Background: MR imaging of the spinal cord (SC) gray matter (GM) at the cervical and lumbar enlargements' level may be particularly informative in lower motor neuron disorders, e. g., spinal muscular atrophy, but also in other neurodegenerative or autoimmune diseases affecting the SC. Radially sampled averaged magnetization inversion recovery acquisition (rAMIRA) is a novel approach to perform SC imaging in clinical settings with favorable contrast and is well-suited for SC GM quantitation. However, before applying rAMIRA in clinical studies, it is important to understand (i) the sources of inter-subject variability of total SC cross-sectional areas (TCA) and GM area (GMA) measurements in healthy subjects and (ii) their relation to age and sex to facilitate the detection of pathology-associated changes. In this study, we aimed to develop normalization strategies for rAMIRA-derived SC metrics using skull and spine-based metrics to reduce anatomical variability. Methods: Sixty-one healthy subjects (age range 11–93 years, 37.7% women) were investigated with axial two-dimensional rAMIRA imaging at 3T MRI. Cervical and thoracic levels including the level of the cervical (C4/C5) and lumbar enlargements (Tmax) were examined. SC T2-weighted sagittal images and high-resolution 3D whole-brain T1-weighted images were acquired. TCA and GMAs were quantified. Anatomical variables with associations of |r| > 0.30 in univariate association with SC areas, and age and sex were used to construct normalization models using backward selection with TCAC4/C5 as outcome. The effect of the normalization was assessed by % relative standard deviation (RSD) reductions. Results: Mean inter-individual variability and the SD of the SC area metrics were considerable: TCAC4/5: 8.1%/9.0; TCATmax: 8.9%/6.5; GMAC4/C5: 8.6%/2.2; GMATmax: 12.2%/3.8. Normalization based on sex, brain WM volume, and spinal canal area resulted in RSD reductions of 23.7% for TCAs and 12.0% for GM areas at C4/C5. Normalizations based on the area of spinal canal alone resulted in RSD reductions of 10.2% for TCAs and 9.6% for GM areas at C4/C5, respectively. Discussion: Anatomic inter-individual variability of SC areas is substantial. This study identified effective normalization models for inter-subject variability reduction in TCA and SC GMA in healthy subjects based on rAMIRA imaging.

Microplastics (MPs) have gained significant attention in the last two decades and have been widely researched in the marine environment. There are, however, less studies on their presence, routes of entry, and impacts on the biota in the soil environment. One of the main issues in the study of MPs is a lack of standardized methods for their identification in environmental samples. Currently the most commonly used techniques are thermal desorption gas chromatography–mass spectrometry (GC–MS) methods and pyrolysis followed by GC–MS. In this study, headspace-solid phase microextraction followed by GC–MS is proposed as a simple and widely applicable method for the determination of commonly present polymer MPs (polyethylene terephthalate, polystyrene, polyvinyl chloride, polyethylene, and polypropylene) in environmental samples, for analytical laboratories with basic equipment worldwide. The proposed method is based on the identification of compounds, which are formed during the well-controlled melting process of specific coarse (1–5 mm) and fine fraction (1 mm–100 μm) MPs. The method was upgraded for the identification of individual polymer type in blends and in complex environmental matrices (soil and algae biomass). The successful application of the method in complex matrices makes it especially suitable for widescale use.

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By a closer inspection of the Friedman-Jorgenson-Kramer algorithm related to the prime geodesic theorem on cofinite Fuchsian groups of the first kind, we refine the constants therein. The newly obtained effective upper bound for Huber’s constant is in the modular surface case approximately 74000 74000 -times smaller than the previously claimed one. The degree of reduction in the case of an upper bound for Faltings’s delta function ranges from 10 8 10^{8} to 10 16 10^{16} .

The aim of this work was to evaluate the influence of cheese milk standardization on chemical composition, fat and protein recovery, yield and sensory properties of Croatian soft Protected Geographical Indication (PGI) Lički škripavac cheese. Standardization of milk to the casein/fat ratio of 0.7 was carried out by adding skimmed milk powder (SMP) to cheese milk and by skimming part of the milk fat. Results showed that losses of fat by whey were significantly (p < 0.05) lower after Lički škripavac cheese produced from standardized milk by skimming part of the milk fat. Standardization of cheese milk by addition of SMP caused higher losses of protein (p < 0.05) and total solids (p < 0.0001) by whey. Both methods of cheese milk standardization caused a significant (p < 0.01) decrease in milk fat and fat in dry matter content in cheese. In contrast, standardization of cheese milk caused a significant (p < 0.01) increase in protein content in cheese milk. Moisture in non-fat substance (MNFS) significantly (p < 0.05) decreased. Optimization of the casein/fat ratio did not cause a significant increase in fat recovery, but protein recovery significantly increased (p < 0.01). Addition of SMP to cheese milk significantly (p < 0.01) increased actual and adjusted cheese yield. The addition of SMP led to a noticeably higher (p = 0.10) sensory score of Lički škripavac cheese.

Background: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. Methods: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case–control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC). Results: The meta-analysis identified associations (P < 4.7 × 10−5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P < 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set in MCCS [N = 134; odds ratio per SD (OR) = 1.37; 95% CI, 1.00–1.90] after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (N = 440; OR = 1.09; 95% CI, 0.91–1.30). Conclusions: Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger data sets. Impact: DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.

Antigen recognition and T-cell mediated cytotoxicity in clear-cell renal cell carcinoma (ccRCC) remains incompletely understood. To address this knowledge gap, we analysed 115 multiregion tumour samples collected from 15 treatment-naive patients pre- and post-nivolumab therapy, and at autopsy in three patients. We performed whole-exome sequencing, RNAseq, TCRseq, multiplex immunofluorescence and flow cytometry analyses and correlated with clinical response. We observed pre-treatment intratumoural TCR clonal expansions suggesting pre-existing immunity. Nivolumab maintained pre-treatment expanded, clustered TCR clones in responders, suggesting ongoing antigen-driven stimulation of T-cells. T-cells in responders were enriched for expanded TCF7+CD8+ T-cells and upregulated GZMK/B upon nivolumab-binding. By contrast, nivolumab promoted accumulation of new TCR clones in non-responders, replacing pre-treatment expanded clonotypes. In this dataset, mutational features did not correlate with response to nivolumab and human endogenous retrovirus expression correlated indirectly. Our data suggests that nivolumab potentiates clinical responses in ccRCC by binding pre-existing expanded CD8+ T-cells to enhance cytotoxicity.

INTRODUCTION:Obstructive Sleep Apnea (OSA)represents the complete or partial obstruction of the airway.Clinically OSA manifests as sleepness during the day,heavy snoring as well as waking up during the night dues the lack of air.Obesity,gender and orthodontic malocclusion are mentioned in the literature as the etiologic factor for Obstructive Sleep Apnea. AIM: The aim of this study was to find the relationship in the analyzed studies between the Obstructive Sleep Apnea and orthodontic malocclusion at non-obese adults. MATERIAL AND METHODS:The electornic search of the database was performed,using PubMed and Googlescholar,with the aim to find the relevante articles which correlate the OSA and orthodontic malocclusion.Keyword included:obstrucitve sleep apnea,orthodontic malocclusion,cephalometric analysis,impact,association,body mass index,obesity,adults,non obesity. Inclusion criteria were:nonobesity,orthodontic malocclusion,adults,articles published from 1999 to 2019,articles in English,full articles avaiable. RESULTS:Two hundred papers included keywords.The number of articles that included the fully set criteria was nine.These nine articles were analyzed in detail. CONCLUSION:Analyzed articles showed that there is relationship between the Obstructive Sleep Apnea and orthodontic malocclusion in non-obese adults.It was also showed that orthodontic malocclusion is etiological factor for OSA in non-obese adults.

This paper describes the influence of deformation by equal-channel angular pressing (ECAP) on the solid particle erosion resistance of the AlSi7Mg0.3 alloy and AlSi7Mg0.3 based composite material reinforced with the addition of 4 % of fly ash (FA) particles. Both, alloy and composite samples were produced using the compo-casting method. The samples have been subjected to ECAP in multiple passes with the rotation of samples around the vertical axis for the angle of 90° after each pass. Particles of silicon carbide (SiC) have been used as erodent while their impact angle was varied (30° and 90°). Observed samples of AlSi7Mg0.3 alloy generally showed higher wear resistance at 90° angle where material fatigue predominates, than at a 30° angle where abrasion-related phenomena predominate. On the other hand, AlSi7Mg0.3 based composite material exhibited erosion wear at 30° angle less than at 90° angle after one ECAP pass. Evaluation of the erosion resistance has been made based on mass and volume loss. After two passes of ECAP, the matrix structure of the AlSi7Mg0.3 based composite material, as well as that of the AlSi7Mg0.3 alloy was improved from the aspect of erosion resistance.