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Incidence And Outcomes Of Hospitalized Acute Ischemic Stroke Patients With Subsequent St-Segment-Elevation Myocardial Infarction, Arhum Mahmood, Song Peng Ang, Yusuf Kamran Qadeer, Hafeez Ul Hassan Virk, Jonathan Alan Tangsrivimol, Iqra Riaz, Zhen Wang, Mahboob Alam, Markus Strauss, Chayakrit Krittanawong Jan 2025

Incidence And Outcomes Of Hospitalized Acute Ischemic Stroke Patients With Subsequent St-Segment-Elevation Myocardial Infarction, Arhum Mahmood, Song Peng Ang, Yusuf Kamran Qadeer, Hafeez Ul Hassan Virk, Jonathan Alan Tangsrivimol, Iqra Riaz, Zhen Wang, Mahboob Alam, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Background: Patients admitted with acute ischemic stroke (AIS) may experience accompanying acute ST-Segment myocardial infarction after AIS. The cardiovascular risks, incidence, complications, and outcomes of acute STEMI in patients hospitalized with AIS remains underexplored.

Methods: We evaluated 2,804,819 patients that presented with AIS who were listed in the National Inpatient Sample from 2016 to 2021. AIS and STEMI were defined according to the ICD-10 Diagnostic Codes. Patients with Non-STEMI were excluded. The risk of specific complications and outcomes were expressed as percentages. Multivariable logistic regression analysis was used to examine the association of STEMI with a primary outcome of mortality …


Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat Jan 2025

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …


Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund Jan 2025

Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund

Faculty, Staff and Students Publications

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat‐to‐neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan‐extending lipid chaperone, lipid binding protein‐3 (LBP‐3), which shuttles dihomo‐γ‐linolenic (DGLA) acid from intestinal fat to neurons. We present the first high‐resolution crystal structure of LBP‐3, which reveals a classic iLBP fold with an unexpected and unique homodimeric …


Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Akanksha Agrawal, Erin L Clayton, Courtney L Cavazos, Benjamin A Clayton, George G Rodney Jan 2025

Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Akanksha Agrawal, Erin L Clayton, Courtney L Cavazos, Benjamin A Clayton, George G Rodney

Faculty, Staff and Students Publications

Aim: Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.

Methods: Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and …


Impact Of An Electronic Medical Record Quality Improvement Intervention On Helicobacter Pylori Treatment And Eradication Rates In A U.S. Hospital System, Shivani Kastuar, Samanthika Devalaraju, Juan Gomez Cifuentes, Hashem B El-Serag, Mimi C Tan Jan 2025

Impact Of An Electronic Medical Record Quality Improvement Intervention On Helicobacter Pylori Treatment And Eradication Rates In A U.S. Hospital System, Shivani Kastuar, Samanthika Devalaraju, Juan Gomez Cifuentes, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background: In this pre- and post-intervention quality improvement (QI) study, the impact of an electronic medical record (EMR) order set for Helicobacter pylori treatment was assessed. We evaluated changes in optimal treatment regimen usage, eradication testing, and successful eradication rates based on the intervention.

Materials and methods: Data were collected from patients within the Harris Health System (Houston, TX) with H. pylori infection. The pre-intervention cohort included patients with a positive H. pylori test from January to February 2022. An EMR order set for H. pylori treatment implemented in May 2022 included optimal treatment recommendations using local antibiotic resistance patterns …


Minimum Standards For Training In Colorectal Endoscopic Mucosal Resection Among Advanced Endoscopy Trainees, Dennis Yang, Ernesto Robalino Gonzaga, Muhammad Khalid Hasan, Arvind Julius Trindade, Mark Radlinski, Rebecca A Burbridge, Jeffrey Mosko, Pushpak Taunk, Salmaan Jawaid, Mohamed O Othman, David L Diehl, Harshit S Khara, Quin Liu, Srinivas Gaddam, Harry Aslanian, Shailendra S Chauhan, Amrita Sethi, John Poneros, Jason Samarasena, Ali M Ahmed, Uzma D Siddiqui, Dennis Chen, Moamen Gabr, Andrew Y Wang Jan 2025

Minimum Standards For Training In Colorectal Endoscopic Mucosal Resection Among Advanced Endoscopy Trainees, Dennis Yang, Ernesto Robalino Gonzaga, Muhammad Khalid Hasan, Arvind Julius Trindade, Mark Radlinski, Rebecca A Burbridge, Jeffrey Mosko, Pushpak Taunk, Salmaan Jawaid, Mohamed O Othman, David L Diehl, Harshit S Khara, Quin Liu, Srinivas Gaddam, Harry Aslanian, Shailendra S Chauhan, Amrita Sethi, John Poneros, Jason Samarasena, Ali M Ahmed, Uzma D Siddiqui, Dennis Chen, Moamen Gabr, Andrew Y Wang

Faculty, Staff and Students Publications

Background and study aims: Data on colorectal endoscopic mucosal resection (C-EMR) training during advanced endoscopy fellowship remain limited. We aimed to determine the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in cognitive and technical C-EMR skills.

Methods: AETs from advanced endoscopy training programs (AETPs) were graded on every C-EMR using a standardized assessment tool. Cumulative sum (CUSUM) analysis was used to generate individual and aggregate learning curves to estimate the minimum number of cases required to achieve competence for overall, technical, and cognitive components of C-EMR. AETs completed a self-assessment questionnaire on C-EMR …


Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore Jan 2025

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …


Correction: Health-Related Quality Of Life After Neonatal Treatment Of Symptomatic Tetralogy Of Fallot: Insights From The Congenital Cardiac Research Collaborative, George T Nicholson, Jeffrey D Zampi, Andrew C Glatz, Bryan H Goldstein, Christopher J Petit, Yun Zhang, Courtney E Mccracken, Athar M Qureshi, Caren S Goldberg, Jennifer C Romano, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Asaad Beshish, Michael L O'Byrne, R Allen Ligon, Kathryn O Stack, Hala Q Khan, Shalin Parekh, Dawn L Ilardi Jan 2025

Correction: Health-Related Quality Of Life After Neonatal Treatment Of Symptomatic Tetralogy Of Fallot: Insights From The Congenital Cardiac Research Collaborative, George T Nicholson, Jeffrey D Zampi, Andrew C Glatz, Bryan H Goldstein, Christopher J Petit, Yun Zhang, Courtney E Mccracken, Athar M Qureshi, Caren S Goldberg, Jennifer C Romano, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Asaad Beshish, Michael L O'Byrne, R Allen Ligon, Kathryn O Stack, Hala Q Khan, Shalin Parekh, Dawn L Ilardi

Faculty, Staff and Students Publications

No abstract provided.


Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey Jan 2025

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …


Id-Gba: Subgraph Extension With Information Distance Guilt By Association In Complex Networks, Predrag Obradovic, Vladimir Kovacevic, Aleksandar Milosavljevic, Varduhi Petrosyan Jan 2025

Id-Gba: Subgraph Extension With Information Distance Guilt By Association In Complex Networks, Predrag Obradovic, Vladimir Kovacevic, Aleksandar Milosavljevic, Varduhi Petrosyan

Faculty, Staff and Students Publications

Here, we introduce the ID-GBA (Information Distance Guilt By Association) method to expand highly connected sets of nodes by deploying a novel algorithm for subgraph extension based on the guilt-by-association principle and information distance. In this study, ID-GBA was utilized to expand disease clusters, and identify novel disease genes. We first validate its ability to expand related disease sets from disease/disease graphs built using Open Targets' gene association scores. We then analyze disease/control gene expression networks and show that ID-GBA recaptures known disease genes in nine disease/control graphs. Compared to existing methods such as Random Walk with Restarts and Personalized …


Epilepsy Clinic Analytics: Leveraging Emr Reporting Tools To Characterize Center Volume And Complexity, Vanuli Arya, Arindam Ghosh Mazumder, Muna Nnamani, Mark A Abboud, Samuel C Lee, Michael S Guzman, Vaishnav Krishnan Jan 2025

Epilepsy Clinic Analytics: Leveraging Emr Reporting Tools To Characterize Center Volume And Complexity, Vanuli Arya, Arindam Ghosh Mazumder, Muna Nnamani, Mark A Abboud, Samuel C Lee, Michael S Guzman, Vaishnav Krishnan

Faculty, Staff and Students Publications

Introduction: Epilepsy centers connect patients to multidisciplinary provider groups that can coordinate surgical interventions and/or investigational treatments. Automated techniques to cross-sectionally review patient volume and complexity may reveal objective metrics to assign appropriate personnel and resources. Here, we leveraged an electronic medical record (EMR) reporting tool to examine how patient and visit volumes, antiseizure medication (ASM) prescriptions and neuromodulation use evolved over an 11-year epoch at a single level 4 adult epilepsy center in Texas, USA.

Methods: Using Epic Workbench Reporting, we acquired the dates of (i) all clinic visits (office or telemedicine), (ii) CPT codes for neuromodulation interrogation/programming, and …


Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim Jan 2025

Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim

Faculty, Staff and Students Publications

Finite element modeling (FEM) is a critical tool in biomechanics and biomedical engineering, offering valuable insights where in vivo or ex vivo investigations are not possible. This review specifically highlights the diverse applications of FEM within obstetrics and gynecology through a comprehensive analysis of the literature. We explore the past use of FEM in analyzing complications affecting pelvic floor structures, urinary continence, and reproduction. The potential contributions of FEM in addressing these challenges are summarized and future directions for its application in obstetrics and gynecology are highlighted.


A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu Jan 2025

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …


Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Daniel A Rodriguez, Alex Song, Anshul Bhatnagar, Christina Y Weng Jan 2025

Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Daniel A Rodriguez, Alex Song, Anshul Bhatnagar, Christina Y Weng

Faculty, Staff and Students Publications

Baby Detect Project, started in September 2022, aimed to create a newborn screening test using targeted next-generation sequencing for all early-onset, treatable, and serious conditions. The elaborated gene panel covers 405 genes, associated with 165 genetic conditions, and includes RB1, linked to retinoblastoma, the only oncological disease tested for. Germline RB1 mutations concern around 50% of all retinoblastoma cases and 100% of the most severe, bilateral cases. Ninety percent of them occur de novo, which delays the diagnosis by about a year with subsequent loss of vision and sometimes the eye itself. Detecting children with germline RB1 mutation at …


Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat Jan 2025

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …


Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Viola Viola, Marlene Aguilar, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal Jan 2025

Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Viola Viola, Marlene Aguilar, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Objective: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation.

Design: Randomized, double-blind, placebo-controlled trial (LITROS).

Methods: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone < 10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism.

Results: Among the …


Clues To Transcription/Replication Collision-Induced Dna Damage: It Was Rnap, In The Chromosome, With The Fork, Matthew B Cooke, Christophe Herman, Priya Sivaramakrishnan Jan 2025

Clues To Transcription/Replication Collision-Induced Dna Damage: It Was Rnap, In The Chromosome, With The Fork, Matthew B Cooke, Christophe Herman, Priya Sivaramakrishnan

Faculty, Staff and Students Publications

DNA replication and RNA transcription processes compete for the same DNA template and, thus, frequently collide. These transcription-replication collisions are thought to lead to genomic instability, which places a selective pressure on organisms to avoid them. Here, we review the predisposing causes, molecular mechanisms, and downstream consequences of transcription-replication collisions (TRCs) with a strong emphasis on prokaryotic model systems, before contrasting prokaryotic findings with cases in eukaryotic systems. Current research points to genomic structure as the primary determinant of steady-state TRC levels and RNA polymerase regulation as the primary inducer of excess TRCs. We review the proposed mechanisms of TRC-induced …


Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low Jan 2025

Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low

Faculty, Staff and Students Publications

Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FRβ). Because FRβ does not bind folate until the monocyte/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FRβ might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FRβ knockout mice. We observe that FRβ knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) …


A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou Jan 2025

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …


Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown Jan 2025

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …


Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer Jan 2025

Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Introduction: Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.

Methods: Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH …


The Influence Of Ultra-Widefield Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Nicole K Scripsema, Tala Al-Khaled, Amy Song, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan Jan 2025

The Influence Of Ultra-Widefield Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Nicole K Scripsema, Tala Al-Khaled, Amy Song, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan

Faculty, Staff and Students Publications

Purpose: To study the influence of ultra-widefield fluorescein angiography (FA) on the diagnosis and management of diabetic retinopathy (DR).

Methods: Ten experts in DR completed an online survey in which they were asked to diagnose and manage DR cases using different imaging modalities. Experts independently reviewed 20 cases of DR and provided a diagnosis and management plan for each case, first based on ultra-widefield color-free and red-free images alone and again with the corresponding ultra-widefield FA images. Experts were polled on their diagnostic confidence, use of FA in clinical practice, and opinions on the value of ultra-widefield FA. Based on …


Primary Polydipsia In A Case Of Genetic Behavioral Variant Frontotemporal Dementia, Yesenia Cantu, Taryn White, Gabriela Austgen, Christine Rizk, Olaoluwa O Okusaga, Melissa B Jones Jan 2025

Primary Polydipsia In A Case Of Genetic Behavioral Variant Frontotemporal Dementia, Yesenia Cantu, Taryn White, Gabriela Austgen, Christine Rizk, Olaoluwa O Okusaga, Melissa B Jones

Faculty, Staff and Students Publications

No abstract provided.


Feasibility And Impact Of Knowledge-Based Automated Radiotherapy Treatment Planning In Low- And Middle-Income Countries, Awusi Kavuma, Solomon Kibudde, Yao Hao, Baozhou Sun Jan 2025

Feasibility And Impact Of Knowledge-Based Automated Radiotherapy Treatment Planning In Low- And Middle-Income Countries, Awusi Kavuma, Solomon Kibudde, Yao Hao, Baozhou Sun

Faculty, Staff and Students Publications

Background and purpose: A high-quality treatment planning process is crucial in advanced radiotherapy techniques to ensure adequate dose to the target volume (TV) and sparing of organs at risk (OARs). This process often requires intensive labor, creating barriers for deployment in low- and middle-income countries (LMICs). We aimed to establish the feasibility of implementing knowledge-based auto-planning to facilitate clinical efficiency and increase patient throughput in an LMIC.

Materials and methods: We evaluated 60 randomly selected VMAT manual plans (VMPs), including 10 for each of the following sites: head and neck, oesophagus, breast, prostate, cervical, and rectal cancers. Using the same …


Correction: Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel Jan 2025

Correction: Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel

Faculty, Staff and Students Publications

This corrects the article "Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials", 1570989.


A Computational Approach For Intramural Length Estimation In Anomalous Aortic Origin Of A Coronary Artery, Vikram Shah, Lauren Ferrino, Dana Reaves-O'Neal, Tam T Doan, Shagun Sachdeva, Craig G Rusin, Dan Lior, Charles Puelz, Prakash M Masand, Silvana Molossi Jan 2025

A Computational Approach For Intramural Length Estimation In Anomalous Aortic Origin Of A Coronary Artery, Vikram Shah, Lauren Ferrino, Dana Reaves-O'Neal, Tam T Doan, Shagun Sachdeva, Craig G Rusin, Dan Lior, Charles Puelz, Prakash M Masand, Silvana Molossi

Faculty, Staff and Students Publications

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is associated with sudden cardiac death. The intramural (IM) length is considered high-risk, yet radiologic measurements by computed tomography angiography (CTA) show variable agreement with measurements at surgery. We aimed to develop a semi-automatic computational method to estimate IM length in a retrospective cohort of surgical AAOCA patients.

Methods: In 58 patients [49 right(R), 9 left(L)], CTA images were used to generate 3D segmentations of the aorta and a centerline of the anomalous coronary. The distance from the centerline to the aortic segmentation was calculated. The IM length was estimated from …


Benchmarking Batch-Effect Correction Methods Towards The Construction Of A Triple-Negative Breast Cancer Cell Atlas, Peter Scheible, Amy H. Tang, Jing He, Jiangwen Sun Jan 2025

Benchmarking Batch-Effect Correction Methods Towards The Construction Of A Triple-Negative Breast Cancer Cell Atlas, Peter Scheible, Amy H. Tang, Jing He, Jiangwen Sun

Computer Science Faculty Publications

Triple-negative breast cancer (TNBC) requires detailed cellular mapping given its aggressive nature, immense tumor heterogeneity and genetic diversity. We integrated 156,794 cells from six scRNA-seq datasets—including tumors, metastases, and cell lines—to build a TNBC scRNA cell atlas, focusing on batch effect mitigation while maintaining biological and molecular details. Preprocessing f ilters noise, normalizes data, and leverages PCA for integration readiness. We utilized scANVI, a semi-supervised tool, to align datasets, preserving TNBC’s complex tumor heterogeneity via marker annotations [1]. UMAPs demonstrate biological clustering in integrated data, contrasted with datasetdriven unintegrated patterns. Assessments verifying effective batch correction. This method aligns with NASA’s …


Multi-Modal Mri Based Segmentation Of Brain Metastases Using Adaptive Self-Attention, Evan Savaria Jan 2025

Multi-Modal Mri Based Segmentation Of Brain Metastases Using Adaptive Self-Attention, Evan Savaria

Computer Science Faculty Publications

Brain metastases (BMs) are the most common adult central nervous system malignancy, affecting 20–40% of cancer patients. Accurate segmentation of metastatic lesions in multi-modal MRI is essential for treatment planning and prognosis however, manual delineation is time consuming and prone to variability. Traditional deep learning models such as U-Net, have improved segmentation accuracy but capture limited long-range dependencies and struggle with variations in metastasis size, shape, and distribution. This study introduces the Adaptive Integrated Multi-modal Segmentation (AIMS) model, an adaptive self-attention framework within a hybrid U-Net and Transformer architecture to enhance BM segmentation by leveraging multi-modal MRI integration. The proposed …


Coldstartcpi: Induced-Fit Theory-Guided Dti Predictive Model With Improved Generalization Performance, Qichang Zhao, Haochen Zhao, Linyuan Gao, Kai Zheng, Yajie Li, Qiao Ling, Jing Tang, Yaohang Li, Jianxin Wang Jan 2025

Coldstartcpi: Induced-Fit Theory-Guided Dti Predictive Model With Improved Generalization Performance, Qichang Zhao, Haochen Zhao, Linyuan Gao, Kai Zheng, Yajie Li, Qiao Ling, Jing Tang, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Predicting compound-protein interactions (CPIs) plays a crucial role in drug discovery. Traditional methods, based on the key-lock theory and rigid docking, often fail with novel compounds and proteins due to their inability to account for molecular flexibility and the high sparsity of CPI data. Here, we introduce ColdstartCPI, a framework inspired by induced-fit theory, which leverages unsupervised pre-training features and a Transformer module to learn both compound and protein characteristics. ColdstartCPI treats proteins and compounds as flexible molecules during inference, aligning with biological insights. It outperforms state-of-the-art sequence-based models, particularly for unseen compounds and proteins, and shows strong generalization capability …


Benchmarking And Improving Foundation Model Dietary Estimates From Meal Images, Yongcheng Mu, Jiangwen Sun, Jing He Jan 2025

Benchmarking And Improving Foundation Model Dietary Estimates From Meal Images, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Accurate quantifying dietary contents, such as calories, proteins, carbohydrates, and fats, from an image of a meal plate is vital for managing diabetes. Recently, Large Multimodal Models (LMMs) have excelled in complex vision-language tasks due to their use of very large, highly diverse data. This study benchmarked the use of seven LMMs that include full and lightweight models of GPT, Gemini, and Llama for nutrition estimation based on Google's Nutrition5k dataset and our own phone-collected DonateAndLearn dataset. We analyzed the performance of LMMs and the RGB-D fusion model, in which the RGB-D model was specifically trained using Nutrition5k data. On …