The Grizzly, February 8, 1994

Ursinus Celebrates 125 Years of Academics • An Evaluation of the 128 Credit System • In Celebration of Black History Month: Al Eaton Brings on His One-Man Show • Ursinus Crimes Reported • Who Freed South Africa? • Guys Pledging Begins on Friday • Suite Etiquette • Senior Profile: Craig Faucher • Airband \u2794 • Come out and Support a U.C. Senior • Berman to Receive Preservation Grant • Woodward Exhibit on Display • Bright Moments to Perform • An Internal Compass Spinning • Eats & Seats • Wrestlers Up to 9-1 • Ursinus Gymnastics Sets New Records • Personal Interest Workshops to be Held • UC Student Almost Becomes Phillies\u27 Biggest Phanhttps://digitalcommons.ursinus.edu/grizzlynews/1329/thumbnail.jp

The Grizzly, February 15, 1994

Pledging Meeting: First in a Series • Berry Announces Plans for Candidacy • Ursinus Given Laboratory Glassware as Gift • Airband to Help Local • Northeast Still Being Hit by Winter • Professor Profile: Tom Whalen • The Power of the Postcard • GALA Retools • Censorship Sucks • UC Baseball to Hold 4th Annual Baseball Clinic • Freshman Black Belt Profiled in National Karate Magazine • New Track & Field Coaches Hired • Wrestling Destroys All Competitionhttps://digitalcommons.ursinus.edu/grizzlynews/1330/thumbnail.jp

Test-retest repeatability of organ uptake on PSMA‐targeted 18F‐DCFPyL PET/CT in patients with prostate cancer

Objectives We evaluated 18F-DCFPyL test–retest repeatability of uptake in normal organs. Methods Twenty-two prostate cancer (PC) patients underwent two 18F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. Results For SUVmean, repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%–14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax, however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%–45.2%). Conclusion We found acceptable repeatability of uptake on 18F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs

The Grizzly, February 2, 1993

Cowboys Tame Buffalo, 52-17 • Upsilon Phi Delta Approved • AIDS Quilt • Al Eaton\u27s We Are the Dream • Day For a King • Power Plays • Bernie Bernie Headflap Wins Battle of the Bands • Lorelei at Chateau Granieri • Ice Skating Fun • The Case of the Disappearing Sevs (Or: Why Collegeville\u27s Most Famous Convenient Mart Upped & Left) • Senior Profile: Chris Kakacek • The New Zack\u27s: Why Hike to WaWa? • What\u27s Up in Wellness • Character was an Issue, Again • The Importance of Effort and A Dream • UC Baseball Preview \u2793 • Gymnasts Hoping For Powerful Season • Lady Bears Make Playoffs • Swimmers Working Hard • Football Awards Banquet Held • Wrestlers Continue Excellence • Men\u27s Basketball Split Twohttps://digitalcommons.ursinus.edu/grizzlynews/1308/thumbnail.jp

Lack of repeatability of radiomic features derived from PET scans: results from a 18F‐DCFPyL test–retest cohort

Objectives PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test–retest setting. The prostate-specific membrane antigen-targeted compound 18F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). Methods Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland–Altman analysis. Results In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07–0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland–Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/−1.30, 0.23/−0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). Conclusion Many common radiomic features derived from a test–retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study

High SUVs have more robust repeatability in patients with metastatic prostate cancer: results from a prospective test-retest cohort imaged with 18F-DCFPyL

OBJECTIVES: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with (18)F-DCFPyL. METHODS: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two (18)F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUV(max)) and mean (SUV(mean)) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA − TV × SUV(mean))). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUV(max) (1.5–80.5) and SUV(mean) (1.4–24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R(2) ≥ 0.99), with high repeatability for SUV(mean) and SUV(max) (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV ≥ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R(2) ≥ 0.98). Moreover, LN-based SUV(mean) also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUV(max) (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUV(max) of the most intense lesion per patient (R(2), 0.99; wCOV, 11.2%). CONCLUSION: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability

Nucleosynthetic molybdenum isotope anomalies in iron meteorites – new evidence for thermal processing of solar nebula material

publisher: Elsevier articletitle: Nucleosynthetic molybdenum isotope anomalies in iron meteorites – new evidence for thermal processing of solar nebula material journaltitle: Earth and Planetary Science Letters articlelink: https://doi.org/10.1016/j.epsl.2017.05.001 content_type: article copyright: © 2017 The Authors. Published by Elsevier B.V.© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1016/j.epsl.2017.05.001

Early Treatment with Fumagillin, an Inhibitor of Methionine Aminopeptidase-2, Prevents Pulmonary Hypertension in Monocrotaline-Injured Rats

Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts