Digital Commons Network^™

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Mucin-Derived Sugars Act As Metabolic Brakes Controlling Growth Initiation In Akkermansia Muciniphila, Bryan D Lakey, Katherine J Wozniak, Robert A Britton, Jeffrey J Tabor

Faculty, Staff and Students Publications

Akkermansia muciniphila is a key member of the gut microbiota and plays important roles in host metabolism and health. In the colon, A. muciniphila extracts nutrients from oligosaccharide-rich mucin glycans that comprise the mucosa. However, this environment is complex and shaped by dietary inputs, microbiome metabolism, and mucin glycan composition varying across hosts, gastrointestinal regions, and physiological states. How strains of A. muciniphila integrate these nutrient signals into growth initiation and niche colonization remains unclear. Here, we compare physiological responses of a human- and mouse-derived strain of A. muciniphila, finding that dietary sugars differentially affect these isolates, suggesting host-associated …

Gut-Derived Bacterial Extracellular Vesicles: The Microbial Dark Matter Contributing To Host Inflammation And Cardiometabolic Disease, Blayne Oliver, Michael Sun, Young Seo Lee, Ssanggoo Cho, Tianyi Zhu, David Durgan, Gary Sweeney

Faculty, Staff and Students Publications

Cardiometabolic diseases (CMDs) represent a growing global health burden, with chronic inflammation and gut microbiota dysbiosis emerging as central contributors to their pathogenesis. Among the diverse microbial products influencing host physiology, bacterial extracellular vesicles (BEVs) have gained attention as potent mediators of interkingdom communication. These nanoscale vesicles, secreted by both gram-positive and gram-negative bacteria, carry a complex cargo of proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs) that interact with host pattern recognition receptors (PRRs) to modulate immune and metabolic responses. BEVs can traverse intestinal barriers, disseminate systemically, and accumulate in cardiometabolic tissues, where they influence inflammation, insulin sensitivity, …

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

Associations Between Trpm4 Gene Variants And Intracranial Pressure Dynamics Following Traumatic Brain Injury, Emily H. Saweris

Summer Research Program Abstracts

No abstract provided.

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Sarah Shin, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Development Of A Culture System For Eosinophils Derived From Human Cord Blood Stem Cells, Christian Lachance

Summer Research Program Abstracts

No abstract provided.

Acceleration Of Coagulation Kinetics For Clot Burst Pressure Assessment, Hanuk Kwon

Summer Research Program Abstracts

No abstract provided.

Forniceal Deep Brain Stimulation Improves Memory In Rett Syndrome Mice By Promoting The Maturation Of Newborn Hippocampal Neurons, Qi Wang, Bin Tang, Zhenyu Wu, Huda Y Zoghbi, Jianrong Tang

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) is associated with an increase in hippocampal neurogenesis and memory benefits, but the causal mechanism is unclear. Here, we use a mouse model of Rett syndrome, a severe learning disability syndrome caused by MECP2 loss of function, to find that DBS promotes the maturation and integration of newborn dentate granule cells (DGCs) into the neural circuit. Suppressing hippocampal neurogenesis prevented DBS from improving learning and memory. Newborn methyl-CpG-binding protein 2 (MeCP2)-deficient DGCs in Rett syndrome mice showed attenuated development and synaptic dysfunction, but DBS rescued DGC dendritic arborization, synaptogenesis, and long-term synaptic plasticity. DBS achieves this, …

Multiple Quality Control Checkpoints Safeguard Small Nuclear Rna Biogenesis And Prevent Assembly Of Aberrant Spliceosomes, Tiantai Ma, Claire Huntington, Zhuoyi Song, Rea M Lardelli, Eric L Van Nostrand, Jens Lykke-Andersen

Faculty, Staff and Students Publications

Defective small nuclear (sn)RNAs are produced from hundreds of human snRNA pseudogenes and mutant snRNA genes associated with human developmental disorders. Machineries that prevent defective snRNAs from disrupting pre-mRNA splicing remain poorly defined. Here, we identify multiple checkpoints in snRNA biogenesis monitored by quality control machineries that subject defective snRNAs to degradation and prevent their assembly into spliceosomes. We show that variant U1 snRNAs produced from human pseudogenes, some at rates approaching canonical snRNAs, are impaired in 3' cleavage and targeted for degradation by the NEXT-exosome while failures in subsequent protein assembly steps promote NEXT-exosome- or terminal uridylyl transferase 4/7-mediated …

Natural History Of Pi-Rads 3 Lesions On Serial Prostate Mpmri, Ron Marom, Yuval Rand, Meitar Atias, Sophie Barnes, Ibrahim Fahoum, Gal Keren-Paz, Mario Sofer, Ofer Yossepowitch, Snir Dekalo, Avi Beri, Roy Mano

Faculty, Staff and Students Publications

Objective: PI-RADS 3 lesions on prostate multiparametric MRI (mpMRI) are indeterminate findings with debated management. We evaluated their radiologic evolution on follow-up mpMRI and correlated imaging changes with biopsy outcomes.

Methods: We retrospectively identified 166 men with at least one PI-RADS 3 lesion on initial mpMRI and at least one follow-up mpMRI without intervening treatment. Lesions were classified at follow-up as regressed (downgraded to PI-RADS ≤ 2), stable (remained PI-RADS 3), or progressed (upgraded to PI-RADS 4-5). Lesions were stratified by zonal location. MRI-targeted biopsy results were reviewed when available (n = 64).

Results: On follow-up, 52% of lesions regressed, …

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Fgfr1/Klb-Mfg-E8 Maintains Microvascular Integrity And Adaptive Cardiac Remodeling, Sanskruti R Gare, Nasser H Alatawi, Xinyi Chen, Jiayan Zhang, Claire Ross, Oveena Fonseka, Yihua Han, Namrita Kaur, Andrea Ruiz-Velasco, Xiangjun Zhao, Yingjuan Liu, Riham R E Abouleisa, Susanne S Hille, Tao Wang, Sabu Abraham, Bernard D Keavney, Martin K Rutter, Elizabeth J Cartwright, Gareth Howell, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Faculty, Staff and Students Publications

Background: Endothelial defects in the heart are a contributor to cardiac pathological remodeling and dysfunction, which can be influenced by cardiomyocytes. Here, we explore cardioprotective crosstalk between cardiomyocytes and endothelial cells under diabetic conditions.

Methods: Type 2 diabetes was induced in male and female mice using a high-fat, high-sucrose diet in conjunction with low-dose streptozotocin. Cardiomyocyte-specific deletion of FGFR1 (fibroblast growth factor receptor 1) or KLB (beta-Klotho) was achieved by crossing floxed mice with αMHC (alpha-myosin heavy chain)-Cre transgenic mice, while the treatment potential was assessed by recombinant adeno-associated virus 9 delivery systems or administration of recombinant protein. Various in …

Cultura, Collaborations, And Chisme: An Mla Caucus’ Oral History Project, Adele V. Justice, Brandon Kennedy, Jessica Diaz, Manuel Pasos, Saily Marrero, Sandra Desjardins

Library Staff Publications

Overview: An MLA Caucus began an oral history project featuring its members. Using a collaborative, community-based approach, the project brings. This poster describes the development of this significant project.   Methods: In Fall 2025 one of our caucus leaders shared that they had a robust oral history project at their library organization. This began the idea of forming an oral history project at the MLA caucus level. Within the caucus, an oral history task force was formed. Next, an online collaborative space was created where caucus members from across the country began drafting their responses to the prepared, open-ended questions. To …

Single-Nuclei Transcriptomics Reveals Cellular Senescence In Pediatric Anthracycline-Induced Cardiomyopathy, Hanna J Tadros, Yi Zhao, Lalita Wadhwa, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Chemotherapy drugs that fight childhood cancer can age heart cells prematurely. We found this "cellular aging" throughout the hearts of children with treatment-related heart failure.

The Antibacterial Properties Of The Infrapatellar Fat Pad Organ, Mark A. Coggins

Summer Research Program Abstracts

No abstract provided.

Engineering Pegylated Chitosan–Gold Nanoparticles For Radiosensitization And Sirna Delivery To Glioblastoma, Wesley Chiu

Summer Research Program Abstracts

No abstract provided.

Diopt: The Drsc Integrative Ortholog Prediction Tool, 2026 Update, Austin Veal, Shinya Yamamoto, Stephanie E Mohr, Norbert Perrimon

Faculty, Staff and Students Publications

Mapping orthologous proteins is a critical step for cross-species literature mining, data integration, experimental design, and more, making the ability to quickly predict orthologs across species a key tool for functional genomic studies. The DRSC Integrative Ortholog Prediction Tool (DIOPT) was initially developed in 2011 to provide a centralized portal for identifying inferred orthologs among major model organisms. By integrating results from multiple ortholog prediction algorithms, DIOPT allows users to compare predictions across methods and prioritize high-confidence ortholog relationships. Over the years, we regularly updated the underlying genome annotations and refreshed predictions from each integrated algorithm. In addition, both the …

Immune Hallmarks Of Recurrent Immune Checkpoint Inhibitor-Mediated Inflammatory Arthritis, Synat Keam, Yuanteng Jeff Li, Yanshuo Chu, Jean H Tayar, Huifang Lu, Michael Wu, Sandeep K Agarwal, Nitin Jain, Pavlos Msaouel, Adi Diab, Linghua Wang, Cara Haymaker, Roza Nurieva, Sang T Kim

Faculty, Staff and Students Publications

Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (IA). However, the mechanisms underlying ICI-mediated IA (ICI-IA), especially its recurrence, are not well understood. In this study, we sought to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal synovial fluid (SF) samples from patients with ICI-IA. SF samples were collected from six patients with ICI-IA at the first and second occurrences of ICI-IA and analyzed with single-cell RNA sequencing (n = 3), single-cell T-cell receptor sequencing (n = 3), single-cell B-cell receptor sequencing (n = 3), and flow cytometry (n = 6). SF samples …

Human Norovirus Infection Does Not Induce Serotonin Secretion In Human Intestinal Organoids, Hephzibah Nwanosike, Vijayalakshmi B Ayyar, Michael J Bolt, Aaya Boussattach, Yi-Ting Shen, Sarah E Blutt, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. The primary symptoms of HuNoV-associated disease are vomiting and diarrhea; yet the mechanisms underlying these symptoms are poorly understood. Neuroactive hormones such as serotonin (5-hydroxytryptamine; 5-HT) secreted by intestinal enteroendocrine cells (EECs) can activate vomiting centers in the brain and play a critical role in regulating emetic signaling. Serotonin release from infected EECs has been implicated in vomiting during other enteric infections. Recent studies have reported the detection of HuNoV RNA and antigen in EECs in jejunal biopsies from immunocompromised patients with chronic HuNoV infection and rhesus macaques. We …

A Rare Recurring Gain-Of-Function Variant In Bmpr2 Causes Neurodevelopmental Phenotypes In Humans And Flies, Zhi Tan, Ariel Brautbar, Maria Descartes, Erica T Gray, Alejandro Iglesias, Scott D Mclean, Morgan Nutter, Olivia Daugherty, Amber Begtrup, Ingrid M Wentzensen, Yufeng Shen, Damian W Young, Martin M Matzuk, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Wendy K Chung, Shinya Yamamoto

Faculty, Staff and Students Publications

Bone morphogenetic protein receptor type 2 (BMPR2) encodes an evolutionarily conserved serine/threonine kinase that phosphorylates type-1 BMP receptors to mediate intercellular communication upon ligand binding. Loss-of-function variants in BMPR2 are known to cause pulmonary arterial hypertension and other cardiovascular disorders. Here, we report a rare recurrent missense variant in BMPR2 (c.1126G>A [GenBank: NM_001204] [p.Glu376Lys]) identified in six individuals, who all present with neurodevelopmental phenotypes including autism spectrum disorder and global developmental delay. Trio analysis demonstrates de novo occurrence of this variant in at least five of the individuals. Using the fruit fly Drosophila melanogaster, we show that this variant …

A Genetic Risk Variant Associated With The Risk Of Primary Biliary Cholangitis Is Inherited From Neanderthals, Heather J Cordell, George F Mells, Richard N Sandford, David E Jones, Gideon Hirschfield, Katherine A Siminovitch, M Eric Gershwin, Brian D Juran, Elizabeth J Atkinson, Angela Cheung, Mariza De Andrade, Aris Baras, Konstantinos N Lazaridis, Rosanna Asselta, Pietro Invernizzi, Manuela Sironi, Sriram Sankararaman, Canadian‐Us Pbc Consortium, Uk‐Pbc Consortium, Italian Pbc Genetics Study Group

Faculty, Staff and Students Publications

Background: Primary Biliary Cholangitis (PBC) is an autoimmune cholangiopathy with polygenic architecture and unknown aetiology. Evidence links Neanderthal-derived genetic variants to autoimmune conditions; however, their contribution to PBC susceptibility remains unexplored.

Objective: We investigate whether archaic alleles influence PBC risk.

Design: Genotype data from four PBC cohorts were analysed: CANUK (4615 cases, 9233 controls), OLD IT (444 cases, 901 controls), NEW IT (255 cases, 579 controls) and MAYO (891 cases, 621 controls). Association testing with 235 592 Neanderthal Informative Markers (NIMs) was performed, adjusting for population stratification. Heritability was estimated using RHE-mc and temporal haplotype dynamics were assessed using ancient …

A Prospective Natural History Study Protocol For Clinical Trial Readiness In Synaptic Disorders, Joeylynn Coyne, Ian Mcsalley, Michael C Kaufman, Bintou Bane, Torrey Chisari, Jonathan Toib, Carlyn Glatts, Sarah Tefft, Julie M Orlando, Viveknarayanan Padmanabhan, Alexander K Gonzalez, Alicia Harrison, Charlene Woo, Stephanie A Zbikowski, Rency Dhaduk, Johanna Mercurio, Macie Mccarthy, Jan H Magielski, Zachary Grinspan, Megan Abbott, Juliet Knowles, Hsiao-Tuan Chao, Katherine Xiong, Elizabeth Berry-Kravis, Sepideh Tabarestani, J Michael Graglia, Kathryn Helde, Virginie Mcnamar, Charlene Son Rigby, James Goss, Scott Demarest, Andrea Miele, Benjamin Prosser, Michael J Boland, Samuel R Pierce, Ingo Helbig

Faculty, Staff and Students Publications

Objective: STXBP1-related disorder (STXBP1-RD) and SYNGAP1-related disorder (SYNGAP1-RD) are two common genetic synaptopathies that are associated with epilepsy, developmental delay, intellectual developmental disorder, and behavioral problems. Both STXBP1-RD and SYNGAP1-RD are potential targets for disease-modifying therapies, but there is limited information in the literature describing the natural history of either disorder, which impedes outcome selection for future clinical trials. The objective of this study is to develop a framework to better define and outline the clinical spectrum and longitudinal trajectories of STXBP1-RD and SYNGAP1-RD natural history, including development, behavior, seizure histories, and electrophysiology.

Methods: Here, we describe a protocol, regulatory …

Clinical Decision Support For Fall Prevention In Primary Care: The Esteps Cluster Randomized Clinical Trial, Nancy K Latham, Erin Hommel, Mackenzie Kiesman, Stuart R Lipsitz, David W Bates, Diane L Carroll, Alexandra C Frost, Pamela M Garabedian, Julia V Loewenthal, Michael Sainlaire, Lipika Samal, Wenyu Song, Matthew Wien, Patricia C Dykes

Faculty, Staff and Students Publications

Importance: Falls are a leading cause of injury among older adults. Although exercise reduces fall risk, implementation in primary care remains limited.

Objective: To assess whether an electronic health record-integrated clinical decision support intervention, Electronic Strategies for Tailored Exercise to Prevent Falls (eSTEPS), reduces falls among older primary care patients at increased risk.

Design, setting, and participants: This matched-pair cluster randomized clinical trial was conducted from June 9, 2023, to May 8, 2025, with 12 to 23 months of follow-up at primary care practices within an integrated health system in the US. Adults aged 65 years or older with a …

Spell: A Scalable Nlp Method Using Regular Expressions And Large Language Models For Clinical Information Extraction, Kathryn J Gray, Vesela P Kovacheva

Faculty, Staff and Students Publications

Background and objectives: Electronic health records (EHRs) contain valuable information for research and decision-making, but much resides in unstructured notes that are challenging to analyze at scale. We developed SPELL (Snippet-Primed rEgex LLM Pipeline), a scalable natural language processing workflow that combines regular-expression-based snippet retrieval with locally hosted large language model (LLM) inference to extract structured variables from large collections of clinical narratives.

Methods: SPELL uses task-specific regular expressions to retrieve short context windows ("snippets") from unstructured texts and applies task-prompted LLM inference on snippets rather than full documents. All processing occurs within institutional computing environments. Accuracy was evaluated on …

Cadherin-11 Regulation Of Type Ii Alveolar Epithelial Cells During Pulmonary Fibrosis, Mesias Pedroza, Sarah To, Jennifer Smith, Tingting W Mills, Thandiwe Chavula, Harry Karmouty-Quintana, Sandeep K Agarwal

Faculty, Staff and Students Publications

Type II alveolar epithelial cell (AT2) injury has been hypothesized to contribute to pulmonary fibrosis. Cadherin-11 (CDH11) is a mediator of fibrosis and is upregulated on AT2s during lung fibrosis. Herein, the regulation of AT2 by CDH11 during pulmonary fibrosis was investigated. CDH11 levels were increased in lung samples from patients with idiopathic pulmonary fibrosis compared with those from healthy controls. CDH11 expression was inversely correlated with lung function. Cdh11-deficient mice were compared with wild-type mice in the intraperitoneal bleomycin model (IP BLM), and the role of AT2 was investigated using Cdh11 floxed-SPC-Cre mice and in vitro techniques. In …

A Spatial Atlas Of Muscle-Invasive Bladder Cancer Reveals Lineage-Specific Vulnerabilities And Immune Architecture, Sajith Nair, Emanuele Crupi, Elshad Hasanov, Ying Mei, Xueshuai Han, Yang Liu, Yunhe Liu, Guangsheng Pei, Fuduan Peng, Jianlong Liao, Enyu Dai, Tian Chu, Kyung Serk Cho, Jiahui Jiang, Xinmiao Yan, Yibo Dai, Jun Wang, Baifeng Zhang, Giannicola Genovese, Nagireddy Putluri, Livia Eberlin, Liuqing Yang, Chunru Lin, Lawrence N Kwong, Diana Shamsutdinova, Khalida M Wani, Bogdan A Czerniak, Wendong Yu, Jianping Zhao, Charles C Guo, Donna Hansel, Curtis Pettaway, Louis Pisters, Kelly Bree, Neema Navai, Byron H Lee, Ashish M Kamat, Padmanee Sharma, Paul Corn, Cindy Y Jiang, Amishi Y Shah, Omar Alhalabi, Pavlos Msaouel, Arlene O Siefker-Radtke, Christopher J Logothetis, Matthew T Campbell, Alexander J Lazar, Jianjun Gao, Linghua Wang

Faculty, Staff and Students Publications

Muscle-invasive bladder cancer (MIBC) is clinically heterogeneous, and current molecular subtyping does not capture the spatial organization of tumor states and microenvironmental context. In this study, we construct a spatial atlas of MIBC by integrating spatial transcriptomics from 22 tumors with matched bulk RNA and whole-exome sequencing data. We identify a continuous, spatially organized luminal-to-basal axis within individual tumors that is associated with greater chromosomal instability and transcriptional plasticity. Luminal tumor cores are enriched for FGFR3 and NECTIN4, whereas basal-like states localize toward invasive margins and are associated with elevated EGFR signaling, epithelial-mesenchymal transition, genomic instability, immune infiltration, and greater …

Reversible Microvascular Ischemia With St-Segment Elevation: An Underrecognized Manifestation Of Antibody-Mediated Rejection In Cardiac Allograft Recipients, Jonathan Ahn, Justin Daneshrad, Liset Stoletniy, Dmitry Abramov

The VAD Journal

Electrocardiographic manifestations of cardiac allograft rejection are often subtle, and stress-induced ST-segment elevation associated with antibody-mediated rejection (AMR) is rarely reported. We describe a 34-year-old heart transplant recipient with progressive exertional angina, nonobstructive coronary disease on angiography, and exercise-induced ST-segment elevation in lead augmented vector right, high-lateral leads I, and augmented voltage left, along with diffuse ST-segment depressions, hypotension, and transient ventricular tachycardia. Concurrent emergence of complement-binding donor-specific antibodies with high mean fluorescence intensity raised concern for AMR, prompting treatment with corticosteroids, plasma exchange, and intravenous immunoglobulin despite the absence of biopsy confirmation. After therapy, symptoms, exercise-induced ischemic electrocardiographic abnormalities, …

Pitx2 Missense Coding Variant Expression In Mice Reveals Direct Function In Atrial Fibrillation, Jeffrey D Steimle, Yue Yuan, Shaohai Fang, Vaibhav Deshmukh, Christine Rodriguez, Fansen Meng, Taotao Tan, Md Abul Hassan Samee, Yun Huang, Na Li, James F Martin

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common sustained human cardiac arrhythmia and linked to a drastic increase in stroke and heart failure risk. While sequence variations in the PITX2 non-coding region are the strongest genetic signature of AF risk, the direct role of PITX2 in AF remains a topic of debate. Here, we generated a mouse model (Pitx2Pro41Ser) of a human PITX2 coding variant linked to increased AF risk in the Finnish population. The Pitx2Pro41Ser mice exhibit near-complete penetrance of pacing-induced AF, and transcriptional profiling indicates that Pitx2Pro41Ser is a loss-of-function mutation. In vivo cleavage under targets and tagmentation (CUT&Tag) …