Medicine and Health Sciences Commons^™

Advances In Targeting Her2 Across Cancer Subtypes: A Pan-Tumor Approach, Taiwo Adesoye, Ecaterina E Dumbrava, Kanwal P S Raghav, Aysegul A Sahin, Hui Chen, Sunyoung S Lee, Milind M Javle, Shubham Pant, Omar Alhalabi, Xiuning Le, Vicente Valero, Paula R Pohlmann, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in multiple solid tumors, particularly breast and gastric cancers. Significant advancements have been made in the development of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates (ADC), and novel bispecific antibodies. These agents have revolutionized the treatment landscape for HER2-positive metastatic cancers, resulting in improved progression-free and overall survival, and quality of life for patients. Beyond breast and gastric cancers, HER2 expression/amplification has been observed in other solid tumors, such as colorectal, lung, bladder, ovarian, and biliary tract cancers, offering new opportunities for personalized therapy in …

Integrative Spatial Multi-Omics Reveal Niche-Specific Inflammatory Signaling And Differentiation Hierarchies In Aml, Enes Dasdemir, Ivo Veletic, Christopher P Ly, Andres E Quesada, Christopher D Pacheco, Fatima Z Jelloul, Pamella Borges, Sreyashi Basu, Sonali Jindal, Zhiqiang Wang, Alexander Lazar, Khalida M Wani, Dinler A Antunes, Patrick K Reville, Preethi H Gunaratne, Robert J Tower, Padmanee Sharma, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a clonal disorder characterized by immature blasts and arrested differentiation that primarily affects the bone marrow (BM) and occasionally presents as extramedullary (EM) disease. EM manifestations highlight AML's adaptability to distinct microenvironments, which we examined using spatial analyses of medullary and EM tissues. We describe a workflow for Visium-based spatial transcriptomics in medullary and EM AML, revealing insights into cell-cell communication and the spatial organization of AML hierarchies. In BM, monocytes and granulocyte-monocyte progenitors colocalized with leukemic populations, sharing molecular signatures with those in EM sample. CXCL12-CXCR4-mediated communication correlated with PI3K/AKT/mTOR signaling in inflammatory niches.

Rare Heterozygous De Novo Variants In Rapgef2 Are Associated With A Neurodevelopmental Disorder, Ali H Bereshneh, Kirkland A Wilson, Xueyang Pan, Shabab B Hannan, Megan A Cooper, Jullianne Diaz, Eyby Leon, Tiana M Moses, Mahshid S Azamian, Daryl A Scott, Ping Yee Billie Au, Juan Pablo Appendino, Ingrid E Scheffer, Antony Kaspi, Melanie Bahlo, Michael S Hildebrand, Angela T Morgan, Ekanem Ekure, Joshua M Shulman, Friedhelm Hildebrandt, Jennifer E Posey, Paul Kruszka, Eric Vilain, Shinya Yamamoto, Oguz Kanca, Seth Berger, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

Methods: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We …

Single-Cell Rna Sequencing Suggests Different Progenitor Lineages Between Idh Mutant And Idhwt Glioma, Iyad Alnahhas, Allison Kayne, Mehak Khan, Wenyin Shi

Department of Neurology Faculty Papers

Introduction Single-cell RNA sequencing has elucidated the heterogeneity in cancer. Single-cell glioblastoma (GBM) analyses have also proposed the resemblance of GBM cells to radial glia and outer radial glia (oRG) supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17-19) and classified NPCs based on their expression of THY1 (CD90), CD24 and EGFR. Ventricular radial glia are THY1⁻CD24⁻EGFR⁺ whereas oRG are THY1⁻CD24⁻EGFR⁻. Early neuron precursors are CD24⁺THY1⁻EGFR …

Selective Deletion Of Slc2a1 From The Rpe Reveals That Rods But Not Cones Depend On Glucose Transport Across The Outer Blood-Retinal Barrier, Lauren L. Daniele, John Y.S. Han, Minzhong Yu, Ravi A. Sangani, Craig D. Beight, Cyrus Rostami, Philip D. Kiser, Neal S. Peachy, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. …

Extra-Axial Cerebrospinal Fluid Volumes From 6 To 24 Months Of Age Are Associated With Poorer Executive Function At School-Age In Children With And Without Autism, Yichi Zhang, Robert C Mckinstry, Natasha Marrus, John R Pruett Jr., Et Al.

2020-Current year OA Pubs

BACKGROUND: Abnormally increased extra-axial cerebrospinal fluid (EA-CSF) volume is present as early as 6 months in infants later diagnosed with autism and is associated with symptom severity at the age of diagnosis, but it is unknown whether early EA-CSF enlargement has long-term impacts on other clinical domains. Executive function (EF) deficits are frequently observed in children with autism and are linked with worse academic outcomes, higher anxiety, and lower adaptive functioning. The current study examines the association between EA-CSF volume at infancy and EF at school age in a longitudinally phenotyped cohort of children with either high (HL) or low …

Effects Of Icosapent Ethyl On Risk And Duration Of Hospitalizations And Death In Reduce-It, Michael Szarek, Deepak L Bhatt, Michael Miller, Eliot A Brinton, Jean-Claude Tardif, Christie M Ballantyne, Steven B Ketchum, Mandeep R Mehra, Ph Gabriel Steg

Faculty, Staff and Students Publications

Aims: Among statin-treated participants with elevated triglycerides and known cardiovascular disease or with diabetes and other risk factors, icosapent ethyl reduced the risk of cardiovascular events in the REDUCE-IT study. In this post hoc analysis of REDUCE-IT, we quantified the effects of icosapent ethyl on total hospitalizations and days lost to hospitalization and death.

Methods: Randomization to treatment with 2 g twice daily of icosapent ethyl or matching placebo was performed among 8179 participants receiving statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69-5.63 mmol/L, and low-density lipoprotein cholesterol …

Onset And Exacerbation Of Obsessive-Compulsive Disorder In The Perinatal Period, Jack Samuels, Mary Kimmel, Janice Krasnow, Rashelle Musci, Paul S Nestadt, Lauren M Osborne, Eric A Storch, Jonathan S Abramowitz, Gerald Nestadt

Faculty, Staff and Students Publications

Purpose: Obsessive-compulsive disorder (OCD) can emerge during pregnancy and the postpartum and may adversely affect mother and newborn. However, little is known about potential risk factors for the onset of OCD in the perinatal period. Therefore, we investigated the onset of diagnosed DSM-5 OCD in women followed from the second trimester of pregnancy to 6-months postpartum.

Methods: We followed 256 women from the 20-24th week of pregnancy to 6-month postpartum. Participants had psychiatric diagnostic interviews at baseline and 6-month postpartum and completed self-report instruments. We compared women with and without incident OCD on sociodemographic characteristics and clinical features.

Results: Of …

Combining Dna Methylation Features And Clinical Characteristics Predicts Ketamine Treatment Response For Ptsd, Amir Valizadeh, John D Roache, Xinyu Zhang, Ying Hu, Ralitza Gueorguieva, Lynnette A Averill, Mohini Ranganathan, Zuoheng Wang, Douglas E Williamson, Paulo R Shiroma, Matthew J Girgenti, Ismene L Petrakis, Argelio L López-Roca, Stacey Young-Mccaughan, Terence M Keane, Alan L Peterson, Chadi G Abdallah, John H Krystal, Ke Xu

Staff and Researcher Publications

Post-traumatic stress disorder (PTSD) exhibits extensive clinical and biological variability, making treatment challenging. The Consortium to Alleviate PTSD (CAP)-ketamine trial, the largest randomized study of ketamine for PTSD, found no overall benefit of ketamine over placebo, underscoring the necessity to identify responsive subgroups. Using pre-treatment blood DNA methylation profiles and clinical measures from the CAP-ketamine trial, we applied machine learning to predict treatment response. A model based on 1,208 methylation sites achieved higher predictive accuracy than models using clinical variables alone, and combining both data types further improved performance. The methylation-derived score distinguished responders with 92.9% accuracy. The predictive CpGs …

Associations Of Arsenic Exposure And Folate In Maternal Leukocyte Dna Methylation: A Case-Control Study Of Mothers With Spina-Bifida Affected Children, Amy M Inkster, Anne K Bozack, Bernardo Lemos, Tabitha Lumour-Mensah, Sudipta Kumar Mukherjee, Shekh Muhammad Ekramullah, D M Arman, Joynul Islam, Xingyan Wang, Liming Liang, Richard H Finnell, Maitreyi Mazumdar, Andres Cardenas

Faculty, Staff and Students Publications

No abstract provided.

Rnai-Based Screen For Pigmentation In Drosophila Melanogaster Reveals Regulators Of Brain Dopamine And Sleep, Samantha L Deal, Danqing Bei, Shelley B Gibson, Harim Delgado-Seo, Yoko Fujita, Kyla Wilwayco, Elaine S Seto, Amita Sehgal, Shinya Yamamoto

Faculty, Staff and Students Publications

The dopaminergic system has a large role in behavior and neurological disease, and understanding dopamine level regulation in vivo is critical. To identify dopamine regulators, we utilized Drosophila melanogaster cuticle pigmentation, where dopamine is a precursor to melanin. We measured dopamine from known pigmentation mutants (e.g., tan, ebony, black) and performed an RNAi-based screen to identify additional regulators. We found 153 hits, enriched for developmental signaling pathways and mitochondria-associated proteins. From 35 prioritized candidates, 11 affected head dopamine levels. Effects on brain dopamine were mild, even knocking down the rate-limiting synthesis enzyme Tyrosine hydroxylase (TH), suggesting …

Peace Innovation And Healing: A Design Justice Framework To Support Change Processes, Strengthen Relationships, Foster Trust, And Build Community, Michelle Helman

Peace and Conflict Studies Journal Conference

Many organizations aiming to achieve peace and health equity outcomes often focus their design processes and innovation efforts externally without addressing how their organizational culture can unintentionally reproduce the very harms they are trying to address. The purpose of this qualitative design research study is to explore the role of a design justice framework in piloting a Peace Innovation Project aimed at facilitating an organizational culture change process. Specifically, the study focuses on better understanding how integrating a design justice approach could support research collaborators to center equity and justice as core components in building a culture of peace and …

Embodying Design Justice: A Peace Education Framework To Strengthen Relationships, Foster Trust And Build Community, Michelle Helman

Peace and Conflict Studies Journal Conference

BACKGROUND

Groups working toward creating peace and equity often focus on external innovation without addressing internal culture shifts necessary to navigate change and achieve their goals. Michelle’s doctoral research and practice address this challenge through a design research study and peace innovation project focused on organizational culture transformation through a design justice framework. Findings suggest that interweaving the framework with storytelling, arts, and embodiment practices are key to support people in navigating change processes to strengthen relationships, foster trust, and build community.

ABOUT

The workshop offers an applied learning experience for participants to explore the concepts of design and innovation …

Reconstructing Life One Clay Pot At A Time, Kelly Allen

The Open Journal of Occupational Therapy

Kate Lewis, a ceramicist and teaching artist based in Grand Rapids, MI, created the artwork for the Winter 2026 issue of the Open Journal of Occupational Therapy (OJOT). The image features a collection of heart-shaped ceramic pinch pots, produced after she was told she may never be able to move her left arm again. She created them on the recommendation of an occupational therapist who understood the value of meaningful occupations for recovery. These vessels represent a pivotal shift in Kate’s rehabilitation from Complex Regional Pain Syndrome (CRPS). Diagnosed in 2018 after sustaining an injury to her wrist, the minor …

Meeting Population Health Needs: Are Occupational Therapy Health Promotion Programs Scalable?, Tracy Chippendale, Szu-Wei Chen

The Open Journal of Occupational Therapy

No abstract provided.

Facilitators And Barriers To Sustainable Global Rehabilitation Projects, Fredrick Pociask, Rosanne Dizazzo-Miller

The Open Journal of Occupational Therapy

The sustainability of projects addressing significant rehabilitation needs in lower-resource countries is considered one of the most critical outcomes of these initiatives. While some information is available from public health and medical projects on promoting sustainability, less evidence exists on facilitators and barriers to the sustainability of global rehabilitation development projects. Interviews with eleven medical and rehabilitation professionals, each with over 8 years of experience in global project development, contributed to the discussion of barriers and facilitators for sustainability with direct implications for occupational therapy practice and research. The presence of established professional standards was a distinctive facilitator, and disruptions …

Brain Gains: A Review Of Remediation Treatment Strategies Using Exercise Following Traumatic Brain Injury, Jessica Smith, Kristin Biggins, Loriann Helgeson

The Open Journal of Occupational Therapy

In this Opinions in the Profession article, we explore remediation treatment strategies using exercise for recovery from post-traumatic brain injury and aim to justify the use of such treatment in the occupational therapy profession to increase skills for functional gain. Common treatment strategies used by occupational therapists after brain injury are compensatory strategies, indicating the client learns a new way to perform the task. Though effective, it is also necessary to consider how remediation and neuroplasticity are essential. Teaching new approaches to complete tasks results in functional gains; however, focusing on foundational skills using exercises to relearn motor patterns to …

Professional Standards As Gateways, Not Barriers, In Occupational Therapy, Ryan Thomure

The Open Journal of Occupational Therapy

No abstract provided.

Understanding Graduate Occupational Therapy Educators’ Use Of Trauma-Informed Approaches In The Classroom, Sean M. Brim

The Open Journal of Occupational Therapy

Traumatic events can alter the brain structure and affect cognitive capacities and academic performance. Educators at all grade levels are responsible for supporting students through trauma-informed approaches. Previous trauma-informed research focused on K–12 education levels. The experience of graduate-level occupational therapy educators who have applied trauma-informed approaches to improve student learning have not been explored. This general qualitative study explored the experiences of occupational therapy educators who used trauma-informed approaches. The conceptual framework was the trauma-informed care model. Ten graduate-level occupational therapy educators with at least 1 year of teaching experience were recruited and participated in semi structured interviews. Data …

Perceived Educational Value Of Different Types Of Simulation In Occupational Therapy Education: A Mixed-Methods Study, Marie-Eve Bolduc, Barbara Shankland, Bernadette Nedelec

The Open Journal of Occupational Therapy

Simulation is an important instructional method in occupational therapy (OT) programs. However, it remains unclear if the various types of simulation hold the same educational value. The objective of this study was to determine the perceived educational value of three different types of simulations (role-play between students, live scenarios with simulated patients [SPs] and tele-simulation with SPs) and the factors that contributed to a higher educational value. This cross-sectional study used a sequential explanatory mixed-methods design. An online questionnaire was used, and two focus groups were conducted to develop a richer understanding of the answers obtained in the questionnaire. Forty-two …

Investigating The Efficacy Of An Online Multigenerational Awareness Course For Occupational Therapy Students – A Pilot Study, Susan Blair, Barbara M. Doucet, Jerilyn Callen, Kirsten Davin, Shelby Hutchinson

The Open Journal of Occupational Therapy

In today’s multigenerational society, particularly in health care settings, thriving can be challenging because of generational differences. Occupational therapy educational programs (OTEPs) prepare students for work environments where three to four different generations may be present. This study examines the effectiveness of an online multigenerational awareness (MGA) course. The secondary objectives include increasing students’ knowledge of enhanced multigenerational collaboration and communication strategies in preparation for future clinical practice. A pilot group of eight participants from various university departments reviewed the course content and completed preenrollment and postenrollment surveys, providing feedback regarding the applicability and perceived usefulness of the multigenerational awareness …

Intentional Resiliency Mentoring: A Mixed Methods Study Exploring A Pilot Mentorship Program For Occupational Therapy Students, Courtney J. Taylor, Ana K. Brussa, Kate G. Barlow

The Open Journal of Occupational Therapy

Because of high levels of reported stress, occupational therapy (OT) students’ ability to employ interpersonal skills and professionally manage conflicts is impeded. This mixed methods pilot study investigated the impact of an Intentional Relationship Model (IRM) informed mentorship program on OT students’ perceived stress and self-efficacy for interpersonal communication. Students (N = 21) completed pre and posttests of the Self Efficacy for Therapeutic Use of Self Scale (SETUS) and the Perceived Stress Scale (PSS-10). Six monthly mentor journals (N = 6) were collected to further explore the student experience. Quantitative findings demonstrated students’ (N = 21) ability to manage stress …

Occupational Therapy Students’ Perspectives On Using Virtual Reality Simulation In Preparation For Objective Structured Clinical Examinations: A Qualitative Study, Pegah Firouzeh, Craig R. St. Jean, Christine Ha, Mary Roduta Roberts

The Open Journal of Occupational Therapy

The use of virtual reality (VR) simulations in clinical education has been receiving increased research attention. The purpose of this study was to investigate first-year occupational therapy (OT) students’ experiences using a VR-simulated clinical interview as part of their preparation for a client history-taking Objective Structured Clinical Examination (OSCE). This qualitative study used focus groups to understand students’ (n = 20) perceptions of the effect of VR simulation on learning and exam readiness. We also explored students’ perceptions of the simulation’s authenticity, strengths, and weaknesses. Qualitative data analysis was conducted to identify codes and develop categories in association with the …

Ruth Coleman Denard (1906-2002): One Of The First Registered Black Occupational Therapists, Mirline Milien

The Open Journal of Occupational Therapy

The experiences and contributions of underrepresented groups in the occupational therapy profession are insufficiently explored and largely absent from occupational therapy education. For instance, the narratives of early Black occupational therapists and students are virtually nonexistent in the literature. As the profession moves toward greater inclusivity, it is essential to uncover these hidden stories and legacies to better understand the profession’s evolution and help shape its future. This article highlights Ruth Coleman Denard, one of the first registered Black occupational therapists in the United States, and provides an overview of her career trajectory. Historical research methods, including a review of …

An Occupation-Based Review Of Assessments Used In Pediatric Occupational Therapy Practice, Alysha Skuthan, Wendy B. Stav, Gracyn Mcvey, Jennifer Martinez, Marissa Hunter, Erin Diroll, Maureen Flanagan

The Open Journal of Occupational Therapy

Assessment tools are a critical component of the occupational therapy evaluation process. Despite the profession’s push toward occupation-centered practice, the classification of assessment tools as occupation-based versus skill-based does not exist. An occupation-based review of pediatric occupational therapy assessment tools was completed and scored according to the Occupation-Based Practice Assessment to classify assessment tools on a continuum of discrete or skill-based to occupation-based. Of the top 11 most frequently used tools, four were classified as occupation-based, three were classified as intermediate, and four were classified as discrete. In total, only 36% of commonly selected assessment tools are occupation-based. Pediatric occupational …

Maternal Role Transition: A Quality Of Life Frame Of Reference For Mothering After Nicu, Wendy Gaughan, Kathryn A. Lemonda

The Open Journal of Occupational Therapy

Occupational therapists are uniquely skilled to address the needs of a new mother and the infant during transition to motherhood, as acquisition of this new role may cause a role strain with other previously held roles. New mothers to infants requiring a neonatal intensive care unit (NICU) hospitalization experience additional stressors and considerations during this role transition. The Maternal Role Transition (MRT) Frame of Reference is a novel, community-based approach to facilitate attainment and integration of mothering occupations and address role strain during the perinatal period. MRT is rooted in the theoretical foundations of Maternal Role Attainment Theory, Self Efficacy …

Rehabilitation Habits And Roles: The Dual Impact Of Iadls And Psychosocial Interventions Poststroke, William Sit, Ryan Hulla, Veronica Smith, Joanna Ruiz, Steve Abraham

The Open Journal of Occupational Therapy

Background: This randomized study assessed an 8-week program for stroke survivors at an outpatient center in the United States. The program focuses on a holistic approach to recovery through habits and roles.

Method: Two researchers randomly divided 19 participants (N = 19) into two groups, with each group focusing on two distinct programs: the Occupational Therapy Instrumental Activities of Daily Living (IADLs) program and the Psychosocial Modules (PS) program for stroke survivors. Participants attended weekly group sessions and individual phone sessions, which reinforced learned strategies, provided personalized guidance, and ensured adherence to program goals. The Canadian Occupational Performance …

Enhancing Self-Esteem In Adolescents During Acute Inpatient Psychiatric Hospitalization: A Mixed Methods Study, Praveen Injeti, Julie D. Kugel, Dragana Krpalek, Liane Hewitt, Lida Gharibvand

The Open Journal of Occupational Therapy

Background: Low self-esteem (LSE) can negatively impact adolescent mental health, leading to suicidal ideation (SI). Social stressors, such as peer rejections, are considered a source of stress that can contribute to LSE, SI, and subsequent admission to psychiatric facilities. This study aimed to assess the effectiveness of an occupational therapy intervention to improve self-awareness and self-esteem during short-term hospitalization.

Method: The research used a mixed methods approach to evaluate the impact of a psychoeducational intervention by an occupational therapist on 16 adolescents. The Rosenberg Self-esteem Scale (RSES) was used before the intervention (pretest), immediately after the intervention (posttest …

A Polyvagal And Sensory Integration And Processing Approach To Supporting Development In Young Children With Autism, Catherine Cavaliere, Nadia Rust, Michelle Rogowski, Alyssa Calderone, Rebecca Marash, Amy Zdrodowski, John Damiao

The Open Journal of Occupational Therapy

Background: The polyvagal theory presents a framework for understanding the autonomic nervous system’s role in influencing behavior, engagement, and connection. Children with autism experience regulation and sensory integration and processing differences that impact their sense of felt safety and engagement in their environment. The Safe and Sound Protocol (SSP) is an auditory program designed to stimulate the vagal system and support nervous system regulation.

Methods: A retrospective multiple subject pretest-posttest design was used to examine the impact of the SSP on regulation, engagement, and skill acquisition in children with autism ages 2 to 3 enrolled in an early intervention center …

More Than Covering Ears: A Clinical Inventory For Characterizing Decreased Sound Tolerance (I-Dst) In Autism, Tana B. Carson, Angela Medina, Katherine L. Long, Yuxi Qiu, Monica Noriega

The Open Journal of Occupational Therapy

Background: Decreased sound tolerance (DST) is among the most common and distressing forms of sensory over-responsivity experienced by children with autism spectrum disorders. DST includes hyperacusis and misophonia, among others, and can limit participation in daily activities. Recently, a new screening tool, the Pediatric Hyperacusis and Misophonia Questionnaire (PMHQ-4) has been developed to allow health professionals to better identify and differentiate these conditions using a single assessment. Additional clinical tools are needed to further characterize DST symptoms to facilitate treatment planning after diagnosis.

Methods: In this mixed-methods study n = 15 parents of autistic children 6 to 17 …