Digital Commons Network^™

Associations Of Sociodemographic, Clinical Factors And Hla-B Alleles With Enthesitis And Peripheral Arthritis In Patients With Ankylosing Spondylitis, Amirali Tahanan, Minjae Lee, Matthew A Brown, Michael H Weisman, John D Reveille

Faculty, Staff and Student Publications

Objectives: Factors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).

Methods: Patients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.

Results: Those with peripheral …

Evaluating The Meditation Practices And Barriers To Adopting Mindful Medicine Among Physicians, Marylou Cardenas-Turanzas, Aila Malik, Radha Korupolu

Faculty, Staff and Student Publications

Background: Chronic pain affects over 25% of U.S. adults and is a leading cause of disability. Mindfulness meditation (MM) is a nonpharmacologic approach to manage pain and improve well-being. Despite mounting evidence supporting its efficacy, MM remains underutilized in medical practice. Understanding physicians' engagement with MM and the barriers they face can inform strategies for integration into clinical care. This study assessed physicians' attitudes toward MM, including barriers to practice and their likelihood of recommending it to patients.

Methods: A cross-sectional survey of U.S. physicians was conducted from April to July 2024. Participants provided information on demographics, health struggles, and …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Exploratory Co-Design On Electronic Health Record Nursing Summaries: Case Study, Suhyun Park, Jenna L Marquard, Robin R Austin, Christie L Martin, David S Pieczkiewicz, Connie W Delaney

The Brown Foundation: Institute of Molecular Medicine

Background: Although electronic health record nursing summaries aim to provide a concise overview of patient data, they often fall short of meeting nurses' information needs, leading to underutilization. This gap arises from a lack of involvement of nurses in the design of health information technologies.

Objective: The purpose of this exploratory co-design case study was to solicit insights from nurses regarding nursing summary design considerations, including key information types and the preferred design prototype.

Methods: We recruited clinical nurses (N=33) from 7 inpatient units at a university hospital in the Midwestern United States using a purposive sampling method. We used …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Molecular Identification Of The Italian Soldiers Found In The Second World War Mass Grave Of Ossero, Monica Concato, Solange Sorçaburu Ciglieri, Alessandro Bosetti, Pierangela Grignani, Eros Azzalini, Yasmine Addoum, Raffaella Vetrini, Fabiano Gentile, Francesco Introna, Serena Bonin, Chiara Turchi, Carlo Previderè, Paolo Fattorini

Faculty, Staff and Students Publications

Background/objectives: DNA analysis is the most reliable method for the identification of human skeletal remains, especially the ones found in mass disasters or recovered from mass graves. To this aim, DNA was extracted from bones and teeth allegedly belonging to 27 Italian soldiers executed during the Second World War and exhumed from a mass grave in Ossero (Croatia).

Methods: A selection of 131 different bone samples (petrous bones, femurs, metacarpal, and metatarsal bones) and 16 molar teeth were used for DNA extraction. Autosomal and Y-chromosome STR profiles were determined using a conventional CE approach, while a panel of 76 microhaplotypes …

Navigating The Landscape Of Reinterventions After Tavr

Faculty, Staff and Students Publications

No abstract provided.

Simvastatin And Rifaximin In Decompensated Cirrhosis: A Randomized Clinical Trial, Daniela Campion, Salvatore Piano, Frank Erhard Uschner, Koos De Wit, Olivier Roux, Kohilan Gananandan, Wim Laleman, Cristina Solé, Sonia Alonso, Berta Cuyàs, Xavier Ariza, Adrià Juanola, Ann T Ma, Laura Napoleone, Jordi Gratacós-Ginès, Marta Tonon, Enrico Pompili, Jordi Sánchez-Delgado, Andrew S Allegretti, Manuel Morales-Ruiz, Marta Carol, Martina Pérez-Guasch, Núria Fabrellas, Judit Pich, Claudia Martell, María Joyera, Gemma Domenech, José Ríos, Ferrán Torres, Miquel Serra-Burriel, Rubén Hernáez, Elsa Solà, Isabel Graupera, Hugh Watson, Germán Soriano, Rafael Bañares, Rajeshwar P Mookerjee, Claire Francoz, Ulrich Beuers, Jonel Trebicka, Paolo Angeli, Carlo Alessandria, Paolo Caraceni, Víctor M Vargas, Juan G Abraldes, Patrick S Kamath, Pere Ginès

Faculty, Staff and Students Publications

Importance: There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.

Objective: To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.

Design, setting, and participants: Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.

Interventions: Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months …

Longitudinal Multi-Omics In Alpha-Synuclein Drosophila Model Discriminates Disease- From Age-Associated Pathologies In Parkinson’S Disease, Justin Moore, Timothy Wu, Justin Dhindsa, Omar El Fadel, Anh Le, Alma Perez, Bismark Amoh, Akash Tarkunde, Katy F Zhu, Matthew Avalos, Eric B Dammer, Duc M Duong, Nicholas T Seyfried, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated …

Avasimibe Abolishes The Efficacy Of Fluvastatin For The Prevention Of Cancer In A Spontaneous Mouse Model Of Breast Cancer, Anjana Bhardwaj, Alexander Koh, Rhea Bhala, Janvi Sandhu, Zhenlin Ju, Jing Wang

Faculty, Staff and Student Publications

The cholesterol biosynthesis pathway is upregulated during breast cancer development and progression. Inhibition of the aberrantly upregulated cholesterol pathway by statins reduces breast tumor incidence and burden by 50% in SV40 C3(1) TAg mice, a mouse model of triple negative breast cancer. We hypothesized that fluvastatin's preventive efficacy could be further enhanced by co-targeting the statin-induced restorative feedback pathways that tightly control the cholesterol pathway and are involved in resistance to statins. Acyl-coenzyme A: cholesterol acyltransferase (

A Journey Of Innovation In Mitral Transcatheter Edge-To-Edge Repair: Lessons From The Repair Registry

Faculty, Staff and Students Publications

No abstract provided.

Leveraging Large Language Models For Knowledge-Free Weak Supervision In Clinical Natural Language Processing

Faculty, Staff and Student Publications

The performance of deep learning-based natural language processing systems is based on large amounts of labeled training data which, in the clinical domain, are not easily available or affordable. Weak supervision and in-context learning offer partial solutions to this issue, particularly using large language models (LLMs), but their performance still trails traditional supervised methods with moderate amounts of gold-standard data. In particular, inferencing with LLMs is computationally heavy. We propose an approach leveraging fine-tuning LLMs and weak supervision with virtually no domain knowledge that still achieves consistently dominant performance. Using a prompt-based approach, the LLM is used to generate weakly-labeled …

Prophylaxis, Clinical Management, And Monitoring Of Datopotamab Deruxtecan-Associated Oral Mucositis/Stomatitis, Funda Meric-Bernstam, Aditya Bardia, Paolo Bossi, Giampaolo Bianchini, Frances Gatlin, Barbara Melosky, Timothy A Yap, Sophie S Kim, Rachana Rajagopalan, Rick M Fairhurst, Stephanie L Graff, Hope S Rugo

Faculty, Staff and Student Publications

Oral mucositis/stomatitis (hereafter stomatitis) is a common dose-limiting toxicity seen with various classes of cancer treatment. Symptoms associated with stomatitis, primarily oral pain, may impact patient quality of life and may lead to dose delay and reduction or treatment discontinuation. Datopotamab deruxtecan (Dato-DXd) is a novel trophoblast cell surface antigen 2-directed antibody-drug conjugate undergoing clinical investigation in multiple solid tumor types. Stomatitis is among the most reported adverse events associated with Dato-DXd, with most cases being grades 1-2. This article reviews the incidence of stomatitis seen with Dato-DXd, including in the phase III pivotal studies TROPION-Lung01 and TROPION-Breast01 (in patients …

Incidence And Correlates Of High-Grade Chemotherapy-Induced Peripheral Neuropathy In Patients With Lung Cancer, Mitchell S Von Itzstein, Sawsan Rashdan, Suzanne E Dahlberg, David E Gerber, Alan B Sandler, David H Johnson, Zhuoxin Sun, Suresh S Ramalingam

Faculty, Staff and Student Publications

Background: High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.

Methods: We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic …

A Phase I/Ii Trial Of Avelumab Combinations With Ivuxolimab, Utomilumab, And Radiation Therapy In Patients With Advanced Gastrointestinal Malignancies, Jibran Ahmed, Anne Knisely, Carlos Torrado, Bettzy Stephen, Yali Yang, Anas Alshawa, Anuja Jhingran, Eugene J Koay, Van Karlyle Morris, Milind Javle, Robert A Wolff, Funda Meric-Bernstam, Shubham Pant, Jordi Rodon, Aung Naing

Faculty, Staff and Student Publications

Background: Checkpoint agonists utomilumab (4-1BB agonist) and ivuxolimab (OX40 agonist) enhance Teffector cell function. Preclinical studies suggest that combining these drugs with avelumab (anti-PD-L1 antibody) can potentially synergize this effect. In addition, tissue abscopal effects of radiation therapy may improve antigen presentation, complementing PD-L1 blockade. We conducted a single institution, open-label, multi-arm, non-randomized, phase 1/2 clinical trial of avelumab in combination with ivuxolimab, with or without utomilumab, and radiation therapy in patients with advanced solid tumors. Herein, we present a subgroup analysis in patients with gastrointestinal (GI) tumors (pancreatic, colon, gastric, and hepatocellular).

Methods: The primary objectives of this study …

Multi-Ancestry Transcriptome-Wide Association Studies Of Cognitive Function, White Matter Hyperintensity, And Alzheimer's Disease, Dima L Chaar, Zheng Li, Lulu Shang, Scott M Ratliff, Thomas H Mosley, Wei Zhao, Jennifer A Smith

Faculty, Staff and Student Publications

Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer's disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWASs on VaD and AD have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European ancestry (EA) …

The Influence Of Body Mass Index On Biomarkers Of Cellular Senescence In Older Adults, Elizabeth Atkinson, Thomas A White, Michaela Mcgree, Susan Weston, Nathan K Lebrasseur

Faculty, Staff and Students Publications

Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index. After adjusting for age, sex, and race, we observed significant increases in activin A, …

Clinical And Genetic Markers Of Vascular Toxicity In Glioblastoma Patients: Insights From Nrg Oncology Rtog-0825, Ang Li, Renke Zhou, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Volker W Stieber, Vinay K Puduvalli, Serah Choi, Nina L Martinez, H Ian Robins, Grant K Hunter, Chi-Fan Lin, Vivian A Guedes, Melissa A Richard, Stephanie L Pugh, Terri S Armstrong, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment.

Methods: In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Rashmi Kanagal-Shamanna, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Consensus Recommendations For An Integrated Diagnostic Approach To Peripheral Nerve Sheath Tumors Arising In The Setting Of Neurofibromatosis Type 1, Calixto-Hope G Lucas, Andrea M Gross, Carlos G Romo, Carina A Dehner, Alexander J Lazar, Melike Pekmezci, Fausto J Rodriguez, Anat Stemmer-Rachamimov, David Viskochil, Arie Perry

Faculty, Staff and Student Publications

Consensus recommendations published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation and enable appropriate intervention …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Rashmi Kanagal-Shamanna, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Using Cognitive Interviewing To Develop Rating Scales Of Suicide Thoughts And Behaviors In Preadolescent Children, Jeremy W. Pettit, Carlos E. Yeguez, Rotem S. Budagzad-Jacobson, Taylar A. Clark, Yasmin Rey, Carla E. Marin, Eli R. Lebowitz, James Jaccard, Wendy K. Silverman

Journal of Applied Research on Children: Informing Policy for Children at Risk

Despite the alarming rise of suicidal thoughts and behaviors (STBs), in preadolescent children over the last two decades, no scales have been developed and validated to assess these troubling tendencies in this population. We describe how we developed English and Spanish language versions of a new scale to assess STBs in children, the Suicide Risk and Ideation Scale for Kids - Child and Parent versions (S-RISK-C/P), using cognitive interviewing. Method. After creating item pools in English and Spanish, we elicited feedback from three clinician content experts and conducted cognitive interviews with 8 children (4 girls; Mage = 10.37 years; …

Genome-Wide Prediction Of Dominant And Recessive Neurodevelopmental Disorder-Associated Genes, Ryan S Dhindsa, Blake A Weido, Justin S Dhindsa, Arya J Shetty, Chloe F Sands, Slavé Petrovski, Dimitrios Vitsios, Anthony W Zoghbi

Duncan NRI Faculty and Staff Publications

Despite great progress, thousands of neurodevelopmental disorder (NDD) risk genes remain to be discovered. We present a computational approach that accelerates NDD risk gene identification using machine learning. First, we demonstrate that models trained solely on single-cell RNA sequencing data can robustly predict genes implicated in autism spectrum disorder (ASD), developmental and epileptic encephalopathy (DEE), and developmental delay (DD). Notably, we find differences in gene expression patterns of genes with monoallelic and bi-allelic inheritance patterns in the developing human cortex. We then integrate expression data with 300 orthogonal features, including intolerance metrics, protein-protein interaction data, and others, in a semi-supervised …

Identification Of Genes Associated With Testicular Germ Cell Tumor Susceptibility Through A Transcriptome-Wide Association Study, Emilio Ugalde-Morales, Rona Wilf, John Pluta, Alexander Ploner, Mengyao Fan, Katja K Aben, Chu Chen, Victoria K Cortessis, Siamak Daneshmand, Alberto Ferlin, Marija Gamulin, Jourik A Gietema, Anna Gonzalez-Niera, Tom Grotmol, Robert J Hamilton, Mark Harland, Trine B Haugen, Russ Hauser, Michelle A T Hildebrandt, Robert Karlsson, Lambertus A Kiemeney, Jung Kim, Davor Lessel, Ragnhild A Lothe, Chey Loveday, Stephen J Chanock, Katherine A Mcglynn, Coby Meijer, Kevin T Nead, Jeremie Nsengimana, Maja Popovic, Thorunn Rafnar, Lorenzo Richiardi, Maria S Rocca, Stephen M Schwartz, Rolf I Skotheim, Kari Stefansson, Douglas R Stewart, Clare Turnbull, David J Vaughn, Sofia B Winge, Tongzhang Zheng, Alvaro N Monteiro, Kristian Almstrup, Peter A Kanetsky, Katherine L Nathanson, Fredrik Wiklund, Testicular Cancer Consortium

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Response To: Correspondence On “Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15” By Ataca Atilla And Atilla, Leonid S Metelitsa

Faculty, Staff and Students Publications

No abstract provided.

Every Jump Is A Leap Of Faith-Just Ask Evel Knievel!

Faculty, Staff and Students Publications

No abstract provided.

A Comprehensive Atlas Of Aav Tropism In The Mouse, Aaron R Cox, Alexa E Martinez, M Cecilia Ljungberg, Denise G Lanza, Marco De Giorgi, Marcel A Chuecos, Michele Alves-Bezerra, Carlos Flores Suarez, Sean M Hartig, Susan G Hilsenbeck, Chih-Wei Hsu, Ethan Saville, Yaned Gaitan, Jeff Duryea, Seth Hannigan, Mary E Dickinson, Oleg Mirochnitchenko, Dan Wang, Cathleen M Lutz, Jason D Heaney, Guangping Gao, Stephen A Murray, William R Lagor

Faculty, Staff and Students Publications

Gene therapy with adeno-associated virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of 10 naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10, and AAVrh74) following systemic delivery into male and female mice. A transgene-expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes, and ovaries. Rare transduced cells within …

Carm1 Regulates Tubulin Autoregulation Through Pi3kc2Α R175 Methylation, Yena Cho, Jee Won Hwang, Mark T Bedford, Dae-Geun Song, Su-Nam Kim

Faculty, Staff and Student Publications

Tubulin is crucial in several cellular processes, including intracellular organization, organelle transport, motility, and chromosome segregation. Intracellular tubulin concentration is tightly regulated by an autoregulation mechanism, in which excess free tubulin promotes tubulin mRNA degradation. However, the details of how changes in free tubulin levels initiate this autoregulation remain unclear. In this study, we identified coactivator-associated arginine methyltransferase 1 (CARM1)-phosphatidylinositol 3-kinase class 2α (PI3KC2α) axis as a novel regulator of tubulin autoregulation. CARM1 stabilizes PI3KC2α by methylating its R175 residue. Once PI3KC2α is not methylated, it becomes unstable, leading to decreased cellular levels. Loss of PI3KC2α results in the release …

Photoacoustic Imaging For Image-Guided Gastric Tube Placement: Ex Vivo Characterization, Samuel John, Yeidi Yuja Vaquiz, Nikhila Nyayapathi, Loay Kabbani, Anoop Nilam, Nicole A Wilson, Mohammad Mehrmohammadi

Faculty, Staff and Student Publications

Over 250,000 gastrostomy tubes (G-tubes) are placed annually in the United States. Percutaneous endoscopic gastrostomy (PEG) is the most widely used clinical method for placing G-tubes within the stomach. However, endoscope detectability is limited due to the scattering of light by tissues. Poor organ visibility and low sensitivity of the palpation techniques cause blind needle insertions, which cause colon/liver perforations, abdominal bleeding, and gastric resections. Additionally, imaging artifacts and the poor distinguishability between water-filled tissues make ultrasound (US) imaging-based techniques incompatible with G-tube placement. The risk of ionizing radiation exposure and the confinement of fluoroscopy to radiology suites limits its …