Lambertsenharrison3452

Chimeric antigen receptor (CAR)-T cell strategies ideally target a surface antigen that is exclusively and uniformly expressed by tumors; however, no such antigen is known for high-grade serous ovarian carcinoma (HGSC). A potential solution involves combinatorial antigen targeting with AND or OR logic-gating. Therefore, we investigated co-expression of CA125, Mesothelin (MSLN) and Folate Receptor alpha (FOLRA) on individual tumor cells in HGSC.

RNA expression of CA125, MSLN, and FOLR1 was assessed using TCGA (HGSC) and GTEx (healthy tissues) databases. Antigen expression profiles and CD3+, CD8+ and CD20+ tumor-infiltrating lymphocyte (TIL) patterns were assessed in primary and recurrent HGSC by multiplex immunofluorescence and immunohistochemistry.

At the transcriptional level, each antigen was overexpressed in >90% of cases; however, MSLN and FOLR1 showed substantial expression in healthy tissues. At the protein level, CA125 was expressed by the highest proportion of cases and tumor cells per case, followed by MSLN and FOLRA. The most promising pairwise combination was CA125 and/or MSLN (OR gate), with 51.9% of cases containing ≥90% of tumor cells expressing one or both antigens. In contrast, only 5.8% of cases contained ≥90% of tumor cells co-expressing CA125 and MSLN (AND gate). Antigen expression patterns showed modest correlations with TIL. Recurrent tumors retained expression of all three antigens and showed increased TIL densities.

An OR-gated CAR-T cell strategy against CA125 and MSLN would target the majority of tumor cells in most cases. Antigen expression and T-cell infiltration patterns are favorable for this strategy in primary and recurrent disease.

An OR-gated CAR-T cell strategy against CA125 and MSLN would target the majority of tumor cells in most cases. Antigen expression and T-cell infiltration patterns are favorable for this strategy in primary and recurrent disease.The management of upper-limb non-unions can be challenging, especially when infection is existent. Thus, pre-operative detection of infection plays a relevant role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for differentiating between aseptic and infected upper-limb non-unions. Osseous perfusion of 50 upper-extremity non-unions (radius/ulna, n = 20; humerus, n = 22; clavicle, n = 8) was prospectively assessed with CEUS before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (in arbitrary units). Significant perfusion differences between aseptic and infected non-unions could be detected (peak enhancement, p less then 0.001). The sensitivity and specificity for the detection of infected upper-limb non-unions were 80% and 94.3% (cutoff peak enhancement 130.8 arbitrary units). CEUS reliably differentiates between aseptic and infected upper-limb non-unions. Consequently, CEUS should be integrated into the daily diagnostic routine algorithm to plan non-union revision surgery more precisely as a single- or multi-step procedure.Progressive liver fibrosis may result in cirrhosis, portal hypertension and increased risk of hepatocellular carcinoma. We performed a meta-analysis to compare liver fibrosis staging in chronic liver disease patients using 2-D shear wave elastography (2-D SWE) and point shear wave elastography (pSWE). The PubMed, Web of Science and Cochrane Library databases were searched until May 31, 2020 for studies evaluating the diagnostic performance of 2-D SWE and pSWE in assessing liver fibrosis. Pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios and area under receiver operating characteristic curve were estimated using the bivariate random effects model. WAY-316606 molecular weight As a result, 71 studies with 11,345 patients were included in the analysis. The pooled sensitivities of 2-D SWE and pSWE significantly differed for the detection of significant fibrosis (F ≥ 2; 0.84 vs. 0.76, p less then 0.001) and advanced fibrosis (F ≥ 3; 0.90 vs. 0.83, p = 0.003), but not for detection of cirrhosis (F = 4; 0.89 vs. 0.85, p = 0.090). The pooled specificities of 2-D SWE and pSWE did not significantly differ for detection of F ≥ 2 (0.81 vs. 0.79, p = 0.753), F ≥ 3 (0.87 vs. 0.83, p = 0.163) or F = 4 (0.87 vs. 0.84, p = 0.294). Both 2-D SWE and pSWE have high sensitivity and specificity for detecting each stage of liver fibrosis. Two-dimensional SWE has higher sensitivity than pSWE for detection of significant fibrosis and advanced fibrosis.Multicentre clinical trials involving a dosimetry component are becoming more prevalent in molecular radiotherapy and are essential to generate the evidence to support individualised approaches to treatment planning and to ensure that sufficient patients are recruited to achieve the statistical significance required. Quality assurance programmes should be considered to support the standardisation required to achieve meaningful results. Trials should be designed to ensure that dosimetry results from image acquisition systems across centres are comparable by incorporating steps to standardise the methodologies used for the quantification of images and dosimetry. Furthermore, it is essential to assess the expertise and resources available at each participating site prior to trial commencement. A quality assurance plan should be drawn up and training provided if necessary. Standardisation of quantification and dosimetry methodologies used in a trial are essential to ensure that results from different centres may be collated. In addition, appropriate uncertainty analysis should be carried out to correct for differences in methodologies between centres. Recommendations are provided to support dosimetry studies based on the experience of several previous and ongoing multicentre trials.

Testosterone is used therapeutically in medical settings. Non-prescribed testosterone use is typically illegal, described as 'enhancement' or 'doping', and considered a problem. However, research has found that some non-prescribed testosterone use may be therapeutic (i.e. self-medication). Little is known about testosterone self-medication. It has been noted among individuals who use image and performance enhancing drugs (IPEDs), but never systematically explored.

This paper describes the findings of a 4-year ethnographic study in online forums and social media groups frequented by people who use IPEDs. It focusses on 31 men who used enhancement doses of testosterone, but who described some of their testosterone use as 'testosterone replacement therapy' (TRT). In particular, it focuses on the 26 (84%) of these individuals who self-medicated TRT. Data was analysed thematically (using NVivo) in order to answer the question 'how and why is testosterone self-medicated?'. Using Bacchi's (2016) problematizationcess to medical treatment.

By documenting the therapeutic use of testosterone outside of medical settings, this paper calls into question previous conceptualisations of all illicit testosterone use as 'abuse', and the utility of the repair/enhancement dichotomy as a foundation for discussions of drug use. It suggests that in some cases the problem may not be non-prescribed testosterone use per se, but policies that prevent access to medical treatment.

Patient-reported outcome measures assess health status and treatment outcomes in orthopedic care, but they may burden patients with lengthy questionnaires. Predictive models using machine learning, known as computerized adaptive testing (CAT), offer a potential solution. This study evaluates the ability of CAT to improve efficiency of the 30-item Disabilities of the Arm, Shoulder, and Hand (DASH) and 11-item QuickDASH questionnaires.

A total of 2,860 DASH and 27,355 QuickDASH respondents were included in the analysis. The CAT system was retrospectively applied to each set of patient responses stored on the instrument to calculate a CAT-specific score for all DASH and QuickDASH entries. The accuracy of the CAT scores, viewed in the context of the minimal clinically important difference for both patient-reported outcome measures (DASH, 12; QuickDASH, 9), was determined through descriptive statistics, Pearson correlation coefficient, intraclass correlation coefficient, and distribution of scores and score diQuickDASH, CAT is an appropriate alternative to full questionnaire implementation for patient outcome score collection.

Tools will gradually deteriorate with repetitive milling. However, tool lifetime can vary depending on the type of milling machine, the hardness of the ceramic material, and the size of the restoration. Studies evaluating the effect of tool deterioration on the trueness of milled restorations are lacking.

The purpose of this study was to evaluate the effect of tool deterioration on the trueness of milled restorations.

A patient requiring a ceramic crown was recruited. Repetitive milling of zirconia crowns (inCoris TZI; Dentsply Sirona) with tungsten carbide rotary instruments and glass-ceramic crowns (VITABLOCS mark II; Vita Zahnfabrik) with diamond rotary instruments was performed by using a 5-axis milling machine (inLab MC X5; Dentsply Sirona) until the machine software indicated replacing the largest tool. The percentage of deterioration for the largest tool was recorded before each milling. The trueness for different crown areas was evaluated by using a 3-dimensional evaluation software (Geomagic Coa. Only proximal areas were affected in the glass-ceramic crowns, whereas external, proximal, occlusal, and marginal areas were affected in the zirconia crowns. Trueness did not necessarily reflect the clinical quality of the crown, as both crown types were clinically satisfactory. Although zirconia crowns were overmilled in comparison with the reference design and glass-ceramic crowns, they had better clinical quality.

The effect of tool deterioration on trueness depended on material type and crown area. Only proximal areas were affected in the glass-ceramic crowns, whereas external, proximal, occlusal, and marginal areas were affected in the zirconia crowns. Trueness did not necessarily reflect the clinical quality of the crown, as both crown types were clinically satisfactory. Although zirconia crowns were overmilled in comparison with the reference design and glass-ceramic crowns, they had better clinical quality.

Interproximal contact lossbetween implant-supported restorations and adjacent natural teeth is a frequently encountered complication that could negatively affect surrounding tissues and/or patient satisfaction with treatment. The effect of interproximal contact loss on peri-implant tissue health and patient awareness of food impaction is currently unknown.

The purpose of this retrospective cross-sectional study was to explore the effect of interproximal contact loss on peri-implant tissue health and determine whether interproximal contact loss leads to increased patient awareness of food impaction around the affected area. This study also aimed to identify whether specific patient or local factors could cause interproximal contact loss.

Eighty-three participants with posterior single-unit implant-supported restorations were examined. The mean follow-up time after prosthesis insertion was 4 ±2.2 years (range 4 months to 10.6 years). Interproximal contacts were evaluated by using waxed dental floss. Patient age, sex, implant location, opposing tooth status, presence of endodontically treated adjacent tooth, and regular use of an occlusal device at night were recorded.