Locus-Specific Methylation of GSTP1, RNF219, and KIAA1539 Genes with Single Molecule Resolution in Cell-Free DNA from Healthy Donors and Prostate Tumor Patients: Application in Diagnostics

The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539 (also known as FAM214B)) in the blood plasma cell-free DNA (cfDNA) of 20 patients with prostate cancer (PCa), 18 healthy donors (HDs), and 17 patients with benign prostatic hyperplasia (BPH) was studied via the MiSeq platform. The methylation status of two CpGs within the same loci were used as the diagnostic feature for discriminating the patient groups. Many variables had good diagnostic characteristics, e.g., each of the variables GSTP1.C3.C9, GSTP1.C9, and GSTP1.C9.T17 demonstrated an 80% sensitivity at a 100% specificity for PCa patients vs. the others comparison. The analysis of RNF219 gene loci methylation allowed discriminating BPH patients with absolute sensitivity and specificity. The data on the methylation of the genes GSTP1 and RNF219 allowed discriminating PCa patients, as well as HDs, with absolute sensitivity and specificity. Thus, the data on the locus-specific methylation of cfDNA (with single-molecule resolution) combined with a diagnostic approach considering the simultaneous methylation of several CpGs in one locus enabled the discrimination of HD, BPH, and PCa patients.

Performance evaluation of a PET insert for preclinical MRI in stand-alone PET and simultaneous PET–MRI modes

Background This study aimed to evaluate the performance of a preclinical PET insert in three configurations: as a stand-alone unit outside the MRI bore, inside the bore of a cryogen-free 3T MRI and, finally, while performing simultaneous PET/MRI studies. Methods The PET insert consists of two rings of six detectors, each detector comprising 8 × 12 SiPMs reading out dual offset layers of pixelated LYSO crystals with a 1.4-mm pitch. The inner diameter is 60 mm, transaxial field of view (FoV) 40 mm and axial FoV 98 mm. Evaluation was based on NEMA NU 4-2008 guidelines with appropriate modifications. Spatial resolution and sensitivity were measured inside and outside the MR bore. Image quality, count rate and quantitative performance were measured in all three configurations. The effect of temperature stability on PET sensitivity during fast spin echo sequences was also evaluated. B0 field homogeneity and T1 and T2 relaxation times were measured using a water-filled phantom, with and without simultaneous PET operation. Finally, PET and MRI scans of a mouse injected with 10 MBq [18F]NaF and a mouse injected with 16 MBq [18F]FDG were performed in sequential and simultaneous modes. Results Peak absolute sensitivity was 10.15% with an energy window of 250–750 keV. Absolute sensitivity values outside and inside the MR bore with MR idle agreed to within 0.1%. Outside the MR bore, spatial resolution was 1.21/1.59 mm FWHM (radial/tangential) 5 mm from the centre of the FoV which compared well with 1.19/1.26 mm FWHM inside the MR bore. There were no substantial differences between all three scan configurations in terms of peak NEC rate (175 kcps at 17 MBq), scatter or random fractions. Uniformity and recovery coefficients were also consistent between scanning modes. B0 field homogeneity and T1 and T2 relaxation times were unaltered by the presence of the PET insert. No significant differences were observed between sequential and simultaneous scans of the animals. Conclusions We conclude that the performance of the PET insert and MRI system is not significantly affected by the scanning mode.

Performance Evaluation of a PET Insert for Preclinical MRI in Standalone PET and Simultaneous PET-MRI Modes

Background: This study aimed to evaluate the performance of a preclinical PET insert in three configurations: as a standalone unit outside the MRI bore, inside the bore of a cryogen-free 3T MRI and, finally, while performing simultaneous PET/MRI studies.Methods: The PET insert consists of 2 rings of 6 detectors, each detector comprising 8x12 SiPMs reading out dual offset layers of pixelated LYSO crystals with a 1.4mm pitch. The inner diameter is 60mm, transaxial Field of View (FoV) 40mm and axial FoV 98mm. Evaluation was based on NEMA NU 4-2008 guidelines with appropriate modifications. Spatial resolution and sensitivity were measured inside and outside the MR bore. Image quality, count rate and quantitative performance were measured in all three configurations. The effect of temperature stability on PET sensitivity during fast spin echo sequences was also evaluated. B0 field homogeneity, T1 and T2 relaxation times were measured using a water-filled phantom, with and without simultaneous PET operation. Finally, PET and MRI scans of a mouse injected with 10 MBq [18F]NaF and a mouse injected with 16 MBq [18F]FDG were performed in sequential and simultaneous modes. Results: Peak absolute sensitivity was 10.15% with an energy window of 250-750 keV. Absolute sensitivity values outside and inside the MR bore with MR idle agreed to within 0.1%. Outside the MR bore spatial resolution was 1.21/1.59 mm FWHM (radial/tangential) 5mm from the centre of the FoV which compared well with 1.19/1.26mm FWHM inside the MR bore. There were no substantial differences between all three scan configurations in terms of peak NEC rate (175 kcps at 17MBq), scatter or random fractions. Uniformity and recovery coefficients were also consistent between scanning modes. B0 field homogeneity and T1 and T2 relaxation times were unaltered by the presence of the PET insert. No significant differences were observed between sequential and simultaneous scans of the animals.Conclusion: We conclude that performance of the PET insert and MRI system are not significantly affected by scanning mode.

Are serum molecular markers more effective than the invasive methods used in the diagnosis of breast cancers?

Objectives The most effective method currently used in breast cancer diagnosis is fine-needle aspiration biopsy. However, if the superiority of serum molecular markers to invasive diagnostic methods can be proven, it will have a great impact on the diagnostic approach and screening programs for breast cancer. The aim of this study is to demonstrate the efficacy of the serum molecular markers in the diagnosis of breast cancer with respect to invasive methods. Materials and Methods In this study, the literature on serum molecular markers and tissue molecular markers obtained using fine needle aspiration biopsy were collected. The absolute sensitivity rates obtained for serum molecular markers and for invasive needle biopsy methods were compared by systematic biostatistical analysis. Results In the diagnosis of breast cancer, the absolute sensitivity rates of serum molecular markers (90.6%) were found to be significantly higher than the absolute sensitivity rates of invasive methods (80.7%) (p<0.001). Conclusions These results indicate that, serum molecular markers, can be used safely in breast cancer screening, definitive diagnosis and follow-up. Therefore, in the near future, serum molecular markers are likely to take a higher priority in breast cancer diagnosis and screening.

NOISE INFLUENCE ON THE RESOLUTION OF THE SENSORS BASED ON MAGNETIC TRANSISTOR STRUCTURES

Absolute sensitivity is a parameter that directly connects the disturbing value with the response to it, is the determining physical characteristic of the absolute majority of the conversion structure, regardless on the operation principle. This parameter is also considered the main criterion for the quality of the product when using such structures as sensors of the corresponding values. Therefore, the problem of the transducer sensitivity increasing remains relevant in connection with the increasing the sensor number built on new principles: new materials, new functionality and increasing the requirements arising from the sensor operating conditions.

Analysis of the prevalence of antibiotic-resistant opportunistic microflora isolated in patients with bronchitis

In Press The study of Staphylococcus and Streptococcus antibiotics sensitivity revealed absolute sensitivity of S. aureus to cefepime and imipenem, S. pyogenes – to amoxiclav, ofloxacin and clindamycin. Staphylococcus showed the greatest resistance to penicillins (50–75%), amoxiclav (35–43%), norfloxacin (40–50%), azithromycin (S. aureus – 14%, S. epidermidis – 84%). Amoxiclav was the most active against Streptococcus (81–100% of sensitive strains). S. pyogenes strains had the greatest resistance to azithromycin (75%), penicillins (50–60%), carbapenems (50–60%). Other Streptococcus were resistant to azithromycin (34–50% cases). Keywords: antibiotics resistance, opportunistic microorganisms, bronchitis.

Recalibrating SARS-CoV-2 antigen rapid lateral flow test relative sensitivity from validation studies to absolute sensitivity for detecting individuals with live virus

Testing for SARS-CoV-2 internationally has focused on COVID-19 diagnosis among symptomatic individuals using reverse transcriptase polymerase chain reaction (PCR) tests. Recently, however, SARS-CoV-2 antigen rapid lateral flow tests (LFT) have been rolled out in several countries for testing asymptomatic individuals in public health programmes. Validation studies for LFT have been largely cross-sectional, reporting sensitivity, specificity and predictive values of LFT relative to PCR. However, because PCR detects genetic material left behind for a long period when the individual is no longer infectious, these statistics can under-represent sensitivity of LFT for detecting infectious individuals, especially when sampling asymptomatic populations. LFTs (intended to detect individuals with live virus) validated against PCR (intended to diagnose infection) are not reporting against a gold standard of equivalent measurements. Instead, these validation studies have reported relative performance statistics that need recalibrating to the purpose for which LFT is being used. We present an approach to this recalibration. We derive a formula for recalibrating relative performance statistics from LFT vs PCR validation studies to give likely absolute sensitivity of LFT for detecting individuals with live virus. We show the differences between widely reported apparent sensitivities of LFT and its absolute sensitivity as a test of presence of live virus. After accounting for within-individual viral kinetics and epidemic dynamics within asymptomatic populations we show that a highly performant test of live virus should show a LFT-to-PCR relative sensitivity of less than 50% in conventional validation studies, which after re-calibration would be an absolute sensitivity of more than 80%. Further studies are needed to ascertain the absolute sensitivity of LFT as a test of infectiousness in COVID-19 responses. These studies should include sampling for viral cultures and longitudinal series of LFT and PCR, ideally in cohorts sampled from both contacts of cases and the general population.

The effect of sorptivity on cumulative infiltration

Hydraulic parameters of the soil play a considerable role in the hydrological cycle, irrigation planning, drainage, groundwater recharge, and water resources management. One of the most important hydraulic parameters of the soil is sorptivity (S), yet there is insufficient research on how it affects the mechanism of infiltration. The main scope of this study is to investigate the effect(/significance) of sorptivity on the mechanism of infiltration of water, through various types of soil medium, from both mathematical and experimental perspective. For this scope, the absolute sensitivity analysis factor of sorptivity was obtained, while two experimental procedures were carried out in the laboratory. Each soil sample was packed into a vertical column, while a constant head of 2 mm was applied at the surface of the soil. The incoming water was measured volumetrically and at the same time, soil moisture, at certain locations, was measured using the TDR method. Sorptivity of each soil was calculated using Parlange's equation. Absolute sensitivity analysis factor of sorptivity showed that a longer duration/period of cumulative infiltration, sorptivity affects strongly the phenomenon as more synectic the soil type. Thus, estimating sorptivity of the soil could lead to better solutions on irrigation planning, flood prediction and water saving.