Digital Commons Network^™

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

Phase 1 Trial Of Withania Somnifera Leaf Extract (Rh324) In Advanced Non-Small Cell Lung Cancer Including [18f]Fdg Pet/Ct As A Short-Term Metabolic Biomarker To Assess Efficacy: A Novel Model For Assessment Of Complimentary Therapies In Early Phase Human Clinical Trials, Jin Uk Heo, Santosh Rao, Herbert B Newton, Afshin Dowlati, Raymond F Muzic, Arash Kardan

Faculty, Staff and Students Publications

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Membrane Il-18 Identifies A Human Macrophage Subset With Distinct Proteomic And Functional Traits, Chiara Vitale, Marco Colonna, Et Al.

2020-Current year OA Pubs

This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Detection Of The Linac Jaw Face Angle Misalignment Using High Energy Electron Beam Symmetry, Song Gao, Andres Cibrian, Jared Ohrt, Peter Balter

Faculty, Staff and Student Publications

Purpose: To demonstrate the usage of a high energy electron beam symmetry measured at different collimator angles to detect jaws face angle misalignments on Varian TrueBeam linear accelerators (linac) during acceptance and commissioning processes.

Methods: During the linac acceptance, all beams were steered to a symmetric shape with the gantry and collimator at 0°. We noted that the symmetries of higher energies electrons (e.g., 16 MeV, 20 MeV) changed over 2% when measured with the collimator at 90° and/or 270° for two linacs commissioned within 5-months of each other. Misaligned applicators were ruled out as the cause of this issue. …

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al.

2020-Current year OA Pubs

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Updating The Epidemiology Of Blastomycosis And Histoplasmosis In The United States, Using National Electronic Health Record Data, 2013-2023., Juliana G E Bartels, Simon K. Camponuri, Theo T. Snow, Brittany L Morgan Bustamante, Natalie J. Kane, Rose Reynolds, Aidan Lee, Mark A. Hoffman, Theodore C. White, Justin V. Remais, Jennifer R. Head

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Where surveillance data are limited, nationally representative electronic health records allow for geographic, temporal, and demographic characterization of the fungal diseases blastomycosis and histoplasmosis.

METHODS: We identified incident blastomycosis and histoplasmosis cases from 2013 to 2023 within Oracle EHR Real-World Data, which comprises 1.6 billion healthcare encounters nationally. To characterize spatiotemporal incidence trends, we used generalized estimating equations weighted for nonrepresentativeness of electronic health record-reporting facilities. We computed standardized incidence rate ratios (sIRRs), which relay relative differences in standardized incidence rates between regions, race/ethnicity, gender, and age subgroups and the national population.

RESULTS: National incidence rates in 2023 were …

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Mbnl Loss Of Function In Smooth Muscle As A Model For Myotonic Dystrophy Associated Gastrointestinal Dysmotility, Janel A M Peterson, Jesus A Frias, Andrew N Miller, Krishnakant G Soni, Yi Zhang, Zheng Xia, John W Day, Geoffrey A Preidis, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of …

Holter Monitor Qt Dispersion And Qtc-Dispersion In Pediatric Long Qt Syndrome And Development Of A Diagnostic And Arrhythmia Risk Prediction Model, Hadeel Allam, Na Le Dang, Edita Karasalihovic, Nathan Miller, Lisa Roelle, William B Orr, Dustin Nash, Anthony G Pompa, Jennifer N A Silva

2020-Current year OA Pubs

BACKGROUND: Holter monitors can provide temporal QT analysis, allowing for calculation of QT dispersion and corrected QT dispersion over time. We describe the results of the QT dispersion and corrected QT dispersion over a 24-hour period in pediatric patients with long QT syndrome (LQTS), compared with a normal cohort, and develop 2 new machine learning models for diagnosis and arrhythmia risk prediction in LQTS.

METHODS: A single-center retrospective case-control study was conducted comparing patients with congenital LQTS and normal controls who underwent a clinically indicated Holter between January 2022 and May 2024. After identifying patients with cardiac events, 2 neural …

Methylation-Based Signature To Distinguish Indolent And Aggressive Prostate Cancer, Muheng Liao, Jace Webster, Amy Ly, Emily Rozycki, Christopher A Maher

2020-Current year OA Pubs

Prostate cancer management faces significant challenges in distinguishing indolent from aggressive disease, particularly since most patients are intermediate-risk and therefore hinders the ability to recommend standardized treatment recommendations. Moreover, current prognostic tools including Gleason scoring and tumor staging demonstrate limited accuracy for predicting disease progression and tumor recurrence. DNA methylation serves as a stable epigenetic modification that directly regulates gene expression, making it an ideal biomarker for cancer prognosis. Therefore, this study leveraged whole-genome enzymatic methylation sequencing on 120 patients to develop a novel prognostic signature for aggressive prostate cancer progression. We analyzed 20,849 differentially methylated regions (DMRs) and employed …

Facts And Hopes Of Chimeric Antigen Receptor-Redirected Nk T Cells, Amy N Courtney, Xin Zhou, Gengwen Tian, Ying Wang, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-engineered invariant NK T cells (CAR-NKT) are a novel cell platform for cancer immunotherapy. Unlike conventional T cells, NKTs are characterized by innate antitumor properties, minimal alloreactivity, and a unique ability to modulate the tumor microenvironment. This article provides a comprehensive overview of preclinical and early clinical studies evaluating CAR-NKTs in both autologous and allogeneic clinical settings. We discuss the contributions of CAR signaling domains, cytokine coexpression, and other functional measures that correlate with CAR-NKT persistence, function, and metabolic fitness. We also discuss the critical role of immunocompetent animal models in elucidating the interactions of CAR-NKTs with …

Protein-Nucleic Acid Language Model-Assisted Design Of Precise And Compact Adenine Base Editor, Jingxuan Ren, Jiawei Yao, Qiuyu Cao, Yinuo Li, Yang Li, Ziyi Zhang, Xiyu Ge, Shengfang Wang, Yang Zhang, Xiaogang Wang, Xiaohui Zhang

Faculty, Staff and Students Publications

Adenine base editors (ABEs) are powerful tools for gene therapy. However, efficient version of ABEs (e.g. ABE8e) always induce excessive bystander and off-target editing events and are large in size, hindering their potential in clinical disease treatment. Here, we develop a pre-trained Protein-Nucleic Acid Constrained Language Model to design ABE8e with high activity, reduced editing window and decreased size. By further engineering, the smallest ABE8e- PNLM-pcABE- with a 27% size reduction, exhibits high activity, precise 3-nt editing window, and reduced off-target events near background level in HEK293T cells. Compared to ABE8e, PNLM-pcABE has up to 133.5-fold precision improvement in pathogenic …

Evolutionarily Convergent Mechanism Of Formin Regulation Coordinates Actin Polymerization In Apicomplexan Parasites, Pengge Qian, Yong Fu, Jianwei Zeng, Michael J Naldrett, Rui Zhang, L David Sibley

2020-Current year OA Pubs

Apicomplexan parasites rely on actin-based motility for host cell invasion and for their dissemination. Although previous studies implicate formin 1 (FRM1) in governing this process in

Stakeholder Criteria For Trust In Artificial Intelligence-Based Computer Perception Tools In Health Care: Qualitative Interview Study, Ansh Rai, Meghan E Hurley, John Herrington, Eric A Storch, Casey J Zampella, Julia Parrish-Morris, Anika Sonig, Gabriel Lázaro-Muñoz, Kristin Kostick-Quenet

Faculty, Staff and Students Publications

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust.

Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care.

Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette …

Glycoside Hydrolase-Mediated Glucomannan Catabolism In Segatella Copri, A Target Of Microbiota-Directed Foods For Malnourished Children, Cyrus Zhou, Matthew C Hibberd, Evan M Lee, Suzanne Henrissat, Marie A Crane, Jiye Cheng, Michael J Barratt, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of

Myocardial Lipin1 Protects The Heart Against Ischemic Injury By Preserving Lipid Homeostasis, Jiaxi Guo, Brian N. Finck, Et Al.

2020-Current year OA Pubs

Impaired cardiac lipid metabolism has been reported to cause heart failure. Lipin1, a multifunctional protein, is a phosphatidate phosphatase that generates diacylglycerol from phosphatidic acid and a transcriptional cofactor that regulates lipid metabolism-related gene expression. Here, we investigated the roles of lipin1 in cardiac remodeling after myocardial infarction (MI). The expression levels of lipin1 significantly decreased in cardiomyocytes of the human failing heart and murine ischemic myocardium. Cardiomyocyte-specific Lpin1 knockout (cKO) mice showed left ventricle enlargement and reduced fractional shortening after MI, compared with control mice. This was accompanied by elevated cardiac fibrosis, accumulation of reactive oxygen species, and increased …

Hsp90 Buffers Deleterious Genetic Variations In Brca1, Brant Gracia, Xing-Han Zhang, Patricia Montes, Tin Chanh Pham, Min Huang, Junjie Chen, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Protein-folding chaperone heat shock protein 90 (HSP90) buffers genetic variation in diverse organisms, but the clinical significance of HSP90 buffering in human disease remains unclear. Here, we show that HSP90 buffers mutations in the BRCT domain of BRCA1. HSP90-buffered BRCA1 mutations result in protein variants that retain interactions with partner proteins and strongly rely on HSP90 for protein stability and function in cell survival. Moreover, HSP90-buffered BRCA1 variants confer poly (ADP-ribose) polymerase (PARP) inhibitor resistance in cancer cells. Low-level HSP90 inhibition overcomes this resistance, revealing a cryptic and mutant-specific HSP90-contingent synthetic lethality. Furthermore, by stabilizing metastable variants across the entirety …

The Clinical Pharmacogenetics Implementation Consortium's Consensus-Based Framework For Assigning Allele Function., Bailey M. Tibben, Andrea Gaedigk, Li Gong, Katrin Sangkuhl, Michelle Whirl-Carrillo, Mary V. Relling, Roseann S. Donnelly, Teri E. Klein, Kelly E. Caudle

Manuscripts, Articles, Book Chapters and Other Papers

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is dedicated to integrating pharmacogenetic testing into clinical practice by developing and disseminating peer-reviewed, evidence-based gene-drug clinical practice guidelines. A critical component of this effort is the assignment of clinical function to pharmacogene alleles, which informs the translation of genetic test results into actionable prescribing decisions. This technology review outlines the standardized procedures and framework used by CPIC to assign allele clinical functional status through the work of Pharmacogene Curation Expert Panels (PCEPs). These panels, comprising multidisciplinary experts, systematically review and evaluate evidence to assign functional status to pharmacogenetic haplotypes. The process includes rigorous …

Impact Of Antibody Fc Engineering On Translational Pharmacology, And Safety: Insights From Industry Case Studies., Frank R Brennan, J Ryan Polli, Jean Sathish, Melissa Ramones, Babette Wolf, Tilman Schlothauer, Shirley J Peters, Curtis C Maier, Changhua Ji, David L Wensel, Derrick Witcher, Patricia C Ryan, T Scott Manetz, Adriano Flora, Brian Soper, Birgit Fogal, Lindsey Dzielak, Xiaoting Wang, Prathap Nagaraja Shastri, Karen Price, Michael Doyle, Nidhi Sharda, Mary Struthers, Maximilian Brinkhaus, Bianca Balbino, Eric Stefanich, Masaki Honda, Jan Terje Andersen, Shermaine Mitchell-Ryan, David P Humphreys

Faculty Research 2025

Therapeutic monoclonal antibodies (mAbs) are often designed to not only bind targets via their antigen-binding domains (Fabs) but to also engage with cell surface receptors, FcγRs and FcRn, through their Fc regions, which may result in a variety of functional outcomes, including antibody- dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) and alteration of circulating half-lives. Engineering the Fc regions to achieve desirable pharmacology and pharmacokinetics is a widely adopted strategy in drug development. Fc regions can be modified through amino acid substitutions and glycoengineering, resulting in enhanced or reduced effector functions, preferential binding to FcR subtypes, …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Bypassing Cisplatin Resistance In Nrf2 Hyperactivated Head And Neck Cancer Through Effective Pi3kinase Targeting, Pedram Yadollahi, Kelli A Mccord, Yang Li, Hussam Dayoub, Kalil Saab, Fonma Essien, Sean Hyslop, Emerald Kan, Kazi M Ahmed, Parker R Kirby, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Patricia Castro, Heath D Skinner, Cristian Coarfa, William K Decker, Abdullah A Osman, Rutulkumar Patel, Jeffrey N Myers, Stephen Y Lai, Nagireddy Putluri, Faye M Johnson, Mitchell J Frederick, William H Hudson, Vlad C Sandulache

Faculty, Staff and Students Publications

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g., NOTCH1 mutations).

Methods: Using state of the science mechanistic, metabolomic and spatial transcriptomic approaches combined with preclinical models of HNSCC, we tested whether a novel PI3K inhibitor, gedatolisib, can bypass hyperactivation of the Nrf2 pathway.

Results: The PI3K pathway is activated in …

Buprenorphine Treatment During The Extended Postpartum Period: A Survey Of Patient Experiences, Bridget Galati, Heather Jacobsen, Melissa Krauss, Melissa Mills, Brittaney Vaughn, Sam Williams, Michael Wenzinger, Cynthia Rogers, Nandini Raghuraman, Jeannie Kelly

2020-Current year OA Pubs

OBJECTIVE: The late postpartum period, defined as greater than 6 weeks to 12 months, is a high-risk time for individuals with opioid use disorder (OUD). Discontinuation rates of buprenorphine treatment for OUD during this period are high. Little is known about patients' subjective experience with buprenorphine treatment during this time. We sought to assess patient treatment experience, goals, facilitators and barriers to continued buprenorphine treatment throughout the extended postpartum period.

METHODS: We performed a cross-sectional survey of postpartum patients who received buprenorphine treatment, including sublingual and long-acting injectable formulations, in an interdisciplinary, wrap-around clinic for maternal OUD between February 2022 …

State Of Omics-Based Microbial Diagnostics Of Crc, Jerome Prusa, Mark G Gorelik, Kevin S Blake, Gautam Dantas

2020-Current year OA Pubs

Colorectal cancer (CRC) remains a major burden of cancer-related morbidity and mortality globally, especially when detected at later stages. Early detection through improved and more accessible diagnostics is critical for reducing the severity of CRC. As our understanding of CRC and the microbial inhabitants of the gastrointestinal tract continues to improve, it has become increasingly recognized that the bacterial component of the gut microbiome may provide diagnostic utility for detecting CRC. This is because CRC is often accompanied by shifts in bacterial taxa, and the metabolites produced or utilized by the CRC-associated gut bacterial community. Advances in sequencing and metabolite …

Pan-Cancer Single Cell Transcriptomic Clustering Reveals Heterogeneous Cd8+ Exhausted T Cell Populations With Different Immune Checkpoint Inhibitor Responses, Rui Mu, Rasha Barakat, David H Gutmann

2020-Current year OA Pubs

In most cancers, T lymphocytes comprise an essential cellular component of the non-neoplastic microenvironment, where they have the capacity to both suppress and support tumor growth. One specialized T lymphocyte population is the CD8

Dual-Level Pattern Tree For Visual Field Improves Glaucoma Progression And Polygenic Risk Prediction, Luo Song, Lucy Q. Shen, Louis R. Pasquale, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Ayellet Segre, Janey L. Wiggs, Constance Turman, Jonathan S. Myers, Tobias Elze, Nazlee Zebardast, David S. Friedman, Jae H. Kang, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: To develop a dual-level pattern tree to characterize visual field (VF) loss subtypes that can be used to better predict glaucoma progression and glaucoma polygenic risk scores (PRSs).

METHODS: This study included 113,030 patients from three datasets, each used for a specific purpose: (1) model training, (2) progression forecasting, and (3) PRS correlations. We applied archetypal analysis to cluster 24-2 VFs into trunk patterns and their branch patterns. The Cox regression model was used to forecast VF progression using mean deviation (MD) slope, MD-fast slope, total deviation (TD) pointwise slope, and visual field index (VFI) slope. Multivariable regression analyses …