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Full-Text Articles in Medicine and Health Sciences

Nurse-Initiated Improvement For Documentation Of Penicillin Adverse Drug Reactions In Pediatric Urgent Care Clinics., Elizabeth Monsees, Diane Petrie, Rana El Feghaly, Sarah Suppes, Brian R. Lee, Megan Whitt, Amanda Nedved Aug 2025

Nurse-Initiated Improvement For Documentation Of Penicillin Adverse Drug Reactions In Pediatric Urgent Care Clinics., Elizabeth Monsees, Diane Petrie, Rana El Feghaly, Sarah Suppes, Brian R. Lee, Megan Whitt, Amanda Nedved

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objective: Penicillin allergy labels (PALs) contribute to broad-spectrum antibiotic use. Thorough documentation can help prescribers identify and remove unnecessary PALs. We aimed to improve documentation of PALs in three pediatric urgent care (PUC) clinics, using a nurse-initiated quality improvement (QI) approach. Methods: QI interventions included a survey to assess prescriber and nurse confidence, an online educational module, and an algorithm to aid in clarifying PALs. We measured the percentage of PALs with a clarified reaction severity as our primary outcome using annotated control charts. Descriptive and inferential statistics evaluated survey responses between nurses and prescribers. Results: Clarified PAL reaction severity …


Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial., David J. Goldberg, Victor Zak, Chenwei Hu, Adam M. Lubert, Rahul H. Rathod, Daniel J. Penny, Robert Whitehill, Kurt R. Schumacher, Salil Ginde, Michelle Ploutz, Gi Beom Kim, Todd T. Nowlen, Michael V. Dimaria, Benjamin P. Frischhertz, Jonathan B. Wagner, Kimberly E. Mchugh, Brian W. Mccrindle, Mark J. Cartoski, Jon Detterich, Anji T. Yetman, Anitha S. John, Marc E. Richmond, Matthew Files, R Mark Payne, Andrew S. Mackie, Christopher K. Davis, William B. Orr, Ruchira Garg, Kevin D. Hill, Jennifer S. Yauck, Michael G. Mcbride, James Yeager, Gail D. Pearson, Stephen M. Paridon, Bryan H. Goldstein Aug 2025

Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial., David J. Goldberg, Victor Zak, Chenwei Hu, Adam M. Lubert, Rahul H. Rathod, Daniel J. Penny, Robert Whitehill, Kurt R. Schumacher, Salil Ginde, Michelle Ploutz, Gi Beom Kim, Todd T. Nowlen, Michael V. Dimaria, Benjamin P. Frischhertz, Jonathan B. Wagner, Kimberly E. Mchugh, Brian W. Mccrindle, Mark J. Cartoski, Jon Detterich, Anji T. Yetman, Anitha S. John, Marc E. Richmond, Matthew Files, R Mark Payne, Andrew S. Mackie, Christopher K. Davis, William B. Orr, Ruchira Garg, Kevin D. Hill, Jennifer S. Yauck, Michael G. Mcbride, James Yeager, Gail D. Pearson, Stephen M. Paridon, Bryan H. Goldstein

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo2 in participants with near-normal baseline exercise performance.

METHODS: Participants were divided into subgroups by baseline predicted peak Vo2 (< 80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo2 < 80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.

RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo2 < 80% predicted. In this subgroup, the primary outcome of peak Vo2 improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; P=0.021). Secondary outcome measures, including Vo2 at …


Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen Aug 2025

Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen

Department of Medical Oncology Faculty Papers

Nasopharyngeal carcinoma (NPC) is a cancer arising from the epithelial cells of the nasopharynx, which is rare in Western countries but extremely prevalent in Borneo and the Southern China region. Present-day hurdles in NPC treatment that lead to poor quality of life and poor survival include distant metastasis and resistance to chemoradiotherapy. Silvestrol and its 5'''-epimer, episilvestrol, are compounds isolated from the plant Aglaia stellatopilosa, which is endemic to Borneo. Silvestrol, a protein synthesis inhibitor, preferentially inhibits the translation of cancer-associated mRNAs. CX-5461 is an inhibitor of RNA polymerase I that catalyzes rRNA synthesis. The present study sought to …


Genomic Editing Of A Pathogenic Sequence Variant In Acta2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome In Mice, Qianqian Ding, Peiheng Gan, Zhisheng Xu, Hui Li, Lei Guo, Camryn Macdonald, Wei Tan, Efrain Sanchez-Ortiz, John R Mcanally, Yu Zhang, Dileep Karri, Lin Xu, Ning Liu, Eric N Olson Aug 2025

Genomic Editing Of A Pathogenic Sequence Variant In Acta2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome In Mice, Qianqian Ding, Peiheng Gan, Zhisheng Xu, Hui Li, Lei Guo, Camryn Macdonald, Wei Tan, Efrain Sanchez-Ortiz, John R Mcanally, Yu Zhang, Dileep Karri, Lin Xu, Ning Liu, Eric N Olson

Faculty, Staff and Student Publications

Background: Vascular smooth muscle cells (SMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. Vascular SMC contractility and function depend on ACTA2 (smooth muscle α-actin 2). The pathogenic variant ACTA2 c.536G>A (p.R179H) causes multisystemic smooth muscle dysfunction syndrome, a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high risk of early death from aneurysms or stroke. No effective treatments exist for multisystemic smooth muscle dysfunction syndrome.

Methods: To develop a comprehensive therapy for multisystemic smooth muscle dysfunction syndrome, we used …


Causes Of Symptoms And Symptom Persistence In Long Covid And Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Anthony L Komaroff, Robert Dantzer Aug 2025

Causes Of Symptoms And Symptom Persistence In Long Covid And Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Anthony L Komaroff, Robert Dantzer

Faculty, Staff and Student Publications

Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural …


Optimizing Motion Management And Baseline Shifts In Magnetic Resonance-Guided Spine Stereotactic Body Radiation Therapy, Yao Ding, Travis C Salzillo, Debra N Yeboa, Martin C Tom, Zhiheng Wang, Parmeswaran Diagaradjane, Ergys Subashi, Jinzhong Yang, Todd Swanson, Thomas Beckham, Chenyang Wang, Amol J Ghia, Tina Briere, Jihong Wang, Fabienne Lathuilière, Sneha Cloake, Eun Young Han Aug 2025

Optimizing Motion Management And Baseline Shifts In Magnetic Resonance-Guided Spine Stereotactic Body Radiation Therapy, Yao Ding, Travis C Salzillo, Debra N Yeboa, Martin C Tom, Zhiheng Wang, Parmeswaran Diagaradjane, Ergys Subashi, Jinzhong Yang, Todd Swanson, Thomas Beckham, Chenyang Wang, Amol J Ghia, Tina Briere, Jihong Wang, Fabienne Lathuilière, Sneha Cloake, Eun Young Han

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety.

PURPOSE: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement …


Therapeutic Targeting Of Syndecan-1 Axis Overcomes Acquired Resistance To Kras-Targeted Therapy In Gastrointestinal Cancers, Madelaine S Theardy, Mitsunobu Takeda, Alexey Sorokin, Shuaitong Chen, Zecheng Yang, Xiaofei Wang, Preeti Kanikarla, Oluwadara Coker, Phuoc Nguyen, Yongkun Wei, Jun Yao, Liang Yan, Yanqing Jin, Yiming Cai, Masakatsu Paku, Ziheng Chen, Kara Z Li, Francesca Citron, Hideo Tomihara, Sisi Gao, Angela K Deem, Jun Zhao, Huamin Wang, Samir Hanash, Ronald A Depinho, Anirban Maitra, Giulio F Draetta, Haoqiang Ying, Scott Kopetz, Wantong Yao Aug 2025

Therapeutic Targeting Of Syndecan-1 Axis Overcomes Acquired Resistance To Kras-Targeted Therapy In Gastrointestinal Cancers, Madelaine S Theardy, Mitsunobu Takeda, Alexey Sorokin, Shuaitong Chen, Zecheng Yang, Xiaofei Wang, Preeti Kanikarla, Oluwadara Coker, Phuoc Nguyen, Yongkun Wei, Jun Yao, Liang Yan, Yanqing Jin, Yiming Cai, Masakatsu Paku, Ziheng Chen, Kara Z Li, Francesca Citron, Hideo Tomihara, Sisi Gao, Angela K Deem, Jun Zhao, Huamin Wang, Samir Hanash, Ronald A Depinho, Anirban Maitra, Giulio F Draetta, Haoqiang Ying, Scott Kopetz, Wantong Yao

Faculty, Staff and Student Publications

The therapeutic benefit of recently developed mutant KRAS (KRAS∗) inhibitors remains limited by the rapid onset of resistance. Here, we aim to delineate mechanisms underlying acquired resistance and identify actionable targets for overcoming this clinical challenge. Previously, we identified syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by KRAS∗. By leveraging both pancreatic and colorectal cancer models, we show that surface SDC1 expression initially diminishes upon KRAS∗ inhibition but recovers in tumor cells that bypass KRAS∗ dependency. Mechanistically, we reveal that YAP1 activation drives the recovery of SDC1 surface localization to enhance macropinocytosis-mediated …


Heart Failure And Death In Older Adults With Elevated Cardiac Biomarkers But Without Risk Factors: The Atherosclerosis Risk In Communities Study, Xiaoming Jia, Mahmoud Al Rifai, Chiadi Ndumele, Amil Shah, Elizabeth Selvin, Salim S Virani, Ron C Hoogeveen, Biykem Bozkurt, Christie M Ballantyne, Vijay Nambi Aug 2025

Heart Failure And Death In Older Adults With Elevated Cardiac Biomarkers But Without Risk Factors: The Atherosclerosis Risk In Communities Study, Xiaoming Jia, Mahmoud Al Rifai, Chiadi Ndumele, Amil Shah, Elizabeth Selvin, Salim S Virani, Ron C Hoogeveen, Biykem Bozkurt, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

No abstract provided.


Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma Aug 2025

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …


Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag Aug 2025

Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag

Duncan NRI Faculty and Staff Publications

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes, fundamentally changing the study of biology. The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics. As such, they are intimately related to aqueous two-phase systems and water-in-water emulsions. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials–. …


Anti-Inflammatory Diet And Probiotic Supplementation As Strategies To Modulate Immune Dysregulation In Autism Spectrum Disorder, Carlos Andrés Naranjo-Galvis, Diana María Trejos-Gallego, Cristina Correa-Salazar, Jessica Triviño-Valencia, Marysol Valencia-Buitrago, Andrés Felipe Ruiz-Pulecio, Luisa Fernanda Méndez-Ramírez, Jovanny Zabaleta, Miguel Andres Meñaca-Puentes, Carlos Alberto Ruiz-Villa, Marcela Orjuela-Rodriguez, Juan Carlos Carmona-Hernández, Luisa Matilde Salamanca-Duque Aug 2025

Anti-Inflammatory Diet And Probiotic Supplementation As Strategies To Modulate Immune Dysregulation In Autism Spectrum Disorder, Carlos Andrés Naranjo-Galvis, Diana María Trejos-Gallego, Cristina Correa-Salazar, Jessica Triviño-Valencia, Marysol Valencia-Buitrago, Andrés Felipe Ruiz-Pulecio, Luisa Fernanda Méndez-Ramírez, Jovanny Zabaleta, Miguel Andres Meñaca-Puentes, Carlos Alberto Ruiz-Villa, Marcela Orjuela-Rodriguez, Juan Carlos Carmona-Hernández, Luisa Matilde Salamanca-Duque

School of Medicine Faculty Publications

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with behavioral and cognitive impairments. Increasing evidence also links ASD with systemic immune dysregulation, including abnormal cytokine profiles and chronic low-grade inflammation. Emerging evidence suggests that targeted dietary strategies and probiotic supplementation may modulate immune responses and gut–brain interactions in patients with ASD. This study aimed to evaluate the immunomodulatory effects of a structured anti-inflammatory diet (NeuroGutPlus) compared to multi-strain probiotics in children with ASD. NeuroGutPlus is a nutritionally complete anti-inflammatory dietary protocol that targets gut integrity, inflammation, and mitochondrial function. It includes a diet low in gluten, FODMAPs, casein, …


Asymmetric Fgf Receptor Dimerization: Implications For Fgf23 Biology And Drug Discovery, Mohammed S. Razzaque, Moosa Mohammadi Aug 2025

Asymmetric Fgf Receptor Dimerization: Implications For Fgf23 Biology And Drug Discovery, Mohammed S. Razzaque, Moosa Mohammadi

School of Medicine Publications

Fibroblast growth factor 23 (FGF23) requires both αKlotho and heparan sulfate proteoglycans (HSPGs) as obligatory coreceptors to bind, dimerize, and activate its FGF receptors (FGFRs) in the kidney, thereby regulating mineral ion and vitamin D homeostasis. Cryogenic electron microscopy studies reveal that FGF23 signaling proceeds through an asymmetric 1:2:1:1 FGF23–FGFR–αKlotho–HS assembly. According to this structural model, αKlotho simultaneously anchors FGF23 and one FGFR chain, referred to as the primary receptor (FGFRP), to form a 1:1:1 FGF23-FGFRP-αKlotho triplex, which boosts FGF23-FGFRP interaction. Subsequently, the HS coreceptor aids the triplex in recruiting a second FGFR chain, or secondary receptor (FGFRS), leading to …


Factors That Influence Female Orthopaedic Surgeons' Decision To Pursue A Career In Sports Medicine: A Mixed-Methods Study, Nichelle M Enata, Katherine M Gerull, Ahmed Hanafy, Mary K Mulcahey, Derrick M Knapik, Matthew V Smith Aug 2025

Factors That Influence Female Orthopaedic Surgeons' Decision To Pursue A Career In Sports Medicine: A Mixed-Methods Study, Nichelle M Enata, Katherine M Gerull, Ahmed Hanafy, Mary K Mulcahey, Derrick M Knapik, Matthew V Smith

2020-Current year OA Pubs

BACKGROUND: Despite the increased percentage of women in medical school and in orthopaedic residency programs, the percentage of women pursuing careers in sports medicine has only increased 3% over the past decade.

PURPOSE: To investigate the experiences and perceptions of female orthopaedic surgeons about sports medicine, identifying factors influencing career interest in this surgical subspecialty.

STUDY DESIGN: Cross-sectional study.

METHODS: A mixed-methods approach, combining an online survey and qualitative interviews, was utilized to compare the clinical experiences and personal perceptions of women in orthopaedic sports medicine with women in other orthopaedic subspecialties. Surveys were distributed to members of the Ruth …


Palpation Characteristics Of An Instrumented Virtual Cricothyroidotomy Simulator, Melih Turkseven, Trudi Di Qi, Ganesh Sankaranarayanan, Suvranu De Aug 2025

Palpation Characteristics Of An Instrumented Virtual Cricothyroidotomy Simulator, Melih Turkseven, Trudi Di Qi, Ganesh Sankaranarayanan, Suvranu De

Engineering Faculty Articles and Research

Cricothyroidotomy (CCT) is a critical, life-saving procedure requiring the identification of key neck landmarks through palpation. Interactive virtual simulation offers a promising, cost-effective approach to CCT training with high visual realism. However, developing the palpation skills necessary for CCT requires a haptic interface with tactile sensitivity comparable to human fingers. Such interfaces are often represented by plastic partial mannequins, which require further adaptation to integrate into virtual environments. This study introduces an instrumented physical palpation interface for CCT, integrated into a virtual surgical simulator, and tested on 10 surgeons who practiced the procedure over a training period. Data on haptic …


Anti-Tumor Activity Of Camptothecin Analog Conjugate Of An Rspo4-Based Peptibody Targeting Lgr4/5/6 In Preclinical Models Of Colorectal Cancer, Yukimatsu Toh, Ling Wu, Jianghua Tu, Zhengdong Liang, Adela M Aldana, Jake J Wen, Li Li, Sheng Pan, Julie H Rowe, Martha E Hensel, Carolyn L Hodo, Rick A Finch, Kendra S Carmon, Qingyun J Liu Aug 2025

Anti-Tumor Activity Of Camptothecin Analog Conjugate Of An Rspo4-Based Peptibody Targeting Lgr4/5/6 In Preclinical Models Of Colorectal Cancer, Yukimatsu Toh, Ling Wu, Jianghua Tu, Zhengdong Liang, Adela M Aldana, Jake J Wen, Li Li, Sheng Pan, Julie H Rowe, Martha E Hensel, Carolyn L Hodo, Rick A Finch, Kendra S Carmon, Qingyun J Liu

The Brown Foundation: Institute of Molecular Medicine

Background: Antibody-drug conjugates (ADCs) are a significant advancement in targeted cancer therapy, but none are approved for colorectal cancer (CRC). LGR4/5/6, highly expressed in most CRCs, are promising targets. While LGR5-targeting ADCs show strong anti-tumor effects, their efficacy is limited by LGR5 loss in some CRC cells. RSPO4, a natural ligand for LGR4/5/6, binds all three receptors with high affinity. This research develops RSPO4-based peptibody drug-conjugates (PDCs) to simultaneously target LGR4/5/6, offering a novel therapeutic approach for CRC.

Methods: LGR4/5/6 expression in CRCs was analysed using RNA-seq datasets and Western blot. Peptibody binding affinities were measured, conjugated to camptothecin analog, …


Simulated Emergency Room Sign-Outs: What They Tell Us About Diagnostic Accuracy And Opportunities For Improvement, Roni Matin, Brent R King, Amit M Mehta, Susan H Fenton, Nathan R Hoot, David J Robinson, Charles L Maddow, Amy Franklin Aug 2025

Simulated Emergency Room Sign-Outs: What They Tell Us About Diagnostic Accuracy And Opportunities For Improvement, Roni Matin, Brent R King, Amit M Mehta, Susan H Fenton, Nathan R Hoot, David J Robinson, Charles L Maddow, Amy Franklin

Faculty, Staff and Student Publications

Objective: Emergency department (ED) sign-outs provide continuity of care for patients at shift changes. However, these periods have been associated with communication breakdowns and medical errors. We explored information factors (stage-of-the-case and the explicitness of the sign-out narrative) to determine their impact on clinicians' diagnostic accuracy and confidence.

Methods: Clinicians from 2 academic ED sites reviewed patient vignettes sign-out narratives (N=69). Using a within-subjects experiment, the explicitness of the sign-out information (i.e., broad statement about labs versus stating each test) and the patient's stage in the diagnostic process (e.g., labs pending, treatment occurring, etc.) at the time of sign-out varied. …


Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval-Augmented Generation, Brandon T Garcia, Lauren Westerfield, Priya Yelemali, Nikhita Gogate, E Andres Rivera-Munoz, Haowei Du, Moez Dawood, Angad Jolly, James R Lupski, Jennifer E Posey Aug 2025

Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval-Augmented Generation, Brandon T Garcia, Lauren Westerfield, Priya Yelemali, Nikhita Gogate, E Andres Rivera-Munoz, Haowei Du, Moez Dawood, Angad Jolly, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Rule-based HPO extraction tools use concept recognition to automatically identify phenotypes, but they often struggle with incomplete phenotype assignment, requiring significant manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement. We present RAG-HPO, a Python-based tool that leverages retrieval-augmented generation (RAG) to elevate accuracy of HPO term assignment by LLM. This approach bypasses the limitations …


High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti Aug 2025

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …


Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova Aug 2025

Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova

Faculty, Staff and Students Publications

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often …


Mechano-Signal Transduction Pathways Of The Diaphragmatic Muscle And Role Of Cytoskeleton, Junaith S Mohamed, Patricia S Pardo, Aladin M Boriek Aug 2025

Mechano-Signal Transduction Pathways Of The Diaphragmatic Muscle And Role Of Cytoskeleton, Junaith S Mohamed, Patricia S Pardo, Aladin M Boriek

Faculty, Staff and Students Publications

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm-a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory …


Improving Diabetes Management Through Evidence-Based Educational Resources In A Federally Qualified Health Center, Linda F. Dunbar Aug 2025

Improving Diabetes Management Through Evidence-Based Educational Resources In A Federally Qualified Health Center, Linda F. Dunbar

Doctor of Nursing Practice Final Project Abstract

Purpose

The purpose of this scholarly project was to implement updated culturally tailored diabetes education materials, conduct staff training sessions, and promote consistent documentation of hemoglobin A1c values and adherence to evidence-based guidelines, aligned with current American Diabetes Association (ADA) standards of care. These interventions aimed to reduce the percentage of adults with HbA1c levels greater than 9%.

Background

The project was implemented at a Federally Qualified Health Center (FQHC) in a rural community of Tomball, Texas. The patient population is 73% Hispanic/Latino, who primarily speak Spanish, and are disproportionately affected by diabetes.

Methodology

The project was implemented using the …


Considering Climate Contexts: Examining Promotive And Punitive School Characteristics Among Diverse High School Students, Ashley Bazin, Maryse Richards, Akila Raoul, Allison Lloyd, Elizabeth Rovegno, Yael Granot Aug 2025

Considering Climate Contexts: Examining Promotive And Punitive School Characteristics Among Diverse High School Students, Ashley Bazin, Maryse Richards, Akila Raoul, Allison Lloyd, Elizabeth Rovegno, Yael Granot

Psychology: Faculty Publications

Schools are a critical developmental context for adolescents that can, depending on certain characteristics, do a better or worse job at promoting student resilience and well- being. In working to meet student needs and respond to student behaviors, schools can exhibit more punitive characteristics, like exclusionary discipline practices, or more promotive characteristics, including restorative practices and marshaling of mental health resources. While punitive factors have been associated with more negative outcomes, especially for marginalized students, and promotive factors have been associated with more positive outcomes for students, these factors have rarely been considered together. We conducted an online survey of …


Circulating Genomic Landscape Following Cyclin-Dependent Kinase 4/6 Inhibitors Exposure In Hr + /Her2- Metastatic Breast Cancer: A Retrospective Multi-Institutional Consortium Analysis, Letizia Pontolillo, Andrew A Davis, Katherine Clifton, Emily Podany, Cynthia X Ma, Et Al. Aug 2025

Circulating Genomic Landscape Following Cyclin-Dependent Kinase 4/6 Inhibitors Exposure In Hr + /Her2- Metastatic Breast Cancer: A Retrospective Multi-Institutional Consortium Analysis, Letizia Pontolillo, Andrew A Davis, Katherine Clifton, Emily Podany, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are the mainstay of treatment for hormone receptor positive, HER2 negative (HR + /HER2-) metastatic breast cancer (MBC). However, disease progression is inevitable and unveiling resistance mechanisms is crucial to guide post-CDK4/6i therapeutic strategies. In this study, we retrospectively analyzed a real-world, multi-institutional cohort of patients with HR + /HER2- MBC characterized by circulating tumor DNA (ctDNA) through next-generation sequencing (NGS) before starting second-line treatment. Among 93 patients previously treated with CDK4/6i, PIK3CA (37.6%), ESR1 (46.2%) and TP53 (31.2%) were the most altered genes. Comparing with a CDK4/6i plus ET naïve …


Novel Neuroactive Steroid Analogs And Voltage-Dependent Blockers Of Cav3.2 Currents, B372 And Yx23, Are Effective Anti-Nociceptives With Diminished Sedative Properties In Intact Female Mice, Benjamin Volvovitz, Rakib Miah, Kibeom Park, Jae Hun Kim, Raul Vargas, Yuanjiang Xu, Mingxing Qian, Douglas F Covey, Slobodan M Todorovic, Vesna Jevtovic-Todorovic Aug 2025

Novel Neuroactive Steroid Analogs And Voltage-Dependent Blockers Of Cav3.2 Currents, B372 And Yx23, Are Effective Anti-Nociceptives With Diminished Sedative Properties In Intact Female Mice, Benjamin Volvovitz, Rakib Miah, Kibeom Park, Jae Hun Kim, Raul Vargas, Yuanjiang Xu, Mingxing Qian, Douglas F Covey, Slobodan M Todorovic, Vesna Jevtovic-Todorovic

2020-Current year OA Pubs

Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies. Low-voltage activated (T-type) calcium channels (Ca


Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills Aug 2025

Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills

School of Graduate Studies Faculty Publications

The opioid crisis remains a critical public health concern, with rising rates of overdose and opioid use disorder. While opioids are effective for managing pain, both chronic use and withdrawal are associated with increased pain sensitivity. Although most prior research has focused on adults, opioid use during adolescence is common and linked to a heightened risk for developing alcohol use disorder and other forms of substance misuse. Like opioids, acute alcohol use can be analgesic, but chronic alcohol exposure and withdrawal lead to increased pain sensitivity. However, the interactive effects of adolescent opioid and adult alcohol exposure on pain remain …


Single Balloon Enteroscopy In The Elderly, Marc J Zuckerman, Majd Michael, Mohammad Bashashati, Alok K Dwivedi, Nancy A Casner, Mohamed O Othman, Sherif E Elhanafi Aug 2025

Single Balloon Enteroscopy In The Elderly, Marc J Zuckerman, Majd Michael, Mohammad Bashashati, Alok K Dwivedi, Nancy A Casner, Mohamed O Othman, Sherif E Elhanafi

Faculty, Staff and Students Publications

Background: Single-balloon enteroscopy (SBE) is a minimally invasive procedure to assess and treat small bowel pathologies. The most common use is to detect suspected small bowel bleeding: Insignificant gastrointestinal (GI) bleeding or iron deficiency anaemia (IDA). The safety and feasibility of SBE in the elderly has not been adequately studied.

Aim: To assess the safety and feasibility of both antegrade and retrograde SBE in elderly patients.

Methods: We performed a retrospective cohort study of all antegrade and retrograde SBE done at our center from March 2011 through May 2020. We collected patient's data including demographics, indications, findings, therapeutic interventions, and …


Old Vs New Local Ancestry Inference In Hchs/Sol: A Comparative Study, Xueying Chen, Hao Wang, Iris Broce, Anders Dale, Bing Yu, Laura Y Zhou, Xihao Li, Maria Argos, Martha L Daviglus, Jianwen Cai, Nora Franceschini, Tamar Sofer Aug 2025

Old Vs New Local Ancestry Inference In Hchs/Sol: A Comparative Study, Xueying Chen, Hao Wang, Iris Broce, Anders Dale, Bing Yu, Laura Y Zhou, Xihao Li, Maria Argos, Martha L Daviglus, Jianwen Cai, Nora Franceschini, Tamar Sofer

Faculty, Staff and Student Publications

Hispanic/Latino populations are admixed, with genetic contributions from multiple ancestral populations. To uncover genetic associations in these populations, researchers often turn to admixture mapping, which relies on inferred counts of "local" ancestry, i.e. the source ancestral population at a locus. Local ancestries are inferred using external reference panels that represent ancestral populations, making the choice of inference method and reference panel critical. This study used a dataset of Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to evaluate how updates in local ancestry inference (LAI) affect results, specifically, the 'old' LAI performed using a popular inference method …


Bioinspired Ruthenium-Manganese-Oxygen Complex For Biocatalytic And Radiosensitization Therapies To Eradicate Primary And Metastatic Tumors, Ruidan Li, Ting Wang, Shengdong Mu, Zhenyu Xing, Zhiying Ding, Qinlong Wen, Zhigong Wei, Xiaolin Wang, Mohsen Adeli, Shuang Li, Chong Cheng, Xingchen Peng Aug 2025

Bioinspired Ruthenium-Manganese-Oxygen Complex For Biocatalytic And Radiosensitization Therapies To Eradicate Primary And Metastatic Tumors, Ruidan Li, Ting Wang, Shengdong Mu, Zhenyu Xing, Zhiying Ding, Qinlong Wen, Zhigong Wei, Xiaolin Wang, Mohsen Adeli, Shuang Li, Chong Cheng, Xingchen Peng

Faculty, Staff and Students Publications

Designing efficient, biocompatible radiation-sensitive materials to activate systemic immune responses can maximize tumoricidal effects against malignant tumors. Here, inspired by natural Mn-peroxidase, we propose the de novo design of the RuMn-oxygen complex (MnBTC-Ru) for biocatalytic and radiosensitization therapies to eradicate primary and metastatic tumors. Our results reveal that Mn-organic ligands can enhance the electron density of Ru clusters, thereby optimizing their binding to oxygen species and resulting in high reactive oxygen species and oxygen generation. Accordingly, MnBTC-Ru with radiation can enhance cell membrane and DNA damage, triggering apoptosis though oxidative damage, heightening radiosensitization, and activating CD8


The Silent Epidemic: Equipment Maintenance Failures And Patient Outcomes In Ghana's Healthcare System, Ramseyer Adekorang Asamoah, Celene Dzreke, Evans Dzreke, David Kanzin Aug 2025

The Silent Epidemic: Equipment Maintenance Failures And Patient Outcomes In Ghana's Healthcare System, Ramseyer Adekorang Asamoah, Celene Dzreke, Evans Dzreke, David Kanzin

Health & Biomedical Sciences Faculty Publications

Broken tools indicate a broken system. This new study reveals how medical equipment failures destroy Ghana's public hospitals, turning life-saving technologies into silent murderers that disproportionately affect rural areas. Moving beyond technical diagnostics, we study the cascading systemic failures, chronic underfunding, critical staff shortages, and fragmented supply chains that leave 40% of vital equipment, such as ventilators, MRI scanners, and dialysis machines, inoperable at any given time. We quantify the devastating human toll through rigorous mixed-methods analysis of equipment downtime records across ten regional hospitals (2018-2023) and profound narratives from 50 frontline stakeholders, doctors forced to improvise without working incubators, …


Newly Diagnosed Acute Myeloid Leukemia In Unfit Patients: 2026 Treatment Algorithms, Naseema Gangat, Courtney D Dinardo Aug 2025

Newly Diagnosed Acute Myeloid Leukemia In Unfit Patients: 2026 Treatment Algorithms, Naseema Gangat, Courtney D Dinardo

Faculty, Staff and Student Publications

Management paradigms for newly-diagnosed acute myeloid leukemia (ND-AML) in patients considered unfit to receive intensive chemotherapy have evolved with improved understanding of disease biology. In this setting, management requires clear delineation of goals of therapy that should include preservation of quality-of-life (QoL). Combination of venetoclax (Ven) and a hypomethylating agent (HMA) is the current standard-of-care in most circumstances with flexible options in regard to drug dose and duration of treatment as well as the addition (triplet combinations) or alternative use of targeted therapies, such as inhibitors of FLT3, IDH1, IDH2, or menin for patients with NPM1MUT …