Evaluation of Oligo-Fucoidan as a potentially beneficial adjunct to BNCT in a novel oral cancer and precancer experimental model.

The high mortality and morbidity of Head and Neck cancer patients and the toxicity associated to oncological treatments suggest the need for more selective and non-toxic therapies. BNCT (Boron Neutron Capture Therapy) is based on the capture reaction between boron-10, selectively targeted to tumor tissue, and a thermal neutron. In this study, an oral cancer and precancer model was used to study the therapeutic effect and radiotoxicity of BNCT mediated by BPA (boronphenylalanine) [BPA-BNCT] at short and medium-term follow-up.

Sox9 in the epicardium: Implications for cell invasion, differentiation, and coronary vascular development.

The epicardium is the mesothelial lining of the heart and is a source of progenitor cells during heart development, giving rise to an invasive population of mesenchymal cells which differentiate into cardiac fibroblasts, mural cells, and other cell types essential for heart structure and function. Previously, we showed that epicardial-specific deletion of the gene encoding SRY-box transcription factor 9 (SOX9) impairs epicardial-derived cell invasion and reduces their contribution to the atrioventricular valve mesenchyme. In this study, we use single-cell RNA-sequencing to investigate broader roles of Sox9 in the epicardium as it relates to epicardial invasion, differentiation, and vascular development.

Breaking research silos to achieve equitable precision medicine in rheumatology.

Health disparities in rheumatic disease are well established and urgently need addressing. Obstacles to precision medicine equity span both the clinical and the research domains, with a focus placed on structural barriers limiting equitable health care access and inclusivity in research. Less articulated factors include the use of inaccurate population descriptors and the existence of research silos in rheumatology research, which creates a knowledge gap that precludes addressing the health disparities and fulfilling the goals of precision medicine to understand the 'full patient'.

Cobaltabis(Dicarbollide) [-COSAN] for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model.

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3'-Co(CBH)], abbreviated as Na[-COSAN]) in the hamster cheek pouch oral cancer model and the Na[-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of B-enriched trimethylammonium salt of -[7,8-CBH]-carborane, along with the cesium and sodium salts of [-COSAN] cobaltabis(dicarbollide) are reported here for the first time.

Clarity for the language of race, ethnicity and genetic ancestry in rheumatology.

As the pace of genetic discovery has accelerated, so too has the need for clinicians and researchers to acknowledge and understand the impact of language in scientific publications. The use of inaccurate language contributes to systemic bias and eugenic ideologies that remain pervasive in biomedical science, including in rheumatology.

Establishing an infrastructure to optimize the integration of genomics into research: Results from a precision health needs assessment.

Researchers across the translational research continuum have emphasized the importance of integrating genomics into their research program. To date capacity and resources for genomics research have been limited; however, a recent population-wide genomic screening initiative launched at the Medical University of South Carolina in partnership with Helix has rapidly advanced the need to develop appropriate infrastructure for genomics research at our institution. We conducted a survey with researchers from across our institution (n = 36) to assess current knowledge about genomics health, barriers, and facilitators to uptake, and next steps to support translational research using genomics.

Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants.

We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling.

Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.

Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated.

Extending an Antiracism Lens to the Implementation of Precision Public Health Interventions.

Precision public health holds promise to improve disease prevention and health promotion strategies, allowing the right intervention to be delivered to the right population at the right time. Growing concerns underscore the potential for precision-based approaches to exacerbate health disparities by relying on biased data inputs and recapitulating existing access inequities. To achieve its full potential, precision public health must focus on addressing social and structural drivers of health and prominently incorporate equity-related concerns, particularly with respect to race and ethnicity.

Therapeutic Efficacy, Radiotoxicity and Abscopal Effect of BNCT at the RA-3 Nuclear Reactor Employing Oligo-Fucoidan and Glutamine as Adjuvants in an Ectopic Colon Cancer Model in Rats.

Boron neutron capture therapy (BNCT) is based on the preferential uptake of B compounds by tumors, followed by neutron irradiation. The aim of this study was to assess, in an ectopic colon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immune response associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (Comb-BNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared to the "standard" BPA-BNCT protocol usually employed in clinical trials. All treatments were carried out at the RA-3 nuclear reactor.

Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer.

Boron neutron capture therapy (BNCT) combines preferential tumor uptake of B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) as the boron carrier in a hamster cheek pouch oral cancer model.

Anticipating adaptation: tracking the impact of planned and unplanned adaptations during the implementation of a complex population-based genomic screening program.

In 2021, the Medical University of South Carolina (MUSC) launched In Our DNA SC. This large-scale initiative will screen 100,000 individuals in South Carolina for three preventable hereditary conditions that impact approximately two million people in the USA but often go undetected. In anticipation of inevitable changes to the delivery of this complex initiative, we developed an approach to track and assess the impact of evaluate adaptations made during the pilot phase of program implementation.

Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis.

Background: Systemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans.

Lessons Learned from the Pilot Phase of a Population-Wide Genomic Screening Program: Building the Base to Reach a Diverse Cohort of 100,000 Participants.

Background and Objectives: Genomic information is increasingly relevant for disease prevention and risk management at the individual and population levels. Screening healthy adults for Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia using a population-based approach can help identify the 1−2% of the US population at increased risk of developing diseases associated with these conditions and tailor prevention strategies. Our objective is to report findings from an implementation science study that evaluates multi-level facilitators and barriers to implementation of the In Our DNA SC population-wide genomic screening initiative.

Social Factors, Epigenomics and Lupus in African American Women (SELA) Study: protocol for an observational mechanistic study examining the interplay of multiple individual and social factors on lupus outcomes in a health disparity population.

Introduction: Despite the disproportional impact of SLE on historically marginalised communities, the individual and sociocultural factors underlying these health disparities remain elusive. We report the design and methods for a study aimed at identifying epigenetic biomarkers associated with racism and resiliency that affect gene function and thereby influence SLE in a health disparity population.

Methods And Analysis: The Social Factors, Epigenomics and Lupus in African American Women (SELA) Study is a cross-sectional, case-control study.

A pragmatic implementation research study for In Our DNA SC: a protocol to identify multi-level factors that support the implementation of a population-wide genomic screening initiative in diverse populations.

Background: In 2021, the Medical University of South Carolina (MUSC) partnered with Helix, a population genetic testing company, to offer population-wide genomic screening for Centers for Disease Control and Preventions' Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia to 100,000 individuals in South Carolina. We developed an implementation science protocol to study the multi-level factors that influence the successful implementation of the In Our DNA SC initiative.

Methods: We will use a convergent parallel mixed-methods study design to evaluate the implementation of planned strategies and associated outcomes for In Our DNA SC.

Nucleic Acid-Sensing and Interferon-Inducible Pathways Show Differential Methylation in MZ Twins Discordant for Lupus and Overexpression in Independent Lupus Samples: Implications for Pathogenic Mechanism and Drug Targeting.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune inflammatory disease with genomic and non-genomic contributions to risk. We hypothesize that epigenetic factors are a significant contributor to SLE risk and may be informative for identifying pathogenic mechanisms and therapeutic targets. To test this hypothesis while controlling for genetic background, we performed an epigenome-wide analysis of DNA methylation in genomic DNA from whole blood in three pairs of female monozygotic (MZ) twins of European ancestry, discordant for SLE.

GPA-Tree: statistical approach for functional-annotation-tree-guided prioritization of GWAS results.

Motivation: In spite of great success of genome-wide association studies (GWAS), multiple challenges still remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), each with small or moderate effect sizes. Second, our understanding of the functional mechanisms through which genetic variants are associated with complex traits is still limited.

Antifibrotic factor KLF4 is repressed by the miR-10/TFAP2A/TBX5 axis in dermal fibroblasts: insights from twins discordant for systemic sclerosis.

Objectives: Systemic sclerosis (SSc) is a complex disease of unknown aetiology in which inflammation and fibrosis lead to multiple organ damage. There is currently no effective therapy that can halt the progression of fibrosis or reverse it, thus studies that provide novel insights into disease pathogenesis and identify novel potential therapeutic targets are critically needed.

Methods: We used global gene expression and genome-wide DNA methylation analyses of dermal fibroblasts (dFBs) from a unique cohort of twins discordant for SSc to identify molecular features of this pathology.

Evaluation of local, regional and abscopal effects of Boron Neutron Capture Therapy (BNCT) combined with immunotherapy in an ectopic colon cancer model.

Objective: The aim of the present study was to evaluate the local and regional therapeutic efficacy and abscopal effect of BNCT mediated by boronophenyl-alanine, combined with Bacillus Calmette-Guerin (BCG) as an immunotherapy agent in this model.

Methods: The local effect of treatment was evaluated in terms of tumor response in the irradiated tumor-bearing right hind flank. Metastatic spread to tumor-draining lymph nodes was analyzed as an indicator of regional effect.

Integrating genetic and social factors to understand health disparities in lupus.

Purpose Of Review: Both social and genetic factors are associated with health outcomes in systemic lupus erythematosus (SLE), thus playing a role in its health disparities. Despite the growing list of social and genetic factors associated with SLE outcomes, studies integrating sociocultural and individual determinants of health to understand health disparities in SLE are lacking. We review the contributions of different social and genetic factors to the disparities in SLE, and propose a socioecological model to integrate and examine the complex interactions between individual and social factors in SLE outcomes.