A First-in-Human Trial to Evaluate the Safety and Immunogenicity of a G Protein-Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18-45 Years of Age.

BACKGROUND: With the enormous morbidity and mortality caused by respiratory syncytial virus (RSV) infections among infants and the elderly, vaccines against RSV infections are in large market demand. METHODS: We conducted a first-in-human (FIH), randomized, double-blind, placebo-controlled dose escalation study to evaluate the safety and immunogenicity response of the rRSV vaccine (BARS13) in healthy adults aged 18-45. A total of 60 eligible participants were randomly assigned to receive one of four dose levels or vaccination regimens of BARS13 or placebo at a 4:1 ratio. RESULTS: The mean age was 27.40, and 23.3% (14/60) were men. No treatment-emergent adverse events (TEAEs) led to study withdrawal within 30 days after each vaccination. No serious adverse event (SAE) was reported. Most of the treatment-emergent adverse events (TEAEs) recorded were classified as mild. The high-dose repeat group had a serum-specific antibody GMC of 885.74 IU/mL (95% CI: 406.25-1931.17) 30 days after the first dose and 1482.12 IU/mL (706.56-3108.99) 30 days after the second dose, both higher than the GMC in the low-dose repeat group (885.74 IU/mL [406.25-1931.17] and 1187.10 IU/ mL [610.01-2310.13]). CONCLUSIONS: BARS13 had a generally good safety and tolerability profile, and no significant difference in terms of adverse reaction severity or frequency was observed between different dose groups. The immune response in repeat-dose recipients shows more potential in further study and has guiding significance for the dose selection of subsequent studies.

Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model.

Genetic optimization of Nucleic Acid immunogens is important for potentially improving their immune potency. A COVID-19 DNA vaccine is in phase III clinical trial which is based on a promising highly developable technology platform. Here, we show optimization in mice generating a pGX-9501 DNA vaccine encoding full-length spike protein, which results in induction of potent humoral and cellular immune responses, including neutralizing antibodies, that block hACE2-RBD binding of live CoV2 virus in vitro. Optimization resulted in improved induction of cellular immunity by pGX-9501 as demonstrated by increased IFN-γ expression in both CD8+ and CD4 + T cells and this was associated with more robust antiviral CTL responses compared to unoptimized constructs. Vaccination with pGX-9501 induced subsequent protection against virus challenge in a rigorous hACE2 transgenic mouse model. Overall, pGX-9501 is a promising optimized COVID-19 DNA vaccine candidate inducing humoral and cellular immunity contributing to the vaccine's protective effects.

Use of MRI and Ga-68 DOTATATE for the detection of neuroendocrine liver metastases.

PURPOSE: To compare detection rates of NET liver metastases of MRI and Ga-68-DOTATATE PET/CT to provide more clarity when selecting diagnostic imaging tests for NET staging. METHODS: In this IRB-approved single-institution retrospective study, all patients with pathology-proven NET who underwent Ga-68-DOTATATE and MRI scans within 8 weeks of each other (3/2017-2/2020) were reviewed. Number of metastases for each patient on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and Ga-68 DOTATATE were recorded by two blinded radiologists, followed by consensus review with two separate blinded readers for MRI and nuclear medicine. Per-lesion and -modality scoring at each lesion location were then performed in consensus. Per-patient linear regression was performed comparing MRI and Ga-68 DOTATATE detection rates for each reader and in consensus, and per-lesion-matched pair difference means were used to compare detection frequency between modalities. RESULTS: 32 patients (mean age 59 years, 59.4% male) and 90 liver metastases were analyzed. Intraclass coefficients (ICC) [95% CI] between the two readers were 0.97 [0.95, 0.99], 0.89 [0.82, 0.94], and 0.98 [0.97, 0.99] for Ga-68 DOTATATE, DWI, and DCE, respectively. Matched per-lesion mean differences were + 0.17 ± 0.07 (p = 0.01) and + 0.22 ± 0.06 (p = < 0.001) for DWI versus Ga-68 DOTATATE and DCE vs Ga-68 DOTATATE, respectively, favoring MRI. Case-based linear regressions estimate that DWI and DCE detect 1.28 [1.07, 1.49] and 1.33 [1.12, 1.54] lesions, respectively, for each one detected on Ga-68 DOTATATE. CONCLUSION: MRI detects more hepatic NET metastasis in comparison to Ga-68 DOTATATE. Liver MRI should be performed in concert with Ga-68 DOTATATE in NET staging.

Quality and diagnostic performance of coronary computed tomography angiogram (CCTA): A comparison between pre-liver and pre-kidney transplant patients.

PURPOSE: Assess and compare the quality and diagnostic performance of CCTA between pre-liver and pre-kidney transplant patients, and gauge impact of CCTA on ICA requirements. METHODS: Patients without known coronary artery disease (CAD) were selected for CCTA if considered high-risk or after abnormal stress testing. All pre-liver and pre-kidney CCTAs between March 2018 and August 2020 were retrospectively included. CCTA quality was qualitatively graded as excellent/good/fair/poor, and CAD graded as < or ≥50% stenosis. Heart rate, coronary artery calcium (CAC) scores, and fractional flow reserve CT (FFRCT) results were collected. CAD stenosis was graded on invasive coronary angiogram (ICA) images, with ≥50% stenosis defined as significant. RESULTS: 162 pre-transplant patients (91 pre-liver, 71 pre-kidney). Pre-kidney patients had poorer CCTA quality (p = 0.04) and higher heart rate (median: 65 bpm vs 60 bpm, p < 0.001). Out of 147 diagnostic CCTAs (pre-liver: 84, pre-kidney: 63), 73 (49.7%) had a ≥50% stenosis (pre-liver: 38 (45.2%), pre-kidney:35 (55.6%)). 12/38 (31.6%) had a significantly reduced FFRCT, and 19/53 (35.8%) had ≥50% stenosis on ICA. Among patients whose CCTA was diagnostic and had ICA, stenosis severity was concordant in 10/23 (43.5%) pre-liver and 10/25 (40%) pre-kidney patients. All discordant cases had stenosis 'over-called' on CCTA. CONCLUSION: Diagnostic-quality CCTAs in high-risk pre-transplant patients are achievable and can greatly reduce ICA requirements by excluding significant CAD. CCTA quality is poorer in pre-kidney transplant patients compared to pre-liver, possibly due to higher heart rate.

A Rare Presentation of Basal Cell Carcinoma Arising within Trichoepithelioma: A Diagnostic Challenge.

Differentiating between trichoepithelioma and basal cell carcinoma (BCC) is sometimes diagnostically challenging. We present a case of a 61-year-old male with a BCC arising within a trichoepithelioma, which is rarely reported in the literature. Clinical and histological diagnosis of trichoepithelioma is sometimes complicated by its many similarities to BCC. Therefore, immunohistochemical analysis and adequate tissue sampling are essential in suspicious lesions. In addition, as represented by our patient's presentation, it is important for clinicians to remember that the presence of a concurrent malignant neoplasm may be masked by the benign nature of a trichoepithelioma and that a superficial shave biopsy may not be sufficient for accurately diagnosing such suspicious lesions.

Bridging the Gap: Identifying Global Trends in Gender Disparity Among the Radiology Physician Workforce.

RATIONALE AND OBJECTIVES: Women make up half of American medical school graduates, but remain underrepresented among radiologists. This study sought to determine whether workforce gender disparities exist in other countries, and to identify any country-specific indices associated with increased female representation. MATERIALS AND METHODS: In this cross-sectional study, 95 professional radiology organizations in 75 countries were contacted via email to provide membership statistics, including proportion of female members, female members aged 35 or under, and women in society leadership positions. Country-specific metrics collected included gross domestic product, Gini index, percent female medical school enrollment, and Gender Development Index for the purposes of univariate multiple regression analysis. RESULTS: Twenty-nine organizations provided data on 184,888 radiologists, representing 26 countries from Europe (n = 12), North America (n = 2), Central/South America (n = 6), Oceania (n = 2), Asia (n = 3), and Africa (n = 1) for a response rate of 34.7% (26/75). Globally, 33.5% of radiologists are female. Women constitute a higher proportion of younger radiologists, with 48.5% of radiologists aged 35 or under being female. Female representation in radiology is lowest in the United States (27.2%), highest in Thailand (85.0%), and most variable in Europe (mean 40.1%, range 28.8%-68.9%). The proportion of female radiologists was positively associated with a country's Gender Development Index (P = .006), percent female medical student enrollment (P = .001), and Gini index (P = .002), and negatively associated with gross domestic product (P = .03). CONCLUSIONS: Women are underrepresented in radiology globally, most notably in the United States. Countries with greater representation of women had higher gender equality and percent female medical school enrollment, suggesting these factors may play a role in the gender gap.

Image-Rich Radiology Reports: A Value-Based Model to Improve Clinical Workflow.

PURPOSE: To determine the value of image-rich radiology reports (IRRR) by evaluating the interest and preferences of referring physicians, potential impact on clinical workflow, and the willingness of radiologists to create them. METHODS: Referring physicians and radiologists were interviewed in this prospective, HIPAA-compliant study. Subject willingness to participate in the study was determined by an e-mail. A single investigator conducted all interviews using a standard questionnaire. All subjects reviewed a video mockup demonstration of IRRR and three methods for viewing embedded images, as follows: (1) clickable hyperlinks to access a scrollable stack of images, (2) scrollable and enlargeable small-image thumbnails, and (3) scrollable but not enlargeable medium-sized images. Questionnaire responses, free comments, and general impressions were captured and analyzed. RESULTS: Seventy-two physicians (36 clinicians, 36 radiologists) were interviewed. Thirty-one clinicians (86%) expressed interest in using IRRR. Seventy-seven percent of subjects believed IRRR would improve communication. Ten clinicians (28%) preferred method 1, 18 (50%) preferred method 2, and 8 (22%) preferred method 3 for embedding images. Thirty clinicians (83%) stated that IRRR would improve efficiency. Twenty-two radiologists (61%) preferred selecting a tool button with a mouse and right-clicking images to embed them, 13 (36%) preferred pressing a function key, and 11 (31%) preferred dictating series and image numbers. The average time radiologists were willing to expend for embedding images was 66.7 seconds. CONCLUSIONS: Referring physicians and radiologist both believe IRRR would add value by improving communication with the potential to improve the workflow efficiency of referring physicians.

Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range.

Differences in absorption and/or scattering of cancerous and normal skin have the potential to provide a basis for noninvasive cancer detection. In this study, we have determined and compared the in vitro optical properties of human epidermis, dermis, and subcutaneous fat with those of nonmelanoma skin cancers in the spectral range from 370 to 1600 nm. Fresh specimens of normal and cancerous human skin were obtained from surgeries. The samples were rinsed in saline solution and sectioned. Diffuse reflectance and total transmittance were measured using an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were calculated from the measured quantities using an inverse Monte Carlo technique. The differences between optical properties of each normal tissue-cancer pair were statistically analyzed. The results indicate that there are significant differences in the scattering of cancerous and healthy tissues in the spectral range from 1050 to 1400 nm. In this spectral region, the scattering of cancerous lesions is consistently lower than that of normal tissues, whereas absorption does not differ significantly, with the exception of nodular basal cell carcinomas (BCC). Nodular BCCs exhibit significantly lower absorption as compared to normal skin. Therefore, the spectral range between 1050 and 1400 nm appears to be optimal for nonmelanoma skin cancer detection.