Digital Commons Network^™

Glucagon-Like Peptide Receptor Agonists (Glp-1ras) As Cardiovascular Risk Modifiers In Obstructive Sleep Apnea And Obesity: A Real-World Study, Jaeun Ahn, Junmin Song, Kyle Admire, Yu Chang, Kuan-Yu Chi, Nathaniel T. Gordon, Joshua M. Sill

Department of Medicine Faculty Publications

Introduction

Obstructive sleep apnea (OSA) is a well-established risk factor for cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated potential in reducing cardiovascular risk and improving OSA severity. However, a significant knowledge gap remains regarding the impact of GLP-1RAs on cardiovascular events in OSA patients.

Methods

We examined patients with a BMI over 30 diagnosed with OSA between January 2010 and November 2021 without a previous diagnosis of heart failure, pulmonary hypertension, or myocardial infarction. Two cohorts were created: those prescribed GLP-1RAs within 1 year of their OSA diagnosis and patients who were never prescribed GLP-1RAs. Propensity score matching …

Association Of Valvular Disease Progression Using Echocardiographic Findings In A Large U.S. Cohort, Abes A. Bautista Neughebauer, Amin Yehya, Raymond L. Benza, Deepak Talreja

Department of Medicine Faculty Publications

Background

The prevalence of valvular disease in the US is approximately 2.5%. Given that over 5 million Americans are affected, it is crucial to find those at higher risk of progression. The goal of this paper is to uncover which patients are more likely to have valvular disease progression using demographic factors, EKG and echocardiogram (ECHO) findings.

Methods

This paper utilized the EchoNext Database, which pairs 100,000 electrocardiograms and echocardiograms based on specific structural heart disease labels. Univariate and multivariate logistic regression were used to find risk factors for progression for aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR), …

Determinants Of Patient Satisfaction In An Academic Primary Care Setting: A Cross-Sectional Study Of The Postpandemic Era, Alvin Maliakal, Rajita Kanapareddy, Zooha Altaf, Janani Anbazhagan, Kristin Olson, Cynthia Avila, Rehan Qayyum

Department of Medicine Faculty Publications

Background

Patient satisfaction, a key indicator of healthcare quality, is associated with improved adherence, continuity, and outcomes. However, limited evidence describes determinants of patient satisfaction in contemporary primary care settings reflecting the postpandemic era, when care delivery models and patient expectations have evolved substantially.

Objective

To evaluate the sociodemographic and clinical factors associated with patient satisfaction in an academic primary care setting following the postpandemic era.

Methods

We conducted a cross-sectional survey of adult patients (≥18 years) attending a primary care clinic. Participants completed a self-administered questionnaire including the Visit-Specific Satisfaction Questionnaire (VSQ-9) and measures of sociodemographic and clinical characteristics. …

Application Of The Lancet Commission Criteria For The Diagnosis Of Obesity To A Clinical Trials Population: The Leap Trial, Faith Anne N Heeren, Kathleen R Ruddiman, Courtney Simmons, Brian N White, Byron C Jaeger, Nicholas M Pajewski, Stephanie A Hooker, Deborah B Horn, Katy Martin-Fernandez, Kimberly A Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis

Faculty, Staff and Student Publications

Objective: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity."

Results: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD …

Advancing Models Of Ptsd-Aud Comorbidity: Protocol For A Multimethod Framework Using Genetics And Ecological Momentary Assessment, Elizabeth A. Stinson, Samhita Lellapalli, Sage E. Hawn, Natalie Merrill, Lance M. Rappaport, Christina M. Sheerin, Vasiliki Michopoulos, Silviu-Alin Bacanu, Roseann E. Peterson, Abigail Powers, Ananda B. Amstadter

Psychology Faculty Publications

Background: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), which are moderately heritable, frequently co-occur and contribute to significant public health burdens, particularly among economically disadvantaged urban communities. There are noted sex differences in PTSD and AUD outcomes, with evidence suggesting women have heightened susceptibility to stress-related alcohol use. Preliminary PTSD-AUD ecological momentary assessment (EMA) findings support bidirectional associations across clinical outcomes. However, no studies to date have used PTSD-AUD comorbidity models as organizing frameworks to examine the temporal ordering and stability of within-person symptom dynamics underlying the maintenance or exacerbation of PTSD and AUD symptoms, including bidirectional and …

Partial Post-Exposure Protection By Topical Inserts Containing Tenofovir Alafenamide Fumarate/Elvitegravir In A Macaque Model Of Rectal Simian Hiv (Shiv) Infection, Natalia Makarova, Tyana Singletary, M. Melissa Peet, Kristen Kelley, Ryan Johnson, Vivek Agrahari, Maria Mendoza, Yi Pan, Walid Heneine, Meredith R. Clark, J. Gerardo García Lerma, Gustavo F. Doncel, James W. Smith

CONRAD Publications

On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis 4 hours before SHIV exposure. Here, we show that the same inserts provide significant postexposure protection (82.9% efficacy) when applied 4 hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.

The Crucial Role Of Machine Learning Models In Predicting Current Childhood Asthma: Model Comparison, Calibration, And Shap-Based Interpretation, Aditya Chakraborty, A. K.M. Raquibul Bashar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background: Asthma is one of the most prominent chronic diseases in children and one of the most challenging ailments to diagnose in infants and preschoolers in the United States. Predictive models can be instrumental in improving early diagnosis, personalized treatment strategies, and disease progression. By utilizing nationalized data, this study focuses on building and comparing high-performing analytical predictive models based on the relevant risk factors and identifying the most influential predictors.

Methods: We analyzed cross-sectional BRFSS Asthma Call-Back Survey data (2011-2020; N = 9,813) and randomly split participants into training and testing sets. An XGBoost model (hyperparameters tuned via grid …

Nanoparticle Albumin-Bound Paclitaxel And Nivolumab For Pd-1 Inhibitor-Refractory Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Douglas Adkins, Jessica C Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt

2020-Current year OA Pubs

INTRODUCTION: Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (nab)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.

METHODS: In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received nab-paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

An Insidious Interstice: Understanding Cognition And Language Behaviour Through The Eyes Of Juvenile Justice Professionals, Anne M. Perrotti, Allison T. Chappell, Tancy Vandecar-Burdin

Human Movement Studies & Special Education Faculty Publications

Introduction

Despite evidence suggesting language and cognition deficits are prevalent for justice involved youth, little research explores how juvenile justice personnel experience language and cognition behaviours in the youth they serve.

Aims

This qualitative study explored how juvenile justice personnel understand language and cognition skills and deficits in justice involved youth.

Methods

Twenty-two U.S. juvenile justice professionals participated in individual, semi-structured interviews. Questions focused on individual understanding of receptive language, expressive language, social communication, and cognition (i.e., problem-solving, predicting consequences and impulsiveness) in juveniles served. Using a phenomenological lens, transcripts were coded identifying themes and sub-themes of participant responses.

Results …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes., Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M. Starke, Marios-Nikos Psychogios, Edgar A. Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A. Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G. Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S. Park, Michael R. Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J. Altschul, Alejandro M. Spiotta, Peter Kan

Department of Medicine Faculty Papers

INTRODUCTION: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

PATIENTS AND METHODS: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

Foot-Specific Exercise Intervention For Forefoot Deformity In Individuals With Type 2 Diabetes And Peripheral Neuropathy: A Randomized Controlled Clinical Trial With 3-Year Follow-Up, J A Zellers, K Steger-May, P K Commean, H-J Jeong, E M Bullard, M J Mueller, M K Hastings

2020-Current year OA Pubs

BACKGROUND: Diabetes with peripheral neuropathy can lead to metatarsophalangeal joint (MTPJ) deformity. The purpose of this study was to estimate the effect of a foot-specific intervention on MTPJ deformity. Secondary aims were determining MTPJ deformity progression over 3 years and predictors of MTPJ deformity progression.

METHODS: Sixty people with type 2 diabetes and peripheral neuropathy were recruited for this randomized controlled clinical trial. Participants were assessed at baseline, 6 months (post-intervention), 1.5 years, and 3 years. A 6-month, foot-specific intervention in the experimental group was compared to a shoulder intervention in the control group. The primary outcome was change in …

Psychological And Clinical Risk Factors For Substance Use In People With And Without Hiv, Joanna M Hobson, Shameka L Cody, Shannon R Gilstrap, Michael A Owens, Myles D Moody, Dyan M White-Gilliam, Stephen Justin Thomas, Emily J Bartley, Burel R Goodin

2020-Current year OA Pubs

BackgroundDespite growing concerns, limited research has demonstrated how psychological factors influence substance use in people with HIV (PWH). Therefore, we examined the association between heightened vigilance and substance use outcomes in people with (PWH) and without HIV (PWoH), while accounting for key risk factors.MethodsParticipants (n = 138) were recruited from an HIV clinic and the surrounding community, completing a urine drug screener (UDS) and questionnaires.ResultsPWH reported greater insomnia (

Characteristics Of Cerebral Palsy In The Midwestern Us, Susie Kim, Kelsey Steffen, Lauren Gottschalk-Henneberry, Jennifer Miros, Amy Robichaux-Viehoever, Karen Taca, Bhooma R Aravamuthan

2020-Current year OA Pubs

OBJECTIVE: Cerebral palsy (CP) is the most common lifelong motor disability worldwide. Yet, data is limited on how CP manifests in the US. Our objective was to characterize and determine factors affecting functional outcomes in a large population of young people with CP in the Midwestern US.

METHODS: We integrated caregiver and clinician-facing standardized data entry into routine clinical care at a tertiary care CP center (https://bit.ly/CP-Intake-Methodology). We extracted this data for people with an ICD10 diagnosis of CP seen between March 22, 2023 and December 28, 2023 and used it to describe CP characteristics and determine factors affecting the …

Prediction Of Continuous Amyloid Positron Emission Tomography With Fluid Measures Of Phosphorylated Tau And Β-Amyloid, Niklas Mattsson-Carlgren, Linda Karlsson, Weizhong Tang, Kaj Blennow, Henrik Zetterberg, Randall J Bateman, Suzanne E Schindler, Nicolas Barthelemy, Sebastian Palmqvist, Erik Stomrud, Shorena Janelidze, Oskar Hansson

2020-Current year OA Pubs

Brain amyloid-β (Aβ) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal Aβ, but it is unclear to what degree they can predict quantitative Aβ-PET. We explored plasma and CSF biomarkers in relation to Aβ-PET in the BioFINDER-2 study (N = 1053), and the BioFINDER-1 study (N = 238). We developed a machine learning pipeline to predict Aβ-PET using CSF and plasma measures. The best models achieved R

Towards Precision Functional Brain Network Mapping In Parkinson's Disease, Jacob Chernicky, Ally Dworetsky, Sarah Grossen, Emma Carr, Abdulmunaim Eid, Meghan C Campbell, Caterina Gratton

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. "Precision" RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.

OBJECTIVES: To evaluate the feasibility and reliability of precision RSFC …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

A Microenvironment-Driven Hla-Ii-Associated Insulin Neoantigen Elicits Persistent Memory T Cell Activation In Diabetes, Neetu Srivastava, Anthony N Vomund, Rongzhen Yu, Orion J Peterson, Yuqing Yang, David P Turicek, Omar Abousaway, Tiandao Li, Pamela Stone, Aisha Ansar, Rima Melhem, Bo Zhang, Chang Liu, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Emil R Unanue, Ana Maria Arbelaez, Cheryl F Lichti, Xiaoxiao Wan, Et Al.

2020-Current year OA Pubs

The antigenic landscape of autoimmune diabetes reflects a failure to preserve self-tolerance, yet how novel neoantigens emerge in humans remains incompletely understood. Here we designed an immunopeptidomics-based approach to probe HLA-II-bound, islet-derived neoepitopes in patients with type 1 diabetes. We uncovered a Cys→Ser transformation, conserved between mice and humans, that reshapes autoreactivity to insulin at the single-residue level. This transformation, which we call C19S, arises from oxidative remodeling of insulin in stressed pancreatic islets and also occurs in cytokine-activated antigen-presenting cells, contributing to a feed-forward loop of neoepitope formation and presentation. Despite involving just one amino acid, C19S is recognized …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

METHODS: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …

A Survey-Based Assessment Of Treatment Preferences For Distal Radius Fractures In Participants Aged 65 Years And Older, Zayd Al Rawi, Elizabeth Graesser, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: The management of distal radius fractures (DRF) in patients aged ≥65 years is debated because there is evidence that operative and nonsurgical treatment yield similar outcomes 1 year after injury. When more than one reasonable treatment option exists, shared decision-making between the patient and physician should be used. This study elicited preferences for the treatment of DRF using a survey of participants aged ≥65 years.

METHODS: A survey for participants ≥65 years was administered using Amazon Mechanical Turk. Participants were presented with a theoretical scenario in which they sustained a DRF, followed by two treatment options (surgery or casting) …

Phase I Trial Of Adp-A2afp Tcr T-Cell Therapy In Patients With Advanced Hepatocellular Or Gastric Hepatoid Carcinoma, Tim Meyer, Benjamin R Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies, necessitating the development of alternative treatments. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP).

METHODS: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection who progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m

RESULTS: Twenty-one participants, 20 with advanced HCC and one with gastric hepatoid carcinoma received ≥1 ADP-A2AFP …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Karen Schwander, Lisa De Las Fuentes, Mary F Feitosa, Anh Do, C Charles Gu, Changwei Li, Michael A Province, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Identification Of Distinct Subtypes In Immune Tolerance After Hematopoietic Cell Transplantation Using The Prospective Able1.0 Pediatric Study Cohort, Bernard Ng, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

The lack of immune tolerance after hematopoietic cell transplantation (HCT) can result in chronic graft-versus-host disease (cGvHD), which is the primary nonrelapse limitation of successful HCT. To date, immune tolerance has been considered a single biological entity, but we hypothesized that post-HCT immune tolerance could develop through multiple pathways. Using the ABLE network database, which comprises measurements of 75 cell populations, 10 cytokines and chemokines, lymphocyte population telomere length, KRECs and TRECs, and 132 metabolites from the largest pediatric cGvHD cohort (n = 241), we applied clustering analysis to patients with primary immune tolerance (PIT; no acute GvHD [aGvHD] or …

Excellent Outcomes In Feasibility Study Of Radiation-Free Conditioning And Transplant In Pediatric Severe Aplastic Anemia, Mithra Lakshmi Narasimhan, Irem Eldem, Jeffrey J Bednarski, Ginny L Schulz, Robert J Hayashi, Shalini Shenoy

2020-Current year OA Pubs

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes …

A Single-Cell Atlas Characterizes Dysregulation Of The Bone Marrow Immune Microenvironment Associated With Outcomes In Multiple Myeloma, William C Pilcher, Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, Mark A Fiala, Chiang I-Ling, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, John F Dipersio, Shaji Kumar, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

Perceived Hiv Risk, Barriers, And Preferences For Hiv Testing In Structurally Vulnerable Communities In St. Louis: A Best-Worst Scaling Survey, Emmanuel K Tetteh, Noelle Le Tourneau, Gregory Gross, Mckenzie Swan, Tyrell Manning, Justin Cole, Katie Wolf, Lawrence Hudson-Lewis, Julia D López, Todd Combs, Virginia R Mckay

2020-Current year OA Pubs

BackgroundPersistent gaps in efforts to end the HIV epidemic in the United States highlight the need for community-specific, evidence-based HIV testing strategies. This study investigated barriers and preferences around HIV testing among underserved populations, including Black, queer, and young adults in the St. Louis, Missouri area.MethodsWe conducted a Best-Worst Scaling (BWS) survey with adults (16+ years) recruited at community events, collecting responses electronically and providing a $25 incentive. The survey assessed the relative importance of 13 potential barriers to HIV testing such as stigma, structural barriers, and perceived HIV risk, chosen based on literature review and community input. Mean preference …

Evaluation Of Mycoplasma Genitalium Positivity And Co-Infection With Chlamydia Trachomatis And/Or Neisseria Gonorrhoeae At Various Care Sites Across The United States, Rebecca Lillis, Stacey House, Et Al.

2020-Current year OA Pubs

OBJECTIVES: We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test.

METHODS: A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed.

RESULTS: Among …