Digital Commons Network^™

The Association Of Caregiver Attitudes, Information Sources, And Trust With Hpv Vaccine Initiation Among Adolescents, Akila Anandarajah, Thembekile Shato, Sarah Humble, Alan R Barnette, Heather M Brandt, Lisa M Klesges, Vetta L Sanders Thompson, Michelle I Silver

2020-Current year OA Pubs

This study described caregiver attitudes and the information sources they access about HPV vaccination for adolescents and determined their influence on human papillomavirus (HPV) vaccination initiation. An online survey was administered to 1,016 adults in July 2021. Participants were eligible if they were the caregiver of a child aged 9-17 residing in Mississippi, Arkansas, Tennessee, Missouri, and select counties in Southern Illinois. Multivariate logistic regression was used to estimate the association of caregiver attitudes and information sources with HPV vaccination. Information from doctors or healthcare providers (87.4%) and internet sources other than social media (31.0%) were the most used sources …

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen

Emergent Microenvironments Of Nucleoli, Matthew R King, Kiersten M Ruff, Rohit V Pappu

2020-Current year OA Pubs

In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types …

Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai

2020-Current year OA Pubs

OBJECTIVE: Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

MATERIALS AND METHODS: Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected …

Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: We aimed to develop and validate a novel multimodal framework

MATERIALS AND METHODS: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal …

Evaluating The Impact Of A Year-Long External Mentorship Pilot Program In Classical Hematology, Zoya Qureshy, Pooja Nair, Sara K Vesely, Allison A King, Alfred I Lee, Nathan T Connell, Annette Von Drygalski, Ida Wong-Sefidan, Martina C Murphy, Ronak H Mistry, Rebecca L Zon, Erin G Reid, Josel Fritz, Soo J Park

2020-Current year OA Pubs

Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology Medical Educators Institute. Thirty-five hematology/oncology fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected …

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Use Of Guideline-Recommended Heart Failure Drugs In High-, Middle-, And Low-Income Countries: A Systematic Review And Meta-Analysis, Gautam Satheesh, Rupasvi Dhurjati, Laura Alston, Fisaha Tesfay, Rashmi Pant, Ehete Bahiru, Claudia Bambs, Anubha Agarwal, Sanne A E Peters, Abdul Salam, Isabelle Johansson

2020-Current year OA Pubs

Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall …

Constitutive Upregulation Of Transcription Factors Underlies Permissive Bradyzoite Differentiation In A Natural Isolate Of Toxoplasma Gondii, Jing Xia, Yong Fu, Wanyi Huang, Taher Uddin, L David Sibley

2020-Current year OA Pubs

UNLABELLED:

IMPORTANCE:

Conditioning With Anti-Cd47 And Anti-Cd117 Plus Jak Inhibition Enables Toxic Payload-Free Allogeneic Transplantation, Stephen P Persaud, Aditya R Yelamali, Julie K Ritchey, John F Dipersio

2020-Current year OA Pubs

No abstract provided.

Efficacy Of Parp Inhibitor Therapy After Targeted Braf/Mek Failure In Advanced Melanoma, Jordan Phillipps, George Nassief, Renee Morecroft, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Ari Vanderwalde, Soo Park, Omar Butt, Alice Zhou, George Ansstas

2020-Current year OA Pubs

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option …

A Genetic Screen In Drosophila Uncovers A Role For Senseless-2 In Surface Glia In The Peripheral Nervous System To Regulate Cns Morphology, Haluk Lacin, Yuqing Zhu, Jose T Dipaola, Beth A Wilson, Yi Zhu, James B Skeath

2020-Current year OA Pubs

Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS maintains its characteristic form. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure in Drosophila, but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila, we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Analysis of whole genome sequencing data wedded to genetic studies uncovered the affected gene for …

Fetal Mavs And Type I Ifn Signaling Pathways Control Zikv Infection In The Placenta And Maternal Decidua, Yael Alippe, Leran Wang, Reyan Coskun, Stéfanie P Muraro, Fang R Zhao, Michelle Elam-Noll, J Michael White, Daiana M Vota, Vanesa C Hauk, Jeffrey I Gordon, Scott A Handley, Michael S Diamond

2020-Current year OA Pubs

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater …

First Case Of Hiv Seroconversion With Integrase Resistance Mutations On Long-Acting Cabotegravir For Prevention In Routine Care, Catherine A Koss, Rupa R Patel, Et Al.

2020-Current year OA Pubs

BACKGROUND: Long-acting cabotegravir (CAB-LA) is highly effective for HIV prevention, but delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance were observed in trials. We report the first case in routine clinical care of HIV infection on CAB-LA with INSTI resistance.

METHODS: The SeroPrEP study enrolls individuals in the United States who acquire HIV on pre-exposure prophylaxis modalities to assess diagnostics, antiretroviral (ARV) drug levels, resistance, and treatment outcomes. Resistance mutations in full-length HIV-1 integrase were identified by single-genome sequencing (SGS). Cabotegravir concentrations in plasma and hair segments were measured by liquid chromatography-tandem mass spectrometry.

RESULTS: A 23-year-old gender-nonbinary …

Cyclic Testing Of Six-Strand Suture Techniques For Zone 2 Flexor Tendon Lacerations, Nozomu Kusano, Melissa A Zaegel, Matthew J Silva

2020-Current year OA Pubs

BACKGROUND: Biomechanical analysis using cyclic testing for repaired flexor tendons is a clinically relevant method. The aim of this study was to evaluate the tensile properties of two six-strand suture techniques, the triple looped suture and Yoshizu #1 suture techniques using cyclic testing under simulating early active mobilization conditions.

METHODS: Twenty-five flexor digitorum profundus tendons harvested from fresh frozen human cadaver hands were repaired in zone 2 utilizing one of three repair techniques: the 2-strand modified Kessler (MK) technique as a control, the triple looped suture (TLS) and Yoshizu #1 suture (Y1) techniques. In each suture technique, 4-0 monofilament nylon …

Beta-Hydroxybutyrate Levels And Risk Of Diabetic Ketoacidosis In Adults With Type 1 Diabetes Treated With Sotagliflozin, Schafer Boeder, Michael J Davies, Janet B Mcgill, Richard Pratley, Manon Girard, Phillip Banks, Jeremy Pettus, Satish Garg

2020-Current year OA Pubs

No abstract provided.

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

Antiretroviral Therapy And Cardiovascular Risk In People With Hiv In The United States-An Updated Analysis, Luis Parra-Rodriguez, John M Sahrmann, Anne M Butler, Margaret A Olsen, William G Powderly, Jane A O'Halloran

2020-Current year OA Pubs

BACKGROUND: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens.

METHODS: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE.

RESULTS: Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months …

Investigating The Use Of Signal Detection Information In Supervised Learning-Based Image Denoising With Consideration Of Task-Shift, Kaiyan Li, Hua Li, Mark A Anastasio

2020-Current year OA Pubs

PURPOSE: Recently, learning-based denoising methods that incorporate task-relevant information into the training procedure have been developed to enhance the utility of the denoised images. However, this line of research is relatively new and underdeveloped, and some fundamental issues remain unexplored. Our purpose is to yield insights into general issues related to these task-informed methods. This includes understanding the impact of denoising on objective measures of image quality (IQ) when the specified task at inference time is different from that employed for model training, a phenomenon we refer to as "task-shift."

APPROACH: A virtual imaging test bed comprising a stylized computational …

Regulatory Transposable Elements In The Encyclopedia Of Dna Elements, Alan Y Du, Jason D Chobirko, Xiaoyu Zhuo, Cédric Feschotte, Ting Wang

2020-Current year OA Pubs

Transposable elements (TEs) comprise ~50% of our genome, but knowledge of how TEs affect genome evolution remains incomplete. Leveraging ENCODE4 data, we provide the most comprehensive study to date of TE contributions to the regulatory genome. We find 236,181 (~25%) human candidate cis-regulatory elements (cCREs) are TE-derived, with over 90% lineage-specific since the human-mouse split, accounting for 8-36% of lineage-specific cCREs. Except for SINEs, cCRE-associated transcription factor (TF) motifs in TEs are derived from ancestral TE sequence more than expected by chance. We show that TEs may adopt similar regulatory activities of elements near their integration site. Since human-mouse divergence, …

A Rad18-Ubc13-Palb2-Rnf168 Axis Mediates Replication Fork Recovery In Brca1-Deficient Cancer Cells, Emily Cybulla, Sierra Wallace, Alice Meroni, Jessica Jackson, Sumedha Agashe, Mithila Tennakoon, Mangsi Limbu, Annabel Quinet, Elena Lomonosova, Hollie Noia, Stephanie Tirman, Matthew Wood, Alessandro Vindigni, Et Al.

2020-Current year OA Pubs

BRCA1/2 proteins function in genome stability by promoting repair of double-stranded DNA breaks through homologous recombination and by protecting stalled replication forks from nucleolytic degradation. In BRCA1/2-deficient cancer cells, extensively degraded replication forks can be rescued through distinct fork recovery mechanisms that also promote cell survival. Here, we identified a novel pathway mediated by the E3 ubiquitin ligase RAD18, the E2-conjugating enzyme UBC13, the recombination factor PALB2, the E3 ubiquitin ligase RNF168 and PCNA ubiquitination that promotes fork recovery in BRCA1- but not BRCA2-deficient cells. We show that this pathway does not promote fork recovery by preventing replication fork reversal …

Dual Color Optogenetic Tool Enables Heart Arrest, Bradycardic, And Tachycardic Pacing In Drosophila Melanogaster, Elena Gracheva, Yuxuan Wang, Jiantao Zhu, Fei Wang, Abigail Matt, Matthew Fishman, Hongwu Liang, Chao Zhou

2020-Current year OA Pubs

In order to facilitate cardiovascular research to develop non-invasive optical heart pacing methods, we have generated a double-transgenic Drosophila melanogaster (fruit fly) model suitable for optogenetic pacing. We created a fly stock with both excitatory H134R-ChR2 and inhibitory eNpHR2.0 opsin transgenes. Opsins were expressed in the fly heart using the Hand-GAL4 driver. Here we describe Hand > H134R-ChR2; eNpHR2.0 model characterization including bi-directional heart control (activation and inhibition) upon illumination of light with distinct wavelengths. Optical control and real-time visualization of the heart function were achieved non-invasively using an integrated light stimulation and optical coherence microscopy (OCM) system. OCM produced high-speed …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Single-Cell Analysis Of Chromatin And Expression Reveals Age- And Sex-Associated Alterations In The Human Heart, David F Read, Yiing Lin, Et Al.

2020-Current year OA Pubs

Sex differences and age-related changes in the human heart at the tissue, cell, and molecular level have been well-documented and many may be relevant for cardiovascular disease. However, how molecular programs within individual cell types vary across individuals by age and sex remains poorly characterized. To better understand this variation, we performed single-nucleus combinatorial indexing (sci) ATAC- and RNA-Seq in human heart samples from nine donors. We identify hundreds of differentially expressed genes by age and sex and find epigenetic signatures of variation in ATAC-Seq data in this discovery cohort. We then scale up our single-cell RNA-Seq analysis by combining …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

2020-Current year OA Pubs

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in

Mice Lacking Astn2 Have Asd-Like Behaviors And Altered Cerebellar Circuit Properties, Michalina Hanzel, Kayla Fernando, Susan E Maloney, Zachi Horn, Shiaoching Gong, Kärt Mätlik, Jiajia Zhao, H Amalia Pasolli, Søren Heissel, Joseph D Dougherty, Court Hull, Mary E Hatten

2020-Current year OA Pubs

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with

Single-Cell Analysis Of Innate Spinal Cord Regeneration Identifies Intersecting Modes Of Neuronal Repair, Vishnu Muraleedharan Saraswathy, Lili Zhou, Mayssa H Mokalled

2020-Current year OA Pubs

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an …

Sac1 Links Phosphoinositide Turnover To Cryptococcal Virulence, Elizabeth A Gaylord, Hau Lam Choy, Guohua Chen, Sydney L Briner, Tamara L Doering

2020-Current year OA Pubs

No abstract provided.

Development Of Vla4 And Cxcr4 Antagonists For The Mobilization Of Hematopoietic Stem And Progenitor Cells, Peter G Ruminski, Michael P Rettig, John F Dipersio

2020-Current year OA Pubs

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and …

Dominance Analysis To Assess Solute Contributions To Multicomponent Phase Equilibria, Daoyuan Qian, Hannes Ausserwoger, Tomas Sneideris, Mina Farag, Rohit V Pappu, Tuomas P J Knowles

2020-Current year OA Pubs

Phase separation in aqueous solutions of macromolecules underlies the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phases. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes. How do different solutes contribute to the driving forces for phase separation? To answer this question, we introduce a formalism we term energy dominance analysis. This approach rests on analysis of shapes of the dilute phase boundaries, slopes of tie lines, and changes to dilute phase concentrations in response to perturbations of concentrations of different solutes. The framework …