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To determine the diagnostic performance of simulated reduced-dose chest CT scans regarding pulmonary T1 tumors and assess the potential impact on patient management, a repository of 218 patients with histologically proven pulmonary T1 tumors was used. Virtual reduced-dose images were simulated at 25%- and 5%-dose levels. Tumor size, attenuation, and localization were scored by two experienced chest radiologists. The impact on patient management was assessed by comparing hypothetical LungRADS scores. The study included 210 patients (41% females, mean age 64.5 ± 9.2 years) with 250 eligible T1 tumors. There were differences between the original and the 5%—but not the 25%—dose simulations, and LungRADS scores varied between the dose levels with no clear trend. Sensitivity of Reader 1 was significantly lower using the 5%-dose vs. 25%-dose vs. original dose for size categorization (0.80 vs. 0.85 vs. 0.84; p = 0.007) and segmental localization (0.81 vs. 0.86 vs. 0.83; p = 0.018). Sensitivities of Reader 2 were unaffected by a dose reduction. A CT dose reduction may affect the correct categorization and localization of pulmonary T1 tumors and potentially affect patient management.

Abstract We evaluated the effectiveness of automated segmentation of the liver and its vessels with a convolutional neural network on non-contrast T1 vibe Dixon acquisitions. A dataset of non-contrast T1 vibe Dixon liver magnetic resonance images was labelled slice-by-slice for the outer liver border, portal, and hepatic veins by an expert. A 3D U-Net convolutional neural network was trained with different combinations of Dixon in-phase, opposed-phase, water, and fat reconstructions. The neural network trained with the single-modal in-phase reconstructions achieved a high performance for liver parenchyma (Dice 0.936 ± 0.02), portal veins (0.634 ± 0.09), and hepatic veins (0.532 ± 0.12) segmentation. No benefit of using multi-modal input was observed (p = 1.0 for all experiments), combining in-phase, opposed-phase, fat, and water reconstruction. Accuracy for differentiation between portal and hepatic veins was 99% for portal veins and 97% for hepatic veins in the central region and slightly lower in the peripheral region (91% for portal veins, 80% for hepatic veins). In conclusion, deep learning-based automated segmentation of the liver and its vessels on non-contrast T1 vibe Dixon was highly effective. The single-modal in-phase input achieved the best performance in segmentation and differentiation between portal and hepatic veins.

A single-chain Fv (scFv) fragment derived from the murine antibody 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted to correct destabilizing residues in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huVκ3-huVH3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic applications. [ABSTRACT FROM AUTHOR]

Motivation: Disulfide bonds are primary covalent crosslinks between two cysteine residues in proteins that play critical roles in stabilizing the protein structures and are commonly found in extracy-toplasmatic or secreted proteins. In protein folding prediction, the localization of disulfide bonds can greatly reduce the search in conformational space. Therefore, there is a great need to develop computational methods capable of accurately predicting disulfide connectivity patterns in proteins that could have potentially important applications. Results: We have developed a novel method to predict disulfide connectivity patterns from protein primary sequence, using a support vector regression (SVR) approach based on multiple sequence feature vectors and predicted secondary structure by the PSIPRED program. The results indicate that our method could achieve a prediction accuracy of 74.4% and 77.9%, respectively, when averaged on proteins with two to five disulfide bridges using 4-fold cross-validation, measured on the protein and cysteine pair on a well-defined non-homologous dataset. We assessed the effects of different sequence encoding schemes on the prediction performance of disulfide connectivity. It has been shown that the sequence encoding scheme based on multiple sequence feature vectors coupled with predicted secondary structure can significantly improve the prediction accuracy, thus enabling our method to outperform most of other currently available predictors. Our work provides a complementary approach to the current algorithms that should be useful in computationally assigning disulfide connectivity patterns and helps in the annotation of protein sequences generated by large-scale whole-genome projects. Availability: The prediction web server and Supplementary Material are accessible at http://foo.maths.uq.edu.au/~huber/disulfide Contact: kb@maths.uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Abstract Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child–Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126–0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p

Langerhans cell histiocytosis (LCH) is a myeloid neoplasm with inflammatory properties. There are few published reports of adult LCH with liver involvement, which is still poorly understood, but shows high morbidity and mortality. We report a case of a 37-year-old woman suffering from hepatitis C showing a LCH affecting the lung as well as the liver. Consistent with histology, we found an early stage of a proliferative/granulomatous phase of hepatobiliary LCH, whereas pulmonary findings showed a nodular stage of adult pulmonary LCH. Although hepatocellular carcinoma is a common malignancy in patients suffering from hepatitis C, it is crucial to keep in mind differential diagnosis for newly appearing liver lesions.

In the present work, a novel burner capable of complete pre-vaporization and stationary combustion of diesel fuel in a laminar diffusion flame has been developed to investigate the effect of the chemical composition of diesel fuel on soot formation. For the characterization of soot formation during diesel combustion we performed a comprehensive morphological characterization of the soot and determined its concentration by coupling elastic light scattering (ELS) and laser-induced incandescence (LII) measurements. With ELS, radii of gyration of aggregates were measured within a point-wise measurement volume, LII was employed in an imaging approach for a 2D-analysis of the soot volume fraction. We carried out LII and ELS measurements at different positions in the flame for two different fuel types, revealing the effects of small modifications of the fuel composition on soot emission during diesel combustion.

We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication. [ABSTRACT FROM AUTHOR]