Digital Commons Network^™

Expanded Analysis Of High-Grade Astrocytoma With Piloid Features Identifies An Epigenetically And Clinically Distinct Subtype Associated With Neurofibromatosis Type 1, Patrick J Cimino, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor …

A Randomized Implementation Trial To Increase Adoption Of Evidence-Informed Consent Practices, Erin D Solomon, Jessica Mozersky, Melody Goodman, Meredith V Parsons, Kari A Baldwin, Annie B Friedrich, Jenine K Harris, James M Dubois

2020-Current year OA Pubs

INTRODUCTION: Several evidence-informed consent practices (ECPs) have been shown to improve informed consent in clinical trials but are not routinely used. These include optimizing consent formatting, using plain language, using validated instruments to assess understanding, and involving legally authorized representatives when appropriate. We hypothesized that participants receiving an implementation science toolkit and a social media push would have increased adoption of ECPs and other outcomes.

METHODS: We conducted a 1-year trial with clinical research professionals in the USA (

RESULTS: Participants who engaged more with the toolkit were more likely to have tried to implement an ECP during the trial …

Development Of A Goal Setting And Goal Management System: Intervention Mapping, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: Although goal setting and goal management (GSGM) is a key component of chronic disease management and rehabilitation practice, there is currently no widely used evidence-based intervention system available. This paper describes the theoretical underpinnings and development of a new intervention called MyGoals. MyGoals is designed to guide occupational therapy (OT) practitioners to implement theory-based, client-engaged GSGM for adults with chronic conditions in community-based OT rehabilitation settings.

METHODS: We first developed a planning team with two adults with chronic conditions, two clinicians, and two researchers. As a collaborative team, we co-developed MyGoals by following Intervention Mapping (IM) steps 1-4 and …

Situating Implementation Science (Is) In Res(Is)Tance: A Conceptual Frame Toward The Integration Of Scholarship From The Black Radical Tradition, Cory D Bradley, Whitney C Irie, Elvin H Geng

2020-Current year OA Pubs

This manuscript undertakes a disciplinary self-critique of the field of implementation science, a field which attempts to bridge the gap between evidence-based interventions and their practical application. Despite the heightened emphasis on health equity and racial disparities, the field's current discourse is limited by key epistemic shortcomings. First, even though prevalence of implementation gaps between racialized groups in the United States necessitates a comprehensive understanding of the systems perpetuating these disparities, the field does not operate with a general explanation for disparities not as a failure of systems, but a system historically and structural designed to produce disparities. Second, the …

Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle

2020-Current year OA Pubs

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain …

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Aromatic Amino Acid Metabolites Alter Interferon Signaling And Influenza Pathogenesis, Gautam Anand, Colin Clark-Dinovo, Alexandra M Perry, Victoria M Goodwin, Emma St Raymond, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

The ability of gut microbial metabolites to influence the host is increasingly recognized. The microbiota extensively metabolizes the three aromatic amino acids, tryptophan, tyrosine, and phenylalanine. Previously we have found that a metabolite of tyrosine, 4-OH-phenylpropionic acid, can enhance type I interferon (IFN) signaling and protect from influenza pathogenesis in a murine model. Herein we screened 17 related aromatic amino acid metabolites for effects on IFN signaling in human lung epithelial cells and monocytes alone and in the presence of IFN-β, influenza, and LPS. While the tryptophan family metabolites reduced IFN signaling in both cell types, the tyrosine and phenylalanine …

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

Impact Of Successful Recanalization And Clinical Outcomes Of Patients With Acute Ichemic Stroke With 5 Or More Thrombectomy Passes, Kazutaka Uchida, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Safety And Efficacy Of Mca‐M2 Thrombectomy In Delayed Time Window: A Propensity Score Analysis From The Star Registry, Kaustubh Limaye, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Understanding Tailoring To Support The Implementation Of Evidence-Based Interventions In Healthcare: The Customise Research Programme Protocol, Sheena M Mchugh, Fiona Riordan, Claire Kerins, Geoff Curran, Cara C Lewis, Justin Presseau, Luke Wolfenden, Byron J Powell

2020-Current year OA Pubs

Although there are effective evidence-based interventions (EBIs) to prevent, treat and coordinate care for chronic conditions they may not be adopted widely and when adopted, implementation challenges can limit their impact. Implementation strategies are "methods or techniques used to enhance the adoption, implementation, and sustainment of a clinical program or practice". There is some evidence to suggest that to be more effective, strategies should be

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020, Kerri L Larovere, Amanda R Kolmar, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …

Association Of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension Of Survival Among Patients With Newly Diagnosed And Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial, Linda M Liau, Jian L Campian, George Ansstas, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.

OBJECTIVE: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to …

Eliminating Central Line Associated Bloodstream Infections In Pediatric Oncology Patients: A Quality Improvement Effort, Daniel N. Willis, Karen Looper, Rema A. Malone, Barbara Ricken, Ashley Slater, Amanda Fuller, Meagan Mccaughey, Angela Niesen, Joan R. Smith, Beverly Brozanski

2020-Current year OA Pubs

UNLABELLED: Central Line-Associated Bloodstream Infections (CLABSI) are the largest contributor to harm across the Children's Hospital's Solutions for Patient Safety network. Pediatric hematology/oncology (PHO) patients are at increased risk for CLABSI due to multiple factors. Consequently, traditional CLABSI prevention strategies are insufficient to eliminate CLABSI in this high-risk population.

METHODS: Our SMART aim was to reduce the CLABSI rate by 50% from a baseline of 1.89/1000 central line days to less than 0.9/1000 central line days by December 31, 2021. We created a multidisciplinary team being mindful to identify roles and responsibilities upfront. We developed a key driver diagram and …

Abundance Of Acvr1b Transcript Is Elevated During Septic Conditions: Perspectives Obtained From A Hands-On Reductionist Investigation, Anucha Preechanukul, Thatcha Yimthin, Sarunporn Tandhavanant, Tobias Brummaier, Chalita Chomkatekaew, Sukanta Das, Basirudeen Syed Ahamed Kabeer, Mohammed Toufiq, Darawan Rinchai, T Eoin West, Damien Chaussabel, Narisara Chantratita, Mathieu Garand

2020-Current year OA Pubs

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon

The Pace Of Biological Aging Helps Explain The Association Between Insomnia And Chronic Low Back Pain, Edwin N Aroke, Asia M Wiggins, Joanna M Hobson, Vinodh Srinivasasainagendra, Tammie L Quinn, Pooja Kottae, Hemant K Tiwari, Robert E Sorge, Burel R Goodin

2020-Current year OA Pubs

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE …

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

The Relationship Of Trait-Like Compassion With Epigenetic Aging: The Population-Based Prospective Young Finns Study, Henrik Dobewall, Liisa Keltikangas-Järvinen, Saara Marttila, Pashupati P Mishra, Aino Saarinen, C Robert Cloninger, Igor Zwir, Mika Kähönen, Mikko Hurme, Olli Raitakari, Terho Lehtimäki, Mirka Hintsanen

2020-Current year OA Pubs

INTRODUCTION: Helping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity.

METHODS: We used data from the Young Finns Study that follows six birth-cohorts from age 3-18 to 19-49. Trait-like compassion for others was measured with the Temperament and Character Inventory in the years 1997 and 2001. Epigenetic age acceleration and telomere length …

Treg-Specific Deletion Of The Phosphatase Shp-1 Impairs Control Of Inflammation In Vivo, Qinlei Gu, Kenneth S Tung, Ulrike M Lorenz

2020-Current year OA Pubs

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this 'activation-suppression' balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

METHODS: We generated a Treg-specific SHP-1 deletion model,

RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates …

The In Vivo Study Of Cardiac Mechano-Electric And Mechano-Mechanical Coupling During Heart Development In Zebrafish, Jonathan S Baillie, Alex Gendernalik, Deborah M Garrity, David Bark Jr, T Alexander Quinn

2020-Current year OA Pubs

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

Qunex-An Integrative Platform For Reproducible Neuroimaging Analytics, Jie Lisa Ji, Matthew F Glasser, Michael P Harms, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability.

METHODS: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment …

The Cerebrospinal Fluid Immune Cell Landscape In Animal Models Of Multiple Sclerosis, Gregory F Wu

2020-Current year OA Pubs

The fluid compartment surrounding the central nervous system (CNS) is a unique source of immune cells capable of reflecting the pathophysiology of neurologic diseases. While human clinical and experimental studies often employ cerebrospinal fluid (CSF) analysis, assessment of CSF in animal models of disease are wholly uncommon, particularly in examining the cellular component. Barriers to routine assessment of CSF in animal models of multiple sclerosis (MS) include limited sample volume, blood contamination, and lack of feasible longitudinal approaches. The few studies characterizing CSF immune cells in animal models of MS are largely outdated, but recent work employing transcriptomics have been …

Targeted Aso-Mediated Atp1a2 Knockdown In Astrocytes Reduces Sod1 Aggregation And Accelerates Disease Onset In Mutant Sod1 Mice, Abhirami K. Iyer, Kathleen M. Schoch, Anthony Verbeck, Grant Galasso, Hao Chen, Sarah Smith, Anna Oldenborg, Timothy M. Miller, Celeste M. Karch, Azad Bonni

2020-Current year OA Pubs

Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor …

Mora And Ensembletfpredictor: An Ensemble Approach To Reveal Functional Transcription Factor Regulatory Networks, Kevin Boyer, Louis Li, Tiandao Li, Bo Zhang, Guoyan Zhao

2020-Current year OA Pubs

MOTIVATION: Our study aimed to identify biologically relevant transcription factors (TFs) that control the expression of a set of co-expressed or co-regulated genes.

RESULTS: We developed a fully automated pipeline, Motif Over Representation Analysis (MORA), to detect enrichment of known TF binding motifs in any query sequences. MORA performed better than or comparable to five other TF-prediction tools as evaluated using hundreds of differentially expressed gene sets and ChIP-seq datasets derived from known TFs. Additionally, we developed EnsembleTFpredictor to harness the power of multiple TF-prediction tools to provide a list of functional TFs ranked by prediction confidence. When applied to …

A Review Of Technological Innovations Leading To Modern Endovascular Brain Aneurysm Treatment, David C Lauzier, Anna L Huguenard, Anja I Srienc, Samuel J Cler, Joshua W Osbun, Arindam R Chatterjee, Ananth K Vellimana, Akash P Kansagra, Colin P Derdeyn, Dewitte T Cross, Christopher J Moran

2020-Current year OA Pubs

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.

Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett

2020-Current year OA Pubs

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear …

What Is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, And Phantom Nerve Pain, Elspeth J R Hill, J Megan M Patterson, Andrew Yee, Lara W Crock, Susan E Mackinnon

2020-Current year OA Pubs

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for …

Disease-Causing Mutations In Genes Encoding Transcription Factors Critical For Photoreceptor Development, Chi Sun, Shiming Chen

2020-Current year OA Pubs

Photoreceptor development of the vertebrate visual system is controlled by a complex transcription regulatory network. OTX2 is expressed in the mitotic retinal progenitor cells (RPCs) and controls photoreceptor genesis. CRX that is activated by OTX2 is expressed in photoreceptor precursors after cell cycle exit. NEUROD1 is also present in photoreceptor precursors that are ready to specify into rod and cone photoreceptor subtypes. NRL is required for the rod fate and regulates downstream rod-specific genes including the orphan nuclear receptor NR2E3 which further activates rod-specific genes and simultaneously represses cone-specific genes. Cone subtype specification is also regulated by the interplay of …

A Novel Approach For Assessing Bias During Team-Based Clinical Decision-Making, Natalie Pool, Megan Hebdon, Esther De Groot, Ryan Yee, Kathryn Herrera-Theut, Erika Yee, Larry A Allen, Ayesha Hasan, Joann Lindenfeld, Elizabeth Calhoun, Molly Carnes, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: …