Diagnostic Test Accuracy of Urinary DNA Methylation-based Biomarkers for the Detection of Primary and Recurrent Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one. METHODS: The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703. KEY FINDINGS AND LIMITATIONS: Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR. CONCLUSIONS AND CLINICAL IMPLICATIONS: DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies. PATIENT SUMMARY: In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.

Bladder Wall Stiffness after Cystectomy in Bladder Cancer Patients: A Preliminary Study.

Bladder cancer (BlCa), specifically urothelial carcinomas, is a heterogeneous disease that derives from the urothelial lining. Two main classes of BlCa are acknowledged: the non-muscle invasive BlCa and the muscle-invasive BlCa; the latter constituting an aggressive disease which invades locally and metastasizes systemically. Distinguishing the specific microenvironment that cancer cells experience between mucosa and muscularis propria layers can help elucidate how these cells acquire invasive capacities. In this work, we propose to measure the micromechanical properties of both mucosa and muscularis propria layers of the bladder wall of BlCa patients, using atomic force microscopy (AFM). To do that, two cross-sections of both the macroscopically normal urinary bladder wall and the bladder wall adjacent to the tumor were collected and immediately frozen, prior to AFM samples analysis. The respective "twin" formalin-fixed paraffin-embedded tissue fragments were processed and later evaluated for histopathological examination. H&E staining suggested that tumors promoted the development of muscle-like structures in the mucosa surrounding the neoplastic region. The average Young's modulus (cell stiffness) in tumor-adjacent specimens was significantly higher in the muscularis propria than in the mucosa. Similarly, the tumor-free specimens had significantly higher Young's moduli in the muscularis propria than in the urothelium. Young's moduli were higher in all layers of tumor-adjacent tissues when compared with tumor-free samples. Here we provide insights into the stiffness of the bladder wall layers, and we show that the presence of tumor in the surrounding mucosa leads to an alteration of its smooth muscle content. The quantitative assessment of stiffness range here presented provides essential data for future research on BlCa and for understanding how the biomechanical stimuli can modulate cancer cells' capacity to invade through the different bladder layers.

Estimation of upper flammability limits of C-H compounds in air at standard atmospheric pressure and evaluation of temperature dependence.

This study focuses on estimating the upper flammability limits of C-H compounds. A method was developed to determine the upper flammability limits in air at standard atmospheric pressure for the following cases: (a) estimation of the UFLs of pure C-H compounds at standard ambient temperature (25°C); (b) estimation of the UFLs of binary mixtures of C-H compounds at standard ambient temperature (25°C); (c) estimation of the UFLs of C-H compounds at different initial temperatures. The method was accurate in all cases. In case (a), for a total set of 115 compounds, the absolute average relative error was 7.27% and a squared correlation coefficient of 0.9248 was obtained. In case (b), the average absolute relative error was 5.55%; in case (c) it was 2.19%.

Estimation of lower flammability limits of C-H compounds in air at atmospheric pressure, evaluation of temperature dependence and diluent effect.

Estimation of the lower flammability limits of C-H compounds at 25 °C and 1 atm; at moderate temperatures and in presence of diluent was the objective of this study. A set of 120 C-H compounds was divided into a correlation set and a prediction set of 60 compounds each. The absolute average relative error for the total set was 7.89%; for the correlation set, it was 6.09%; and for the prediction set it was 9.68%. However, it was shown that by considering different sources of experimental data the values were reduced to 6.5% for the prediction set and to 6.29% for the total set. The method showed consistency with Le Chatelier's law for binary mixtures of C-H compounds. When tested for a temperature range from 5 °C to 100 °C, the absolute average relative errors were 2.41% for methane; 4.78% for propane; 0.29% for iso-butane and 3.86% for propylene. When nitrogen was added, the absolute average relative errors were 2.48% for methane; 5.13% for propane; 0.11% for iso-butane and 0.15% for propylene. When carbon dioxide was added, the absolute relative errors were 1.80% for methane; 5.38% for propane; 0.86% for iso-butane and 1.06% for propylene.

Flammability limits of hydrated and anhydrous ethanol at reduced pressures in aeronautical applications.

There is interest in finding the flammability limits of ethanol at reduced pressures for the future use of this biofuel in aeronautical applications taking into account typical commercial aviation altitude (<40,000 ft). The lower and upper flammability limits (LFL and UFL, respectively) for hydrated ethanol and anhydrous ethanol (92.6% and 99.5% p/p, respectively) were determined for a pressure of 101.3 kPa at temperatures between 0 and 200°C. A heating chamber with a spherical 20-l vessel was used. First, LFL and the UFL were determined as functions of temperature and atmospheric pressure to compare results with data published in the scientific literature. Second, after checking the veracity of the data obtained for standard atmospheric pressure, the work proceeded with reduced pressures in the same temperature range. 295 experiments were carried out in total; the first 80 were to calibrate the heating chamber and compare the results with those given in the published scientific literature. 215 experiments were performed both at atmospheric and reduced pressures. The results had a correlation with the values obtained for the LFL, but values for the UFL had some differences. With respect to the water content in ethanol, it was shown that the water vapor contained in the fuel can act as an inert substance, narrowing flammability.

Flammability limits: a review with emphasis on ethanol for aeronautical applications and description of the experimental procedure.

The lower and upper flammability limits of a fuel are key tools for predicting fire, assessing the possibility of explosion, and designing protection systems. Knowledge about the risks involved with the explosion of both gaseous and vaporized liquid fuel mixtures with air is very important to guarantee safety in industrial, domestic, and aeronautical applications. Currently, most countries use various standard experimental tests, which lead to different experimental values for these limits. A comprehensive literature review of the flammability limits of combustible mixtures is developed here in order to organize the theoretical and practical knowledge of the subject. The main focus of this paper is the review of the flammability data of ethanol-air mixtures available in the literature. In addition, the description of methodology for experiments to find the upper and lower limits of flammability of ethanol for aeronautical applications is discussed. A heated spherical 20L vessel was used. The mixtures were ignited with electrode rods placed in the center of the vessel, and the spark gap was 6.4mm. LFL and the UFL were determined for ethanol (hydrated ethanol 96% °INPM) as functions of temperature for atmospheric pressure to compare results with data published in the scientific literature.