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The 13th sentence of the first paragraph of the Materials and Methods subsection Animals, regarding the antibiotic/antiparasitic treatment regimen, is incorrect. The authors do not believe that the differences in the antibiotic/antiparasitic treatment used prior to the study affected the results and conclusions. The correct text is: Prior to the study and as part of the facility animal management, 22 animals received an oral antibiotic/antiparasitic regimen between 1 and 10 months prior to study which included metronidazole (50 mg + 21mg/kg or 50 mg/kg once or twice daily for 5-10 days) and fenbendazole (50 mg/kg once daily for 3-5 days), with some of these animals (n = 15) also receiving enrofloxacin (10 mg/kg once daily for 7 days). [Extracted from the article]

Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n  = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies. [ABSTRACT FROM AUTHOR]

Background: While prostate specific membrane antigen (PSMA) is overexpressed in high-grade prostate cancers, it is also expressed in tumor neovasculature and other malignancies, including hepatocellular carcinoma (HCC). Importantly, no functional imaging for HCC is clinically available, making diagnosis and surveillance following local therapies particularly challenging. 18F-DCFPyL binds with high affinity to PSMA yet clears rapidly from the blood pool. PET imaging with 18F-DCFPyL may represent a new tool for staging, surveillance and assessment of treatment response in HCC. The purpose of this Functional Imaging Liver Cancer (FLIC) trial is to assess the ability of 18F-DCFPyL-PET/CT to detect sites of HCC. Methods: This is a phase II multi-site prospective imaging trial with a plan to enroll 50 subjects with suspected HCC on standard of care CT or MRI and eligible for standard local treatment. Participants will undergo a baseline 18F-DCFPyL-PET/CT, prior to therapy. Subjects will also be scanned with 18F-FDG-PET/CT within 2 weeks of 18F-DCFPyL-PET/CT. Participants will undergo histopathologic assessment and standard of care local treatment for HCC within a multidisciplinary team context. Participants with histopathologic confirmation of HCC and a positive baseline 18F-DCFPyL-PET/CT will undergo a post-treatment 18F-DCFPyL-PET/CT during the first routine follow-up, typically within 4–8 weeks. Subjects with negative baseline 18F-DCFPyL-PET/CT will not be re-scanned after treatment but will remain in follow-up. Participants will be followed for 5-years to assess for progression-free-survival. The primary endpoint is the positive predictive value of 18F-DCFPyL-PET for HCC as confirmed by histopathology. Secondary endpoints include comparison of 18F-DCFPyL-PET/CT with CT, MRI, and 18F-FDG-PET/CT, and evaluation of the value of 18F-DCFPyL-PET/CT in assessing treatment response following local treatment. Exploratory endpoints include next generation sequencing of tumors, and analysis of extracellular vesicles to identify biomarkers associated with response to therapy. Discussion: This is a prospective imaging trial designed to evaluate whether PSMA-PET/CT imaging with 18F-DCFPyL can detect tumor sites, assess local treatment response in HCC patients, and to eventually determine whether PSMA-PET/CT could improve outcomes of patients with HCC receiving standard of care local therapy. Importantly, this trial may help determine whether PSMA-selective radiopharmaceutical therapies may be beneficial for patients with HCC. Clinical trial registration: NIH IND#133631. Submission date: 04-07-2021. Safe-to-proceed letter issued by FDA: 05.07.2021. NIH IRB #00080. ClinicalTrials.gov Identifier NCT05009979. Date of Registry: 08-18-2021. Protocol version date: 01-07-2022. [ABSTRACT FROM AUTHOR]

Introduction: Multiple scoring systems have been proposed for prostate MRI reporting. We sought to review the clinical impact of the new Prostate Imaging Reporting and Data System v2 (PI-RADS) and compare those results to our proposed Simplified Qualitative System (SQS) score with respect to detection of prostate cancers and clinically significant prostate cancers. Methods: All patients who underwent multiparametric prostate MRI (mpMRI) had their images interpreted using PI-RADS v1 and SQS score. PI-RADS v2 was calculated from prospectively collected data points. Patients with positive mpMRIs were then referred by their urologists for enrollment in an IRB-approved prospective phase III trial of mpMRI-Ultrasound (MR/TRUS) fusion biopsy of suspicious lesions. Standard 12-core biopsy was performed at the same setting. Clinical data were collected prospectively. Results: 1060 patients were imaged using mpMRI at our institution during the study period. 341 participants were then referred to the trial. 312 participants underwent MR/TRUS fusion biopsy of 452 lesions and were included in the analysis. 202 participants had biopsy-proven cancer (64.7%) and 206 (45.6%) lesions were positive for cancer. Distribution of cancer detected at each score produced a Gaussian distribution for SQS while PI-RADS demonstrates a negatively skewed curve with 82.1% of cases being scored as a 4 or 5. Patient-level data demonstrated AUC of 0.702 (95% CI 0.65 to 0.73) for PI-RADS and 0.762 (95% CI 0.72 to 0.81) for SQS (p< 0.0001) with respect to the detection of prostate cancer. The analysis for clinically significant prostate cancer at a per lesion level resulted in an AUC of 0.725 (95% CI 0.69 to 0.76) and 0.829 (95% CI 0.79 to 0.87) for the PI-RADS and SQS score, respectively (p< 0.0001). Conclusions: mpMRI is a useful tool in the workup of patients at risk for prostate cancer, and serves as a platform to guide further evaluation with MR/TRUS fusion biopsy. SQS score provided a more normal distribution of scores and yielded a higher AUC than PI-RADS v2. However until our findings are validated, we recommend reporting of detailed sequence-specific findings. This will allow for prospectively collected data to be utilized in determining the impact of ongoing changes to these scoring systems as our understanding of mpMRI interpretation evolves. [ABSTRACT FROM AUTHOR]

Purpose: Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets. Materials and methods: We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset. Results: Our model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data. Conclusion: We trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP). Materials/Methods: From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability. Results: Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02). Conclusion: The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers. [ABSTRACT FROM AUTHOR]