Real-time quaking-induced conversion assay is accurate for Lewy body diseases: a meta-analysis.

OBJECTIVE: Real-time quaking-induced conversion (RT-QuIC) is a novel in vitro acellular seed amplification analysis and has been widely used to detect prion diseases. Due to the similar mechanism of abnormal aggregation of α-synuclein, RT-QuIC has great potential for diagnosing Lewy body diseases. This meta-analysis was performed to evaluate the diagnostic accuracy of RT-QuIC for Lewy body diseases. METHODS: This study followed the PRISMA statement. We searched six databases for relevant studies published until February 20, 2022. Meta-analysis was conducted using RevMan 5.3, Stata 17.0, and Meta-Disc 1.4. Subgroup analyses were performed to explore sources of heterogeneity. RESULTS: A total of 16 studies were included in this study. The pooled sensitivity and specificity were 0.91 (95%CI: 0.85-0.94) and 0.95 (95%CI: 0.90-0.97), respectively. The pooled positive and negative likelihood ratios were 17.16 (95% CI: 9.16-32.14) and 0.10 (95% CI: 0.06-0.17), respectively. The pooled diagnostic odds rate and area under the summary receiver operating characteristic curve were 171.16 (95% CI: 66.64-439.62) and 0.97 (95% CI: 0.96-0.99), respectively. CONCLUSIONS: This study was the first meta-analysis on RT-QuIC for Lewy body diseases. RT-QuIC is a reliable and accurate method to diagnose Lewy body diseases.

Value of Assessment of Different Neoplasias in the Adnexa in the Differential Diagnosis of Malignant Ovarian Tumor and Benign Ovarian Tumor: A Meta-analysis.

To evaluate the accuracy of the assessment of different neoplasias in the adnexa (ADNEX) model in the differential diagnosis of malignant and benign ovarian tumors, the optimal cutoff value and the accuracy in diagnosing ovarian tumors at different stages, PubMed, Web of Science and Cochrane Library databases were retrieved to search literature with per-patient analysis until publication of the last study in November 2021. STATA 14.1, Meta-Disc 1.4 and Revman software 5.3 were used in the performance of meta-analysis. To explore sources of heterogeneity, a subgroup analysis was conducted for the ADNEX model. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood, negative likelihood ratio and area under the summary receiver operating characteristic curve were 0.91 (95% confidence interval [CI]: 0.89-0.93), 0.84 (95% CI: 0.80-0.88), 55.55 (95% CI: 40.47-76.26), 5.71 (95% CI: 4.49-7.26), 0.10 (95% CI: 0.08-0.13) and 0.94 (95% CI: 0.92-0.96) in differentiating benign and malignant ovarian tumors, respectively. The area under the curve in identifying benign, borderline, stage I and stages II-IV were 0.93, 0.73, 0.27 and 0.92. The ADNEX model had high diagnostic performance was influential in the diagnosis of benign and stage II-IV ovarian tumors.

Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.

OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis. METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry. RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2  = 18784, p < 0.001; χ2  = 47.1, p < 0.001; χ2  = 20, p < 0.001). CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.

Using CatBoost algorithm to identify middle-aged and elderly depression, national health and nutrition examination survey 2011-2018.

Depression is one of the most common mental health problems in middle-aged and elderly people. The establishment of risk factor-based depression risk assessment model is conducive to early detection and early treatment of high-risk groups of depression. Five machine learning models (logistic regression (LR); back propagation (BP); random forest (RF); support vector machines (SVM); category boosting (CatBoost) were used to evaluate the depression among 8374 middle-aged people and 4636 elderly people in the NHANES database from 2011 to 2018. In the 2011-2018 cycle, the estimated prevalence of depression was 8.97% in the middle-aged participants and 8.02% in the elderly participants. Among the middle-aged and elderly participants, CatBoost was the best model to identify depression, and its area under the working characteristic curve (AUC) reaches the highest. The second is LR model and SVM model, while the performance of BP and RF model was slightly worse. The primary influencing factor of depression in middle-aged male is alanine aminotransferase. All five machine learning models can identify the occurrence of depression in the NHANES data set through social demographics, lifestyle, laboratory data and other data of middle-aged and elderly people, and among five models, the CatBoost model performed best.

Accuracy of rapid diagnostic test to diagnose malaria in children under 5 years of age, a meta-analysis.

OBJECTIVE: To assess the accuracy of the rapid diagnostic test for malaria diagnosis in children under 5 years of age. METHODS: As of August 31, 2020, PubMed, Web of Science and Cochrane Library databases had been systematically searched. Relevant data were extracted and meta-analysis was carried out. A random effects model was used for subgroup analysis. RESULTS: According to the inclusion criteria, a total of 26 studies were included in this meta-analysis. The pooled sensitivity and specificity were 0.92 (95% confidence interval 0.83-0.96) and 0.92 (0.86-0.95), the parasite-specific lactate dehydrogenase-based test were 0.96 (0.85-0.98) and 0.93 (0.86-0.95), the histidine-rich protein 2-based test were 0.94 (0.84-0.98) and 0.86 (0.77-0.91). CONCLUSIONS: This meta-analysis showed that rapid diagnostic test had good accuracy in diagnosing malaria in children under 5 years of age. And the diagnostic performance of parasite-specific lactate dehydrogenase test was better than that of the histidine-rich protein 2 test.

Clinical characteristics and risk factors for in-hospital mortality of lung cancer patients with COVID-19: A multicenter, retrospective, cohort study.

BACKGROUND: Data on clinical, laboratory, and radiographic characteristics and risk factors for in-hospital mortality of lung cancer patients with COVID-19 are scarce. Here, we aimed to characterize the early clinical features of lung cancer patients with COVID-19 and identify risk factors associated with in-hospital mortality. METHODS: All consecutive lung cancer patients with laboratory-confirmed COVID-19 admitted to 12 hospitals in Hubei province, China, from 3 January to 6 May 2020 were included in the study. Patients without definite clinical outcomes during the period were excluded. Data on initial clinical, laboratory and radiographic findings were compared between survivors and nonsurvivors. Univariable and multivariable logistic regression analyses were used to explore the risk factors associated with in-hospital mortality. RESULTS: Of the 45 lung cancer patients (median [interquartile range] age, 66 [58-74] years; 68.9% males) included, 34 (75.6%) discharged and 11 (24.4%) died. Fever (73.3%) and cough (53.3%) were the dominant initial symptoms, and respiratory symptoms were common. Lung cancer patients also presented atypical appearances of COVID-19. In the multivariable analysis, prolonged prolongation prothrombin time (PT) (OR = 2.1, 95% CI: 1.00-4.41, P = 0.0497) and elevated high sensitivity cardiac troponin I (hs-TNI) (OR = 7.65, 95% CI: 1.24-47.39, P = 0.0287) were associated with an increased risk of in-hospital mortality. CONCLUSIONS: Lung cancer patients with COVID-19 have high in-hospital mortality. Prolonged PT and elevated hs-TNI are independent risk factors for in-hospital mortality of lung cancer patients with COVID-19. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Lung cancer patients with COVID-19 have atypical early symptoms and imaging features. The prolonged prothrombin time and elevated high sensitivity cardiac troponin I are independent risk factors for in-hospital mortality of lung cancer patients with COVID-19. WHAT THIS STUDY ADDS: This study characterizes the early clinical features of lung cancer patients with COVID-19 in China, and identifies the risk factors associated with in-hospital mortality of lung cancer patients with COVID-19.

Evaluation of high-resolution precipitation estimates from satellites during July 2012 Beijing flood event using dense rain gauge observations.

Satellite-based precipitation estimates products, CMORPH and PERSIANN-CCS, were evaluated with a dense rain gauge network over Beijing and adjacent regions for an extremely heavy precipitation event on July 21 2012. CMORPH and PEERSIANN-CSS misplaced the region of greatest rainfall accumulation, and failed to capture the spatial pattern of precipitation, evidenced by a low spatial correlation coefficient (CC). CMORPH overestimated the daily accumulated rainfall by 22.84% while PERSIANN-CCS underestimated by 72.75%. In the rainfall center, both CMORPH and PERSIANN-CCS failed to capture the temporal variation of the rainfall, and underestimated rainfall amounts by 43.43% and 87.26%, respectively. Based on our results, caution should be exercised when using CMORPH and PERSIANN-CCS as input for monitoring and forecasting floods in Beijing urban areas, and the potential for landslides in the mountainous zones west and north of Beijing.

Protection of podocytes from hyperhomocysteinemia-induced injury by deletion of the gp91phox gene.

In this study, mice lacking the gp91(phox) gene were used to address the role of NADPH oxidase in hyperhomocysteinemia-induced podocyte injury. It was found that a folate-free diet increased plasma homocysteine levels, but failed to increase O(2)(-) production in the glomeruli from gp91(phox) gene knockout (gp91(-/-)) mice, compared with wild-type (gp91(+/+)) mice. Proteinuria and glomerular damage index (GDI) were significantly lower, whereas the glomerular filtration rate (GFR) was higher in gp91(-/-) than in gp91(+/+) mice when they were on the folate-free diet (urine albumin excretion, 21.23+/-1.88 vs 32.86+/-4.03 microg/24 h; GDI, 1.17+/-0.18 vs 2.59+/-0.49; and GFR, 53.01+/-4.69 vs 40.98+/-1.44 microl/min). Hyperhomocysteinemia-induced decrease in nephrin expression and increase in desmin expression in gp91(+/+) mice were not observed in gp91(-/-) mice. Morphologically, foot process effacement and podocyte loss due to hyperhomocysteinemia were significantly attenuated in gp91(-/-) mice. In in vitro studies of podocytes, homocysteine was found to increase gp91(phox) expression and O2(*)(-) generation, which was substantially inhibited by gp91(phox) siRNA. Functionally, homocysteine-induced decrease in vascular endothelial growth factor-A production was abolished by gp91(phox) siRNA or diphenyleneiodonium, a NADPH oxidase inhibitor. These results suggest that the functional integrity of NADPH oxidase is essential for hyperhomocysteinemia-induced podocyte injury and glomerulosclerosis.

Redox signaling via lipid raft clustering in homocysteine-induced injury of podocytes.

Our recent studies have indicated that hyperhomocysteinemia (hHcys) may induce podocyte damage, resulting in glomerulosclerosis. However, the molecular mechanisms mediating hHcys-induced podocyte injury are still poorly understood. In the present study, we first demonstrated that an intact NADPH oxidase system is present in podocytes as shown by detection of its membrane subunit (gp91(phox)) and cytosolic subunit (p47(phox)). Then, confocal microscopy showed that gp91(phox) and p47(phox) could be aggregated in lipid raft (LR) clusters in podocytes treated with homocysteine (Hcys), which were illustrated by their colocalization with cholera toxin B, a common LR marker. Different mechanistic LR disruptors, either methyl-beta-cyclodextrin (MCD) or filipin abolished such Hcys-induced formation of LR-gp91(phox) or LR-p47(phox) transmembrane signaling complexes. By flotation of detergent-resistant membrane fractions we found that gp91(phox) and p47(phox) were enriched in LR fractions upon Hcys stimulation, and such enrichment of NADPH oxidase subunits and increase in its enzyme activity were blocked by MCD or filipin. Functionally, disruption of LR clustering significantly attenuated Hcys-induced podocyte injury, as shown by their inhibitory effects on Hcys-decreased expression of slit diaphragm molecules such as nephrin and podocin. Similarly, Hcys-increased expression of desmin was also reduced by disruption of LR clustering. In addition, inhibition of such LR-associated redox signaling prevented cytoskeleton disarrangement and apoptosis induced by Hcys. It is concluded that NADPH oxidase subunits aggregation and consequent activation of this enzyme through LR clustering is an important molecular mechanism triggering oxidative injury of podocytes induced by Hcys.

Formation of lipid raft redox signalling platforms in glomerular endothelial cells: an early event of homocysteine-induced glomerular injury.

The present study tested the hypothesis that homocysteine (Hcys)-induced ceramide production stimulates lipid rafts (LRs) clustering on the membrane of glomerular endothelial cells (GECs) to form redox signalling platforms by aggregation and activation of NADPH oxidase subunits and thereby enhances superoxide (O2*-) production, leading to glomerular endothelial dysfunction and ultimate injury or sclerosis. Using confocal microscopy, we first demonstrated a co-localization of LR clusters with NADPH oxidase subunits, gp91(phox) and p47(phox) in the GECs membrane upon Hcys stimulation. Immunoblot analysis of floated detergent-resistant membrane fractions found that in LR fractions NADPH oxidase subunits gp91(phox) and p47(phox) are enriched and that the activity of this enzyme dramatically increased. We also examined the effect of elevated Hcys on the cell monolayer permeability in GECs. It was found that Hcys significantly increased GEC permeability, which was blocked by inhibition of LR redox signalling platform formation. Finally, we found that Hcys-induced enhancement of GEC permeability is associated with the regulation of microtubule stability through these LR-redox platforms. It is concluded that the early injurious effect of Hcys on the glomerular endothelium is associated with the formation of redox signalling platforms via LR clustering, which may lead to increases in glomerular permeability by disruption of microtubule network in GECs.