Pilgrimage Project

The University of North Florida Pilgrimage Project combines interdisciplinary approaches with digital and STEM technologies and applies them to the study of pilgrimage with a special focus on the Camino de Santiago

2012 Annual Report - Advanced Biomedical Information Technology Core

This material is based upon work supported in part by the following funding agencies and grant awards: • Lilly Endowment, for its support of the Indiana Genomics Initiative (INGEN) – 2000; Indiana Metabolomics and Cytomics Initiative (METACyt); Indiana Pervasive Computing Research (IPCRES) initiative and Pervasive Technology Institute (1999 and 2008 respectively) • National Science Foundation under grants 01116050 MRI: Creation of the AVIDD Data Facility: A Distributed Facility for Managing, Analyzing and Visualizing Instrument-Driven Data (Michael A. McRobbie, PI); 0521433 MRI: Acquisition of a High-Speed, High Capacity Storage System to Support Scientific Computing: The Data Capacitor (Craig A. Stewart, PI); 0521433 ABI Development: National Center for Genome Analysis Support (Craig A. Stewart, PI) • National Institutes of Health NIAAA awards U24 AA014818-01 (Craig A. Stewart, PI) and U24 AA014818-04 (William K. Barnett, PI) Informatics Core for the Collaborative Initiative on Fetal Alcohol Spectrum Disorder • Subcontracts through the following NIH grant awards: 5P40RR024928 (Kenneth Cornetta, PI), 2U01AA014809 (Tatiana Foroud, PI), 1DP2OD007363-01 (Alexander Niculescu, PI), UL1RR025761-01 (Anantha Shekhar, PI), 3UL1RR025761-04S2 (Anantha Shekhar, PI), and 3UL1RR025761-04S3 (Anantha Shekhar, PI) • Funding from the general funds of Indiana University Any opinions expressed in this document are those of the authors and do not necessarily reflect the views of the funding agencies above

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Annotation of Schizophyllum commune mating-type loci reveals distinct patterns of evolution

Schizophyllum commune is a mushroom-forming fungus that has long-served as a model system for investigating the molecular control of development through study of its complex mating system. The products of the genes encoded within the mating-type loci interact in non-self combinations to activate the initial events of sexual development. Recently, this fungus has also been noted for a high level of sequence diversity between strains which is hypothesized to be due to a high mutation rate and inefficient DNA repair mechanism. The A mating type loci, that partially control sexual development, stand out even in this highly diverse fungus as extreme outliers in low sequence identity between strains, leading to a hypothesis that this area is under selection for both sequence divergence at the nucleotide level and conservation of function at the protein level. Annotation and sequence comparison of the A-alpha mating-type loci in the twenty strains for which genomic sequences are available reveal a distinct pattern of sequence identity between strains differing in mating-type and a confirm an abrupt boundary in sequence identity between strains at the borders of the mating-type regions. We are expanding our methods of analysis to provide further information on the nature of sequence evolution between strains at the A-alpha mating-type locus

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc