Digital Commons Network^™

Redox-Responsive Hyaluronic Acid-Based Nanogels For The Topical Delivery Of The Visual Chromophore To Retinal Photoreceptors, Amine M. Laradji, Alexander V. Kolesnikov, Bedia B. Karakoçak, Vladimir J. Kefalov, Nathan Ravi

Open Access Publications

No abstract provided.

A Priori Activation Of Apoptosis Pathways Of Tumor (Aaapt) Technology: Development Of Targeted Apoptosis Initiators For Cancer Treatment, Raghu S. Pandurangi, Marco Tomasetti, Sekar T. Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput, Manjushree Anjanappa, Harikrishna Nakshatri

Open Access Publications

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. Amongst many, the principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer …

Proteomic And Functional Mapping Of Cardiac Nav1.5 Channel Phosphorylation Sites, Maxime Lorenzini, Emily Wagner, Kiersten M. Ruff, Rohit V. Pappu, Jeanne M. Nerbonne, Jonathan R. Silva, R. Reid Townsend, Et Al

Open Access Publications

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative …

Tumor-Associated Neutrophils (Tans) In Human Carcinoma-Draining Lymph Nodes: A Novel Tan Compartment, Silvia Lonardi, William Vermi, Et Al.

Open Access Publications

No abstract provided.

Measuring Activities Of Daily Living In Stroke Patients With Motion Machine Learning Algorithms: A Pilot Study, Pin-Wei Chen, Nathan A Baune, Igor Zwir, Jiayu Wang, Victoria Swamidass, Alex W K Wong

Open Access Publications

Measuring activities of daily living (ADLs) using wearable technologies may offer higher precision and granularity than the current clinical assessments for patients after stroke. This study aimed to develop and determine the accuracy of detecting different ADLs using machine-learning (ML) algorithms and wearable sensors. Eleven post-stroke patients participated in this pilot study at an ADL Simulation Lab across two study visits. We collected blocks of repeated activity ("atomic" activity) performance data to train our ML algorithms during one visit. We evaluated our ML algorithms using independent semi-naturalistic activity data collected at a separate session. We tested Decision Tree, Random Forest, …

Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols

Open Access Publications

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These …

The Dark Side Of The Gut: Virome-Host Interactions In Intestinal Homeostasis And Disease, Yuhao Li, Scott A. Handley, Megan T. Baldridge

Open Access Publications

The diverse enteric viral communities that infect microbes and the animal host collectively constitute the gut virome. Although recent advances in sequencing and analysis of metaviromes have revealed the complexity of the virome and facilitated discovery of new viruses, our understanding of the enteric virome is still incomplete. Recent studies have uncovered how virome-host interactions can contribute to beneficial or detrimental outcomes for the host. Understanding the complex interactions between enteric viruses and the intestinal immune system is a prerequisite for elucidating their role in intestinal diseases. In this review, we provide an overview of the enteric virome composition and …

Integrating Imaging And Rna-Seq Improves Outcome Prediction In Cervical Cancer, Jin Zhang, Ramachandran Rashmi, Matthew Inkman, Kay Jayachandran, Fiona Ruiz, Michael R Waters, Perry W Grigsby, Stephanie Markovina, Julie K Schwarz

Open Access Publications

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene …

Concordance Of Antibiotic Prescribing With The American Dental Association Acute Oral Infection Guidelines Within Veterans' Affairs (Va) Dentistry, Daniel B Carlsen, Michael J Durkin, Gretchen Gibson, M Marianne Jurasic, Ursula Patel, Linda Poggensee, Margaret A Fitzpatrick, Kelly Echevarria, Jessina Mcgregor, Charlesnika T Evans, Katie J Suda

Open Access Publications

OBJECTIVE: United States dentists prescribe 10% of all outpatient antibiotics. Assessing appropriateness of antibiotic prescribing has been challenging due to a lack of guidelines for oral infections. In 2019, the American Dental Association (ADA) published clinical practice guidelines (CPG) on the management of acute oral infections. Our objective was to describe baseline national antibiotic prescribing for acute oral infections prior to the release of the ADA CPG and to identify patient-level variables associated with an antibiotic prescription.

DESIGN: Cross-sectional analysis.

METHODS: We performed an analysis of national VA data from January 1, 2017, to December 31, 2017. We identified cases …

Rural-Urban Differences In Antibiotic Prescribing For Uncomplicated Urinary Tract Infection, Abbye W Clark, Michael J Durkin, Margaret A Olsen, Matthew Keller, Yinjiao Ma, Caroline A O'Neil, Anne M Butler

Open Access Publications

OBJECTIVE: To examine rural-urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI).

DESIGN: Observational cohort study.

METHODS: Using the IBM MarketScan Commercial Database (2010-2015), we identified US commercially insured women aged 18-44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural-urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural-urban status and inappropriate antibiotic receipt, accounting for …

Trem2 Sustains Macrophage-Hepatocyte Metabolic Coordination In Nonalcoholic Fatty Liver Disease And Sepsis, Jinchao Hou, Yingyue Zhou, Marco Colonna, Et Al

Open Access Publications

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of …

A Pilot Study Examining The Prognostic Utility Of Tumor Shrinkage On Cone-Beam Computed Tomography (Cbct) For Stage Iii Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation, Kylie H Kang, Jimmy T Efird, Tarun K Podder, Yuxia Zhang, Afshin Dowlati, Mitchell Machtay, Charulata Jindal, Tithi Biswas

Open Access Publications

There has been growing interest in utilizing information from cone-beam computed tomography (CBCT) to help guide both treatment delivery and prognosis. In this assessment of locally advanced unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation, we aimed to determine the survival advantage associated with using CBCT to measure tumor regression. Patient, tumor, and treatment characteristics were collected. The serial tumor shrinkage for each patient was determined from tumor volume contours on weekly CBCTs. Survival analysis was performed using the Kaplan-Meier technique and a Cox proportional hazards model. At least two-thirds of patients had a tumor volume …

Atoh7-Independent Specification Of Retinal Ganglion Cell Identity, Justin Brodie-Kommit, Brian S Clark, Fion Shiau, Philip A Ruzycki, Et Al

Open Access Publications

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor

Microbiota Signals Suppress B Lymphopoiesis With Aging In Mice, Joseph R Krambs, Darlene A Monlish, Feng Gao, Laura G Schuettpelz, Daniel C Link

Open Access Publications

Aging is associated with significant changes in hematopoiesis that include a shift from lymphopoiesis to myelopoiesis and an expansion of phenotypic hematopoietic stem cells (HSCs) with impaired self-renewal capacity and myeloid-skewed lineage differentiation. Signals from commensal flora support basal myelopoiesis in young mice; however, their contribution to hematopoietic aging is largely unknown. Here, we characterize hematopoiesis in young and middle-aged mice housed under specific pathogen free (SPF) and germ-free (GF) conditions. The marked shift from lymphopoiesis to myelopoiesis that develops during aging of SPF mice is mostly abrogated in GF mice. Compared with aged SPF mice, there is a marked …

Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh

Open Access Publications

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with

Continuous Renal Replacement Therapy For Two Neonates With Hyperammonemia, Christopher Markham, Caroline Williams, Cory Miller, Dorothy K Grange, T Keefe Davis, Kenneth E Remy

Open Access Publications

No abstract provided.

Resting-State Functional Magnetic Resonance Imaging Networks As A Quantitative Metric For Impact Of Neurosurgical Interventions, Peter H Yang, Carl D Hacker, Bhuvic Patel, Andy G S Daniel, Eric C Leuthardt

Open Access Publications

No abstract provided.

Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Yun Ju Sung, Karen Schwander, Lisa De Las Fuentes, C Charles Gu, Laura Bierut, Dabeeru C. Rao, Et Al

Open Access Publications

No abstract provided.

Evaluation Of Kratom Opioid Derivatives As Potential Treatment Option For Alcohol Use Disorder, Anna M Gutridge, Soumen Chakraborty, Balazs R Varga, Elizabeth S Rhoda, Alexander R French, Arryn T Blaine, Quinten H Royer, Haoyue Cui, Jinling Yuan, Robert J Cassell, Márk Szabó, Susruta Majumdar, Richard M Van Rijn

Open Access Publications

No abstract provided.

Consensus Guidelines For Improving Quality Of Assessment And Training For Neuromuscular Diseases, Tina Duong, Kristin J Krosschell, Meredith K James, Leslie Nelson, Lindsay N Alfano, Katy Eichinger, Elena Mazzone, Kristy Rose, Linda P Lowes, Anna Mayhew, Julaine Florence, Wendy King, Claudia R Senesac, Michelle Eagle

Open Access Publications

Critical components of successful evaluation of clinical outcome assessments (COAs) in multisite clinical trials and clinical practice are standardized training, administration, and documented reliability of scoring. Experiences of evaluators, alongside patient differences from regional standards of care, may contribute to heterogeneity in clinical center's expertise. Achieving low variability and high reliability of COA is fundamental to clinical research and to give confidence in our ability to draw rational, interpretable conclusions from the data collected. The objective of this manuscript is to provide a framework to guide the learning process for COAs for use in clinics and clinical trials to maximize …

Training Leaders To Accelerate Global Mental Health Disparities Research (Lead) Program: A Research Training Program Protocol, Ozge Sensoy Bahar, Patricia Cavazos-Rehg, Fred M Ssewamala, Betsy Abente, Laura Peer, Proscovia Nabunya, Lourdes E Soto De Laurido, Theresa S Betancourt, Arvin Bhana, Tonya Edmond

Open Access Publications

No abstract provided.

Pharmacological And Biophysical Characteristics Of Picrotoxin-Resistant, Δsubunit-Containing Gabaa Receptors, Hong-Jin Shu, Xinguo Lu, John Bracamontes, Joe Henry Steinbach, Charles F Zorumski, Steven Mennerick

Open Access Publications

GABA

Successful Treatment Of Noise-Induced Hearing Loss By Mesenchymal Stromal Cells: An Rnaseq Analysis Of Protective/Repair Pathways, Athanasia Warnecke, Jennifer Harre, Matthew Shew, Adam J Mellott, Igor Majewski, Martin Durisin, Hinrich Staecker

Open Access Publications

Mesenchymal stromal cells (MSCs) are an adult derived stem cell-like population that has been shown to mediate repair in a wide range of degenerative disorders. The protective effects of MSCs are mainly mediated by the release of growth factors and cytokines thereby modulating the diseased environment and the immune system. Within the inner ear, MSCs have been shown protective against tissue damage induced by sound and a variety of ototoxins. To better understand the mechanism of action of MSCs in the inner ear, mice were exposed to narrow band noise. After exposure, MSCs derived from human umbilical cord Wharton's jelly …

Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini

Open Access Publications

No abstract provided.

Viral Evasion Of Innate Immune Defense: The Case Of Resistance Of Pandemic H1n1 Influenza A Virus To Human Mannose-Binding Proteins, Mitchell R White, Nikolaos M Nikolaidis, Francis Mccormack, Erika C Crouch, Kevan L Hartshorn

Open Access Publications

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAV

Zo-1 Intracellular Localization Organizes Immune Response In Non-Small Cell Lung Cancer, Déborah Neyrinck-Leglantier, Julien Lesage, Silvia Blacher, Arnaud Bonnomet, Walter Hunziker, Agnès Noël, Valérian Dormoy, Béatrice Nawrocki-Raby, Christine Gilles, Myriam Polette

Open Access Publications

Delocalization of zonula occludens-1 (ZO-1) from tight junctions plays a substantial role in epithelial cell plasticity observed during tumor progression.

Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic

The Worldwide Alzheimer's Disease Neuroimaging Initiative: Adni-3 Updates And Global Perspectives, Christopher J Weber, Richard J Perrin, John C Morris, Et Al

Open Access Publications

The Worldwide Alzheimer's Disease Neuroimaging Initiative (WW-ADNI) is a collaborative effort to investigate imaging and biofluid markers that can inform Alzheimer's disease treatment trials. It is a public-private partnership that spans North America, Argentina, Australia, Canada, China, Japan, Korea, Mexico, and Taiwan. In 2004, ADNI researchers began a naturalistic, longitudinal study that continues today around the globe. Through several successive phases (ADNI-1, ADNI-GO, ADNI-2, and ADNI-3), the study has fueled amyloid and tau phenotyping and refined neuroimaging methodologies. WW-ADNI researchers have successfully standardized analyses and openly share data without embargo, providing a rich data set for other investigators. On August …

Helminth-Virus Interactions: Determinants Of Coinfection Outcomes, Pritesh Desai, Michael S Diamond, Larissa B Thackray

Open Access Publications

Viral infections are often studied in model mammalian organisms under specific pathogen-free conditions. However, in nature, coinfections are common, and infection with one organism can alter host susceptibility to infection with another. Helminth parasites share a long coevolutionary history with mammalian hosts and have shaped host physiology, metabolism, immunity, and the composition of the microbiome. Published studies suggest that helminth infection can either be beneficial or detrimental during viral infection. Here, we discuss coinfection studies in mouse models and use them to define key determinants that impact outcomes, including the type of antiviral immunity, the tissue tropism of both the …

Cost Burden Of Post-Transplant Lymphoproliferative Disease Following Kidney Transplants In Medicare-Eligible Patients By Survival Status, Allyson Hart, Yoon Son Ahn, Crystal Watson, Melissa Skeans, Arie Barlev, Bryn Thompson, Vikas R Dharnidharka

Open Access Publications

AIMS AND OBJECTIVES: Patients diagnosed with post-transplant lymphoproliferative disease (PTLD) experience high mortality within the first 2 years of diagnosis; however, few data exist on the economic burden of PTLD in these patients. We determined the healthcare resource utilization (HRU) and cost burden of post-kidney transplant PTLD and evaluated how these differ by survival status.

MATERIALS AND METHODS: Utilizing data from the United States Renal Data System and the Scientific Registry of Transplant Recipients, we identified 83,818 Medicare-covered kidney transplant recipients between 2007 and 2016, of which 347 had at least one Medicare claim during the first year after diagnosis …