Digital Commons Network^™

How Augmin Establishes The Angle Of The Microtubule Branch Site, Sophie M Travis, Jodi Kraus, Collin T Mcmanus, Kiana Golden, Rui Zhang, Sabine Petry

2020-Current year OA Pubs

How microtubules (MTs) are generated in the proper orientation is essential to understanding how the cytoskeleton organizes a cell and MT-dependent events such as cell division. In the spindle, most MTs are generated through the branching MT nucleation pathway. In this pathway, new MTs are nucleated from the side of existing MTs and oriented at a shallow angle by the branching factor augmin, ensuring that both MTs have the same polarity. Yet, how augmin binds MTs and sets the branch angle has remained unclear. Here, we report the cryo-electron microscopy structure of an augmin subcomplex on the MT. This structure …

Complement Activation In Secondary Thrombotic Microangiopathies, Johann Morelle, Fernando Caravaca-Fontan, Fadi Fakhouri, Eleni Frangou, Annette Bruchfeld, Jürgen Floege, Safak Mirioglu, Sarah M Moran, Stefanie Steiger, Kate I Stevens, Onno Y K Teng, Selda Aydin, Anuja Java, Sjoerd A M E G Timmermans, Andreas Kronbichler

2020-Current year OA Pubs

Secondary thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases associated with a high risk of kidney failure and death despite available therapeutic strategies. Strong evidence implicates complement activation in the pathogenesis of secondary TMA, and emerging data increasingly suggest that pharmacological blockade of the complement improves the outcomes in patients with secondary TMA. Certain forms of secondary TMA, including postpartum TMA, TMA with coexisting hypertensive emergency and de novo TMA after kidney transplantation exhibit a high prevalence of pathogenic variants in complement genes, similar to those observed in primary atypical haemolytic uraemic syndrome. These conditions should be considered as …

Brca2 Deficiency And Replication Stress Drive Apobec3-Mediated Genomic Instability, Kathy Situ, Abby M Green, Et Al.

2020-Current year OA Pubs

BRCA2 plays a critical role in stabilizing stalled replication forks, yet critical gaps remain in understanding how BRCA2 deficiency triggers fork collapse and drives genomic instability. Here, we identify cytidine deaminase APOBEC3B as a key driver of this process. Using a unique uracil-in-DNA probe, we show that BRCA2 loss promotes APOBEC3B-mediated uracil accumulation in single-stranded DNA (U-ssDNA) at stalled forks. These lesions when processed by UNG2 and APE1, trigger fork collapse and release ssDNA fragments into the cytoplasm, activating NF-κB signaling. This in turn upregulates APOBEC3B expression, establishing a self-reinforcing loop that amplifies cytidine deamination at stalled forks and exacerbates …

Chromatin Profiling Identifies Putative Dual Roles For H3k27me3 In Regulating Cell Type-Specific Genes And Transposable Elements In Choanoflagellates, James M Gahan, Lily W Helfrich, Laura A Wetzel, Natarajan V Bhanu, Zuo-Fei Yuan, Benjamin A Garcia, Robert J Klose, Alex De Mendoza, David S Booth

2020-Current year OA Pubs

Chromatin-based mechanisms contribute to the exquisite regulation of gene expression during animal development. But how those mechanisms evolved remains elusive. Here we investigate chromatin regulatory features in the closest relatives of animals, choanoflagellates. In a model choanoflagellate Salpingoeca rosetta, we compare chromatin accessibility and histone modifications to gene expression. Accessible genomic regions in S. rosetta primarily correspond to gene promoters, and we find no evidence of distal gene regulatory elements that resemble enhancers deployed to regulate developmental genes in animals. Remarkably, the histone modification H3K27me3 decorates genes with cell type-specific expression, revealing a functional similarity in S. rosetta and animals. …

Enampt/Tlr4 Signaling Drives Pah Cellular Phenotypic Switching And Lung Vascular Remodeling, Mohamed Ahmed, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

BACKGROUND: The attenuation of cellular phenotypic switchingdriving PAH vascular remodeling remains an unmet therapeutic need. As eNAMPT (nicotinamide phosphoribosyltransferase)/TLR4 signaling significantly contributes to PH pathobiology, an eNAMPT-neutralizing ALT-100 mAb was utilized to rescue monocrotaline (MCT) and hypoxia/Sugen (Hy/Su) preclinical PH rat models and to evaluate eNAMPT/TLR4 involvement in endothelial cell (EC), smooth muscle cell (SMC) and monocyte/macrophage phenotypic switching.

METHODS: MCT-PH or Hy/Su-PH rats received IgG or ALT-100 mAb (subQ, beginning week 4) with measurements of PH severity and lung tissue scRNAseq at day 42.

RESULTS: PH severity indices (hemodynamic, histologic, vascular remodeling) were significantly attenuated in MCT-PH and Hy/Su-PH …

Impact Of Transplant Conditioning, Npm1 Mutations, And Measurable Residual Disease In Flt3-Itd Acute Myeloid Leukemia, Mark J Levis, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in …

Bioresponsive Hydrogel For On-Demand Nonhormonal Contraception, Giovanni M Pauletti, Pankaj Dwivedi, Ping Li, Aluet Borrego-Alvarez, Hidemi S Yamamoto, Julie Lewis, Sarah Alobaidi, Amel Ibrahim, Raina N Fichorova, Celia M Santi

2020-Current year OA Pubs

The utility of bioresponsive multifunctional hydrogel compositions for biomedical applications is rapidly increasing due to the diverse array of biological stimuli that can profoundly alter physicochemical gel properties that benefit therapeutic interventions. The purpose of this research is to explore a bioresponsive hydrogel as a drug-free bioengineering concept to fortify the natural physical contraceptive barriers at the cervicovaginal junction. The results of this research demonstrate that a hydrogel comprising 4% (

Associations Of Early-Adulthood Adiposity With Breast Parenchymal Tissue Complexity Within Premenopausal Women, Sneha Das Gupta, Kayla Getz, Juanita Hernandez Lopez, Debbie L Bennett, Adetunji T Toriola, Aimilia Gastounioti

2020-Current year OA Pubs

BACKGROUND: Early-adulthood adiposity is associated with breast cancer risk. This study aims to evaluate the associations of early-adulthood adiposity with an emerging biomarker of breast cancer risk, breast parenchymal complexity, within premenopausal women.

METHODS: We retrospectively analyzed early-adulthood adiposity data and screening digital mammograms (DMs) of 326 premenopausal women (age in years; median: 48; range: 34-58) recruited at our institution. Adiposity measures were either assessed by trained personnel or self-reported by participants. DMs were analyzed using a well-validated computational imaging pipeline consisting of automated breast segmentation and radiomic feature extraction modules. The extracted radiomic features were fused into woman-specific breast …

Whole-Genome Sequencing Reveals Individual And Cohort Level Insights Into Chromosome 9p Syndromes., Yingxi Wang, Eleanor I Sams, Rachel Slaugh, Sandra Crocker, Emily Cordova Hurtado, Sophia Tracy, Ying-Chen Claire Hou, Christopher Markovic, Kostandin Valle, Victoria Tate, Khadija Belhassan, Elizabeth Appelbaum, Titilope Akinwe, Rodrigo T Starosta, Yang Cao, Amber Neilson, Yu Liu, Nathaniel Jensen, Reza Ghasemi, Tina Lindsay, Juana Manuel, Sophia Couteranis, Milinn Kremitzki, Jack Ustanik, Thomas Antonacci, Jeffrey K Ng, Andrew Emory, Laura Metz, Tracie Deluca, Katherine N Lyons, Toni Sinnwell, Brianne Thomeczek, Katherine A King, Christina A Gurnett, Susan K Dutcher, Catherine Gooch, Yang E Li, Amjad Horani, Michael Heinz, Richard Head, Robert Fulton, Lucinda Antonacci-Fulton, Xiaoxia Cui, Robi D Mitra, F Sessions Cole, Julie Neidich, Patricia I Dickson, Jeffrey Milbrandt, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous genomic efforts on chromosome 9p deletion and duplication syndromes have utilized low-resolution strategies (i.e., karyotypes, chromosome microarrays). These studies have provided important initial insights into these syndromes. This current study is the first large-scale whole-genome sequencing (WGS) study of 100 individuals from families with chromosome 9p syndromes.

METHODS: Through the newly formed 9P-ARCH (Advanced Research in Chromosomal Health: Genomic, Phenotypic, and Functional Aspects of 9p-Related syndromes) research network, we assembled a cohort of individuals from families with chromosome 9p syndromes. WGS was applied to 100 individuals, and other genomic technologies were applied to a subset of individuals. To …

Socioeconomic Disparities And Severity Of Gunshot Injuries In Israel: A Retrospective Review Of National Trauma Registry Data From Public Hospitals 2019-2022, Ahmad Awwad, Layalee Abo Naser, Arnona Ziv, Adi Givon, Jennifer Moriatis Wolf, Jason A Strelzow, Eli Farhat, Shai Luria, Israel Trauma Group

2020-Current year OA Pubs

BACKGROUND: Socioeconomic status (SES) is correlated with gunshot violence. This study examined the associations between SES and the severity of gunshot injuries in Israel.

METHODS: The Israel National Trauma Registry was reviewed for all violence-related gunshot wound patients who were admitted to all public hospitals in Israel from 2019 to 2022. Self-inflicted injuries were excluded. This time frame preceded the regional military conflict that began in October 2023 and did not include any military-related activity. The registry records patient demographics including ethnicity. Severity was assessed on the Injury Severity Score (ISS), and SES was categorized into 10 clusters based on …

Post-Traumatic Stress And Genetic Interactions Affect Tobacco And Alcohol Use After Trauma: Findings From A Multi-Ancestry Cohort, Henri M. Garrison-Desany, Stacey L. House, Et Al.

2020-Current year OA Pubs

No abstract provided.

Transgenerational Adaptation To Hypoxia, Kathleen Kim, Ariel Telger, Gautam Sarkar, Sharan Surya, M Hafiz Rothi, Michael P Meers, Simon Yuan Wang, Eric Lieberman Greer

2020-Current year OA Pubs

Epigenetic inheritance alerts naïve descendants to prepare for stresses that could still be present, whereas distant descendants return to a basal state after several generations without stress. However, organisms are frequently exposed to stresses successively across generations. We found that parental hypoxia exposure increased P0 longevity, caused intergenerational lipid reduction, and elicited transgenerational fertility reduction that was dependent on generationally transmitted small RNAs. Here, we find that

Transdiagnostic Alterations In White Matter Microstructure Associated With Suicidal Thoughts And Behaviours In The Enigma Suicidal Thoughts And Behaviours Consortium, Laura S. Van Velzen, Alexander S. Hatoum, Et Al.

2020-Current year OA Pubs

No abstract provided.

Ambient Trichloroethylene Exposure And Parkinson Disease Risk In Medicare Beneficiaries, Brittany Krzyzanowski, Kassu Mehari Beyene, Jay R. Turner, Brad A. Racette

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Trichloroethylene (TCE) is an important environmental contaminant in the United States due to widespread use industrially. Epidemiologic studies suggest that occupational exposure to TCE and TCE-contaminated drinking water may increase the risk of Parkinson disease (PD). The aim of this study was to investigate the nationwide relationship between ambient TCE and PD risk.

METHODS: We performed a nationwide, population-based, case-control study to investigate the association between incident PD in US Medicare beneficiaries aged 67 years and older in 2016-2018 and their residential exposure to ambient (outdoor) TCE in 2002. We assigned residence based on the latitude and …

Facilitation As An Effective Strategy To Reduce Excessive Antibiotic Prophylaxis In Children's Hospitals: A Stepped-Wedge Cluster Randomized Controlled Trial, Virginia Mckay, Sara Malone, Emmanuel Tetteh, Jacqueline Saito, Shawn Rangel, Kelly Bono, Jade Tao, Jingxia Liu, Harry Obeng, Andrew Atkinson, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Excessive use of postoperative prophylactic antibiotics in children's hospitals is a significant public health concern, leading to increased risks of infections like Clostridioides difficile, multidrug-resistant organisms, and unnecessary healthcare costs. Antibiotic stewardship programs (ASPs) are designed to optimize antibiotic use, but ideal strategies for implementing evidence-based guidelines remain unclear. We tested facilitation, a dynamic process where trained individuals support healthcare personnel in bridging evidence-practice gaps, as a promising strategy for the de-implementation of unnecessary postoperative antibiotics in healthcare.

METHODS: The OPerAtiC trial employed a stepped-wedge cluster randomized controlled design across nine hospitals to compare the effectiveness of two ASP-led …

Genetic Influences For Distinct Impulsivity Domains Are Differentially Associated With Early Substance Use Initiation: Results From The Abcd Study, Ethan Kinstler, Aaron J Gorelik, Sarah E Paul, Adamya Aggarwal, Emma C Johnson, Melissa A Cyders, Arpana Agrawal, Ryan Bogdan, Alex P Miller

2020-Current year OA Pubs

BACKGROUND: Impulsivity is among the strongest correlates of substance involvement (i.e. a broad continuum of substance-related behaviors), and distinct domains (e.g. sensation seeking [SS] and urgency) are differentially correlated, phenotypically and genetically, with unique substance involvement stages. Examining whether polygenic influences for distinct impulsivity domains are differentially predictive of early substance use initiation - a major risk factor for later problematic use - may improve our understanding of the role of impulsivity in addiction etiology.

METHODS: Data collected from participants of genetically inferred European ancestry enrolled in the Adolescent Brain Cognitive Development Study

RESULTS: SS-PGS was significantly associated with any …

Viral Oncogenes Drive Biphenotypic Lymphoproliferative Malignancy In Transgenic Mice, Daniel A Rauch, John Harding, Ancy Joseph, Lee Ratner

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma (ATLL) and viral oncogenic proteins, Tax and Hbz, are critical drivers of malignancy. Expression of both CD2 and CD20 has been described in a subset of ATLL cases. Transgenic mice were engineered to monitor lymphoma and leukemia after expression of Hbz and doxycycline-inducible Tax in activated T cells under the regulation of the human granzyme B (GZMB) promoter. These mice spontaneously developed lymphoproliferative disease characterized by the expansion and transformation of Cd2 + Cd20 + cells resulting in lymphoma and / or leukemia with involvement of …

Time-Of-Day And Age-Related Patterns In Cerebrospinal Fluid Glucose And Protein, Joshua P Koleske, Shelei Pan, Thanda Meehan, Maren Loe, Diego M Morales, Brendan P Lucey, Erik Musiek, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Known circadian variations in cerebrospinal fluid (CSF) flow and composition include fluctuations in electrolytes, hormones, and neurotransmitters. However, how commonly measured CSF constituents, such as protein and glucose, vary by time-of-day is understudied. Here, we identify and compare time-of-day differences in CSF protein and glucose from patients who underwent CSF collection during clinical care.

METHODS: Patients with CSF collected between June 2018 and May 2023 at thirteen hospitals within our institution's health system were identified. Clinical, demographic and laboratory results were recorded. CSF results were divided into 1- and 4-hour intervals based on time-of-day and patient age. Patients were …

Type I Hybrid Effectiveness-Implementation Randomised Controlled Trial To Address Intergenerational Impact Of War Trauma And Resilience Among Second-Generation Refugee Children In The Usa: Resettled Refugee Families For Healing (Rrf4h) Study Protocol, Nhial T Tutlam, Tewodros W Liyew, Theresa S Betancourt, Byron J Powell, Shenyang Guo, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

INTRODUCTION: Children from refugee families resettled in the USA face higher risks of serious mental health challenges compared with their native-born peers. Research shows that refugee youth in high-income countries frequently suffer from trauma-associated disorders such as post-traumatic stress disorder (PTSD), depression and anxiety. The high prevalence of trauma-associated mental health problems among these youth may be attributed to their own trauma exposure, especially if born in conflict zones, and post-resettlement challenges like poverty, acculturation difficulties, racism and discrimination. However, they may also suffer from the effects of intergenerational trauma, where parental war trauma impacts them. This study aims to …

Genetic Determinants And Genomic Consequences Of Non-Leukemogenic Somatic Point Mutations, Joshua S. Weinstock, C Charles Gu, Et Al.

2020-Current year OA Pubs

No abstract provided.

Vaccine Effectiveness Against Influenza A(H1n1), A(H3n2), And B-Associated Hospitalizations, United States, 1 September 2023 To 31 May 2024, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023 to February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season.

METHODS: During 1 September 2023 to 31 May 2024, a multistate sentinel surveillance network of 24 medical centers in 20 US states enrolled adults aged ≥18 years hospitalized with acute respiratory illness. Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine effectiveness (VE) against influenza-associated hospitalization …

Consensus-Based Disease Definitions For Endocrine Immune-Related Adverse Events Of Immune Checkpoint Inhibitors, Ling Zhu, Huda Al-Bahadili, Et Al.

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements …

Dendritic Atoh1a+ Cells Serve As Merkel Cell Precursors During Skin Development And Regeneration, Evan W Craig, Erik C Black, Samantha Z Fernandes, Ahlan S Ferdous, Camille E A Goo, Sheridan M Sargent, Elgene J A Quitevis, Avery Angell Swearer, Nathaniel G Yee, Jimann Shin, Lilianna Solnica-Krezel, Jeffrey P Rasmussen

2020-Current year OA Pubs

Sensory cells often adopt specific morphologies that aid in the detection of external stimuli. Merkel cells encode gentle touch stimuli in vertebrate skin and adopt a reproducible shape characterized by spiky actin-rich microvilli that emanate from the cell surface. The mechanisms by which Merkel cells acquire this stereotyped morphology from keratinocyte progenitors are unknown. Here, we establish that dendritic Merkel cells (dMCs) express atonal homolog 1a (atoh1a), extend dynamic filopodial processes, and arise in transient waves during zebrafish skin development and regeneration. We find that dMCs share molecular similarities with both basal keratinocytes and Merkel cells, yet display mesenchymal-like behaviors, …

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, …

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 …

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 …

Modeling Neurodegeneration In The Retina And Strategies For Developing Pan-Neurodegenerative Therapies, Emily L Ward, Aaron Diantonio, Et Al.

2020-Current year OA Pubs

BACKGROUND: Glaucoma Research Foundation's third Catalyst for a Cure team (CFC3) was established in 2019 to uncover new therapies for glaucoma, a leading cause of blindness. In the 2021 meeting "Solving Neurodegeneration," (detailed in Mol Neurodegeneration 17(1), 2022) the team examined the failures of investigational monotherapies, issues with translatability, and other significant challenges faced when working with neurodegenerative disease models. They emphasized the need for novel, humanized models and proposed identifying commonalities across neurodegenerative diseases to support the creation of pan-neurodegenerative disease therapies. Since then, the fourth Catalyst for a Cure team (CFC4) was formed to explore commonalities between glaucoma …

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 …