Predictions of PD-L1 Expression Based on CT Imaging Features in Lung Squamous Cell Carcinoma.

Purpose: To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. Materials and Methods: A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Results: For the total patient group, the AUC of the 'total significant features model' (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the 'selected feature model' (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the 'selected feature model' (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Conclusion: Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1.

MRI features of symptomatic amputation neuromas.

OBJECTIVES: To demonstrate the magnetic resonance imaging (MRI) features of amputation neuromas in lower extremity amputees and investigate independent predictive MRI features for symptomatic neuromas. METHODS: This retrospective study included 45 amputation neuromas in 44 lower extremity amputees. Two radiologists assessed the imaging features, including shape, size, type (end-bulb or spindle), signal intensity (SI), heterogeneity, margins, enlarged fascicles, dark outer rim, tail sign, target sign, enhancement, perilesional fibrosis, and muscle denervation. The neuromas were categorized into symptomatic (n = 24) or asymptomatic (n = 21). Symptomatic neuromas were determined based on neuropathic pain characteristics, the presence of Tinel's sign or tenderness, and response to local anesthetic injection. Univariate and multivariate analyses were performed to identify independent predictive MRI features. RESULTS: Of 45 neuromas, 80% (36/45) were end-bulb neuromas and 20% (9/45) were spindle-type neuromas. Eighty percent of the neuromas (36/45) were heterogeneous on T2-weighted images (WIs). Enlarged fascicles were present in 42% (19/45) and dark outer rims in 27% (12/45) of the neuromas. Among the 23 neuromas with enhanced images, 78% (18/23) showed enhancement. Heterogeneity on T2-WIs and enhancement ratios were significantly different between the asymptomatic and symptomatic neuroma groups (p < 0.05). The multivariate analyses indicated that heterogeneity on T2-WIs was an independent factor associated with symptomatic neuromas (p < 0.001). CONCLUSIONS: Heterogeneity on T2-WIs could be a predictive indicator for symptomatic neuromas in lower extremity amputees. KEY POINTS: • Amputation neuromas are classified as either end-bulb or spindle-type. They can show enlarged fascicles, dark outer rims, and enhancement. • Heterogeneity on T2-weighted images could be a predictive indicator for symptomatic neuromas. • Predicting the symptomatic neuroma on MRI would help in effective management of stump pain.

Validation of Deep-Learning Image Reconstruction for Low-Dose Chest Computed Tomography Scan: Emphasis on Image Quality and Noise.

OBJECTIVE: Iterative reconstruction degrades image quality. Thus, further advances in image reconstruction are necessary to overcome some limitations of this technique in low-dose computed tomography (LDCT) scan of the chest. Deep-learning image reconstruction (DLIR) is a new method used to reduce dose while maintaining image quality. The purposes of this study was to evaluate image quality and noise of LDCT scan images reconstructed with DLIR and compare with those of images reconstructed with the adaptive statistical iterative reconstruction-Veo at a level of 30% (ASiR-V 30%). MATERIALS AND METHODS: This retrospective study included 58 patients who underwent LDCT scan for lung cancer screening. Datasets were reconstructed with ASiR-V 30% and DLIR at medium and high levels (DLIR-M and DLIR-H, respectively). The objective image signal and noise, which represented mean attenuation value and standard deviation in Hounsfield units for the lungs, mediastinum, liver, and background air, and subjective image contrast, image noise, and conspicuity of structures were evaluated. The differences between CT scan images subjected to ASiR-V 30%, DLIR-M, and DLIR-H were evaluated. RESULTS: Based on the objective analysis, the image signals did not significantly differ among ASiR-V 30%, DLIR-M, and DLIR-H (p = 0.949, 0.737, 0.366, and 0.358 in the lungs, mediastinum, liver, and background air, respectively). However, the noise was significantly lower in DLIR-M and DLIR-H than in ASiR-V 30% (all p < 0.001). DLIR had higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) than ASiR-V 30% (p = 0.027, < 0.001, and < 0.001 in the SNR of the lungs, mediastinum, and liver, respectively; all p < 0.001 in the CNR). According to the subjective analysis, DLIR had higher image contrast and lower image noise than ASiR-V 30% (all p < 0.001). DLIR was superior to ASiR-V 30% in identifying the pulmonary arteries and veins, trachea and bronchi, lymph nodes, and pleura and pericardium (all p < 0.001). CONCLUSION: DLIR significantly reduced the image noise in chest LDCT scan images compared with ASiR-V 30% while maintaining superior image quality.

Functional hierarchy of herpes simplex virus type-1 membrane proteins in corneal infection and virus transmission to ganglionic neurons.

PURPOSE: To determine the relative importance of viral glycoproteins gK, gM, gE and the membrane protein UL11 in infection of mouse corneas and ganglionic neurons. METHODS: Mouse eyes were scarified and infected with herpes simplex virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs of ocular disease were monitored daily. Virus shedding was determined at 24, 48 and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified by quantitative PCR at 30 d post infection. RESULTS: The gE-null virus replicated as efficiently as the parental virus and formed viral plaques approximately half-the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM-null viruses replicated approximately one log less efficiently than the wild-type virus, and formed plaques that were on average one-third the size and one-half the size of the wild-type virus, respectively. The gK-null virus replicated more than 3-logs less efficiently than the wild-type virus and formed very small plaques (5-10 cells). Mice infected with the wild-type virus exhibited mild clinical ocular symptoms, while mice infected with the mutant viruses did not show any significant ocular changes. The wild-type virus produced the highest virus shedding post infection followed by the gM-null, gE-null and UL11-null viruses, while no gK-null virus was detected at any time point. All TG collected from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice infected with the UL11-null virus contained high numbers of viral genomes. The gE-null and gM-null-infected ganglia contained moderate-to-low number of viral genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected in ganglionic tissues obtained from gK-null eye infections. CONCLUSIONS: The results show that gK plays the most important role among gM, gE and UL11 in corneal and ganglionic infection in the mouse eye model.

Herpes simplex virus 1 glycoprotein M and the membrane-associated protein UL11 are required for virus-induced cell fusion and efficient virus entry.

Herpes simplex virus 1 (HSV-1) facilitates virus entry into cells and cell-to-cell spread by mediating fusion of the viral envelope with cellular membranes and fusion of adjacent cellular membranes. Although virus strains isolated from herpetic lesions cause limited cell fusion in cell culture, clinical herpetic lesions typically contain large syncytia, underscoring the importance of cell-to-cell fusion in virus spread in infected tissues. Certain mutations in glycoprotein B (gB), gK, UL20, and other viral genes drastically enhance virus-induced cell fusion in vitro and in vivo. Recent work has suggested that gB is the sole fusogenic glycoprotein, regulated by interactions with the viral glycoproteins gD, gH/gL, and gK, membrane protein UL20, and cellular receptors. Recombinant viruses were constructed to abolish either gM or UL11 expression in the presence of strong syncytial mutations in either gB or gK. Virus-induced cell fusion caused by deletion of the carboxyl-terminal 28 amino acids of gB or the dominant syncytial mutation in gK (Ala to Val at amino acid 40) was drastically reduced in the absence of gM. Similarly, syncytial mutations in either gB or gK did not cause cell fusion in the absence of UL11. Neither the gM nor UL11 gene deletion substantially affected gB, gC, gD, gE, and gH glycoprotein synthesis and expression on infected cell surfaces. Two-way immunoprecipitation experiments revealed that the membrane protein UL20, which is found as a protein complex with gK, interacted with gM while gM did not interact with other viral glycoproteins. Viruses produced in the absence of gM or UL11 entered into cells more slowly than their parental wild-type virus strain. Collectively, these results indicate that gM and UL11 are required for efficient membrane fusion events during virus entry and virus spread.

Histologic characteristics of hepatocellular carcinomas showing atypical enhancement patterns on 4-phase MDCT examination.

OBJECTIVE: To retrospectively define which histologic characteristics of small-sized hepatocellular carcinomas (HCCs) are related to atypical dynamic enhancement on multi-detector computed tomography (MDCT) imaging. MATERIALS AND METHODS: Seventy-three patients with 83 HCCs (3 cm or less in diameter) were included in this study. All patients underwent 4-phase MDCT imaging and subsequent surgery within eight weeks. Two independent radiologists blinded to the histologic findings retrospectively classified the HCCs as either typical (showing increased enhancement on arterial phase images followed by washout in late phase images) or atypical lesions demonstrating any other enhancement pattern. From the original pathologic reports, various histologic characteristics including gross morphology, nuclear histologic grades, presence of capsule formation, and capsule infiltration when a capsule was present, were compared among the two groups. RESULTS: An atypical enhancement pattern was seen in 30 (36.2%) of the 83 HCCs. The mean size of atypical HCCs (1.71 ± 0.764) was significantly smaller than that of typical HCCs (2.31 ± 0.598, p < 0.001). Atypical HCCs were frequently found to be vaguely nodular in gross morphology (n = 13, 43.3%) and to have grade I nuclear grades (n = 17, 56.7%). Capsule formation was significantly more common in typical HCCs (p < 0.001). Capsular infiltration was also more common in typical HCCs (p = 0.001). CONCLUSION: HCCs showing atypical dynamic enhancement on MDCT imaging are usually smaller than typical HCCs, vaguely nodular type in gross morphology in most cases, and well-differentiated in nuclear grades, and they lack of capsule formation or capsular infiltration.

Functional hierarchy of herpes simplex virus 1 viral glycoproteins in cytoplasmic virion envelopment and egress.

Herpes simplex virus 1 (HSV-1) viral glycoproteins gD (carboxyl terminus), gE, gK, and gM, the membrane protein UL20, and membrane-associated protein UL11 play important roles in cytoplasmic virion envelopment and egress from infected cells. We showed previously that a recombinant virus carrying a deletion of the carboxyl-terminal 29 amino acids of gD (gDΔct) and the entire gE gene (ΔgE) did not exhibit substantial defects in cytoplasmic virion envelopment and egress (H. C. Lee et al., J. Virol. 83:6115-6124, 2009). The recombinant virus ΔgM2, engineered not to express gM, produced a 3- to 4-fold decrease in viral titers and a 50% reduction in average plaque sizes in comparison to the HSV-1(F) parental virus. The recombinant virus containing all three mutations, gDΔct-ΔgM2-ΔgE, replicated approximately 1 log unit less efficiently than the HSV-1(F) parental virus and produced viral plaques which were on average one-third the size of those of HSV-1(F). The recombinant virus ΔUL11-ΔgM2, engineered not to express either UL11 or gM, replicated more than 1 log unit less efficiently and produced significantly smaller plaques than UL11-null or gM-null viruses alone, in agreement with the results of Leege et al. (T. Leege et al., J. Virol. 83:896-907, 2009). Analyses of particle-to-PFU ratios, relative plaque size, and kinetics of virus growth and ultrastructural visualization of glycoprotein-deficient mutant and wild-type virions indicate that gDΔct, gE, and gM function in a cooperative but not redundant manner in infectious virion morphogenesis. Overall, comparisons of single, double, and triple mutant viruses generated in the same HSV-1(F) genetic background indicated that lack of either UL20 or gK expression caused the most severe defects in cytoplasmic envelopment, egress, and infectious virus production, followed by the double deletion of UL11 and gM.

Delayed wound healing in Mac-1-deficient mice is associated with normal monocyte recruitment.

The Mac-1 integrin is an important mediator of migration and inflammatory activation of neutrophils and monocytes. However, the role of Mac-1 in modulating macrophage emigration and activation and its subsequent impact on cutaneous wound healing have not been fully elucidated. To examine the significance of Mac-1 to murine wound healing, we measured epithelialization and granulation tissue formation in partial-thickness ear wounds and full-thickness head wounds, respectively, in Mac-1-deficient mice. Wounds were histologically analyzed at postwounding days 3, 5, and 7. The gap measured between the leading edges of inward-migrating granulation tissue was significantly increased in knockout mice compared with control animals at day 5 (3.8+/-0.3 vs. 2.6+/-0.5 mm; p<0.001) and day 7 (2.2+/-0.4 vs. 0.96+/-0.73 mm; p=0.005). Epithelial gap measurements were also increased in knockout mice vs. wild-type controls at days 3 (0.62+/-0.02 vs. 0.54+/-0.07 mm; p<0.05) and 5 (0.58+/-0.06 vs. 0.39+/-0.08 mm; p<0.001). Immunohistochemistry showed equal numbers of macrophages in knockout and control wounds. These findings show that Mac-1 is required for normal wound healing but that the attenuation in the deposition of granulation tissue and wound epithelialization in Mac-1 knockout mice is not associated with decreased monocyte migration into the wound.

Molecular epidemiology of rabies virus isolates from South Korea.

A molecular epidemiological study was performed on 13 Korean virus isolates, which were collected from wild and domestic animals diagnosed as rabid between 1998 and 2004. Seven samples were from domestic animals such as dogs and cattle infected by rabid raccoon dogs (Nyctereutes procyonoides koreensis), and the rest of the six samples were from raccoon dogs in the wild. The study was carried out based on the comparison of nucleotide and amino acid sequences of nucleoprotein (N) and glycoprotein (G) coding regions and nucleotide sequence of the G-L intergenic (Psi) non-coding region of the isolates. The similarities of nucleotide and amino acid sequence were at least 97.8 and 98.5%, respectively, between all Korean isolates. Phylogenetic analyses of the isolate showed that they formed a monophyletic group closely related to the Arctic strains but distant from other Asian strains, including Chinese strains. The fact that the raccoon dog is the main epidemic carrier of rabies in Korea and the results of these studies supported the conclusion of previous studies (Kuzmin et al.) that the raccoon dogs take part in the circulation of rabies virus within their natural territories in the Far East. The Korean isolates can be divided into two subgroups. All the topology of the most likelihood tree of Korean isolates using nucleotide and amino acid sequences of N, G and G-L region reflected not the species but the year of isolation and geographical location of the virus isolates. This study presents the detailed description of the molecular epidemiology of rabies virus in Korea.