Digital Commons Network^™

Testing And Evaluation Of Generative Large Language Models In Electronic Health Record Applications: A Systematic Review, Xinsong Du, Zhengyang Zhou, Yifei Wang, Ya-Wen Chuang, Yiming Li, Richard Yang, Wenyu Zhang, Xinyi Wang, Xinyu Chen, Hao Guan, John Lian, Pengyu Hong, David W Bates, Li Zhou

Faculty, Staff and Students Publications

Background: The use of generative large language models (LLMs) with electronic health record (EHR) data is rapidly expanding to support clinical and research tasks. This systematic review characterizes the clinical fields and use cases that have been studied and evaluated to date.

Methods: We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to conduct a systematic review of articles from PubMed and Web of Science published between January 1, 2023, and November 9, 2024. Studies were included if they used generative LLMs to analyze real-world EHR data and reported quantitative performance evaluations. Through data extraction, we identified …

Incidence Of Cancers Among Children Living With Hiv In Malawi After Widespread Availability Of Antiretroviral Therapy: A Population-Based Study, Casey L Mcatee, Fatsani Manase, William Kamiyango, Jimmy Villiera, Mark Zobeck, Joseph Mhango, Allison Silverstein, Samuel Maloya, Apatsa Matatiyo, Eluness Simwela, Honour Mhango, Desire Hellings, Brigid O'Brien, Claudia Wallrauch, Tom Heller, Matthew Painschab, Kate Westmoreland, Atupele Mpasa, Rizine Mzikamanda, Nmazuo Ozuah, Joseph Lubega, Nader Kim El-Mallawany, Carl E Allen, Michael E Scheurer

Faculty, Staff and Students Publications

Purpose: Few data describe the modern epidemiology of pediatric HIV-associated cancers in sub-Saharan Africa, home to over 80% of the world's children living with HIV. This study evaluated the incidence of cancers among these children over 15 years after widespread antiretroviral therapy (ART) adoption in Malawi.

Methods: We conducted a retrospective population-based cohort study leveraging multiple independent data sources comprehensive of all cancer diagnoses among children living with HIV in Northern and Central Malawi between 2010 and 2024. HIV-associated cancers were defined as those cancers with well-established epidemiologic associations with HIV. Cumulative incidence and average annual percent change were estimated …

Comparing Observed With Self-Reported Hand Hygiene Adherence Among Bedside Nurses And Physicians At Two Hospitals In The United States, Prathit A Kulkarni, M Todd Greene, Sanjay Saint, Karen E Fowler, Serene Jacob, Laura Dillon, Michelle Espiritu, Nathan Houchens, Huberta T Cozart, Barbara W Trautner

Faculty, Staff and Students Publications

Background: Hand hygiene is a core component of infection prevention in healthcare settings. One potential reason for lack of adherence to recommended hand hygiene practices is erroneous self-perception. We aimed to compare perceptions about hand hygiene compliance with objective data.

Methods: Direct observations of hand hygiene performance by nurses and physicians during typical workflow in inpatient general medicine wards were conducted from 12 September 2022 to 27 October 2022 at two academic Veterans Affairs medical centers. Participants were surveyed regarding perceptions about their hand hygiene performance relative to recommended practices.

Results: Among nurses, hand hygiene was performed in 1,397/3,690 (37.9%) …

Spatial Profiling Reveals Distinct Molecular And Immune Evolution Of Mouse Lung Adenocarcinoma Precancers With Or Without Carcinogen Exposure, Bo Zhu, Muhammad Aminu, Pingjun Chen, Jian-Rong Li, Chuanpeng Dong, Chenyang Li, Yanhua Tian, Shao-Wei Lu, Hong Chen, Chenxi Ma, Xin Hu, Jie Ye, Andrew Y Liu, Beibei Huang, Frank R Rojas, Parra Cuentas Edwin Roger, Ou Shi, Monique B Nilsson, Alissa Poteete, Khaja B Khan, Wei Lu, Luisa M Solis Soto, Junya Fujimoto, Cara Haymaker, Ignacio I Wistuba, Zhubo Wei, Linghua Wang, Don L Gibbons, Ken Chen, Alexandre Reuben, Jason M Schenkel, John V Heymach, Chao Cheng, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

Tumor evolution involves genetic, transcriptional, and phenotypic alterations that shape cancer cell behavior and interactions with the microenvironment. While single‐cell technologies have advanced our understanding of this process, spatial dynamics remain incompletely characterized. Here, whole‐exome sequencing (WES), imaging mass cytometry (IMC), and spatial transcriptomics (ST) were integrated to study molecular evolution and immune responses in two lung adenocarcinoma (LUAD) mouse models: a genetically engineered model (129S4/Sv‐KrasLSL‐G12D, termed 129S4 K) and a carcinogen‐induced precancer model (129S4 U). Compared to 129S4 K, 129S4 U tumors exhibited higher mutational, neoantigen but lower copy number variation (CNV) burdens at matched developmental timepoints, consistent with …

Physical Activity In Osteosarcoma Patients During And Post Therapy: A Single Site Prospective Observational Study, Elysia R Cohen, Clark Andersen, Karen Moody, Maria C Swartz, Michael C Robertson, Alakh Rajan, Theresa Honey, Sandra Lugo, Grace Waterman, Keri Schadler

Faculty, Staff and Student Publications

PURPOSE: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Many patients face long-term impairments in their mobility and function after treatment, leading to a decrease in their quality of life. Exercise has been shown to improve functional recovery and improve quality of life in patients with cancer, though data specific to children with osteosarcoma are sparse. Exercise has also been shown to be feasible in patients undergoing chemotherapy, with numerous potential benefits to health and quality of life. To design the most effective exercise interventions for children and adolescents with osteosarcoma, we must first understand the …

Potential Missed Opportunities To Administer Intravenous Thrombolysis To Patients With Acute Ischemic Stroke, Babak B Navi, Mengxi Wang, Jose-Miguel Yamal, Suja S Rajan, Alexandra L Czap, Stephanie A Parker, May Nour, Ilana Spokoyny, Saad Mir, Mathew E Fink, Joshua Z Willey, William J Jones, James C Grotta

Faculty, Staff and Student Publications

Background: Recent years have seen improvements in stroke-care pathways, including mobile stroke units (MSUs), and this may have affected the rate, predictors, and outcomes of patients with acute ischemic stroke who qualify for but do not receive treatment with intravenous thrombolysis (IVT).

Methods: This was a secondary observational cohort analysis of the prospective, multicenter BEST-MSU trial (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared With Standard Management by Emergency Medical Services), conducted in 7 US cities from 2014 to 2020, comparing MSU management versus standard emergency department management for patients with suspected acute ischemic stroke. The analytical …

Development And Initial Testing Of An Online Security Prime Writing Intervention During Covid-19, Angie S Leroy, Andreas Weyland, Jade Kanemitsu, Arya Tsay-Jones, Vincent D Lai, E Lydia Wu-Chung, Nyla Vela, Amanda Perozo, Valentina I Maza, Sierra Wickline, Katherine Beach, Robert Suchting

Faculty, Staff and Student Publications

Background and objectives: During the COVID-19 pandemic, we tested the efficacy of a one-week online security prime (SP) writing intervention in reducing distress among 254 adults (60+ years and/or having an underlying health condition). The efficacy of writing interventions can depend on several factors. Attachment orientations, characterized by dimensions of anxiety and avoidance, reflect individuals' tendencies in how they seek proximity to and rely on others for support, and influence how people experience and regulate their emotions.

Design and methods: Participants were randomly assigned to one of three conditions: Security Priming (SP), where people wrote about what made them feel …

Influence Of Pullback Pressure Gradient On Residual Angina At One Year, Takuya Mizukami, Kazumasa Ikeda, Daniel Munhoz, Koshiro Sakai, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Tatyana Storozhenko, Frédéric Bouisset, Domenico Galante, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad A Ali, Ethan Korngold, Eric Wyffels, Adriaan Wilgenhof, Nico Pijls, Bernard De Bruyne, Nils P Johnson, Carlos Collet

Faculty, Staff and Student Publications

Background: The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year.

Methods: PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease …

Severe Renal Phenotype Across A Multigenerational Tuberous Sclerosis Complex (Tsc) Family, Elena Tuller, Joshua A Samuels, Hope Northrup, Kate Richardson

Faculty, Staff and Student Publications

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in the brain, kidney, and heart, along with other complex clinical manifestations, including TSC-associated neuropsychiatric disorder (TAND). Development of genotype-phenotype correlations within TSC can aid clinicians in providing prognostic data and improve clinical management. We present here a multigenerational family who has a pathogenic variant in TSC2 displaying a severe renal phenotype.

Methods: A 23-year-old Caucasian male (Patient 1) was determined to have a molecularly confirmed diagnosis of TSC at approximately 2 months of age. The nonsense pathogenic variant (c.1372C>T (p.Arg458*)) in …

Disposition At Equipoise: A Qualitative Study Of Emergency Physicians' Decision-Making About Hospitalizing People With Dementia, Anita N Chary, Annika R Bhananker, Rebecca Franks, Jason Bowman, Adrian D Haimovich, Victoria Martell, Elizabeth M Schoenfeld, Cameron J Gettel, Shan W Liu, Kei Ouchi, Maura Kennedy, Aanand Naik, Manish N Shah

Faculty, Staff and Student Publications

Background: People with dementia are often hospitalized from the emergency department (ED) for conditions that could potentially be treated in the outpatient setting. In scenarios of clinical equipoise-where either admission or discharge may be appropriate-little is known about how emergency physicians make disposition decisions.

Methods: We conducted a qualitative study with attending emergency physicians at a single academic medical center. Interviews included open-ended questions about disposition decision-making in general as well as structured case scenarios using a think-aloud protocol. We used an inductive approach to code interview data and elucidate themes about the factors emergency physicians consider in disposition decisions …

Soft Skills For Medical Physicists: Evolving A Profession., Tomas Kron, Julie Raffi, Shada Wadi-Ramahi, Abdelkader Toutaoui, Bilal Jalal, Peter A Sandwall, Graciela Velez, Dario Sanz, Godfrey Azangwe

Oncology Articles

PURPOSE: Medical physicists are essential healthcare professionals who bridge the gap between technology and patient care, particularly in radiation oncology and medical imaging. With the profession expanding its clinical and global roles, the need for competencies beyond technical expertise-such as communication, leadership, and cultural awareness-is increasingly evident. These competencies, commonly referred to as soft skills, are critical for patient-centered care but remain insufficiently integrated into formal education and training pathways. The aim of the present work was to identify soft skills relevant to medical physics practice and investigate where in a career they are acquired and used.

METHODS: This paper …

Barriers To Occupational And Physical Therapy Utilization For Children With Cancer, Maria C Swartz, Shiming Zhang, Donna Kelly, Clark R Andersen, Keri Schadler, Alakh P Rajan, Eduardo Gonzalez Villarreal, Stephanie J Wells, Amy Heaton, Karen Moody

Faculty, Staff and Student Publications

Introduction: Occupational and physical therapy (OT/PT) referrals and utilization barriers for childhood cancer patients have not been adequately examined. The current study investigated factors influencing referrals to and utilization of OT/PT services among children with cancer at an NIH-designated cancer center.

Methods: This retrospective cohort study included pediatric cancer patients (up to 18.99 years) presenting to the center over a 33.5-month period. Variables that could influence referrals to OT/PT were extracted from the electronic medical record (EMR) including OT and PT referrals (inpatient and outpatient), OT and PT consult completion, age at diagnosis, cancer type, sex, race/ethnicity, insurance, cancer treatment, …

Optimizing Feasibility And Acceptability Of An Online Expressive Writing Intervention For Survivors Of Adolescent And Young Adult Cancer: A Pilot Randomized Trial Of Iterative Modifications And Outcomes, Eunju Choi, Yusi Aveva Xu, Celia Cy Wong-Meli, Michael E Roth, Yisheng Li, Qian Lu

Faculty, Staff and Student Publications

Objective: To evaluate the feasibility of an online expressive writing (EW) intervention for survivors of adolescent and young adult (AYA) cancer and determine whether iterative, theory-driven modifications can enhance response, adherence, and completion rates.

Methods: In this randomized pilot trial, survivors of AYA cancer were recruited through a hospital-based AYA oncology clinic and an online community. Forty participants were randomly assigned to the EW intervention or control group. To improve on lower-than-expected adherence and completion rates in a previous cohort, the protocol was iteratively revised using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Modifications included …

A Comprehensive Biomechanical Material Characterization Of The Human Breast Fibro-Structural Support System, Aroj Bhattarai, Gregory P Reece, Kristy K Brock, Krishnaswamy Ravi-Chandar

Faculty, Staff and Student Publications

Breast surgery for aesthetic purposes, such as breast augmentation or breast reduction, and breast reconstruction after cancer treatment require an accurate structural (anatomical) and mechanical (functional) understanding of the breast components, including the fascial-ligamentous support system of the breast, to achieve optimal results. This paper aims to provide a comprehensive description of the mechanical behavior of the ligamentous and fascial connective tissues of the human female breast. Fasciae and ligaments obtained from 17 patients between 35 and 85 years of age who were undergoing mastectomy and three female cadavers were tested. Uniaxial tensile tests were conducted, and three constitutive models …

Molecular Landscape In Limb Anomalies: Diagnostic Yield And New Candidate Genes., Akram Mokhtari, Jade Charbonneau, Valancy Miranda, Khadijé Jizi, Marie-Ange Delrue, Patricia Egerszegi, Isabelle Thiffault, Philippe M. Campeau

Manuscripts, Articles, Book Chapters and Other Papers

Congenital limb anomalies remain without an etiological diagnosis in up to 65% of patients. To help close this gap, we describe the genetic diagnostic outcomes of a large cohort. Patients whose primary indication for genetic consultation was a limb anomaly were included from 2014 to 2024. Demographic, investigation, and diagnostic information were extracted, described, and compared. One hundred and thirty-two patients were included in the final cohort, with an average molecular diagnostic yield of 36%. The most common conditions were polydactyly (24%) and radial anomalies (19%). Fifty percent had syndromic features. Seven (5%) patients underwent chromosomal microarray (CMA) only, 81 …

Unilateral Online Ultrasound Stimulation Of Early Visual Cortex Suppresses Responses To Contralateral Visual Stimuli, Suraya Dunsford, Keith Murphy, Ema Darrieutort, Elsa Fouragnan, Giorgio Ganis

School of Psychology

INTRODUCTION: Transcranial ultrasound stimulation (TUS) shows great promise for inducing neuroplastic changes that persist long after stimulation. Evidence of stimulation-locked (online) neural changes would enable the development of closed-loop application of TUS. However, such responses have been difficult to distinguish from coincident neural activity caused by auditory and somatosensory effects of TUS.

METHODS: To dissociate genuine online neuromodulatory effects from peripheral confounds, we leveraged the contralateral retinotopic organization of the early visual cortex in nineteen subjects. Using a hemifield visual stimulation paradigm combined with high-precision, functional MRI-guided TUS, we applied TUS to the left early visual cortex while participants viewed …

Influence Of Exercise Training On Nitric Oxide Pathways And Their Physiological Effects, Jonas Benjamim, Stephen J Bailey, Leonardo Da Silva Gonçalves, Mia Burleigh, Mario Siervo, Andrew R Coggan, Raúl Bescos

School of Health Professions

Nitric oxide (NO) is a critical signalling molecule in cardiovascular, metabolic, and muscular function. Endogenous NO production occurs via two primary metabolic pathways: 1) the classical nitric oxide synthases (NOS) pathway, and 2) the alternative (nitrate-nitrite-NO) pathway, in which inorganic nitrate (NO 3 -) is sequentially reduced to nitrite (NO 2 -) and other NO intermediates (e.g., S-nitrosothiol). The latter pathway relies heavily on the oral microbiota, which catalyze the two-electron partial reduction of NO 3 - to NO 2 -, which is influenced by oral physiology, microbial composition and salivary flow. While the role of exercise training in enhancing …

Aav Gene Therapy For Mps Iva With Induction Of Immune Tolerance Via Oral Administration Of Epitope Peptides Of N-Acetylgalactosamine-6-Sulfate Sulfatase, Sampurna Saikia, Yasuhiko Ago, Fnu Nidhi, Shaukat Khan, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by the accumulation of undegraded glycosaminoglycans due to the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. MPS IVA manifests as progressive systemic skeletal dysplasia. Gene therapy (GT) is potentially a one-time treatment in which the enzyme is continuously produced, circulated, and delivered to target tissues. However, immune responses to gene products can diminish therapeutic efficacy. We hypothesized that oral delivery of tolerogenic peptides induces immune tolerance to human GALNS (hGALNS) in MPS IVA mice, enhancing therapeutic efficacy. Neonatal mice deficient in mouse GALNS (mGALNS) were treated orally with three T-cell/B-cell epitope peptides or hGALNS …

Alpha And Beta Emitters In Translational Nuclear Medicine: Clinical Advances, Challenges, And Future Direction, Hanieh Karimi, Thomas H. Shaffer, Erik Stauff, Vinay V. R. Kandula, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017-2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and …

Recognizing Structural And Social Determinants Of Health In The Diagnosis And Care Of Dementia, Shana D Stites, Sharnita Midgett, Nisha Patel, Kimberly Halberstadter, Rosalie Schumann, Marissa L Streitz, Yidan Shi, John C Morris, Jason Flatt, Crystal M Glover, Dawn Mechanic-Hamilton

2020-Current year OA Pubs

Structural and social determinants of health are environmental conditions that affect individuals' health and functioning across the life course. These determinants are salient factors at the apex of individual psychology, community variables, and larger sociological factors, exerting prominent effects on individuals' wellbeing. The National Institute on Aging seeks to understand their influence on aging and Alzheimer's disease. We propose that the benefits of doing so may reach beyond knowledge of disease mechanisms - it may also improve clinical outcomes. We describe efforts introducing structural and social determinants of health data into the national network of Alzheimer's disease research centers. We …

Supporting Evidence-Based Responses To Emotional Needs In Emphysema (Serene): Protocol For A Randomized, Open-Label Mechanistic Trial Comparing Coping Skills Training And Disease-Specific Education For Depressive Symptoms Conducted In United States Health Systems, Joanna L. Hart, Daniel Carter, Chloe Hinton, James Grilli, Lily A. Brown, Nora Brier, Yingying Lu, Casey Whitman, Michael O. Harhay, Michael Sims, Carmen Alvarez, Lisa R. Miller-Matero, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Depressive symptoms and anxiety are highly prevalent among people with chronic obstructive pulmonary disease (COPD), strongly associated with poor outcomes, and rarely recognized or treated. Integrating families into interventions may amplify supportive care treatment effects and overcome common challenges, yet this strategy is understudied. The Supporting Evidence-based Responses to Emotional Needs in Emphysema (SERENE) trial's main objective is to identify the mechanisms through which a family-partnered Coping Skills Training (CST) reduces depressive symptoms among patients with COPD, testing five putative mechanisms: family relationship quality, patient and caregiver self-efficacy, patient loneliness, and caregiver psychological distress.

METHODS: SERENE will enroll 375 …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

Modulation Of Α-Synuclein Oligomer And Aggregate Populations By Ph And Metal Ions, Ananya Nair, Punarvash Mitta, Lathan Lucas, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

α-Synuclein (α-syn) aggregation underlies synucleinopathies, yet the physicochemical determinants that govern which assembly states form under defined solution conditions remain incompletely resolved. Here, we examine how pH and metal ions reshape α-syn self-assembly. Across acidic and physiological pH conditions, α-syn populates monomeric, nanoscale oligomeric, and mesoscale aggregate states whose relative abundances evolve over time. Fluorescence microscopy reveals robust mesoscale assembly at pH 5, minimal aggregation at pH 7, and transient assemblies at pH 3, highlighting the limitations of imaging-based detection alone. Therefore, we use dynamic light scattering (DLS) to resolve oligomeric populations and quantify pH-dependent redistribution of assembly mass. Toxicity-mitigating …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Evolving Strategies In Prostate Cancer: Emerging Approaches And Unmet Needs From The Bridging The Gaps In Prostate Cancer Expert Panel, Rana Mckay, Benjamin Maughan, Alicia Morgans, Neal Shore, Evan Yu, Ravi Madan, Jacob Berchuck, Bradley Carthon, Steven Finkelstein, Leonard Gomella, Michael Gorin, Andrew Hahn, Stacy Loeb, Vivek Narayan, Daniel Petrylak, Charles Ryan, Karine Tawagi, Phuoc Tran, Tanya Dorff

Department of Urology Faculty Papers

BACKGROUND: The expansion of treatment options for prostate cancer (PC) has improved disease-specific and overall survival outcomes but has also raised questions about the optimal level of treatment needed for patients based on their individual prognosis and accounting for potential toxicity, incorporating quality of life considerations.

METHODS: A panel of experts met to discuss current controversies in the care of patients with PC across the disease continuum. Multidisciplinary experts review advances and persistent uncertainties in biomarker-guided assessment, imaging, and systemic therapy for prostate cancer. The discussion outlines priority gaps in evidence that must be addressed to optimize individualized patient care. …

Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli

Faculty, Staff and Student Publications

Background: Protection of telomere 1 (POT1) tumor predisposition syndrome (POT1-TPD) is a hereditary leukemia syndrome that is identified in ∼5% of patients with chronic lymphocytic leukemia (CLL) and is characterized by a predisposition to other cancers, including gliomas, melanomas, and angiosarcomas. This study reports clinical and genetic characteristics of a large cohort of individuals with POT1-TPD.

Materials and methods: Individuals with pathogenic/likely pathogenic germline POT1 variants referred to the Hereditary Hematologic Malignancy Clinic at The University of Texas MD Anderson Cancer Center were included. Individuals with variants of uncertain significance were included if found to have telomeres >90th percentile of …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

Performance Of An Automated Sleep Scoring Approach For Actigraphy Data In Children And Adolescents, Pin-Wei Chen, Erica C Jansen, Christopher M Cielo, Ariel A Williamson, Margaret Banker, Michael Kaye, Peter X K Song, Karen E Peterson, Alejandra Cantoral, Martha María Téllez-Rojo, Cathy Goldstein, Khadija Zanna, Akane Sano, Jennette P Moreno, Heidi Kalkwarf, Babette S Zemel, Jonathan A Mitchell

Children’s Nutrition Research Center Staff Publications

Study objectives: GGIR is an R package for processing raw acceleration data to estimate sleep health parameters. We aimed to (1) assess the performance of three sleep algorithms within GGIR against PSG for detecting sleep/wake in clinically referred, typically-developing children (criterion validity); and (2) describe GGIR-derived sleep estimates from typically developing children enrolled in multiple cohort studies (face validity).

Methods: For criterion evaluation, children (8-16 years, N = 30) wore an actigraphy device for one night during in-lab polysomnography with performance assessed using epoch-by-epoch analyses. For face validity evaluation, four community/free living datasets were used: (1) Bone Mineral Accretion in …

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …