A urine-based liquid biopsy for detection of upper tract urothelial carcinoma: a self-matched study.

BACKGROUND: To establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer. OBJECTIVE: To evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology. MATERIALS AND METHODS: We included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn. RESULTS: The median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53. CONCLUSION: The test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method. NOVELTY & IMPACT STATEMENTS: We evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed.

Analyzing the Impact of Traffic Congestion Mitigation: From an Explainable Neural Network Learning Framework to Marginal Effect Analyses.

Computational graphs (CGs) have been widely utilized in numerical analysis and deep learning to represent directed forward networks of data flows between operations. This paper aims to develop an explainable learning framework that can fully integrate three major steps of decision support: Synthesis of diverse traffic data, multilayered traffic demand estimation, and marginal effect analyses for transport policies. Following the big data-driven transportation computational graph (BTCG) framework, which is an emerging framework for explainable neural networks, we map different external traffic measurements collected from household survey data, mobile phone data, floating car data, and sensor networks to multilayered demand variables in a CG. Furthermore, we extend the CG-based framework by mapping different congestion mitigation strategies to CG layers individually or in combination, allowing the marginal effects and potential migration magnitudes of the strategies to be reliably quantified. Using the TensorFlow architecture, we evaluate our framework on the Sioux Falls network and present a large-scale case study based on a subnetwork of Beijing using a data set from the metropolitan planning organization.

Comparison of DNA methylation and cytology tests in urine to detect upper tract urothelial carcinoma: A paired-design diagnostic study.

OBJECTIVES: To evaluate the diagnostic efficacy of a DNA methylation test, compare that test with cytology alone, fluorescence in situ hybridization (FISH) alone, and cytology plus FISH, and explore reasons that may influence the accuracy of liquid biopsy. METHODS: We included 37 patients and 12 negative control individuals between April 2019 and May 2022. All patients had undergone radical nephroureterectomy, nephrectomy, diagnostic ureteroscopy, or tissue biopsy. Urine samples were collected for DNA methylation testing, cytology, and FISH. Test performance was calculated, and receiver operating characteristic curves were drawn for comparison. RESULTS: Median patient age was 66 years, and κ = 0.576 (P < .001) for the DNA methylation test and tissue pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DNA methylation test were 76%, 100%, 100%, and 74%, respectively, compared with 31%, 100%, 100%, and 50%, respectively, for cytology. The sensitivity, specificity, PPV, and NPV of cytology plus FISH were 66%, 100%, 100%, and 67%, respectively. The area under the curve (AUC) of the DNA methylation test was 0.879 (P < .001), and the AUC of cytology plus FISH was 0.828 (P < .001). CONCLUSIONS: The test performance of DNA methylation was satisfactory. The DNA methylation test for the detection of upper tract urothelial carcinoma demonstrated better sensitivity than did cytology alone or cytology with FISH, but the accuracy of the combined tests was still acceptable. Further prospective studies with larger samples are needed to confirm the clinical value of this promising method.

A meta-analysis on the impact of resistance training on phase angle in middle-aged and older individuals.

PURPOSE: To determine the impact of resistance training (RT) on phase angle (PhA) in middle-aged and older individuals via meta-analysis, explore effects in subgroups, and identify optimal RT protocol. MATERIALS AND METHODS: We searched five databases using predefined criteria, assessed literature quality per Cochrane 5.1 Handbook, and used Revman 5.3 for effect size aggregation, bias assessment, sensitivity analysis, and subgroup analysis. RESULTS: RT improved PhA in middle-aged and older individuals (d = 0.34, 95 % CI: 0.27-0.40, P < 0.05). Effective subgroups included Suspension (d = 0.62, 95 % CI: 0.33-0.90, P < 0.05), free-weights and machine (d = 0.36, 95 % CI: 0.28-0.45, P < 0.05), equipment training (d = 0.24, 95 % CI: 0.13-0.36, P < 0.05), and moderate-intensity RT (d = 0.34, 95 % CI: 0.27-0.42, P < 0.05). RT was conducted 2-3 times/week (d = 0.20, 95 % CI: 0.01-0.38, P < 0.05) or (d = 0.38, 95 % CI: 0.30-0.47, P < 0.05). PhA improved after 8 weeks (d = 0.37, 95 % CI: 0.23-0.51, P < 0.05), 12 weeks (d = 0.35, 95 % CI: 0.26-0.44, P < 0.05), and ≥ 24 weeks (d = 0.26, 95 % CI: 0.11-0.41, P < 0.05) of RT in aged and older individuals. Low- and high-intensity RT, elastic band training, and weekly exercises did not significantly improve PhA. CONCLUSIONS: RT enhances PhA in middle-aged and older adults. For optimal results, we recommend 2-3 weekly sessions of free weights and machine training lasting at least 8 weeks.

Hemodynamic analysis of the frontal cortex using multi-task fNIRS in major depressive disorder.

BACKGROUND: Appropriate task selection is the key to fNIRS-based major depressive disorder (MDD) diagnosis and treatment; however, there exists no unified rule for task selection, which limits its clinical application. METHODS: Four tasks were employed to investigate the hemodynamic characteristics of MDD during motor, emotional, cognitive, and combinational tasks. A total of 69 subjects were studied: 50 with MDD and 19 healthy controls. The integral value of oxy-hemoglobin and the asymmetric characteristics of the bilateral frontal lobe were used to demonstrate the hemodynamic changes in MDD during different tasks. A detailed analysis and comparison among different tasks were conducted. RESULTS: Compared with deoxy-hemoglobin (deoxy-Hb), oxy-Hb was more significant to differentiate between MDD subjects and healthy controls. In subjects with MDD, lower activation of the frontal lobe and smaller integral values of oxy-Hb were observed. In most task paradigms, MDD subjects and healthy controls exhibited diametrically opposite left-right frontal asymmetry. For the integral value of oxy-Hb and the asymmetric characteristics of the bilateral frontal lobe, the differences between MDD subjects and healthy controls under the combinational task were more significant than that under the single tasks. LIMITATIONS: Brain fatigue patterns over time and their effect on the hemodynamic analysis of MDD should be studied further. CONCLUSIONS: The difference in hemodynamic characteristics between MDD subjects and healthy controls is closely related to the choice of task, and the combinational task showed better discrimination than the single tasks. It provides guidance for the appropriate task design for MDD in clinics.

Clinicopathological features of Kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE), an intermediate tumor of endothelial origin in childhood, is often associated with Kasabach-Merritt phenomenon (KMP). In this study, 22 cases of KHE were immunochemically studied for CD31, CD34, ERG, smooth muscle actin (SMA), D240, GLUT1 and Ki67. The patients (15 males and 7 females) ranged in age from 13 days to 7 years (median, 2 mo). Lesion developed on the extremities/joint (12 cases), chest/abdominal wall (6 cases), head/neck (4 cases), and presented both superficial and deep soft tissue. The superficial change was commonly enlarging cutaneous lesion with ill-defined red to purple indurated plaque. 15 of the 22 cases (68%) developed KMP, with consumptive thrombocytopenia or bleeding complications. Tumors consisted of infiltrating nodules of fascicles of spindleshaped endothelial cells and slitlike vascular channels with irregular tumor margins. On immunohistochemistry (IHC), endothelial cells were diffusely positive for CD34, CD31 and ERG but negative for GLUT1, and the peripheral area of proliferative capillaries were markedly positive for D240. Adjuvant medical therapy and sclerotherapy were prepared for the tumor and the associated KMP, and then all patients were treated by complete surgical excision. Follow-up information was available in 22 patients (8 to 26 months, mean 15 mo), and indicated that 1 died of multiple organ failure and 21 were alive without residual disease. In conclusion, our results suggest that KHE can occur in the embryonic period, and patients with KMP often have earlier onset time and larger lesional size. KHE patients given with adjuvant corticosteroids and urea injection and complete resection rarely relapse.