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Pacs Viewbook 2024-2025, Program In Audiology And Communication Sciences

PACS News

No abstract provided.

Clinical Research Coordinator Orientation Manual With Accompanying New Employee Checklist For Managers, Kaitlin Moore, Jean Flanagan, Tarisa Mantia, Kristin Geile, Kelly Koogler, Sarah Fowler-Dixon

HRPO Publications

No abstract provided.

Washington University Magazine, December 2024

Washington University Magazine

No abstract provided.

Washington University Magazine, August 2024

Washington University Magazine

No abstract provided.

A Latent Class Analysis Of Personality Traits In Adults Experiencing Homelessness, Nathaniel A. Dell, Michael Mancini, Michael Vaughn, Brandy R. Maynard, Jin Huang

Psychiatry Faculty Publications

No abstract provided.

Washington University Magazine, April 2024

Washington University Magazine

No abstract provided.

Delayed Macrophage Targeting By Clodronate Liposomes Worsens The Progression Of Cytokine Storm Syndrome, Kunjan Khanna, Emily Eul, Hui Yan, Roberta Faccio

2020-Current year OA Pubs

Excessive macrophage activation and production of pro-inflammatory cytokines are hallmarks of the Cytokine Storm Syndrome (CSS), a lethal condition triggered by sepsis, autoimmune disorders, and cancer immunotherapies. While depletion of macrophages at disease onset protects from lethality in an infection-induced CSS murine model, patients are rarely diagnosed early, hence the need to characterize macrophage populations during CSS progression and assess the therapeutic implications of macrophage targeting after disease onset. In this study, we identified MHCII

Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were …

Phosphorylation Regulates Viral Biomolecular Condensates To Promote Infectious Progeny Production, Nicholas Grams, Matthew Charman, Edwin Halko, Richard Lauman, Benjamin A Garcia, Matthew D Weitzman

2020-Current year OA Pubs

Biomolecular condensates (BMCs) play important roles in diverse biological processes. Many viruses form BMCs which have been implicated in various functions critical for the productive infection of host cells. The adenovirus L1-52/55 kilodalton protein (52K) was recently shown to form viral BMCs that coordinate viral genome packaging and capsid assembly. Although critical for packaging, we do not know how viral condensates are regulated during adenovirus infection. Here we show that phosphorylation of serine residues 28 and 75 within the N-terminal intrinsically disordered region of 52K modulates viral condensates in vitro and in cells, promoting liquid-like properties. Furthermore, we demonstrate that …

Neurosteroids: Mechanistic Considerations And Clinical Prospects, Jamie L Maguire, Steven Mennerick

2020-Current year OA Pubs

Like other classes of treatments described in this issue's section, neuroactive steroids have been studied for decades but have risen as a new class of rapid-acting, durable antidepressants with a distinct mechanism of action from previous antidepressant treatments and from other compounds covered in this issue. Neuroactive steroids are natural derivatives of progesterone but are proving effective as exogenous treatments. The best understood mechanism is that of positive allosteric modulation of GABA

Surviving Septic Patients Endotyped With A Functional Assay Demonstrate Active Immune Responses, Adam D Price, Andrew H Walton, Sydney Miles, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that

METHODS: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing …

The Potential Impact Of Exercise On Affect And Neuroinflammation In Older Adults Living With Fibromyalgia: A Scoping Review, Taylor L Taylor, Fitzgerald Dodds, Mckenna Tharpe, Emily L Zumbro, Michael Hankes, Raymond Jones, Deanna Rumble, Lisa Antoine, Kristen Allen-Watts, Andrew Sims, Reshu Chandra, Burel R Goodin, Jarred Younger, Thomas W Buford

2020-Current year OA Pubs

INTRODUCTION: Fibromyalgia (FM) is a widespread chronic pain condition with prevalence increasing in older adults. Older adults living with FM experience longer pain symptom durations that can negatively impact their quality of life. Affect and neuroinflammation are potential factors that can exacerbate pain symptoms. Exercise is a recommended intervention to manage pain symptoms; however, adherence limitations persist. Drawing on the Biopsychosocial Framework of Chronic Pain, this scoping review explores how exercise impacts factors related to neuroinflammation and affect, and how these factors contribute to exercise adherence in older adults living with FM.

METHODS: We conducted a scoping search of articles …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Chemotherapy-Induced Neutropenia Management In A Patient With Metastatic Breast Cancer And Shwachman-Diamond Syndrome (Sds): A Case Report, Renee Morecroft, Constantine N. Logothetics, Stefan P. Tarnawsky, Andrew A. Davis

2020-Current year OA Pubs

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome associated with cytopenia and the development of hematologic malignancies. Solid tumor occurrence is rare and, historically, these patients have had poor outcomes due to chemotherapy-induced myelosuppression and increased susceptibility to infections. We report the administration of cytotoxic systemic therapy with granulocyte colony-stimulating factor (G-CSF) in a patient with SDS and metastatic breast cancer. We describe the risk-benefit profile of utilizing G-CSF in managing this patient to improve her therapeutic outcome and review the prior literature.

CASE DESCRIPTION: A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen …

Lessons Learned From The Moment Study On How To Recruit And Retain A Target Population Online, Across Borders, And With Automated Remote Data Collection, Andrew Belfiglio, Shayleigh Dickson Page, Sara Pettersson, Michelle Van Rijn, Ercole Vellone, Heleen Westland, Kenneth E. Freedland, Christopher Lee, Anna Strömberg, Douglas Wiebe, Subhash Aryal, Barbara Riegel, Tiny Jaarsma

2020-Current year OA Pubs

Increasingly, studies use social media to recruit, enroll, and collect data from participants. This introduces a threat to data integrity: efforts to produce fraudulent data to receive participant compensation, e.g., gift cards. MOMENT is an online symptom-monitoring and self-care study that implemented safeguards to protect data integrity. Facebook, Twitter, and patient organizations were used to recruit participants with chronic health conditions in four countries (USA, Italy, The Netherlands, Sweden). Links to the REDCap baseline survey were posted to social media accounts. The initial study launch, where participants completed the baseline survey and were automatically re-directed to the LifeData ecological momentary …

Predicting Cognitive Decline: Which Is More Useful, Baseline Amyloid Levels Or Longitudinal Change?, Gengsheng Chen, Nicole S Mckay, Brian A Gordon, Jingxia Liu, Nelly Joseph-Mathurin, Suzanne E Schindler, Jason Hassenstab, Andrew J Aschenbrenner, Qing Wang, Stephanie A Schultz, Yi Su, Pamela J Lamontagne, Sarah J Keefe, Parinaz Massoumzadeh, Carlos Cruchaga, Chengjie Xiong, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-

Characterization Of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels In Oligodendrocytes., Kyle A Lyman, Ye Han, Andrew P Robinson, Samuel E Weinberg, Daniel W Fisher, Robert J Heuermann, Reagan E Lyman, Dong Kyu Kim, Andreas Ludwig, Navdeep S Chandel, Mark D Does, Stephen D Miller, Dane M Chetkovich

2020-Current year OA Pubs

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I

Extensive Reactive Cutaneous Histiocytic Infiltrate Resembling Non-Langerhans Cell Histiocytosis As The Presenting Sign Of Underlying Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome, Cynthia X Wang, Christine C Yokoyama, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

Leveraging Murine Models Of The Neurofibromatosis Type 1 Cancer Predisposition Syndrome To Elucidate The Cellular Circuits That Drive Pediatric Low-Grade Glioma Formation And Progression, David H Gutmann

2020-Current year OA Pubs

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Optic Chiasm Glioma In An Older Adult Patient, Ulviyya Gasimova, Osasu Adah, Matahi Muradova, Kaleigh Roberts, Sonika Dahiya, Rashmi Verma, Lokesh Rukmangadachar

2020-Current year OA Pubs

We present a case of an adult patient experiencing progressive visual loss. An initial presentation was concerning for neuromyelitis optica with optic chiasm involvement. However, persistent contrast enhancement observed in follow-up brain and orbit images raised suspicion for optic tract malignant neoplasm. Histopathological evolution of optic nerve biopsy confirmed the diagnosis of an optic chiasm glioma. The patient was then referred to oncology for chemotherapy.

A Critical Evaluation Of "Leakage" At The Cochlear Blood-Stria-Barrier And Its Functional Significance, Kevin K Ohlemiller, Noël Dwyer, Veronica Henson, Kaela Fasman, Keiko Hirose

2020-Current year OA Pubs

The blood-labyrinth-barrier (BLB) is a semipermeable boundary between the vasculature and three separate fluid spaces of the inner ear, the perilymph, the endolymph and the intrastrial space. An important component of the BLB is the blood-stria-barrier, which shepherds the passage of ions and metabolites from strial capillaries into the intrastrial space. Some investigators have reported increased "leakage" from these capillaries following certain experimental interventions, or in the presence of inflammation or genetic variants. This leakage is generally thought to be harmful to cochlear function, principally by lowering the endocochlear potential (EP). Here, we examine evidence for this dogma. We find …

The Molecular Landscape Of Sepsis Severity In Infants: Enhanced Coagulation, Innate Immunity, And T Cell Repression, Susie Shih Yin Huang, Mohammed Toufiq, Pirooz Eghtesady, Nicholas Van Panhuys, Mathieu Garand

2020-Current year OA Pubs

INTRODUCTION: Sepsis remains a major cause of mortality and morbidity in infants. In recent years, several gene marker strategies for the early identification of sepsis have been proposed but only a few have been independently validated for adult cohorts and applicability to infant sepsis remains unclear. Biomarkers to assess disease severity and risks of shock also represent an important unmet need.

METHODS: To elucidate characteristics driving sepsis in infants, we assembled a multi-transcriptomic dataset from public microarray datasets originating from five independent studies pertaining to bacterial sepsis in infant < 6-months of age (total n=335). We utilized a COmbat co-normalization strategy to enable comparative evaluation across multiple studies while preserving the relationship between cases and controls.

RESULTS: We found good concordance with only two out of seven …

Transcriptomic Profiling Of Thymic Dysregulation And Viral Tropism After Neonatal Roseolovirus Infection, Andrei Belean, Eden Xue, Benjamin Cisneros, Elisha D O Roberson, Michael A Paley, Tarin M Bigley

2020-Current year OA Pubs

INTRODUCTION: Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation.

METHODS: In the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study …

Case Report: Increased Efficacy Of Cetuximab After Pembrolizumab Failure In Cutaneous Squamous Cell Carcinoma, Renee Morecroft, Jordan Phillipps, Alice Zhou, Omar Butt, Karam Khaddour, Tanner Johanns, George Ansstas

2020-Current year OA Pubs

Immunotherapy is the first-line option for treating advanced cutaneous squamous cell carcinoma (cSCC). However, up to half of patients experience no benefit and treatment resistance, warranting newer therapeutic approaches. Combinatory approaches, including cetuximab, may help overcome immunotherapy resistance and improve response rates in advanced cSCC. We report three cases of metastatic cSCC that achieved significant clinical responses after cetuximab therapy following initial progression on pembrolizumab. We have retrospectively reviewed these cases at a single academic center between 2018 and 2023. All patients initially progressed on pembrolizumab, after which cetuximab (mono- or combination therapy) was added with two complete responses and …

Overall And Non- Lung Cancer Incidence And Mortality In The National Lung Screening Trial: Opportunities For Multi-Cancer Early Detection, Alpa V. Patel, Ellen T. Chang, Allan Hackshaw, Sam M. Janes, Diana S.M. Buist, Earl Hubbell, Christina A. Clarke, Graham A. Colditz

2020-Current year OA Pubs

No abstract provided.

Health System Barriers To Hypertension Care In Peru: Rapid Assessment To Inform Organizational-Level Change, Kendra N. Williams, Lindsay J. Underhill, Lisa De Las Fuentes, Elvin H. Geng, Victor G. Davila-Roman, Et Al.

2020-Current year OA Pubs

Traditional patient- and provider-level hypertension interventions have proven insufficient to halt hypertension as the leading cause of morbidity and mortality globally. Systems-level interventions are required to address factors challenging hypertension control across a social ecological framework, an under-studied topic particularly salient in low- and middle-income countries (LMICs) such as Peru. To inform such interventions, we sought to identify key health systems barriers to hypertension care in Puno, Peru. A participatory stakeholder workshop (October 2021) and 21 in-depth interviews (October 2021-March 2022) were conducted with 55 healthcare professionals (i.e., doctors, nurses, midwives, dentists, nutritionists), followed by a deductive qualitative analysis of …

Microglycodb: A Database Of Microbial Glycans Using Semantic Web Technologies, Sunmyoung Lee, Louis-David Leclercq, Yann Guerardel, Christine M Szymanski, Thomas Hurtaux, Tamara L Doering, Takane Katayama, Kiyotaka Fujita, Kazuhiro Aoki, Kiyoko F Aoki-Kinoshita

2020-Current year OA Pubs

Glycoconjugates are present on microbial surfaces and play critical roles in modulating interactions with the environment and the host. Extensive research on microbial glycans, including elucidating the structural diversity of the glycan moieties of glycoconjugates and polysaccharides, has been carried out to investigate the function of glycans in modulating the interactions between the host and microbes, to explore their potential applications in the therapeutic targeting of pathogenic species, and in the use as probiotics in gut microbiomes. However, glycan-related information is dispersed across numerous databases and a vast amount of literature, which makes it laborious and time-consuming to identify and …

First-In-Human Assessment Of Gut Permeability In Crohn's Disease Patients Using Fluorophore Technology, Lori R Holtz, B Darren Nix, Sewuese E Akuse, Carla Hall-Moore, Rodney D Newberry, Matthew A Ciorba, Parakkal Deepak, Maria Zulfiqar, Jeng-Jong Shieh, James R Johnson, I Rochelle Riley, Richard B Dorshow

2020-Current year OA Pubs

BACKGROUND AND AIMS: The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn's disease (CD).

METHODS: We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 …

Characterization And Z-Score Calculation Of Cardiovascular Magnetic Resonance Imaging Parameters In Patients After The Fontan Operation: A Fontan Outcome Registry Using Cardiovascular Magnetic Resonance Examinations Study, Tarek Alsaied, Manish Aggarwal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cardiac magnetic resonance (CMR) offers valuable hemodynamic insights post-Fontan, but is limited by the absence of normative single ventricle data. The Fontan Outcomes Registry using CMR Examinations (FORCE) is a large international Fontan-specific CMR registry. This study used FORCE registry data to evaluate expected CMR ventricular size/function and create Fontan-specific z-scores adjusting for ventricular morphology (VM) in healthier Fontan patients.

METHODS: "Healthier" Fontan patients were defined as patients free of adverse outcomes, who are New York Heart Association class I, have mild or less valve disease, and < 30% aortopulmonary collateral burden. General linear modeling was performed on 70% of the dataset to create z-scores for volumes and function. Models were tested using the remainder (30%) of the data. The z-scores were compared between children and adults. The z-scores were also compared between "healthier" Fontan and patients with adverse outcomes (death, listing for transplantation, or multiorgan disease).

RESULTS: The "healthier" Fontan population included 885 patients (15.0 ± 7.6 years) …