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Washington University School of Medicine

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Articles 5911 - 5940 of 10535

Full-Text Articles in Medicine and Health Sciences

The Ifn-Γ Receptor Promotes Immune Dysregulation And Disease In Sting Gain-Of-Function Mice, W. Alexander Stinson, Cathrine A. Miner, Fang R. Zhao, Annena Jane Lundgren, Subhajit Poddar, Jonathan J. Miner Sep 2022

The Ifn-Γ Receptor Promotes Immune Dysregulation And Disease In Sting Gain-Of-Function Mice, W. Alexander Stinson, Cathrine A. Miner, Fang R. Zhao, Annena Jane Lundgren, Subhajit Poddar, Jonathan J. Miner

2020-Current year OA Pubs

STING gain-of-function mutations cause STING-associated vasculopathy with onset in infancy (SAVI) in humans, a disease characterized by spontaneous lung inflammation and fibrosis. Mice with STING gain-of-function mutations (SAVI mice) develop αβ T cell-dependent lung disease and also lack lymph nodes. Although SAVI has been regarded as a type I interferonopathy, the relative contributions of the three interferon receptors are incompletely understood. Here, we show that STING gain of function led to upregulation of IFN-γ-induced chemokines in the lungs of SAVI mice and that deletion of the type II IFN receptor (IFNGR1), but not the type I IFN receptor (IFNAR1) or …


Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Mary F. Feitosa, Et Al Sep 2022

Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Mary F. Feitosa, Et Al

2020-Current year OA Pubs

No abstract provided.


Feasibility And Sensitivity Study Of Radiomic Features In Photoacoustic Imaging Of Patient-Derived Xenografts, Lorena Escudero Sanchez, Emma Brown, Leonardo Rundo, Stephan Ursprung, Evis Sala, Sarah E Bohndiek, Ignacio Xavier Partarrieu Sep 2022

Feasibility And Sensitivity Study Of Radiomic Features In Photoacoustic Imaging Of Patient-Derived Xenografts, Lorena Escudero Sanchez, Emma Brown, Leonardo Rundo, Stephan Ursprung, Evis Sala, Sarah E Bohndiek, Ignacio Xavier Partarrieu

2020-Current year OA Pubs

Photoacoustic imaging is an increasingly popular method of exploring the tumour microenvironment, which can provide insight into tumour oxygenation status and potentially treatment response assessment. Currently, the measurements most commonly performed on such images are the mean and median of the pixel values of the tumour volumes of interest. We investigated expanding the set of measurements that can be extracted from these images by adding radiomic features. In particular, we found that Skewness was sensitive to differences between basal and luminal patient derived xenograft cancer models with an [Formula: see text] of 0.86, and that it was robust to variations …


Idiopathic Ventricular Fibrillation In A Previously Healthy Recreational Athlete, Caleb Norton, Daniel H Cooper, Gregory Ewald, Mustafa Husaini Sep 2022

Idiopathic Ventricular Fibrillation In A Previously Healthy Recreational Athlete, Caleb Norton, Daniel H Cooper, Gregory Ewald, Mustafa Husaini

2020-Current year OA Pubs

There are several clinical challenges in the survivor of sudden cardiac arrest (SCA), including ensuring that a comprehensive diagnostic evaluation has been performed and providing counseling on return to activity. We report a case of a highly conditioned athlete who presented following aborted SCA during exercise with a diagnosis of idiopathic ventricular fibrillation arrest. (


Effectiveness And Minimum Effective Dose Of App-Based Mobile Health Interventions For Anxiety And Depression Symptom Reduction: Systematic Review And Meta-Analysis, Sheng-Chieh Lu, Mindy Xu, Mei Wang, Angela Hardi, Abby L Cheng, Su-Hsin Chang, Po-Yin Yen Sep 2022

Effectiveness And Minimum Effective Dose Of App-Based Mobile Health Interventions For Anxiety And Depression Symptom Reduction: Systematic Review And Meta-Analysis, Sheng-Chieh Lu, Mindy Xu, Mei Wang, Angela Hardi, Abby L Cheng, Su-Hsin Chang, Po-Yin Yen

2020-Current year OA Pubs

BACKGROUND: Mobile health (mHealth) apps offer new opportunities to deliver psychological treatments for mental illness in an accessible, private format. The results of several previous systematic reviews support the use of app-based mHealth interventions for anxiety and depression symptom management. However, it remains unclear how much or how long the minimum treatment "dose" is for an mHealth intervention to be effective. Just-in-time adaptive intervention (JITAI) has been introduced in the mHealth domain to facilitate behavior changes and is positioned to guide the design of mHealth interventions with enhanced adherence and effectiveness.

OBJECTIVE: Inspired by the JITAI framework, we conducted a …


Multimodal Single Cell Sequencing Implicates Chromatin Accessibility And Genetic Background In Diabetic Kidney Disease Progression, Parker C Wilson, Yoshiharu Muto, Haojia Wu, Anil Karihaloo, Sushrut S Waikar, Benjamin D Humphreys Sep 2022

Multimodal Single Cell Sequencing Implicates Chromatin Accessibility And Genetic Background In Diabetic Kidney Disease Progression, Parker C Wilson, Yoshiharu Muto, Haojia Wu, Anil Karihaloo, Sushrut S Waikar, Benjamin D Humphreys

2020-Current year OA Pubs

The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess …


Concentrated Incarceration And The Public-Housing-To-Prison Pipeline In New York City Neighborhoods, Jay Holder, Ivan Calaff, Brett Maricque, Van C Tran Sep 2022

Concentrated Incarceration And The Public-Housing-To-Prison Pipeline In New York City Neighborhoods, Jay Holder, Ivan Calaff, Brett Maricque, Van C Tran

2020-Current year OA Pubs

Using public housing developments as a strategic site, our research documents a distinct pathway linking disadvantaged context to incarceration-the public-housing-to-prison pipeline. Focusing on New York City Housing Authority (NYCHA) housing developments as a case study, we find that incarceration rates in NYCHA tracts are 4.6 times higher than those in non-NYCHA tracts. More strikingly, 94% of NYCHA tracts report rates above the median value for non-NYCHA tracts. Moreover, 17% of New York State's incarcerated population originated from just 372 NYCHA tracts. Compared with non-NYCHA tracts, NYCHA tracts had higher shares of Black residents and were significantly more disadvantaged. This NYCHA …


Issues With Variability In Electronic Health Record Data About Race And Ethnicity: Descriptive Analysis Of The National Covid Cohort Collaborative Data Enclave, Lily Cook, Juan Espinoza, Nicole G Weiskopf, Nisha Mathews, David A Dorr, Kelly L Gonzales, Adam Wilcox, Charisse Madlock-Brown, N3c Consoritium Sep 2022

Issues With Variability In Electronic Health Record Data About Race And Ethnicity: Descriptive Analysis Of The National Covid Cohort Collaborative Data Enclave, Lily Cook, Juan Espinoza, Nicole G Weiskopf, Nisha Mathews, David A Dorr, Kelly L Gonzales, Adam Wilcox, Charisse Madlock-Brown, N3c Consoritium

2020-Current year OA Pubs

BACKGROUND: The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations.

OBJECTIVE: This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large …


Novel Antiinflammatory Biologics Shaped By Parasite-Host Coevolution, Stephanie M Ryan, Makedonka Mitreva, Et Al Sep 2022

Novel Antiinflammatory Biologics Shaped By Parasite-Host Coevolution, Stephanie M Ryan, Makedonka Mitreva, Et Al

2020-Current year OA Pubs

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of …


Killer-Cell Immunoglobulin-Like Receptor Diversity In An Admixed South American Population, Marlon Castrillon, Nancy D Marin, Amado J Karduss-Urueta, Sonia Y Velasquez, Cristiam M Alvarez Sep 2022

Killer-Cell Immunoglobulin-Like Receptor Diversity In An Admixed South American Population, Marlon Castrillon, Nancy D Marin, Amado J Karduss-Urueta, Sonia Y Velasquez, Cristiam M Alvarez

2020-Current year OA Pubs

Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR).


An Ex Vivo Culture Model Of Kidney Podocyte Injury Reveals Mechanosensitive, Synaptopodin-Templating, Sarcomere-Like Structures, Shumeng Jiang, Farid Alisafaei, Yin-Yuan Huang, Yuan Hong, Xiangjun Peng, Chengqing Qu, Pongpratch Puapatanakul, Sanjay Jain, Jeffrey H Miner, Guy M Genin, Hani Y Suleiman Sep 2022

An Ex Vivo Culture Model Of Kidney Podocyte Injury Reveals Mechanosensitive, Synaptopodin-Templating, Sarcomere-Like Structures, Shumeng Jiang, Farid Alisafaei, Yin-Yuan Huang, Yuan Hong, Xiangjun Peng, Chengqing Qu, Pongpratch Puapatanakul, Sanjay Jain, Jeffrey H Miner, Guy M Genin, Hani Y Suleiman

2020-Current year OA Pubs

Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte …


Smyd3 Impedes Small Cell Lung Cancer Sensitivity To Alkylation Damage Through Rnf113a Methylation-Phosphorylation Cross-Talk, Valentina Lukinović, Clement Oyeniran, Ning Tsao, Joshua R Brickner, Rebecca Rodell, Nima Mosammaparast, Et Al Sep 2022

Smyd3 Impedes Small Cell Lung Cancer Sensitivity To Alkylation Damage Through Rnf113a Methylation-Phosphorylation Cross-Talk, Valentina Lukinović, Clement Oyeniran, Ning Tsao, Joshua R Brickner, Rebecca Rodell, Nima Mosammaparast, Et Al

2020-Current year OA Pubs

Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of …


The Metabolism Of Human Soluble Amyloid Precursor Protein Isoforms Is Quantifiable By A Stable Isotope Labeling-Tandem Mass Spectrometry Method, Justyna A Dobrowolska Zakaria, Randall J Bateman, Monika Lysakowska, Ammaarah Khatri, Dinorah Jean-Gilles, Matthew E Kennedy, Robert Vassar Sep 2022

The Metabolism Of Human Soluble Amyloid Precursor Protein Isoforms Is Quantifiable By A Stable Isotope Labeling-Tandem Mass Spectrometry Method, Justyna A Dobrowolska Zakaria, Randall J Bateman, Monika Lysakowska, Ammaarah Khatri, Dinorah Jean-Gilles, Matthew E Kennedy, Robert Vassar

2020-Current year OA Pubs

Evidence suggests that β-secretase (BACE1), which cleaves Amyloid Precursor Protein (APP) to form sAPPβ and amyloid-β, is elevated in Alzheimer's disease (AD) brains and biofluids and, thus, BACE1 is a therapeutic target for this devastating disease. The direct product of BACE1 cleavage of APP, sAPPβ, serves as a surrogate marker of BACE1 activity in the central nervous system. This biomarker could be utilized to better understand normal APP processing, aberrant processing in the disease setting, and modulations to processing during therapeutic intervention. In this paper, we present a method for measuring the metabolism of sAPPβ and another APP proteolytic product, …


Genome Scanning Of Behavioral Selection In A Canine Olfactory Detection Breeding Cohort, Alexander W Eyre, Isain Zapata, Elizabeth Hare, Katharine M N Lee, Claire Bellis, Jennifer L Essler, Cynthia M Otto, James A Serpell, Carlos E Alvarez Sep 2022

Genome Scanning Of Behavioral Selection In A Canine Olfactory Detection Breeding Cohort, Alexander W Eyre, Isain Zapata, Elizabeth Hare, Katharine M N Lee, Claire Bellis, Jennifer L Essler, Cynthia M Otto, James A Serpell, Carlos E Alvarez

2020-Current year OA Pubs

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration's (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed …


Exit Rates Of Accountable Care Organizations That Serve High Proportions Of Beneficiaries Of Racial And Ethnic Minority Groups, Sunny C Lin, Karen E Joynt Maddox, Andrew M Ryan, Nicholas Moloci, Addison Shay, John Malcolm Hollingsworth Sep 2022

Exit Rates Of Accountable Care Organizations That Serve High Proportions Of Beneficiaries Of Racial And Ethnic Minority Groups, Sunny C Lin, Karen E Joynt Maddox, Andrew M Ryan, Nicholas Moloci, Addison Shay, John Malcolm Hollingsworth

2020-Current year OA Pubs

Importance: The Medicare Shared Savings Program provides financial incentives for accountable care organizations (ACOs) to reduce costs of care. The structure of the shared savings program may not adequately adjust for challenges associated with caring for patients with high medical complexity and social needs, a population disproportionately made up of racial and ethnic minority groups. If so, ACOs serving racial and ethnic minority groups may be more likely to exit the program, raising concerns about the equitable distribution of potential benefits from health care delivery reform efforts.

Objective: To evaluate whether ACOs with a high proportion of beneficaries of racial …


Lrp1 Is A Neuronal Receptor For Α-Synuclein Uptake And Spread, Kai Chen, David M Holtzman, Et Al. Sep 2022

Lrp1 Is A Neuronal Receptor For Α-Synuclein Uptake And Spread, Kai Chen, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The aggregation and spread of α-synuclein (α-Syn) protein and related neuronal toxicity are the key pathological features of Parkinson's disease (PD) and Lewy body dementia (LBD). Studies have shown that pathological species of α-Syn and tau can spread in a prion-like manner between neurons, although these two proteins have distinct pathological roles and contribute to different neurodegenerative diseases. It is reported that the low-density lipoprotein receptor-related protein 1 (LRP1) regulates the spread of tau proteins; however, the molecular regulatory mechanisms of α-Syn uptake and spread, and whether it is also regulated by LRP1, remain poorly understood.

METHODS: We established …


Minimal Change Prion Retinopathy: Morphometric Comparison Of Retinal And Brain Prion Deposits In Creutzfeldt-Jakob Disease, Vanessa S Goodwill, Ian Dryden, Jihee Choi, Chiara De Lillo, Katrin Soldau, Jorge Llibre-Guerra, Henry Sanchez, Christina J Sigurdson, Jonathan H Lin Sep 2022

Minimal Change Prion Retinopathy: Morphometric Comparison Of Retinal And Brain Prion Deposits In Creutzfeldt-Jakob Disease, Vanessa S Goodwill, Ian Dryden, Jihee Choi, Chiara De Lillo, Katrin Soldau, Jorge Llibre-Guerra, Henry Sanchez, Christina J Sigurdson, Jonathan H Lin

2020-Current year OA Pubs

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrP


Opioids Alter Paw Placement During Walking, Confounding Assessment Of Analgesic Efficacy In A Postsurgical Pain Model In Mice, Victoria E Brings, Maria A Payne, Robert W Gereau Iv Sep 2022

Opioids Alter Paw Placement During Walking, Confounding Assessment Of Analgesic Efficacy In A Postsurgical Pain Model In Mice, Victoria E Brings, Maria A Payne, Robert W Gereau Iv

2020-Current year OA Pubs

Introduction: Hind paw-directed assays are commonly used to study the analgesic effects of opioids in mice. However, opioid-induced hyperlocomotion can obscure results of such assays.

Objectives: We aimed to overcome this potential confound by using gait analysis to observe hind paw usage during walking in mice.

Methods: We measured changes in the paw print area after induction of postsurgical pain (using the paw incision model) and treatment with oxycodone.

Results: Paw incision surgery reduced the paw print area of the injured hind paw as mice avoided placing the incised section of the paw on the floor. Surprisingly, oxycodone caused a …


Risk Factors For Shoulder Disorders Among French Workers: Prospective Cohort Study, Julie Bodin, Ronan Garlantézec, Alexis Descatha, Bradley Evanoff, Thierry Thomas, Yves Roquelaure Sep 2022

Risk Factors For Shoulder Disorders Among French Workers: Prospective Cohort Study, Julie Bodin, Ronan Garlantézec, Alexis Descatha, Bradley Evanoff, Thierry Thomas, Yves Roquelaure

2020-Current year OA Pubs

OBJECTIVES: Shoulder disorders are common in the working population. This longitudinal study aimed to explore the relationships between personal factors and occupational organisational, psychosocial, and biomechanical factors and the incidence of shoulder disorders.

METHODS: A total of 3710 workers in the Pays de la Loire region (Loire Valley area, France) were randomly included by their occupational physician in the Cosali cohort between 2002 and 2005. All workers completed a self-administered questionnaire about personal factors and work exposure, and using a standardised physical examination, occupational physicians diagnosed shoulder disorders. Between 2007 and 2010, 1611 workers were re-examined by their occupational physician. …


Remote Symptom Monitoring Of Patients With Cancer Undergoing Radiation Therapy, Ryan Wahidi, Rachel Mintz, Temitope Agabalogun, Lindsey Mayer, Shahed Badiyan, Matthew B. Spraker Sep 2022

Remote Symptom Monitoring Of Patients With Cancer Undergoing Radiation Therapy, Ryan Wahidi, Rachel Mintz, Temitope Agabalogun, Lindsey Mayer, Shahed Badiyan, Matthew B. Spraker

2020-Current year OA Pubs

The goal of the study was to develop and test an automated short message service (SMS) and web service platform using CareSignal for remote symptom monitoring in a diverse population of patients with cancer. Twenty-eight patients with cancer undergoing radiotherapy were recruited at the start of their treatment regimen. Patients received a weekly SMS symptom survey to assess the severity of the side effects they experienced from treatment. An assessment of patient perceptions of the system in terms of patient-provider communication, feasibility, and overall satisfaction was conducted, finding overall good compliance in a sick patient population and patient willingness to …


High-Coverage Whole-Genome Sequencing Of The Expanded 1000 Genomes Project Cohort Including 602 Trios, Marta Byrska-Bishop, Haley J Abel, Allison A Regier, Ira M Hall, Et Al. Sep 2022

High-Coverage Whole-Genome Sequencing Of The Expanded 1000 Genomes Project Cohort Including 602 Trios, Marta Byrska-Bishop, Haley J Abel, Allison A Regier, Ira M Hall, Et Al.

2020-Current year OA Pubs

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning …


Exposure Contrasts Of Pregnant Women During The Household Air Pollution Intervention Network Randomized Controlled Trial, Michael Johnson, Lindsay J Underhill, Et Al. Sep 2022

Exposure Contrasts Of Pregnant Women During The Household Air Pollution Intervention Network Randomized Controlled Trial, Michael Johnson, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to

OBJECTIVES: This paper reports exposure reductions achieved by a liquified petroleum gas (LPG) stove and fuel intervention for pregnant mothers in the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial.

METHODS: The HAPIN trial included 3,195 households primarily using biomass for cooking in Guatemala, India, Peru, and Rwanda. Twenty-four-hour exposures to

RESULTS: Median postrandomization exposures of particulate matter (PM) with aerodynamic diameter

DISCUSSION: Postintervention


Sex Differences In Wild-Type Transthyretin Amyloidosis: An Analysis From The Transthyretin Amyloidosis Outcomes Survey (Thaos), Courtney M Campbell, Samantha Lorusso, Angela Dispenzieri, Arnt V Kristen, Mathew S Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo Garcia-Pavia, Martha Grogan, Doug Chapman, Leslie Amass, Thaos Investigators Sep 2022

Sex Differences In Wild-Type Transthyretin Amyloidosis: An Analysis From The Transthyretin Amyloidosis Outcomes Survey (Thaos), Courtney M Campbell, Samantha Lorusso, Angela Dispenzieri, Arnt V Kristen, Mathew S Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo Garcia-Pavia, Martha Grogan, Doug Chapman, Leslie Amass, Thaos Investigators

2020-Current year OA Pubs

INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

METHODS: THAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021).

RESULTS: Of 1386 patients with ATTRwt …


First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al Sep 2022

First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al

2020-Current year OA Pubs

PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors.

PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed.

RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was …


Risk Factors And Medical Resource Utilization In Us Adults Hospitalized With Influenza Or Respiratory Syncytial Virus In The Hospitalized Acute Respiratory Tract Infection Study, Jessica Hartnett, Prina Donga, Gabriela Ispas, Yannick Vandendijck, David Anderson, Stacey House, Selim Suner Sep 2022

Risk Factors And Medical Resource Utilization In Us Adults Hospitalized With Influenza Or Respiratory Syncytial Virus In The Hospitalized Acute Respiratory Tract Infection Study, Jessica Hartnett, Prina Donga, Gabriela Ispas, Yannick Vandendijck, David Anderson, Stacey House, Selim Suner

2020-Current year OA Pubs

BACKGROUND: Influenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.

METHODS: HARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017-2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post-discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, …


Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick Sep 2022

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …


Association Of Male Hypogonadism With Risk Of Hospitalization For Covid-19, Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan Sep 2022

Association Of Male Hypogonadism With Risk Of Hospitalization For Covid-19, Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan

2020-Current year OA Pubs

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh).

Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh.

Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021.

Exposures: The primary exposure was gonadal status …


Accumulation Of Copy-Back Viral Genomes During Respiratory Syncytial Virus Infection Is Preceded By Diversification Of The Copy-Back Viral Genome Population Followed By Selection, Sébastien A Felt, Emna Achouri, Sydney R Faber, Carolina B López Sep 2022

Accumulation Of Copy-Back Viral Genomes During Respiratory Syncytial Virus Infection Is Preceded By Diversification Of The Copy-Back Viral Genome Population Followed By Selection, Sébastien A Felt, Emna Achouri, Sydney R Faber, Carolina B López

2020-Current year OA Pubs

RNA viruses generate nonstandard viral genomes during their replication, including viral genomes of the copy-back (cbVGs) type that cannot replicate in the absence of a standard virus. cbVGs play a crucial role in shaping virus infection outcomes due to their ability to interfere with virus replication and induce strong immune responses. However, despite their critical role during infection, the principles that drive the selection and evolution of cbVGs within a virus population are poorly understood. As cbVGs are dependent on the virus replication machinery to be generated and replicated, we hypothesized that host factors that affect virus replication exert selective …


An Evaluation Of Patient-Reported Outcomes In Sickle Cell Disease Within A Conceptual Model., Marsha J Treadwell, Swapandeep Mushiana, Sherif M Badawy, Liliana Preiss, Allison A King, Barbara Kroner, Yumei Chen, Jeffrey Glassberg, Victor Gordeuk, Nirmish Shah, Angela Snyder, Theodore Wun, Sickle Cell Disease Implementation Consortium (Scdic) Sep 2022

An Evaluation Of Patient-Reported Outcomes In Sickle Cell Disease Within A Conceptual Model., Marsha J Treadwell, Swapandeep Mushiana, Sherif M Badawy, Liliana Preiss, Allison A King, Barbara Kroner, Yumei Chen, Jeffrey Glassberg, Victor Gordeuk, Nirmish Shah, Angela Snyder, Theodore Wun, Sickle Cell Disease Implementation Consortium (Scdic)

2020-Current year OA Pubs

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains.

METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare.

RESULTS: Higher …


Pregnancy Outcomes Related To The Treatment Of Sarcomas With Anthracyclines And/Or Ifosfamide During Pregnancy, Devon Miller, John A Livingston, Yeonhee Park, Kristi Posey, Sonia Godbole, Keith Skubitz, Steven I Robinson, Mark Agulnik, Lara E Davis, Brian A Van Tine, Angela C Hirbe, Amanda Parkes Sep 2022

Pregnancy Outcomes Related To The Treatment Of Sarcomas With Anthracyclines And/Or Ifosfamide During Pregnancy, Devon Miller, John A Livingston, Yeonhee Park, Kristi Posey, Sonia Godbole, Keith Skubitz, Steven I Robinson, Mark Agulnik, Lara E Davis, Brian A Van Tine, Angela C Hirbe, Amanda Parkes

2020-Current year OA Pubs

BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas.

PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples.

RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and …