Volume 12

Introduction, Dr. Roger A. Byrne, Dean From the Editor, Dr. Larissa Kat Tracy From the Designers, Rachel English, Rachel Hanson Immortality in the Mortal World: Otherworldly Intervention in Lanval and The Wife of Bath\u27s Tale by Haleigh James Analysis of Phenolic Compounds in Moroccan Olive Oils by HPLC by Hannah Meyls Art by Hope Irvin The Effects of Cell Phone Use on Gameplay Enjoyment and Frustration by Megan E. Hlavaty, Samara L. Gall, and Austin J. Funk Care, No Matter What: Planned Parenthood\u27s Use of Organizational Rhetoric to Expand its Reputation by Karyn Keane Analysis of Petroleum Products for Forensic and Environmental Applications by Sarah Ghali, Antonio Harvey, and Katelynn McCrillis Art by Andrew Jones The Triangle Shirtwaist Factory Fire by Rachel Hazelwood Art by Madison Schmitz Ercilla y la imitacion: Araucanos al estilo europeo by Marija Venta Design by Haley Tebo Design by Jeremiah Gilmer White Supremacist\u27s Appropriation of the Persuasion of Passivity in Marvel\u27s Captain America by Bridget Dunn Design by Benjamin Sullivan Art by McKenzie Johnso

Impact of weight loss on cancer-related proteins in serum: results from a cluster randomised controlled trial of individuals with type 2 diabetes

Background Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development. Methods Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analysis using the Olink Oncology-II platform (48% of participants were female; 52% male). To identify proteins which may be altered by the weight-loss intervention, the difference in protein levels between groups at baseline and 1 year was examined using linear regression. Mendelian randomization (MR) was performed to extend these results to evaluate cancer risk and elucidate possible biological mechanisms linking type 2 diabetes and cancer development. MR analyses were conducted using independent datasets, including large cancer meta-analyses, UK Biobank, and FinnGen, to estimate potential causal relationships between proteins modified during intentional weight loss and the risk of colorectal, breast, endometrial, gallbladder, liver, and pancreatic cancers. Findings Nine proteins were modified by the intervention: glycoprotein Nmb; furin; Wnt inhibitory factor 1; toll-like receptor 3; pancreatic prohormone; erb-b2 receptor tyrosine kinase 2; hepatocyte growth factor; endothelial cell specific molecule 1 and Ret proto-oncogene (Holm corrected P-value <0.05). Mendelian randomization analyses indicated a causal relationship between predicted circulating furin and glycoprotein Nmb on breast cancer risk (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67–0.99, P-value = 0.03; and OR = 0.88, 95% CI = 0.78–0.99, P-value = 0.04 respectively), though these results were not supported in sensitivity analyses examining violations of MR assumptions. Interpretation Intentional weight loss among individuals with recently diagnosed diabetes may modify levels of cancer-related proteins in serum. Further evaluation of the proteins identified in this analysis could reveal molecular pathways that mediate the effect of adiposity and type 2 diabetes on cancer risk

Genome-wide association study identifies three novel susceptibility loci for severe <em>Acne vulgaris</em>

Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, Pcombined=3.23 × 10−11, odds ratio (OR)=1.20), 5q11.2 (rs38055, Pcombined=4.58 × 10−9, OR=1.17) and 1q41 (rs1159268, Pcombined=4.08 × 10−8, OR=1.17). All three loci contain genes linked to the TGFβ cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGFβ-mediated signalling in susceptibility to acne

Choroidal Thickness Profiles in Myopic Eyes of Young Adults in the Correction of Myopia Evaluation Trial Cohort

PurposeTo examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort.DesignCross-sectional, multicenter study.MethodsIn addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid in both eyes at their last visit (14 years after baseline). Using digital calipers, 2 independent readers measured choroidal thickness in the right eye (left eye if poor quality; n = 37) at 7 locations: fovea and 750, 1500, and 2250 μm nasal (N) and temporal (T) to the fovea.ResultsChoroidal thickness measurements were available from 294 of 346 (85%) imaged participants (mean age: 24.3 ± 1.4 years; 44.9% male) with mean myopia of -5.3 ± 2.0 diopters and mean AL of 25.5 ± 1.0 mm. Overall, choroidal thickness varied by location (P &lt; .0001) and was thickest at the fovea (273.8 ± 70.9 μm) and thinnest nasally (N2250, 191.5 ± 69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (P ≤ .001) and presence of peripapillary crescent at all locations except T1500 and T2250 (P ≤ .0001). Choroidal thickness varied by ethnicity at N2250 (P &lt; .0001), with Asians having the thinnest and African Americans the thickest choroids.ConclusionChoroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically