Digital Commons Network^™

Dnmt3a Deficiency In The Skin Causes Focal, Canonical Dna Hypomethylation And A Cellular Proliferation Phenotype, David Y. Chen, Ian M. Ferguson, Krista A. Braun, Leslie A. Sutton, Nichole M. Helton, Sai Mukund Ramakrishnan, Amanda M. Smith, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Phase 3 Randomized Trial Of Chemotherapy With Or Without Oblimersen In Older Aml Patients: Calgb 10201 (Alliance), Alison R. Walker, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

Identifying Risk Factors And Patterns For Early Recurrence Of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study, Charlotte M Heidsma, Ryan Fields, Bradley A Krasnick, Et Al

Open Access Publications

BACKGROUND: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting.

METHODS: Patients undergoing surgical resection for pNETs between 1998-2018 were identified using a multi-institutional database. Using a minimum

RESULTS: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest

CONCLUSION: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years …

Tailoring Of Arteriovenous Graft‑To‑Vein Anastomosis Angle To Attenuate Pathological Flow Fields, Dillon Williams, Eric C. Leuthardt, Guy M. Genin, Mohamed Zayed

Open Access Publications

No abstract provided.

Taxonomic Changes In The Gut Microbiota Are Associated With Cartilage Damage Independent Of Adiposity, High Fat Diet, And Joint Injury, Kelsey H. Collins, Drew J. Schwartz, Kristin L. Lenz, Charles A. Harris, Farshid Guilak

Open Access Publications

No abstract provided.

Transcriptional-Regulatory Convergence Across Functional Mdd Risk Variants Identified By Massively Parallel Reporter Assays, Bernard Mulvey, Joseph D. Dougherty

Open Access Publications

No abstract provided.

Genomic And Clinical Characterization Of Early T-Cell Precursor Lymphoblastic Lymphoma, Xinjie Xu, Christian N. Paxton, Robert J. Hayashi, Kimberly P. Dunsmore, Stuart S. Winter, Stephen P. Hunger, Naomi J. Winick, William L. Carroll, Mignon L. Loh, Meenakshi Devidas, Thomas G. Gross, Catherine M. Bollard, Sherrie L. Perkins, Rodney R. Miles

Open Access Publications

No abstract provided.

Autophagy Of Mucin Granules Contributes To Resolution Of Airway Mucous Metaplasia, J.M. Sweeter, K. Kudrna, K. Hunt, P. Thomas, B. F. Dickey, S. L. Brody, J. D. Dickinson

Open Access Publications

No abstract provided.

Endothelial Ether Lipids Link The Vasculature To Blood Pressure, Behavior, And Neurodegeneration, Larry D. Spears, Sangeeta Adak, Guifang Dong, Xiaochao Wei, George Spyropoulos, Qiang Zhang, Li Yin, Chu Feng, Donghua Hu, Irfan J. Lodhi, Fong-Fu Hsu, Rithwick Rajagopal, Kevin K. Noguchi, Carmen M. Halabi, Lindsey Brier, Annie R. Bice, Brian V. Lananna, Erik S. Musiek, Oshri Avraham, Valeria Cavalli, Jerrah K. Holth, David M. Holtzman, David F. Wozniak, Joseph P. Culver, Clay F. Semenkovich

Open Access Publications

No abstract provided.

Comparison Of Complication Risk For Open Carpal Tunnel Release: In-Office Versus Operating Room Settings, Dustin J. Randall, Kate Peacock, Katelin B. Nickel, Margaret Olsen, Andrew R. Tyser, Nikolas H. Kazmers

Open Access Publications

No abstract provided.

Temporal Trends In Incidence Rates Of Lower Extremity Amputation And Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 To 2018, Miao Cai, Yan Xie, Benjamin Bowe, Andrew K. Gibson, Mohamed A. Zayed, Tingting Li, Ziyad Al-Aly

Open Access Publications

Importance: Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized.

Objective: To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018.

Design, Setting, and Participants: This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models …

Preliminary, Real-World, Multicenter Experience With Omadacycline For Mycobacterium Abscessus Infections, Taylor Morrisette, Sara Alosaimy, Julie V. Philley, Carly Wadle, Catessa Howard, Andrew J. Webb, Michael P. Veve, Melissa L. Barger, Jeannette Bouchard, Tristan W. Gore, Abdalhamid M. Lagnf, Iman Ansari, Carlos Mejia-Chew, Keira A. Cohen, Michael J. Rybak

Open Access Publications

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for

Apobec1 Complementation Factor Overexpression Promotes Hepatic Steatosis, Fibrosis, And Hepatocellular Cancer, Valerie Blanc, Jesse D Riordan, Saeed Soleymanjahi, Joseph H Nadeau, Ilke Nalbantoglu, Yan Xie, Elizabeth A Molitor, Blair B Madison, Elizabeth M Brunt, Jason C Mills, Deborah C Rubin, Irene O Ng, Yeonjung Ha, Lewis R Roberts, Nicholas O Davidson

Open Access Publications

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose …

Evaluation Of Diffusion-Weighted Mri And Geometric Distortion On A 0.35t Mr-Linac At Multiple Gantry Angles, Benjamin Lewis, Anamaria Guta, Stacie Mackey, H Michael Gach, Sasa Mutic, Olga Green, Taeho Kim

Open Access Publications

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all …

Using Lorenz Curves To Measure Racial Inequities In Covid-19 Testing, Aaloke Mody, Kristin Pfeifauf, Elvin H. Geng

Open Access Publications

No abstract provided.

Adherence Of Internet-Based Cancer Risk Assessment Tools To Best Practices In Risk Communication: Content Analysis, Erika A Waters, Jeremy L Foust, Laura D Scherer, Amy Mcqueen, Jennifer M Taber

Open Access Publications

BACKGROUND: Internet-based risk assessment tools offer a potential avenue for people to learn about their cancer risk and adopt risk-reducing behaviors. However, little is known about whether internet-based risk assessment tools adhere to scientific evidence for what constitutes good risk communication strategies. Furthermore, their quality may vary from a user experience perspective.

OBJECTIVE: This study aims to understand the extent to which current best practices in risk communication have been applied to internet-based cancer risk assessment tools.

METHODS: We conducted a search on August 6, 2019, to identify websites that provided personalized assessments of cancer risk or the likelihood of …

Focused Ultrasound-Enhanced Delivery Of Intranasally Administered Anti-Programmed Cell Death-Ligand 1 Antibody To An Intracranial Murine Glioma Model, Dezhuang Ye, Jinyun Yuan, Yimei Yue, Joshua B Rubin, Hong Chen

Open Access Publications

Immune checkpoint inhibitors have great potential for the treatment of gliomas; however, their therapeutic efficacy has been partially limited by their inability to efficiently cross the blood-brain barrier (BBB). The objective of this study was to evaluate the capability of focused-ultrasound-mediated intranasal brain drug delivery (FUSIN) in achieving the locally enhanced delivery of anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain. Both non-tumor mice and mice transcranially implanted with GL261 glioma cells at the brainstem were used in this study. aPD-L1 was labeled with a near-infrared fluorescence dye (IRDye 800CW) and administered to mice through the nasal route to …

Successful Administration Of Sequential Tvec And Pembrolizumab Followed By Temozolomide In Immunotherapy Refractory Intracranial Metastatic Melanoma With Acquired B2m Mutation, Karam Khaddour, Joshua Dowling, Jiayi Huang, Martha Council, David Chen, Lynn Cornelius, Tanner Johanns, Sonika Dahiya, George Ansstas

Open Access Publications

Despite the substantial advances in the management of metastatic melanoma with the introduction of immune checkpoint inhibitors (ICI), many patients develop disease progression during treatment with immunotherapy. This has been suggested to be mediated by several mechanisms that contribute to acquired resistance to ICI, one of which is acquired beta-2 microgloubulin (B2M) mutation. Talimogene laherparepvec (TVEC) is a genetically modified oncolytic virus that can enhance antitumor immunity. Temozolomide (TMZ) is an oral alkylating agent that has been suggested to augment anti-tumor immune response. The clinical significance of TVEC and TMZ in metastatic melanoma patients who are refractory to immunotherapy is …

Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty

Open Access Publications

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, …

Neutrophil Elastase Facilitates Tumor Cell Intravasation And Early Metastatic Events, Elena Deryugina, Alexia Carré, Veronica Ardi, Tomoki Muramatsu, Jonas Schmidt, Christine Pham, James P Quigley

Open Access Publications

Functional roles of neutrophil elastase (NE) have not been examined in distinct steps of the metastatic cascade. NE, delivered to primary tumors as a purified enzyme or within intact neutrophils or neutrophil granule content, enhanced human tumor cell intravasation and subsequent dissemination via NE-mediated formation of dilated intratumoral vasculature. These effects depended on picomole range of NE activity, sensitive to its natural inhibitor, α1PI. In

Neuroplastin Modulates Anti-Inflammatory Effects Of Manf, Takuya Yagi, Rie Asada, Kohsuke Kanekura, Ave Eesmaa, Maria Lindahl, Mart Saarma, Fumihiko Urano

Open Access Publications

Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads to cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER-localized protein whose expression and secretion is induced by ER stress and a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due to the lack of knowledge of its receptor. Here we show that Neuroplastin (NPTN) is such a receptor for MANF. Biochemical analysis shows the physiological interaction between MANF and NPTN on the cell surface. Binding of MANF to NPTN mitigates the inflammatory response and apoptosis via suppression …

Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al

Open Access Publications

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL …

Evaluation Of Surrogate Tests For The Presence Of Meca-Mediated Methicillin Resistance In Staphylococcus Capitis, Staphylococcus Haemolyticus, Staphylococcus Hominis, And Staphylococcus Warneri, Romney M Humphries, Paul Magnano, C A Burnham, Jennifer Dien Bard, Tanis C Dingle, Katrina Callan, Lars F Westblade

Open Access Publications

Testing of staphylococci other than

A Clinical Epidemiology And Molecular Attribution Evaluation Of Adenoviruses In Pediatric Acute Gastroenteritis: A Case-Control Study, Kanti Pabbaraju, Raymond Tellier, Xiao-Li Pang, Jianling Xie, Bonita E Lee, Linda Chui, Ran Zhuo, Otto G Vanderkooi, Samina Ali, Phillip I Tarr, Anna Funk, Stephen B Freedman

Open Access Publications

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (

A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems …

Self-Administered Questionnaire To Screen For Polycystic Ovarian Syndrome, Bronwyn S Bedrick, Ashley M Eskew, Jorge E Chavarro, Emily S Jungheim

Open Access Publications

No abstract provided.

Discoidin Domain Receptor 1 Activation Links Extracellular Matrix To Podocyte Lipotoxicity In Alport Syndrome, Jin-Ju Kim, Jeffrey H Miner, Et Al

Open Access Publications

BACKGROUND: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is activated by collagens that is involved in the pathogenesis of fibrotic disorders. Interestingly, de novo production of the collagen type I (Col I) has been observed in Col4a3 knockout mice, a mouse model of Alport Syndrome (AS mice). Deletion of the DDR1 in AS mice was shown to improve survival and renal function. However, the mechanisms driving DDR1-dependent fibrosis remain largely unknown.

METHODS: Podocyte pDDR1 levels, Collagen and cluster of differentiation 36 (CD36) expression was analyzed by Real-time PCR and Western blot. Lipid droplet accumulation and content …

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m