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Articles 6121 - 6150 of 160035
Full-Text Articles in Medicine and Health Sciences
Trial Interviews To Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy, Diane M Turner-Bowker, Jessica Butler, Shayna Egan, David A Weinstein, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, Rebecca Riba-Wolman, John J Mitchell, Christina Theodore-Oklota
Trial Interviews To Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy, Diane M Turner-Bowker, Jessica Butler, Shayna Egan, David A Weinstein, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, Rebecca Riba-Wolman, John J Mitchell, Christina Theodore-Oklota
Faculty, Staff and Student Publications
Background: Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive deficiency of glucose-6-phosphatase (G6Pase), an enzyme necessary in glycogenolysis and gluconeogenesis. To maintain normal blood glucose levels and ensure survival, individuals living with GSDIa must frequently consume complex carbohydrates (eg, uncooked cornstarch). Dietary management can result in chronic complications and significant patient burden. DTX401 (pariglasgene brecaparvovec) is an investigational adeno-associated virus serotype 8 vector (AAV8)-based gene therapy designed to restore endogenous glucose production.
Objectives: Patient experience interviews were conducted as part of an open-label, phase 1/2 dose-escalation trial (NCT03517085) evaluating the safety and efficacy of …
Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani
Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani
Faculty, Staff and Student Publications
This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …
Infliximab For Grade Iii Or Iv Immune Checkpoint Inhibitor Nephritis Clinical And Translational Evidence, Nada Youssef, Masroor Habeeb, Hong Chen, Zainab Alhamal, Omar Mamlouk, Heather Lin, Valda Page, Amanda Tchakarov, Sreyashi Basu, Adi Diab, Padmanee Sharma, Ala Abudayyeh
Infliximab For Grade Iii Or Iv Immune Checkpoint Inhibitor Nephritis Clinical And Translational Evidence, Nada Youssef, Masroor Habeeb, Hong Chen, Zainab Alhamal, Omar Mamlouk, Heather Lin, Valda Page, Amanda Tchakarov, Sreyashi Basu, Adi Diab, Padmanee Sharma, Ala Abudayyeh
Faculty, Staff and Student Publications
Introduction: Acute interstitial nephritis (AIN) is a common presentation of immune checkpoint inhibitor (ICI) toxicity. Increased tumor necrosis factor (TNF)-α expression has been observed in ICI-induced AIN (ICI-AIN). In this study, we compared treatment with glucocorticoids plus infliximab to glucocorticoids only in stage III or IV ICI-AIN. We conducted retrospective NanoString analysis of ICI-exposed kidney samples to identify associated gene signatures and possible association with TNF-α expression.
Methods: We reviewed the records of patients who received ICI, developed acute kidney injury (AKI), and underwent kidney biopsy at MD Anderson Cancer Center from January 2022 to October 2024. Fifty-five patients had …
Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno
Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno
Faculty, Staff and Student Publications
The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is …
T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan
T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan
Faculty, Staff and Student Publications
The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …
The Effects Of Fitness Self-Testing With Instant Feedback On Changes In Health-Related Fitness Among Chinese Male College Students, Yongshun Wang, Xiaofen D Hamilton, Rulan Shangguan, Anlu Yang, Na Xiao, Chenhao Wu, Sizhe Liu, Ren Yang, Jiren Zhang, Mark F Hamilton
The Effects Of Fitness Self-Testing With Instant Feedback On Changes In Health-Related Fitness Among Chinese Male College Students, Yongshun Wang, Xiaofen D Hamilton, Rulan Shangguan, Anlu Yang, Na Xiao, Chenhao Wu, Sizhe Liu, Ren Yang, Jiren Zhang, Mark F Hamilton
Faculty, Staff and Student Publications
Background: The decline in health-related physical fitness resulting from physical inactivity remains a critical global public health concern. Technology-supported fitness self-testing has the potential not only to improve students' testing experiences but also to enhance their health-related fitness. However, the effectiveness of such approaches has not yet been systematically examined, and their validity within university populations remains largely unestablished.
Method: A quasi-experimental research design with a control group (n = 45) and an experimental group (n = 44), incorporating pre- and post-tests, was employed in this study. The experimental group completed monthly self-testing sessions accompanied by GAI-generated instant feedback over …
The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra
The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra
Faculty, Staff and Student Publications
Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …
Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder
Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder
Faculty, Staff and Student Publications
Purpose: The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined.
Methods: We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS).
Results: Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more …
Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs
Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs
Faculty, Staff and Student Publications
Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …
Initial Experience With Remote Mri Scanning Support In An Oncology Focused Practice: Opportunities For Expanded Access To Radiology Care, Christopher M Walker, Maria G Maldonado, Megan C Jacobsen, Suprateek Kundu, Michelle L Underwood, Joshua P Yung, Brandy J Reed, David Jaffray, R Jason Stafford, Marshall E Hicks, Caroline Chung, Aradhana M Venkatesan
Initial Experience With Remote Mri Scanning Support In An Oncology Focused Practice: Opportunities For Expanded Access To Radiology Care, Christopher M Walker, Maria G Maldonado, Megan C Jacobsen, Suprateek Kundu, Michelle L Underwood, Joshua P Yung, Brandy J Reed, David Jaffray, R Jason Stafford, Marshall E Hicks, Caroline Chung, Aradhana M Venkatesan
Faculty, Staff and Student Publications
Background: As medical imaging demand grows, there is increasing stress on the currently available workforce to deliver consistent, high-quality imaging studies while ensuring rapid study turnaround times and round-the-clock radiology coverage. Advances in remote access technology facilitating remote scan assistance and control are now commercially available to address these pressing clinical needs.
Methods: This work evaluated an early clinical application of a virtual scanner operations system (syngo Virtual Cockpit (VA13A, Siemens Healthineers, Erlangen, Germany) for remote magnetic resonance imaging (MRI) monitoring and scan control at three geographically distant outpatient sites associated with our primary institution.
Results: The system facilitated execution …
Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz
Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz
Faculty, Staff and Student Publications
No abstract provided.
Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee
Faculty, Staff and Student Publications
Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …
Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan
Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan
Faculty, Staff and Student Publications
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …
A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn
A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn
Faculty, Staff and Student Publications
Datasets used in machine learning often contain sensitive information, including personally identifiable health and financial details. A common challenge faced by organizations and researchers is the risk of privacy breaches when using real-world data. Synthetic data can be used as an alternative to the real-world data. In existing synthetic data generation techniques, an encoder processes the real-world data to map it into a lower-dimensional latent space. Random sampling is then performed in this latent space. Subsequently, a decoder network is utilized to generate synthetic data from these sampled points in the latent space. Such approaches typically require generating a large …
Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang
Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang
Faculty, Staff and Student Publications
Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …
A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay
A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay
Faculty, Staff and Student Publications
Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen …
Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin
Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin
Faculty, Staff and Student Publications
This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …
Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner
Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner
Faculty, Staff and Student Publications
Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …
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
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 …
Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail
Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail
Faculty, Staff and Student Publications
Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …
Developing Provider Digital Twins For Personalized Provider-Patient Communication Via A Rag-Based Conversational Framework, Pengze Li, Yutong Hu, Jianfu Li, Garit Gemeinhardt, Fang Li, Muhammad Amith, Licong Cui, Antonio J Forte, Cui Tao
Developing Provider Digital Twins For Personalized Provider-Patient Communication Via A Rag-Based Conversational Framework, Pengze Li, Yutong Hu, Jianfu Li, Garit Gemeinhardt, Fang Li, Muhammad Amith, Licong Cui, Antonio J Forte, Cui Tao
Faculty, Staff and Student Publications
Digital twins have emerged as a paradigm in precision and personalized medicine, enabling data-driven modeling of individuals to support tailored interventions. While most existing work focuses on patient-oriented twins, little attention has been given to modeling the provider’s role, particularly in clinical communication. In this study, we present GRACE (Generalized RAG-Enhanced Conversation Framework), a framework for constructing a provider digital twin (ProDT) that emulates key aspects of clinicians’ communicative and cognitive behavior. GRACE integrates three modules: a physician-informed dialog script generation and optimization module for provider-patterned conversation, a Retrieval-Augmented Generation (RAG) pipeline for factual grounding and timely knowledge updating, and …
Predicting Dementia Risk: Progress, Pitfalls, And Priorities, Patricia Nistor, Osvaldo Espin-Garcia, Zul Merali, Shehzad Ali
Predicting Dementia Risk: Progress, Pitfalls, And Priorities, Patricia Nistor, Osvaldo Espin-Garcia, Zul Merali, Shehzad Ali
Brain and Mind Institute
As populations age, identifying individuals at high risk for dementia has become a cornerstone of prevention-oriented public health policy. Accurate and scalable risk stratification could enable early intervention and resource targeting. However, existing models face methodological limitations, including constraints in available data and follow-up duration, challenges in dementia ascertainment, heterogeneity in modelling approaches, and limited external validation. This commentary discusses these challenges and identifies methodological priorities for developing dementia risk algorithms that are robust and suitable for real-world implementation.
Intratracheal Interleukin-10 Administration Reduces Acute Lung Injury Induced By Sulfur Dioxide Exposure In Mice, Amy J. Nelson, Todd A. Wyatt, Bradley W. Richmond, Belinda Diaz, Angela Gleason, Michael J. Duryee, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole
Intratracheal Interleukin-10 Administration Reduces Acute Lung Injury Induced By Sulfur Dioxide Exposure In Mice, Amy J. Nelson, Todd A. Wyatt, Bradley W. Richmond, Belinda Diaz, Angela Gleason, Michael J. Duryee, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole
Journal Articles: Environmental, Agricultural & Occupational Health
Therapies capable of reducing acute high-consequence airborne chemical exposure-induced lung disease are lacking. This study seeks to determine the therapeutic potential of interleukin (IL)-10 administered following acute sulfur dioxide (SO2) exposure in mice. C57BL/6 male and female mice were exposed to SO2 gas at 125 ppm for 4 h and subsequently treated 2-3 h later with IL-10 (1 μg) or vehicle control by intratracheal instillation for a total of 3 doses over 2 days with comparisons to sham-treated mice (N = 20 mice/group). IL-10 treatment reduced SO2-induced weight loss with corresponding reductions in SO2 …
Place Matters: Investigating The Social And Environmental Drivers Of Hypertension In Nashville, Marquinta Harvey, Michael D. Oliver, Tatum Brown, Deya Rassul, Thomas Strickler, Jarod Parrish, Catherine Bass
Place Matters: Investigating The Social And Environmental Drivers Of Hypertension In Nashville, Marquinta Harvey, Michael D. Oliver, Tatum Brown, Deya Rassul, Thomas Strickler, Jarod Parrish, Catherine Bass
Funded Scholarship
Hypertension disparities persist across communities, driven by interactions between social determinants of health (SDOH) and behavioral factors. This study examines geographic and demographic patterns of hypertension in Nashville, Tennessee, to assess how socioeconomic, environmental, and behavioral factors contribute to inequities in prevalence, treatment, and control. Granular ZIP code-level analyses highlight community-specific drivers and the need for policy reforms to advance health equity.
Non-Instrumented Dva: Assessment Of Performance And Clinical Feasibility In Children Ages 2 Through 13 Years, Cathey P. Norton, Nancy S. Darr, Mary Katherine Beshears, Katherine Catalano, Tyra Dillard, Mahayla J.K. Gamble, Magdalene Olerich, Sadie Rodell Rupp
Non-Instrumented Dva: Assessment Of Performance And Clinical Feasibility In Children Ages 2 Through 13 Years, Cathey P. Norton, Nancy S. Darr, Mary Katherine Beshears, Katherine Catalano, Tyra Dillard, Mahayla J.K. Gamble, Magdalene Olerich, Sadie Rodell Rupp
Funded Scholarship
Background/Objectives: Vestibular disorders can have functional consequences for children, including balance and gross motor delays, academic difficulties and behavioral manifestations; however, they are frequently undiagnosed in children. The purposes of this study were to evaluate the feasibility and clinical utility of performing a non-instrumented dynamic visual acuity (DVA) test as a primary screening tool for children and to examine typical performance on this non-instrumented DVA test in a large sample of children ages 2 through 13 years.
Methods: A clinical DVA test was administered to a convenience sample of 208 children aged 2–13 years. Static visual acuity was assessed using …
Correlates Of Recovery Capital Among Women In Jails: Leveraging A Dimensional Recovery Framework, Amanda Fallin-Bennett, Martha Tillson, Jaxin Annett, Hartley Feld, Michele Staton
Correlates Of Recovery Capital Among Women In Jails: Leveraging A Dimensional Recovery Framework, Amanda Fallin-Bennett, Martha Tillson, Jaxin Annett, Hartley Feld, Michele Staton
Nursing Faculty Publications
Background: Recovery capital encompasses internal and external factors that support recovery from substance use disorder, such as employment, social support, and physical and mental health. There is a need for more research on recovery capital among women who are incarcerated, who often face complex barriers to recovery, such as poverty, unemployment, and histories of trauma.
Methods: Women (N ¼ 900) were recruited from Kentucky jails as part of the broader NIDA-funded Kentucky Justice Community Opioid Innovation Network (JCOIN) cooperative project. Measures from baseline interviews (during incarceration) were selected in alignment with the Substance Abuse Mental Health Service Administration (SAMHSA)’s four …
“Being Treated As The Expert:” A Blueprint For A Community Advisory Board Approach To Elevate The Voice Of People With Living Experience With Substance Use In Academic Research, Trevor Moffitt, Survivors Union Of The Bluegrass, Bryson Henson, April M. Young, Sharon L. Walsh, Rachel Vickers-Smith, Junior Cruz, Jeremy Byard, Brook West, Amanda Fallin-Bennett
“Being Treated As The Expert:” A Blueprint For A Community Advisory Board Approach To Elevate The Voice Of People With Living Experience With Substance Use In Academic Research, Trevor Moffitt, Survivors Union Of The Bluegrass, Bryson Henson, April M. Young, Sharon L. Walsh, Rachel Vickers-Smith, Junior Cruz, Jeremy Byard, Brook West, Amanda Fallin-Bennett
Nursing Faculty Publications
Introduction: Researchers have traditionally engaged Community Advisory Boards (CABs) to meaningfully involve community members in the research process. However, CABs are often formed only after a grant is funded, leading to criticisms of functioning merely as “ethical approvers.” For substance use researchers, the inclusion of people with living experience (PWLE; current experience with drug use) across all stages of research is especially important as they have historically been the experts in the needs of their community. Methods: In response to this need for community engagement in research, the University of Kentucky, in partnership with a local recovery community center (RCC; …
Coalition Building And Citizen Science For Radon Risk Reduction, Stacy Stanifer, Kathy Rademacher, Whitney Sedio, Naomi Cheek, David Gross, Caitlyn Curtis, Amanda Thaxton-Wiggins, Mary Kay Rayens, Ellen J. Hahn
Coalition Building And Citizen Science For Radon Risk Reduction, Stacy Stanifer, Kathy Rademacher, Whitney Sedio, Naomi Cheek, David Gross, Caitlyn Curtis, Amanda Thaxton-Wiggins, Mary Kay Rayens, Ellen J. Hahn
Nursing Faculty Publications
We evaluated the implementation of local coalitions led in partnership with citizen scientists, community-based organizations, and public libraries in four rural communities to lower exposure to radon in the home. The objectives were to (1) describe the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) of four radon coalitions, and (2) compare RE-AIM factors among citizen scientists who participated in the coalitions and those who did not. A larger community-engaged research project embedded coalition building using a citizen science approach. Three of the four coalitions focused on health and wellness more broadly (18–34 members); one focused solely on radon (10 members). Coalition membership and activities varied …
Evaluation Of A Tobacco Treatment Specialist Training Program Targeted To Behavioral Health Professionals, Chizimuzo T. C. Okoli, Sarret Seng, Bassema Abu Farsakh, Emily Koyagi, Heather Beck, Audrey Darville
Evaluation Of A Tobacco Treatment Specialist Training Program Targeted To Behavioral Health Professionals, Chizimuzo T. C. Okoli, Sarret Seng, Bassema Abu Farsakh, Emily Koyagi, Heather Beck, Audrey Darville
Nursing Faculty Publications
Tobacco use remains disproportionately high among adults living with mental illnesses (MIs), contributing to excess morbidity and mortality, particularly in high-burden states such as Kentucky. Behavioral healthcare providers are well-positioned to address this disparity but often lack formal training in evidence-based tobacco treatment. Tobacco Treatment Specialist (TTS) training provides healthcare providers with skills to deliver evidence-based tobacco treatment; however, traditional TTS training models often rely on synchronous, in-person or live virtual formats, which may limit accessibility for some healthcare workforces. Asynchronous, web-based delivery models may reduce these barriers. This study evaluates a targeted, asynchronous TTS training program designed for providers …
Optimal Control Analysis Of Malaria Transmission In The Presence Of Insecticide Resistance And Climate Variability In Kenya, Lorna Chepkemoi, Titus Okello Orwa, Samuel Mwalili, Rachel Waema Mbogo, Steeven Belvinos Affognon, Daisy Salifu, Henri E.Z. Tonnang
Optimal Control Analysis Of Malaria Transmission In The Presence Of Insecticide Resistance And Climate Variability In Kenya, Lorna Chepkemoi, Titus Okello Orwa, Samuel Mwalili, Rachel Waema Mbogo, Steeven Belvinos Affognon, Daisy Salifu, Henri E.Z. Tonnang
All Peer-Reviewed Publications
Malaria remains a major public health concern in Kenya, where changing climatic conditions, insecticide resistance, and mosquito behavioral adaptations continue to challenge control efforts. This study develops and analyzes a climate-sensitive malaria transmission model that incorporates mosquito behavior, insecticide resistance, and vector–human ecological dynamics to identify optimal control strategies for the Kenyan context. The model’s well-posedness was established, the basic reproduction number (R0) computed using the next-generation matrix method, and the stability of equilibrium points assessed. Spatial analysis of R0 was performed using temperature and rainfall raster data to map transmission risk across Kenya under varying insecticide use scenarios. Results …