Digital Commons Network^™

Cigarette Smoke Induces Fasn-Dependent Fatty Acid Metabolic Rewiring To Drive Bladder Cancer Progression, Chandra Sekhar Amara, Danthasinghe Waduge Badrajee Piyarathna, Abu Hena Mostafa Kamal, Yuen San Chan, Karthik Reddy Kami Reddy, Chandra Shekar R Ambati, Mohammed Khurshidul Hassan, Pratik Shriwas, Tanmay Gandhi, Antrix Jain, Tanja Gangnus, Pooja Popli, Roshan Borkar, Sung Wook Kang, Silvia L Summers, Vasanta Putluri, Sandra L Grimm, Sharan Venkatesh, Ningxin Song, Erin H Seeley, Jenna Hedlich-Dwyer, Shu-Hsia Chen, Nupam P Mahajan, Abhinav K Jain, Lacey Elizabeth Dobrolecki, Gabrielle A Wells, Hugo Villanueva, Jenny Li, Xuefeng Liu, Roni J Bollag, Anna Malovannaya, Sung Yun Jung, Hyun-Sung Lee, Irfan A Asangani, Martha K Terris, Chad J Creighton, Leomar Y Ballester, Balasubramanyam Karanam, Suyu Liu, Minjae Lee, Rajeeva R Raju, M Minhaj Siddiqui, Livia S Eberlin, Ramakrishna Kommagani, Arun Sreekumar, Jianjun Gao, Nicolas L Young, H Courtney Hodges, Cristian Coarfa, Natalie R Gassman, Seth P Lerner, Yair Lotan, Nagireddy Putluri

Faculty, Staff and Students Publications

Cigarette smoke promotes bladder tumor growth by enhancing cancer cell survival and proliferation through smoke mediated carcinogens. FASN, a key enzyme in fatty acid synthesis, is dysregulated in many cancers and correlates with aggressive phenotypes. In this study, we demonstrate elevated fatty acid levels and FASN specifically in smokers with bladder cancer. Elevated FASN under smoke exposure imparted epigenetic alterations, particularly histone acetylation, impacts DNA repair and DNA-binding transcription factors which regulate metabolic pathways. Under cigarette smoke, bladder cancer cells undergo a metabolic shift, utilizing glutamine as a major carbon source through reductive carboxylation to fuel fatty acid biosynthesis via …

Shared Neural Geometries For Bilingual Semantic Representations In Human Hippocampal Neurons, Xinyuan Yan, Ana G Chavez, Melissa Franch, Kalman A Katlowitz, Ivy Gautam, Brian Kim, Aaditya Krishna, Aadit Shrivastava, Katie Van Arsdel, James Belanger, Assia Chericoni, Taha Ismail, Elizabeth A Mickiewicz, Danika Paulo, Hanlin Zhu, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Eleonora Bartoli, Nicole R Provenza, Seng Bum Michael Yoo, Benjamin Y Hayden, Sameer A Sheth

Duncan NRI Faculty and Staff Publications

The human brain has the remarkable ability to comprehend and express similar concepts in multiple languages. To understand how it does so, we examined responses of hippocampal neurons during passive listening, directed speaking, and spontaneous conversation in both English and Spanish in a small group of balanced bilinguals. We found a small number of putative "cross-language neurons," whose responses to equivalent words (e.g., "tierra" and "earth") are correlated. However, neurons' semantic tunings differed substantially by language, suggesting language-specific neural implementations. Instead, the crucial driver of translation was a preserved geometric organization of neural responses between the two languages, one that …

The Past, The Present, And The Future Of Preclinical Mouse Models For Alzheimer's Disease And Related Dementias., Adrian L Oblak, Michael Sasner, Gregory W. Carter, Gareth R Howell, Stacey J Sukoff Rizzo, Karina Leal, Paul R Territo, Bruce T Lamb

Faculty Research 2026

Over the past decade, the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium has transformed preclinical Alzheimer's disease (AD) research by addressing critical limitations in traditional mouse models that failed to translate to human disease. By leveraging human genetic discoveries, MODEL-AD has developed > 70 genetically informed mouse models, standardized phenotyping pipelines, and an open-access data infrastructure aligned with late-onset AD biology. These models incorporate human risk variants, environmental factors, and aging to better capture disease complexity, including emerging recognition of mixed pathologies such as vascular contributions, Lewy body disease, and TDP-43 proteinopathy. Despite substantial progress, key challenges …

A Collaborative Framework For Uncovering Molecular And Cellular Drivers Of Vcid: Foundations For Future Interventions In Dementia., M Luisa Iruela-Arispe, Jason D Hinman, Andrew C Yang, Fabrice Dabertrand, Jin-Moo Lee, Gareth R Howell, The Vcid Centers Without Walls Network

Faculty Research 2026

Vascular-related factors are now considered major contributors to most forms of dementia, including Alzheimer's disease. However, the degree to which vascular deficits contribute to risk, onset, and progression of cognitive impairment and dementia has only recently been appreciated. Our understanding of the mechanisms by which vascular deficits drive cognitive decline in dementia is still limited. Further, the testing of therapeutic approaches to prevent vascular deficits to treat dementia are few. These factors motivated the establishment of the Vascular Contributions to Cognitive Impairment and Dementia (VCID) Center Without Walls (CWOW) network, comprising institutes across the United States. We describe the current …

Inhibition Of Moesin And Cd44 In Stem Cell-Derived Neurons Affects The Pathological Genetic Signature Associated With Alzheimer's Disease., Eiden H Brewer, Charles A Williams, Gregory Cary, Ranjita Betarbet, Inez K A Pranoto, Elizabeth L Zoeller, Haian Fu, Allan I Levey, Jesse C Wiley, Gregory W. Carter, Jessica E Young, Treat-Ad Consortium

Faculty Research 2026

INTRODUCTION: Post mortem proteomic analysis of Alzheimer's disease (AD) brain tissue has identified novel target genes and proteins for potential therapeutic development. Moesin (MSN) and CD44 were identified as candidate targets. Using human induced pluripotent stem cells (hiPSCs)-derived neurons, we assayed how reducing gene expression of MSN and CD44 affected amyloid beta secretion, tau phosphorylation, and transcriptional state.

METHODS: Knockdown of MSN and CD44 in hiPSC-derived neurons was performed using short hairpin RNA (shRNA). Amyloid precursor protein processing and intracellular tau phosphorylation was measured using chemiluminescent ELISA assays. Global gene expression was analyzed by bulk RNA sequencing (RNA-seq).

RESULTS: Knockdown …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

Notch Signaling Regulates The Secretion Of Pro-Metastatic Factors In Extracellular Vesicles In Liposarcoma, Menchus Quan, Yi-Kai Liu, Ying Zhao, Madeline Kay, Kai Sun, Timothy P Gavin, Raphael E Pollock, W Andy Tao, Shihuan Kuang

The Brown Foundation: Institute of Molecular Medicine

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that …

The Biological Response Of Human Np Cells To Soluble Collagen Vi, Jonathan Dalton, Srikanth N. Divi, Yasmine Eichbaum, Panya Luksanapruksa, Mitchell K. Ng, Rachel Huang, Alan S. Hilibrand, Alex R. Vaccaro, Dessislava Z. Markova, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

Extracellular matrix (ECM) dysregulation plays a significant role in the development of intervertebral disc disease (IVDD). The ECM around the chondrocytes in the nucleus pulposus (NP) is unique in that it contains ColVI. While linked to chondrocyte proliferation in cartilage, ColVI's specific role in IVD degeneration is less clear. Our aim was to determine the expression of ColVI in NP cells from degenerative IVDs, along with the effects of soluble ColVI on NP cells. Thus, we compared the expression levels of ColVI in human degenerated IVD samples, along with the effect of soluble ColVI on primary human NP cells. A …

The Best Of Both Worlds: How Combining A Large Language Model And A Rule-Based Algorithm Makes Catheter-Associated Urinary Tract Infection Surveillance More Efficient, Joshua Nordman, Claire Najjuuko, Nicholas Jeschke, Rachael E Snyders, Maria Cristina Vazquez Guillamet, Hilary Babcock, Patrick Reich, Andrew Atkinson, Jonas Marschall, Abby Sung, Et Al.

2020-Current year OA Pubs

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) surveillance is critical for patient safety. Many healthcare systems use electronic algorithms to flag candidate infection events but still require manual chart review to confirm CAUTI cases. We evaluated the use of a large language model (LLM) to enhance CAUTI surveillance.

METHODS: We analyzed 919 potential CAUTI cases flagged by the electronic surveillance algorithm at Barnes-Jewish Hospital from 2021 to 2024. These cases were previously classified as 291 CAUTIs and 628 non-CAUTIs by trained infection preventionists (IPs). Several approaches for applying the National Healthcare Safety Network (NHSN) CAUTI definition after extracting clinical data from …

Molecular Mechanism Leading To Human Coronary Atherosclerosis Assessed By Proteomic Analysis And Rna Sequences, Sarah J Parker, Chunhong Mao, David L Caudell, Austin Lyle Seals, Yizhi Wang, Thomas D Green, Joseph M Mcclung, Joshua T Maxwell, Jacolby T Roddey, Kiarash Shakeriastani, Chiung-Ting Wu, Yingzhou Lu, Do-Kyun Kim, Justyna Fert-Bober, Dongping Du, Archana Bhat, Niveda Sundararaman, Matthew Ayres, Rakhi Pandey, Saurabh Bhardwaj, Genesio M Karere, Dana Troxclair, Fannie Jackson, Gordon L Love, Richard Vander Heide, James Hixson, Jennifer E Van Eyk, Yue Wang, David Herrington

Faculty, Staff and Student Publications

Background and aims: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt …

Interstitial Fluid N-Glycans Serve As A Proxy For Serum Biomarker Discovery In A Pilot Study, Radka Saldova, Talus K. Gaymore, Caitriona Walsh, Eder Zavala, Paula M. Mendes

Student Papers, Posters & Projects

Protein glycosylation is the most prevalent post-translational modification and is known to undergo profound alterations in disease. While serum N-glycosylation has been extensively studied, interstitial fluid is gaining prominence as a minimally invasive biomarker source, underscored by the widespread clinical adoption of wearable glucose monitors in diabetic patients. However, the glycomic landscape of interstitial fluid remains largely unexplored. Here, we have performed a comparative analysis of the N-glycome from interstitial fluid and matched plasma from five healthy volunteers using liquid chromatography, mass spectrometry and exoglycosidase digestions. Strikingly, the interstitial fluid N-glycome closely shows overlapping profiles with the plasma of each …

Llm-As-A-Judge For Infection Prevention And Control And Antimicrobial Resistance Impact: Comparing Three Main Llms Vs. Human Experts' Assessment, Marcello Di Pumpo, Leonardo Villani, Maria Rosaria Gualano, Danilo Buonsenso, Francesca Raffaelli, Daniele Donà, Patrizia Laurenti, Vittorio Maio, Stefania Boccia, Walter Ricciardi

College of Population Health Faculty Papers

BACKGROUND: Large language models (LLMs) are increasingly used to generate health information, yet their reliability as evaluators remains unclear. This study investigated the feasibility of an LLM-as-a-judge methodology in the context of infection prevention and antimicrobial resistance (AMR), comparing automated ratings with human expert benchmarks.

METHODS: We performed a secondary analysis of an expert-annotated dataset of health messages. Three leading LLMs (ChatGPT, Claude, Gemini) independently evaluated the same messages using an adapted DISCERN tool across five domains: information reliability, quality, AMR impact, persuasiveness, and overall score. We utilized descriptive statistics, intra-rater reliability tests, and mixed-effects ordinal regression to analyze divergence …

Unbiased Avidity-Based Isolation Of Antigen-Specific T Cells, Amanda Montoya, Meredith L Frank, Peixin Jiang, Hui Nie, Minying Zhang, Emily Bontekoe, Jared K Slone, Ludovica L Posta, Sofia Rosy Caterina Sorice, Tina Cascone, Maura Gillison, Don L Gibbons, Jianjun Zhang, Eleonora Dondossola, Lydia Kavraki, Pamela L Wenzel, John V Heymach, Alexandre Reuben

The Brown Foundation: Institute of Molecular Medicine

Background: Cancer immunotherapies have significantly improved treatment efficacy and patient survival by exploiting antigen-specific T cells to eliminate cancer cells. However, current approaches for identifying and isolating antigen-specific T cells typically require prior knowledge of target antigens, limiting discovery, and reducing the ability to consistently detect rare tumor-reactive T cells. We therefore sought to develop an unbiased platform for the identification and enrichment of antigen-specific T cells using naturally processed and presented tumor antigens.

Methods: We developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a microfluidic platform that applies controlled shear stress and leverages tumor cells …

Biophysical Insights Into A Cryptic Ligand Site In The Hydrophobic Core Of Human Pcna, Alexis N. Dispensa, Sharon N, Greenwood, Jason Yang, Daniel E. Logatto, James Fusco, E. Railey White, Roderic G. Eckenhoff, Zhiwei Liu, Brian P. Weiser

Department of Anesthesiology Faculty Papers

Proteins contain small pockets that form due to imperfections in residue packing or the rotational and conformational movement of amino acids. In this work, we used the fluorescent probe 1-aminoanthracene (AMA) to detect a small ligand pocket in the hydrophobic core of human proliferating cell nuclear antigen (PCNA), which is a critical protein for DNA replication and repair. Fluorescence measurements of AMA reported that the core of PCNA had a dielectric constant (ε) of 4, which was very apolar and similar to cyclohexane (ε = 2). Protein mutagenesis, photoaffinity labeling, and molecular dynamics simulations localized the binding site for AMA …

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

Current State And Needs Of Clinical Laboratories In Latin America: A Cross-Country Assessment., Alejandro R. Molinelli, Elizabeth L. Palavecino, José C. Jara-Aguirre, Kerry Cosby, Allison Targowski, Barbara Goldsmith, Rosa Sierra-Amor, Juan D. García, Alicia Algeciras-Schimnich, Eugenio H. Zabaleta, Veronica I. Luzzi, Jessica M. Colón-Franco

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The Association for Diagnostics & Laboratory Medicine (ADLM) aims to improve health by providing education to laboratory scientists worldwide. Different regions of the world face unique challenges shaped by their national and regional contexts. However, the needs of clinical laboratories worldwide remain largely understudied. To address this gap, we conducted a comprehensive needs assessment survey among laboratory professionals in the Latin American region. The survey was distributed to over 2708 individuals across Latin American countries and yielded 148 responses. Most respondents were from urban areas (74%) and worked in private hospital laboratories (45%), with microbiology (25%) and chemistry (23%) identified …

Nano-Bio Interfacial Effects Modulating Protein Adsorption In Dialdehyde Lentinan-Crosslinked Polysaccharide Sponges Reinforced With Zein Nanoflowers, Dorota Chelminiak-Dudkiewicz, Miloslav Machacek, Hana Janová, Klara Konecna, Ondrej Jandourek, Jana Kejmarová, Kinga Mylkie, Aleksander Smolarkiewicz-Wyczachowski, Marta Ziegler-Borowska

The Brown Foundation: Institute of Molecular Medicine

The interfacial organization of porous biomaterials critically influences protein adsorption and subsequent cell-material interactions at hydrated biointerfaces relevant to wound-contacting environments. Herein, hybrid sponges were developed by rationally assembling chitosan, lentinan, levan, and fucoidan into a covalently defined macromolecular network featuring nano-bio interfacial effects. The materials were designed to modulate interfacial biological performance via engineered pore-wall structures, with protein-layer formation at sponge interfaces associated with downstream cell-material responses. A dialdehyde lentinan was deliberately employed to establish a chemically defined pore-wall interface via dense Schiff-base junctions with chitosan. The incorporation of zein nanoflowers introduced additional nanoscale structure features, providing additional anchoring …

Functional Characterization Of Uhrf1 Variants In Facilitating Dna Methylation, Bigang Liu, Kaila Nayvelt, Swanand Hardikar, Kimie Kondo, Marcos R Estecio, Xiaodong Cheng, Taiping Chen

The Brown Foundation: Institute of Molecular Medicine

Ubiquitin-like with plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) is essential for DNA methylation inheritance. However, the functional impacts of several natural and engineered UHRF1 variants are either insufficiently characterized or obscured by conflicting results, with some discrepancies likely stemming from cellular toxicity and adaptive responses induced by DNA methylation changes. In this study, we utilized mouse embryonic stem cells (mESCs)-which uniquely tolerate the complete loss of DNA methylation-to evaluate the functional consequences of clinical mutations, isoform variation, and epitope tagging. Using rescue experiments in Uhrf1-deficient mESCs, we characterized two UHRF1 mutations identified in …

Erk-Mediated Phosphorylation Of Yap Defines A Noncanonical Fgf Signaling Mechanism In Stem Cells, Xiaolei Zhao, Shannon Erhardt, Li Tang, Xiaotong Chen, Stephen M Farmer, Zixiu Cheng, Wen Chen, Ella Ziyuan Lu, Kihan Sung, Chang-Ru Tsai, Mingjie Zheng, Sheng Zhang, Yang Liu, Jianxin Wang, Min Li, James F Martin, Jun Wang

Faculty, Staff and Student Publications

While Fgf and Hippo-Yap signaling are fundamental for proper development, homeostasis, and disease, their crosstalk remains largely unknown. Here, we identified that Yap and Taz, canonical Hippo effectors, function as noncanonical effectors of Fgf signaling to maintain the proper function of neural crest (NC) lineages. NC cells are a multipotent stem cell population during vertebrate embryogenesis that contribute to numerous structures and diverse cell lineages, including craniofacial and cardiac tissues, neurons, and suture mesenchymal cells (SMCs), a specified cell population required for cranial bone growth and repair. We observed that activation of Fgf signaling in NC cells and NC-derived SMCs …

Clinical Document Metadata Extraction: A Scoping Review, Kurt Miller, Qiuhao Lu, William Hersh, Kirk Roberts, Steven Bedrick, Andrew Wen, Hongfang Liu

Faculty, Staff and Student Publications

Objectives: Clinical document metadata, such as document type, structure, author role, medical specialty, and encounter setting, is essential for accurate interpretation of information captured in clinical documents. However, vast documentation heterogeneity and drift over time challenge harmonization of document metadata. Automated extraction methods have emerged to coalesce metadata from disparate practices into target schema. This scoping review aims to catalog research on clinical document metadata extraction, identify methodological trends and applications, and highlight gaps warranting further investigation.

Methods: We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to identify articles from Ovid …

Medadl: High-Throughput Information Extraction Of Functional Status From Electronic Health Records To Advance Frailty Assessment In Older Adults, Sunyang Fu, Zhiyi Yue, Jennyly T Nguyen, Huipeng Liu, Jaerong Ahn, Vanessa Ramirez, Jude Des Bordes, Hongfang Liu, Min Ji Kwak, Nahid J Rianon

Faculty, Staff and Student Publications

Background: Functional status is essential for assessing frailty and planning care in older adults but is often under-documented in the structured fields of electronic health records. Manual chart review can capture functional status information but is labor-intensive and time-consuming. In this study, we developed and validated a scalable natural language processing (NLP) model to extract functional status information from unstructured electronic health record (EHR) notes.

Methods: This retrospective cohort study included 110 older adults seen at a geriatric osteoporosis clinic. A large language model-augmented symbolic NLP pipeline (MedADL) was developed to extract activities of daily living (ADL) and instrumental activities …

A Phase-Ii Randomized Controlled Pilot Study Of Nicotinamide Riboside Supplementation In Older Adults With Amnestic Mild Cognitive Impairment, Christopher Martens, Kevin Decker, Theodore Deconne, Faria Sanjana, Fiona Horvat, Nicholas Rizzi, Catherine Awad, Elizabeth Habash, Joshua Hobson, Mary Kramer, Michael Armstrong, Nichole Reisdorph, Ryan Pohlig, Alyssa Lanzi, Curtis Johnson, Matthew Cohen, James Ellison

Department of Psychiatry and Human Behavior Faculty Papers

INTRODUCTION: Declining nicotinamide adenine dinucleotide (NAD+) may elevate risk of Alzheimer's disease.

METHODS: We conducted a 12-week double-blind, randomized, placebo-controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD+ precursor, nicotinamide riboside (NR), for enhancing cognitive function and cerebral blood flow (CBF) in adults with amnestic mild cognitive impairment (aMCI).

RESULTS: 42 participants completed the study (NR = 22, placebo = 20). Adherence was similar between groups with no serious adverse effects. Blood NAD+ increased twofold in the NR group. There were no improvements in cognitive function (primary outcome), total CBF, or blood pressure (secondary outcomes). …

Functional Assessment Of A Convergent Gene Network Underlying Allergic Diseases And Ige., Pradeep Eranti, Raphaël Vernet, Christophe Linhard, Bing Ge, Laura Beaumier, Anne-Marie Madore, Sébastien Chanoine, Bénédicte L. Tremblay, Xiaojian Shao, Isabelle Pin, Mark Lathrop, Elin Grundberg, Valérie Siroux, Tomi Pastinen, Catherine Laprise, Emmanuelle Bouzigon, Florence Demenais

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The relationships between allergic diseases (AD) and IgE levels are complex.

OBJECTIVE: We sought to identify genes associated with AD and IgE having close proximity in the interactome and to elucidate the associated biological mechanisms.

METHODS: We integrated a comprehensive interactome with data from genome-wide (GWAS) and epigenome-wide (EWAS) association studies of AD and IgE levels, respectively. We used the SigMod algorithm to identify gene modules enriched in AD- and IgE-associated signals. We performed a connectivity analysis of these two modules to characterize direct cross-trait connections. Finally, we conducted an in-depth functional analysis of the directly-connected AD and IgE …

Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).

METHODS: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were …

High-Throughput Quantitation Of Pathogen-Induced Calcium Signals Captured Through Live-Cell Fluorescence Microscopy, J Thomas Gebert, Ethan M Huleatt, Francesca J Scribano, Michael R Eledge, Lauren E Dorn, Sammy K Hasmi, Joseph M Hyser

Faculty, Staff and Students Publications

Many intracellular pathogens manipulate host cell calcium to facilitate their survival and replication. Live-cell microscopy using fluorescent calcium indicators has become an indispensable tool for characterizing the mechanisms underlying both homeostatic and pathogen-induced cellular calcium dynamics, but such imaging must be coupled with robust quantitative analysis. Further, calcium imaging is most powerful when paired with reductive studies targeting calcium-modulating proteins. The lack of specific inhibitors or agonists to directly target most pathogen-induced calcium signals precludes many of the approaches that have allowed for robust characterization of major eukaryotic cell calcium signaling mechanisms, such as ER Ca2+ release by inositol triphosphate …

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …

Blinded, Bias-Controlled Multi-Rater Evaluation Of Human-Versus-Ai Brain Metastasis Segmentation Using A Hybrid Foundation-Model Framework, Yiding Han, Enze Zhu, Mhd Hasan Ai Mekdash, Omar Awad, Piyush Pathak, Shixiao Liang, Daniel Allan Hamstra, Xizhe Zhang, Zaid Ali Siddiqui, Baozhou Sun

Faculty, Staff and Students Publications

Background: Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance.

Purpose: To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment.

Methods: TUM-SAM integrates nnU-Net-based lesion detection with a …

Crispr/Cas9-Based Genome Editing: Understanding Differences In Dna Repair Pathways, Profiles, And Outcomes, Samuel Effah, Shirley Barrera, Nahia Urturi Ortiz, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the …