Background: The darknet hosts an increasing number of hidden services dedicated to the distribution of child sexual abuse material (CSAM). Given that by contributing CSAM to the forum members subject themselves to criminal prosecution, questions regarding the motivation for members contributing to darknet CSAM forums arise.
Objective: Building on insights gained from research into clearnet communities, here we examine the extent to which social incentives generated by the online CSAM community may explain members' posting behavior on darknet CSAM forums.
Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution.
View Article and Find Full Text PDFThe checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC.
View Article and Find Full Text PDFPancreatic intraepithelial neoplasia (PanIN) is a precursor to pancreatic cancer and represents a critical opportunity for cancer interception. However, the number, size, shape, and connectivity of PanINs in human pancreatic tissue samples are largely unknown. In this study, we quantitatively assessed human PanINs using CODA, a novel machine-learning pipeline for 3D image analysis that generates quantifiable models of large pieces of human pancreas with single-cell resolution.
View Article and Find Full Text PDFA central challenge in biology is obtaining high-content, high-resolution information while analyzing tissue samples at volumes relevant to disease progression. We address this here with CODA, a method to reconstruct exceptionally large (up to multicentimeter cubed) tissues at subcellular resolution using serially sectioned hematoxylin and eosin-stained tissue sections. Here we demonstrate CODA's ability to reconstruct three-dimensional (3D) distinct microanatomical structures in pancreas, skin, lung and liver tissues.
View Article and Find Full Text PDFObjective: Increased blood lactate levels reflect tissue oxygen debt and might be indicative of low cardiac output. We hypothesized that the rate of increase in serum lactate would be an ideal marker to discriminate between infants at high and low risk of a poor outcome after surgical repair of congenital heart disease using cardiopulmonary bypass.
Methods: In the present prospective, observational study in a pediatric cardiac intensive care unit, infants (aged <12 months) undergoing cardiac surgery had serial whole blood lactate levels measured with every arterial blood gas drawn for the first 24 postoperative hours.