Digital Commons Network^™

Applying Diagnosis Support Systems In Electronic Health Records To Identify Wild-Type Transthyretin Amyloid Cardiomyopathy Risk, Connor Willis, Alexandre H Watanabe, Justin Hughes, Kimberly Nolen, Jason O'Meara, Alexander Schepart, Marianna Bruno, Joseph Biskupiak, Kensaku Kawamoto, Nawar Shara, Thomas Kannampallil

2020-Current year OA Pubs

No abstract provided.

The Clinical Cell-Cycle Risk (Ccr) Score Is Associated With Metastasis After Radiation Therapy And Provides Guidance On When To Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation, Jonathan Tward, Hiram A. Gay, Jeff Michalski, Et Al.

2020-Current year OA Pubs

PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT).

METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). …

Ex Vivo Propagation In A Novel 3d High-Throughput Co-Culture System For Multiple Myeloma, Johannes M Waldschmidt, Stefan J Fruttiger, Dagmar Wider, Johannes Jung, Andreas R Thomsen, Tanja N Hartmann, Justus Duyster, Martin J Hug, Kareem A Azab, Manfred Jung, Ralph Wäsch, Monika Engelhardt

2020-Current year OA Pubs

PURPOSE: Multiple myeloma (MM) remains an incurable hematologic malignancy which ultimately develops drug resistance and evades treatment. Despite substantial therapeutic advances over the past years, the clinical failure rate of preclinically promising anti-MM drugs remains substantial. More realistic in vitro models are thus required to better predict clinical efficacy of a preclinically active compound.

METHODS: Here, we report on the establishment of a conical agarose 3D co-culture platform for the preclinical propagation of primary MM cells ex vivo. Cell growth was compared to yet established 2D and liquid overlay systems. MM cell lines (MMCL: RPMI-8226, U266, OPM-2) and primary patient …

Veliparib Plus Carboplatin And Paclitaxel Versus Investigator's Choice Of Standard Chemotherapy In Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis.

MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis …

Bone Metastases In Non-Small Cell Lung Cancer: A Narrative Review, Brendan J. Knapp, Siddhartha Devarakonda, Ramaswamy Govindan

2020-Current year OA Pubs

Background and Objective: Bone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.

Methods: An …

Strategies To Prevent Central Line-Associated Bloodstream Infections In Acute-Care Hospitals: 2022 Update, Niccolò Buetti, Jonas Marschall, Marci Drees, Mohamad G Fakih, Lynn Hadaway, Lisa L Maragakis, Elizabeth Monsees, Shannon Novosad, Naomi P O'Grady, Mark E Rupp, Joshua Wolf, Deborah Yokoe, Leonard A Mermel

2020-Current year OA Pubs

No abstract provided.

Functional Analysis Of A Novel De Novo Variant In Ppp5c Associated With Microcephaly, Seizures, And Developmental Delay, Sara M Fielder, Jill A Rosenfeld, Lindsay C Burrage, Lisa Emrick, Seema Lalani, Ruben Attali, Joshua N Bembenek, Hieu Hoang, Dustin Baldridge, Gary A Silverman, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak

2020-Current year OA Pubs

We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was …

Efficacy And Safety Of Bempedoic Acid In Patients Not Receiving Statins In Phase 3 Clinical Trials, Ulrich Laufs, Christie M Ballantyne, Maciej Banach, Harold Bays, Alberico L Catapano, P Barton Duell, Anne C Goldberg, Antonio M Gotto, Lawrence A Leiter, Kausik K Ray, Leanne T Bloedon, Diane Macdougall, Yang Zhang, G B John Mancini

2020-Current year OA Pubs

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.

OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.

METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for …

Cardiac Mesenchymal Stem Cells Promote Fibrosis And Remodeling In Heart Failure: Role Of Pdgf Signaling, Tariq Hamid, Yuanyuan Xu, Mohamed Ameen Ismahil, Gregg Rokosh, Miki Jinno, Guihua Zhou, Qiongxin Wang, Sumanth D. Prabhu

2020-Current year OA Pubs

Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post-myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post-myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC-myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor …

Anxiety Symptoms Among Patients With Systemic Lupus Erythematosus Persist Over Time And Are Independent Of Sle Disease Activity, Daphne Lew, Xinliang Huang, Sara R Kellahan, Hong Xian, Seth Eisen, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study are to identify patterns of anxiety symptomology over time among patients with systemic lupus erythematosus (SLE) and to assess the longitudinal relationship between SLE disease activity and anxiety symptomology.

METHODS: Longitudinal data from 139 patients with American College of Rheumatology or Systemic Lupus International Collborating Clinic (SLICC)-classified SLE were analyzed. Anxiety symptomology was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress: Anxiety Short Form 8a. SLE disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 (S2K) and S2K Responder Index 50 (S2K RI-50). Group-based trajectory modeling (GBTM) …

Postviral Gastroparesis Associated With Sars-Cov-2 Infection In A Pediatric Patient, Courtney M. Rusch, Jerome M. Molleston, Matthew F. Glasser, Steven Don, Sakil S. Kulkarni

2020-Current year OA Pubs

Postviral gastroparesis has been described in children, but it has not yet been attributed to SARS-CoV-2 infection. Our case report describes a teenager with abdominal pain, early satiety, and vomiting who likely had an asymptomatic SARS-CoV-2 infection 2 months before presentation. Through investigation of epidemiologic links, antibody testing, and clinical course, it is hypothesized that her significant reduction in gastric emptying was due to postviral gastroparesis secondary to SARS-CoV-2. She was treated with supportive care and prokinetic agents. The patient demonstrated symptom resolution and near normalization of gastric emptying by the time of 1 month follow up.

Sars-Cov-2 Infection And Covid-19 Outcomes In Rheumatic Diseases: A Systematic Literature Review And Meta-Analysis, Richard Conway, Alfred H J Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients.

METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality …

Optimization Of Care For Patients With Hereditary Angioedema Living In Rural Areas, Marc A Riedl, Douglas T Johnston, John Anderson, J Allen Meadows, Daniel Soteres, Stephen B Leblanc, H James Wedner, David M Lang

2020-Current year OA Pubs

BACKGROUND: People living in rural areas of the United States experience greater health inequality than individuals residing in urban or suburban locations and encounter several barriers to obtaining optimal health care. Health disparities are compounded for patients with rare diseases such as hereditary angioedema (HAE), an autosomal dominant genetic disorder characterized by recurrent, severe abdominal pain and life-threatening oropharyngeal or laryngeal swelling.

OBJECTIVE: To explore the challenges of managing patients with HAE in rural areas and suggest possible improvements for optimizing care.

DATA SOURCES: PubMed was searched for articles on patient care management, treatment challenges, rural health, and HAE.

STUDY …

Poems Syndrome: Real World Experience In Diagnosis And Systemic Therapy - 108 Patients Multicenter Analysis, Artur Jurczyszyn, Mark Fiala, Ravi Vij, Et Al.

2020-Current year OA Pubs

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present …

How Risky Are Risk Factors? An Analysis Of Prenatal Risk Factors In Patients Participating In The Congenital Upper Limb Differences Registry, Tyler Schaeffer, Maria F Canizares, Lindley B Wall, Deborah Bohn, Suzanne Steinman, Julie Samora, Mary Claire Manske, Douglas T Hutchinson, Apurva S Shah, Andrea S Bauer, Could Study Group

2020-Current year OA Pubs

PURPOSE: Risk factors for congenital upper limb differences (CoULDs) are often studied at the general population level. The CoULD registry provides a unique opportunity to study prenatal risk factors within a large patient sample.

METHODS: All patients enrolled between June 2014 and March 2020 in the prospective CoULD registry, a national multicenter database of patients diagnosed with a CoULD, were included in the analysis. We analyzed self-reported, prenatal risk factors, including maternal smoking, alcohol use, recreational drug use, prescription drug use, gestational diabetes mellitus (GDM), and gestational hypertension. The outcome measures included comorbid medical conditions, proximal involvement of limb difference, …

A Systematic Review Of Patient-Reported Outcome Measures Patients With Chronic Limb-Threatening Ischemia, Philip Goodney, Samir Shah, Yiyuan David Hu, Bjoern Suckow, Scott Kinlay, David G Armstrong, Patrick Geraghty, Megan Patterson, Matthew Menard, Manesh R Patel, Michael S Conte

2020-Current year OA Pubs

Chronic limb-threatening ischemia (CLTI) causes significant morbidity with profound negative effects on health-related quality of life. As the prevalence of peripheral artery disease and diabetes continue to rise in our aging population, the public health impact of CLTI has escalated. Patient-reported outcome measures (PROMs) have become common and important measures for clinical evaluation in both clinical care and research. PROMs are important for the measurement of clinical effectiveness and cost effectiveness and for shared decision-making on treatment options. However, the PROMs used to describe the experience of patients with CLTI are heterogeneous, incomplete, and lack specific applicability to the underlying …

American Society For Transplantation And Cellular Therapy Series: #5-Management Of Clostridioides Difficile Infection In Hematopoietic Cell Transplant Recipients, Carolyn D Alonso, Gabriela Maron, Mini Kamboj, Paul A Carpenter, Arun Gurunathan, Kathleen M Mullane, Erik R Dubberke

2020-Current year OA Pubs

The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E …

Cd19 + Cd21lo/Neg Cells Are Increased In Systemic Sclerosis-Associated Interstitial Lung Disease, Erin M Wilfong, Katherine N Vowell, Kaitlyn E Bunn, Elise Rizzi, Narender Annapureddy, Rosemarie B Dudenhofer, April Barnado, Rachel H Bonami, Joyce E Johnson, Leslie J Crofford, Peggy L Kendall

2020-Current year OA Pubs

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017-6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, …

Exploring Reasons For Md-Phd Trainees' Experiences Of Impostor Phenomenon, Devasmita Chakraverty, Jose E Cavazos, Donna B Jeffe

2020-Current year OA Pubs

BACKGROUND: Acceptance into U.S. MD-PhD dual-degree programs is highly competitive, and the lengthy training program requires transitioning between multiple phases (pre-clinical-, PhD-research-, and clinical-training phases), which can be stressful. Challenges faced during MD-PhD training could exacerbate self-doubt and anxiety. Impostor phenomenon is the experience of feeling like a fraud, with some high-achieving, competent individuals attributing their successes to luck or other factors rather than their own ability and hard work. To our knowledge, impostor phenomenon among MD-PhD trainees has not been described. This study examined impostor phenomenon experiences during MD-PhD training and reasons trainees attributed to these feelings.

METHODS: Individuals …

Proposed Research Criteria For Prodromal Behavioural Variant Frontotemporal Dementia, Megan S Barker, Jill Goldman, Et Al.

2020-Current year OA Pubs

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal …

An Alternate Technique For Goniotomy: Description Of Procedure And Preliminary Results, Thomas Shute, Wesley Green, James Liu, Arsham Sheybani

2020-Current year OA Pubs

PURPOSE: Multiple glaucoma treatment modalities seek to lower IOP by bypassing or removing a portion of the juxtacanalicular trabecular meshwork. These procedures often require expensive implants or specialized surgical instruments. The authors developed a technique for ab interno goniectomy utilizing a standard disposable 25-gauge hypodermic needle. The surgical procedure-termed bent ab interno needle goniectomy (BANG)-and preliminary results are presented here.

METHODS: A retrospective chart review was performed for all patients who underwent goniotomy using a modified hypodermic needle by one of the three authors between July 2017 and June 2018. The mean and standard deviation pre- and postoperative IOP and …

Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.

India's Ban On Antimicrobial Fixed-Dose Combinations: Winning The Battle, Losing The War?, Giorgia Sulis, Richeek Pradhan, Anita Kotwani, Sumanth Gandra

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: India, the country with the largest market availability of antimicrobial fixed-dose combinations (FDCs), banned certain antimicrobial FDCs in September 2018. Our objective was to examine the impact of Government ban on the sales of antimicrobial FDCs.

METHODS: The sales patterns of 14 of the 26 banned antimicrobial FDCs were analyzed using monthly private sector drug sales data from IQVIA (a comprehensive and nationally representative drug sales database) between January 2018 and December 2019. We carried out descriptive analyses to evaluate the trend in sales over time for banned and non-banned antimicrobial FDCs using cumulative sales volumes.

RESULTS: …

Vaccine Protection Against The Sars-Cov-2 Omicron Variant In Macaques, Abishek Chandrashekar, Adrianus C. M. Boon, Et Al.

2020-Current year OA Pubs

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers …

High Rates Of Undiagnosed And Uncontrolled Hypertension Upon A Screening Campaign In Rural Rwanda: A Cross-Sectional Study, Evariste Ntaganda, Victor G Davila-Roman, Kenneth Schechtman, Angela L Brown, Lisa De Las Fuentes, Dominic Reeds, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention.

DESIGN AND METHOD: This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.4% females and mean BMI 26.6 ± 3.7 SD. Data were collected through a screening campaign in rural area of Kirehe District, Eastern of Rwanda, with the objective to characterize and examine the prevalence of elevated blood pressure (BP) and other CVD risk factors. An adapted …

Products Of Gut Microbial Toll/Interleukin-1 Receptor Domain Nadase Activities In Gnotobiotic Mice And Bangladeshi Children With Malnutrition, James S Weagley, Mark Zaydman, Siddarth Venkatesh, Yo Sasaki, Neha Damaraju, Alex Yenkin, William Buchser, Dmitry A Rodionov, Andrei Osterman, Tahmeed Ahmed, Michael J Barratt, Aaron Diantonio, Jeffrey Milbrandt, Jeffrey I Gordon

2020-Current year OA Pubs

Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a …

Silencing Alanine Transaminase 2 In Diabetic Liver Attenuates Hyperglycemia By Reducing Gluconeogenesis From Amino Acids, Michael R. Martino, Manuel Gutiérrez-Aguilar, Nicole K. H. Yiew, Andrew J. Lutkewitte, Jason M. Singer, Kyle S. Mccommis, Daniel Ferguson, Kim H. H. Liss, Jun Yoshino, M. Katie Renkemeyer, Gordon I. Smith, Kevin Cho, Justin A. Fletcher, Samuel Klein, Gary J. Patti, Shawn C. Burgess, Brian N. Finck

2020-Current year OA Pubs

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation of

Ptsd Is Associated With Impaired Event Processing And Memory For Everyday Events, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks

2020-Current year OA Pubs

Current theories of posttraumatic stress disorder (PTSD) propose that memory abnormalities are central to the development and persistence of symptoms. While the most notable memory disturbances in PTSD involve memory for the trauma itself, individuals often have trouble remembering aspects of everyday life. Further, people with PTSD may have difficulty segmenting ongoing activity into discrete units, which is important for our perception and later memory of the activity. The current study investigated whether PTSD diagnosis and symptom severity predicted event segmentation and memory for everyday activities. To do so, 63 people with PTSD and 64 controls with a trauma history …

A Proposed Role For Interactions Between Argonautes, Mirisc, And Rna Binding Proteins In The Regulation Of Local Translation In Neurons And Glia, Sarah K Koester, Joseph D Dougherty

2020-Current year OA Pubs

The first evidence of local translation in the CNS appeared nearly 40 years ago, when electron microscopic studies showed polyribosomes localized to the base of dendritic spines. Since then, local translation has been established as an important regulatory mechanism for gene expression in polarized or functionally compartmentalized cells. While much attention has been placed on characterizing the local transcriptome and regulatory "grammar" directing mRNA localization in neurons and glia, less is understood about how these cells subsequently de-repress mRNA translation in their peripheral processes to produce a rapid translational response to stimuli. MicroRNA-mediated translation regulation offers a possible solution to …

Directed Mutational Scanning Reveals A Balance Between Acidic And Hydrophobic Residues In Strong Human Activation Domains, Max V Staller, Eddie Ramirez, Sanjana R Kotha, Alex S Holehouse, Rohit V Pappu, Barak A Cohen

2020-Current year OA Pubs

Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of …