Digital Commons Network^™

The Association Of Radiation Dose With Overall Survival For Patients Treated With Prostate Stereotactic Body Radiation Therapy, Michael R. Waters, Neal Andruska, Benjamin W. Fischer-Valuck, Temitope Agabalogun, Randall J. Brenneman, Hiram Gay, Jeff M. Michalski, Brian Baumann

2020-Current year OA Pubs

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/β = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials …

The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker

2020-Current year OA Pubs

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify …

Cytosolic Epcam Cooperates With H-Ras To Regulate Epithelial To Mesenchymal Transition Through Zeb1, Fatma A. Omar, Taylor C. Brown, William E. Gillanders, Timothy P. Fleming, Michael A. Smith, Ross M. Bremner, Narendra V. Sankpal

2020-Current year OA Pubs

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, …

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 …

The Immunology Of Takotsubo Syndrome, Kenji Rowel Q Lim, Douglas L Mann, Tsuneaki Kenzaka, Tomohiro Hayashi

2020-Current year OA Pubs

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully …

Rare Predicted Loss-Of-Function Variants Of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19, Daniela Matuozzo, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.

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 …

Vigorous-Intensity Exercise As A Modulator Of Cardiac Adipose Tissue In Women With Obesity: A Cross-Sectional And Randomized Pilot Study, Sumsen Thapa, Bharath S Selvaraj, Paige N Davis, Bryan Smith, Amy H Givan, Jose A Perez-Rivera, Pamela K Woodard, Jon D Klingensmith, Maria Fernandez-Del-Valle

2020-Current year OA Pubs

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T Batchelor, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …

Functional Trajectories During Innate Spinal Cord Repair, Nicholas O Jensen, Brooke Burris, Lili Zhou, Hunter Yamada, Catrina Reyes, Zachary Pincus, Mayssa H Mokalled

2020-Current year OA Pubs

Adult zebrafish are capable of anatomical and functional recovery following severe spinal cord injury. Axon growth, glial bridging and adult neurogenesis are hallmarks of cellular regeneration during spinal cord repair. However, the correlation between these cellular regenerative processes and functional recovery remains to be elucidated. Whereas the majority of established functional regeneration metrics measure swim capacity, we hypothesize that gait quality is more directly related to neurological health. Here, we performed a longitudinal swim tracking study for 60 individual zebrafish spanning 8 weeks of spinal cord regeneration. Multiple swim parameters as well as axonal and glial bridging were integrated. We …

Racial Disparities In Access To Dbs: Results Of A Real-World U.S. Claims Data Analysis, Michael Frassica, Drew S Kern, Mitra Afshari, Allison T Connolly, Chengyuan Wu, Nathan Rowland, Juan Ramirez-Castaneda, Mwiza Ushe, Claudia Salazar, Xenos Mason

2020-Current year OA Pubs

INTRODUCTION: Deep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson's Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients.

METHODS: A retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were …

Caregiver Perspectives On The Continued Impact Of The Covid-19 Pandemic On Children With Intellectual/Developmental Disabilities, R A Northrup, E Jones, V Singh, C Holingue, M Meck, C A Gurnett, M Van Stone, L G Kalb

2020-Current year OA Pubs

The COVID-19 pandemic has significantly impacted caregivers, especially those raising a child with an intellectual/developmental disability (IDD). While research has shown substantial disruption to the family, school, and occupational lives of the IDD community, little is known about the long-term impacts of COVID-19. To address this question, 249 caregivers were surveyed via an online questionnaire, between April and August of 2022 (more than 2 years into the pandemic) about potential impacts of the COVID-19 pandemic on their child's access to health- and school-based therapeutic services, caregiver mental health, and family life. The majority of caregivers reported disruptions in access to …

Oxidation Driven Reversal Of Pip2-Dependent Gating In Girk2 Channels, Sun-Joo Lee, Shoji Maeda, Jian Gao, Colin G Nichols

2020-Current year OA Pubs

Physiological activity of G protein gated inward rectifier K

Intra-Articular Aav9 Α-L-Iduronidase Gene Replacement In The Canine Model Of Mucopolysaccharidosis Type I, Raymond Yu-Jeang Wang, Shih-Hsin Kan, Haoyue Zhang, Jodi D Smith, Afshin Aminian, Elizabeth Snella, Jackie K Jens, Sarah P Young, Patricia I Dickson, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type I (MPS I), an inherited lysosomal storage disorder characterized by deficiency of

Machine Learning Pipelines Developed For The Prediction Of Cancelation Of Inappropriate Parathyroid Hormone-Related Peptide Orders Demonstrate Poor Performance In Predicting Provider Behavior, Nicholas C. Spies, Christopher W. Farnsworth, Ronald Jackups, Mark A. Zaydman

2020-Current year OA Pubs

No abstract provided.

Seventy-Five Years Of Service: An Overview Of The College Of American Pathologists' Proficiency Testing Program In Histocompatibility And Identity Testing, H Cliff Sullivan, Manish J Gandhi, Sujata Gaitonde, Ramya Narasimhan, Ketevan Gendzekhadze, Soumya Pandey, Rhonda K Roby, George C Maha, Harmeet Kaur, Jennifer J Schiller, Julie Mcdowell, Maria Smith, Chang Liu, Gerald P Morris

2020-Current year OA Pubs

The Histocompatibility and Identity Testing Committee offers an overview of the College of American Pathologists' (CAP) Proficiency Testing (PT) program, commemorating its significant 75th anniversary in 2024. The CAP PT program has undergone significant growth and evolution over the years, ultimately achieving Centers for Medicare and Medicaid Services approval. In 1979, CAP's partnership with the American Association for Clinical Histocompatibility Testing marked a pivotal moment, leading to the creation of the first proficiency testing survey in 1980. This laid the foundation for various PT programs managed by the CAP Histocompatibility and Identity Testing Committee, including HLA antibody testing, HLA molecular …

Molecular Techniques Drive Cutting Edge Advancements In Management Of Cutaneous T Cell Lymphoma, Mitchell N Lefebvre, Nicholas Borcherding, Ryan J Reis, Eric Mou, Vincent Liu, Ali Jabbari

2020-Current year OA Pubs

Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M. Willems, Ping An, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

How Penalizing Substance Use In Pregnancy Affects Treatment And Research: A Qualitative Examination Of Researchers' Perspectives, Seema K Shah, Leishla Perez-Cardona, Khrystyna Helner, Suena H Massey, Ashish Premkumar, Renee Edwards, Elizabeth S Norton, Cynthia E Rogers, Emily S Miller, Christopher D Smyser, Matthew M Davis, Lauren S Wakschlag

2020-Current year OA Pubs

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood.

METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.

RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal …

Characterization Of Cerebrospinal Fluid (Csf) Microbiota At The Time Of Initial Surgical Intervention For Children With Hydrocephalus, Shailly Pandey, Kathryn B. Whitlock, Matthew R. Test, Paul Hodor, Christopher E. Pope, David D. Limbrick, Patrick J. Mcdonald, Jason S. Hauptman, Lucas R. Hoffman, Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in …

Predicting Incident Cardiovascular Disease Among African-American Adults: A Deep Learning Approach To Evaluate Social Determinants Of Health In The Jackson Heart Study, Matthew C. Morris, Hamidreza Moradi, Maryam Aslani, Mario Sims, David Schlundt, Chrystyna D. Kouros, Burel Goodin, Crystal Lim, Kerry Kinney

2020-Current year OA Pubs

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) …

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.

Designing Implementation Strategies To Improve Identification, Cascade Testing, And Management Of Families With Familial Hypercholesterolemia: An Intervention Mapping Approach, Laney K Jones, Ross C Brownson, Anne C Goldberg, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.

METHODS: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific …

Cell Wall Composition In Cryptococcus Neoformans Is Media Dependent And Alters Host Response, Inducing Protective Immunity, Rajendra Upadhya, Woei C Lam, Camaron R Hole, Joseph G Vasselli, Jennifer K Lodge

2020-Current year OA Pubs

INTRODUCTION:

OBJECTIVE: The purpose of this study was to determine how different media influenced the amount of chitin and chitosan in the cell wall, which in turn impacted the cell wall architecture and host response.

METHODS: Yeast extract, peptone, and dextrose (YPD) and yeast nitrogen base (YNB) are two commonly used media for growing Cryptococcus before use in in vitro or in vivo experiments. As a result,

RESULTS: We observed that the growth of wild-type

CONCLUSION: These findings emphasize the importance of culture media and pH during growth in shaping the content and organization of the

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Allele-Specific Quantification Of Human Leukocyte Antigen Transcript Isoforms By Nanopore Sequencing, Andrew E O Hughes, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

INTRODUCTION: While tens of thousands of HLA alleles have been identified by DNA sequencing, the contribution of alternative splicing to HLA diversity is not well characterized. In this study, we sought to determine if long-read sequencing could be used to accurately quantify allele-specific HLA transcripts in primary human lymphocytes.

METHODS: cDNA libraries were prepared from peripheral blood lymphocytes from 12 donors and sequenced by nanopore long-read sequencing. HLA reads were aligned to donor-specific reference sequences based on the known type of each donor. Allele-specific exon utilization was calculated as the proportion of reads aligning to each allele containing known exons, …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Evaluation Of Gliovascular Functions Of Aqp4 Readthrough Isoforms, Shayna M Mueller, Kelli Mcfarland White, Stuart B Fass, Siyu Chen, Zhan Shi, Xia Ge, John A Engelbach, Seana H Gaines, Annie R Bice, Michael J Vasek, Joel R Garbow, Joseph P Culver, Zila Martinez-Lozada, Martine Cohen-Salmon, Joseph D Dougherty, Darshan Sapkota

2020-Current year OA Pubs

Aquaporin-4 (AQP4) is a water channel protein that links the astrocytic endfeet to the blood-brain barrier (BBB) and regulates water and potassium homeostasis in the brain, as well as the glymphatic clearance of waste products that would otherwise potentiate neurological diseases. Recently, translational readthrough was shown to generate a C-terminally extended variant of AQP4, known as AQP4x, which preferentially localizes around the BBB through interaction with the scaffolding protein α-syntrophin, and loss of AQP4x disrupts waste clearance from the brain. To investigate the function of AQP4x, we generated a novel AQP4 mouse line (AllX) to increase relative levels of the …

Open-Source Statistical And Data Processing Tools For Wide-Field Optical Imaging Data In Mice, Lindsey M. Brier, Joseph P. Culver

2020-Current year OA Pubs

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data.

AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from …