Digital Commons Network^™

The Present And Future Of Precision Oncology And Tumor-Agnostic Therapeutic Approaches, Nakul M Shah, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Precision oncology has transformed the treatment landscape for patients with advanced solid tumors. Tumor-agnostic therapies, those that have been approved based on genetic mutations or biomarkers across tumor histology types, are important examples of how the implementation of precision oncology can expand therapeutic options for patients, especially those with rare cancer types and treatment-refractory disease. In this review, we first discuss how advances in next-generation sequencing and molecular profiling have enabled the identification of shared actionable alterations. Subsequently, we explore the current landscape of tumor-agnostic therapies that have received approval from the Food and Drug Administration. We discuss the strengths …

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

Prediction Of Methotrexate Neurotoxicity Using Clinical, Sociodemographic, And Area-Based Information In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, Maria Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Center for Medical Ethics and Health Policy Staff Publications

Background: Methotrexate is a critical component of pediatric acute lymphoblastic leukemia (ALL) therapy that can result in neurotoxicity which has been associated with an increased risk of relapse. We leveraged machine learning to develop a neurotoxicity risk prediction model in a diverse cohort of children with ALL.

Methods: We included children (age 2-20 years) diagnosed with ALL (2005-2019) and treated in Texas without pre-existing neurologic disease. Clinical information was obtained by medical record review. Neurotoxicity occurring post-induction and prior to maintenance therapy was defined as neurologic episodes occurring within 21 days of methotrexate. Suspected cases were independently confirmed by 2 …

Oxygen Saturation Targeting In The Neonatal Intensive Care Unit, Faeq Almudares, Bheru Gandhi, Jonathan Davies, Xanthi Couroucli, Natalie Villafranco, Nidhy Paulose Varghese, Milenka Cuevas Guaman, Charleta Guillory, Binoy Shivanna

Faculty, Staff and Students Publications

Oxygen (O2) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O2) and hyperoxia (excess tissue O2), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O2 saturation targets and therapeutic titration. Most current neonatal O2 targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles …

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …

In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Tong Huo, Wenfang Zhang, Zhili Yu, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi

Faculty, Staff and Students Publications

The MacAB-TolC tripartite efflux pump is widely distributed in Gram-negative bacteria, extruding antibiotics and virulence factors that lead to multidrug resistance and pathogenicity. However, the in situ structure and assembly mechanism of MacAB-TolC remain unclear. Here, we resolve the in situ structures of the MacAB-TolC efflux pump in Escherichia coli by electron cryo-tomography and subtomogram averaging. In the cells without antibiotic treatment, we observe a fully assembled MacAB-TolC pump. When Escherichia coli cells are treated with erythromycin, in addition to the tripartite pumps, we also discover the emergence of MacA-TolC subcomplexes without MacB, indicating flexible binding of MacB in the …

Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Zhenjiang Li, Shudi Pan, Brittney O Baumert, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Background: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: We conducted a longitudinal study involving 60 adolescents with severe obesity …

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …

Evaluation Of Social Worker Knowledge Of Human Trafficking At The Oregon State Hospital: A Qualitative And Quantitative Analysis Of Education, Training, And Victim Identification, Jamie Sue Pryde

Dissertations and Theses

The prevalence of human trafficking continues to increase worldwide, and the implementation of human trafficking education and victim identification within institutions is slow to catch up. The Oregon State Hospital is a psychiatric in-patient hospital that currently does not provide human trafficking education or a screening tool for staff and does not know how to provide treatment to trafficked victims. Interviews were conducted with employed social workers at the Oregon State Hospital to obtain a baseline understanding of their previous education, training, and knowledge of human trafficking to aid in the creation of a trafficking screening tool. Results indicate participants …

Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, Steve Parrish, David Fuentes

Faculty, Staff and Student Publications

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very …

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …

Iron Deficiency Without Anemia And Reduced Basal Ganglia Iron Content In Youths, Dimitri Fiani, Joo-Won Kim, Mianzhi Hu, Ramiro Salas, Sarah Heilbronner, Jacquelyn Powers, Muhammad Haque, Stephanie Dinh, Xiaofan Huang, Darrell Worthy, Sridevi Devaraj, Junqian Xu, Chadi Calarge

Faculty, Staff and Students Publications

Importance: Although brain iron is necessary for neurogenesis, myelination, and neurotransmitter synthesis, iron deficiency (ID) is defined solely based on hematological outcomes.

Objective: To examine the association of ID without anemia with basal ganglia (BG) iron content and its structural and functional sequelae in adolescents.

Design, setting, and participants: This cross-sectional study enrolled participants using the electronic medical record system from a large network of pediatrics clinics between December 2020 and April 2024. Otherwise healthy, unmedicated participants aged 10 to 17 years with a depressive or anxiety disorder or with no psychopathology were consecutively enrolled. Anemia and acute inflammation led …

Anemia: An Uncommon Cause Of Cerebral Venous Sinus Thrombosis, Iqra Athar, Afrah Malik, Neelma Naz Khattak, Tashfain Shifa, Zukhruf Zayian

Pakistan Journal of Neurological Sciences (PJNS)

Cerebral venous sinus thrombosis (CVST) is a multifactorial illness seen more commonly in females as compared to males. Its diagnosis is often delayed due to variable clinical presentations. It is now identified more often due to advancements in neuroimaging modalities. We present an uncommon case of CVST caused by anemia in a 23-year-old female. Our patient presented with complaints of headache since the past two days and left sided hemiplegia since past one day. Later on during her hospital stay she developed generalized tonic clonic seizures. MRI and MRV brain with contrast revealed right cerebral venous (vein of Trolard) thrombosis. …

Insights On Human Papillomavirus Among Medical Students And Professionals, Fathima Thansiha, Amogha Shree, Rashmi S

Digital Journal of Clinical Medicine

Background: As per World Health Organization, in 2022, 660000 women were diagnosed with cervical cancer worldwide and 350000 women died from the disease. Sexual behaviour is the major risk factor and exposure to Human Papillomavirus has been established as a causative agent in 70-80% of the cases for development of cervical cancer. Most infections with HPV resolve spontaneously and cause no symptoms, persistent infection can cause cervical cancer in women. Effective primary (HPV vaccination) and secondary prevention approaches (screening and treating precancerous lesions) will prevent most cervical cancer cases. Thus, study was conducted with the objective of assessing the knowledge …

Issue 13: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 13

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

Topics: Original Study Summaries from early 2025 with clinical implications:

pGGNs thresholds, Phosphodiesterase-5 Inhibitors with COPD, TTIP ventilation, TAPSE/sPAP Ratio, Propofol, Triglycerides, & Pancreatitis, PEERLESS trial, Metagenomic NGS for SCAP, Termination of Resuscitation (TOR) Guidelines, Intermittent Fasting …

Impact Of Cessation Of Caffeine Citrate Therapy On Intermittent Hypoxemia Patterns Among Preterm Infants Born Before 34 Weeks, Peter Kipkurui Mashep, Roseline Ochieng, Jesse Coleman, Mary Waiyego, Amy Sarah Ginsburg, Dorothy Chomba, Morris Ogero Ondieki, Grace Irimu, William Macharia, Mark Ansermino

Paediatrics and Child Health, East Africa

Introduction: Intermittent hypoxemia (IH) is defined as oxygen saturation (SpO₂) drop ≥5% from the baseline (set at 90 s preceding the event) to a level less than 90% lasting for ≥5 s. Caffeine citrate, the standard of care for apnea of prematurity, reduces IH events. IH contributes to both short and long-term adverse neurologic outcomes. Standard patient monitors cannot detect IH events due to long averaging times.

Objective: Describe change in patterns of IH events in preterms < 34 weeks before and after cessation of caffeine citrate and factors associated.

Methods: Interrupted time series study design. Data was collected from 1 December 2022 to 30 June 2023. MASIMO RAD-G oximeter was …

Understanding And Addressing Mental Health Challenges Of Families Admitted To The Neonatal Intensive Care Unit., Ashley D. Osborne, Daphna Yasova Barbeau, Tiffany Gladdis, Kara Hansen, Tonia Branche, Emily R. Miller, Christine C. Pazandak, Margaret K. Hoge, Michelle Spencer, Diana Montoya-Williams, Ryan Barbeau, Heather Padratzik, Stephen Lassen

Manuscripts, Articles, Book Chapters and Other Papers

This article reviews the psychological distress experienced by NICU families, including anxiety, postpartum depression (PPD), and post-traumatic stress disorder (PTSD), in addition to providing recommendations for clinicians at the individual, institutional, and national level. Currently, mental health screenings, specialized evaluations, and treatment options are not routinely offered to NICU families and are frequently under-utilized when offered. Here we provide expert opinion recommendations to address challenges in supporting universal screening, offering bedside interventions, including trained mental health professionals in care plans, updating neonatology training competencies, and advocating for policies that support the mental health of NICU families. We advocate that mental …

Whole-Exome Sequencing Identified Molecular Variants Linked To The Progression Of Gastric Precancerous Lesions In Patients From Southwestern Colombia—An Exploratory Approach., Lizeth Mejia-Ortiz, Jovanny Zabaleta, Jone Garai, Luis Eduardo Bravo, Andres Castillo

School of Graduate Studies Faculty Publications

No abstract provided.

Development And Mechanistic Investigation Of Recombinant Type Iii Humanized Collagen Gel For Mid-Facial Soft Tissue Repair, Qian Wang, Qifei An, Yuanzhou Wang, Jingbo Yang, Xiujuan Zhang, Shibo Jiang, Min Chen, Lu Lu, Yun Zhu

Center for Translational Medicine Faculty Papers

Mid-facial depression is a key sign of facial aging, primarily caused by the loss of collagen leading to depletion of the extracellular matrix (ECM). However, the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression. Therefore, we herein report the development of a novel recombinant humanized type III collagen gel (C3Gel) through rational design and modification of a commercially available recombinant type III humanized collagen lyophilized fiber product. Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo. C3Gel formed a dense fibrous structure around cells, significantly improving …

Developmental Lead Exposure And Aggression In Male Rats: Influences Of Maternal Care And Environmental Enrichment, Shamaila Zafar, Courtney K. Williams, Jaehyun Joo, Blanca E. Himes, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Developmental lead (Pb) exposure results in a variety of cognitive deficits and behavioral issues including increased antisocial behavior and aggression. This study investigated the effect of developmental Pb exposure on aggression and violent behavior in male rats and the potential modulatory influences of quality of maternal care and enriched/non-enriched housing conditions. Long-Evans male rats with or without Pb exposure (perinatal or early postnatal) from low or high maternal care mothers (based on amounts of licking/grooming and arched- back nursing) were randomly assigned to live in enriched or non-enriched environments at weaning. At post- natal day 120–190, offensive aggression was assessed …

Association Of Sars-Cov-2 With Health-Related Quality Of Life 1 Year After Illness Using Latent Transition Analysis, Lauren Wisk, Michael Gottlieb, Peizheng Chen, Huihui Yu, Kelli O'Laughlin, Kari Stephens, Graham Nichol, Juan Carlos Montoy, Robert Rodriguez, Michelle Santangelo, Kristyn Gatling, Erica Spatz, Arjun Venkatesh, Kristin Rising, Mandy Hill, Ryan Huebinger, Ahamed Idris, Michael Willis, Efrat Kean, Samuel Mcdonald, Joann Elmore, Robert Weinstein

Department of Emergency Medicine Faculty Papers

BACKGROUND: Long-term sequelae after SARS-CoV-2 infection may impact health-related quality-of-life (HRQoL), yet it is unknown how HRQoL changes during recovery. We compared patient-reported HRQoL among adults with COVID-19-like illness who tested SARS-CoV-2 positive (COVID+) with those who tested negative (COVID-).

METHODS: Participants in this prospective, multicenter, longitudinal registry study were enrolled from December 2020 through August 2022 and completed 3-month follow-up assessments until 12 months after enrollment. Participants were adults (≥18 years) with acute symptoms suggestive of COVID-19 who received a Food and Drug Administration-approved SARS-CoV-2 test. Participants received questions from PROMIS-29 (subscales: physical function, anxiety, depression, fatigue, social participation, …

Spectrum Of Demyelinating Diseases In Pakistan: A Multicenter Cross-Sectional Study, Zainab Aslam Saeed Memon, Safia Awan, Haris Majid Rajput, Qamar Un Nisa, Muhammad Subhan, Lal Chand, Muhammad Wazir Ali Khan

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective: Demyelinating diseases are a heterogeneous group of disorders of the central nervous system, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute disseminated encephalomyelitis (ADEM). Data from South Asia remain scarce, despite potential regional variations in disease spectrum and outcomes. The objective of this study was to characterize the demographic, clinical, and disability profile of patients with demyelinating disorders across Pakistan.

Methods: This multicenter cross-sectional study was conducted between August 2017 and December 2019 across 39 neurology centers in Pakistan. Adult patients (≥18 years) diagnosed with demyelinating disorders using standardized criteria were included. Data on …

22q11.2 Enhanced Recovery After Surgery Pathway (Eras), Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Early Life Exposure To Fine Particulate Matter And Fine Motor Function, Attentional Function, And Working Memory Among Spanish School-Aged Children, Kristina W Whitworth, Aitana Lertxundi, Mingze Yuan, Alison Rector-Houze, Wei-Jen Chen, Mònica Guxens, Jordi Julvez, Michael Swartz, Elaine Symanski, Antonia Valentin, Carmen Iniguez, Llúcia L González-Safont, Jesús Ibarluzea

Faculty, Staff and Student Publications

Background: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.

Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …