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There was a trend toward lower IL-12p70 values among ENDS users with these covariates. Findings reveal dysregulation of salivary immune profiles toward a TH1 phenotype in emerging adult ENDS users and short-term immune function may be dysregulated in young adult e-cigarette users.Background and purpose 4D CT images often contain artifacts that are suspected to affect treatment planning quality and clinical outcome of lung and liver SBRT. The present study investigates the correlation between the presence of artifacts in SBRT planning 4D CT data and local metastasis control. Materials and methods The study includes 62 patients with 102 metastases (49 in the lung and 53 in the liver), treated between 2012 and 2016 with SBRT for mainly curative intent. For each patient, 10-phase 4D CT images were acquired and used for ITV definition and treatment planning. Gefitinib molecular weight Follow-up intervals were 3 weeks after treatment and every 3-6 months thereafter. Based on the number and type of image artifacts, a strict rule-based two-class artifact score was introduced and assigned to the individual 4D CT data sets. Correlation between local control and artifact score (consensus rating based on two independent observers) were analyzed using uni- and multivariable Cox proportional hazards models with random effects. Metastatic site, target volume, metastasis motion, breathing irregularity-related measures, and clinical data (chemotherapy prior to SBRT, target dose, treatment fractionation) were considered as covariates. Results Local recurrence was observed in 17/102 (17%) metastases. Significant univariable factors for local control were artifact score (severe CT artifacts vs. few CT artifacts; hazard ratio 8.22; 95%-CI 2.04-33.18) and mean patient breathing period (>4.8 s vs. ≤4.8 s; hazard ratio 3.58; 95%-CI 1.18-10.84). Following multivariable analysis, artifact score remained as dominating prognostic factor, although statistically not significant (hazard ratio 10.28; 95%-CI 0.57-184.24). Conclusion The results support the hypothesis that image artifacts in 4D CT treatment planning data negatively influence clinical outcome in SBRT of lung and liver metastases, underlining the need to account for 4D CT artifacts and improve image quality.Duvelisib, a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor, was recently approved in the USA as the therapeutic drug for patients with the diseases of relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In the present study of our research, a quick and simple bioanalytical method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was fully explored and established for the quantification of plasma duvelisib concentrations from beagle dog in which gilteritinib was used as the internal standard (IS). After a simple and quick protein precipitation treated with acetonitrile, the chromatographic separation of the analyte was carried out on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) conducted in a gradient elution procedure where acetonitrile (solvent A) and 0.1 % formic acid in water (solvent B) consisted as the mobile phase. The measurements of the analyte and IS were explored using a XEVO TQS triple quadrupole tandem mass spectrometer, which was comprised with electrospray ionization (ESI) source in positive ion mode. Selected reaction monitoring (SRM) mode was employed to detect the parent-to-daughter ion transitions as follows m/z 416.88 → 281.88 for duvelisib, and m/z 553.09 → 436.01 for IS, respectively. The assay was successfully established in the calibration range from 0.5 to 3000 ng/mL for duvelisib, where the lower limit of quantification (LLOQ) was set at 0.5 ng/mL. The precisions of intra-day and inter-day for duvelisib were all below 12.6 %, and the accuracies were from -2.5% to 14.1%. Both matrix effect and mean recovery of the analyte and IS were all acceptable, and the analyte was stable during the assay and storage in dog plasma samples. The novel established bioanalytical method based on UPLC-MS/MS technique was effectively employed to the investigation of the pharmacokinetic profile of duvelisib in beagle dogs following a 1.34 mg/kg single dose of oral administration.Therapeutic drug monitoring (TDM) of immunosuppressive drugs is crucial in organ-transplanted patients to prevent rejection or toxic effects due to inadequate dosage. Mycophenolic acid (MPA) is a commonly used immunosuppressant in this setting. Nowadays, MPA concentrations are monitored by Enzyme Multiplied Immunoassay Technology (EMIT), and Liquid Chromatography (LC)-based techniques, particularly coupled to Tandem Mass Spectrometry (LC-MS/MS). This study evaluates the concordance between TDM results for MPA obtained through CE-IVD EMIT and LC-MS/MS assays in plasma samples. LC-MS/MS quantification was based on a commercial kit and the analytical performance in terms of accuracy was tested through external proficiency tests and inter-laboratory comparison with a home-made HPLC-UV method. Both these evaluations confirmed the reliability of the LC-MS/MS method (1.6 % and 9.0 % of bias, respectively). Conversely, the comparison between EMIT and LC-MS/MS showed overestimation by EMIT of 33.5 %. This bias resulted concentration-dependent, ranging from 46.4 % in the concentration range of 1-2 mg/L, to 21.4 % over 4 mg/L. Considering the theoretical clinical impact of this overestimation, a fraction comprised between 12.4 % and 31.4 % of samples which resulted over three different minimum effective concentration values by EMIT (no indication for dose adjustment) had discordant indications by LC-MS/MS (dose adjustment needed). Concluding, this study highlights a clinically relevant systematic overestimation of MPA concentration by EMIT, supporting the switch to LC-MS/MS techniques for TDM purpose. However, further prospective studies are needed in order to evaluate the clinical impact of switching the TDM activity from EMIT to LC-MS/MS in a larger cohort in a long period.Purpose To test the hypothesis that removing the assumption of material homogeneity will improve the spatial accuracy of stiffness estimates made by Magnetic Resonance Elastography (MRE). Methods An artificial neural network was trained using synthetic wave data computed using a coupled harmonic oscillator model. Material properties were allowed to vary in a piecewise smooth pattern. This neural network inversion (Inhomogeneous Learned Inversion (ILI)) was compared against a previous homogeneous neural network inversion (Homogeneous Learned Inversion (HLI)) and conventional direct inversion (DI) in simulation, phantom, and in-vivo experiments. Results In simulation experiments, ILI was more accurate than HLI and DI in predicting the stiffness of an inclusion in noise-free, low-noise, and high-noise data. In the phantom experiment, ILI delineated inclusions ≤ 2.25 cm in diameter more clearly than HLI and DI, and provided a higher contrast-to-noise ratio for all inclusions. In a series of stiff brain tumors, ILI shows sharper stiffness transitions at the edges of tumors than the other inversions evaluated.

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