Medicine and Health Sciences Commons^™

Effect Of Age On Isth-Bat Scores And Low Vwf Diagnosis In The Zimmerman Program, Ferdows Atiq, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

An essential component of low von Willebrand factor (VWF)/type 1 von Willebrand disease (VWD) diagnosis is to identify patients with an increased bleeding phenotype, as most individuals with VWF levels in the 30 to 50 IU/dL range do not bleed. The International Society on Thrombosis and Haemostasis-bleeding assessment tool (ISTH-BAT), widely used for assessing bleeding severity, has recently been shown to be age dependent. Although age may also influence ISTH-BAT scores in individuals with VWF levels between 30 and 50 IU/dL, and subsequently affect low VWF diagnosis, this relationship has not been investigated. Therefore, we analyzed 325 participants from the …

Antibiotic Treatment Limits Survival Of Peripheral And Bone Marrow B-Cell Populations, Lila S Sanning, Forrest C Walker, Arushana A Maknojia, Leran Wang, Haina Jin, Gowri Kalugotla, Crystal Lovato, Katherine Y King, Megan T Baldridge

2020-Current year OA Pubs

Prolonged or broad-spectrum antibiotic courses are associated with intestinal dysbiosis and cytopenias, and depletion of hematopoietic progenitor populations after antibiotics is associated with loss of peripheral immune cells, leading to increased susceptibility to systemic infections. We evaluated the bone marrow hematopoietic compartment in a murine model of antibiotic exposure. Single-cell RNA sequencing revealed a substantial and previously unrecognized depletion of bone marrow B cells at all stages of development in antibiotic-treated mice, further confirmed by flow cytometric analysis. Depletion of the microbiota was associated with rapid changes in the peripheral B-cell compartment, yet fecal microbiota transfer did not rescue either …

Optimal Antibiotic Use In The Intensive Care Unit, Scott T Micek, M Cristina Vazquez Guillamet, Daniel Reynolds, Sarah Matuszak, Lauren Kolodziej, Marin H Kollef

2020-Current year OA Pubs

BACKGROUND: Antibiotic resistance has emerged as one of the most important factors influencing the outcomes of patients with life-threatening infections in the ICU. The increasing prevalence of antibiotic-resistant infections globally highlights the importance of this issue for all intensivists.

MAIN BODY: Antibiotic utilization in the ICU should be optimized to ensure that timely appropriate treatment is administered in a way that minimizes the subsequent emergence of antibiotic resistance. Antibiotic strategies have been developed to assist clinicians in achieving this important balance. Familiarity with local ICU pathogens and their antibiotic susceptibilities is at the forefront of optimizing ICU antibiotic practices. Moreover, …

Integrated Single-Cell Multiomic Profiling Of Caudate Nucleus Suggests Key Mechanisms In Alcohol Use Disorder, Nicholas C Green, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

Alcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq and ATAC-seq on caudate samples from 143 human postmortem brains, including 74 with AUD, we identified 17 distinct cell types. A significant portion of the alcohol-related differences in gene expression were accompanied by a corresponding difference in chromatin accessibility within the gene. We observed transcriptional differences in medium spiny neurons that impact RNA metabolism and immune response pathways. A small cluster of D1/D2 hybrid neurons showed AUD-induced differences distinct from the D1 and D2 types, …

Establishing Priority Pediatric Antimicrobial Stewardship Interventions In The Us: Findings From A Delphi Consensus Study, Harry Obeng, Emmanuel Tetteh, Sara Malone, Matthew Sattler, Monica Abdelnour, Virginia R Mckay, Et Al.

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases.

METHOD: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases …

Dissecting Regulatory Non-Coding Gwas Loci Reveals Fibroblast Causal Genes With Pathophysiological Relevance To Heart Failure, Richard Gill, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Heart failure is caused in part by cardiac remodeling processes that include the death of cardiac myocytes and their replacement by cardiac fibroblasts. Here, we hypothesize that cardiac fibroblasts may harbor epigenetic contexts in which heart disease-associated non-coding SNPs perturb gene expression relevant to disease. To test this, we utilized male primary cardiac fibroblasts to generate high-resolution Hi-C data and integrate it with functional genomic information to annotate and link putative distal regulatory elements in heart disease-associated loci to gene promoters. We identify several target genes with established roles in cardiac fibrosis and/or heart disease (GJA1, TBC1D32, CXCL12, IL6R, and …

Prevalence Of Sleep Disturbance And Associated Risk Factors In Degenerative Cervical Myelopathy, Salim Yakdan, Karan Joseph, Jingyi Zhang, Miguel A Ruiz-Cardozo, Aryan Pradhan, Alisha Dhallan, Faraz Arkam, Willliam Mualem, Garrison Bentz, Diogo P Moniz Garcia, Benjamin Plog, Alexander T Yahanda, Daniel Hafez, Wilson Z Ray, Camilo A Molina, Jacob K Greenberg

2020-Current year OA Pubs

Retrospective Case-Control.

Histologic Assessment In Ulcerative Colitis: A Survey Of Pathologists' Practices And Perspectives, Krithika D Shenoy, Jiannan Li, Adam L Booth, Xiuli Liu

2020-Current year OA Pubs

BACKGROUND: Histologic remission is increasingly recognized as an important endpoint in ulcerative colitis (UC) management. Consensus guidelines on adopting histologic scoring systems in clinical practice are lacking in the United States. This study aimed to assess the knowledge, attitudes, and practices of pathologists, primarily located in North America, regarding histologic evaluation in UC.

METHODS: This study surveyed a group of pathologists who have completed postdoctoral medical training with demonstrated interest and involvement in the field of gastrointestinal pathology to evaluate their knowledge, practices, and perspectives on histologic assessment using standardized scoring systems in clinical practice in UC patients. The survey …

Orsay Virus Variants Isolated From Wild Caenorhabditis Elegans Nematodes, France, Chika Fujii, Susan Vernon, Marie-Anne Félix, David Wang

2020-Current year OA Pubs

Four new variants of Orsay virus were identified from wild isolates of

A Plain Language Summary Publication Of Patients' Survival With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel, Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

What is the purpose of this PLS-P? The purpose of this plain language summary of publication is to help you understand recent findings from Part 1 of the RUBY study (full name ENGOT-EN6/GOG3031/RUBY trial). • Researchers sometimes study new combinations of already approved individual treatments to see if the combinations work well together and if they are safe to prescribe to patients. • In Part 1 of the RUBY study, the combination of

Hydroxyapatite Microspheres Induce Durable Pleurodesis And Are Rapidly Cleared By Pleural Osteoclasts, Yusuke Tanaka, Yuki Takahashi, Yuma Shindo, Lori B. Pitstick, Steven L. Teitelbaum, Wei Zou, Xiangning Wang, Jason C. Woods, Kathryn A. Wikenheiser-Brokamp, Francis X. Mccormack

2020-Current year OA Pubs

Talc pleurodesis is highly effective for preventing recurrence of pneumothorax and pleural effusion, but it can be complicated by dissemination, acute lung injury, lead exposure, and foreign body-induced chronic inflammation and pain. Our objective is to develop a safe, biodegradable, contaminant-free particle for pleurodesis. We used mouse models of pneumothorax and malignant pleural effusion to compare the efficacy and safety of pleurodesis with talc and hydroxyapatite microspheres (HAM). Intrapleural instillation of microspheres induced pleural adhesions, fibrosis, and symphysis as effectively as talc and resulted in more durable protection from experimental pneumothorax. HAM and talc both induced an osteoclastogenic, inflammatory, and …

Gabaergic Interneurons Contribute To The Fatal Seizure Phenotype Of Cln2 Disease Mice, Keigo Takahashi, Nicholas R. Rensing, Elizabeth M. Eultgen, Letitia L. Williams, Sophie H. Wang, Hemanth R. Nelvagal, Steven Q. Le, Marie S. Roberts, Balraj Doray, Edward B. Han, Patricia I. Dickson, Michael Wong, Mark S. Sands, Jonathan D. Cooper

2020-Current year OA Pubs

The cellular etiology of seizures in CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), remains elusive. Given that Cln2R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical GABAergic interneuron populations, we hypothesized that these 2 events might be causally related. To study the cell-autonomous effects of interneuron-specific TPP1 deficiency, we first generated transgenic mice expressing loxP-flanked lysosomal membrane-tethered TPP1 (TPP1LAMP1 mice) on the Cln2R207X/R207X genetic background, and then crossed TPP1LAMP1 mice with Vgat-Cre mice. These Vgat-Cre; TPP1LAMP1 mice accumulated storage material in cortical and striatal interneurons. Vgat-Cre; …

Barriers And Facilitators Of Implementing A Community Workshop Series To Mitigate Maternal-Child Food Insecurity: A Mixed-Methods Re-Aim Evaluation, Kristen Herlosky, Ana Baumann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Community-led workshops offer promising health education models to advance maternal-child health equity by providing culturally congruent spaces for information sharing, resource access, and social support building. This study aimed to (1) document the participatory co-creation of a Community Workshop Series with topics across the Nurturing Care Framework domains (health, nutrition, early learning, security/safety, responsive caregiving) to mitigate maternal-child food insecurity, (2) evaluate CWS effectiveness in increasing participants' knowledge across the Nurturing Care Framework, and (3) identify CWS implementation barriers and facilitators.

METHODS: The study employed two-phases: Phase One engaged members of a Community Advisory Board in participatory research to …

Transcriptional Responses Of Mouse Proximal Colon And Colonoids During Early Whipworm Infection, Hyeim Jung, Joseph F Urban, Bruce A Rosa, Makedonka Mitreva

2020-Current year OA Pubs

Trichuriasis, caused by the parasitic nematode

Pathologist-Like Explainable Ai For Interpretable Gleason Grading In Prostate Cancer, Gesa Mittmann, Nidia Messias, Et Al.

2020-Current year OA Pubs

No abstract provided.

Performance Evaluation Of A Commercial Multiplex Pathogen Panel For Detection Of Bacteria In Sputum Specimens From Non-Icu Patients With Suspected Lower Respiratory Tract Infection, Madeline Gemoules, Tristan T Timbrook, Elizabeth Neuner, Rebekah E Dumm, Tamara Krekel

2020-Current year OA Pubs

Rapid diagnostic testing can improve pathogen detection and lead to targeted antibiotics. The BioFire FilmArray Pneumonia Panel (BFPP) is a multiplex PCR that has displayed strong concordance with traditional microbiologic techniques. However, most existing literature focuses on deep respiratory specimens, and there is sparse literature on performance in sputum specimens. This retrospective, single-center study included adult patients between 1 September 2022 and 31 August 2024 who had collection of a BFPP with standard of care (SOC) culture from a sputum specimen on a non-intensive care unit (ICU) floor or in the emergency department if admitted to a non-ICU floor. Out …

Fiber Recruitment Drives A Phase Transition Of Cell Polarization At A Critical Cell Spacing In Matrix-Mediated Tissue Remodeling, Xiangjun Peng, Yuxuan Huang, Wenyu Kong, Yanan Du, Elliot L Elson, Xi-Qiao Feng, Guy M Genin

2020-Current year OA Pubs

Biological tissues exhibit sharp phase transitions where cells collectively transition from disordered to ordered states at critical densities. We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from a nonmonotonic dependence on nonlinear extracellular matrix (ECM) mechanics: mechanical communication between cells is optimized at intermediate stiffness values where cells can both generate sufficient forces and create strain-stiffened tension bands in the ECM. This balance establishes a critical cell spacing threshold for cell-cell communication ([Formula: see text]100 to 200 [Formula: see text]m) that is conserved across experimental observations for a broad range of cell types and collagen densities. Our model …

Fate Mapping Of Peripherally-Derived Macrophages After Traumatic Brain Injury In Mice Reveals A Long-Lasting Population With A Distinct Transcriptomic Signature, Maria Serena Paladini, Benjamin A Yang, Kristof A Torkenczy, Elma S Frias, Xi Feng, Karen Krukowski, Rene Sit, Maurizio Morri, Wendy Lam, Valentina Pedoia, Stefka Tyanova, Marco Colonna, Amber L Nolan, Susanna Rosi

2020-Current year OA Pubs

Traumatic brain injury (TBI) is an environmental risk factor for dementia and long-term neurological deficits, posing a significant public health challenge. TBI-induced neuroinflammation involves both brain-resident microglia and peripheral monocyte-derived macrophages (MDMs). Previous research has shown that MDMs contribute to the development of long-term memory deficits, yet their long-term behavior following brain infiltration remains unclear. To address this, our study uses two complementary fate-mapping mouse lines, CCR2-creERT2 and Ms4a3-cre, for precise and lasting tracking of MDMs in vivo. Here we show that MDMs persist in the brain for at least 8 months post-TBI in both male and female mice. MDMs …

Genomic Insights Into A Diarrheal Outbreak In Bangladesh Reveal Novel Etec Lineages And Expansion Of Cs23 Colonization Factor, Sadia Isfat Ara Rahman, James M Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic

Estimated Waste Generation From 1 Million Basic Metabolic Panels: A Multisite U.S. Study, Seema Khattri Bhandari, Kwaku Twum, Erving T Laryea, Yaqing Du, Raeshun T Glover, Rachel G Brackbill, William Butler, Khushbu Patel, Christopher W Farnsworth, Christina C Pierre, Steven W Cotten, Joesph R Wiencek

2020-Current year OA Pubs

OBJECTIVES: Clinical laboratory operations consume large amounts of electricity and water and generate considerable quantities of solid waste. In this study, we quantified and compared the estimated solid waste produced from performing one million basic metabolic panels (BMPs) across five major high-throughput chemistry analyzer systems commonly used in the United States. Additionally, we estimated the carbon emissions associated with the electricity and water usage of each analyzer to better understand their environmental impact.

METHODS: Five academic medical centers each using a different clinical chemistry analyzer system, collected their respective annual vendor purchase data (January 2022-December 2022). Consumables including reagent cartridges, …

Apoe-Calypse Tau: Apoe-Tau Synergy In Alzheimer's Disease, Matthew Paul Lennol, Chiara Bordier, Léana Kamelher, Jason D Ulrich, David M Holtzman, Maud Gratuze

2020-Current year OA Pubs

Alzheimer's disease (AD), the most common cause of dementia, is characterized by the accumulation of amyloid-β (Aβ) in senile plaques and abnormally hyperphosphorylated tau proteins in neurofibrillary tangles. While much of the research has focused on Aβ, tau-mediated neurodegeneration is more closely associated with synaptic loss and cognitive decline in AD, emphasizing the need for a deeper understanding of tau pathology. In this context, the interaction between tau and APOE, particularly the main genetic risk factor for AD APOE ε4, remains underexplored. APOE encodes apolipoprotein E (apoE), a protein important in lipid metabolism. In addition to promoting Aβ deposition, emerging …

Investigation Of Lncrna Expression In Newly Diagnosed Multiple Myeloma Reveals A Linc01432-Celf2 Axis As An Inhibitor Of Apoptosis, Richa Mishra, Prasanth Thunuguntla, Dhanusha Duraiyan, Alani Perkin, Katelyn Bagwill, Savannah Gonzales, Catheryn Sizemore, Vanessa Brizuela, Jaiyana King, Stephen Daly, Yoon Jae Chang, Mahdote Abebe, Yash Rajana, Kelly Wichmann, Christ Enyan, Shruthi Rangineni, Mark Fiala, Julie Fortier, Reyka Jayasinghe, Mark Schroeder, Li Ding, Ravi Vij, John Dipersio, Jessica Silva-Fisher

2020-Current year OA Pubs

Multiple myeloma (MM) is an incurable malignancy of plasma cells, with over 35,000 new cases diagnosed annually in the United States. Despite an expanding arsenal of approved therapies, nearly all patients relapse, and mechanisms underlying disease progression remain poorly understood. In particular, the role of long non-coding RNAs (lncRNAs) in MM progression and treatment response is largely unexplored. To address this gap, we performed transcriptome sequencing of newly diagnosed MM (NDMM) patient samples and compared individuals with short progression-free survival (PFS; < 24 months) to those with prolonged PFS (>24 months) following standard first-line therapy. We identified 157 lncRNAs upregulated in patients with short PFS, and prioritized the …

Understanding The Role Of Street Medicine In Harm Reduction: A Case Study Of Street Medicine St. Louis, Ari Gzesh, Jeremiah S Truel, Danielle R Adams, Luke Zabotka, Sara Malone, Nathanial S Nolan

2020-Current year OA Pubs

BACKGROUND: Homelessness results from, and exacerbates, various social determinants of health, including poverty, racism, and inadequate healthcare access, which are further compounded by physical and mental health challenges. The street medicine movement seeks to address these disparities by providing direct medical care and harm reduction services to unsheltered homeless in low-barrier settings. The development of trust is critical to providing this form of care. Few studies have sought to understand the factors influencing trust development in street medicine encounters.

METHODS: This case study of Street Medicine St. Louis aims to explore the factors that influence trust and how trust development …

Rev-Erbα Regulates Brain Nad+ Levels And Tauopathy Via An Nfil3-Cd38 Axis, Jiyeon Lee, Ryeonghwa Kang, Sohui Park, Ibrahim O Saliu, Minsoo Son, Jaymie R Voorhees, Julie M Dimitry, Elsa I Quillin, Brian V Lananna, Young-Ah Goo, Guoyan Zhao, Erik S Musiek, Et Al.

2020-Current year OA Pubs

Nicotinamide adenine dinucleotide (NAD

Chimeric Antigen Receptor Natural Killer (Car-Nk) Cells: From Preclinical Promise To Clinical Reality In Cancer Immunotherapy, Hunter Cassidy Cochran, Kevin Ashkan Ghobadi, Armin Ghobadi

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR-NK cells offer the potential for "off-the-shelf" treatments with a favorable safety profile, due in part to their innate capacity for HLA-unrestricted tumor targeting and an absence of graft-versus-host disease. Landmark clinical studies using cord blood - derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the …

The Triglyceride-Glucose Index And Risk Of End-Stage Renal Disease Across Different Durations Of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study, Mi-Sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee

2020-Current year OA Pubs

BACKGRUOUND: This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.

METHODS: We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.

RESULTS: Over 6,967,381 person-years of …

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Jessie R Zhang, Liana M Valin, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Lisa Emrick, William J Craigen, Stephen M Sykes, Tim Schedl, Stephen C Pak, Et Al.

2020-Current year OA Pubs

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

Using Implementation Mapping To Optimize The Impact Of Universal School Meals: A Type Iii Hybrid Implementation-Effectiveness Study Protocol, Gabriella M Mcloughlin, Angel Smith, Alex R Dopp, Resa Jones, Omar Martinez, Shiriki Kumanyika, Recai Yucel, Ross C Brownson, Jennifer Orlet Fisher

2020-Current year OA Pubs

BACKGROUND: Provision of government subsidized school meals at no charge to all students in income-eligible schools (Universal School Meals) is a critical policy approach to address food insecurity and risk for obesity in school-aged children. However, despite documented benefits, implementation challenges remain, which limit the uptake and associated impact of this provision. To ensure the longevity of this policy approach, equity-focused solutions that center the needs of those tasked with implementation and the most vulnerable Universal School Meals recipients are necessary. The aims of this study are to develop equity-focused implementation strategies and test them through a hybrid type III …

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Aging And The Spectral Properties Of Brain Hemodynamics, Ki Yun Park, Abraham Z Snyder, Manu S Goyal, Timothy O Laumann, John J Lee, Babatunde Adeyemo, Nicholas Metcalf, Andrei G Vlassenko, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

Cerebral glucose metabolism (CMRGlc) systematically decreases with advancing age. We sought to identify correlates of decreased CMRGlc in the spectral properties of fMRI signals imaged in the task-free state. Lifespan resting-state fMRI data acquired in 455 healthy adults (ages 18-87 years) and cerebral metabolic data acquired in a separate cohort of 94 healthy adults (ages 25-45 years, 65-85 years) were analyzed. The spectral properties of the fMRI data were characterized in terms of the relative predominance of slow versus fast activity using the spectral slope (SS) measure. We found that the relative proportion of fast activity increases with advancing age …