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Δευτέρα 30 Ιανουαρίου 2023

A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces

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Abstract
Primary aromatic amines (PAAs) are a class of hazardous substances where many compounds are classified as carcinogen, mutagen, and reproduction toxin (CMR). PAAs can be taken up by dermal exposure. In the polyurethane industry, a valid and trustworthy method for the quantification of PAAs in the presence of isocyanates that could interfere is of great interest, especially on workplaces where a regular contact to PAAs cannot be excluded. The aim of this work is the development, validation, and verification of a novel sampling device to quantify selectively the PAA load on work surfaces. We describe the synthesis of Cell-ßALA-PEMSA analytical papers and their characterization by infrared spectroscopy and thermogravimetric analysis. The recovery of TDA and MDA spiked on these filters is satisfactory. An excellent selectivity of Cell-ßALA-PEMSA papers towards PAAs in the presence of isocyanates of almost 100% was found by wipe tests of amine/isocya nate contaminated surfaces. First positive field tests were achieved at certain areas in a Polyurethane Technical Application Department where surface contamination with PAAs was expected, and the Cell-ßALA-PEMSA analytical papers were superior to an established method of surface sampling. However, recovery of these amines from surfaces shows a large variability, and more work is required to address influencing surface properties.
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Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

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ABSTRACT
Background
Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron).
Methods
This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status.
Results
The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status.
Conclusions
Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.
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Κυριακή 29 Ιανουαρίου 2023

Role of non‐coding RNAs with emphasis on long non‐coding RNAs as cervical cancer biomarkers

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Abstract

Cervical cancer is a significant public health problem in developing countries, as most cases present at an advanced stage. This review aimed to analyze the role of non-coding RNAs as diagnostic and prognostic biomarkers in cervical cancers. Published studies on specific microRNA signatures in body fluids and cervical cancer tissues are highly heterogeneous, and there are no validated assays. The precision of the various immune-associated lncRNA signatures should be assessed in clinical samples. Even though lncRNAs are tissue and cancer-specific, safe and appropriate methods for delivery to tumor tissues, toxicities and side effects are to be explored. Few studies have evaluated deregulated lncRNA expression levels with clinicopathological factors in a limited number of clinical samples. Prospective studies assessing the diagnostic and prognostic roles of circulating lncRNAs and P-Element-induced wimpy testis interacting PIWI RNAs (Piwil RNAs) in cervical ca ncer cases are essential. For the clinical application of lnc-RNA-based biomarkers, comprehensive research is needed as the impact of non-coding transcripts on molecular pathways is complex. The standardization and validation of deregulated ncRNAs in non-invasive samples of cervical cancer cases are needed.

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Novel Murine Glioblastoma Models That Reflect the Immunotherapy Resistance Profile of Human Disease

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Abstract
Background
The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We therefore developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and underlying mechanisms.
Methods
The differential responsiveness of QPP lines was assessed in the brain and flank in untreat ed, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on responsiveness of each tumor was measured through whole exome sequencing. The immune microenvironments of sensitive (QPP7) versus resistant (QPP8) lines were compared in the brain using flow cytometry. Drivers of flank sensitivity versus brain resistance were also measured for QPP8.
Results
QPP lines are syngeneic to C57BL/6J mice and demonstrate varied sensitivities to T cell immune checkpoint blockade ranging from curative responses to complete resistance. Infiltrating tumor immune analysis of QPP8 reveals improved T cell fitness and augmented effector to suppressor ratios when implanted subcutaneously (sensitive), which are absent upon implantation in the brain (resistant). Upregulation of PD-L1 across the myeloid stroma acts to establish this state of immune privilege in the brain. In contrast, QPP7 responds to checkpoint immunotherapy even in the brain likely resulting from its elevated neoa ntigen burden.
Conclusions
These syngeneic QPP models of glioblastoma demonstrate clinically-relevant profiles of immunotherapeutic sensitivity and potential utility for both mechanistic discovery and evaluation of immune therapies.
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Immunological efficacy of pneumococcal vaccination including the 13-valent pneumococcal vaccine in adult patients with sickle-cell disease: results of the randomized DREVAC controlled trial

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Abstract
Background
Patients with sickle-cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.
Methods
This was a randomized open-labelled phase 2 study of the immunogenicity of PCV13 at week (W)0, followed by PPSV23 at W4, compared to PPSV23 alone at W4 in adult patients with SCD. The proportion of responders (four-fold increase of serotype-specific IgG antibodies) to at least 10-shared serotypes was assessed at W8. Secondary endpoints were: i) geometrical mean titers (GMTs), ii) responders to 0-1, 2-5, 6-9, and 10-12 serotypes, iii) pneumococcal opsonophagocytic (OPA) activity, and iv) response durability at W24 and W96.
Results
In total, 128 patients were randomized in the PCV13/PPSV23 (n=63) or PPSV23-alone groups (n=65). At W8, 24.5 6% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary endpoint (p=0.016). These numbers were 36.2% and 8.7% for OPA responders (p=0.002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, and 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At W96, GMTs were significantly higher in the PCV13/PPSV23 than in the PPSV23 alone group for five serotypes (4, 14, 19A, 19F, 23F).
Conclusions
A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415
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68Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma: A Head-to-Head Comparison With: 18: F-FDG

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imageMetastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18F-FDG and 68Ga-FAPI PET/CT scans for comparative analysis. 68Ga-DOTA.SA.FAPI emerged as an excellen t diagnostic agent for ACC and performed similar to 18F-FDG.
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18F-THK5351 PET Can Evaluate Tumor Extension in Intravascular Large B-Cell Lymphoma: Comparison With: 11: C-Methionine PET and: 18: F-FDG PET

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imageA 79-year-old man presenting with gait disturbance and cognitive decline was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by random skin biopsy. Some IVLBCL lesions were identified by PET examinations using 11C-methionine, 18F-FDG, and 18F-THK5351. 11C-methionine and 18F-FDG uptake, which likely reflects the presence of the lymphoma cells themselves, increased clearly in the left putamen but weakly in the left deep white matter. 18F-THK5351 uptake increased in all lesions, likely reflecting perivascular astrogliosis caused by IVLBCL. Hence, 18F-THK5351 PET can evaluate tumor extension in IVLBCL lesions wh ere 11C-methionine and 18F-FDG PET may fail in its visualization.
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Bone Scan With Pulmonary Uptake in Scleroderma

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imageWe present a 61-year-old woman with a history of scleroderma and suspicion of osteomyelitis in her left wrist. She underwent a 3-phase bone scan for evaluation of osteomyelitis. Incidentally, the scan showed bilateral pulmonary MDP uptake, especially in lower lobes, which was proven to be due to the nonfibrotic form of nonspecific interstitial pneumonia.
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Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme

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imageA 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fi broblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas.
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Complete Femoral Osteonecrosis in the Setting of Myelodysplastic Syndrome

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imageA 76-year-old man was diagnosed with a hematological neoplasm combining myelodysplastic and myeloproliferative characteristics back in July 2021. Five months after the diagnosis, his condition got more severe when the blasts rose up to 14%, so he was started on hypomethylating agent–based therapy. A few weeks later, the patient was hospitalized after developing fever and a pain in the right thigh. To exclude any source of occult infection, an 18F-FDG PET/CT was performed. FDG PET/CT showed a complete lack of metabolism in the right femur. An MRI and a biopsy confirmed the suspected diagnosis of osteonecrosis.
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