Ghosts of the Horseshoe to Ward One

Ghosts of the Horseshoe and Ward One are critical interactive applications that offer two distinct yet complementary examples for how questions such as the ones just posed might be addressed on-site and in real-time. In what follows, we offer an account of each application and its context. Subsequently, we provide a theoretically informed discussion of how these projects elicit “empathic awareness” and, by extension, inspire a sense of responsibility for a past that remains unacknowledged – one that has ensured the existence and expansion of the physical campus of the University of South Carolina– Columbia.

Fostering Distance Education: Lessons From a United States-England Partnered Collaborative Online International Learning Approach

Collaborative Online International Learning (COIL) is a teaching and learning approach whereby entire courses or modules are co-developed and team taught by instructors from different institutions for students of both institutions. Since 2006, the approach has been gaining in mass appeal; however, considering our present-day global coronavirus pandemic, COILs have a renewed relevance in academia. Faculty from the University of South Carolina (United States) and Coventry University (England) embarked on a COIL partnership yielding a valuable experience that can serve as a model for other institutions that are interested in developing innovative and cross-cultural distance learning opportunities. The purpose of this paper is to explain how the institutional partnership emerged, describe the course content, and provide lessons that our team learned through the COIL development and implementation process. Our experience as a first-time COIL partnership is a model for others to consider as the landscape for the academic enterprise expands the confines of brick-and-mortar institutions.

Análisis de contenido de Twitter: sequía en España (2017-2020)

Este informe es resultado de un análisis de la red social Twitter sobre contenidos relacionados con la sequía en España en el período 2017-2020 en el marco de los trabajos del Observatorio Ciudadano de la Sequía. El informe está basado en el análisis de tweets geolocalizados cedidos por el Geoinformation and Big Data Research Laboratory (GIBD) de la University of South Carolina (Estados Unidos), y permite comprender mejor la percepción social y la opinión pública sobre la sequía en España.

Immunotherapy Targeting ST2/IL-33 Signaling in Myeloid Leukemia Stem Cells

Therapies for acute myeloid leukemia (AML) has barely changed over 30 years, while treatment for other blood cancers have made remarkable leaps forward. Recent advances in genomics have allowed molecular targeted therapies (i.e. FLT3-ITD, IDH, c-KIT inhibitors) extending survival, but most patients still succumb (Burd et al. Nat Med 2020). Therefore, developing more efficient, less toxic, and immune-based therapies for AML is an urgent unmet need. Previous studies showed that stromal cell-derived IL-33 stimulates myeloproliferative neoplasms (Mager et al. J Clin Invest 2015). Stimulation-2 (ST2), IL-33 receptor, contributes to leukemia stem cells (LSCs) survival in Cbfb-MYH11 mice (Wang et al . Sci Rep 2019). We showed that ST2 blockade enhanced graft versus leukemia activity against MLL-AF9 egfp AML after hematopoietic cell transplantation (Zhang et al . Sci Transl Med 2015). We and others, also, found that ST2 is expressed on normal murine and human hematopoietic stem cells (HSCs), respectively (Capitano et al. Blood Cells Mol Dis 2020; Alt et al. Biol Blood Marrow Transplant 2019). These data suggest a leukemia-promoting role of ST2/IL-33 signaling. To determine clinical relevance of ST2 in AML, we generated Kaplan-Meier curves using TCGA (n=173) and TARGET AML (n=187) databases. Decreased survival was observed in patients with high IL1RL1 (ST2 gene) which was validated in an independent database (AMLCG 1999 trial, n=417) (Fig. 1A). Since ST2 is expressed on HSCs, we interrogated if ST2 is expressed on LSCs defined as CD34 +CD38 - in the Princess Margaret Leukemia biobank (n=192), and found ST2 is higher on LSCs vs CD34 -CD38 +/- cells (Fig. 1B). We then sought to analyze ST2 on bone marrow samples comparing complete responders vs refractory patients to note that ST2 expression was increased in refractory patients' LSCs (Fig. 1C). To scrutinize the role of ST2 in initiating leukemogenesis, we performed limiting dilution transplantation using 500, 200, and 50 Lin -Sca-1 +c-KIT +-sorted LSCs from WT vs ST2 -/- MLL-AF9 egfp transduced cells. Frequency of LSCs in ST2 -/- cells was decreased by ~15-fold as opposed to WT cells [1:2141 (1:546-1:8405) vs 1:145 (1:75-1:283), p=3.37e-05] (Fig. 2A). We also tested leukemia maintenance, secondary transplantations from the primary recipients resulted in leukemia growth delay in ST2 -/- vs WT cells which was confirmed in tertiary transplantations (Fig. 2B-E). Self-renewal ability of LSCs is correlated to reactive oxygen species (ROS) (Testa et al. Exp Hematol 2016), and we found that ROS levels in ST2 -/- leukemic cells are markedly diminished in contrast to WT leukemic cells (Fig. 2F). ST2 deficiency in leukemic cells arrests G2/S/M cell cycle progression in LSCs (Fig. 2G-J). These data indicated that ST2 is indispensable for initiating and maintaining LSCs in MLL-AF9 AML. We next developed murine and human Fc-silenced-bispecific antibodies engaging mouse or human ST2 and CD3 (BsAb) built on the IgG[L]-scFv platform with proven ability to drive T cells into human tumors for effective tumor ablation (Santich et al. Sci Transl Med 2020; Park et al. J Immunother Cancer 2021) (Fig. 3A, 3E). Both BsAbs showed >90% purity by HPLC, stability under heat stress and low endotoxin. Animals did not exhibit any in vivo toxicity at BsAb doses of 0.4, 2, 5, 10 μg ip q 3 days x 6 doses (not shown). In the immunocompetent MLL-AF9 mice, murine anti-ST2 BsAb (BC281) treatment (10 μg i.p, 4 days post-AML challenge and given every three days for a total of 6 injections) resulted in extended survival compared to isotype control mice (Fig. 3B). Leukemic cells and LSCs were accordingly decreased in treated vs control group (Fig. 3C-D). We modeled humanized leukemic mice with MOLM-14 egfp cells and weekly injection of human CD8 + T cells in NOD.Cg-Prkdc scid Il2rg tm1Wjl/SzJ (NSG) mice (Fig. 3F). Animals treated with human anti-ST2 BsAb (BC282), using a similar regimen as for the immunocompetent model, led to better survival when compared to animals treated with mutated non-functional anti-ST2 BsAb (BC283) (Fig. 3G). Frequency of MOLM-14 egfp cells was lower in the BC282 vs BC283 group (Fig. 3H). These results suggested that anti-ST2 BsAbs can inhibit AML growth to improve survival. We concluded that ST2 is a potential therapeutic target, and ST2-specific T cell engaging BsAbs represent promising immunotherapeutics for AML. Figure 1 Figure 1. Disclosures Cheung: Medical University of South Carolina: Patents & Royalties: inventor on the ST2 bispecific antibody patent application; Y-mabs Therapeutics and Abpro-Labs Inc: Patents & Royalties: inventor on multiple patents filed by MSK, including those licensed to Ymabs Therapeutics, Biotec Pharmacon, and Abpro-labs; Eureka Therapeutics: Membership on an entity's Board of Directors or advisory committees. Paczesny: Medical University of South Carolina: Patents & Royalties: inventor on the ST2 bispecific antibody patent application.

The National Conference on Health Disparities Student Research Forum

The annual National Conference on Health Disparities (NCHD) was launched in 2000. It unites health professionals, researchers, community leaders, and government officials, and is a catalyzing force in developing policies, research interventions, and programs that address prevention, social determinants, health disparities, and health equity. The NCHD Student Research Forum (SRF) was established in 2011 at the Medical University of South Carolina to build high-quality biomedical research presentation capacity in primarily underrepresented undergraduate and graduate/professional students. This paper describes the unique research training and professional development aspects of the NCHD SRF. These include guidance in abstract development, a webinar on presentation techniques and methods, a vibrant student-centric conference, and professional development workshops on finding a mentor and locating scholarship/fellowship funding, networking, and strategies for handling ethical issues in research with mentors. Between 2011 and 2018, 400 undergraduate and graduate/professional students participated in the NCHD SRF. Most students were women (80.5%). Approximately half were African American or black (52.3%), 18.0% were white, and 21.3% were of Hispanic/Latinx ethnicity. The NCHD SRF is unique in several ways. First, it provides detailed instructions on developing a scientific abstract, including content area examples. Second, it establishes a mandatory pre-conference training webinar demonstrating how to prepare a scientific poster. Third, it works with the research mentors, faculty advisors, department chairs, and deans to help identify potential sources of travel funding for students with accepted abstracts. These features make the NCHD SRF different from many other conferences focused on students’ scientific presentations.

First person – Youwen Zhang

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Youwen Zhang is first author on ‘ Propensity to endoplasmic reticulum stress in deer mouse fibroblasts predicts skin inflammation and body weight gain’, published in DMM. Youwen is a PhD student in the lab of Hippokratis Kiaris at the University of South Carolina, Columbia, SC, USA, investigating the underlying pathogenic mechanisms associated with disruption of energy and protein homeostasis in organisms.

Two Kinds of Sectarianism

In the era of the early republic, Thomas Jefferson at the University of Virginia headed the leading effort to promote nonsectarian higher education, freed from religious control. Throughout the colonies the Presbyterians, representing in alliance with New Englanders the Reformed heritage, had become the principal rivals in establishing colleges. They pointed out that Jefferson’s views were not neutral, but just a different sort of sectarianism. That led to conflicts, especially in the South, where Jefferson’s ally, Thomas Cooper, was eventually removed from the presidency of the University of South Carolina. Within a generation of Jefferson’s death, rather than steadily liberalize as he had imagined, most American colleges were under more traditionalist Protestant influence. In 1845 Presbyterian William H. McGuffey became Professor of Moral Philosophy at the University of Virginia.

An Interview with Joy Priest

Joy Priest is the author of HORSEPOWER (Pitt Poetry Series, 2020), winner of the Donald Hall Prize for Poetry. She is the recipient of a 2021 NEA fellow- ship and a 2019-2020 Fine Arts Work Center fellowship, and has won the 2020 Stanley Kunitz Memorial Prize from APR, and the Gearhart Poetry Prize from The Southeast Review. Her poems have appeared in the Academy of American Poets’ Poem-a-Day, The Atlantic, and Virginia Quarterly Review, among others. Her essays have appeared in The Bitter Southerner, Poets & Writers, ESPN, and The Undefeated, and her work has been anthologized in Breakbeat Poets: New American Poetry in the Age of Hip-Hop, The Louisville Anthology, A Measure of Belonging: Writers of Color on the New American South, and Best New Po- ets 2014, 2016 and 2019. Joy received her M.F.A. in poetry, with a certificate in Women & Gender Studies from the University of South Carolina. She is currently a doctoral student in Literature & Creative Writing at the University of Houston.

Asynchronous Online Course Designs: Articulating Theory, Best Practices, and Techniques for Everyday Doctoral Education

Early online course materials were text-based and relied heavily on discussion forums as the de facto tool for interactions. Faculty members today, however, have many other choices for course design and course materials. There is not consensus for online course design guidelines or principles, though. Choices in course design by faculty members directly impact the quality of instruction and student learning experience. This article shares some of our theoretical and practical decisions faculty members at the University of South Carolina employ for online course design. Our experiences and decision-making may be useful for other members of the Online Ed.D. CPED Improvement Group (Online Ed.D. CIG), as well as other programs who may be experiencing emergency remote teaching as a result of the COVID-19 pandemic, making an evolutionary transition to online or blended education, or considering a future transition to a fully online program. Links to the strategies and tools mentioned throughout this essay are collated in a list at the end.

Enhancing Research Data Infrastructure to Address the Opioid Epidemic: The Opioid Overdose Network (02-Net)

Objective: Opioid Overdose Network is an effort to generalize and adapt an existing research data network, the Accrual to Clinical Trials (ACT) Network, to support the design of trials for survivors of opioid overdoses presenting to emergency departments (ED). Four institutions (Medical University of South Carolina (MUSC), Dartmouth Medical School (DMS), University of Kentucky (UK), and University of California San Diego (UCSD)) worked to adapt ACT network. This paper reports their progress. Materials and Methods: The approach that was taken to enhancing ACT network focused on four activities: cloning and extending the ACT infrastructure, developing an e-phenotype and corresponding registry, developing portable natural language processing (NLP) tools to enhance data capture, and developing automated documentation templates to enhance extended data capture. Results: All four institutions were able to replicate their i2b2 and Shared Health Research Information Network (SHRINE) infrastructure. A five-category e-phenotype model based on ICD-10 coding was developed from prior published work. Ongoing work is refining this via machine learning and artificial intelligence methods. Portable NLP tools, focused on the sentence level, were also developed to identify uncoded opioid overdose-related concepts in provider notes. Optimal performance was seen in NLP tools that combined rule-based with deep learning methods (F score, 0.94). A template for ED overdose documentation was developed to improve primary data capture. Interactive prompts to physicians inside ED progress notes were effective in promoting the use of the template. The template had good system usability and net promoter scores (0.72 and 0.75, respectively, n=13). Discussion: Results suggested that tailoring of existing multipurpose research networks to a specific task is feasible: however, substantial efforts were required for coordination of the subnetwork and development of new tools for extension of available data.