants. No significant differences were observed between 2015–2019 and 2020–2024 (72.0% vs. 69.8%), while yearly differences were of borderline significance, ranging from 62.4 to 77.3%. The overall seropositivity increased progressively with age from 49.6% in the 16–20 age group to 77.5% in the 36–40 age group. Significant regional differences in IgG seroprevalence were observed: 68.6% in the City of Zagreb/Northern Croatia, 78.5% in Pannonian Croatia, and 71.9% in Adriatic Croatia, while differences between settlement types were not significant. IgG seroprevalence was higher in women with an unfavorable obstetric history (85.3%) than in non-pregnant women and those with a normal pregnancy (70.6% and 66.5%, respectively). IgM antibodies were detected in 278 (9.8%) of participants. Acute infections were more common in younger participants, with rates decreasing from 13.6% in the youngest age group to 6.7% in the oldest. Logistic regression showed that age was a significant predictor of both IgG and IgM positivity. Region and obstetric history were significant predictors of IgG seropositivity, while settlement was a significant predictor of IgM seropositivity. Full article

Introduction: Dengue virus (DENV) remains a global health threat, with four distinct serotypes (DENV1-4) that complicate vaccine development due to low-affinity, cross-reactive antibodies that increase the risk of antibody-dependent enhancement (ADE). Objective: To address the challenge of inducing strictly serotype-specific immune responses, this study explored the use of targeting individual lymph nodes (LNs) for the creation of simultaneous but independent immune responses as a targeted approach to reduce cross-reactivity and improve vaccine specificity. Methods: In the initial experiments, targeting individual LN successfully induced specific germinal centers (GCs) for different antigens in distinct LNs, highlighting its potential to enhance immune specificity. This approach was further tested using two virus-like particle (VLP)-based vaccines based on AP205 for DENV1 and DENV4, selected due to their genetic divergence and to probe the potential to minimize cross-reactive immune responses. In this setup, AP205-DV1 and AP205-DV4 were administered in targeted separate LNs, and the specificity of the immune response was compared to subcutaneous administration of a mixture of both vaccines. Results: Our data show that targeting distinct LNs elicited antibodies with significantly higher avidity, which is a critical factor in determining the neutralizing capacity of the immune response. Avidity measurements confirmed that this segregation approach results in a more refined selection of high-affinity B cells. Neutralization experiments demonstrated that targeting distinct LNs with individual vaccines induced a more potent and serotype-specific neutralizing response, compared to the injection of a vaccine mixture. Conclusions: These findings suggest that targeting individual LNs could be a promising method for enhancing both the specificity and potency of immune responses, particularly for flaviviruses. Targeting distinct LNs by direct administration of individual vaccines into distinct watersheds rather than individual lymph nodes will offer the opportunity to facilitate the approach in humans. Full article

In recent years, avidity has emerged as a critical parameter in antibody design, yet most current analytical instruments are limited to measuring affinity alone. This study aims to evaluate the capabilities and advantages of a novel surface plasmon resonance imaging instrument, CellVysion, designed to quantify cell–antibody avidity using a continuous antibody density gradient. A key feature of this approach is the identification of a “tipping point”—the specific ligand density, measured in µRIUs, at which cells remain bound to the sensor surface under defined shear flow conditions. In this paper, we present the technical principles and application of this method, demonstrating how avidity can be quantitatively assessed across different antibody–cell line combinations. Full article

Rubella is typically a mild viral illness, but it can lead to severe complications when contracted during pregnancy, such as pregnancy loss or developmental defects in the fetus (congenital rubella syndrome). Therefore, it is crucial to develop and maintain protective immunity in women of childbearing age. In this study, we assessed the transcriptional factors associated with rubella-specific immune outcomes (IgG binding antibody and avidity, neutralizing antibody, and memory B cell ELISpot response) following a third MMR vaccine dose in women of reproductive age to identify key factors/signatures impacting the immune response. We identified baseline (Day 0) and differentially expressed (Day 28–Day 0) genes associated with several RV-specific immune outcomes, including the transferrin receptor 2 (TFR2), which is an important factor regulating iron homeostasis and macrophage functional activity, and a close functional homolog of TFR1, the cellular receptor of the New World hemorrhagic fever arenaviruses. We also identified enriched KEGG pathways, “cell adhesion molecules”, “antigen processing and presentation”, “natural killer cell-mediated cytotoxicity”, and “immune network for IgA production”, relevant to immune response priming and immune activation to be associated with RV-specific immune outcomes. This study provides novel insights into potential biomarkers of rubella-specific immunity in women of childbearing age. Full article

Background/Objectives: The purpose of this study is to determine the added value of 18F-FDG PET/CT scan in pediatric LCH compared to other imaging modalities (CT and MRI) at initial staging, during assessment of disease reactivation, and after treatment. Methods: This is a retrospective study of children diagnosed with LCH between 1 June 2007 and 8 December 2022 who met the inclusion criteria. 18F-FDG PET CT imaging was compared to CT and/or MRI when available. The interclass correlation coefficient (ICC) was used to assess the agreement between methods. p-Values of less than 0.05 were considered statistically significant. Results: A total of 39 children had undergone 18F-FDG PET/CT studies. Median (range) age at presentation was 10 years (1.3–17 y), with a female-to-male ratio of 0.7:1. Excellent concordance (ICC = 1; p < 0.0001) between 18F-FDG PET/CT and other imaging methods was found. Median SUVmax of the positive FDG-avid lesions at initial staging was 2.7 [range 1.3–16.7]. Conclusions: 18F-FDG PET/CT has been shown to be complementary to diagnostic CT and MRI, with the advantage of demonstrating additional metabolic information at initial staging, during assessment of disease reactivation, and to assess interval changes post therapy. These preliminary findings warrant further investigation. Full article

Background/Objectives: Electrochemotherapy (ECT) has emerged as a promising locoregional treatment modality for patients with cutaneous and subcutaneous melanoma metastases. While systemic therapies have improved overall disease control, effective local tumor management remains crucial, particularly in oligometastatic or symptomatic disease. This pilot study investigates the role of metabolic imaging with [¹⁸F]FDG PET/CT to assess tumor metabolism in melanoma patients undergoing ECT, building on prior evidence that PET offers valuable functional information beyond anatomical changes detected by conventional imaging. Methods: This retrospective study included 11 patients with histologically confirmed melanoma and cutaneous or subcutaneous metastases treated with ECT. [¹⁸F]FDG PET/CT scans were performed either before ECT, after ECT, or both. Metabolic response was assessed by measuring the tracer uptake (SUV_max) of the ten hottest lesions. Morphological changes were evaluated using CT. Local progression-free survival was determined. Results: A total of 66 lesions were analyzed. Patients with PET/CT only after ECT showed significantly higher SUV_max and lesion size compared to those imaged before treatment (mean SUV_max: 9.9 ± 11.2 vs. 10.3 ± 5.5; p = 0.034). Progression-free survival differed significantly based on pre-ECT SUV_max values (χ² = 3.90; p = 0.048). Among two patients with follow-up imaging, one showed new lesions on CT with only mild FDG uptake, while the other developed newly FDG-avid metastases after ECT. Conclusions: FDG PET/CT provides valuable information on tumor viability and treatment response in melanoma patients undergoing ECT, demonstrated by significant differences in metabolic activity between lesions imaged before and after treatment. The lack of longitudinal intra-individual imaging limits definitive conclusions about the direct metabolic effects of ECT. Full article

Childbearing-aged and pregnant women represent a risk group for Toxoplasma gondii infection due to possible transplacental transmission resulting in congenital toxoplasmosis. We analyzed the seroepidemiological trends of toxoplasmosis in Croatia over ten years (2015–2024). A total of 2791 childbearing-aged and pregnant women were included. Toxoplasma gondii-specific IgM/IgG antibodies were detected using an enzyme-linked fluorescence assay. Samples with positive IgM and IgG antibodies were tested for IgG avidity. IgG antibodies were detected in 695 (24.9%) participants, while acute toxoplasmosis (IgM antibodies and low avidity IgG antibodies) was confirmed in 32 (1.2%) of participants. The IgG seroprevalence showed a declining trend over the years. Residents of suburban/rural areas were more often seropositive than those in urban areas (31.4 vs. 22.3%). Logistic regression analysis revealed that year of testing, age, and settlement were associated with the risk of seropositivity. For each later calendar year, the log odds of being IgG-positive decreased, while for each additional year of age, the log odds increased. Residence in an urban area was associated with lower log odds. The region was not a significant predictor in the logistic regression. The differences in seropositivity observed across regions can be mainly attributed to Pannonian Croatia, which showed significantly higher odds of IgG seropositivity. Data about the toxoplasma serological status is useful for planning prevention campaigns. Full article

A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted on blood work or cerebrospinal fluid analysis. Tumor markers were within normal limits. As part of her diagnostic workup, a positron emission tomography (PET) scan was performed, which showed a highly FDG-avid solitary 7 mm left axillary lymph node. Ultrasound-guided percutaneous biopsy revealed metastatic poorly differentiated carcinoma. Histopathological examination could not conclusively distinguish between adenocarcinoma and squamous cell carcinoma. She was diagnosed with seronegative opsoclonus-myoclonus ataxia syndrome of paraneoplastic origin from an occult primary malignancy and started on pulsatile corticosteroids and intravenous immunoglobulin (IVIG), with only moderate symptomatic improvement. Given the anatomic location and immunohistochemical staining pattern of the lymph node, the malignancy was considered as being of primary breast origin. A left axillary lymph node dissection was performed, with 1/12 nodes testing positive for poorly differentiated carcinoma. The patient experienced significant improvement in her neurological symptoms 2–3 days following resection of the solitary malignant lymph node, largely regaining her functional independence. She went on to receive adjuvant radiotherapy to the breast and axilla, as well as adjuvant hormonal therapy. Full article

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species. Full article

Phosphoinositide-binding pleckstrin homology (PH) domains interact with both phospholipids and proteins, often complicating their use as specific lipid biosensors. In this study, we introduced specific mutations into the phosphatidylinositol 3,4,5-trisphosphate (PIP₃)-specific PH domains of protein kinase B (Akt) and general receptor for phosphoinositides 1 (GRP1) that disrupt protein-mediated interactions while preserving lipid binding, in order to enhance biosensor specificity for PIP₃, and evaluated their impact on plasma membrane (PM) localization and lipid-tracking ability. Using bioluminescence resonance energy transfer (BRET) and confocal microscopy, we assessed the localization of PH domains in HEK293A cells under different conditions. While Akt-PH mutants showed minimal deviations from the wild type, GRP1-PH mutants exhibited significantly reduced PM localization both at baseline and after stimulation with epidermal growth factor (EGF), insulin, or vanadate. We further developed tandem mutant GRP1-PH domain constructs to enhance PM PIP₃ avidity. Additionally, our investigation into the influence of ADP ribosylation factor 6 (Arf6) activity on GRP1-PH-based biosensors revealed that while the wild-type sensors were Arf6- dependent, the mutants operated independently of Arf6 activity level. These optimized GRP1-PH constructs provide a refined biosensor system for accurate and selective detection of dynamic PIP₃ signaling, expanding the toolkit for dissecting phosphoinositide-mediated pathways. Full article