Digital Commons Network^™

B Cells Mediate Lung Ischemia/Reperfusion Injury By Recruiting Classical Monocytes Via Synergistic B Cell Receptor/Tlr4 Signaling, Khashayar Farahnak, Yun Zhu Bai, Yuhei Yokoyama, Deniz B. Morkan, Zhiyi Liu, Junedh M. Amrute, Alejandro De Filippis Falcon, Yuriko Terada, Fuyi Liao, Wenjun Li, Hailey M. Shepherd, Ramsey R. Hachem, Varun Puri, Kory J. Lavine, Andrew E. Gelman, Ankit Bharat, Daniel Kreisel, Ruben G. Nava

2020-Current year OA Pubs

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte …

Mypathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment Of A Tissue-Agnostic Cohort Of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors, Christopher J Sweeney, Ron Bose, Et Al.

2020-Current year OA Pubs

No abstract provided.

Drug Preparation, Injection-Related Infections, And Harm Reduction Practices Among A National Sample Of Individuals Entering Treatment For Opioid Use Disorder, Laura R Marks, Michael J Durkin, Kelly Ayres, Matthew Ellis

2020-Current year OA Pubs

BACKGROUND: The rise in injection drug use in the USA has led to an increase in injection site infections. We performed a national survey of people who use drugs to evaluate common drug use preparation, harm reduction practices, and experiences with injection site infections.

METHODS: A survey was disseminated to members of the Survey of Key Informants' Patients Program from 2021 to 2022 and distributed to patients 18 years or older newly entering one of 68 substance use disorder treatment programs across the USA with a primary diagnosis of an opioid use disorder. Participants were surveyed about practices when preparing …

Comprehensive Workflow And Its Validation For Simulating Diffuse Speckle Statistics For Optical Blood Flow Measurements, Lisa Kobayashi Frisk, Manish Verma, Faruk Bešlija, Chen-Hao P Lin, Nishighanda Patil, Sumana Chetia, Jason W Trobaugh, Joseph P Culver, Turgut Durduran

2020-Current year OA Pubs

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (

Identification Of Molecular Subphenotypes In Two Cohorts Of Paediatric Ards, Nadir Yehya, Matt S Zinter, Jill M Thompson, Michelle J Lim, Mark R Hanudel, Mustafa F Alkhouli, Hector Wong, Matthew N Alder, Daniel J Mckeone, E Scott Halstead, Pratik Sinha, Anil Sapru

2020-Current year OA Pubs

BACKGROUND: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions.

METHODS: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers.

FINDINGS: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a …

Factors Affecting The Ability Of Patients With Complex Vascular Anomalies To Navigate The Healthcare System, Bryan Sisk, Sunny Lin, Anna M Kerr

2020-Current year OA Pubs

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the …

Post-Exposure Intranasal Ifnα Suppresses Replication And Neuroinvasion Of Venezuelan Equine Encephalitis Virus Within Olfactory Sensory Neurons, Matthew D Cain, N Rubin Klein, Xiaoping Jiang, Hamid Salimi, Qingping Wu, Mark J Miller, William B Klimstra, Robyn S Klein

2020-Current year OA Pubs

BACKGROUND: Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied.

METHODS: We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure.

RESULTS: We found that immature OSN, which …

Progressive Left Ventricular Remodeling For Predicting Mortality In Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry, Paul F Kantor, Charles E Canter, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes.

METHODS AND RESULTS: We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year …

Human Pluripotent Stem Cell Modeling Of Alveolar Type 2 Cell Dysfunction Caused By Abca3 Mutations, Yuliang L Sun, Erin E Hennessey, Hillary Heins, Ping Yang, Carlos Villacorta-Martin, Julian Kwan, Krithi Gopalan, Marianne James, Andrew Emili, F. Sessions Cole, Jennifer A. Wambach, Darrell N. Kotton

2020-Current year OA Pubs

Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP …

A Flexible, Quantitative Plasmonic-Fluor Lateral Flow Assay For The Rapid Detection Of Orthoebolavirus Zairense And Orthoebolavirus Sudanense, Abraham J Qavi, Qisheng Jiang, M Javad Aman, Hong Vu, Larry Zetlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Frederick Holtsberg, Scott L Crick, Gaya K Amarasinghe

2020-Current year OA Pubs

Filoviruses comprise a family of single-stranded, negative-sense RNA viruses with a significant impact on human health. Given the risk for disease outbreaks, as highlighted by the recent outbreaks across Africa, there is an unmet need for flexible diagnostic technologies that can be deployed in resource-limited settings. Herein, we highlight the use of plasmonic-fluor lateral flow assays (PF-LFA) for the rapid, quantitative detection of an Ebolavirus-secreted glycoprotein, a marker for infection. Plasmonic fluors are a class of ultrabright reporter molecules that combine engineered nanorods with conventional fluorophores, resulting in improved analytical sensitivity. We have developed a PF-LFA for

Overview Of Covid-19 Infection, Treatment, And Prevention In Children, Carol M Kao

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) …

Age-Related Differences In Motor Skill Transfer With Brief Memory Reactivation, Kylie B Tomlin, Brian P Johnson, Kelly P Westlake

2020-Current year OA Pubs

Motor memories can be strengthened through online practice and offline consolidation. Offline consolidation involves the stabilization of memory traces in post-practice periods. Following initial consolidation of a motor memory, subsequent practice of the motor skill can lead to reactivation and reconsolidation of the memory trace. The length of motor memory reactivation may influence motor learning outcomes; for example, brief, as opposed to long, practice of a previously learned motor skill appears to optimize intermanual transfer in healthy young adults. However, the influence of aging on reactivation-based motor learning has been scarcely explored. Here, the effects of brief and long motor …

Associations Between Coordination And Wearable Sensor Variables Vary By Recording Context But Not Assessment Type, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang

2020-Current year OA Pubs

Motor coordination is an important driver of development and improved coordination assessments could facilitate better screening, diagnosis, and intervention for children at risk of developmental disorders. Wearable sensors could provide data that enhance the characterization of coordination and the clinical utility of that data may vary depending on how sensor variables from different recording contexts relate to coordination. We used wearable sensors at the wrists to capture upper-limb movement in 85 children aged 6-12. Sensor variables were extracted from two recording contexts.

Effects Of Cooking With Liquefied Petroleum Gas Or Biomass On Stunting In Infants, William Checkley, Lindsay J Underhill, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown.

METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length …

Liquefied Petroleum Gas Or Biomass Cooking And Severe Infant Pneumonia, Eric D. Mccollum, Victor G. Davila-Roman, Lindsay J. Underhill, Et Al.

2020-Current year OA Pubs

No abstract provided.

Heterozygous Mutations In The C-Terminal Domain Of Copa Underlie A Complex Autoinflammatory Syndrome, Selket Delafontaine, Tarin M. Bigley, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular …

Pathways To Care For Psychosis In Rural Uganda: Mixed-Methods Study Of Individuals With Psychosis, Family Members, And Local Leaders, Yang Jae Lee, Sophie Waimon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Low- and middle-income countries (LMICs) bear a disproportionate burden of mental illness, with limited access to biomedical care. This study examined pathways to care for psychosis in rural Uganda, exploring factors influencing treatment choices.

METHODS: We conducted a mixed-methods study in Buyende District, Uganda, involving 67 in-depth interviews and 4 focus group discussions (data collection continued until thematic saturation was reached) with individuals with psychotic disorders, family members, and local leaders. Structured questionnaires were administered to 41 individuals with psychotic disorders.

RESULTS: Three main themes emerged: (1) Positive attitudes towards biomedical providers, (2) Barriers to accessing biomedical care (3) …

Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer

2020-Current year OA Pubs

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This …

Implementation And Outcomes Of A Pilot Collaborative Surgical Hydrocele Training In Côte D'Ivoire, Kevin Montes, Georgina Angoa, Catherine M Bjerum, Adama Guira, Olivier K Kouadio, Allassane F Ouattara, Gary J Weil, Peter U Fischer, Aboulaye Meite, Benjamin G Koudou, Philip J Budge

2020-Current year OA Pubs

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative …

Implications Of Preoperative Depression For Lumbar Spine Surgery Outcomes: A Systematic Review And Meta-Analysis, Saad Javeed, Braeden Benedict, Salim Yakdan, Samia Saleem, Justin K Zhang, Kathleen Botterbush, Madelyn R Frumkin, Angela Hardi, Brian Neuman, Jay F Piccirillo, Burel R Goodin, Thomas L Rodebaugh, Wilson Z Ray, Jacob K Greenberg, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive.

OBJECTIVE: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery.

DATA SOURCES: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023.

STUDY SELECTION: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between …

Contrast Response Function Estimation With Nonparametric Bayesian Active Learning, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Samyukta Jayakumar, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour

2020-Current year OA Pubs

Multidimensional psychometric functions can typically be estimated nonparametrically for greater accuracy or parametrically for greater efficiency. By recasting the estimation problem from regression to classification, however, powerful machine learning tools can be leveraged to provide an adjustable balance between accuracy and efficiency. Contrast sensitivity functions (CSFs) are behaviorally estimated curves that provide insight into both peripheral and central visual function. Because estimation can be impractically long, current clinical workflows must make compromises such as limited sampling across spatial frequency or strong assumptions on CSF shape. This article describes the development of the machine learning contrast response function (MLCRF) estimator, which …

A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh

2020-Current year OA Pubs

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and …

Process Evaluation Of A Double-Blind Randomized Controlled Trial To Assess The Efficacy And Safety Of A Quadruple Ultra-Low-Dose Treatment For Hypertension Within A Federally Qualified Health Center Network (Quartet Usa), Olutobi A Sanuade, Tyler A Jacobson, Adriana Quintana, Fallon M Flowers, Hiba Abbasi, My H Vu, Abigail S Baldridge, Jairo Mejia, Danielle Lazar, Jody D Ciolino, Mark D Huffman, Namratha R Kandula

2020-Current year OA Pubs

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management.

METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, …

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

PACS News

No abstract provided.

The Response Of Dual-Leucine Zipper Kinase (Dlk) To Nocodazole: Evidence For A Homeostatic Cytoskeletal Repair Mechanism, Laura Devault, Chase Mateusiak, John Palucki, Michael Brent, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNA-seq. This signature includes genes likely …

Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill

2020-Current year OA Pubs

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study.

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Deanna M. Barch, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Washington University Magazine, August 2024

Washington University Magazine

No abstract provided.

Washington University Magazine, April 2024

Washington University Magazine

No abstract provided.

Washington University Magazine, December 2024

Washington University Magazine

No abstract provided.