Medicine and Health Sciences Commons^™

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

Comparative Analysis Of Outcomes In Adult Spinal Deformity Patients With Proximal Junctional Kyphosis Or Failure Initially Fused To Upper Versus Lower Thoracic Spine, Oluwatobi O Onafowokan, Munish Chandra Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Biomechanics Of Fibrillin Microfibrils: Lessons From The Ciliary Zonule, Pooja Rathaur, Juan Rodriguez, John Kuchtey, Samuel Insignares, Wendell B Jones, Rachel W Kuchtey, Steven Bassnett

2020-Current year OA Pubs

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints <  5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …

M1 Recruitment During Interleaved Practice Is Important For Encoding, Not Just Consolidation, Of Skill Memory, Taewon Kim, Hakjoo Kim, Benjamin A Philip, David L Wright

2020-Current year OA Pubs

The primary motor cortex (M1) is crucial for motor skill learning. We examined its role in interleaved practice, which enhances retention (vs. repetitive practice) through M1-dependent consolidation. We hypothesized that cathodal transcranial direct current stimulation (ctDCS) to M1 would disrupt retention. We found that ctDCS reduced retention due to weakened encoding during acquisition, not disrupted consolidation. These results highlight M1's broad role in encoding and retention of novel motor skills.

Number Of Prescription Medications And Overall Survival In Metastatic Castrate-Resistant Prostate Cancer, Carley R Pickett, Daniel B Eaton, Krishny Karunanandaa, Emily Cybulla, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Melanie P Subramanian, Varun Puri, Martin W Schoen

2020-Current year OA Pubs

No abstract provided.

Addressing Lung Truncation In 99mtc-Maa Spect/Ct For 90y Microsphere Radioembolization Treatment Planning, M Allan Thomas, Richard Laforest, John Karageorgiou, Dan Giardina, Tyler J Fraum, Chris D Malone, Justin K Mikell

2020-Current year OA Pubs

BACKGROUND: Prior studies have established that macroaggregated albumin (MAA)-SPECT/CT offers more robust lung shunt fraction (LSF) and lung mean absorbed dose (LMD) estimates in

METHODS: Lung truncation was simulated in 56 cases with adequate (> 90%, mean: 98%) lung coverage in MAA-SPECT/CT by removing slices in ~ 5 mm increments from the lung apices to the diaphragm. A wide range of lung coverages from 100% to <  1% in ~ 2% increments were created. LSF and LMD were calculated with four methods. (1) 2D planar imaging standard (not truncated), truncated lung SPECT/CT data was: (2) used with no corrections (SPECT

RESULTS: Averaged across simulated lung coverages from 40 to 80%, percent errors relative to non-truncated data for SPECT

CONCLUSION: LSF and LMD can be estimated for

Microglial Cd2ap Deficiency Exerts Protection In An Alzheimer's Disease Model Of Amyloidosis, Lingliang Zhang, David M. Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer's disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.

METHODS: CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. …

The Improving Treatment Decisions For Patients With Aortic Stenosis Through Shared Decision Making (Impact Sdm) Study: Study Protocol For A Cluster Randomized Stepped Wedge Trial, Karen Sepucha, Nishath Quader, Alexander A Brescia, Et Al.

2020-Current year OA Pubs

BACKGROUND: The American College of Cardiology, American Heart Association, and Centers for Medicare and Medicaid Services recommend shared decision-making (SDM) for patients with severe aortic stenosis choosing between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Although tools such as patient decision aids (DAs) and training in SDM have been shown to improve SDM, implementation of SDM and DAs is limited. The IMproving treatment decisions for Patients with AortiC stenosis Through Shared Decision Making (IMPACT SDM) study aims to (1) determine the effectiveness of the interventions (a DA and clinician SDM training) in achieving SDM (primary outcome) …

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …

Conventional Cytogenetic Analysis Of Solid Tumor Abnormalities: A 25-Year Review Of Proficiency Test Results From The College Of American Pathologists/American College Of Medical Genetics And Genomics Cytogenetics Committee, Rachel K Vanderscheldon, Yang Cao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Experimental Pain Sensitivity And Parental Pain Catastrophizing, Gourav Banerjee, Joel Brown, Alana Mcmichael, Arbi Ben Abdallah, Sarah Buday, Deanna M Barch, Thomas Baranski, Simon Haroutounian, Jacob Aubuchon, Hadas Nahman-Averbuch

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Variability in biopsychosocial factors can explain the interindividual variability in pain. One factor that can impact pain is the pain catastrophizing level. Interestingly, parental pain catastrophizing is related to the severity of the clinical pain of their children. This study explored whether parental pain catastrophizing is also associated with their children's experimental pain sensitivity.

METHODS: Forty-five healthy girls (mean age 12.07 ± 1.47 years) and one of their parents participated in this study. Parents completed the Pain Catastrophizing Scale (PCS) about their child's pain (PCS-Parent

RESULTS: No significant relationships were found between the experimental pain sensitivity measures and either …

Understanding Rare Genetic Variants Within The Terminal Pathway Of Complement System In Preeclampsia, A Inkeri Lokki, Michael Triebwasser, Emma Daly, Finnpec Core Investigator Group, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri

2020-Current year OA Pubs

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p value = 0.01). In addition, one predisposing rare variant …

First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al.

2020-Current year OA Pubs

PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the rate of dose-limiting toxicities, adverse events (including immune mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of …

Changes In Reproductive Health Information-Seeking Behaviors After The Dobbs Decision: Systematic Search Of The Wikimedia Database, Mackenzie Lemieux, Cyrus Zhou, Caroline Cary, Jeannie Kelly

2020-Current year OA Pubs

BACKGROUND: After the US Supreme Court overturned Roe v. Wade, confusion followed regarding the legality of abortion in different states across the country. Recent studies found increased Google searches for abortion-related terms in restricted states after the Dobbsv. Jackson Women's Health Organization decision was leaked. As patients and providers use Wikipedia (Wikimedia Foundation) as a predominant medical information source, we hypothesized that changes in reproductive health information-seeking behavior could be better understood by examining Wikipedia article traffic.

OBJECTIVE: This study aimed to examine trends in Wikipedia usage for abortion and contraception information before and after the Dobbs decision.

METHODS: Page …

Transcriptomic Landscape Of Mammalian Ventral Pallidum At Single-Cell Resolution, Lite Yang, Lisa Z Fang, Michelle R Lynch, Chang S Xu, Hannah J Hahm, Yufen Zhang, Monique R Heitmeier, Vincent D Costa, Vijay K Samineni, Meaghan C Creed

2020-Current year OA Pubs

The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used single-nucleus RNA sequencing and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding …

Genomic Surveillance Of Sars-Cov-2 In Nepal, Binod Khadka, Kathie A Mihindukulasuriya, Lindsay Droit, Anne M Paredes, Scott A Handley, David Wang, Et Al.

2020-Current year OA Pubs

During the COVID-19 pandemic, Nepal, like other countries, faced emerging SARS-CoV-2 variants. To evaluate the circulating variants, 278 samples collected between September 2021 and March 2022 were sequenced in the country. From these, 229 high-quality genomes were obtained (82.97% Omicron and 17.03% Delta) highlighting the genomic diversity of SARS-CoV-2 in Nepal.

Out-Of-Focus Signal Rejection For In Vivo Po2 Measurements Using Two-Photon Phosphorescence Lifetime Microscopy, Qi Pian, Baoqiang Li, Ikbal Şencan-Eğilmez, Xiaojun Cheng, Jay Dubb, Xinyue Huang, Buyin Fu, Srinivasa Rao Allu, Mohammad Abbas Yaseen, Anna Devor, Sergei A Vinogradov, Sava Sakadžić

2020-Current year OA Pubs

Two-photon phosphorescence lifetime microscopy has been a key tool for studying cerebral oxygenation in mice. However, the accuracy of the partial pressure of oxygen (pO

Estimation Of Prevalence Of Autoimmune Diseases In The United States Using Electronic Health Record Data, Aaron H. Abend, Albert M. Lai, Et Al.

2020-Current year OA Pubs

BACKGROUNDPrevious epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease.METHODSTo estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time.RESULTSOur findings indicate that over 15 million people, or 4.6% of …

A Potent Pan-Sarbecovirus Neutralizing Antibody Resilient To Epitope Diversification, Laura E Rosen, Zhuoming Liu, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, …

Malaria Parasites Require A Divergent Heme Oxygenase For Apicoplast Gene Expression And Biogenesis, Amanda Mixon Blackwell, Yasaman Jami-Alahmadi, Armiyaw S Nasamu, Shota Kudo, Akinobu Senoo, Celine Slam, Kouhei Tsumoto, James A Wohlschlegel, Jose Manuel Martinez Caaveiro, Daniel E Goldberg, Paul A Sigala

2020-Current year OA Pubs

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection,

Whole-Blood Model Reveals Granulocytes As Key Sites Of Dengue Virus Propagation, Expanding Understanding Of Disease Pathogenesis, Hansa Praneechit, Somchai Thiemmeca, Dararat Prayongkul, Kessiri Kongmanas, Dumrong Mairiang, Nuntaya Punyadee, Adisak Songjaeng, Nattaya Tangthawornchaikul, Nasikarn Angkasekwinai, Kanokwan Sriruksa, Yupin Suputtamongkol, Wannee Limpitikul, John P Atkinson, Panisadee Avirutnan

2020-Current year OA Pubs

Dengue virus (DENV) infection poses a significant global health threat, yet our understanding of its immunopathogenesis remains incomplete due to limitations of existing models. Here, we establish an

Incidence, Healthcare And Out-Of-Pocket Costs, And Mortality Of Clostridioides Difficile Infection Among Us Adults Aged 18 To 64 Years, Holly Yu, Tamuno Alfred, Jingying Zhou, Jennifer Judy, Margaret A. Olsen

2020-Current year OA Pubs

No abstract provided.

Unraveling The Role Of Uils, A Urea-Induced Acyl-Homoserine Lactonase That Enhances Serratia Marcescens Fitness, Interbacterial Competition, And Urinary Tract Infection, Marisel R Tuttobene, Brayan S Arango Gil, Gisela Di Venanzio, Javier F Mariscotti, Rodrigo Sieira, Mario F Feldman, María Soledad Ramirez, Eleonora García Véscovi

2020-Current year OA Pubs

UNLABELLED:

IMPORTANCE: This work reveals the acyl-homoserine lactonase

Type I Interferon Signaling In Dendritic Cells Limits Direct Antigen Presentation And Cd8+ T Cell Responses Against An Arthritogenic Alphavirus, Christopher B Bullock, Leran Wang, Brian C Ware, Ngan Wagoner, Ray A Ohara, Tian-Tian Liu, Pritesh Desai, Bjoern Peters, Kenneth M Murphy, Scott A Handley, Thomas E Morrison, Michael S Diamond

2020-Current year OA Pubs

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8

Type I Ifn-Mediated Net Release Promotes Mycobacterium Tuberculosis Replication And Is Associated With Granuloma Caseation, Chanchal Sur Chowdhury, Rachel L Kinsella, Michael E Mcnehlan, Sumanta K Naik, Daniel S Lane, Priyanka Talukdar, Asya Smirnov, Neha Dubey, Ananda N Rankin, Samuel R Mckee, Reilly Woodson, Abigail Hii, Sthefany M Chavez, Darren Kreamalmeyer, Wandy Beatty, Joshua T Mattila, Christina L Stallings

2020-Current year OA Pubs

Neutrophils are the most abundant cell type in the airways of tuberculosis patients. Mycobacterium tuberculosis (Mtb) infection induces the release of neutrophil extracellular traps (NETs); however, the molecular regulation and impact of NET release on Mtb pathogenesis are unknown. We find that during Mtb infection in neutrophils, PAD4 citrullinates histones to decondense chromatin that gets released as NETs in a manner that can maintain neutrophil viability and promote Mtb replication. Type I interferon promotes the formation of chromatin-containing vesicles that allow NET release without compromising plasma membrane integrity. Analysis of nonhuman primate granulomas supports a model where neutrophils are exposed …

A Trivalent Mucosal Vaccine Encoding Phylogenetically Inferred Ancestral Rbd Sequences Confers Pan-Sarbecovirus Protection In Mice, James Brett Case, Shilpa Sanapala, Suzanne M Scheaffer, Déborah Carolina Carvalho Dos Anjos, Lucas J Adams, Nadia Soudani, Chieh-Yu Liang, Baoling Ying, Adrianus C M Boon, Daved H Fremont, Sean P J Whelan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains. Using genetic and immunological approaches, we demonstrate that vaccine-induced protection unexpectedly is conferred principally …

Prenatal Social Disadvantage Is Associated With Alterations In Functional Networks At Birth, Ashley N Nielsen, Regina L Triplett, Lourdes M Bernardez, Ursula A Tooley, Max P Herzberg, Rachel E Lean, Sydney Kaplan, Dominique Meyer, Jeanette K Kenley, Dimitrios Alexopoulos, David Losielle, Aidan Latham, Tara A Smyser, Arpana Agrawal, Josh S Shimony, Joshua J Jackson, J Philip Miller, Marcus E Raichle, Barbara B Warner, Cynthia E Rogers, Chad M Sylvester, Deanna M Barch, Joan L Luby, Christopher D Smyser

2020-Current year OA Pubs

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated …

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, As Monotherapy And In Combination With Targeted Therapy In Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib Ember Study, Komal L Jhaveri, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in

METHODS: An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label.

RESULTS: Overall, 262 patients with ER+/HER2- ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 …