Digital Commons Network^™

Pact Is Requisite For Prostate Cancer Cell Proliferation, Dianne J. Beveridge, Andrew J. Woo, Kirsty L. Richardson, Rikki A.M. Brown, Lisa M. Stuart, Manjot Singh, Andrew D. Redfern, Peter J. Leedman

Research outputs 2022 to 2026

PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein with defined antiviral defense and cytoplasmic RNA-induced silencing actions in mammals. We previously described a further role for PACT as a modulator of nuclear receptor (NR)-regulated gene expression. Here, we investigated the role of PACT in prostate cancer (PCa) using a loss-of-function approach. Depletion of PACT in multiple PCa cell lines resulted in a reduction in cell proliferation, but viability was maintained. RNA-sequencing analysis of LNCaP PCa cells ± PACT revealed a depletion of biological processes involved in cell cycle, mitochondrial function, and NR-response pathways in the PACT …

Postinactivity Exercise Training Improves Sarcopenia Traits In 40–60-Year-Old Women Regardless Of Fortified Milk Supplementation, Joanne Trezise, Ricardo M. Lima, Sally D. Poppitt, Aaron C. Fanning, Amanda Devine, Anthony J. Blazevich

Research outputs 2022 to 2026

Background: The term sarcopenia was introduced to describe the age-related decline in muscle mass, but current definitions also include measures of muscle strength and function. Menopause increases sarcopenia risk and may exacerbate the adverse effects of physical inactivity. Exercise training is a potent stimulus to restore muscle health, and nutritional supplementation can further improve the outcomes. The purposes of this study were to examine the changes in a set of sarcopenia-related phenotypes induced by a 14-day step-reduction period followed by a 12-week exercise training programme, with or without fortified milk supplementation in healthy 40–60-year-old females, and to determine whether menopausal …

Hamstring Strength And Architectural Properties Are Associated With Running Biomechanics, Nicholas Ripley, Christopher Bramah, Paul Comfort, John Mcmahon

Research outputs 2022 to 2026

Applied muscular strain and hamstring strain capacity have a joint interaction on hamstring strain injury (HSI) with modifiable risk factors frequently assessed. However, to date there is limited observations on the interaction between these factors. The purpose of the present study was to observe if spatiotemporal characteristics, running kinematics and muscle activation were related to modifiable risk factors of HSI. Twenty-two competitive team sport athletes (24.7 ± 4.3 years, 1.82 ± 0.07 m, 84.9 ± 8.5 kg) participated whereby the Bicep femoris long head (BFLH) fascicle length assessed via ultrasound and isokinetic eccentric hamstring strength was assessed. With running assessment …

Comparison Of Respiratory Responses To Exercise Under Different Heat-Stressful Environments Between Oral Contraceptive And Naturally Menstruating Ovulating Female Athletes, Nanako Hayashi, Toby Mündel, Tze Huan Lei, Claire Badenhorst

Research outputs 2022 to 2026

The present study conducted a secondary analysis of previous data (Lei et al., 2017, 2019) to compare exercise-induced respiratory responses under heat stress between the early follicular (EF)/ quasi -EF and mid-luteal (ML)/ quasi -ML phases in naturally menstruating and oral contraceptive pill (OCP)-using female athletes. Additionally, the study aimed to examine the associations between respiratory responses, thermoregulation, and hormonal profiles within each group. Sixteen endurance-trained female athletes participated: eight with a natural menstrual cycle (NM group) and eight using OCP (OCP group). Each participant completed four trials, comprising fixed-intensity cycling (at 125 and 150 W) followed by a 30-min …

Effects Of Exercise Or Diet Or Combined Interventions On Treatment Efficacy Of Chemotherapy For Cancer: A Systematic Review, Cristina Crespo-Garcia, Francesco Bettariga, Dennis R. Taaffe, Carolyn J. Peddle-Mcintyre, John P. Campbell, Emily Jeffery, Anna Maria Markarian, Anita Borsati, Alice Avancini, Sara Pilotto, Daniel A. Galvao, Robert U. Newton

Research outputs 2022 to 2026

Purpose of Review: While exercise and dietary interventions in patients with cancer undergoing chemotherapy have been demonstrated to be safe and feasible and improve patient-reported outcomes, the effects on treatment efficacy have not been widely examined and remain unclear. This review aimed to examine the effects of exercise, dietary, and combined interventions on tumour response and time-to-event outcomes in patients with cancer undergoing chemotherapy. Recent Findings: A systematic review of intervention studies was conducted based on PRISMA guidelines Databases searched were PubMed, Medline, CINAHL, Embase, and Web of Science. Methodological quality and risk of bias were assessed using the RoB2 …

Deficiencies In Non-Emergency Medical Transportation For Aging Rural Residents Of Iosco County, Michigan, Richard L. Douglass, Donald Stansloski, James Mortimer, Sam Purdy, Dale Evilsizer, Scott Rice

Michigan Journal of Public Health

Introduction: The rural aging population in Michigan struggles to access medical care often available only at significant distances due to limited health system resources and provider shortages. Access to routine care is challenged by lack of non-emergency medical transportation (NEMT). The Iosco County Commission on Aging provides home-delivered meals to eligible county residents. The Rural Health Group investigated the needs of home-delivered meal recipients (aged ≥60 years) for healthcare transportation access. Utilizing data from this investigation, we examined if medical care needs were hindered by problems with transportation in rural Iosco County, Michigan.

Methods: We conducted a cross-sectional survey with …

Physical Therapy Direct Access To Unrestricted Access In The State Of Michigan- Is Michigan Ready To Embrace Change? A Policy Analysis, Erica M. Fernandes, Mary D. Lagerwey, Kieran Fogarty

Michigan Journal of Public Health

Michigan’s Direct Access Provision of 2015 (Enrolled Senate Bill No. 690, 201), which aimed to increase patient access to physical therapy and reduce waiting times, has created hurdles for patient access and for physical therapy as an autonomous profession. The purposes of this policy analysis were: 1) to analyze the Direct Access (DA) policy including examining existing challenges resulting from implementation, 2) provide recommendations for implementing an alternative policy, and 3) outline the benefits of the alternative policy. The DA policy with provisions was examined using the Patton and Sawicki (1993) framework, which provides a basic approach that …

The Effect Of Simulation On Nurses’ Confidence With Providing Post-Fetal Death Support To Bereaved Parents, Monique Scholine, Shannon Zalewski, Erin M. Franklin, Sandria Jamieson, Janelle Diaz, Donna Davis, Kristi Vargo, Nicole Adokou, Kettia Antoine, Natalie Bermudez

Nursing & Health Sciences Research Journal

Introduction: Fetal death (FD) affects one in 10 women worldwide and is associated with negative sequelae such as complicated grief. The negative effects of FD may potentially be mitigated through provision of bereavement support (BS) by trained healthcare workers.

Purpose: The purpose of this study was to explore the effect of simulation on registered nurses’ (RN) confidence in providing BS following FD.

Methods: This was a quasi-experimental study conducted within a South Florida community hospital. Nurses were recruited via email/flyers. Participation in the study entailed attending a post-FD simulation session, and completion of the Perinatal Bereavement Care Confidence Scale (PBCCS) …

Metabolomic Signatures Of Prediabetes In Mexican Americans: The Role Of Genetics And Macronutrients, Shinhye Chung, Charles Evans, Charles F Burant, Han Chen, Bing Yu, David Aguilar, Eric L Brown, Craig L Hanis, Goo Jun

Faculty, Staff and Student Publications

Prediabetes is one of the main health concerns in public health, and various etiological factors contribute to its onset. This study aimed to evaluate genetic associations and gene‐macronutrient interaction with prediabetes‐related metabolites to understand how genetic variation and dietary intake contribute to dysglycemia. We analyzed a total of 482 self‐identified Mexican American participants recruited from Starr County, Texas in 2018‐2019. Untargeted metabolomic profiling was performed using LC‐MS. Nutrient densities of six macronutrients were derived from a 106‐item food frequency questionnaire. Genetic associations for each metabolite were tested using Generalized linear Mixed Model Association Tests (GMMAT). Gene‐macronutrient interactions on prediabetes‐associated metabolites …

Clinical And Genomic Characterization Of Serratia Bloodstream Infections, Roberta Monardo, Lawrence P Park, Felicia Ruffin, Phillip Cox, An Q Dinh, Rachel E Korn, Parisa Farahani, Marco Ripa, Antonella Castagna, Blake M Hanson, Vance G Fowler, Joshua T Thaden, Stacey A Maskarinec

Faculty, Staff and Student Publications

Background: Previously considered a rare opportunistic pathogen, Serratia is now an emerging cause of bacteremia. We compared the risk factors and outcomes of patients with Serratia bacteremia relative to other Enterobacterales in a cohort of hospitalized patients.

Methods: Patients were prospectively enrolled from 2002-2021 at Duke University. Characteristics and outcomes were compared among bacteremic patients due to Serratia and other Enterobacterales. Regression models were used to determine features associated with outcomes. Whole genome sequencing (WGS) was performed to characterize the phylogenetic diversity of Serratia isolates associated with device infections.

Results: Of 2676 patients, 173 (6.5%) had Serratia bacteremia. Among patients …

Capsinoids, Non-Pungent Trpv1 Agonists, Induce A Mild Hypothermia That Provides Short- And Long-Term Neuroprotection After Ischemic Stroke, Alexander Andersohn, Alexander Andersohn

Dissertations and Theses (Open Access)

Therapeutic hypothermia (TH) has demonstrated neuroprotection in instances of cardiac arrest and neonatal hypoxia/ischemia but faces different challenges in application to stroke due to the activation of cold defense mechanisms in conscious patients. This dissertation examines the efficacy and specificity of capsinoids (a purified mixture of capsiate and dihydrocapsiate) to induce a sustained mild hypothermia in conscious mice that is neuroprotective after stroke. Capsinoids function as TRPV1 agonists. However, unlike capsaicin, capsinoids are vulnerable to esterase-mediated breakdown, thus significantly restricting their action to the site of delivery. We showed that capsinoids delivered intraperitoneally (IP) to mice induced a TRPV1-dependent drop …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Maternal Folic Acid Supplement Use, Folate Intake, And Preterm Birth Among Infants With Spina Bifida, Renata H Benjamin, Katherine L Ludorf, Rachel P Allred, Jenil R Patel, Wendy N Nembhard, Gary M Shaw, Suzan L Carmichael, Tania A Desrosiers, Eirini Nestoridi, Eva M Williford, A J Agopian

Faculty, Staff and Student Publications

Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida.

Methods: We conducted a retrospective population-based study using the National Birth Defects Prevention Study (NBDPS; 1999-2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid-containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status.

Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD-STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations …

Epidemiological Patterns And Variability In Acute Brain Injury: A Multicenter Registry Analysis In South Korea's Neurocritical Care Units, Heewon Jeong, So Hee Park, Yoon-Hee Choo, Dong-Wan Kang, Yong Soo Kim, Bosco Seong Kyu Yang, Huimahn Alex Choi, Sung-Min Cho, Eun Jin Ha, Jiwoong Oh, Han-Gil Jeong

The Brown Foundation: Institute of Molecular Medicine

Background: Specialized neurocritical care (NCC) improves outcomes in acute brain injury (ABI), but significant variability exists in practices across and hospitals within South Korea's developing national NCC system. This study aims to assess clinical variability among patients with ABI across six tertiary NCC units (NCCUs) in South Korea and evaluate center-specific effects on clinical outcomes.

Methods: A multicenter registry of patients with ABI admitted to NCCUs between April 2023 and April 2024 was analyzed. A descriptive analysis was conducted to evaluate demographic, clinical, and treatment characteristics across centers. Variability across centers was quantified using the average standardized mean difference (SMD) …

Ddt Exposure Induces Microglial Activation And Disease-Associated Microglial Signatures: Relevance To Mechanisms Of Alzheimer’S Disease, Isha Mhatre-Winters, Aseel Eid, Nicole Blum, Yoonhee Han, Ferass M Sammoura, Long-Jun Wu, Jason R Richardson

The Brown Foundation: Institute of Molecular Medicine

Background: Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective: Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods: DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady Roshchupkin, Tim D'Aoust, Marie-Gabrielle Duperron, Muralidharan Sargurupremraj, Ami Tsuchida, Masaru Koido, Marziehsadat Ahmadi, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Koichi Matsuda, Yutaka Suzuki, Yoshiya Oda, Akinori Kanai, Pouria Jandaghi, Markus Munter, Daniel Auld, Iana Astafeva, Raquel Puerta, Jerome I Rotter, Bruce M Psaty, Joshua C Bis, W T Longstreth, Thierry Couffinhal, Pablo García-González, Vanesa Pytel, Marta Marquié, Amanda Cano, Mercè Boada, Marc Joliot, Mark Lathrop, Quentin Le Grand, Lenore J Launer, Joanna M Wardlaw, Myriam Heiman, Agustin Ruiz, Paul M Matthews, Sudha Seshadri, Myriam Fornage, Hieab Adams, Aniket Mishra, David-Alexandre Trégouët, Yukinori Okada, Manolis Kellis, Philip L De Jager, Christophe Tzourio, Yoichiro Kamatani, Fumihiko Matsuda, Carlos Cruchaga, Stéphanie Debette

Faculty, Staff and Student Publications

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Public Health Trade-Offs During A Pandemic: Mobility Decline And Hypertension Risk In India, Arpita Khanna, Tomoki Fujii

Research Collection School Of Economics

The Covid pandemic dramatically altered patterns of daily life, particularly through widespread declines in mobility due to lockdowns and social distancing measures. While the economic and epidemiological effects of these restrictions have been widely studied, their broader health implications remain underexplored. This paper investigates the relationship between mobility decline during the Covid pandemic and hypertension outcomes in India. Leveraging district-level variation in mobility from Google Community Mobility Reports and health data from the 2019–2021 Indian Demographic and Health Survey (DHS), we find that a 1 percentage point reduction in mobility over the 30 days prior to interview is associated with …

Potential Adverse Effects On Lifestyle And Food Intake Pattern In Night Shift Workers, Stacie L. Coleman

Electronic Theses, Projects, and Dissertations

Abstract

Night shift work is prevalent in healthcare and other industries, yet its effects on lifestyle factors such as food intake, sleep quality, and mental health remain underexplored. This study investigates the impact of night shift schedules on nurses’ wellness, focusing on eating patterns, sleep, physical activity, and mood. A sample of 13 nurses were divided into two shift groups: day (n=5) and night (n=8); and they completed a questionnaire to assess the variables related to their behavior, food choices, eating habits, sleep patterns.

The results of previous research studies indicate that night shift nurses are more likely to adopt …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

The Impact Of Social Media Use On Postpartum Depression, Jaila Randle

Capstone Experience: Master of Public Health

Postpartum depression (PPD) is a serious form of depression that affects one in eight women. Symptoms include feeling sad all the time, being anxious, and having trouble bonding with their child. As social media sites like Facebook and Twitter become more important for moms to find support and health information, it has become a public health concern to learn how they affect mental health after giving birth. This literature review explores the positive and negative impacts of social media use on postpartum depression among mothers. A systematic search identified peer-reviewed studies published between 2014 and 2025. Studies were selected using …

Acceptability Of Corticosteroid Use In The Treatment Of Infant Bronchiolitis: Utilizing The Theoretical Framework Of Acceptability To Design Research Instruments, Caroline R. Smetanka

Capstone Experience: Master of Public Health

Bronchiolitis is the leading cause of hospitalization among infants under six months, yet treatment remains largely supportive due to clinical guidelines that discourage pharmacologic intervention. Recent research suggests that bronchiolitis is not a uniform condition, and a subgroup of infants (those classified within “Profile A”) may benefit from targeted corticosteroid therapy. However, these treatments remain outside current clinical guidelines, and their successful adoption depends on stakeholder acceptability. This Capstone project developed and refined four data collection instruments- two questionnaires and two interview guides- designed to assess how healthcare providers and caregivers perceive the acceptability of corticosteroid treatment for Profile A …

Utilization Of Tricare’S Childbirth And Breastfeeding Support Demonstration: Access To Lactation Services Among Military Families, Holly Johnson

Capstone Experience: Master of Public Health

In January 2022, the Department of Defense launched a five-year pilot program called the TRICARE Childbirth and Breastfeeding Support Demonstration. This demonstration aimed to cover lactation services for Tricare beneficiaries. This project included an electronic survey and was created and completed by 577 participants. Eligible participants needed to have given birth in the last 24 months and have TRICARE as their primary insurance. Participants completed this survey to help understand if they were aware of lactation benefits, if they utilized the service, and if it improved their breastfeeding experience.

Out of the 577 participants, 485 were eligible for the project. …

The Effectiveness Of Interventions In Reducing Sexually Transmitted Infections Among African American Adolescents: A Comprehensive Literature Review, Brandy M. Leaver

Capstone Experience: Master of Public Health

In the United States, an estimated 20 million new sexually transmitted infections occur annually, with half of the cases occurring in adolescents. The infection rate among African American adolescents is four times higher than that among white adolescents. Although many types of interventions exist, few are specifically designed for African American adolescents. In conducting this comprehensive literature review and synthesis, I examined the effectiveness of existing interventions in creating behavioral change among African American adolescents by applying the health belief model to interpret and organize the findings. The databases PubMed, Embase, and Google Scholar were searched on October 1, 2025. …

Reducing Sleep-Related Infant Deaths In Douglas County, Lauren J. Maskin

Capstone Experience: Master of Public Health

Douglas County, including the city of Omaha, covers 339.6 square miles along the border of the Missouri River in Nebraska with a population of 517,110 (https://www.douglascounty-ne.gov/) and is one of seven large urban counties in the state. There are approximately 8,000 infants born in Douglas County annually (Nebraska Vital Statistics Birth Dashboard). The Douglas County Health Department (DCHD), established in 1854, is one of the oldest county health departments in the state and manages multiple public health projects annually. In 2024-2025, a renewed focus for DCHD has been its infant mortality rate (IMR). In 2024, 44 infant mortalities occurred in …

Fam13a Polymorphism Is Associated With A Usual Interstitial Pneumonia Pattern In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Elana J Bernstein, Francesco Boin, Brett Elicker, Yiming Luo, Yawen Ren, Meng Zhang, John Varga, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and …

Nocturnal Oxygen Therapy For Central Sleep Apnea In Patients With Heart Failure: A Multisite, Double-Blind, Sham-Controlled Randomized Clinical Trial (Loft-Hf), Susan Redline, Dongdong Li, Shahrokh Javaheri, Sanjay R Patel, Sairam Parthasarathy, James C Fang, Lee K Brown, Mark Dunlap, M Safwan Badr, Neomi Shah, Luqi Chi, Ruckshanda Majid, Mihaela Teodorescu, Garrick Stewart, Eileen Hsich, Tamar Polonsky, Justin Vader, Maryl R Johnson, Dennis Auckley, Henry Klar Yaggi, Andrew Kao, Ali Azarbarzin, Raichel Alex, Michael Rueschman, Lisa Wolfe, Daniel J Gottlieb, Scott A Sands, Phyllis C Zee, Reena Mehra, Babak Mokhlesi, Rami Khayat, Eldrin F Lewis, William T Abraham, Rui Wang

Faculty, Staff and Student Publications

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF but has not been rigorously studied. Objectives: To compare NOT with sham NOT (control) in heart failure (HF) patients receiving guideline-based HF therapy on the composite outcome of first occurrence of either mortality due to any cause, a lifesaving cardiovascular intervention, or an unplanned hospitalization for worsening HF, together with other secondary outcomes.

Methods: A multisite, double-blind, sham-controlled randomized clinical trial was conducted …

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells For Parkinson's Disease: A Randomized Trial., Mya C Schiess, Jessika Suescun, Juan D Martinez-Lemus, Charles Green, Tia S Thomas, Mohammad Shahnawaz, Emily Tharp, Nikunj B Satani, Jerome G Saltarrelli, Christopher Adams, Marie-Francoise Doursout, Vanessa Thyne, Rula Abuamouneh, Elsa M Rodarte, Sean I Savitz, Timothy M Ellmore

Faculty, Staff and Student Publications

Background: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo-hMSCs) may reduce neuroinflammation and improve motor symptoms.

Objectives: To evaluate the efficacy of repeated intravenous doses of 10 × 106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP).

Methods: In this phase 2, randomized, placebo-controlled trial (November 2020-July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …