Digital Commons Network^™

Foreword: Addressing Diagnostic Error: The First 10 Years, Mark L Graber, Edward P Hoffer, Hardeep Singh

Faculty, Staff and Students Publications

No abstract provided.

Beyond Seizures As An Outcome Measure: A Global Severity Scoring System For Cdkl5 Deficiency Disorder, Peter Jacoby, Eric D Marsh, Scott Demarest, Jacinta M Saldaris, Helen Leonard, Heather E Olson, Joni N Saby, Elia Pestana-Knight, Rajsekar Rajaraman, Dana Price, Judith Weisenberg, Bernhard Suter, Jenny Downs, Tim A Benke

Faculty, Staff and Students Publications

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance …

A Rare Molecular Diagnosis In A Patient With Hepatocerebral Syndrome Contributes To The Expansion Of The Phenotypic Spectrum Of Polg2 -Related Mitochondrial Disorder, Vittoria Rossi, Dan Brooks, Hongzheng Dai, Elizabeth Mizerik, Karla Salazar, Daniel Davila-Williams, Yishay Ben-Moshe, Seema R Lalani, Sarah H Elsea, Charul Gijavanekar, Daryl A Scott, Keren Machol, Mir Reza Bekheirnia, Fernando Scaglia

Faculty, Staff and Students Publications

POLG2 encodes an accessory subunit in DNA polymerase gamma that is required for mitochondrial DNA synthesis. Monoallelic pathogenic variants in POLG2 are associated primarily with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant type 4 (PEOA4, MIM #610131). We report a rare case of severe infantile hepatocerebral syndrome associated with biallelic variants in POLG2. The proband, a 5-week-old female infant, presented with seizures and acute liver failure. Extensive metabolic workup, including untargeted metabolomics analysis and elevated plasma growth differentiation factor 15, was suggestive of mitochondrial dysfunction. Rapid trio genome sequencing identified compound heterozygous variants, a likely pathogenic variant and …

Can Interpersonal Trust Predict And Account For Symptom Change During Group Cognitive Processing Therapy For Ptsd? An Investigation Of The Iterated Trust Game, M Wright Williams, Christopher Hunt, David P Graham, Matt Estey, Lia Smith, Katherine Mccurry, Brooks King-Casas, Pearl Chiu

Faculty, Staff and Students Publications

Objective: Group cognitive processing therapy (GCPT) is frequently utilized to treat PTSD within the VA healthcare system, but its mechanisms are not well understood. Interpersonal trust could be an important change process in GCPT given its relevance to group-based therapy and its role in CPT, but self-report measures are inadequate for capturing the dynamic interplay that defines interpersonal trust. Here, we examined the degree to which interpersonal could predict and account for PTSD symptom change in GCPT using the iterated trust game (ITG)-a behavioral task used to approximate real-world trust behavior.

Methods: Participants were Veterans with PTSD who participated in …

Ambulatory Acute Kidney Injury In Patients With Cirrhosis Is Common And Burdensome, Kavish R Patidar, Ruben Hernaez, Yan Liu, George Cholankeril, Jennifer R Kramer, Thom Taylor, Prasun Jalal, Tzu-Hao Lee, Avegail G Flores, Giuseppe Cullaro, Andrew S Allegretti, Pere Gines, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: Little is known about ambulatory acute kidney injury (A-AKI), which develops in an outpatient setting.

Methods: We conducted a retrospective cohort study of patients diagnosed with cirrhosis between January 1, 2018, and December 31, 2019 from 130 hospitals in the Veterans Affairs healthcare system. Patients were classified as having incident A-AKI if they met the International Club of Ascites AKI criteria in an outpatient setting. We used multivariable regression models to identify factors associated with A-AKI development within 1 year of cirrhosis diagnosis. We also conducted a structured implicit review of patients' medical charts to determine the …

Predicting Craving-Related Emotions Among Opioid Use Disorder Patients: Preliminary Results, Zachary King, Zoe Setiadi, Liana Hamdan, Hajar Ahmed, Bishal Lamichhane, Ashutosh Sabharwal, Ramiro Salas, Nidal Moukaddam, Akane Sano

Faculty, Staff and Students Publications

Individuals with Opioid Use Disorder (OUD) often struggle to maintain sobriety, with many experiencing relapse within the first year. While medication-assisted treatment (MAT) is among the most effective approaches, access to intensive care is often limited by financial barriers. Mobile health (mHealth) technologies offer a promising, cost-effective alternative by enabling continuous monitoring and timely intervention through tools such as ecological momentary assessments (EMAs), wearable sensors, and smartphone data. In this study, we explore the feasibility of using mHealth data to predict emotions that align with cravings in OUD patients undergoing MAT. Using data collected from EMAs, wearables, smartphone tracking, and …

Low Socioeconomic Status Adversely Influences Outcomes After Coronary Artery Bypass Grafting, Paige E Brlecic, Christopher B Sylvester, Katie J Hogan, Qianzi Zhang, Joseph S Coselli, Marc R Moon, Todd K Rosengart, Subhasis Chatterjee, Ravi K Ghanta

Faculty, Staff and Students Publications

Objectives: Although socioeconomic status (SES) is believed to affect patient outcomes after coronary artery bypass grafting (CABG), readmission data are sparse. In a national cohort, we analyzed the influence of SES on readmission, resource utilization, and mortality after CABG.

Methods: We queried the Nationwide Readmissions Database to identify patients who underwent isolated CABG from January 2016 through December 2018. We derived low, middle, and high SES from International Classification of Diseases, 10th Revision, Clinical Modification codes, patient demographics, and neighborhood-level factors. The effect of SES on risk-adjusted outcomes was assessed with multivariable analysis.

Results: Of 523,042 patients who underwent CABG, …

Paediatric Difficult Intubations And The Impact Of Timing Of Weekend Versus Weekday Cases: An Analysis Of The Pediatric Difficult Intubation Registry, Christy J Crockett, Judit Szolnoki, Sabina Khan, Angela C Lee, Alexander Kaizer, Patrick Olomu, Melissa Brooks Peterson

Faculty, Staff and Students Publications

Background: Off-hours presentation has been shown to be independently associated with tracheal intubation-related adverse events in patients with predicted difficult airway. The comparison of the complication rates of paediatric difficult intubations on weekends vs weekdays is unknown. The primary objective of this retrospective review is to determine the complication rates for paediatric difficult intubation cases that occur on a weekend vs a weekday.

Methods: We performed a retrospective review of data from the Pediatric Difficult Intubation registry, with service dates June 8, 2012 to May 9, 2023, to compare complication rates (total complications, hypoxaemia, non-hypoxaemia complications, and first-attempt success rate) …

Targeting The Hippo Pathway For Cardiac Regeneration, Rich Gang Li, Fansen Meng, James F Martin

Faculty, Staff and Students Publications

Ischemic heart disease, which affects more than 200 million people worldwide, is caused by reduced blood flow to the heart and leads to widespread cardiomyocyte death. Due to the limited regenerative potential of cardiomyocytes, the lost tissue is replaced by a fibrotic scar, resulting in reduced cardiac function and progression to heart failure. Current therapeutic interventions aim to improve blood flow but cannot address the inability of cardiomyocytes to renew after injury. However, multiple studies have shown that modulating the Hippo signaling pathway to activate Yes-associated protein (YAP), a transcription coactivator, in adult murine and porcine cardiomyocytes induces robust cardiomyocyte …

High Risk Of Persistence And Risk Of Dysplasia After Diagnosis Of Ultrashort Barrett's Esophagus, Wasseem Skef, Jasmine Haydel, Ashwin Rao, Ronan Allencherril, Rollin George, Gyanprakash A Ketwaroo, Aaron P Thrift, Hashem B El-Serag, Theresa Nguyen Wenker

Faculty, Staff and Students Publications

Introduction: The management of ultrashort (< 1 cm) Barrett's esophagus (BE) remains unclear. We aimed to determine the prevalence of ultrashort BE (USBE) at index diagnosis, identify factors associated with persistent BE after USBE diagnosis, and identify risk of dysplasia after initial USBE in a population of US veterans.

Methods: This was a retrospective cohort study at the Veterans Affairs hospital in Houston, TX, of consecutive patients with new BE diagnosis from November 1990 to June 2022 with follow-up through April 2023. Using a pathology database, we identified patients with a new USBE diagnosis and any subsequent follow-up esophagogastroduodenoscopy (EGD). We examined the association of sociodemographic and clinical risk factors of persistent USBE cohort compared with longer-length segment BE and those with a negative follow-up EGD after index USBE with χ 2 tests and logistic regression models. Last, we calculated the prevalence and …

Pharmacological Treatment For Patients With Obesity And Heart Failure: Focus On Glucagon-Like Peptide-1 Receptor Agonists. European Journal Of Heart Failure Expert Consensus Document, Luca Monzo, Gianluigi Savarese, Wilfried Mullens, Amr Abdin, Biykem Bozkurt, Ovidiu Chioncel, Seif El Hadidi, Thomas M Gorter, Riccardo M Inciardi, Mark C Petrie, Gabriele G Schiattarella, Davide Stolfo, Marco Metra, Nicolas Girerd

Faculty, Staff and Students Publications

There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP-1 RAs and GIP/GLP-1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body …

Urinary Markers In Heart Failure – Types, Timing And Thresholds. European Journal Of Heart Failure Expert Consensus Document, Masatake Kobayashi, Biykem Bozkurt, Peder Langeland Myhre, Juan Carlos Lopez Azor, Mateusz Guzik, Gracjan Iwanek, Guillaume Baudry, Marta Cobo-Marcos, Òscar Miró, Jeroen Dauw, Piotr Ponikowski, Wilfried Mullens, Alberto Palazzuoli, Marco Metra, Jan Biegus

Faculty, Staff and Students Publications

Several urinary markers reflect disease severity and have the potential to support the management of heart failure (HF). Collecting urine samples is easy and inexpensive, and urine sample composition can be altered not only by underlying kidney impairments (i.e. filtration barrier damage and tubular injury) but also via neurohormonal and inflammatory activation, ageing, comorbidities, other medical conditions and pharmacological interventions. For instance, urinary sodium may help to predict the response to loop diuretic therapy in acute HF, while albuminuria is used as a risk marker and therapeutic target for the progression of cardiovascular and kidney diseases in chronic HF, especially …

Albuminuria As A Diagnostic Criterion And A Therapeutic Target In Heart Failure And Other Cardiovascular Disease, Biykem Bozkurt, Patrick Rossignol, Joseph A Vassalotti

Faculty, Staff and Students Publications

The high disease burden and bidirectional relationship of chronic kidney disease (CKD), heart failure (HF) and other cardiovascular disease (CVD) necessitate the need for early diagnosis of these diseases. While current screening and detection methods are recommended by CKD and CVD guidelines, their adoption in practice is low. Urine albumin-to-creatinine ratio (uACR) is recognized as a diagnostic marker for CKD and a prognostic marker for CKD progression, HF and CVD outcomes, therefore albuminuria changes have been accepted as a surrogate outcome for kidney and cardiovascular endpoints. Furthermore, clinical trials investigating guideline-directed medical therapies have shown that uACR reductions are accompanied …

Evaluating Molecular And Immune Biomarkers In Predicting Bladder Cancer Recurrence And Survival: A Systematic Review, Saad Masood, Abdullah Shaikh, Yasin Brar

Faculty, Staff and Students Publications

This systematic review comprehensively evaluates current evidence on molecular and biochemical biomarkers for predicting recurrence and prognosis in bladder cancer. A literature search was conducted across PubMed, Scopus, and Web of Science databases up to September 2025, identifying 347 records. After rigorous screening and eligibility assessment, five studies met the inclusion criteria. The included research encompassed a range of biomarker types, including circulating tumor DNA (ctDNA), immune infiltration markers, methylation signatures, systemic inflammatory indices, and gene expression-based predictive models such as COXEN. Despite heterogeneity in study designs, methodologies, and endpoints, consistent findings indicated that integrated molecular profiling substantially improves the …

Gregor: Accelerating Genomics For Rare Diseases, Moez Dawood, Ben Heavner, Marsha M Wheeler, Rachel A Ungar, Jonathan Lotempio, Laurens Wiel, Seth Berger, Jonathan A Bernstein, Jessica X Chong, Emmanuèle C Délot, Evan E Eichler, James R Lupski, Ali Shojaie, Michael E Talkowski, Alex H Wagner, Chia-Lin Wei, Christopher Wellington, Matthew T Wheeler, Gregor Partner Members, Claudia M B Carvalho, Richard A Gibbs, Casey A Gifford, Susanne May, Danny E Miller, Heidi L Rehm, Kaitlin E Samocha, Fritz J Sedlazeck, Eric Vilain, Anne O'Donnell-Luria, Jennifer E Posey, Lisa H Chadwick, Michael J Bamshad, Stephen B Montgomery, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium

Faculty, Staff and Students Publications

Rare diseases are collectively common, affecting approximately 1 in 20 individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in next-generation sequencing, development of new computational and functional genomics approaches to prioritize genes and variants and increased global sharing of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize and evaluate emerging genomics technologies …

Optic Nerve Injury Impairs Intrinsic Mechanisms Underlying Electrical Activity In A Resilient Retinal Ganglion Cell, Thomas E Zapadka, Nicholas M Tran, Jonathan B Demb

Faculty, Staff and Students Publications

Retinal ganglion cells (RGCs) are the sole output neurons of the retina and convey visual information to the brain via their axons in the optic nerve. Following injury to the optic nerve, RGCs axons degenerate and many cells die. For example, a model of axon injury, the optic nerve crush (ONC), kills ~80% of RGCs after two weeks. Surviving cells are biased towards ‘resilient’ types, including several with sustained firing to light stimulation. RGC survival may depend on activity, and there is limited understanding of how or why activity changes following optic nerve injury. Here we quantified the electrophysiological properties …

Neurodevelopmental Abnormalities Underlying Behavioral Deficits In A Model Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Michael R Williamson, Vaishnav Krishnan, Mahyar J Hedayatpour, Adam C Adler, Nandani Adyapak, Chris S Ward, Russell Ray, David Durgan, Farrah Kheradmand, Benjamin Deneen

Faculty, Staff and Students Publications

Rationale: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

Objectives: To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

Methods: We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the …

Sim And Learn: Simulation And Its Value In Neurology Education, Laveena Singla, Fariha Jamal, Anju Abu, Dana Ionel, Amtul Farheen

Faculty, Staff and Students Publications

Background: Simulation is a widely used health care education tool. Its use is increasing in acute neurologic conditions and has great potential to help trainees better perform procedures and enhance communication and professionalism.

Observations: This article describes the different neurologic simulations used as educational tools and the evidence that demonstrates their value. It also details the benefits afforded by simulations (eg, improved adherence to protocols, reduced door-to-needle time in stroke care) and areas of opportunity. It includes the use of virtual reality to allow trainees to interact with 3-dimensional models of the brain as well as augmented reality to view …

Pkr-Driven Isr Signaling Controls Synaptic Translation And Structural Plasticity In An Age-Dependent Manner, Nicolás W Martínez, Felipe Gómez, Ariel Tapia-Godoy, Juan Francisco Roa, Fernanda Moreso-Contreras, Yuwei Liu, Claudia Jara, Cheril Tapia-Rojas, Iván Alfaro, Mauro Costa-Mattioli, Soledad Matus

Faculty, Staff and Students Publications

The integrated stress response (ISR) modulates protein homeostasis in response to both intracellular and extracellular signals. The four kinases involved in the ISR all phosphorylate the same target, the alpha subunit of eukaryotic initiation factor 2 (eIF2α), to integrate various stress signals, thereby regulating cell fate. The activation of the ISR reprograms the proteome by inhibiting general protein synthesis while increasing the translation of specific mRNAs. In the brain, the ISR regulates the type of synaptic plasticity necessary for forming long-term memory. More importantly, the activation of the ISR has emerged as a causal mechanism underlying cognitive decline associated with …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

Using Video Ethnography And Stimulated Recall Interviews To Describe The Diagnostic Process In The Emergency Department, Milisa Manojlovich, Caitlin Cassady, Sarah J Parker, Ellie Davis, Charlotte Ahr, David Ryamukuru, Anna Wang, Kalyan Pasupathy, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.

Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED …

Pleiotropy And The Increasing Complexity Of Parkinson's Disease Genetics, Jonggeol Kim, Joshua M Shulman

Faculty, Staff and Students Publications

No abstract provided.

Ubiquitous Dysregulation Of The Wnt Pathway In Immune Thrombocytopenia Genetic Susceptibility, Estelle Lecluze, Stennio Da Silva Faria, Manon Saby, Jason Yu, Véronique Lisi, Vincent-Philippe Lavallée, Taylor Olmsted Kim, Michael E Scheurer, Amanda B Grimes, Thomas Pincez

Faculty, Staff and Students Publications

The pathogenesis of immune thrombocytopenia (ITP) is complex and incompletely understood. Multiple cell types have been implicated, and their respective contribution is unclear. A recent genome-wide association study identified single-nucleotide polymorphisms (SNPs) associated with pediatric ITP within or near 5 genes in the canonical Wnt signaling pathway. To investigate whether this pathway was dysregulated in ITP and identify which cell types were involved, we leveraged extensive functional genomics and single-cell RNA sequencing (scRNA-seq) data. By linking the identified SNPs to likely regulated genes, we showed an enrichment in the Wnt pathway and identified 2 additional genes in this pathway involved …

Real-World Effectiveness And Safety Of Upadacitinib In Crohn's Disease: A Multicenter Study, Jalpa Devi, Anthony Xu, Molly Stone, Anish Patel, Abdul Khan, Nikhil Reddy, Jeremy Klein, Navreet Chowla, Caroline Benson, Bryan Christopher Luu, Katherine Huang, Fnu Jaiprada, Marc Fenster, Ryan Ungaro, Joel Pekow, Amanda M Johnson, Andres J Yarur, Richa Shukla, Julia Huecker, Shrinivas Bishu, Reboot Ibd Consortium, Parakkal Deepak

Faculty, Staff and Students Publications

Background & aims: We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor, in patients with Crohn's disease (CD).

Methods: A retrospective analysis was conducted across 9 centers in the United States, focusing on adults with CD treated with UPA, 45 mg, as induction therapy for active luminal disease. The coprimary end points were clinical remission at 12 weeks (Harvey Bradshaw Index ≤4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (Simplified Endoscopic Mucosal Assessment for Crohn's Disease score of 0-1 or absence of ulcers). Secondary …

Alterations In Cardiovascular Parameters In 5xfad Murine Model, Andrea G Marshall, Dominique Stephens, Kit Neikirk, Sepiso K Masenga, Bryanna Shao, Amber Crabtree, Zer Vue, Heather K Beasley, Edgar Garza-Lopez, Estevão Scudese, Benjamin I Rodriguez, Han Le, Steven Damo, George E Taffet, Okwute M Ochayi, Ronald Mcmillan, Jeremiah M Afolabi, Vernat Exil, Ashton Oliver, Vineeta Sharma, Pamela Martin, Amadou Gaye, Chanel Harris, Briar Tomeau, Lacara Bell, Markis Hamilton, Taneisha Gillyard, Railyn Webster, Marcus Jackson, Prem Prakash, Shanilah Frierson, Chandravanu Dash, Margaret Mungai, Annet Kirabo, Jennifer A Gaddy, Nelson Wandira, Antentor Hinton, Anilkumar K Reddy

Faculty, Staff and Students Publications

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

Coco-St Detects Global And Local Biological Structures In Spatial Transcriptomics Datasets, Muhammad Aminu, Bo Zhu, Natalie Vokes, Hong Chen, Lingzhi Hong, Jianrong Li, Junya Fujimoto, Mehdi Chaib, Yuqiu Yang, Bo Wang, Alissa Poteete, Monique B Nilsson, Xiuning Le, Tina Cascone, David Jaffray, Nicholas Navin, Tao Wang, Lauren A Byers, Don L Gibbons, John Heymach, Ken Chen, Chao Cheng, Jianjun Zhang, Jia Wu

Faculty, Staff and Students Publications

Spatial domain detection methods often focus on high-variance structures, such as tumour-adjacent regions with sharp gene expression changes, while missing low-variance structures with subtle gene expression shifts, like those between adjacent normal and early adenoma regions. Here, to address this, we introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive feature representation framework. By comparing a target sample with a background sample, CoCo-ST detects both high-variance, broadly shared structures and low-variance, tissue-specific features. It offers technical advantages, including multisample integration, batch-effect correction and scalability across technologies from spot-level Visium data to single-cell Xenium Prime 5K and subcellular Visium HD …

The Ifit2-Ifit3 Antiviral Complex Targets Short 5′ Untranslated Regions On Viral Mrnas For Translation Inhibition, Dustin R Glasner, Candace Todd, Brian Cook, Agustina D'Urso, Shivani Khosla, Elena Estrada, Jaxon D Wagner, Mason D Bartels, Chuan-Tien Hung, Pierce Ford, Jordan Prych, Kathryn S Hatch, Brian A Yee, Kaori M Ego, Qishan Liang, Sarah R Holland, James Brett Case, Kevin D Corbett, Michael S Diamond, Benhur Lee, Gene W Yeo, Mark A Herzik, Eric L Van Nostrand, Matthew D Daugherty

Faculty, Staff and Students Publications

Recognition of foreign RNA is critical for the innate immune response to viruses. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFIT) 2 and 3 are highly upregulated following viral infection, but mechanistic insight into their antiviral role is lacking. Here we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can serve as a molecular pattern for innate immune recognition via IFIT2 and IFIT3. Structure determination of the IFIT2-IFIT3 complex at 3.2 Å using cryo-EM reveals a domain-swapped heterodimer that is required for recognition of the viral mRNA 5' end, translation inhibition and antiviral activity. Critically, viral …