Medicine and Health Sciences Commons^™

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 …

Common Single-Base Insertions In The Vntr Of The Carboxyl Ester Lipase (Cel) Gene Are Benign And Also Likely To Arise Somatically In The Exocrine Pancreas, Ranveig S Brekke, Anny Gravdal, Khadija El Jellas, Grace E Curry, Jianguo Lin, Steven J Wilhelm, Solrun J Steine, Eric Mas, Stefan Johansson, Mark E Lowe, Bente B Johansson, Xunjun Xiao, Karianne Fjeld, Anders Molven

2020-Current year OA Pubs

The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in …

Hiv-1 Capsid Stability And Reverse Transcription Are Finely Balanced To Minimize Sensing Of Reverse Transcription Products Via The Cgas-Sting Pathway, Jenna E Eschbach, Maritza Puray-Chavez, Shawn Mohammed, Qiankun Wang, Ming Xia, Lin-Chen Huang, Liang Shan, Sebla B Kutluay

2020-Current year OA Pubs

UNLABELLED: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization

IMPORTANCE: …

Deficiency Of Il-22-Binding Protein Enhances The Ability Of The Gut Microbiota To Protect Against Enteric Pathogens, José L Fachi, Blanda Di Luccia, Susan Gilfillan, Hao-Wei Chang, Christina Song, Jiye Cheng, Marina Cella, Marco Aurelio Vinolo, Jeffrey I Gordon, Marco Colonna

2020-Current year OA Pubs

Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the

Wormbase 2024: Status And Transitioning To Alliance Infrastructure, Paul W Sternberg, Tim Schedl, Et Al.

2020-Current year OA Pubs

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate …

Stay On Track: A Pilot Randomized Control Trial On The Feasibility Of A Diet And Exercise Intervention In Patients With Breast Cancer Receiving Radiotherapy, Gopika Senthilkumar, Aronne M Schottstaedt, Lindsay L Peterson, Lauren N Pedersen, Christopher R Chitambar, Alexis Vistocky, Anjishnu Banerjee, John M Longo, Tracy Kelly, Adam Currey, Melinda R Stolley, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy.

EXPERIMENTAL DESIGN: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations. The control group (n = 22) was administered a diet/exercise information binder. All patients received a Fitbit, and at …

Examining The Gateway Hypothesis And Mapping Substance Use Pathways On Social Media: Machine Learning Approach, Yunhao Yuan, Erin Kasson, Jordan Taylor, Patricia Cavazos-Rehg, Munmun De Choudhury, Talayeh Aledavood

2020-Current year OA Pubs

BACKGROUND: Substance misuse presents significant global public health challenges. Understanding transitions between substance types and the timing of shifts to polysubstance use is vital to developing effective prevention and recovery strategies. The gateway hypothesis suggests that high-risk substance use is preceded by lower-risk substance use. However, the source of this correlation is hotly contested. While some claim that low-risk substance use causes subsequent, riskier substance use, most people using low-risk substances also do not escalate to higher-risk substances. Social media data hold the potential to shed light on the factors contributing to substance use transitions.

OBJECTIVE: By leveraging social media …

Novel Loss-Of-Function Variants Expand Abcc9-Related Intellectual Disability And Myopathy Syndrome, Stephanie Efthymiou, Robert C Tryon, Colin G Nichols, Et Al.

2020-Current year OA Pubs

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle …

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Alport Syndrome And Alport Kidney Diseases - Elucidating The Disease Spectrum, Pongpratch Puapatanakul, Jeffrey H. Miner

2020-Current year OA Pubs

PURPOSE OF REVIEW: With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 , and COL4A5 , represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases".

RECENT FINDINGS: Several research studies have focused on the genotype-phenotype correlation under the latest classification scheme of AS. The historic diagnoses of …

Patient Engagement In Designing, Conducting, And Disseminating Clinical Pain Research: Immpact Recommended Considerations, Simon Haroutounian, Katherine J. Holzer, Et Al.

2020-Current year OA Pubs

In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are …

Interferons And Tuft Cell Numbers Are Bottlenecks For Persistent Murine Norovirus Infection, Somya Aggarwal, Forrest C. Walker, James S. Weagley, Broc T. Mccune, Xiaofen Wu, Lawrence A. Schriefer, Heyde Makimaa, Dylan Lawrence, Pratyush Sridhar, Megan T. Baldridge

2020-Current year OA Pubs

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes …

Impact Of Gram-Negative Bacilli Resistance Rates On Risk Of Death In Septic Shock And Pneumonia, Alison M Hixon, Scott Micek, Victoria J Fraser, Marin Kollef, M Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship.

METHODS: We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We …

National Hiv And Hcv Screening Rates For Hospitalized People Who Use Drugs Are Suboptimal And Heterogeneous Across 11 Us Hospitals, Leo Knudsen Westgard, Laura R Marks, Et Al.

2020-Current year OA Pubs

BACKGROUND: To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD.

METHODS: Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations.

RESULTS: Hospitals …

Preexisting Diabetes And Breast Cancer Treatment Among Low-Income Women, Bayu Begashaw Bekele, Min Lian, Chester Schmaltz, Tracy Greever-Rice, Pratibha Shrestha, Ying Liu

2020-Current year OA Pubs

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain.

OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023.

EXPOSURE: Preexisting …

Complement Regulation In The Eye: Implications For Age-Related Macular Degeneration, Georgia A. Wilke, Rajendra S. Apte

2020-Current year OA Pubs

Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and …

Targeting Dendritic Cell Dysfunction To Circumvent Anti-Pd1 Resistance In Head And Neck Cancer, Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri

2020-Current year OA Pubs

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed.

EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.

RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due …

Spatial Mapping Of Hematopoietic Clones In Human Bone Marrow, Andrew L Young, Hannah C Davis, Maggie J Cox, Tyler M Parsons, Samantha C Burkart, Diane E Bender, Lulu Sun, Stephen T Oh, Grant A Challen

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution …

Accelerating Medicines Partnership® Schizophrenia (Amp® Scz): Rationale And Study Design Of The Largest Global Prospective Cohort Study Of Clinical High Risk For Psychosis, Cassandra M J Wannan, Michael P. Harms, Daneil Mamah, Spero C. Nicholas, Et Al.

2020-Current year OA Pubs

No abstract provided.

Implementation Of Health It For Cancer Screening In Us Primary Care: Scoping Review, Constance Owens-Jasey, Maura M Kepper, Alex T Ramsey, Et Al.

2020-Current year OA Pubs

BACKGROUND: A substantial percentage of the US population is not up to date on guideline-recommended cancer screenings. Identifying interventions that effectively improve screening rates would enhance the delivery of such screening. Interventions involving health IT (HIT) show promise, but much remains unknown about how HIT is optimized to support cancer screening in primary care.

OBJECTIVE: This scoping review aims to identify (1) HIT-based interventions that effectively support guideline concordance in breast, cervical, and colorectal cancer screening provision and follow-up in the primary care setting and (2) barriers or facilitators to the implementation of effective HIT in this setting.

METHODS: Following …

Pml::Rara And Gata2 Proteins Interact Via Dna Templates To Induce Aberrant Self-Renewal In Mouse And Human Hematopoietic Cells, Casey D S Katerndahl, Olivia R S Rogers, Ryan B Day, Ziheng Xu, Nichole M Helton, Sai Mukund Ramakrishnan, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin "pioneering factor" GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies …

Disordered Clock Protein Interactions And Charge Blocks Turn An Hourglass Into A Persistent Circadian Oscillator, Meaghan S Jankowski, Daniel Griffith, Divya G Shastry, Jacqueline F Pelham, Garrett M Ginell, Joshua Thomas, Pankaj Karande, Alex S Holehouse, Jennifer M Hurley

2020-Current year OA Pubs

Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa. We identified residues required for FRQ's interaction with its partner protein FRH, the mutation of which demonstrated FRH is necessary for persistent clock oscillations but not repression of …

Myadm Binds Human Parechovirus 1 And Is Essential For Viral Entry, Wenjie Qiao, Christopher M Richards, Youlim Kim, James R Zengel, Siyuan Ding, Harry B Greenberg, Jan E Carette

2020-Current year OA Pubs

Human parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we …

Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification, Christopher J Buswinka, Jinkyung Kim, Anthony J Ricci, Mark A Rutherford, Et Al.

2020-Current year OA Pubs

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …

Biomolecular Condensates Form Spatially Inhomogeneous Network Fluids, Furqan Dar, Samuel R Cohen, Diana M Mitrea, Aaron H Phillips, Gergely Nagy, Wellington C Leite, Christopher B Stanley, Jeong-Mo Choi, Richard W Kriwacki, Rohit V Pappu

2020-Current year OA Pubs

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct …

Single-Cell T-Cell Receptor Repertoire Profiling In Dogs, My H Hoang, Zachary L Skidmore, Hans Rindt, Shirley Chu, Bryan Fisk, Jennifer A Foltz, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan J Bivens, Carol N Reinero, Todd A Fehniger, Malachi Griffith, Jeffrey N Bryan, Obi L Griffith

2020-Current year OA Pubs

Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). scTCRseq and integration with scRNA data have not been demonstrated on companion dogs with cancer. Here, five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma are selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. Single-cell suspensions of PBMCs or lymph node aspirates are profiled using scRNA and dog-specific scTCRseq primers. In total, 77,809 V(D)J-expressing cells are detected, with an average of 3498 …

An Approach To Identify Gene-Environment Interactions And Reveal New Biological Insight In Complex Traits, Xiaofeng Zhu, Yihe Yang, Noah Lorincz-Comi, Gen Li, Amy R Bentley, Paul S De Vries, Michael Brown, Alanna C Morrison, Charles N Rotimi, W James Gauderman, Dabeeru C Rao, Hugues Aschard, Charge Gene-Lifestyle Interactions Working Group

2020-Current year OA Pubs

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci …

Evidence And Sources Of Placebo Effects In Transcranial Direct Current Stimulation During A Single Session Of Visuospatial Working Memory Practice, Andrew Hooyman, Nicole K Haikalis, Peiyuan Wang, Heidi M Schambra, Keith R Lohse, Sydney Y Schaefer

2020-Current year OA Pubs

Transcranial direct current stimulation (tDCS) can be used to non-invasively augment cognitive training. However, the benefits of tDCS may be due in part to placebo effects, which have not been well-characterized. The purpose of this study was to determine whether tDCS can have a measurable placebo effect on cognitive training and to identify potential sources of this effect. Eighty-three right-handed adults were randomly assigned to one of three groups: control (no exposure to tDCS), sham tDCS, or active tDCS. The sham and active tDCS groups were double-blinded. Each group performed 20 min of an adapted Corsi Block Tapping Task (CBTT), …