Digital Commons Network^™

Antibodies In Healthcare Personnel Following Severe Acute Respiratory Syndrome Coronavirus Virus 2 (Sars-Cov-2) Infection, Rachel E Bosserman, Christopher W Farnsworth, Caroline A O'Neil, Candice Cass, Daniel Park, Claire Ballman, Meghan A Wallace, Emily Struttmann, Henry Stewart, Olivia Arter, Kate Peacock, Victoria J Fraser, Philip J Budge, Margaret A Olsen, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters

2020-Current year OA Pubs

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Creation Of Philadelphia Chromosome By Crispr/Cas9-Mediated Double Cleavages On Bcr And Abl1 Genes As A Model For Initial Event In Leukemogenesis, Minori Tamai, Kenji Kamimoto, Kohei Omachi, Et Al.

2020-Current year OA Pubs

The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …

Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco

2020-Current year OA Pubs

Most neuroimaging studies of post-stroke recovery rely on analyses derived from standard node-centric functional connectivity to map the distributed effects in stroke patients. Here, given the importance of nonlocal and diffuse damage, we use an edge-centric approach to functional connectivity in order to provide an alternative description of the effects of this disorder. These techniques allow for the rendering of metrics such as normalized entropy, which describes the diversity of edge communities at each node. Moreover, the approach enables the identification of high amplitude co-fluctuations in fMRI time series. We found that normalized entropy is associated with stroke lesion severity …

Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan

2020-Current year OA Pubs

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most …

The Future Of Ad Clinical Trials With The Advent Of Anti-Amyloid Therapies: An Ctad Task Force Report, J Delrieu, R J Bateman, J Touchon, M Sabbagh, J Cummings

2020-Current year OA Pubs

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer's disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. …

A Conformational Variant Of P53 (U-P53az) As Blood-Based Biomarker For The Prediction Of The Onset Of Symptomatic Alzheimer's Disease, S Piccirella, L Van Neste, C Fowler, C L Masters, J Fripp, J D Doecke, C Xiong, D Uberti, P Kinnon

2020-Current year OA Pubs

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer's disease (AD).

OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years.

DESIGN: Retrospective Longitudinal Prognostic biomarker study.

SETTING: Single-center study based on the AIBL cohort.

PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses.

MEASUREMENTS: The …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

The Incidence Of Candidate Binding Sites For Β-Arrestin In Drosophila Neuropeptide Gpcrs, Paul H. Taghert

2020-Current year OA Pubs

To support studies of neuropeptide neuromodulation, I have studied beta-arrestin binding sites (BBS's) by evaluating the incidence of BBS sequences among the C terminal tails (CTs) of each of the 49 Drosophila melanogaster neuropeptide GPCRs. BBS were identified by matches with a prediction derived from structural analysis of rhodopsin:arrestin and vasopressin receptor: arrestin complexes [1]. To increase the rigor of the identification, I determined the conservation of BBS sequences between two long-diverged species D. melanogaster and D. virilis. There is great diversity in the profile of BBS's in this group of GPCRs. I present evidence for conserved BBS's in a …

Exploring The Feasibility Of Utilizing Limited Gene Panel Circulating Tumor Dna Clearance As A Biomarker In Patients With Locally Advanced Non-Small Cell Lung Cancer, Brendan Knapp, Laura Mezquita, Siddhartha Devarakonda, Mihaela Aldea, Saiama N Waqar, Kym Pepin, Jeffrey P Ward, Angela Botticella, Karen Howarth, Charlene Knape, Clive Morris, Ramaswamy Govindan, Benjamin Besse, Daniel Morgensztern

2020-Current year OA Pubs

INTRODUCTION: Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC.

METHODS: Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst

RESULTS: Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable …

Bruton's Tyrosine Kinase Supports Gut Mucosal Immunity And Commensal Microbiome Recognition In Autoimmune Arthritis, Rachel H Bonami, Christina E Thurman, Sonam Verma, Camille S Westlake, Lindsay E Nyhoff, Bridgette B Barron, Andrea Reboldi, Peggy L Kendall

2020-Current year OA Pubs

Bruton's tyrosine kinase (

Epidermolysis Bullosa With Congenital Absence Of Skin: Congenital Corneal Cloudiness And Esophagogastric Obstruction Including Extended Genotypic Spectrum Of Plec, Lamc2, Itgb4 And Col7a1, Pharuhad Pongmee, Sanchawan Wittayakornrerk, Ramrada Lekwuttikarn, Sasikarn Pakdeeto, Piangor Watcharakuldilok, Chatchay Prempunpong, Thipwimol Tim-Aroon, Chawintee Puttanapitak, Piyawan Wattanasoontornsakul, Thitiporn Junhasavasdikul, Parith Wongkittichote, Saisuda Noojarern, Duangrurdee Wattanasirichaigoon

2020-Current year OA Pubs

Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of

Phase 1 Clinical Trial Evaluating The Safety And Anti-Tumor Activity Of Adp-A2m10 Spear T-Cells In Patients With Mage-A10+ Head And Neck, Melanoma, Or Urothelial Tumors, David S Hong, Russell K Pachynski, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered autologous T-cells that express a high-affinity melanoma-associated antigen (MAGE)-A10-specific T-cell receptor (TCR) targeting MAGE-A10-positive tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-004 is a phase 1, dose-escalation trial to evaluate the safety and anti-tumor activity of ADP-A2M10 in three malignancies (https://clinicaltrials.gov: NCT02989064).

METHODS: Eligible patients were HLA-A*02 positive with advanced head and neck squamous cell carcinoma (HNSCC), melanoma, or urothelial carcinoma (UC) expressing MAGE-A10. Patients underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the MAGE-A10 TCR, and expanded. Patients underwent lymphodepletion with fludarabine …

Hand Transplants, Daily Functioning, And The Human Capacity For Limb Regeneration, Susan M Fitzpatrick, David Brogan, Prateek Grover

2020-Current year OA Pubs

Unlike some of our invertebrate and vertebrate cousins with the capacity to regenerate limbs after traumatic loss, humans do not have the ability to regrow arms or legs lost to injury or disease. For the millions of people worldwide who have lost a limb after birth, the primary route to regaining function and minimizing future complications is

Relief Of Chronic Pain Associated With Increase In Midline Frontal Theta Power, Nabi Rustamov, Elizabeth A. Wilson, Alexandra E. Fogarty, Lara W. Crock, Eric C. Leuthardt, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored.

OBJECTIVES: The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain.

METHODS: In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram …

The Enantiomer Of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Takeshi Yoshitomi, Kathiresan Krishnan, Douglas F Covey, Charles F Zorumski, Yukitoshi Izumi

2020-Current year OA Pubs

In an

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Kenneth E Remy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Functional And Phylogenetic Characterization Of Bacteria In Bovine Rumen Using Fractionation Of Ruminal Fluid, Ruth Hernández, Maryam Chaib De Mares, Hugo Jimenez, Alejandro Reyes, Alejandro Caro-Quintero

2020-Current year OA Pubs

Cattle productivity depends on our ability to fully understand and manipulate the fermentation process of plant material that occurs in the bovine rumen, which ultimately leads to the improvement of animal health and increased productivity with a reduction in environmental impact. An essential step in this direction is the phylogenetic and functional characterization of the microbial species composing the ruminal microbiota. To address this challenge, we separated a ruminal fluid sample by size and density using a sucrose density gradient. We used the full sample and the smallest fraction (5%), allowing the enrichment of bacteria, to assemble metagenome-assembled genomes (MAGs). …

Follistatin Protein Enhances Satellite Cell Counts In Reinnervated Muscle, Mark A. Feger, Jonathan Isaacs, Satya Mallu, Dorne Yager, Mary Shall, Gaurangkumar Patel, Omar Protzuk, Akhil S Bokkisam

2020-Current year OA Pubs

No abstract provided.

Proportional Constrained Longitudinal Data Analysis Models For Clinical Trials In Sporadic Alzheimer's Disease, Guoqiao Wang, Lei Liu, Yan Li, Andrew J Aschenbrenner, Randall J Bateman, Paul Delmar, Lon S Schneider, Richard E Kennedy, Gary R Cutter, Chengjie Xiong

2020-Current year OA Pubs

INTRODUCTION: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power).

METHODS: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression.

RESULTS: Compared with the traditional cLDA/MMRM models, PcLDA or pMMRM lead to …

Post-Transplant Thrombotic Microangiopathy Due To A Pathogenic Mutation In Complement Factor I In A Patient With Membranous Nephropathy: Case Report And Review Of Literature, Maryam Saleem, Sana Shaikh, Zheng Hu, Nicola Pozzi, Anuja Java

2020-Current year OA Pubs

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary …

Skeletal Muscle Contractile Function In Heart Failure With Reduced Ejection Fraction - A Focus On Nitric Oxide, Lauren K Park, Andrew R Coggan, Linda R Peterson

2020-Current year OA Pubs

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it …

Further Evidence That Inhibition Of Neuronal Voltage-Gated Calcium Channels Contributes To The Hypnotic Effect Of Neurosteroid Analogue, 3Β-Oh, Tamara Timic Stamenic, Francesca M Manzella, Stefan Maksimovic, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

2020-Current year OA Pubs

We recently reported that a neurosteroid analogue with T-channel-blocking properties (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rat pups without triggering neuronal apoptosis. Furthermore, we found that the inhibition of the Ca

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Avoid Or Embrace? Practice Effects In Alzheimer's Disease Prevention Trials, Andrew J Aschenbrenner, Jason Hassenstab, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects"). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials …

The Longitudinal Impact Of Maternal Depression And Neighborhood Social Context On Adolescent Mental Health, Daphne Lew, Hong Xian, Travis Loux, Enbal Shacham, Darcell Scharff

2020-Current year OA Pubs

PURPOSE: Maternal depression and neighborhood characteristics are known to be associated both with each other and with adolescent mental health outcomes. These exposures are also subject to change throughout the life of a child. This study sought to identify multi-trajectories of maternal depression (MD) and self-reported neighborhood collective efficacy (NCE) over a 12-year period and determine whether these trajectories are differentially associated with adolescent mental health.

METHODS: Data from the Fragile Families and Child Wellbeing study, a longitudinal cohort study of new parents and their children, were used. Maternal depression (MD) and self-reported NCE when the child was 3, 5, …