Digital Commons Network^™

Letter Of Concern From The Association Of Academic Chairs Of Emergency Medicine Regarding Acgme Proposed Changes, Richard J. Hamilton, Lance B. Becker, Richard E. Wolfe, D. Adam Algren, Arnold Thomas, Michael Baumann, Ross P. Berkeley, Terrell S. Caffery, Chad Cannon, Theodore J. Corbin, Michael E. Chansky, Harinder S. Dhindsa, Charles L. Emerman, David A. Farcy, Chris Fox, Michael A. Gibbs, Christopher S. Goode, Steven "Andy" Godwin, Dietrich Jehle, David Johnson, Samuel M. Keim, Babak Khazaeni, Barry J. Knapp, Clint Hawthorne, John D. Hoyle Jr., Michael Christopher Kurz, Evan Leibner, Robert Mcnamara, Robert F. Mccormack, Edward A. Michelson, Chadwick Miller, Ashley Norse, Andrew Nugent, Brian J. O'Neil, David T. Overton, Edward A. Panacek, William F. Paolo, Denis R. Pauzé, Amanda L. Perez, Ralph J. Riviello, Scott W. Rodi, Peter S. Pang, Juan A. Gonzalez Sanchez, David P. Sklar, Ben C. Smith, Jeffrey R. Stowell, Marc D. Squillante, J. Jeremy Thomas, Terry Vanden Hoek, Gregory A. Volturo, E. Lea Walters, Thomas E. Wyatt, Donald M. Yealy

Department of Emergency Medicine Faculty Publications

This letter, signed by over 50 academic chairs of emergency medicine, urges the ACGME to reconsider a proposed mandate requiring all emergency medicine residency programs to adopt a four-year training model. The authors argue that current three-year programs are supported by data demonstrating equivalent educational and clinical outcomes compared to four-year formats. They criticize the flawed survey methodology underpinning the proposal, note the loss of milestone-based training flexibility, and highlight the lack of added scholarly or clinical value in the fourth year. The letter also outlines negative consequences for fellowship participation, workforce development, trainee debt, and diversity. The signatories advocate …

Gene Expression Changes In Human Cerebral Arteries Following Hemoglobin Exposure: Implications For Vascular Responses In Sah, Chathathayil M Shafeeque, Arif O Harmanci, Sithara Thomas, Ari C Dienel, Devin W Mcbride, Kumar T Peeyush, Spiros L Blackburn

Faculty, Staff and Student Publications

Subarachnoid hemorrhage (SAH), characterized by the presence of hemoglobin (Hb) in the subarachnoid space, significantly impacts cerebral vessels, leading to various pathological outcomes. The toxicity of cell-free Hb released from erythrocytes and its metabolites after SAH causes vasoconstriction and neuronal damage, and correlates with delayed ischemic neurological deficits (DIND). While animal models have provided substantial and invaluable data in the research of aneurysmal SAH, the specific effects of subarachnoid blood on cerebral arteries remain greatly understudied. Here, we describe the changes in the genetic profile of human cerebral arteries exposed to free Hb for 48 h. We performed an ex …

Facilitated Group Care For Maternal And Child Health Model Fidelity: A Scoping Review, Ashley Gresh, Phoebe Parker, Anne Batchelder, Jalana Lazar, Christina X. Marea, Camilla Bjelland, Rohan D. Jeremiah, Giovanna Cristina Machado-Kayzuka, Hayden Geibel, Dhruvi R. Patel, Esnath Kapito, Kathleen F. Norr, Crystal L. Patil

Department of Pediatrics Faculty Publications

Group care is a transformative model of prenatal, postnatal, and well-child care. The Centering-based group care model has three core components: health care, interactive learning, and community building. It has been implemented in 33 countries with associated improved maternal and child health outcomes. Maintaining fidelity to the model is essential for its effectiveness. However, to date no standardised measure of fidelity to the group care model exists. This review aimed to explore how fidelity is measured in group care and identify common themes to understand what is essential to maintain fidelity. We used the scoping review framework by Arksey & …

A Decision-Space Model Explains Context-Specific Decision Making, Dirk W. Beck, Cory N. Heaton, Luis D. Davila, Lara I. Rakocevic, Sabrina M. Drammis, Danil Tyulmankov, Atanu Giri, Shreeya Umashankar Beck, Qingyang Zhang, Michael Pokojovy, Kenichiro Negishi, Alexis A. Salcido, Neftali F. Reyes, Andrea Y. Macias, Serina A. Batson, Paulina Vara, Raquel J. Ibáñez Alcalá, Safa B. Hossain, Graham L. Waller, Laura E. O'Dell, Travis M. Moschak, Ki A. Goosens, Alexander Friedman

Mathematics & Statistics Faculty Publications

Optimal decision-making requires consideration of internal and external contexts. Biased decision-making is a transdiagnostic symptom of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a context-dependent mathematical space for decision-making computations, and how the matrix compartment uses this space to define action value. The model explains multiple experimental results and unifies other theories like reward prediction error, roles of the direct versus indirect pathways, and roles of the striosome versus matrix, under one framework. We also found, through new analyses, that striosome and matrix neurons increase their synchrony during difficult tasks, caused …

High-Resolution Modeling Of Extreme Heat Events With Socioeconomic Consideration: A Real-Case Wrf-Les Approach, Maryam Golbazi, Frank Liu, Yin-Hsuen Chen, Timothy W. Juliano, Heather Richter

ODU Articles

The overarching goals of this work is to explore best practices for micro-scale modeling of a real case, identify relevant phenomena by using high-resolution modeling, and to explore their implications for public health, and climate resilience strategies in Hampton Roads, VA, USA. This project employs the Weather Research and Forecasting (WRF) model to conduct a comprehensive study of Hampton Roads, utilizing a coupled mesoscale to microscale modeling capable of resolving boundary layer turbulence. This study has three primary objectives: (1) to establish the optimal mesoscale to Large-Eddy Simulation (LES) configurations for complex geographical regions such as the Hampton Roads (HR) …

Integrating Human And Animal Health In The Stop Spillover Outbreak Scenarios, Kathleen E. Angell, He Julia Bai, Katherine C. Prager, Janetrix H. Amuguni, Felicia B. Nutter, Jonathan D. Gass Jr, David Brett-Major

Journal Articles: Epidemiology

OBJECTIVES: To generate and employ scenarios of sentinel human and animal outbreak cases in local contexts that integrate human and animal health interests and practices and facilitate outbreak risk management readiness.

METHODS: We conducted a scoping review of past outbreaks and the strengths and weaknesses of response efforts in USAID STOP Spillover program countries. This information and iterative query-and-response with country teams and local stakeholders led to curated outbreak scenarios emphasizing One Health human:animal interfaces at sub-national levels.

RESULTS: Two core scenarios were generated adapted to each of 4 countries’ pathogen priorities and workflows in Africa and Asia, anchoring on …

Drone-Based Medication Delivery For Rural, Flood-Prone Coastal Cities, Yin-Hsuen Chen, Amro M. El-Adle, Kevin J. O'Brien, Taylor Wentworth, Heather G. Richter

Center for Geospatial Science, Education & Analytics Faculty Publications

Access to healthcare remains a critical challenge for rural populations, particularly in flood-prone coastal communities where transportation barriers limit access to essential medical services. This study evaluates the effectiveness of drone-based medication delivery in improving healthcare accessibility for vulnerable populations on Virginia’s Eastern Shore. Compared to traditional personal vehicle travel, drone delivery reduced trip times from up to 50 minutes to under 10 minutes for more than 80% of the population, including elderly patients. Using publicly available datasets, we developed two transportation vulnerability indices that incorporate age, travel time, and flood risk to prioritize patients for drone-based pharmaceutical delivery. These …

The Rise And Fall Of Religion: An Agent-Based Model Of Secularisation, Security And Prosociality, Ivan Puga-Gonzalez, F. Leron Shults, Ross Gore, Konrad Talmont-Kaminski

Center for Secure and Intelligent Critical Systems (CSICS) Publications

The relationship between religion, society, and individual behaviour has been a subject of extensive inquiry, drawing upon a rich collection of historical and contemporary perspectives. The scientific study of religion at the social level has often found its roots in the foundational work of Durkheim (Durkheim, 1912), who posited that religion serves as a catalyst for social order and the promotion of prosocial behaviour. At the same time, Malinowski’s observations regarding the connection between ritual and anxiety have led to a number of lines of inquiry that have come to extend to other aspects of religion. Yet, taken together, these …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Microglial Trem2 Promotes Phagocytic Clearance Of Damaged Neurons After Status Epilepticus, Dale B Bosco, Vaclav Kremen, Koichiro Haruwaka, Shunyi Zhao, Lingxiao Wang, Blake A Ebner, Jiaying Zheng, Manling Xie, Aastha Dheer, Jadyn F Perry, Abhijeet Barath, Aivi T Nguyen, Gregory A Worrell, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus …

“No One Told You Life Was Gonna Be This Way”: A Qualitative Exploration Of Friendship Expectations And Reality In University Life, Michael Priestley, Hannah Rachael Slack, Miss Madiha Islam, Delia Fuhrmann, Emily Long, Sarah Crook, Juliet Foster, Sophie Homer, Nicola Byrom

School of Psychology

Introduction: Young adulthood (ages 18–25) is a high-risk period for loneliness, particularly during educational transitions. Loneliness has negative consequences for mental health, physical health, and educational achievement. Psychologists conceptualize loneliness as emerging from a discrepancy between expected and experienced social connection, but this has been under-explored during young adulthood. Method: Drawing on thematic analysis of eight focus groups with 21 young adults in the UK, this paper explores the differences between retrospective expectations and experience of social connection during the transition into university and the implications for loneliness. Results: Whilst social expectations, experiences, and preferences vary considerably, young adults' perception …

Match Accuracy Of Burned Teeth: A Pilot Study Of Allied Dental Professionals, Brenda T. Bradshaw, Marsha A. Voelker, Samantha C. Vest, Sinjini Sikdar

Dental Hygiene Faculty Publications

Purpose: The purpose of this pilot study was to assess allied dental professionals' match accuracy of burned teeth; a skill required by disaster victim identification (DVI) team members.

Methods: This cross-sectional study used a convenience sample of registered dental hygienists (RDH) (n=15) and dental assistants (DA) (n=15) to assess their match accuracy of burned teeth with simulated antemortem (AM) and postmortem (PM) images. Fifteen human teeth were heated at 400°C for 15 minutes. Prior to and following heat alteration, each tooth was photographed and radiographed. Images were presented to participants in randomized order, and they were instructed to correctly match …

Improving Dental Hygiene Students' Knowledge, Attitudes, And Confidence Toward Prenatal Oral Health Through Experiential Learning, Denise C. Mckinney, Sinjini Sikdar, Shillpa Naavaal

Dental Hygiene Faculty Publications

Purpose Maintaining optimal oral health is essential for maternal health as well as the health of their child. The purpose of this pilot study was to examine dental hygiene (DH) students' knowledge of prenatal oral health before and after receiving an asynchronous prenatal oral health care training (POHCT), and their attitudes and self-perceived confidence before and after receiving an experiential learning opportunity with a pregnant and/or post-partum client at a Women's Infants and Children nutrition program (WIC) clinic.

Methods A one-group pre/post-test design was used. This IRB-approved study (#2027439-4) utilized a convenience sample of DH student participants (n=37) in their …

Prevalence Of Sexuality Implicit Bias In Entry-Level Dental Hygiene Students, Monica Drew, Emily Ludwig, Jessica Suedbeck, Adaira Howell

Dental Hygiene Faculty Publications

Purpose Bias and discrimination may create barriers and affect the delivery of culturally competent care to sexual minorities. An awareness of biases early in education may promote more equitable oral health care delivery to diverse populations. The purpose of this study was to determine the prevalence of sexuality-implicit attitudes in entry-level dental hygiene students at one university.

Methods This cross-sectional survey study included a convenience sample of dental hygiene students from one university (n=74). The Implicit Associations Test (IAT), a validated tool for measuring implicit bias, was modified for use in dentistry with permission from Project Implicit(®) The IAT requires …

Use Of Clinical Competency Examinations For Dental Hygiene Licensure, Jocelyn D. Weinhagen, Tara L. Newcomb, Brenda T. Bradshaw

Dental Hygiene Faculty Publications

Dental hygiene licensure with a clinical competency examination (CCE) using a live patient has been required by state licensing boards since 1929. Clinical competency examinations were initially used when dental training was poorly developed, non-standardized, and largely based on the apprenticeship model. Currently, Canada and the state of California have removed the requirement of passing a CCE for dental hygiene licensure, provided certain requirements have been met. Dentistry is the last health care profession to mandate that graduates pass a CCE. The vast majority of dental licensing boards continue to require that third party testing agencies validate the clinical skills …

Frequency And Perceived Influence Of Menopausal Symptoms On Training And Performance In Female Endurance Athletes, Heather M. Hamilton, Natalie M. Yarish, Kristin E. Heron

Rehabilitation Sciences Faculty Publications

Menopause is associated with several negative health concerns and common menopausal symptoms. Physical activity is essential to mitigate these negative effects, but menopausal symptoms may interfere with participation in physical activity. The purpose of this study was to determine the frequency and the perceived negative effect of menopausal symptoms among female endurance athletes. Female runners, cyclists, swimmers, and triathletes 40–60 years of age were recruited (N = 187). Participants completed an online, anonymous survey that included self-reported menopausal status; the Menopausal Rating Scale (MRS), a validated measure for assessing menopausal symptoms; and the perceived effect of menopausal symptoms on …

Newly Credentialed Athletic Trainers' Onboarding Process During The Transition To Practice, Ashley B. Thrasher, Stacy E. Walker, Julie M. Cavallario

Rehabilitation Sciences Faculty Publications

Context: As new athletic trainers (ATs) transition into their roles, some employers provide orientation and onboarding to assist with the transition to practice. Research in which authors outline the ideal onboarding process for new ATs transitioning to practice is lacking.

Objective: To examine the onboarding process for new ATs.

Design: Grounded theory.

Setting: College or university, secondary school, and hospital or clinic.

Patients or other participants: Seventeen newly credentialed, employed ATs who recently graduated from professional masters' programs (11 female, 6 male; 25.6 ± 2.2 years) and 12 employers (6 female, 6 male; years in role supervising new ATs: 8.5 …

'I Did Not Know We Could Exercise This Small Premature Baby': Challenges Experienced By Parents While Implementing Early Intervention For Their Preterm Infants-A Qualitative Perspective, Manasa Kolibylu Raghupathy, Selim Jahangir, Sonia Khurana, Leslie Edward S. Lewis, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Background

Preterm birth is a highly stressful experience for both parents and infants. Parental participation in care enhances developmental outcomes, fosters parent-infant interactions and builds parental confidence. However, low parental adherence has always been a challenge in the successful implementation of intervention programs both in the NICU and at home. It is imperative to understand parents' perspectives and view the challenges that they experience through their lens while providing early intervention to their infants born preterm. This study is aimed at identifying new parents' challenges when implementing early intervention programs for their infants during the transition from hospital to home. …

Clinician Perspectives On Virtual Reality Use In Physical Therapy Practice In The United States, Danielle T. Felsberg, Jared T. Mcguirt, Scott E. Ross, Louisa D. Raisbeck, Charlend K. Howard, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

The primary goal of physical rehabilitation is to assess movement impairments and restore function to improve overall quality of life. Virtual reality (VR) may provide the optimal environment to promote these goals due to its motivating and modifiable nature which can be difficult to accomplish through traditional real-world therapeutic methods. Current research of VR for rehabilitation has demonstrated that VR interventions can produce clinically meaningful change in motor outcomes. Despite this, adoption and usage of VR by physical therapy professionals is unclear due to the limited research in this area. Thus, the purpose of this study was to identify the …

An 11-Year (2012-2022) Review Of Journal Of Athletic Training Publication Study Designs And Sample Sizes, Zachary K. Winkelmann, Samantha E. Scarneo-Miller, Emily C. Smith, Ryan M. Argetsinger, Lindsey E. Eberman

Rehabilitation Sciences Faculty Publications

Background

Research findings must be representative by creating a sample of individuals, ensuring the results can be generalized and applicable to a larger population, which has historically been guided by a power analysis. However, the varied research design methods require a unique approach to sampling and a formula for recruitment and size. Therefore, the purpose of this study was to analyze historical data from published manuscripts in the Journal of Athletic Training (JAT) relative to study design and sample sizes. A secondary purpose was to further explore metrics for survey-based research.

Methods

This descriptive analysis explored 1267 publications in each …

American Society Of Hematology/International Society On Thrombosis And Haemostasis 2024 Updated Guidelines For Treatment Of Venous Thromboembolism In Pediatric Patients, Paul Monagle, Muayad Azzam, Rachel Bercovitz, Marisol Betensky, Rukhmi Bhat, Tina Biss, Brian Branchford, Leonardo R. Brandão, Anthony K.C. Chan, E. Vincent S. Faustino, Julie Jaffray, Sophie Jones, Hassan Kawtharany, Bryce A. Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie-Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh M. Raulji, Sarah E. Sartain, Clifford M. Takemoto, Cristina Tarango, C. Heleen Van Ommen, Maria C. Velez, Sara K. Vesely, John Wiernikowski, Suzan Williams, Hope P. Wilson, Gary Woods, Ayesha Zia, Reem A. Mustafa

Journal Articles: Pediatrics

BACKGROUND: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials.

OBJECTIVE: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH). These ASH/ISTH evidence-based guidelines are intended to support patients, clinicians, and other health care professionals in the management of pediatric patients with VTE.

METHODS: ASH/ISTH formed a multidisciplinary guideline panel to minimize potential bias from …

The Alcohol Exposome, Nousha H. Sabet, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Science is now in a new era of exposome research that strives to build a more all-inclusive, panoramic view in the quest for answers; this is especially true in the field of toxicology. Alcohol exposure researchers have been examining the multivariate co-exposures that may either exacerbate or initiate alcohol-related tissue/organ injuries. This manuscript presents selected key variables that represent the Alcohol Exposome. The primary variables that make up the Alcohol Exposome can include comorbidities such as cigarettes, poor diet, occupational hazards, environmental hazards, infectious agents, and aging. In addition to representing multiple factors, the Alcohol Exposome examines the various types …

Differential Plasma Carotenoid Profiles In Hypertensive Disorders Of Pregnancy, Colman Freel, Jonah Scheffler, Rebecca Drakowski, Elizabeth Lyden, Matthew Van Ormer, Melissa K. Thoene, Paras K. Mishra, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Background: Hypertensive disorders of pregnancy (HDP) affect one in six pregnancies globally. The etiology of HDP remains unclear but is known to involve oxidative stress. While the body produces endogenous antioxidants, antioxidative nutrients, like carotenoids, remain critical in modulating oxidative stress. The statuses of several carotenoids have been linked to hypertension in both pregnant and non-pregnant populations. However, their associations with the spectrum of HDP, including gestational hypertension (GH), chronic hypertension (CH), and preeclampsia (PE), remains unclear. Our objective was to quantify and compare carotenoid intake and plasma levels among HDP. Methods: We conducted a prospective cohort study …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.

Co-Morbid Indomethacin-Responsive Headaches In A Woman In Her Late 60s With Paroxysmal Hemicrania And Hypnic Headache: A Case Report, Ashlyn Brown, Randolph W Evans, Claudia Carrizo, Mark Burish

Faculty, Staff and Student Publications

Paroxysmal hemicrania (PH) and hypnic headache (HH) are rare indomethacin-responsive headache syndromes. This case report details the new onset of both disorders in a woman in her late 60s. One headache type presented as severe pain centered on the right eyebrow, lasting 30 minutes, occurring more than 8 times daily, and associated with ipsilateral lacrimation and rhinorrhea. The second type was a right frontal severe pain, with onset at 4 a.m., occurring only during sleep, lasting 30 minutes, and with no associated factors. The patient's response to indomethacin for both headache types was confirmed through an unblinded ABAB study design: …

A Bayesian Deep Segmentation Framework For Glioblastoma Tumor Segmentation Using Follow-Up Mris, Tanjida Kabir, Kang-Lin Hsieh, Luis Nunez, Yu-Chun Hsu, Juan C Rodriguez Quintero, Octavio Arevalo, Kangyi Zhao, Jay-Jiguang Zhu, Roy F Riascos, Mahboubeh Madadi, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) is the most common malignant brain tumor with an abysmal prognosis. Since complete tumor cell removal is impossible due to the infiltrative nature of GBM, accurate measurement is paramount for GBM assessment. Preoperative magnetic resonance images (MRIs) are crucial for initial diagnosis and surgical planning, while follow-up MRIs are vital for evaluating treatment response. The structural changes in the brain caused by surgical and therapeutic measures create significant differences between preoperative and follow-up MRIs. In clinical research, advanced deep learning models trained on preoperative MRIs are often applied to assess follow-up scans, but their effectiveness in this …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα …