El antígeno de células neoplásicas escamosas (SCCA) solo o formando el complejo SCCA-igM es un biomarcador precoz de carcinoma hepatocelular.

Background: Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and is a major health problem. Every year more than 6.7 million deaths and 10.9 million new cancer cases were diagnosed. Early detection of HCC still is difficult due to the lack of adequate biomarkers that show high sensitivity and specificity. Currently, alpha-fetoprotein (AFP) is the most commonly used biomarker, but only 50-70% of patients affected by HCC have high levels of AFP, which is also difficult to distinguish HCC early stage of other diseases. The SerpinB3, the squamous cell carcinoma antigen (SCCA) is overexpressed in liver cancer and circulating SCCA-IgM complexes have been described in patients with HCC. Current screening programs for all cirrhotics are controversial and a personalized screening is an unmet need in the precision medicine era. Aim: To know long-term predictive accuracy of SCCA and SCCA-IgM alone or together with AFP in early diagnosis of HCC. To determine the role of SCCA-IgM predicting long-term appearance of HCC. Methods: After a systematic review of the relevant studies, the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio (DOR) and area under curve (AUC) for the diagnosis of HCC were pooled using bivariate meta-analysis. Hierarchic summary receiver operating characteristic curves were used to summarize the overall test performance. Bivariate boxplots were used to confirm whether the threshold effect existed. A Fagan nomogram was used to assess the clinical utility. Heterogeneity was explored by sensitivity analysis, univariable meta-regression and subgroup analysis. Patients: Two-hundred and three cirrhotic patients (Child A 74.9%, B 21.2%, C 3.9%) were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to EASL guidelines. The estimation cohort was obtained from Italy (30.5%; 62/203) and validation cohort from Spain (69.5%; 141/203). Patients underwent to evaluate SCCA-IgM by ELISA (Hepa-IC, Xeptagen, Venice, Italy). Patients were followed-up for 60 months, being censored at the time of the appearance of HCC. Results: Eleven studies that had HCC diagnosis as their purpose were ultimately included in the quantitative analysis. The summary estimates were as follows: SCCA [AUC: 0.80 (95% CI: 0.76 - 0.83)] and SCCA-IgM [AUC: 0.77 (95% CI: 0.74 - 0.83)] demonstrated similar diagnostic performance, while a combination of AFP and SCCA-IgM had an AUC of 0.90 (95% CI: 0.87 - 0.92) and a DOR of 22.87 (95% CI: 8.38 – 62.40). Meta-regression showed that patient selection, cut-off values, reference standards and tumor biopsy as the diagnostic method significantly influenced the heterogeneity of the included studies. There were 10.8% and 23.1% of two- and five-year follow up of HCC development. Patients with HCC showed higher levels of SCCA-IgM than those without it (425.72 ± 568.33 AU/ml vs. 195.93 ± 188.40 AU/ml, p = 0.009) during the five-year follow-up. In multivariate analysis, after adjusting by age, sex and AST, the following factors were independently associated with HCC: SCCA-IgM (HR 1.001 95% CI 1.000 - 1.002; p = 0.003), AFP (HR 1.028 95% CI 1.009 - 1.046; p = 0.003) and creatinine (HR 1.564 95% CI 1.151 - 2.124; p = 0.004). The log-rank test of the combination resulted in a 7.488 (p = 0.024) in the estimation cohort and 11.061 (p = 0.004) in the validation cohort, and 100% of correctly classified rate in both cohorts to identify low-risk group patients in two-year of follow-up. Conclusion: Both SCCA and SCCA-IgM showed a moderate diagnostic accuracy for HCC screening; the combination of SCCA-IgM and AFP is the best diagnostic option. We have constructed a predictive model based on the combination of SCCA-IgM and AFP that enhanced the predictive value for detecting HCC followed by tailored HCC surveillance for individual patients, especially to identify patients with low-risk.Antecedentes: El carcinoma hepatocelular (CHC) representa más del 90% de los cánceres primarios de hígado y constituye un problema de salud mundial. La detección temprana de CHC todavía es difícil debido a la falta de biomarcadores adecuados que muestren una alta sensibilidad y especificidad. En la actualidad, la alfa-fetoproteína (AFP) es el biomarcador más utilizado, pero solo el 50-70% de los pacientes afectados por CHC presentan niveles elevados de AFP. El antígeno de carcinoma de células escamosas (SCCA) se sobre-expresa en el cáncer de hígado e inmuno-complejos circulantes SCCA-IgM se han descrito en pacientes con CHC. El actual programa de vigilancia de CHC recomendado por la guía de práctica clínica "one-size fits all" para la detección temprana de tumores es controvertido en la era de la medicina de precisión. Objetivos: 1) Realizamos un meta-análisis para evaluar el rendimiento diagnóstico de SCCA y SCCA-IgM y de ambos combinados con alfa-fetoproteína. 2) Validamos el papel de la SCCA-IgM en la predicción del riesgo de hepatocarcinoma a largo plazo en pacientes con cirrosis hepática. Métodos: Después de una revisión sistemática de los estudios pertinentes, se combinaron la sensibilidad, la especificidad, las razones de verosimilitud positiva y negativa, la odds ratio de diagnóstico (DOR) y el área debajo de la curva (AUC) para el diagnóstico de CHC mediante el meta-análisis bivariado. Las curvas características operativas del receptor resumido jerárquico se usaron para resumir el rendimiento general de la prueba. Los diagramas de caja bivariados se usaron para confirmar si el efecto umbral existía. Se utilizó un nomograma de Fagan para evaluar la utilidad clínica. La heterogeneidad se exploró mediante análisis de sensibilidad, meta-regresión univariante y análisis de subgrupos. Pacientes: Se incluyeron 203 pacientes cirróticos (Child A 74,9%, B 21,2%, C 3,9%) seguidos prospectivamente cada seis meses para detectar el CHC por ultrasonido de acuerdo con las guías EASL. La cohorte de estimación se obtuvo de Italia (30,5%; 62/203) y la cohorte de validación de España (69,5%; 141/203). Los pacientes fueron sometidos a evaluación de SCCA-IgM por ELISA (Hepa-IC, Xeptagen, Venecia, Italia). Los pacientes fueron seguidos durante 60 meses, siendo censurados en el momento de la aparición del CHC. Resultados: Once estudios que tenían el diagnóstico de CHC como objetivo principal se incluyeron finalmente en el análisis cuantitativo. Las estimaciones resumidas fueron las siguientes: SCCA [AUC: 0,80 (IC 95%: 0,76-0,83)] y SCCA-IgM [AUC: 0,77 (IC 95%: 0,74-0,83)] mostraron un rendimiento diagnóstico similar, mientras que una combinación de AFP y SCCA-IgM tuvieron un AUC de 0,90 (IC del 95%: 0,87-0,92) y un DOR de 22,87 (IC del 95%: 8,38 - 62,40). La meta regresión mostró que la selección del paciente, los valores de corte, los estándares de referencia y la biopsia tumoral como método de diagnóstico influyeron significativamente en la heterogeneidad de los estudios incluidos. Hubo un 10.8% y 23,1% de desarrollo de CHC a dos y cinco años de seguimiento. Los pacientes con CHC mostraron niveles más altos de SCCA-IgM que los que no (425,72 ± 568,33 AU / ml frente a 195,93 ± 188,40 AU / ml, p = 0,009) durante el seguimiento de cinco años. En el análisis multivariado, después de ajustar por edad, sexo y AST, los siguientes factores se asociaron independientemente con CHC: SCCA-IgM (HR 1,001 IC 95% 1,000 - 1,002; p = 0,003), AFP (HR 1,028 IC 95% 1,009 - 1,046; p = 0,003) y creatina (HR 1,564 IC 95% 1,151 - 2,124; p = 0,004). La prueba de log-rank de la combinación mostró un valor de 7,488 (p = 0,024) en la cohorte de estimación y 11,061 (p = 0,004) en la cohorte de validación y una tasa del 100% de pacientes correctamente clasificados al identificar el grupo de bajo riesgo a dos años de seguimiento. Conclusión: Tanto los niveles de SCCA como de SCCA-IgM mostraron una precisión diagnóstica moderada para el cribado de CHC; la combinación de SCCA-IgM y AFP es la mejor opción de diagnóstico. SCCA-IgM podría representar un nuevo biomarcador para CHC a largo plazo. Hemos construido un modelo predictivo de la combinación de SCCA-IgM y AFP que mejoró el valor predictivo para detectar CHC seguido de una vigilancia de CHC adaptada para pacientes individuales, especialmente para identificar pacientes con bajo riesgo

Effect of Cr3C2 Content on the Microstructure and Wear Resistance of Fe3Al/Cr3C2 Composites

In this paper, an engine piston ring coating comprising composite material of Fe3Al and Cr3C2 mixed powder was prepared by laser cladding onto carbon structural steel. The microstructure and tribological properties of the cladding materials were investigated through X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), and wear tests. The influence mechanism of the Cr3C2 content in cladding powder was studied. During the process of wear, the soft Fe3Al/Fe2AlCr matrix is first ground off, and the hard Cr7C3 phase initially supports the abrasive surface before being worn away into hard particles, resulting in abrasive wear. With the increase in Cr3C2 content, the hardness of the cladding layer increases, the proportion of the Cr7C3 phase increases, and the morphology changes from a sparse network to a dense floccule. Of the cladding layers with different Cr3C2 content, the 15 wt.% Cr3C2 cladding layer had the lowest friction coefficient, and the 25 wt.% Cr3C2 cladding layer had the lowest wear rate. The low wear rate of the 25 wt.% Cr3C2 cladding layer can be attributed to the fact that adhesive wear does not easily occur and the fine microstructure of the strengthening phase, which facilitates better separation in the grinding surfaces

Research On Evaluation Index System of China’s Inter-Provincial Electricity Market Operation

As China's electricity market develops rapidly in recent years, market evaluation turns out to be more necessary than before to make a comprehensive evaluation of market construction and operation, and ensure a fair and health electricity market. In this study, the international experience of market monitoring and assessment is firstly summarized. Then considering the feature of China's inter-provincial power market, the evaluation index system is proposed for the operation effectiveness of inter-provincial electricity market. At last, a case of comparing the short-term and long-term inter-provincial market modes is presented to validate the proposed market evaluation index system

Capturing the Phylogeny of Holometabola with Mitochondrial Genome Data and Bayesian Site-Heterogeneous Mixture Models

After decades of debate, a mostly satisfactory resolution of relationships among the 11 recognized holometabolan orders of insects has been reached based on nuclear genes, resolving one of the most substantial branches of the tree-of-life, but the relationships are still not well established with mitochondrial genome data. The main reasons have been the absence of sufficient data in several orders and lack of appropriate phylogenetic methods that avoid the systematic errors from compositional and mutational biases in insect mitochondrial genomes. In this study, we assembled the richest taxon sampling of Holometabola to date (199 species in 11 orders), and analyzed both nucleotide and amino acid data sets using several methods. We find the standard Bayesian inference and maximum-likelihood analyses were strongly affected by systematic biases, but the site-heterogeneous mixture model implemented in PhyloBayes avoided the false grouping of unrelated taxa exhibiting similar base composition and accelerated evolutionary rate. The inclusion of rRNA genes and removal of fast-evolving sites with the observed variability sorting method for identifying sites deviating from the mean rates improved the phylogenetic inferences under a site-heterogeneous model, correctly recovering most deep branches of the Holometabola phylogeny. We suggest that the use of mitochondrial genome data for resolving deep phylogenetic relationships requires an assessment of the potential impact of substitutional saturation and compositional biases through data deletion strategies and by using site-heterogeneous mixture models. Our study suggests a practical approach for how to use densely sampled mitochondrial genome data in phylogenetic analyses

Dynamics of Cloud-Top Generating Cells in Winter Cyclones. Part III: Shear and Convective Organization

Cloud-top generating cells (GCs) are a common feature atop stratiform clouds within the comma head of winter cyclones. The dynamics of cloud-top GCs are investigated using very high-resolution idealized WRF Model simulations to examine the role of shear in modulating the structure and intensity of GCs. Simulations were run for the same combinations of radiative forcing and instability as in Part II of this series, but with six different shear profiles ranging from 0 to 10ms21 km21 within the layer encompassing the GCs. The primary role of shear was to modulate the organization of GCs, which organized as closed convective cells in simulations with radiative forcing and no shear. In simulations with shear and radiative forcing, GCs organized in linear streets parallel to the wind. No GCs developed in the initially stable simulations with no radiative forcing. In the initially unstable and neutral simulations with no radiative forcing or shear, GCs were exceptionally weak, with no clear organization. In moderate-shear (Du/Dz 5 2, 4ms21 km21) simulations with no radiative forcing, linear organization of the weak cells was apparent, but this organization was less coherent in simulations with high shear (Du/Dz 5 6, 8, 10ms21 km21). The intensity of the updrafts was primarily related to the mode of radiative forcing but was modulated by shear. The more intense GCs in nighttime simulations were either associated with no shear (closed convective cells) or strong shear (linear streets). Updrafts within GCs under conditions with radiative forcing were typically ;1–2 ms21 with maximum values , 4ms21