n fixation.Purpose To evaluate interreader agreement in annotating semantic features on preoperative CT images to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Materials and methods Preoperative, contrast material-enhanced triphasic CT studies from 89 patients (median age, 64 years; age range, 36-85 years; 70 men) who underwent hepatic resection between 2008 and 2017 for a solitary HCC were reviewed. Three radiologists annotated CT images obtained during the arterial and portal venous phases, independently and in consensus, with features associated with MVI reported by other investigators. The assessed factors were the presence or absence of discrete internal arteries, hypoattenuating halo, tumor-liver difference, peritumoral enhancement, and tumor margin. Testing also included previously proposed MVI signatures radiogenomic venous invasion (RVI) and two-trait predictor of venous invasion (TTPVI), using single-reader and consensus annotations. Cohen (two-reader) and Fleiss (three-reader) κ and the bootstrap method were used to analyze interreader agreement and differences in model performance, respectively. Results Of HCCs assessed, 32.6% (29 of 89) had MVI at histopathologic findings. Two-reader agreement, as assessed by pairwise Cohen κ statistics, varied as a function of feature and imaging phase, ranging from 0.02 to 0.6; three-reader Fleiss κ varied from -0.17 to 0.56. For RVI and TTPVI, the best single-reader performance had sensitivity and specificity of 52% and 77% and 67% and 74%, respectively. In consensus, the sensitivity and specificity for the RVI and TTPVI signatures were 59% and 67% and 70% and 62%, respectively. Conclusion Interreader variability in semantic feature annotation remains a challenge and affects the reproducibility of predictive models for preoperative detection of MVI in HCC.Supplemental material is available for this article.© RSNA, 2020.Purpose To determine the performance of CT-based radiomic features for noninvasive prediction of histopathologic features of tumor grade, extracapsular spread, perineural invasion, lymphovascular invasion, and human papillomavirus status in head and neck squamous cell carcinoma (HNSCC). Materials and methods In this retrospective study, which was approved by the local institutional ethics committee, CT images and clinical data from patients with pathologically proven HNSCC from The Cancer Genome Atlas (n = 113) and an institutional test cohort (n = 71) were analyzed. https://www.selleckchem.com/products/ag-1478-tyrphostin-ag-1478.html A machine learning model was trained with 2131 extracted radiomic features to predict tumor histopathologic characteristics. In the model, principal component analysis was used for dimensionality reduction, and regularized regression was used for classification. Results The trained radiomic model demonstrated moderate capability of predicting HNSCC features. In the training cohort and the test cohort, the model achieved a mean area under the receiver operating characteristic curve (AUC) of 0.75 (95% confidence interval [CI] 0.68, 0.81) and 0.66 (95% CI 0.45, 0.84), respectively, for tumor grade; a mean AUC of 0.64 (95% CI 0.55, 0.62) and 0.70 (95% CI 0.47, 0.89), respectively, for perineural invasion; a mean AUC of 0.69 (95% CI 0.56, 0.81) and 0.65 (95% CI 0.38, 0.87), respectively, for lymphovascular invasion; a mean AUC of 0.77 (95% CI 0.65, 0.88) and 0.67 (95% CI 0.15, 0.80), respectively, for extracapsular spread; and a mean AUC of 0.71 (95% CI 0.29, 1.0) and 0.80 (95% CI 0.65, 0.92), respectively, for human papillomavirus status. Conclusion Radiomic CT models have the potential to predict characteristics typically identified on pathologic assessment of HNSCC.Supplemental material is available for this article.© RSNA, 2020.Although graphene-based biosensors provid extreme sensitivity for the detection of atoms, gases, and biomolecules, the specificity of graphene biosensors to the target molecules requires surface decoration of graphene with bifunctional linkers such pyrene derivatives. Here, we demonstrate that the pyrene functionalization influences graphene's electrical properties by yielding partial formation of bilayer graphene which was confirmed by Raman 2D spectrum. Based on this observation, we introduce quadratic fit analysis of the nonlinear electrical behavior of pyrene-functionalized graphene near the Dirac point. Compared to the conventional linear fit analysis of the transconductance at a distance from the Dirac point, the quadratic fit analysis of the nonlinear transconductance near the Dirac point increased the overall protein detection sensitivity by a factor of 5. Furthermore, we show that both pyrene linkers and gating voltage near the Dirac point play critical roles in sensitive and reliable detection of proteins' biological activities with the graphene biosensors.Snake species within the Bothrops complex (sensu lato) are of medical relevance in Latin America, but knowledge on their venom characteristics is limited, or even unavailable, for some taxa. Perú harbors 17 species of pit vipers, within the genera Bothrops, Bothriechis, Bothrocophias, Porthidium, Crotalus, and Lachesis. This study compared the venoms of twelve species, through chromatographic and electrophoretic profiles, as well as proteolytic and phospholipase A2 (PLA2) activities. Also, proteomic profiles were analyzed for nine of the venoms using a shotgun approach. Results unveiled conspicuous differences in the expression of venom PLA2s among species, six of them presenting scarce levels as judged by RP-HPLC profiles. Since most species within the bothropoid lineage possess venoms with high to intermediate abundances of this protein family, our findings suggest the existence of a phenotypic duality in the expression of venom PLA2s within the Bothrops (sensu lato) complex. Bothrops barnetti and Bothrocophias andianus venoms, very scarce in PLA2s, were shown to lack significant myotoxic activity, highlighting that the observed variability in PLA2 expression bears toxicological correlations with effects attributed to these proteins. Finally, an attempt to identify phylogenetic relationships of bothropoid species from Perú presenting low- or high-PLA2 venom phenotypes showed an interspersed pattern, thus precluding a simple phylogenetic interpretation of this venom compositional dichotomy.
n fixation.Purpose To evaluate interreader agreement in annotating semantic features on preoperative CT images to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Materials and methods Preoperative, contrast material-enhanced triphasic CT studies from 89 patients (median age, 64 years; age range, 36-85 years; 70 men) who underwent hepatic resection between 2008 and 2017 for a solitary HCC were reviewed. Three radiologists annotated CT images obtained during the arterial and portal venous phases, independently and in consensus, with features associated with MVI reported by other investigators. The assessed factors were the presence or absence of discrete internal arteries, hypoattenuating halo, tumor-liver difference, peritumoral enhancement, and tumor margin. Testing also included previously proposed MVI signatures radiogenomic venous invasion (RVI) and two-trait predictor of venous invasion (TTPVI), using single-reader and consensus annotations. Cohen (two-reader) and Fleiss (three-reader) κ and the bootstrap method were used to analyze interreader agreement and differences in model performance, respectively. Results Of HCCs assessed, 32.6% (29 of 89) had MVI at histopathologic findings. Two-reader agreement, as assessed by pairwise Cohen κ statistics, varied as a function of feature and imaging phase, ranging from 0.02 to 0.6; three-reader Fleiss κ varied from -0.17 to 0.56. For RVI and TTPVI, the best single-reader performance had sensitivity and specificity of 52% and 77% and 67% and 74%, respectively. In consensus, the sensitivity and specificity for the RVI and TTPVI signatures were 59% and 67% and 70% and 62%, respectively. Conclusion Interreader variability in semantic feature annotation remains a challenge and affects the reproducibility of predictive models for preoperative detection of MVI in HCC.Supplemental material is available for this article.© RSNA, 2020.Purpose To determine the performance of CT-based radiomic features for noninvasive prediction of histopathologic features of tumor grade, extracapsular spread, perineural invasion, lymphovascular invasion, and human papillomavirus status in head and neck squamous cell carcinoma (HNSCC). Materials and methods In this retrospective study, which was approved by the local institutional ethics committee, CT images and clinical data from patients with pathologically proven HNSCC from The Cancer Genome Atlas (n = 113) and an institutional test cohort (n = 71) were analyzed. https://www.selleckchem.com/products/ag-1478-tyrphostin-ag-1478.html A machine learning model was trained with 2131 extracted radiomic features to predict tumor histopathologic characteristics. In the model, principal component analysis was used for dimensionality reduction, and regularized regression was used for classification. Results The trained radiomic model demonstrated moderate capability of predicting HNSCC features. In the training cohort and the test cohort, the model achieved a mean area under the receiver operating characteristic curve (AUC) of 0.75 (95% confidence interval [CI] 0.68, 0.81) and 0.66 (95% CI 0.45, 0.84), respectively, for tumor grade; a mean AUC of 0.64 (95% CI 0.55, 0.62) and 0.70 (95% CI 0.47, 0.89), respectively, for perineural invasion; a mean AUC of 0.69 (95% CI 0.56, 0.81) and 0.65 (95% CI 0.38, 0.87), respectively, for lymphovascular invasion; a mean AUC of 0.77 (95% CI 0.65, 0.88) and 0.67 (95% CI 0.15, 0.80), respectively, for extracapsular spread; and a mean AUC of 0.71 (95% CI 0.29, 1.0) and 0.80 (95% CI 0.65, 0.92), respectively, for human papillomavirus status. Conclusion Radiomic CT models have the potential to predict characteristics typically identified on pathologic assessment of HNSCC.Supplemental material is available for this article.© RSNA, 2020.Although graphene-based biosensors provid extreme sensitivity for the detection of atoms, gases, and biomolecules, the specificity of graphene biosensors to the target molecules requires surface decoration of graphene with bifunctional linkers such pyrene derivatives. Here, we demonstrate that the pyrene functionalization influences graphene's electrical properties by yielding partial formation of bilayer graphene which was confirmed by Raman 2D spectrum. Based on this observation, we introduce quadratic fit analysis of the nonlinear electrical behavior of pyrene-functionalized graphene near the Dirac point. Compared to the conventional linear fit analysis of the transconductance at a distance from the Dirac point, the quadratic fit analysis of the nonlinear transconductance near the Dirac point increased the overall protein detection sensitivity by a factor of 5. Furthermore, we show that both pyrene linkers and gating voltage near the Dirac point play critical roles in sensitive and reliable detection of proteins' biological activities with the graphene biosensors.Snake species within the Bothrops complex (sensu lato) are of medical relevance in Latin America, but knowledge on their venom characteristics is limited, or even unavailable, for some taxa. Perú harbors 17 species of pit vipers, within the genera Bothrops, Bothriechis, Bothrocophias, Porthidium, Crotalus, and Lachesis. This study compared the venoms of twelve species, through chromatographic and electrophoretic profiles, as well as proteolytic and phospholipase A2 (PLA2) activities. Also, proteomic profiles were analyzed for nine of the venoms using a shotgun approach. Results unveiled conspicuous differences in the expression of venom PLA2s among species, six of them presenting scarce levels as judged by RP-HPLC profiles. Since most species within the bothropoid lineage possess venoms with high to intermediate abundances of this protein family, our findings suggest the existence of a phenotypic duality in the expression of venom PLA2s within the Bothrops (sensu lato) complex. Bothrops barnetti and Bothrocophias andianus venoms, very scarce in PLA2s, were shown to lack significant myotoxic activity, highlighting that the observed variability in PLA2 expression bears toxicological correlations with effects attributed to these proteins. Finally, an attempt to identify phylogenetic relationships of bothropoid species from Perú presenting low- or high-PLA2 venom phenotypes showed an interspersed pattern, thus precluding a simple phylogenetic interpretation of this venom compositional dichotomy.
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