Digital Commons Network^™

Expanding And Refining The Mammalian Phenotype Ontology To Enhance Disease Model Discovery., Susan M. Bello, Anna V Anagnostopoulos, Leigh Carmody, Nicolas Matentzoglu, Cynthia Smith

Faculty Research 2025

The mouse is a premier model system for investigating gene function and modeling human disease. For almost 40 years, Mouse Genome Informatics has worked to capture and integrate the data generated from mouse studies. A critical component of this integration is the development and use of the Mammalian Phenotype (MP) Ontology to capture the morphological and physiological effects of alterations to gene function in the mouse. As the wealth of phenotype data captured using the MP has expanded, its utility in the diagnosis of human disease has increased. Tools have been developed to use mouse and human phenotypes in variant …

Migraine-Related Disability According To Headache Frequency Subclassifications: A Systematic Review And Meta-Analysis, Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd Schwedt, Michel Lanteri-Minet, Mark Obermann

Department of Jefferson Headache Center Papers and Presentations

BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results …

Morphometric Analysis Of Spina Bifida After Fetal Repair Shows New Subtypes With Associated Outcomes., L K Mann, S Pandiri, N Agarwal, H Northrup, K S Au, Elin Grundberg, E P Bergh, M T Austin, R Patel, B Miller, S Zhu, J S Feinberg, D Lai, K Tsao, S A Fletcher, R Papanna

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies. This study aimed to characterize types of spina bifida lesion and correlate them with preoperative presentation and postoperative outcome.

METHODS: This was a secondary analysis of a prospective cohort of patients referred for fetal spina bifida who underwent fetoscopic repair between 2020 and 2023 at a single center. We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. The reproducibility of lesion classification was assessed using the Kappa …

Proceedings Of The 2025 Santa Fe Bone Symposium: Current Concepts In The Care Of Patients With Osteoporosis, Parathyroid Disorders, And Rare Bone Diseases., E Michael Lewiecki, Robert A. Adler, Paul A. Anderson, John P. Bilezikian, David W. Dempster, Pouneh K. Fazeli, Michael R. Mcclung, Eric T. Rush, Christine M. Swanson, S Bobo Tanner

Manuscripts, Articles, Book Chapters and Other Papers

The 2025 Santa Fe Bone Symposium (SFBS) was a combined in-person and virtual "hybrid" meeting based in Santa Fe, New Mexico, USA, on August 8-9, 2025. There were an equivalent number of in-person and remote attendees from throughout the USA and other countries. The SFBS was immediately preceded, on August 6-7, 2025, by the 2-day Endocrine Fellows Foundation-Santa Fe Bone Symposium Workshop on Metabolic Bone Diseases. This preceptorship included basic bone biology, osteoporosis, parathyroid and rare bone diseases. Most of the fellows attended the SFBS, for a total of 4 days of non-stop education in skeletal health. The topics covered …

Assessment And Management Of Magnesium And Trace Element Status In Children With Ckd Stages 2-5, On Dialysis And Post-Transplantation: Clinical Practice Points From The Pediatric Renal Nutrition Taskforce., Jetta Tuokkola, Caroline E. Anderson, Sheridan Collins, Pearl Pugh, Molly R Wong Vega, Matthew Harmer, Lyndsay A. Harshman, Christina L. Nelms, Barry Toole, An Desloovere, Fabio Paglialonga, Nonnie Polderman, José Renken-Terhaerdt, Rukshana Shroff, Evelien Snauwaert, Stella Stabouli, Johan Vande Walle, Bradley A. Warady, Vanessa Shaw, Larry A. Greenbaum

Manuscripts, Articles, Book Chapters and Other Papers

Children and young people with chronic kidney disease (CKD) are at risk for deficiency or excess of magnesium and trace elements. Kidney function, dialysis, medication, and dietary and supplemental intake can affect their biochemical status. There is much uncertainty about the requirements of magnesium and trace elements in CKD, which leads to variation in practice. The Pediatric Renal Nutrition Taskforce is an international team of pediatric kidney dietitians and pediatric nephrologists, formed to develop evidence-based clinical practice points to improve the nutritional care of children with CKD. PICO (patient, intervention, comparator, and outcomes) questions led the literature searches, which were …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis

Faculty, Staff and Students Publications

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …

Analyzing The Learning Curve Of Vnotes Sacrocolpopexy By The Cumulative Summation Test: A Cohort Study, Wenyu Liu, Nannan Sun, Yuejiao Zhang, Yuyan Li, Weihao Lai, Youjun Zhou, Xiaoming Guan, Juan Liu

Faculty, Staff and Students Publications

Background: The learning curve of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) in the treat of pelvic organ prolapse (POP) is critical yet underexplored. Our objective is to describe the learning curve and surgical complications of vNOTES-SC, taking into account the factors that affect operative time and evaluate the long-term follow-up outcomes of this surgery.

Methods: We conducted a hospital-based cohort study involving patients who underwent vNOTES-SC from June 2017 to May 2024. All surgeries were performed by a single surgeon with over 20 years of surgical experience. This study employed cumulative summation test (CUSUM) analysis to quantify the learning …

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough

Faculty, Staff and Students Publications

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.

Methods: A double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n …

Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez

Faculty, Staff and Students Publications

Importance: Investments in emergency care systems are vital to ensuring universal health coverage and improving health outcomes in low- and middle-income countries.

Objective: To assess whether a package of emergency care interventions is associated with improved patient mortality and clinical care quality.

Design, setting, and participants: This pre-post quality improvement study was conducted at a single urban referral hospital emergency unit (EU) in Monrovia, Liberia, to assess clinical and educational outcomes resulting from the implementation of a package of interventions from January 1, 2018, through June 30, 2019. Final analysis was performed in November 2023. Data from a random subset …

Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith

Faculty, Staff and Students Publications

Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …

Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Background: While exposure with response prevention (ERP) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), not all patients benefit. Impairments in extinction learning are implicated in pediatric OCD's etiology and treatment, with impaired pre-treatment extinction learning associated with worse ERP outcomes. However, available methods for assessing patients' difficulties with fear extinction are costly and underdeveloped. In response, we used person-centered profiles to characterize latent fear extinction patterns among youth with OCD, and investigated the degree to which scores on common rating scales correspond to profile membership.

Methods: Youth with OCD (n=98) completed a diagnostic clinical battery followed by a …

Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud

Faculty, Staff and Students Publications

Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.

Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.

Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …

High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies

Faculty, Staff and Students Publications

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …

Concussion Knowledge, Attitudes, And Behaviors: A Comparison Study Of Youth Athletes And Their Parents, Summer D Ott, Sukhnandan K Cheema, Holden Axel, Seema S Aggarwal, Natalie R Parks, Nikhil Gattu, Philip Schatz

Faculty, Staff and Student Publications

Objective: Given the rising participation in high school athletics and the concerning trend of underreporting concussions, this study aims to identify and compare factors influencing sports-related concussion (SRC) awareness and reporting among youth athletes to their parents.'

Methods: Surveys were completed by 239 student-athletes (ages 13-19) and their parents, using a modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) and demographic questionnaires. Statistical analyses, including paired sample t-tests, ANOVAs, and Spearman's correlations, compared knowledge and attitudes between groups and examined demographic influences.

Results: Parents showed significantly higher concussion knowledge (CKI: t(230) = 5.18, p < .001) and safer attitudes (CAI: t(230) = 10.62, p < .001) than their children. Knowledge scores varied significantly by race and socioeconomic status, with White parents scoring higher than Hispanic and African American parents (F(3,224) = 8.97, p < .001). Child knowledge scores also differed by race (F(4,223) = 3.73, p = .006) …

Menopause Factors And Alterations In Gut Microbiota And Insulin Homeostasis: A Cross-Sectional Analysis Of The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Vincent J Maffei, Alain G Bertoni, Alexis C Wood, Jerome I Rotter, Osa Crago, Yii-Der I Chen, Joseph F Petrosino, Kristi L Hoffman, Mark O Goodarzi, Elizabeth T Jensen

Children’s Nutrition Research Center Staff Publications

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, …

Sleep Eeg And Respiratory Biomarkers Of Sudden Unexpected Death In Epilepsy (Sudep): A Case-Control Study, Oman Magana-Tellez, Rama Maganti, Norma J Hupp, Xi Luo, Sandhya Rani, Johnson P Hampson, Manuela Ochoa-Urrea, Sudha S Tallavajhula, Rup K Sainju, Daniel Friedman, Maromi Nei, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the most common category of epilepsy-related mortality. Centrally mediated respiratory dysfunction has been observed to lead to death in the majority of cases of SUDEP. SUDEP also mainly occurs during nighttime sleep. This study seeks to identify sleep EEG and sleep-related respiratory biomarkers of SUDEP risk.

Methods: In this case-control study, we compared demographic, clinical, EEG, and respiratory data from people with epilepsy who later died of SUDEP (the SUDEP group) with data from age and sex-matched living people with epilepsy, classified as high risk of SUDEP (with ≥1 generalised tonic-clonic seizure …

Consensus Recommendations For Hyperpolarized [1- 13c]Pyruvate Mri Multi-Center Human Studies, Shonit Punwani, Peder E Z Larson, Christoffer Laustsen, Jan Vandermeulen, Jan Henrik Ardenkjær-Larsen, Adam W Autry, James A Bankson, Jenna Bernard, Robert Bok, Lotte Bonde Bertelsen, Jenny Che, Albert P Chen, Rafat Chowdhury, Arnaud Comment, Charles H Cunningham, Duy Dang, Ferdia A Gallagher, Adam Gaunt, Yangcan Gong, Jeremy W Gordon, Ashley Grimmer, James Grist, Esben Søvsø Szocska Hansen, Mathilde Hauge Lerche, Richard L Hesketh, Jan-Bernd Hoevener, Ching-Yi Hsieh, Kayvan R Keshari, Sebastian Kozerke, Titus Lanz, Dirk Mayer, Mary Mclean, Jae Mo Park, Jim Slater, Damian Tyler, Jean-Luc Vanderheyden, Cornelius Von Morze, Fulvio Zaccagna, Vlad Zaha, Duan Xu, Daniel Vigneron

Faculty, Staff and Student Publications

MRI of hyperpolarized (HP) [1‐13C]pyruvate allows in vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. To determine consensus on best practice for multi‐center studies for development of clinical applications. This paper presents the results of a two‐round formal consensus building exercise carried out by experts with HP [1‐13C]pyruvate human study experience. Twenty‐nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data analysis with the goal of providing recommendations and best practice statements on conduct of multi‐center human studies of HP [1‐13C]pyruvate MRI. Overall, the group …

Three-Dimensional Noise Characteristics Of Clinical Photon Counting Detector Ct, Humberto Monsivais, Xinming Liu, Frank Dong, Megan C Jacobsen, John Rong, Corey T Jensen, Ke Li

Faculty, Staff and Student Publications

Background: Since the introduction of whole-body photon-counting detector CT (PCD-CT) into clinical practice, extensive physics assessments have been conducted to elucidate its image quality advantages over energy-integrating detector CT (EID-CT) and to support its clinical adoption. However, evaluations of its three-dimensional (3D) noise power spectrum (NPS), which simultaneously quantifies in-plane and through-plane noise texture and magnitude, remain limited.

Purpose: To experimentally evaluate the 3D NPS of an NAEOTOM Alpha PCD-CT system and its dependence on scan mode, reconstruction image type, quantum iterative reconstruction (QIR) strength, mono-energy (keV) level, spiral pitch, and radiation dose.

Methods: Repeated scans of a 20 cm …

First Experience With Third-Party Validations: A Robust Calibration And Qa Procedure For Proton Flash Delivery, Chih-Chiang Chang, Balaji Selvaraj, Xingyi Zhao, Jacob Rembish, Paige A Taylor, Alexander Bookbinder, Chingyun Cheng, J Isabelle Choi, Charles B Simone, Haibo Lin, Minglei Kang

Faculty, Staff and Student Publications

Background: Proton FLASH radiotherapy, delivering ultra-high dose rates, shows promise in reducing normal tissue toxicity while maintaining tumor control. However, accurate dosimetry and quality assurance (QA) for FLASH remain challenging due to the extreme dose rates involved. Developing reliable calibration and QA procedures is crucial for advancing FLASH towards clinical implementation.

Purpose: To present an effective routine calibration and QA procedure for proton FLASH delivery to ensure high-quality dosimetry performance for preclinical and clinical delivery.

Methods: A high temporospatial resolution strip ionization chamber array (SICA) detector was mounted to the treatment nozzle, which was calibrated using an Advanced Markus ion …

A Comparative Study Of Clinically Used Fast Monte Carlo Dose Engines For Proton Therapy, Sherif M Gadoue, Narayan Sahoo

Faculty, Staff and Student Publications

Background: Several fast Monte Carlo (MC) codes have been implemented and used to simulate proton transport and calculate patient doses in proton therapy. The resulting dose is typically compared to full MC codes, rather than other fast MC codes.

Purpose: The primary goal of this study was to compare the gamma pass rates (GPRs) of dose calculation from different fast MC codes to evaluate the accuracy of the computation and modeling among these codes.

Methods: Two GPU codes and one CPU MC code were commissioned to model our clinical proton beamline at University of Texas MD Anderson Cancer Center. The …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Rosalind Candelaria, Wei Yang, Miral Patel, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …