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Articles 331 - 360 of 8831
Full-Text Articles in Entire DC Network
Examining Sleep-Related Problems In Youth With Misophonia, Kevin M Wagner, Matti Cervin, Catherine E Rast, Mered Parnes, Nicholas Murphy, Samuel Spencer, Eric A Storch, Andrew G Guzick
Examining Sleep-Related Problems In Youth With Misophonia, Kevin M Wagner, Matti Cervin, Catherine E Rast, Mered Parnes, Nicholas Murphy, Samuel Spencer, Eric A Storch, Andrew G Guzick
Faculty, Staff and Students Publications
The relationship between misophonia and sleep-related problems (SRPs) in youth is underexplored. This paucity of research is concerning because SRPs might be elevated among youth with misophonia. If left untreated, SRPs can contribute to long-term health consequences. Thus, in this study we examined the link between misophonia and SRPs in youth aged 8 to 17. In this study, we compared SRPs in 102 children and adolescents with clinically significant misophonia to SRPs in a normative youth sample and a sample of 94 youth with anxiety disorders. We also examined the extent to which SRPs were associated with misophonia severity. Approximately …
Nasopharyngeal Microbiome-Epigenome-Wide Association Analysis In Infants With Severe Bronchiolitis, Ryohei Shibata, Yijun Li, Anat Yaskolka Meir, Sara Javornik Cregeen, Matthew Clayton Ross, Janice A Espinola, Ashley F Sullivan, Liming Liang, Kohei Hasegawa, Carlos A Camargo, Zhaozhong Zhu
Nasopharyngeal Microbiome-Epigenome-Wide Association Analysis In Infants With Severe Bronchiolitis, Ryohei Shibata, Yijun Li, Anat Yaskolka Meir, Sara Javornik Cregeen, Matthew Clayton Ross, Janice A Espinola, Ashley F Sullivan, Liming Liang, Kohei Hasegawa, Carlos A Camargo, Zhaozhong Zhu
Faculty, Staff and Students Publications
Background: Bronchiolitis exposes infants to both acute burdens (e.g., hospitalization in cases of severe bronchiolitis) and increased risks for chronic respiratory sequelae (e.g., asthma). In severe bronchiolitis, recent evidence suggests distinct pathobiological roles of microbiota (e.g., viruses, bacteria) and host responses influenced by genetic and epigenetic factors. However, the relationship of airway microbiota with host DNA methylation (DNAm) in infants with severe bronchiolitis remains unknown.
Methods: In a multi-center prospective cohort of 504 multi-ethnic infants with severe bronchiolitis (age < 1 year), using nasopharyngeal microbiome (exposure) and blood DNAm (outcome, Infinium MethylationEPIC BeadChip, Illumina) data within 24 h of the hospitalization, we conducted microbiome-epigenome-wide association studies (mbEWAS). We examined microbiota-associated differentially methylated CpGs (mbDMCs, false discovery rate [FDR] < 0.05), regions (mbDMRs, FDR < 0.05), and DNAm age acceleration. We also determined the associations of DNAm age acceleration with asthma development by age 6 years. Furthermore, we focused on asthma-related pathogenic bacteria-Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae-for functional analyses by examining serum mbDMR-related proteins (Proseek Multiplex, Olink) and their enriched pathways (FDR < 0.10).
Results: Across 23 common taxa-observed at least in 25% of the infants, we identified 1 mbDMC (S. pneumoniae, cg16594639, chr20: 39528675) …
Aav Gene Therapy For Mps Iva With Induction Of Immune Tolerance Via Oral Administration Of Epitope Peptides Of N-Acetylgalactosamine-6-Sulfate Sulfatase, Sampurna Saikia, Yasuhiko Ago, Fnu Nidhi, Shaukat Khan, Zhengyu Ma, Shunji Tomatsu
Aav Gene Therapy For Mps Iva With Induction Of Immune Tolerance Via Oral Administration Of Epitope Peptides Of N-Acetylgalactosamine-6-Sulfate Sulfatase, Sampurna Saikia, Yasuhiko Ago, Fnu Nidhi, Shaukat Khan, Zhengyu Ma, Shunji Tomatsu
Department of Pediatrics Faculty Papers
Mucopolysaccharidosis IVA (MPS IVA) is caused by the accumulation of undegraded glycosaminoglycans due to the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. MPS IVA manifests as progressive systemic skeletal dysplasia. Gene therapy (GT) is potentially a one-time treatment in which the enzyme is continuously produced, circulated, and delivered to target tissues. However, immune responses to gene products can diminish therapeutic efficacy. We hypothesized that oral delivery of tolerogenic peptides induces immune tolerance to human GALNS (hGALNS) in MPS IVA mice, enhancing therapeutic efficacy. Neonatal mice deficient in mouse GALNS (mGALNS) were treated orally with three T-cell/B-cell epitope peptides or hGALNS …
Recognizing Structural And Social Determinants Of Health In The Diagnosis And Care Of Dementia, Shana D Stites, Sharnita Midgett, Nisha Patel, Kimberly Halberstadter, Rosalie Schumann, Marissa L Streitz, Yidan Shi, John C Morris, Jason Flatt, Crystal M Glover, Dawn Mechanic-Hamilton
Recognizing Structural And Social Determinants Of Health In The Diagnosis And Care Of Dementia, Shana D Stites, Sharnita Midgett, Nisha Patel, Kimberly Halberstadter, Rosalie Schumann, Marissa L Streitz, Yidan Shi, John C Morris, Jason Flatt, Crystal M Glover, Dawn Mechanic-Hamilton
2020-Current year OA Pubs
Structural and social determinants of health are environmental conditions that affect individuals' health and functioning across the life course. These determinants are salient factors at the apex of individual psychology, community variables, and larger sociological factors, exerting prominent effects on individuals' wellbeing. The National Institute on Aging seeks to understand their influence on aging and Alzheimer's disease. We propose that the benefits of doing so may reach beyond knowledge of disease mechanisms - it may also improve clinical outcomes. We describe efforts introducing structural and social determinants of health data into the national network of Alzheimer's disease research centers. We …
Evolving Epigenomics Of Immune Cells At Single-Nucleus Resolution In Children En Route To Type 1 Diabetes., Tomi Pastinen, Elin Grundberg, Todd Bradley, Jarno Honkanen, Warren A. Cheung, Arja Vuorela, Jeffrey J. Johnston, Byunggil Yoo, Santosh Khanal, Rebecca Mclennan, Jorma Ilonen, Outi Vaarala, Jeffrey P. Krischer, Mikael Knip
Evolving Epigenomics Of Immune Cells At Single-Nucleus Resolution In Children En Route To Type 1 Diabetes., Tomi Pastinen, Elin Grundberg, Todd Bradley, Jarno Honkanen, Warren A. Cheung, Arja Vuorela, Jeffrey J. Johnston, Byunggil Yoo, Santosh Khanal, Rebecca Mclennan, Jorma Ilonen, Outi Vaarala, Jeffrey P. Krischer, Mikael Knip
Manuscripts, Articles, Book Chapters and Other Papers
The appearance of diabetes-associated autoantibodies is the first detectable sign of the disease process leading to type 1 diabetes (T1D). Evidence suggests that T1D is a heterogenous disease, where the type of antibodies first formed implies subtypes. Here, we leverage longitudinal samples collected from 98 European TRIGR participants (49 children who subsequently presented with T1D, and 49 matched controls), and profile single-cell epigenomics at different time points of disease development. Quantitation of cell and nuclei populations, complemented by analysis of transcriptome and open-chromatin states, indicates robust, early, replicable monocyte lineage differences between cases and controls, suggesting the early emergence of …
The Path Forward For T Cell Engagers In Patients With Prostate Cancer, Sumit K. Subudhi, Bilal A. Siddiqui, Kevin K. Zarrabi, William K. Kelly, Charles G. Drake
The Path Forward For T Cell Engagers In Patients With Prostate Cancer, Sumit K. Subudhi, Bilal A. Siddiqui, Kevin K. Zarrabi, William K. Kelly, Charles G. Drake
Department of Medical Oncology Faculty Papers
T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to induce antitumor immune responses. TCEs have demonstrated promising clinical responses in patients with metastatic castration-resistant prostate cancer and have advanced into phase 3 clinical trials. Here we provide an overview of the mechanisms of action of TCEs, including both CD3-targeted and CD28-targeted agents, and review the clinical development of these agents for prostate cancer. We propose a path forward for TCEs in prostate cancer, in which innovative clinical trials will facilitate a biological understanding of mechanisms of efficacy and toxicity to inform: (1) development of predictive biomarkers …
Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar
Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar
Faculty Research 2026
BACKGROUND. The SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.
METHODS. We longitudinally profiled SARS-CoV-2–naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).
RESULTS. We discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1–2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was …
Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar
Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar
Faculty Research 2026
BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and …
Economic Evaluation Of Perioperative Pembrolizumab Plus Standard Of Care As Treatment For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma In The United States, Feng Qian, Arielle G Bensimon, Anjela Tzontcheva, Kimberly Benjamin, Ravindra Uppaluri, Douglas Adkins, Geoffrey Johnson, Catherine Fernan, Dandan Zheng, Yuexin Tang, Biruk Chafamo, Dominic Muston
Economic Evaluation Of Perioperative Pembrolizumab Plus Standard Of Care As Treatment For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma In The United States, Feng Qian, Arielle G Bensimon, Anjela Tzontcheva, Kimberly Benjamin, Ravindra Uppaluri, Douglas Adkins, Geoffrey Johnson, Catherine Fernan, Dandan Zheng, Yuexin Tang, Biruk Chafamo, Dominic Muston
2020-Current year OA Pubs
AIMS: In the phase 3 KEYNOTE-689 trial (NCT03765918) among patients with resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC), perioperative pembrolizumab (pembrolizumab before surgery, then continued with standard-of-care [SOC] radiotherapy +/- cisplatin after surgery followed by pembrolizumab alone) significantly prolonged event-free survival vs. SOC alone, both in the intention-to-treat population and PD-L1 combined positive score (CPS) ≥1 subgroup. Perioperative pembrolizumab + SOC received Food and Drug Administration approval in June 2025 for resectable LA HNSCC expressing PD-L1 (CPS ≥ 1). The present study evaluated the cost-effectiveness of perioperative pembrolizumab + SOC versus SOC in this indication, from …
Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur
Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur
Faculty, Staff and Students Publications
Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …
General Anesthesia Versus Conscious Sedation For Mechanical Thrombectomy In Patients With Acute Ischemic Stroke In The Most Trial, Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye
General Anesthesia Versus Conscious Sedation For Mechanical Thrombectomy In Patients With Acute Ischemic Stroke In The Most Trial, Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye
2020-Current year OA Pubs
BACKGROUND: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi-arm Optimization of Stroke Thrombolysis) trial.
METHODS: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The …
Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger
Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger
Faculty, Staff and Student Publications
Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …
Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage
Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage
Faculty, Staff and Students Publications
Forensic human identification relies on length-based differences in short tandem repeats (STRs) across autosomal and Y chromosomes, which require separate reactions and provide limited resolution. While next-generation sequencing offers greater discriminatory power, most platforms are expensive and restricted to traditional lab settings. Nanopore sequencing has the potential to change this with the real-time, portable MinION sequencer. However, forensic-specific tools that generate STR profiles compatible with established length-based databases are lacking. To address this, we developed STRspy2.0, which simultaneously profiles autosomal and Y-STRs using nanopore reads. STRspy2.0 produced accurate profiles for 54 multiplexed control libraries and 41 mock casework samples (blood, …
Evolving Strategies In Prostate Cancer: Emerging Approaches And Unmet Needs From The Bridging The Gaps In Prostate Cancer Expert Panel, Rana Mckay, Benjamin Maughan, Alicia Morgans, Neal Shore, Evan Yu, Ravi Madan, Jacob Berchuck, Bradley Carthon, Steven Finkelstein, Leonard Gomella, Michael Gorin, Andrew Hahn, Stacy Loeb, Vivek Narayan, Daniel Petrylak, Charles Ryan, Karine Tawagi, Phuoc Tran, Tanya Dorff
Evolving Strategies In Prostate Cancer: Emerging Approaches And Unmet Needs From The Bridging The Gaps In Prostate Cancer Expert Panel, Rana Mckay, Benjamin Maughan, Alicia Morgans, Neal Shore, Evan Yu, Ravi Madan, Jacob Berchuck, Bradley Carthon, Steven Finkelstein, Leonard Gomella, Michael Gorin, Andrew Hahn, Stacy Loeb, Vivek Narayan, Daniel Petrylak, Charles Ryan, Karine Tawagi, Phuoc Tran, Tanya Dorff
Department of Urology Faculty Papers
BACKGROUND: The expansion of treatment options for prostate cancer (PC) has improved disease-specific and overall survival outcomes but has also raised questions about the optimal level of treatment needed for patients based on their individual prognosis and accounting for potential toxicity, incorporating quality of life considerations.
METHODS: A panel of experts met to discuss current controversies in the care of patients with PC across the disease continuum. Multidisciplinary experts review advances and persistent uncertainties in biomarker-guided assessment, imaging, and systemic therapy for prostate cancer. The discussion outlines priority gaps in evidence that must be addressed to optimize individualized patient care. …
Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli
Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli
Faculty, Staff and Student Publications
Background: Protection of telomere 1 (POT1) tumor predisposition syndrome (POT1-TPD) is a hereditary leukemia syndrome that is identified in ∼5% of patients with chronic lymphocytic leukemia (CLL) and is characterized by a predisposition to other cancers, including gliomas, melanomas, and angiosarcomas. This study reports clinical and genetic characteristics of a large cohort of individuals with POT1-TPD.
Materials and methods: Individuals with pathogenic/likely pathogenic germline POT1 variants referred to the Hereditary Hematologic Malignancy Clinic at The University of Texas MD Anderson Cancer Center were included. Individuals with variants of uncertain significance were included if found to have telomeres >90th percentile of …
Epigenetic Age Acceleration In Young Adults With Congenital Heart Disease, Parag N Jain, Beryl C Zhuang, Joanne Whitehead, Julia L Macisaac, Kristy Dever, Mallory Gahm, Peter Ermis, Thomas W Mcdade, Michael S Kobor, Paul A Checchia
Epigenetic Age Acceleration In Young Adults With Congenital Heart Disease, Parag N Jain, Beryl C Zhuang, Joanne Whitehead, Julia L Macisaac, Kristy Dever, Mallory Gahm, Peter Ermis, Thomas W Mcdade, Michael S Kobor, Paul A Checchia
Faculty, Staff and Students Publications
Background: Adults with congenital heart disease (ACHD) having undergone palliative surgery experience chronic stress due to altered physiology and repeated surgical interventions since infancy.
Objectives: To investigate whether ACHD, who had experienced chronic physiological stress from their underlying condition and early-life cardiac surgeries, was associated with epigenetic age acceleration (EAA) and other DNA methylation (DNAm)-based biomarkers, and to assess the potential contribution of derived inflammatory markers to EAA.
Methods: A case-control study comparing ACHD patients and healthy adults. Whole blood DNAm profile was used to estimate DNAm-based blood cell type proportions, multiple epigenetic age measures, and interleukin-6 (IL-6) and C-reactive …
Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán
Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán
Faculty, Staff and Student Publications
Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …
A Framework For Assessing The Trustworthiness Of Scientific Research Findings, Brian A Nosek, David B Allison, Kathleen Hall Jamieson, Marcia Mcnutt, A Beau Nielsen, Susan M Wolf
A Framework For Assessing The Trustworthiness Of Scientific Research Findings, Brian A Nosek, David B Allison, Kathleen Hall Jamieson, Marcia Mcnutt, A Beau Nielsen, Susan M Wolf
Children’s Nutrition Research Center Staff Publications
Vigorous debate has erupted over the trustworthiness of scientific research findings in a number of domains. The question "what makes research findings trustworthy?" elicits different answers depending on whether the emphasis is on research integrity and ethics, research methods, transparency, inclusion, assessment and peer review, or scholarly communication. Each provides partial insight. We offer a systems approach that focuses on whether the research is accountable, evaluable, well-formulated, has been evaluated, controls for bias, reduces error, and whether the claims are warranted by the evidence. We tie each of these components to measurable indicators of trustworthiness for evaluating the research itself, …
Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley
Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley
Faculty, Staff and Students Publications
Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance …
Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither
Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither
2020-Current year OA Pubs
Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …
Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither
Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither
2020-Current year OA Pubs
Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …
Dupilumab Beyond The Airway: Decreased Morbidity In A Real-World Analysis, Emma J. Anisman, Spencer Short, Emma Tam, Benjamin F. Bitner, Abdulghafoor Alani, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Elina Toskala, Gurston G. Nyquist
Dupilumab Beyond The Airway: Decreased Morbidity In A Real-World Analysis, Emma J. Anisman, Spencer Short, Emma Tam, Benjamin F. Bitner, Abdulghafoor Alani, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Elina Toskala, Gurston G. Nyquist
Department of Otolaryngology - Head and Neck Surgery Faculty Papers
Background: Post hoc analyses of clinical trials have characterized dupilumab's adverse effects, yet the real-world impact in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is not well described. This study aims to characterize the risks of lymphoma, cardiovascular events, eosinophilia, joint pain, inflammatory arthritis, and sleep apnea in dupilumab-treated CRSwNP and/or asthma patients compared to those not taking dupilumab, and to other biologics.
Methods: This retrospective cohort study used TriNetX, a de-identified database containing over 100 million patient records. Demographics and adverse effects associated with immunotherapy use were collected.
Results: We identified 21,249 dupilumab-treated CRSwNP and/or asthma patients. After …
Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler
Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler
Faculty, Staff and Students Publications
Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.
Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.
Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …
Evidence-Based Team Intervention To Reduce Diagnostic Errors In Anaemia And Ckd Diagnoses In Primary Care: Protocol For A Stepped-Wedge Cluster Rct, Zhanna Novikov, Nikhilesh Mehra, Xiao Li, Rebecca Wells, Madelene Ottosen, Kevin Hwang, Elenir B C Avritscher, Charles Green, Kyung Hyun Lee, Xochitl Oguin, Mariesa Janecka, Mary Espinoza, Bolanle Adebowale, Alejandro Araya, Amer Wahed, Eric Thomas
Evidence-Based Team Intervention To Reduce Diagnostic Errors In Anaemia And Ckd Diagnoses In Primary Care: Protocol For A Stepped-Wedge Cluster Rct, Zhanna Novikov, Nikhilesh Mehra, Xiao Li, Rebecca Wells, Madelene Ottosen, Kevin Hwang, Elenir B C Avritscher, Charles Green, Kyung Hyun Lee, Xochitl Oguin, Mariesa Janecka, Mary Espinoza, Bolanle Adebowale, Alejandro Araya, Amer Wahed, Eric Thomas
Faculty, Staff and Student Publications
Introduction: Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.
Methods and analysis: The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or …
Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.
Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.
2020-Current year OA Pubs
OBJECTIVES: The impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.
METHODS: We genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic …
Protocol For Personalised Prediction Of Persistent Postsurgical Pain, Katherine J Holzer, Harutyun Alaverdyan, Ziqi Xu, Madelyn R Frumkin, Karen A Frey, Stephen H Gregory, Thomas L Rodebaugh, Chenyang Lu, Christopher R King, Denise Head, Thomas Kannampallil, Simon Haroutounian
Protocol For Personalised Prediction Of Persistent Postsurgical Pain, Katherine J Holzer, Harutyun Alaverdyan, Ziqi Xu, Madelyn R Frumkin, Karen A Frey, Stephen H Gregory, Thomas L Rodebaugh, Chenyang Lu, Christopher R King, Denise Head, Thomas Kannampallil, Simon Haroutounian
2020-Current year OA Pubs
INTRODUCTION: Persistent postsurgical pain (PPSP) affects up to 15% of patients after major surgery, impairing physical function, quality of life and increasing risk for long-term opioid use. Current PPSP prediction models rely on static or retrospective data and fail to incorporate dynamic perioperative factors. The Personalised Prediction of Persistent Postsurgical Pain (P5) study aims to develop individualised, multimodal prediction models by integrating preoperative behavioural, psychophysical and neurocognitive assessments and high-frequency symptom monitoring.
METHODS AND ANALYSIS: P5 is a prospective, single-centre cohort study enrolling 2500 adults aged 18-75 undergoing major surgery at a tertiary academic hospital. Participants complete baseline surveys, cognitive …
Two Faces Of Mitral Stenosis: Uncovering Structural And Hemodynamic Signatures Of Rheumatic And Mitral Annular Calcification-Induced Disease, Mohammad S. Hashemi, Peter Abdelmaseeh, Atif Nehvi, Gregg S. Pressman, Arash Kheradvar
Two Faces Of Mitral Stenosis: Uncovering Structural And Hemodynamic Signatures Of Rheumatic And Mitral Annular Calcification-Induced Disease, Mohammad S. Hashemi, Peter Abdelmaseeh, Atif Nehvi, Gregg S. Pressman, Arash Kheradvar
Einstein Health Papers
BACKGROUND: Mitral annular calcification (MAC) is common and associated with increased cardiovascular risk and, when severe, mitral stenosis (MS). MAC-related MS differs anatomically and hemodynamically from rheumatic MS (RMS), challenging standard diagnostic methods. This study compares structural and flow characteristics, including kinetic energy losses, across MAC-related MS, RMS, and normal mitral valves, and evaluates the applicability of conventional diagnostic metrics in MAC.
METHODS: Three-dimensional transesophageal echocardiographic data sets from 70 patients (22 normal mitral valves, 26 RMS valves, 22 MAC valves) were used to obtain linear, area, and volumetric measurements for valve comparison. Representative valves from each group were converted …
Intercalated Bacterial Biofilms Are Intrinsic Internal Components Of Calcium-Based Kidney Stones, William C Schmidt, Henry L Schreiber, Rachael E S Hammann, Chloe L P Obernuefemann, Karla Bergeron, Aleksandra Klim, Daniel Wong, Kefu Du, Scott J Hultgren, Et Al.
Intercalated Bacterial Biofilms Are Intrinsic Internal Components Of Calcium-Based Kidney Stones, William C Schmidt, Henry L Schreiber, Rachael E S Hammann, Chloe L P Obernuefemann, Karla Bergeron, Aleksandra Klim, Daniel Wong, Kefu Du, Scott J Hultgren, Et Al.
2020-Current year OA Pubs
Calcium oxalate stones comprise greater than 70% of all kidney stones. In the current conceptual framework, the initial stone nidus is thought to include the aggregation of inorganic crystallites, the formation of which is favored by elevated concentrations of dissolved constituents. Here, we show that this highly prevalent stone type comprises a form of organic-inorganic polycrystalline biocomposite with integrated bacterial biofilms. Evidence from electron microscopy and fluorescence microscopy reveal the unanticipated internal structure of kidney stones from human patients, where bacterial biofilms are intercalated between polycrystalline mineral layers, even in stones identified as "noninfectious" clinically, including those in patients without …
Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich
Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich
Faculty, Staff and Students Publications
Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.
Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged …
Clinician Perceptions Of Barriers And Strategies To Improve Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Fabliha Khurshan, Samuel Gidding, Varsha Zadokar, Jonathan M Miller, Anne E Kazak
Clinician Perceptions Of Barriers And Strategies To Improve Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Fabliha Khurshan, Samuel Gidding, Varsha Zadokar, Jonathan M Miller, Anne E Kazak
Department of Pediatrics Faculty Papers
IMPORTANCE: Pediatric hypertension remains underrecognized despite its high prevalence (approximately 5%) and long-term cardiovascular implications. Although guidelines for screening and diagnosis exist, less than 25% of affected children are diagnosed, and more than half do not receive timely follow-up care. Clinician-specific implementation barriers and directly informed strategies, which may alleviate this gap, are insufficiently described.
OBJECTIVE: To identify clinician-reported barriers and actionable recommendations to improve pediatric hypertension detection and follow-up in primary care using the Consolidated Framework for Implementation Research.
DESIGN, SETTING, AND PARTICIPANTS: Semistructured qualitative interviews were conducted between November 1, 2022, and March 31, 2023, with health care …