Digital Commons Network^™

Genetic And Transcriptional Contributions To Relapse In Normal Karyotype Acute Myeloid Leukemia, Allegra A Petti, Saad M Khan, Ziheng Xu, Nichole Helton, Catrina C Fronick, Robert Fulton, Sai M Ramakrishnan, Sridhar Nonavinkere Srivatsan, Sharon E Heath, Peter Westervelt, Jacqueline E Payton, Matthew J Walter, Daniel C Link, John Dipersio, Christopher Miller, Timothy J Ley

2020-Current year OA Pubs

To better understand clonal and transcriptional adaptations after relapse in patients with acute myeloid leukemia (AML), we collected presentation and relapse samples from six normal karyotype AML cases. We performed enhanced whole-genome sequencing to characterize clonal evolution, and deep-coverage single-cell RNA sequencing on the same samples, which yielded 142,642 high-quality cells for analysis. Identifying expressed mutations in individual cells enabled us to discriminate between normal and AML cells, to identify coordinated changes in the genome and transcriptome, and to identify subclone-specific cell states. We quantified the coevolution of genetic and transcriptional heterogeneity during AML progression, and found that transcriptional changes …

Psychiatric Diagnoses And Medications In Wolfram Syndrome, Angela M Reiersen, Jacob S Noel, Tasha Doty, Richa A Sinkre, Anagha Narayanan, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the

OBJECTIVE: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

METHOD: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

RESULTS: Study participants with Wolfram …

Mega-Analysis Methods In Enigma: The Experience Of The Generalized Anxiety Disorder Working Group, André Zugman, Jennifer Harper, Michael Myers, Michael T Perino, Qiongru Yu, Chad M Sylvester, Et Al.

2020-Current year OA Pubs

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as …

The Enigma Stroke Recovery Working Group: Big Data Neuroimaging To Study Brain-Behavior Relationships After Stroke, Sook-Lei Liew, Catherine E Lang, Anup K Bhattacharya, Et Al.

2020-Current year OA Pubs

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data …

Animal Source Foods, Rich In Essential Amino Acids, Are Important For Linear Growth And Development Of Young Children In Low- And Middle-Income Countries, Panam Parikh, Richard Semba, Mark Manary, Sumathi Swaminathan, Emorn Udomkesmalee, Rolf Bos, Bee Koon Poh, Nipa Rojroongwasinkul, Jan Geurts, Rini Sekartini, Tran Thuy Nga

2020-Current year OA Pubs

Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and delayed neurocognitive developments are most common. Fortunately, this is also the period when diet exercises its greatest influence. Growing up in an adverse environment, with a deficient diet, as typically seen in low- and middle-income countries (LMICs), hampers growth and development of children …

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

Conceptual Tensions And Practical Trade-Offs In Tailoring Implementation Interventions, Sheena M Mchugh, Fiona Riordan, Geoff M Curran, Cara C Lewis, Luke Wolfenden, Justin Presseau, Rebecca Lengnick-Hall, Byron J Powell

2020-Current year OA Pubs

Tailored interventions have been shown to be effective and tailoring is a popular process with intuitive appeal for researchers and practitioners. However, the concept and process are ill-defined in implementation science. Descriptions of how tailoring has been applied in practice are often absent or insufficient in detail. This lack of transparency makes it difficult to synthesize and replicate efforts. It also hides the trade-offs for researchers and practitioners that are inherent in the process. In this article we juxtapose the growing prominence of tailoring with four key questions surrounding the process. Specifically, we ask: (1) what constitutes tailoring and when …

Transient Equilibrium Determination Of Dopamine D2/D3 Receptor Densities And Affinities In Brain, Jenny-Ann Phan, Dean F Wong, Natalie H S Chang, Yoshitaka Kumakura, William R Bauer, Albert Gjedde

2020-Current year OA Pubs

Long-term alteration of dopaminergic neurotransmission is known to modulate the D