A Novel Structure Fusion Attention Model to Detect Architectural Distortion on Mammography.

Architectural distortion (AD) is one of the most common findings on mammograms, and it may represent not only cancer but also a lesion such as a radial scar that may have an associated cancer. AD accounts for 18-45% missed cancer, and the positive predictive value of AD is approximately 74.5%. Early detection of AD leads to early diagnosis and treatment of the cancer and improves the overall prognosis. However, detection of AD is a challenging task. In this work, we propose a new approach for detecting architectural distortion in mammography images by combining preprocessing methods and a novel structure fusion attention model. The proposed structure-focused weighted orientation preprocessing method is composed of the original image, the architecture enhancement map, and the weighted orientation map, highlighting suspicious AD locations. The proposed structure fusion attention model captures the information from different channels and outperforms other models in terms of false positives and top sensitivity, which refers to the maximum sensitivity that a model can achieve under the acceptance of the highest number of false positives, reaching 0.92 top sensitivity with only 0.6590 false positive per image. The findings suggest that the combination of preprocessing methods and a novel network architecture can lead to more accurate and reliable AD detection. Overall, the proposed approach offers a novel perspective on detecting ADs, and we believe that our method can be applied to clinical settings in the future, assisting radiologists in the early detection of ADs from mammography, ultimately leading to early treatment of breast cancer patients.

Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine.

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.

Chemically activatable viral capsid functionalized for cancer targeting.

AIM: To design a theranostic capsule using the virus-like nanoparticle of the hepatitis E virus modified to display breast cancer cell targeting functional group (LXY30). METHODS: Five surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. Engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye. RESULTS: LXY30-HEV VLP was checked for its binding and entry to a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. The engineered virus-like nanoparticle not only targeted cancer cells, but also appeared immune silent to native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site. CONCLUSION: These results demonstrate the production of a theranostic capsule suitable for cancer diagnostics and therapeutics based on surface modification of a highly stable virus-like nanoparticle.

The effect of oxidative metabolism on spontaneous Pol zeta-dependent translesion synthesis in Saccharomyces cerevisiae.

DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispair. When DNA repair is compromised in Saccharomyces cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which a frameshift is accompanied by one or more base pair substitutions. These "complex frameshifts" are dependent upon the TLS polymerase Pol zeta, and provide a mutational signature for mutagenic Pol zeta-dependent activity. In the current study, we have found that a specific subset of the Pol zeta-dependent mutational events requires oxidative metabolism. These results suggest that translesion bypass of spontaneously oxidized DNA bases can be a significant source of mutagenesis in repair compromised cells.