Digital Commons Network^™

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Restoring P53 Wild-Type Conformation In Tp53-Y220c-Mutant Acute Myeloid Leukemia, Bing Z Carter, Po Yee Mak, Edward Ayoub, Xiaogang Wu, Baozhen Ke, Yuki Nishida, Andrew Futreal, Lauren B Ostermann, Andrea D Bedoy, Steffen Boettcher, Courtney D Dinardo, Anna Puzio-Kuter, Masha V Poyurovsky, Arnold J Levine, Michael Andreeff

Faculty, Staff and Student Publications

TP53-Y220C is a recurrent hotspot mutation in cancers and leukemias. It is observed predominantly in acute myeloid leukemia (AML)/myelodysplastic syndromes among hematological malignancies and is associated with poor outcome. The mutation creates a structural pocket in the p53 protein. PC14586 (rezatapopt) is a small molecule designed to bind to this pocket and thus restore a p53-wild type (p53-WT) conformation. We demonstrate that PC14586 converts p53-Y220C into a p53-WT conformation and activates p53 transcriptional targets, but surprisingly induces limited/no apoptosis in TP53-Y220C AML. Mechanistically, MDM2 induced by PC14586-activated conformational p53-WT and the nuclear exporter XPO1 reduce the transcriptional activities of p53, …

Genomic Rare Variant Mechanisms For Congenital Cardiac Laterality Defect: A Digenic Model Approach, Archana Rai, Jonathan Klonowski, Bo Yuan, Karen J Coveler, Zain Dardas, Iman Egab, Jiaoyang Xu, Philip J Lupo, A J Agopian, Dennis Kostka, Cecilia W Lo, S Stephen Yi, Bruce D Gelb, Christine E Seidman, Eric Boerwinkle, Jennifer E Posey, Richard A Gibbs, James R Lupski, Shaine A Morris, Zeynep Coban-Akdemir

Faculty, Staff and Students Publications

Laterality defects are defined by perturbations in the usual left-right asymmetry of organs. The genetic etiology that underlies congenital heart disease (CHD) is often unknown (less than 40%), so we used a digenic model approach for the identification of contributing variants in known laterality-defect-associated genes (n = 115) in the exome/genome sequencing (ES/GS) data from individuals with clinically diagnosed laterality defects. The unsolved ES/GS data were analyzed from three CHD cohorts: Baylor College of Medicine-Genomics Research to Elucidate the Genetics of Rare Diseases (BCM-GREGoR; n= 251 proband ES), Gabriella Miller Kids First Pediatric Research Program (Kids First; n = 158 …

Recurrent De Novo Variants In The Spliceosomal Factor Crnkl1 Are Associated With Severe Microcephaly And Pontocerebellar Hypoplasia With Seizures, Sankalita Ray Das, Rosie Sullivan, Mischa S G Ruegg, Julia Horsfield, Jordan Doran, Gemma Poke, Nathalie De Vries, Sarah Duerinckx, Damien Lederer, Muzhirah Haniffa, Wee-Teik Keng, Gaik-Siew Ch'ng, David A Parry, Andrew P Jackson, Masamune Sakamoto, Naomichi Matsumoto, Noriko Miyake, Shin Nabatame, Hidetoshi Taniguchi, Emma Wakeling, Katrin Õunap, Pilvi Ilves, Ghayda Mirzaa, Andrew Timms, Emily Pao, Kimberly A Aldinger, William Dobyns, Axel Bohring, Beate Behre, Daniel G Calame, James R Lupski, Juan M Pascual, Marc Abramowicz, Gregory Gimenez, Louise S Bicknell

Faculty, Staff and Students Publications

Splicing is a complex process that is required to create the transcriptomic diversity needed for specialized functions in higher eukaryotes. The spliceosome contains more than 100 proteins and RNA molecules, which coordinate this dynamic process. Despite the ubiquity of splicing, pathogenic variants in spliceosomal components often cause a tissue-specific phenotype, hinting at further complexities that are not yet fully understood. We have identified a cohort of ten families with de novo missense variants in a spliceosomal component, CRNKL1, where nine individuals harbor one of two missense variants that both affect the same amino acid, Arg267. All affected individuals share a …

Hallmarks Of Stem Cell Aging, Thomas A Rando, Anne Brunet, Margaret A Goodell

Faculty, Staff and Students Publications

As organisms age, somatic stem cells progressively lose their ability to sustain tissue homeostasis and support regeneration. Although stem cells are relatively shielded from some cellular aging mechanisms compared with their differentiated progeny, they remain vulnerable to both intrinsic and extrinsic stressors. In this review, we delineate five cardinal features that characterize aged stem cells and examine how these alterations underlie functional decline across well-studied stem cell compartments. These hallmarks not only provide insight into the aging process but also serve as promising targets for therapeutic strategies aimed at rejuvenating stem cell function and extending tissue health span.

Testosterone Deficiency And Treatments: Common Misconceptions And Practical Guidance For Patient Care, Mohit Khera, James M Hotaling, Martin Miner

Faculty, Staff and Students Publications

Introduction: Misconceptions about testosterone therapy are prevalent and there is an unmet need for a review of current literature that can be leveraged by physicians to deliver safe and effective care for men with hypogonadism.

Objectives: This review aims to address common misconceptions about testosterone therapy using current literature and synthesize practical guidance for clinicians with patients who are starting testosterone therapy.

Methods: A literature search of PubMed, Embase, CINAHL was carried out to identify associations between testosterone therapy and prostate cancer, cardiovascular risk, and hepatic toxicity; definitions of hypogonadism; and practical guidance for clinician with patients starting testosterone therapy. …

Commentary On Quality Improvement Case Series: Leukemic Arthritis Mimicking Septic Arthritis In A Pediatric Patient, Alexandre Arkader, Mihir M Thacker, Karim Masrouha

Department of Medicine Faculty Papers

No abstract provided.

Factors Related To Hypertension In Pediatric Patients Who Do Not Have Obstructive Sleep Apnea: A Retrospective Chart Study, Alyssa Exarchakis, Alexandra Cohen, Penghao Wang, Seema Rani, Diana Martinez

Department of Medicine Faculty Papers

Background/Objectives: The relationship between OSA and adult hypertension has been extensively studied; however, it remains understudied in pediatric patients without OSA. The aim of this study is to identify factors associated with pediatric hypertension without OSA, through an IRB-approved retrospective chart review of patients who underwent polysomnography at Nemours Children's Hospital, DE/NJ between January 2020 and July 2023. Methods: Eligibility criteria included children 8-17 years, completed PSG, and clinic visit blood pressure (BP). Anthropometrics, demographics, social determinants, and medical history were obtained from electronic medical records. Hypertension was defined as the average systolic and/or diastolic BP that is …

The Trapping Of Live Neutrophils By Macrophages During Infection, Kelley N Cooper, Marina Terekhova, Barbara Potempa, Ana D'Aubeterre, Jerome Timbol, Si An Chen, Antoine Dufour, Shunying Jin, Maxim N Artyomov, Jan Potempa, Juhi Bagaitkar

2020-Current year OA Pubs

Neutrophils are highly abundant in the oral mucosal tissues, and their balanced activation and clearance are essential for immune homeostasis. Here, we demonstrate that neutrophils infected with the bacterial pathogen Porphyromonas gingivalis (Pg) are captured alive by macrophages in a manner that bypasses all known receptor-ligand interactions involved in the phagocytosis of either live or dead cells. Mechanistically, upon interaction with Pg, or its protease RgpB (gingipains), live neutrophils undergo rapid remodeling of their proteomes, generating neoepitopes. N-terminomics-based proteomic profiling identified multiple RgpB cleavage sites on several azurophilic granule proteins that are translocated to the surface of live neutrophils via …

Developing Affirmative Housing And Building Community For Older Lgbtq+ Adults In Spokane, Washington, Katie Diane Miller

2025 Symposium

This qualitative, exploratory study seeks to propose potential community interventions that will increase access to inclusive housing and decrease social isolation among LGBTQ+ individuals over 50 years of age based on currently available data. Social isolation has been recognized as a public health issue widely impacting communities across the United States. The older LGBTQ+ population is especially impacted by social isolation because of systemic discrimination and limitations. LGBTQ+ older adults in the US have historically faced a lack of legal protections, gaps in healthcare access, and structural and interpersonal inequity because of system development that support binary beliefs. These factors …

“A Time Of Fire And Cataclysm”: The Centrality Of Cosmic War In Tolkien’S Round World Cosmologies, Kristine Larsen

Journal of Tolkien Research

In the etiological mythology of Middle-earth, heavenly battles routinely invoke astronomical events, signs of Melkor’s marring of the world or mighty weapons in his arsenal of destruction. In this conference paper I specifically focus on battles involving the Sun and Moon, especially in Tolkien's later "Round Earth" cosmologies, where the Sun Maiden is "ravished" by Melkor.

Satellites For Development, Broadcasting And Information

Communication Research Trends

The symbol of the 'global village' is the communications satellite. For over twenty years, ever since the. USSR launched Sputnik in 1957, the USA and the USSR in particular, and other countries too, have been devoting ever more financial and human resources to the building of ever more elaborate satellite systems; Today a host of communication satellites are positioned in geostationary orbit 22,282 miles (35,860 kilometres) above the equator. The globe is encircled by a communications network that links the most distant parts of the earth in a matter of seconds.

A communications satellite system consists of three parts. The …

Gaining Insights Into Community Engagement Efforts: Learning From Preservice Stem Educators, Amy G. Maples, Lynn L. Hodge, Nick Kim

Journal of Community Engagement and Higher Education

This study seeks to extend research in the field by exploring literature examining preservice teachers’ perceptions of community engagement efforts. We then report findings from a thematic analysis of a survey conducted with teacher candidates at a university in the southeastern U.S. who took part in school- and community-based STEM events, and provide implications and suggestions for utilizing community engagement opportunities as a means of enriching preservice teachers’ understandings of local school and community contexts.

This Is Why We Do It: Faculty Motivations For Embracing Community-Engaged Pedagogy, Magdalena Denham, Lee M. Miller, Joyce K. Mccauley, Danica Schieber, Taylor L. Morrison, Chuck Drumm

Journal of Community Engagement and Higher Education

Institutions of higher education are increasingly highlighting community engagement activities to make the benefits of higher education more visible. The most transformational community engagement is linked to curriculum, so it is faculty who must incorporate community-engaged pedagogy. This content analysis of faculty narratives about community engagement reveals motivations for faculty to engage in this work. These findings connect to social capital theory and suggest a new direction for faculty development efforts to promote community engagement.

The Role Of Cultural Brokers In Community-Based Research, Rachel Boit, Joy Birabwa, Dhoha Altaki, Savannah Bayer, Michele Kamau, Linda Hestenes

Journal of Community Engagement and Higher Education

Cultural brokers play a critical role of helping researchers navigate cultural and language barriers to gain insight into communities. This paper focuses on one cultural broker who helped facilitate community-based research among the refugee community. Her professionalism, expertise and knowledge of the community made her a valuable resource for both the researchers and the community. This work acknowledges the position of power and privilege that cultural brokers hold in community research.

Town And Gown: Engagement And Collaboration Between Local Municipalities And Institutions Of Higher Education, Vivian González Cueto

Journal of Community Engagement and Higher Education

The role of the local government within the context of engagement and collaboration with universities has largely been understudied. Employing a cross-sectional design, this study of 67 universities and 78 municipalities from 29 states examines how collaborative capacity impacts university and local government perceptions of engagement and collaboration with each other. The findings indicate that local government trust is the primary catalyst for both engagement and collaboration between the parties.

Community Engagement In Music Therapy: Reflections From The Field, Jess Rushing, Denise M. Cumberland

Journal of Community Engagement and Higher Education

This paper reflects on a music therapy community engagement project that incorporates clinical training, service learning, and community music therapy. Two faculty members and a practicum student in a Midwestern university engaged community members connected to Parkinson’s disease to create a music-based program. We offer a conceptual framework that connects approaches situated within community music therapy (CoMT) qualities and community-based participatory research (CBPR) principles. We share project processes, findings, and recommendations, emphasizing all as equal stakeholders.

Modeling, Analysis, And Prediction Of Covid-19 Dynamics With Interacting Subpopulations And Implicit Behavior Using Physics-Informed Neural Networks, Naima Aubry-Romero, Alonso Ogueda-Oliva, Padmanabhan Seshaiyer

Spora: A Journal of Biomathematics

In this paper, we consider an extended SEIR compartmental model that incorporates young and old interacting subpopulations, allowing for cross-group transmission dynamics. Implicit behavioral changes are included to determine the influence of social behavior on coronavirus transmission dynamics. The basic reproduction number, the average number of secondary cases of infection produced by a single primary case, is derived for both the explicit and implicit model using the next-generation matrix method. We solve the associated differential equation systems and estimate useful parameters in the explicit model using physics-informed neural networks (PINNs). Our results point to how the PINNs approach offers an …

Book Publishing In A Changing Environment

Communication Research Trends

In 1982 Unesco held the first World Congress of Books in London. Its aim was to promote the idea of the 'reading society'. As if to underline ,he problem facing Unesco in achieving its aim, 1982 was also Information Technology Year in Britain. The juxtaposition of traditional and modern forms of communication is an apt symbol of the theme of this issue.

Since the time of Gutenberg the printed book has held a prominent place in the Western cultural and intellectual system. Today book production continues to increase around the world and developing countries are ever more anxious to combat …

First Case Of Sexual Cannibalism In Leiurus Abdullahbayrami Yağmur, Koç & Kunt, 2009 (Scorpiones: Buthidae) From Lebanon, Rami Khashab

Euscorpius

This study presents the first report of sexual cannibalism in the medically significant scorpion Leiurus abdullahbayrami Yağmur, Koç & Kunt, 2009, that was recorded during a herpetological field trip to the semi-desert area in northern Lebanon. It broadens the understanding of sexual cannibalism in scorpions and adds a new prey item to the dietary spectrum of the scorpion.

Improving Children's Television

Communication Research Trends

Few areas of television programming have provoked such strong public concern and protest as children's programmes. Parents and educators fear that television may be disrupting the balanced development of children's personalities or implanting harmful values. Most of the early research on children's television was an attempt to determine more accurately whether content was truly violent or manipulative and whether violence, advertising or other content was having destructive effects.

This public reaction also sparked moves in the late 1960s to carefully design programmes such as Sesame Street which would be entertaining, instructive and contribute to the intellectual-emotional growth of the child. …

Positively Impacting Traffic Safety Culture For Indigenous Youth: A Heritage-Focused Approach, Jacob Steven Pehrson, Ahmed Abdel-Rahim, Logan Prescott

Journal of Community Engagement and Higher Education

This paper presents the development of heritage-focused outreach materials with the objectives of positively impacting traffic safety culture for Indigenous youth to reduce the number and severity of traffic crashes impacting these communities. The approach presented in this paper includes involving local community leaders in traffic safety education and incorporating culturally based material in outreach education. This could empower Tribal communities to preserve their cultural identities while acquiring the expertise needed to promote traffic safety.

Service Learning As A Mode To Deliver Course Learning Outcomes In A Research-Based Exercise Science College Course, Jennifer Lape Kaiser, Madison Skaggs

Journal of Community Engagement and Higher Education

The following case study presents an approach to teaching research courses in undergraduate exercise science programs. Research courses are commonly required in the curriculum for this degree. Service learning (SL) is an effective way to promote student learning outcomes (SLOs) by providing hands-on experience for the students, and should be considered in exercise science research courses. Quantitative and qualitative survey results from students over two semesters of SL in an exercise science course are presented.

A Father-Friendliness Survey: How Do Community Organizations Report Engaging Fathers?, Kyle Miller, Jordan A. Arellanes

Journal of Community Engagement and Higher Education

This community-based project explored levels of father-friendliness across local organizations, agencies, and schools. A community coalition of individuals from diverse backgrounds and roles created a community survey to gather quantitative and qualitative information from individuals who worked with children or families. An analysis of survey responses (N=122) led to descriptive and thematic results of how the community served or marginalized fathers. Results were used to guide efforts in father engagement across various professional sectors.

Stepping Up, Keeping On Track, And Pulling Your Own Weight: Collaborative Arts-Based Service-Learning Metaphors, Marcy Meyer

Journal of Community Engagement and Higher Education

In this study, the author explores metaphors related to students’ experiences conducting collaborative arts-based ethnographic research in a U.S. nonprofit organization. A metaphor analysis of 25 students’ essays revealed they were most likely to frame their experiences with arts-based service learning as a journey or a sports contest. The author examines the extent to which students’ metaphors legitimize or delegitimize arts-based service learning, as well as the degree of novelty that characterizes these metaphors. She explores the implications of her findings for teaching and promoting arts-based service learning in the academy.

Incorporating Community-Engaged Pedagogy In Online Classes: Benefits, Challenges, And Strong Practices, Emmy Price, Margaret Thomas-Evans

Journal of Community Engagement and Higher Education

Community-engagement in virtual classrooms comes with unique benefits and challenges. Between 2018-2021, technical writing e-service-learning students from Indiana University East (Richmond, Indiana) raised a total of $149,239 through grant writing projects. This e-servicelearning project gave students real-world experiences and opportunity to connect with local organizations, prompting one student to choose grant writing as a career. Many students were able to successfully obtain funding for their chosen nonprofits, giving students a sense of social responsibility.

Social-Emotional Learning In A Week-Long Theatre Camp For Youth, Emily E. Virtue, Lisa C. Mann, Hannah Diener

Current Issues in Middle Level Education

Understanding how social-emotional learning develops in middle level education is important for educators and parents as they work to guide youth toward healthy relationships and responsible citizenship. Many studies demonstrate that students who participate in theatre have shown greater emotional health and more capacity to move through conflict positively. This study asks if social-emotional learning through theatre education can still happen outside of a formal educational setting. This study is a mixed methods investigation of a week-long theatre camp in the summer for upper elementary and middle school youth. Four aspects of social emotional learning were studied: task articulation, self-regulation, …

Exploring The Impact Of A Middle Level School Therapy Dog On Students And Staff And Connections To Best Practices In Middle School Education, Brandye Nobiling, Sherry Maykrantz, Tara Downes, Joshua Nobiling

Current Issues in Middle Level Education

The presence of therapy dogs in schools has increased due to the growing body of research showing positive effects of assisted-animal interaction. But there is little published research on how an innovation such as a therapy dog connects to best practices in middle level education. The goal of the research was to use the Diffusion of Innovation (DOI) theory to connect the implementation of a therapy dog to the Association for Middle Level Education’s (AMLE) essential attributes and characteristics as well as components of the Centers for Disease Control and Prevention’s Whole School, Whole Community, Whole Child (WSCC) model. Focus …

Building Community With Middle Level Preservice Teachers, Carolyn A. Weber

Current Issues in Middle Level Education

This paper addresses how community building can be implemented in a class for preservice middle level teachers. The preservice teachers connected community building to their success in the course and reported ways they could build community in their future classrooms.

"It Makes It More Real.”: Teacher Candidate Perceptions Of A Clinically-Rich Middle Grades Teacher Preparation Program, Shawn A. Faulkner, Michael Dicicco

Current Issues in Middle Level Education

The persistent divide between theory and practice in teacher education has long been a subject of concern among researchers and scholars (Darling-Hammond, 2006; Zeichner, 2010). This paper explores teacher candidate perceptions of a clinically-rich (NASUP, 2021) middle grades teacher preparation program that has worked to create a “third space” (Zeichner, 2010) through a school-university partnership with a local middle school. Semi-structured interviews were conducted with teacher candidates (n=23) at the time of program completion. Findings suggest teacher candidates felt prepared and valued clinically-based activities and experiences. Teacher candidates suggest future improvements to the program should include more experiences tied to …