Development and analytical validation of a novel nasopharynx swab-based Epstein-Barr virus C promoter methylation quantitative assay for nasopharyngeal carcinoma detection.

OBJECTIVES: Epstein-Barr virus (EBV) C promoter (Cp) hypermethylation, a crucial factor for EBV latent infection of nasopharyngeal epithelial cells, has been recognized as a promising biomarker for nasopharyngeal carcinoma (NPC) detection. In this study, we develop a novel EBV Cp methylation quantification (E-CpMQ) assay and evaluate its diagnostic performance for NPC detection. METHODS: A novel qPCR assay for simultaneous quantification of methylated- and unmethylated EBV Cp was developed by the combinational modification of MethyLight and QASM, with an innovative calibrator to improve the detection accuracy and consistency. The NP swab samples and synthetic standards were used for the analytical validation of the E-CpMQ. The diagnostic efficacy of the developed E-CpMQ assay was validated in 137 NPC patients and 137 non-NPC controls. RESULTS: The E-CpMQ assay can detect the EBV Cp methylation ratio in one reaction system under 10 copies with 100 % recognition specificity, which is highly correlated to pyrosequencing with a correlation coefficient over 0.99. The calibrated E-CpMQ assay reduces the coefficient of variation by an average of 55.5 % with a total variance of less than 0.06 units standard deviation (SD). Linear methylation ratio detection range from 4.76 to 99.01 %. The sensitivity and specificity of the E-CpMQ respectively are 96.4 % (95 % CI: 91.7-98.8 %), 89.8 % (95 % CI: 83.5-94.3 %). CONCLUSIONS: The developed E-CpMQ assay with a calibrator enables accurate and reproducible EBV Cp methylation ratio quantification and offers a sensitive, specific, cost-effective method for NPC early detection.

The impact of social relationships on the risk of stroke and post-stroke mortality: a systematic review and meta-analysis.

BACKGROUND: The association between poor social relationships and post-stroke mortality remains uncertain, and the evidence regarding the relationship between poor social relationships and the risk of stroke is inconsistent. In this meta-analysis, we aim to elucidate the evidence concerning the risk of stroke and post-stroke mortality among individuals experiencing a poor social relationships, including social isolation, limited social networks, lack of social support, and loneliness. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library databases to systematically identify pertinent studies. Data extraction was independently performed by two researchers. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either a random-effects or fixed-effects model. Sensitivity analyses were conducted to evaluate the reliability of the results. Random-effects meta-regression was performed to explore the sources of heterogeneity in stroke risk estimates between studies. Assessment for potential publication bias was carried out using Egger's and Begg's tests. RESULTS: Nineteen studies were included, originating from 4 continents and 12 countries worldwide. A total of 1,675,707 participants contributed to this meta-analysis. Pooled analyses under the random effect model revealed a significant association between poor social relationships and the risk of stroke (OR = 1.30; 95%CI: 1.17-1.44), as well as increased risks for post-stroke mortality (OR = 1.36; 95%CI: 1.07-1.73). Subgroup analyses demonstrated associations between limited social network (OR = 1.52; 95%CI = 1.04-2.21), loneliness (OR = 1.31; 95%CI = 1.13-1.51), and lack of social support (OR = 1.66; 95%CI = 1.04-2.63) with stroke risk. The meta-regression explained 75.21% of the differences in reported stroke risk between studies. Random-effect meta-regression results indicate that the heterogeneity in the estimated risk of stroke may originate from the continent and publication year of the included studies. CONCLUSION: Social isolation, limited social networks, lack of social support, and feelings of loneliness have emerged as distinct risk factors contributing to both the onset and subsequent mortality following a stroke. It is imperative for public health policies to prioritize the multifaceted influence of social relationships and loneliness in stroke prevention and post-stroke care. TRIAL REGISTRATION: The protocol was registered on May 1, 2024, on the Prospero International Prospective System with registration number CRD42024531036.

Associations between serum trace elements and the risk of nasopharyngeal carcinoma: a multi-center case-control study in Guangdong Province, southern China.

Background: Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined. Methods: This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein-Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma-mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models. Results: Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation. Conclusion: Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.

A rotation meanout network with invariance for dermoscopy image classification and retrieval.

The computer-aided diagnosis (CAD) system can provide a reference basis for the clinical diagnosis of skin diseases. Convolutional neural networks (CNNs) can not only extract visual elements such as colors and shapes but also semantic features. As such they have made great improvements in many tasks of dermoscopy images. The imaging of dermoscopy has no principal orientation, indicating that there are a large number of skin lesion rotations in the datasets. However, CNNs lack rotation invariance, which is bound to affect the robustness of CNNs against rotations. To tackle this issue, we propose a rotation meanout (RM) network to extract rotation-invariant features from dermoscopy images. In RM, each set of rotated feature maps corresponds to a set of outputs of the weight-sharing convolutions and they are fused using meanout strategy to obtain the final feature maps. Through theoretical derivation, the proposed RM network is rotation-equivariant and can extract rotation-invariant features when followed by the global average pooling (GAP) operation. The extracted rotation-invariant features can better represent the original data in classification and retrieval tasks for dermoscopy images. The RM is a general operation, which does not change the network structure or increase any parameters, and can be flexibly embedded in any part of CNNs. Extensive experiments are conducted on a dermoscopy image dataset. The results show that our method outperforms other anti-rotation methods and achieves great improvements in skin disease classification and retrieval tasks, indicating the potential of rotation invariance in the field of dermoscopy images.