Digital Commons Network^™

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, …

Automated Measurement Of Net Water Uptake From Baseline And Follow-Up Cts In Patients With Large Vessel Occlusion Stroke, Atul Kumar, Yasheng Chen, Aaron Corbin, Ali Hamzehloo, Amin Abedini, Zeynep Vardar, Grace Carey, Kunal Bhatia, Laura Heitsch, Jamal J Derakhshan, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks …

The Past, Present, And Future Of A Human T-Cell Leukemia Virus Type 1 Vaccine, Joshua J Tu, Victoria Maksimova, Lee Ratner, Amanda R Panfil

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5-10 million persons are infected with HTLV-1 worldwide - a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and …

Use Of Implementation Mapping With Community-Based Participatory Research: Development Of Implementation Strategies Of A New Goal Setting And Goal Management Intervention System, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

AIMS: This study aims to identify implementation determinants, mechanisms of action, implementation strategies, and implementation outcome evaluation plans for a new theory-based rehabilitation goal setting and goal management intervention system, called MyGoals, using Implementation Mapping with community-based participatory research principles.

METHODS: We completed Implementation Mapping tasks 1 to 4 as a planning team consisting of MyGoals target implementers (occupational therapists (OTs), MyGoals intervention target clients (adults with chronic conditions), and the research team. We are currently conducting mapping task 5. These processes were guided by the Consolidated Framework for Implementation Research, social cognitive theory, the taxonomy of behavior change methods, …

Hdl Composition, Heart Failure, And Its Comorbidities, Ahmed Diab, Carla Valenzuela Ripoll, Zhen Guo, Ali Javaheri

2020-Current year OA Pubs

Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart …

Differential Sphingosine-1-Phosphate Receptor-1 Protein Expression In The Dorsolateral Prefrontal Cortex Between Schizophrenia Type 1 And Type 2, Ganesh B Chand, Hao Jiang, J Philip Miller, C Harker Rhodes, Zhude Tu, Dean Foster Wong

2020-Current year OA Pubs

Understanding the etiology and treatment approaches in schizophrenia is challenged in part by the heterogeneity of this disorder. One encouraging progress is the growing evidence that there are subtypes of schizophrenia. Recent

Modification Of Neurogenic Colonic Motor Behaviours By Chemogenetic Ablation Of Calretinin Neurons, Jing Feng, Tim J Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J Spencer, Hongzhen Hu

2020-Current year OA Pubs

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossing

The Temporal Relationship Between Local School Closure And Increased Incidence Of Pediatric Diabetic Ketoacidosis, Casey K Mccluskey, Janine E Zee-Cheng, Margaret J Klein, Matthew C Scanlon, Alexandre T Rotta, Kenneth E Remy, Christopher L Carroll, Steven L Shein

2020-Current year OA Pubs

IMPORTANCE: The incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown.

OBJECTIVE: To evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence.

DESIGN: A multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018-2019. Interrupted …

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Efficacy Of Laser Interstitial Thermal Therapy (Litt) For Newly Diagnosed And Recurrent Idh Wild-Type Glioblastoma, John F De Groot, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent

METHODS: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on

RESULTS: A total of 29 new and 60 recurrent

CONCLUSIONS: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for

Leptomeningeal Disease And Tumor Dissemination In A Murine Diffuse Intrinsic Pontine Glioma Model: Implications For The Study Of The Tumor-Cerebrospinal Fluid-Ependymal Microenvironment, Shelei Pan, Dezhuang Ye, Yimei Yue, Lihua Yang, Christopher P Pacia, Dakota Defreitas, Prabagaran Esakky, Sonika Dahiya, David D Limbrick, Joshua B Rubin, Hong Chen, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor-CSF-ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG.

METHODS: A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic …

Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation,

METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.

RESULTS: When controlling for factors with known prognostic significance including

CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six …