Digital Commons Network^™

Workflow Improvements From Automated Large Vessel Occlusion Detection Algorithms Are Dependent On Care Team Engagement, Emmanuel C Ebirim, Ngoc Mai Le, Joseph N Samaha, Hussain Azeem, Ananya Iyyangar, Anjan N Ballekere, Saagar Dhanjani, Luca Giancardo, Eunyoung Lee, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Automated machine learning (ML)-based large vessel occlusion (LVO) detection algorithms have been shown to improve in-hospital workflow metrics including door-to-groin time (DTG). The degree to which care team engagement and interaction are required for these benefits remains incompletely characterized.

Methods: This analysis was conducted as a pre-planned post-hoc analysis of a randomized prospective clinical trial. ML-based LVO detection software was implemented at four comprehensive stroke centers (CSCs) from January 1, 2021, to February 27, 2022. Patients were included if they underwent endovascular thrombectomy for LVO acute ischemic stroke. ML software utilization was quantified as the total number of active …

A Chemogenetic Approach For Temporal And Cell-Specific Activation Of Endogenous Gpcrs In Vivo, Gwendolyn Shingles, Qianqian Pang, Jian Weng, Ryan Singer, Waleed Babar, Jiaqi Shen, Luis Vazquez-Rivera, Yao Chen, Peng Li, Wenjing Wang

2020-Current year OA Pubs

Cell-specific regulation of endogenous G protein-coupled receptors (GPCRs) is crucial for understanding their roles in physiological processes. We present chemogenetic tools using shield-1-dependent irreversible protein switches to regulate peptide agonist activity. To demonstrate this platform, we engineered chemogenetically regulated pituitary adenylate cyclase activating polypeptide (cPACAP), which exhibited >15-fold chemical-dependent regulation of endogenous receptor activity. In vivo application of cPACAP allowed neuronal activation via the endogenous receptor for PACAP, engaging neural circuits that control respiratory and feeding behaviors. By integrating cPACAP with transgenic mice, we selectively activated endogenous PACAP receptor signaling in hypocretin-expressing neurons of the lateral hypothalamic area (LHA), revealing …

Matched Unrelated Vs Haploidentical Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide, Dipenkumar Modi, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is now standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Previous studies comparing MUD and haploidentical donor HCT using PTCy were limited in size and follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n = 5873) receiving MUD (n = 1973) or haploidentical (n = 3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (MDS; 25.8%) reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021 were included. Primary end points were 3-year …

Efficacy And Safety Of Oral Pcsk9 Inhibitor Enlicitide In Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial, Christie M Ballantyne, Laura Gellis, Jean-Claude Tardif, Puja Banka, Ann Marie Navar, Emil Andreas Asprusten, Russell Scott, Erik S G Stroes, Samar Froman, Geraldine Mendizabal, Fan Wang, Alberico L Catapano

Faculty, Staff and Students Publications

Importance: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies.

Objective: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy.

Design, setting, and participants: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …

Induction Of Moderate Dna Damage Enhances Megakaryopoiesis And Platelet Production, Virginia Camacho, Luis Francisco Zirnberger Batista, Et Al.

2020-Current year OA Pubs

Megakaryocytes (MKs) are large, hematopoietic cells with a polyploid, multilobulated nucleus. Although DNA replication in MKs (endomitosis) is well studied, limited investigations have examined the impact of DNA instability on megakaryopoiesis. Poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors are chemotherapeutics that result in accumulation of DNA damage and are commonly associated with thrombocytopenia, presumably mediated through platelet progenitors, MKs. To explore PARP inhibitor-induced thrombocytopenia, we treated mice with the PARP inhibitor niraparib. Although high-dose niraparib treatment led to thrombocytopenia, consistent with clinical observations, lower-dose treatment led to a significant increase in bone marrow MKs, MK progenitors (MkPs), and circulating platelets. …

Self-Efficacy Change Among Diverse Family Caregivers In Dementia Care, Deborah M Oyeyemi, Erich J Greene, Yunshan Xu, David R Lee, Rafael Samper-Ternent, Maya L Lichtenstein, Alan Stevens, Jeff D Williamson, Arun S Karlamangla, Debra Saliba, David B Reuben

Faculty, Staff and Student Publications

Objectives: To determine whether changes in caregiver self-efficacy (beliefs about one's ability to manage dementia-related problems and access help) differed by caregiver race and ethnicity across all participants enrolled in a large pragmatic trial of comprehensive dementia care.

Methods: In the Dementia Care Study (D-CARE), community-dwelling older adults with dementia and their unpaid family caregivers were randomized to receive usual care, community-based, or health system-based comprehensive dementia care. Caregiver self-efficacy was assessed at baseline, 6 months, and 18 months using a 4-item scale (range 4-20, higher scores indicate greater self-efficacy). Among all caregivers, we compared least squares means for overall …

Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions And Induce Cell-Cycle Arrest, Jorge Luis Galeano Niño, Falk Ponath, Victor A Ajisafe, Clara R Becker, Andrew G Kempchinsky, Martha A Zepeda-Rivera, Javier A Gomez, Hanrui Wu, Jessica G Terrazas, Heather Bouzek, Elizabeth Cromwell, Pritha Chanana, Matthew Wong, Ashish Damania, Michael G White, Y Nancy You, Scott Kopetz, Nadim J Ajami, Jennifer A Wargo, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals …

Spatial Omics At The Forefront: Emerging Technologies, Analytical Innovations, And Clinical Applications, Yunhe Liu, Yibo Dai, Linghua Wang

Faculty, Staff and Student Publications

Spatial omics transforms our understanding of cancer by revealing how tumor cells and the microenvironment are organized, interact, and evolve within tissues. Here, we synthesize advances in spatial technologies that map tumor ecosystems with unprecedented fidelity. We highlighted analytical breakthroughs-including multimodal integration and emerging spatial foundation models-that resolve functional niches and spatial communities, converting spatial patterns into mechanistic insights. We summarize how spatially organized features, from immune hubs to microbiota and neural interfaces, shape tumor evolution and clinical outcomes. We then outline how spatial approaches illuminate precancer biology, metastatic adaptation, and therapy response. Bridging discovery and translation, we provide a …

Neighborhood-Level Deprivation Measures In The United States: A Scoping Review And Reference Guide For Investigators, Jaesung Choi, Madeline R Horan, Mary G Nusloch, Yikyung Park, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, I-Chan Huang

2020-Current year OA Pubs

PURPOSE: The extent to which existing measures cover the spectrum of neighborhood-level social determinants of health (SDOH) has not yet been assessed. This review compared the content of U.S.-based neighborhood-level SDOH measures and summarized the use of these measures in empirical research. METHODS: We conducted a comprehensive search on PubMed and Google Scholar, identifying review articles published from 1990–2023, and complemented this search by manually examining the original articles on measure development. We identified 85 measures and categorized them into two groups (42 with a specific name and 43 with no name) and used a framework including 14 domains of …

Social Prescribing Within Five European Countries: A Protocol Of A Cross-Country Qualitative Analysis, Stephanie Tierney, Debra Westlake, Farhad Rezvani, Daniela Rojatz, Juliane Köberlein-Neu, Trutz Bommhardt, Sónia Dias, Maria João Marques, Donata Kurpas, Hendrik Napierala, Wolfram Herrmann, K Husk

Peninsula Medical School

Introduction Social prescribing is an approach to addressing non-medical issues affecting people’s health and well-being (eg, loneliness, housing or financial problems). It has gained international traction over recent years as complementary to medical care. A larger research project, comparing social prescribing across European countries, is considering how to tailor provision for the following groups: (a) LGBTIQ+persons, (b) refugees and first-generation immigrants and (c) older adults living alone. As part of this research, a qualitative study will address the question: What are the enabling and limiting factors associated with implementing social prescribing, across different European countries, from the perspective of key …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …

Characteristics And Effectiveness Of Maternal Health Interventions To Prevent Mother-To-Child Transmission (Pmtct) Of Syphilis In A Global Setting: A Scoping Review Using Intervention Mapping As A Framework, Jinni Tang, Anusha Sajja, Christine Markham, Emily T Hebert, Irene Stafford, Sheryl Dacso, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Despite the availability of cost-effective treatments, maternal syphilis continues to contribute significantly to preventable stillbirths and congenital syphilis cases worldwide. This scoping review aimed to identify and characterize maternal health interventions designed to prevent mother-to-child transmission (PMTCT) of syphilis globally, using a modified Intervention Mapping (IM) framework.

Methods: We conducted a scoping review of maternal health interventions targeting PMTCT of syphilis published between January 2010 and August 2023. Searches were performed in PubMed, Medline Ovid, and Embase, supplemented by manual reference screening. Eligible studies described at least one maternal health intervention addressing syphilis PMTCT and were analyzed using a …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …

The Computationally Designed Tri2-2 Miniprotein Inhibitor Protects Against Multiple Sars-Cov-2 Omicron Variants, Jimin Lee, James Brett Case, Young-Jun Park, Rashmi Ravichandran, Daniel Asarnow, M Alejandra Tortorici, Jack T Brown, Shilpa Sanapala, Lauren Carter, David Baker, Michael S Diamond, David Veesler

2020-Current year OA Pubs

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Daily Locomotor Activity Declines With Tumor Growth And Disease Progression In Glioblastoma, Maria F Gonzalez-Aponte, Sofia V Salvatore, Anna R. Damato, Ruth Gn Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2-3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the …

Mobile Apps For Psychotic Disorders: A Systematic Review Protocol, Ananya Ananthakrishnan, Aditya Narain Sharma, David Anderson, Rohit Shankar, Edward Meinert

Peninsula Medical School

BackgroundEarly intervention for psychotic spectrum disorders can improve long-term outcomes, but service availability and quality can vary globally. Mobile apps have the potential to provide personalised and accessible support for people with psychotic disorders via features such as symptom monitoring, medication reminders, and self-management interventions. Existing reviews have provided an overview of such apps and their feasibility but lack a synthesis of their efficacy, safety, and acceptability. Addressing this gap would guide future app designs and facilitate their implementation by informing clinical and policy decisions. The purpose of this systematic review will be to synthesise the evidence about existing mobile …

Optimal Timing Of Cranioplasty Post-Decompressive Craniectomy In Traumatic Brain Injury: A Systematic Review, Meta-Analysis, And Overview Of Ongoing Trials, Ashviniy Thamilmaran, Shaan Patel, Shiva A. Nischal, Honey Panchal, Kush Kale, Pious D. Patel, Jack Jallo, James S. Harrop

Department of Neurosurgery Faculty Papers

BACKGROUND: The optimal timing of cranioplasty (CP) following decompressive craniectomy (DC) for the management of traumatic brain injury (TBI) remains debated. Prior studies comparing early CP (EC) and late CP (LC) report conflicting outcomes, compounded by inconsistent timing thresholds and limited attention to effect modifiers such as implant material.

OBJECTIVE: To perform a systematic review and meta-analysis comparing outcomes of EC (≤ 90 days) versus LC (> 90 days) after DC for TBI, with particular evaluation of ultra-EC (<  35 days) and implant material.

METHODS: MEDLINE, Embase, and CENTRAL were electronically searched from inception to April 2025, supplemented by manual screening of references and grey …

Gh Alters Lymphatic Vessels In Female Mice And Stat5 Phosphorylation In Human Lymphatic Endothelial Cells, Christopher Walsh, Emily Scott, Elise Wagner, Jerome Walsh, Shashank Reddy, Arshad Ahmad, Reetobrata Basu, Eva Sevick-Muraca, Rich Brody, Uday Sandbhor, Sebastian Neggers, John J Kopchick

The Brown Foundation: Institute of Molecular Medicine

Disruption of lymphatic function underlies a broad spectrum of inflammatory and metabolic disorders, yet the hormonal pathways that regulate lymphatic biology remain poorly defined. GH, which is implicated in similar disease states, has an unclear role in lymphatic homeostasis. To address this gap, we investigated how chronic alterations in GH signaling alter lymphatic structure and function. Using transgenic mouse lines with increased, decreased, or absent GH action, we quantified the effect of GH on lymphatic pumping rate and lymphangiogenic remodeling during wound healing using near-infrared fluorescent imaging. We also measured markers of lymphatic endothelial cells using Western blot and immunohistochemistry …

Comparison Of Surgery And Medicine On The Impact Of Diverticulitis (Cosmid) Trial: A Protocol For A Pragmatic Randomised Study Of Diverticulitis Treatment In The Usa, Mariam N Hantouli, Robert H Schmicker, Janice E Tufte, Fadwa G Ali, Robert D Bennett, Jessica N Cohan, Bryan A Comstock, Thomas Curran, Giana H Davidson, Samuel Eisenstein, Katherine N Fischkoff, Fergal J Fleming, Irena Gribovskaja-Rupp, Mehraneh Dorna Jafari, Larry G Kessler, Mukta K Krane, Sarah O Lawrence, James T Mccormick, Stefanos G Millas, Arden M Morris, Kelsey M Pullar, Caroline E Reinke, Julia T Saraidaridis, Vlad V Simianu, Suzanne P Watkins, Nicole B White, Elizabeth C Wick, Nicole Wieghard, David R Flum, Thomas E Read

Faculty, Staff and Student Publications

Introduction: Each year, millions of people experience recurrent diverticulitis episodes. Elective sigmoid colon resection reduces the risk of recurrence, but The American Society of Colon and Rectal Surgeons recommends individualising surgical decisions based on the impact of the condition on a patient's quality of life (QoL). However, no threshold for QoL impairment has been established to guide decision-making, and evidence comparing elective colectomy with medical management in terms of QoL limitation is limited. To address these gaps and to guide treatment decision-making, we designed the Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial.The COSMID trial is …

Antecedent Enhancer Activity Predicts Future Susceptibility To Seizures In Mice, Benjamin D Boros, Mariam A Gachechiladze, Juanru Guo, Dylan A Galloway, Shayna M Mueller, Mark Shabsovich, Allen Yen, Xuhua Chen, Alexander J Cammack, Tao Shen, Robi D Mitra, Joseph D Dougherty, Timothy M Miller

2020-Current year OA Pubs

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci …

Bayesian Multi-Cell Type Models For The Analysis Of Complex Immune Cell Populations With Application To Ovarian Cancer., Chase J. Sakitis, Jose Laborde, Julia Wrobel, Alex C. Soupir, Christelle M. Colin-Leitzinger, Benjamin G. Bitler, Mary K. Townsend, Andrew B. Lawson, Joellen M. Schildkraut, Shelley S. Tworoger, Kathryn L. Terry, Lauren C. Peres, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

To understand how the tumor immune microenvironment (TIME) impacts clinical outcomes and treatment response, researchers have been leveraging single-cell protein multiplex imaging techniques. These technologies measure multiple protein markers simultaneously within a tissue sample, providing a more complete assessment of the TIME. However, statistical challenges arise from the over-dispersed and zero-inflated nature of the data and from relationships among different immune cell populations. To address these challenges, we developed a Bayesian hierarchical method using a beta-binomial (BB) distribution to model the abundance of multiple immune cell types simultaneously while incorporating relationships and immune cell differentiation paths. We applied the model …

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

Assessing The Effects Of Ehealth Literacy And The Area Deprivation Index On Barriers To Electronic Patient Portal Use For Orthopedic Surgery: Cross-Sectional Observational Study, Audrey Lynn Litvak, Nicholas Lin, Kelly Hynes, Jason Strelzow, Jeffrey G Stepan

2020-Current year OA Pubs

BACKGROUND: As electronic patient portals (EPPs) continue to gain popularity and systems transition to online tools for scheduling, communication, and telehealth, patients without access or skills to use these tools may be overlooked.

OBJECTIVE: This study analyzed patient and neighborhood-level factors, including eHealth literacy level and the Area Deprivation Index (ADI), that may limit EPP access for orthopedic surgery.

METHODS: A cross-sectional, survey-based study was performed at a single urban tertiary academic medical center in the United States across foot and ankle, hand and upper extremity, and orthopedic trauma subspecialty clinics from June 21, 2022, to August 12, 2022. Survey …

Pathways, Outputs And Impact Of Nih-Supported Bioinformatics And Genomics Graduate Trainees In Africa, Daudi Jjingo, Andrew Walakira, Suhaila Hashim, Cisse Cheickna, Ronald Galiwango, Caleb Kibet, Florence N Kivunike, Gerald Mboowa, Fredrick Elishama Kakembo, Babajide Ayodele, Jean-Baka Domelevo Entfellner, Santie De Villiers, Karen Wambui, Segun Fatumo, Tinashe Chikowore, John Mukisa, Alfred Ssekagiri, Nicholas Bbosa, Julius Mulindwa, Samuel Kyobe, Mike Nsubuga, Grace Kebirungi, Eric Katagirya, Savannah Mwesigwa, Ibra Lujumba, Rogers Kamulegeya, Samuel Kirimunda, Stephen Kanyerezi, Shahiid Kiyaga, Ivan Sserwadda, Davis Kiberu, Bernard S Bagaya, Julius Okwir, Patricia Nabisubi, Grace Nabakooza, Mugume Twinamatsiko Atwine, Ricard Sserunjogi, Rolanda Julius, Mariam Quiñones, Meghan Mccarthy, Phillip Cruz, Karlynn Noble, Christopher J Whalen, Darrell Hurt, Maria Y Giovanni, Michael Tartakovsky, Deogratius Ssemwanga, John M Kitayimbwa, Steven J Reynolds, Christopher C Whalen, Andrew Kambugu, Neil A Hanchard, Li Jian, Peter Amoako-Yirenkyi, Graeme Mardon, I King Jordan, Samson Pandam Salifu, Mamadou Wele, Ezekiel Adebiyi, Jeffrey G Shaffer, Seydou Doumbia, David Patrick Kateete, Michelle Skelton, Nicola Mulder, Jonathan K Kayondo, Daniel Masiga, H3africa Consortium

Faculty, Staff and Students Publications

Global biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to …

The Do-Kb Knowledgebase 2026 Update: Expanding Programmatic And Language Access., J Allen Baron, Claudia M Sánchez-Beato Johnson, Michael A Schor, Dustin Olley, Lance Nickel, Victor Felix, Susan M. Bello, Carol Greene, Richard Lichenstein, Katharine Bisordi, Rima Koka, Cynthia Bearer, Regina Macatangay, Nischal Ada, Kaitlin Ballenger, Emily Bliss, Lauren Colliver, Grace Dobbins, Harrison Heitzig, Shannan Dixon, Patrick Semesky, Jennifer Garth, Matthew Fairchild, Peter Gaskin, Sarina Zahid, Rachel Castillo, Sarah Edwards, Astrid Widjaja, Yamei Usui, Erin Lynch, Melissa Clarkson, Todd Detwiler, Lynn M Schriml

Faculty Research 2026

The Human Disease Ontology Knowledgebase (DO-KB; https://disease-ontology.org/), a Global Core Biodata Resource, serves as a reference framework for multiscale biomedical data integration and analysis, within a unifying etiology-based disease classification. In this 2026 update of the Human Disease Ontology (DO) and DO-KB resource, we present significant advances in programmatic data retrieval and disease representation since our previous NARdb publication. Here we report on the development of a DO Nosology education program, the Spanish translation of the DO website and ontology content, and expansion of disease knowledge representation.

Music Therapy Versus Cognitive Behavioral Therapy Via Telehealth For Anxiety In Survivors Of Cancer: A Randomized Clinical Trial, Kevin T. Liou, Joke Bradt, M. Beatriz Currier, Raymond Baser, Katherine Panageas, Jodi Macleod, Desiree Walker, Susan Q. Li, Ana Maria Lopez, Kelly Mcconnell, Jun J. Mao

Department of Medical Oncology Faculty Papers

PURPOSE: Anxiety is prevalent, disruptive, and undertreated among survivors of cancer. Cognitive behavioral therapy (CBT) is the first-line treatment, but not all individuals have access, respond to treatment, or prefer this option because of stigma. Music therapy is effective for short-term anxiety reduction, but it is unknown whether it is noninferior to first-line CBT for long-term anxiety reduction.

METHODS: This comparative effectiveness trial randomly assigned English- or Spanish-speaking survivors of cancer to seven weekly telehealth sessions of music therapy or CBT. The coprimary end points were changes in the Hospital Anxiety and Depression Scale (HADS) anxiety score at weeks 8 …

A Phase 1, First-In-Human, Dose Escalation Study Of Jnj-80038114, A Psmaxcd3 Bispecific Antibody, In Participants With Metastatic Castration-Resistant Prostate Cancer, Andrew Hudson, Anuradha Jayaram, Benjamin Garmezy, Nicholas Zorko, Kevin Zarrabi, Ligi Mathews, Brent Rupnow, Mengjie Li, Debopriya Ghosh, Karen Urtishak, Peter Francis, Sherry Wang, Edward Attiyeh, Johann De Bono

Department of Medical Oncology Faculty Papers

PURPOSE: Prostate-specific membrane antigen (PSMA) has been identified as a therapeutic target for metastatic castration-resistant prostate cancer (mCRPC). The recent success of radioligands targeting PSMA spurred development of new PSMA-targeting agents including immunotherapy. JNJ-80038114 is a bispecific antibody that binds PSMA on tumor cells and CD3 on T cells to induce anti-tumor activity.

METHODS: This was a phase 1, open-label, multicenter study of JNJ-80038114 in participants with mCRPC and ≥ 1 prior systemic therapy. JNJ-80038114 was administered subcutaneously every 3 weeks (Q3W), starting at 0.1 mg. The primary endpoint was safety. Secondary endpoints included pharmacokinetics (PK), immunogenicity, and prostate-specific antigen …

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

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