Medicine and Health Sciences Commons^™

Fusion: A Web-Based Application For In-Depth Exploration Of Multi-Omics Data With Brightfield Histology, Samuel P Border, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, …

Association Of Chronic Conditions With Bladder Health In Women: Cross-Sectional Results From The Rise For Health Study, Camille P Vaughan, Gerald Mcgwin, Jean F Wyman, Siobhan Sutcliffe, Diane K Newman, Ariana L Smith, Colleen M Fitzgerald, Todd Rockwood, James Griffith, Sheila Gahagan, Alayne D Markland, Prevention Of Lower Urinary Tract Symptoms (Plus) Research Consortium

2020-Current year OA Pubs

INTRODUCTION: Women with multiple chronic conditions are more likely than women without them to report lower urinary tract symptoms (LUTS); understanding the association of common and coexisting chronic conditions with bladder health across adulthood may inform prevention efforts.

METHODS: Data were collected from May 2022 through December 2023 from a regionally representative cohort of community-dwelling adult women in the US. Chronic conditions were assessed by self-report and bladder health, and LUTS were measured using validated questionnaires. Analyses were limited to women aged 40 years or older and included multivariable linear and logistic regression models, adjusted for age, body mass index, …

Site-1 Protease Is A Negative Regulator Of Sarcolipin Promoter Activity, Isha Sharma, Meredith O Kelly, Katelyn Hanners, Ella S Shin, Muhammad G Mousa, Shelby Ek, Gretchen A Meyer, Rita T Brookheart

2020-Current year OA Pubs

The timed contraction and relaxation of myofibers in tissues such as the heart and skeletal muscle occur via the tightly regulated movement of calcium ions into and out of the sarcoplasmic reticulum (SR). In skeletal muscle, this phenomenon enables humans to exercise, perform day-to-day tasks, and to breathe. Sarcolipin, a small regulatory protein, prevents calcium ions from entering the SR by binding to and inhibiting SERCA, contributing to myofiber contraction. Disruptions in sarcolipin (SLN) expression are implicated in the pathophysiology of obesity and musculoskeletal disease. However, the mechanisms regulating sarcolipin expression are not clearly understood. We recently showed that site-1 …

Humanization Of Cd47 Enables Development Of Functional Human Neutrophils Via Postirradiation Remodeling Of The Bone Marrow, Esen Sefik, Liang Shan, Et Al.

2020-Current year OA Pubs

Murine and human immune systems differ significantly, particularly within the myeloid lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor cells into genetically modified mice, are invaluable to study human immune development and function in vivo. However, a major limitation of current models is suboptimal myelopoiesis, particularly lack of functional human neutrophils, hampering the modeling of human immune responses and chronic diseases. Here, we describe a humanized mouse model, named MaGIC for genes replaced, in the

Stable Cas9 Expression Regulates Cell Growth By Facilitating Mtorc2 Activation, Le Yu, Yi Jin, Jianfeng Chen, Zhichuan Zhu, Siyuan Su, Emily M Wilkerson, Joanna Gongora, Erica W Cloer, Michael B Major, Pengda Liu

2020-Current year OA Pubs

Clustered regularly interspaced short palindromic repeats (CRISPR), widely used for gene editing, relies on bacterial endonucleases like Cas9 to study gene functions and develop therapies. However, its potential effects on mammalian cellular behavior remain unclear. Here, we systematically profiled effects of stable Cas9 expression on growth of 32 cell lines spanning 9 cancer types and non-cancerous cells, finding growth alterations in a subset. To investigate mechanisms, we established the SpCas9 interactome in DU145 and MDA-MB-231 cells, both showing Cas9-enhanced growth, and identified ribosomal proteins as the top shared interactors. RNA-seq analysis revealed that Cas9 expression in DU145 cells activated PI3K …

A Community-Engaged Approach To Enhancing Participation In Genomic Research In Rare And Understudied Cancer Populations, Saira Khan, Bailey Martin-Giacalone, Kayla Wallace, Briana Wilson, Christine Marx, Erin Linnenbringer, Jessica Mozersky, Melinda Bachini, Nancy Chollet, Dionne Stalling, Li Ding, Ryan C Fields, Graham A Colditz, Bettina F Drake

2020-Current year OA Pubs

UNLABELLED: Few studies provide insights on how to incorporate community members' perspectives of genomic research during the early phases of study development. Engaging with community members early and consistently throughout the research lifecycle could help identify and mitigate barriers to genomic research participation, particularly among groups with rare and understudied cancers.

METHODS: The Washington University Participant Engagement and Cancer Genome Sequencing (WU-PE-CGS) study formed a Participant Engagement Advisory Board (PEAB) consisting of patients, patient advocates, and patient advocacy organizations who represented the three understudied cancer populations: cholangiocarcinoma, early-onset colorectal cancer in Black Americans, and multiple myeloma in Black Americans. PEAB …

Gata2 Mutation Is Associated With Immune Dysfunction And Increased Mycobacterium Haemophilum Susceptibility In Immunocompromised Individuals, Ananya Gupta, Shail B. Mehta, Abhimanyu, Bruce A. Rosa, John Martin, Mushtaq Ahmed, Shyamala Thirunavukkarasu, Farheen Fatma, Gaya K. Amarasinghe, Makedonka Mitreva, Thomas C. Bailey, David B. Clifford, Shabaana A. Khader

2020-Current year OA Pubs

Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by M. haemophilum (Mh, n = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in GATA2 gene, which was absent in healthy controls (HCs, n = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to Mh stimulation for IL-1β, IL-6, IL-8, MIP-1α and MIP-1β, but not to phytohemagglutinin (PHA) or another NTM, M. abscessus. Impaired …

Global Variations In Surgical Techniques For Primary Anterior Cruciate Ligament Reconstruction At Minimum 2-Year Follow-Up: A Systematic Review Of Randomized Clinical Trials, Sina Tartibi, Derrick M Knapik, S Ryan Pierson, Christopher K Bozorgmehr, Daniel C Touhey, Matthew J Matava, Matthew V Smith, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Regional differences in primary anterior cruciate ligament (ACL) reconstruction (ACLR) remain largely unknown.

PURPOSE: To systematically review the literature examining Level 1 and Level 2 studies to identify global differences in surgical techniques associated with primary ACLR.

STUDY DESIGN: Scoping review; Level of evidence, 1.

METHODS: A literature search was conducted following the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using keywords and Boolean phrases in Embase, Cochrane, and PubMed on October 25, 2024. A total of 741 articles were identified. The inclusion criteria were as follows: Level 1 and Level 2 human studies reporting …

Can Predictive And Functional Methods Locate The Dysplastic Hip Joint Center?, Michael Harris, Emma C. Behrman, Keith R. Lohse, Molly C. Shepherd, Bruce A. Macwilliams, Erin M. Mannen

2020-Current year OA Pubs

BACKGROUND: Properly characterizing biomechanics in populations with known hip deformities, such as developmental dysplasia of the hip (DDH), requires accurately identifying the hip joint center (HJC). Many studies have assessed the accuracy or repeatability of predictive and functional methods to locate the HJC in normally shaped hips, but not for hips with DDH.

RESEARCH QUESTION: For patients with DDH, which of three common functional and four common predictive HJC methods is most accurate compared to a magnetic-resonance-imaging-based anatomic method?

METHODS: HJC method accuracy was calculated as the resultant vector distance from the anatomic HJCs. Bias was calculated as distance errors …

Human Single-Neuron Activity Is Modulated By Intracranial Theta Burst Stimulation Of The Basolateral Amygdala, Justin M Campbell, Shuo Wang, Lawrence N Eisenman, James Swift, Tao Xie, Peter Brunner, Jon Timothy Willie, Et Al.

2020-Current year OA Pubs

Direct electrical stimulation of the human brain has been used for numerous clinical and scientific applications. At present, however, little is known about how intracranial stimulation affects activity at the microscale. In this study, we recorded intracranial EEG data from a cohort of patients with medically refractory epilepsy as they completed a visual recognition memory task. During the memory task, brief trains of intracranial theta burst stimulation (TBS) were delivered to the basolateral amygdala (BLA). Using simultaneous microelectrode recordings, we isolated neurons in the hippocampus, amygdala, orbitofrontal cortex, and anterior cingulate cortex and tested whether stimulation enhanced or suppressed firing …

1,2,4-Triazole-Based First-In-Class Non-Nucleoside Inhibitors Of The Bacterial Enzyme Mray, Tomayo Berida, Tzu-Yu Huang, Stefanie C Weck, Marcel Lutz, Samuel R Mckee, Nathalie Kagerah, Destinee L Manning, Mohamed E Jahan, Sushil Mishra, Jennifer Herrmann, Rolf Müller, Robert J Doerksen, Christina L Stallings, Christian Ducho, Sudeshna Roy

2020-Current year OA Pubs

MraY is an essential bacterial enzyme for peptidoglycan synthesis in cell walls and serves as a promising but unrealized target for developing effective antibacterial drugs. Nature has provided a remarkable array of nucleoside inhibitors of MraY, and researchers have skillfully refined these structures to develop inhibitors that effectively mimic natural products. Yet, both natural products and their synthetic variants often face challenges regarding inadequate

Development Of A Novel Algorithm For Tip Fold-Over Detection In Cochlear Implants And Evaluation On Bench And Multiple Clinical Data Bases, Mehrangiz Ashiri, Tony Spahr, Azret Botash, Ashish Mehta, Jordan J Varghese, Craig A Buchman, Andrea J Defreese, Patrick Boyle, Matthew Miller, Syed F Ahsan, Christopher Danner, Kyle P Allen, Loren Bartels, Kanthaiah Koka

2020-Current year OA Pubs

No abstract provided.

Concomitant Anterior Cruciate Ligament And Medial Collateral Ligament Reconstruction: A Systematic Review, Daniel C Touhey, Francisco N Garcia, Sina Tartibi, Robert H Brophy, Matthew J Matava, Matthew V Smith, Derrick M Knapik

2020-Current year OA Pubs

BACKGROUND: Concomitant anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries are among the most commonly reported injury patterns in high-energy knee injuries. Concomitant ACL and MCL reconstruction (ACLR + MCLR) is indicated in patients with full-thickness tears and persistent valgus laxity.

PURPOSE: To systematically review the literature to identify studies reporting on patients undergoing concurrent primary ACLR + MCLR to better understand current indications, surgical techniques, complications, and outcomes.

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 702 studies published in PubMed, EMBASE, and the …

Evaluating And Optimizing Just-In-Time Adaptive Interventions In A Digital Mental Health Intervention (Wysa For Chronic Pain) For Middle-Aged And Older Adults With Chronic Pain: Protocol For A Series Of Randomized Trials, Abby L Cheng, Joanna Abraham, Sarah M Hartz, Eric B Laber, J Philip Miller

2020-Current year OA Pubs

BACKGROUND: On a population level, digital mental health interventions effectively reduce depression and anxiety symptoms. However, middle-aged and older adults with chronic pain and coexisting depression or anxiety have not been adequately represented in digital mental health studies.

OBJECTIVE: The goal of this study is to refine an existing mobile, digital mental health intervention (Wysa for Chronic Pain) that addresses symptoms of depression, anxiety, and coexisting chronic pain for the unique challenges and technology use patterns of middle-aged and older adults.

METHODS: Using a mixed methods, human-centered design approach and a series of randomized trials, we will test and iteratively …

Trajectories Of Recovery After Intravenous Propofol Versus Inhaled Volatile Anaesthesia (Thrive) Randomised Controlled Trial In The Usa: A Protocol, Bethany R Tellor Pennington, Laura Swisher, Mara L Bollini, Michael S Avidan, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

METHODS AND ANALYSIS: This protocol was …

Rural Providers' Attitudes Toward Integrating Harm Reduction Strategies And Prep Prescribing Into Rural Primary Care Settings In The Us. Southeast And Midwest, Phillip L Marotta, Miryam Biaid, Virginia Mckay, Hilary Reno, Lindsey Filiatreau, Kaileigh Backes, Patricia Cavazos-Rehg, Et Al.

2020-Current year OA Pubs

BACKGROUND: People with opioid use disorders (OUD) living in the South and Midwest are under-prescribed pre-exposure prophylaxis (PrEP) despite an increasing number of providers writing PrEP prescriptions in other regions of the United States. Greater research is needed into attitudes toward integrating harm reduction strategies into primary care and PrEP prescribing among prescribers working in rural primary care settings. The objective of this paper was to examine relationships between providers' attitudes toward buprenorphine and methadone, comprehensive harm reduction (e.g., fentanyl test strips) and self-reported PrEP prescribing in the past year.

METHODS: Relationships were examined between attitudes toward buprenorphine and harm …

Advice For Improving The Experience Of Web-Based Patient Portals: Qualitative Interviews With Caregiver-Adolescent Dyads, Rachel E Granberg, Jessica M Goldberg, Alison L Antes, Christine Bereitschaft, Fabienne Bourgeois, James Dubois, Bryan A Sisk

2020-Current year OA Pubs

BACKGROUND: Web-based patient portals can benefit adolescents and their caregivers by increasing access and providing greater understanding of one's health information, enhancing communication with clinicians, and supporting caregiver influence. Despite these benefits, adolescent uptake has been low with high attrition rates. Feedback from adolescents and caregivers is essential to improve the uptake and usability of the web-based patient portal.

OBJECTIVE: The aim of the study is to identify advice for medical informatics administrators and clinicians directed at improving the adolescent and caregiver experience with the web-based patient portal.

METHODS: Caregivers completed a demographic survey followed by separate qualitative, semistructured interviews …

Real-World Adoption Of Adjuvant Therapies For Resected Stage Ib-Iii Non-Small-Cell Lung Cancer, Arvind Kumar, Steven Tohmasi, Nahom Seyoum, Whitney S Brandt, Theodore S Thomas, Nikki E Rossetti, Su-Hsin Chang, Yan Yan, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Brendan T Heiden, Et Al.

2020-Current year OA Pubs

No abstract provided.

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Laura Wright, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Metabolic Rewiring Of Isoniazid Sensitivity In Mycobacterium Tuberculosis, Erin R Wang, Kevin Cho, Gregory A Harrison, Asya Smirnov, Samuel R Mckee, George S Ghabrial, Kelly N Flentie, Wandy Beatty, Thomas Hurtaux, Liza Loza, Tamara L Doering, Gary J Patti, Christina L Stallings, Et Al.

2020-Current year OA Pubs

Isoniazid (INH) inhibits mycolic acid synthesis in

Endothelin B Receptor Inhibition Rescues Aging-Dependent Neuronal Regenerative Decline, Rui Feng, Sarah F Rosen, Irshad Ansari, Sebastian John, Michael B Thomsen, Oshri Avraham, Cedric G Geoffroy, Valeria Cavalli

2020-Current year OA Pubs

Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single-cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron soma residing in the dorsal root ganglia (DRG), express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBR ex vivo …

Community Engagement Studios To Improve Racial Diversity And Health Equity In Parkinson's, Eunyoung Kang, Dominique Woodhouse, Kandace Davis, Jane Q Yap, Peter S Myers, Meghan C Campbell, Yvonne D Hughes, Joyce E Balls-Berry, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: Black or African Americans (AA) with Parkinson's disease (PD) are underrepresented in both care and research and experience significant health disparities. The existing literature provides limited guidance on how to enhance the engagement of AA individuals in PD care and research, particularly from the perspectives of AA patients, care partners, and healthcare providers. This project aimed to (1) describe the use of Community Engagement (CE) Studios as a community-engaged research approach to inform culturally appropriate and inclusive research and (2) examine factors influencing AA engagement in PD-related activities.

METHODS: We conducted three CE Studios: one with AA with PD …

Association Between Conversational Multitasking And Clinician Work Behaviors At A Large Us Health Care System: Cohort Study, Linlin Xia, Daphne Lew, Laura Baratta, Elise Eiden, Sunny Lou, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: Clinical communication is central to the delivery of effective, timely, and safe patient care. The use of text-based tools for clinician-to-clinician communication-commonly referred to as secure messaging-has increased exponentially over the past decade. The use of secure messaging has a potential impact on clinician work behaviors, workload, and cognitive burden.

OBJECTIVE: The objective of this study is to investigate the relationship between conversational multitasking-engaging in multiple concurrent, text-based secure messaging conversations-and clinician workload and cognitive burden for inpatient care.

METHODS: This observational cohort study included attending physicians, trainee physicians, and advanced practice providers who worked in an inpatient setting …

Fatty Acid 2-Hydroxylase Facilitates Rotavirus Uncoating And Endosomal Escape, Enkai Li, Ruochen Zang, Takahiro Kawagishi, Wei Zhang, Kruthika Iyer, Gaopeng Hou, Qiru Zeng, Rita M Meganck, Susan R Ross, Xin Wang, Xiong Su, Siyuan Ding

2020-Current year OA Pubs

Despite the clinical significance of many nonenveloped viruses, the molecular mechanisms of their internalization and membrane penetration are not well understood. Rotaviruses (RVs) are nonenveloped double-stranded RNA viruses and the leading cause of severe dehydrating diarrhea in infants and young children. We identified fatty acid 2-hydroxylase (encoded by

Impacts Of Environmental Distractions And Interruptions On Unsupervised Digital Cognitive Assessments In Older Adults: Cognitive Ecological Momentary Assessment Study, Matthew Welhaf, Hannah Wilks, Andrew J Aschenbrenner, Samhita Katteri, John C Morris, Jason J Hassenstab

2020-Current year OA Pubs

BACKGROUND: Unsupervised cognitive assessments are becoming commonly used in studies of aging and neurodegenerative diseases. As assessments are completed in everyday environments and without a proctor, there are concerns about how common distractions may impact performance and whether these distractions may differentially impact those experiencing the earliest symptoms of dementia.

OBJECTIVE: We examined the impact of self-reported interruptions, testing location, and social context during testing on remote cognitive assessments in older adults.

METHODS: Participants from the Ambulatory Research in Cognition smartphone study were classified as cognitively normal (n=380) or as having very mild dementia (n=37). Participants completed daily tests of …

Postoperative Fluid Restriction To Prevent Delayed Hyponatremia After Endoscopic Transsphenoidal Surgery, Doriann Klaassen, Shinghei Mok, Jenie Y Hwang, Kelley J Williams, Brendan M Fong, Ralph G Dacey, Nyssa F Farrell, Joshua W Osbun, Keith M Rich, Lauren T Roland, John S Schneider, Gregory J Zipfel, Chongliang Luo, Albert H Kim, Julie M Silverstein, Et Al.

2020-Current year OA Pubs

BACKGROUND: Readmission following endoscopic endonasal transsphenoidal surgery (EETS) for pituitary neuroendocrine tumor (PitNET) and other sellar pathology is most commonly due to delayed hyponatremia. Studies suggest postoperative fluid restriction (FR) reduces delayed hyponatremia. We present a prospective randomized controlled study evaluating post-EETS FR.

METHODS: 300 participants were scheduled for EETS (2016-2023) at a single institution. Patients with CKD, CHF, arginine vasopressin deficiency on postoperative day (POD) 3, chronic hyponatremia, and untreated adrenal insufficiency or hypothyroidism were excluded. Groups included control (ad-lib, n = 94), moderate FR (1.8 L/day or 2 L/day weight > 100 kg, n = 39), and strict FR …

Chemo-Rast With Bortezomib Inhibits Multiple Myeloma Relapse, Anchal Ghai, Alexander Zheleznyak, Christopher Egbulefu, Nicole Blasi, Kvar Black, Rui Tang, Matthew L Cooper, Kiran Vij, Ravi Vij, John Dipersio, Monica Shokeen, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Intestinal Microbiome Changes In Response To Amino Acid And Micronutrient Supplementation: Secondary Analysis Of The Amaze Trial, Monica N Mweetwa, Kazi Ahsan, John Louis-Auguste, Ellen Besa, Joram M Posma, Nathan Mcnulty, Micheal J Barrat, Jeff Gordon, Paul Kelly

2020-Current year OA Pubs

Microbial dysbiosis has been linked to environmental enteropathy (EE) and alterations in nutrient absorption; however, compositional modifications following exposure to supplementary nutrients are poorly understood. Here, we report the effect of amino acid and micronutrient supplementation on the gut microbiome of adults with EE. In the AMAZE trial, adults with EE were randomized to amino acids (AA) and/or micronutrients (MM) for 16 weeks in a 2 × 2 factorial design against placebo. Endoscopy was performed before and after intervention, during which duodenal aspirates were collected as well as fecal samples. 16S rRNA amplicon sequencing was performed on both these samples, …

Blue Light As An Anti-Inflammatory And Analgesic Strategy In Thoracic Trauma (Blaastt): Protocol For A Randomised Controlled Trial In Adult Trauma Inpatients With Painful Rib Fractures, Rebecca E Kotcher, Matthew R Rosengart, Luca La Colla, Hsing-Hua Sylvia Lin, Keith M Vogt, Yan Xu, Matthew D Neal

2020-Current year OA Pubs

INTRODUCTION: Blue light (peak wavelength 442 nm) has been shown to modulate the immune response in preclinical models of intra-abdominal sepsis and pneumonia.

METHODS AND ANALYSIS: This is a randomised controlled trial in which adult trauma inpatients (

ETHICS AND DISSEMINATION: Full ethical approval for this trial has been granted by the University of Pittsburgh Institutional Review Board. On study completion, results will be published in the peer-reviewed literature and at ClinicalTrials.gov.

TRIAL REGISTRATION NUMBER: NCT06626334.

Preconditioning With Low-Dose Radiation Improves Antitumor Immunity And Survival In Dc-Vaccinated Mice, Eric Kwon, Shelby Namen, Colin J Willoughby, Solomon Kang, Gaurav Pandey, Alexander B Kim, Carl J Deselm

2020-Current year OA Pubs

Preconditioning regimens are essential for the immunologic success of cell therapies like CAR T cells. Nevertheless, their effect on cancer vaccines is underexplored, and preconditioning regimens are generally absent from cancer vaccine clinical trials. To address this knowledge gap, we evaluated the impact of various preconditioning strategies on dendritic cell (DC) vaccine efficacy in a murine tumor model. Mice bearing syngeneic tumors received preconditioning with 2 Gy low-dose radiation therapy (LD RT; whole-body or tumor-only), cyclophosphamide, paclitaxel, LD RT plus cyclophosphamide, or no preconditioning, followed by administration of antigen-loaded DCs. Whether whole-body or tumor-directed, LD RT preconditioning significantly enhanced vaccine-induced …