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Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to report visual, topographic, and satisfaction comparative results between symmetrical and asymmetrical presbyLASIK after 18 months., Methods: Longitudinal, comparative case series of hyperopic presbyopes who underwent presbyLASIK, in a private clinical setting. Monovision symmetrical (plano target both eyes) versus asymmetrical [dominant eye (DE) = plano target; nondominant eye (NDE) = -0.50 diopter (D) target]. Pre- and postoperative variables included monocular and binocular, distance and near, uncorrected visual acuity (VA), best corrected visual acuity, spherical equivalent, addition (Add), topography SimK (Km), and topographic astigmatism. Topographic central corneal power increase was measured 3 and 18 months postoperatively. Data were reported as mean, range, and standard deviation and analyzed with Student t-test (P < 0.05 for statistical significance) and Pearson correlation coefficients., Results: The symmetrical group consisted of 16 patients and the asymmetrical group of 14 patients, with a mean age of 53.5 ± 2.3 and 51.9 ± 2.5 years. Postoperative results, after 18 months, for symmetrical versus asymmetrical presbyLASIK were as follows: distance UCVA 0.8 ±0.20; 0.9 ± 0.2 (P < 0.01); near UCVA 0.9 ± 0.2; 0.8 ± 0.2 (P < 0.01); SE -0.20 ± 0.50; -0.3 ± 0.3D (P < 0.01); Add 0.5 ± 0.5; 0.9 ± 0.9 (P < 0.01); mean Km 44.8 ± 1 D; 43.9 ± 1.1 D (P < 0.01); mean central corneal power differential 1.4 ± 0.8 D; 1.7 ± 1.1 D (P < 0.01), respectively. Stability: -0.16 D, DE -0.13 D and NDE -0.16 D, and SE predictability -0.40; DE -0.28 D and NDE -0.53 D. Safety index 1.0; 1.0, efficacy distance VA 0.8; 0.9, and near VA 0.90; 0.8. More than 90% were within ±0.50 D of the intended target. Twenty eyes required enhancement, and results were not significantly different. Mean satisfaction (0-10 points) for symmetrical patients was 7.0 ± 2.6 and 7.3 ± 2.8 points for asymmetrical patients., Conclusions: Symmetrical and asymmetrical presbyLASIK significantly improved distance UCVA, near UCVA, after 18 months.