Digital Commons Network^™

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Peripheral Blood Gene Expression Profiling And Prognostic Significance For The Course Of Interstitial Lung Disease In Patients With Systemic Sclerosis, Shervin Assassi, Christopher P Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan

Faculty, Staff and Student Publications

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated …

Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein Ftsz Potentially Disrupt Slma-Mediated Nucleoid Occlusion And Reversible Biomolecular Condensation, Marta Sobrinos-Sanguino, Inés Barros-Medina, Lorenzo Suigo, Alessia Lanzini, Ermanno Valoti, William Margolin, Valentina Straniero, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring …

Molecular And Immunological Features Associated With Long-Term Benefits In Metastatic Nsclc Patients Undergoing Immune Checkpoint Blockade, Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Adrià Rossell, Xavier Villanueva, Mario Giner, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola

Faculty, Staff and Student Publications

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. …

Caspase 3-Specific Cleavage Of Ubiquitin-Specific Peptidase 48 Enhances Drug-Induced Apoptosis In Aml, Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong

Faculty, Staff and Student Publications

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

Meniscal Repair In The Setting Of Revision Anterior Cruciate Ligament Reconstruction: 6-Year Follow-Up Results From The Mars Cohort, Jake A Fox, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Daniel E Cooper, Thomas M Deberardino, Warren R Dunn, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, Annunziato Ned Amendola, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler V, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Col Ret Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York, Rick W Wright

Faculty, Staff and Student Publications

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented.

Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair.

Study design: Prospective cohort study; Level of evidence, 2.

Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Assessing The Impact Of Maternal Oral Health On The Risk Of Adverse Birth Outcomes, May Amr Salama

Health Services Research Dissertations

Preterm birth (PTB) and low birth weight (LBW) are leading causes of neonatal morbidity and mortality. Maternal periodontal disease (PD) has been increasingly linked to these adverse birth outcomes (ABOs), yet questions about causality and treatment effectiveness persist due to study design heterogeneity and potential unmeasured confounding. These gaps hinder the development of clear clinical and public health guidelines. This dissertation addresses these gaps through three interconnected studies assessing the relationship between maternal oral health and ABOs.

The first study employed a meta-epidemiological analysis of 62 original studies from nine systematic reviews to evaluate the impact of unmeasured confounding on …

Graduate Physical Therapy Students Perceived Benefit Of Prior Anatomy Experiences Following Their First Semester Graduate Physical Therapy Anatomy Course, Austin Alexander

EVMS School of Health Professions Theses & Dissertations

Human anatomy stands as a cornerstone prerequisite for admission into graduate-level Physical Therapy Programs. As such, prior anatomy experiences need to prepare students for success in graduate-level coursework. However, studies have demonstrated that undergraduate anatomy courses vary in their ability to predict success in graduate Physical Therapy anatomy coursework. This research aimed to utilize students' perceptions of their undergraduate anatomy experiences to predict grades in graduate-level Physical Therapy anatomy coursework. The multinomial logistic regression in this study revealed that the absence of perceived preparedness was a significant predictor of membership in the C graduate anatomy grade group. Students who did …

Decomposition Processes And Insect Indicators In Forensic Investigations, Eli Taylor

University Honors Theses

Insects play an essential biological and ecological role in human life, and their predictable relationship with decomposing remains has positioned them as a cornerstone of modern forensic science. Since the early 20th century, forensic entomology has provided critical evidence for estimating the postmortem interval (PMI), relying on patterns of colonization, species succession, and insect developmental timelines. Accurate PMI estimations are vital to medicolegal investigations, influencing the interpretation of biological evidence, guiding resource allocation, and informing determinations of cause and manner of death. However, insect activity is profoundly shaped by environmental and ecological variables, including temperature, humidity, seasonal shifts, and geographic …

Decorin Deficiency Promotes D-Galactose-Induced Skeletal Muscle Atrophy And Fibrosis By Regulating Itgb1/Akt/Mtor Signalling Pathway, Xiaoqin Luo, Mengxue Zhang, Lili Chen, Ruichang Wang, Jiabing Lian, Zhe Yang, Renato V. Iozzo, Jin Wang, Yan Zhang, Xiuli Bi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Primary sarcopenia is an age-associated disorder with progressive and generalised loss of skeletal muscle strength and mass. Skeletal muscle fibrosis is one of the significant pathological manifestations of age-associated sarcopenia. Decorin, a small dermatan-sulfate proteoglycan, participates in extracellular matrix assembly. In numerous studies, the involvement of decorin is not restricted to matrix structural proteins, and it also affects a diverse variety of biological functions like cell growth, adhesion, migration, proliferation and differentiation. Additionally, it modulates the process of inflammation and fibrillogenesis. Based on these preclinical evidences, we hypothesised that decorin may potentially play an important role in skeletal muscles …

High Test-Retest Reliability Of Nucleus Accumbens Activity During Reward Anticipation, Nathaniel Bouton

Graduate Theses and Dissertations

Recent research has questioned the reliability of Functional Magnetic Resonance Imaging (FMRI). The findings suggest poor test-retest reliability of FMRI measures across brain areas and tasks, and specifically in subcortical brain areas during reward-related tasks. Further, data from the Adolescent Brain Cognitive Development (ABCD) study showed low reliability and low stability of the fitted coefficients from whole-brain regression analyses of the Monetary Incentive Delay (MID) task. However, optimizing methods might improve reliability, for example: (1) acquiring single-band rather than multi-band FMRI sequences, (2) extracting raw activity rather than fitted coefficients, and (3) honing analyses to target brain areas during specific …

Linking Training To Confidence: A Literature Review On Advancing Nutrition Environments In Child Care Programs, Jeanne M. Vanorsdal

Capstone Experience: Master of Public Health

This comprehensive literature review examined child care nutrition training interventions using the Health Belief Model (HBM) to understand how to increase providers’ ability to serve nutritious food. By analyzing HBM constructs such as perceived severity, benefits, and barriers, the review assessed how training influences provider abilities and identified barriers and facilitators to consistently offering healthy meals and snacks. Studies were 1) published in English; 2) research conducted in the United States; 3) population involved home-based or center-based child care providers caring for children from birth to age 5; 4) articles published from January 1, 2015, to October 5, 2025; 5) …

Abca4-Mutant Human Retinal Organoids Sequencing Reveals Organoids Application In Inherited Retinal Diseases, Yourong Bao, Sujung Soh, Jean Li, Zhen Zuo, Salma Ferdous, Xinye Qian, Jin Li, Jiaxiong Lu, Xuesen Cheng, Anna Matynia, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

In the studies of Inherited Retinal Diseases (IRDs), the knockout of traditional animal models like mice often fails to accurately replicate human phenotypes due to genetic and anatomical differences. Human retinal organoids (ROs) derived from stem cells have emerged as promising developmental models in retinal studies to delineate cell growth, but their ability to represent the characteristics of late-onset IRDs remains unclear. This study aims to validate ROs as a disease model for Stargardt's Disease (STGD) caused by ABCA4 mutations. Using single-cell RNA sequencing, ROs from 2 STGD patients were compared with healthy control-derived ROs at two developmental stages on …

Adenovirus Types In Us Children Hospitalized Or Seen In The Emergency Department With Acute Respiratory Illness, 2016-2019, Tess Stopczynski, Varvara Probst, Adam Gailani, Justin Z Amarin, Olla Hamdan, Haya Hayek, Laura S Stewart, Herdi K Rahman, Rangaraj Selvarangan, Jennifer E Schuster, Christopher J Harrison, Mary E Moffatt, Marian G Michaels, John V Williams, Julie A Boom, Leila C Sahni, Vasanthi Avadhanula, Mary Allen Staat, Elizabeth P Schlaudecker, Christina Quigley, Geoffrey A Weinberg, Peter G Szilagyi, Janet A Englund, Eileen J Klein, Aaron T Curns, Heidi L Moline, Ariana P Toepfer, James D Chappell, Andrew J Spieker, Natasha B Halasa

Faculty, Staff and Students Publications

Background: Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI), contributing to 5-13% of cases worldwide. Clinical manifestations vary by HAdV species and type; therefore, delineating type-specific disease presentations and understanding severity of specific HAdV types' disease may help develop targeted interventions.

Methods: We conducted a multicenter, prospective study within the New Vaccine Surveillance Network to characterize HAdV types. Children < 18 years old with ARI were enrolled in the emergency department or inpatient setting at 7 US children's hospitals from 1 December 2016 to 30 November 2019. Respiratory specimens were collected and tested for HAdV and other viruses. Subsequently, typing was conducted on HAdV specimens using single-plex real-time PCR assays targeting sequences in the hexon gene. Comparisons between HAdV types were performed to determine differences in characteristics and outcomes. Generalized linear mixed effects models were used to evaluate severity.

Results: Among the 1843 HAdV-positive cases, 1402 specimens (76%) were typed. The most common types detected were HAdV-C1 (n = 439), HAdV-C2 (n = 393), and HAdV-B3 (n = 221). Children with HAdV-B7 (n = 78) …

Bypassing Cisplatin Resistance In Nrf2 Hyperactivated Head And Neck Cancer Through Effective Pi3kinase Targeting, Pedram Yadollahi, Kelli A Mccord, Yang Li, Hussam Dayoub, Kalil Saab, Fonma Essien, Sean Hyslop, Emerald Kan, Kazi M Ahmed, Parker R Kirby, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Patricia Castro, Heath D Skinner, Cristian Coarfa, William K Decker, Abdullah A Osman, Rutulkumar Patel, Jeffrey N Myers, Stephen Y Lai, Nagireddy Putluri, Faye M Johnson, Mitchell J Frederick, William H Hudson, Vlad C Sandulache

Faculty, Staff and Students Publications

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g., NOTCH1 mutations).

Methods: Using state of the science mechanistic, metabolomic and spatial transcriptomic approaches combined with preclinical models of HNSCC, we tested whether a novel PI3K inhibitor, gedatolisib, can bypass hyperactivation of the Nrf2 pathway.

Results: The PI3K pathway is activated in …

Method For Generation And Ex Vivo Expansion Of Genetically Edited Mouse Tregs, Yosef Gilad, Adam M Dean, Yan Xia, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Regulatory T cells (Tregs) play a crucial role in the immune system, and their dysfunction can lead to the development of autoimmune conditions. In cancer, tumors frequently hijack the immunosuppressive function of Tregs to evade immune responses. Due to their central role in key pathological processes, Tregs have gained increasing attention as promising targets for various clinical applications. However, their relative scarcity (∼5% to 10% of CD4+ T cells) and instability presents a technical challenge for research and therapeutic development. In congenic animal models used to investigate autologous cell transfer-based therapies, this challenge is even greater, as Treg donor animals …

Rbm8a Deficiency Causes Hematopoietic Defects By Modulating Wnt/Pcp Signaling, Agnese Kocere, Elena Chiavacci, Charlotte Soneson, Seth T Jacobson, Emma N Harrison, Kevin Manuel Méndez-Acevedo, Jacalyn S Macgowan, Harrison H Wells, Max S Hiltabidle, Azhwar Raghunath, Jordan A Shavit, Daniela Panáková, Margot L K Williams, Mark D Robinson, Christian Mosimann, Alexa Burger

Faculty, Staff and Students Publications

Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic rbm8a zebrafish, we observe a reduction of cd41-positive thrombocytes. rbm8a-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced rbm8a …

Functional Head Tremor: Contrasting Features With Other Tremor Etiologies, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Background: Functional tremor (FT) is considered the most common phenomenology among patients with functional movement disorders (FMDs). Most patients have limb tremor, but they can also present with tremor involving the head and trunk.

Objectives and methods: We aimed to assess the clinical phenomenology of functional head tremor (FHT) and contrast it with features of HT observed in 125 patients with other tremor etiologies (OTE), including 71 patients with essential tremor (ET).

Results: There were 101 consecutive patients (68.3% females) with FT from which n = 36 (35.6%) had FHT. Yes-yes tremor was the most common directionality (47.2%). Functional trunk …

Feasibility Of Expiratory Muscle Strength Training In Individuals With Progressive Supranuclear Palsy, Katya Villarreal-Cavazos, James C Borders, James A Curtis, Jordanna S Sevitz, Nora Vanegas-Arroyave, Michelle S Troche

Faculty, Staff and Students Publications

Introduction: Dysphagia is common among individuals with Progressive Supranuclear Palsy (PSP). Expiratory muscle strength training (EMST) is a treatment used to increase expiratory muscle force production for airway protection deficits. To our knowledge, no studies have tested EMST in this population. The objective of this study was to determine the feasibility of EMST in individuals with PSP.

Methods: Twenty-nine participants completed baseline measures of maximum expiratory pressure and underwent a trial session of EMST. EMST was considered feasible if participants were able to complete at least 10 repetitions at 30% of their maximum expiratory pressure. Qualitative analyses were also completed …

A Multimodal Non-Invasive Approach For Intracranial Pressure Assessment: A Single-Center Study, Dana Klavansky, Helaina Lehrer, Aris Desai, Gabriela Keeton, Neha Dangayach, Alexandra Reynolds, Spyridoula Tsetsou

Faculty, Staff and Students Publications

Background: Intracranial pressure (ICP) monitoring is an integral part of acute brain injury management. While invasive ICP monitoring is the gold standard, there are several medical conditions that preclude its placement. The aim of the present study is to validate a multimodal approach for increasing ICP detection.

Material and methods: In this retrospective study, patients with acute brain injury who had an external ventricular drain (EVD) placement were included. We measured bilateral optic nerve sheath diameter (ONSD) and assessed for optic nerve disk elevation (ONDE) by using ocular ultrasound, bilateral middle cerebral artery pulsatility index (PI) by using transcranial Doppler, …

Exploration Of Zileuton Protective Mechanisms Against Vancomycin-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Rongjin Sun, Linh T Vuong, Luan D Truong, David Sheikh-Hamad, Masayuki Nigo, Ming Hu, Vincent H Tam

Faculty, Staff and Students Publications

Vancomycin is one of the most commonly used parenteral antibiotics for treating drug-resistant bacterial infections, however, it is hindered by nephrotoxicity. We previously demonstrated that zileuton could delay the onset of vancomycin-associated nephrotoxicity in rats. Here, we sought to understand the mechanism(s) of zileuton renal protection. Sprague-Dawley rats were administered vancomycin (200 mg/kg) and zileuton (1 and 4 mg/kg) daily for 10 days. After 3 days, kidneys were collected from select animals for histopathological analysis of renal injury. Single-dose vancomycin serum pharmacokinetics and renal tissue spatial distribution with adjuvant zileuton were evaluated. In vitro, proximal tubular cells were exposed …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Students Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Standard Complete Blood Count To Predict Long-Term Outcomes In Febrile Infection-Related Epilepsy Syndrome (Fires): A Multicenter Study, Martin Guillemaud, Aurélie Hanin, James J Riviello, Mario Chavez, Ayush Batra, Megan Berry, Francesca Bisulli, Carlos Castillo-Pinto, Carla Cobos-Hernandez, Sophie Demeret, Krista Eschbach, Raquel Farias-Moeller, Madeline Fields, Nicolas Gaspard, Elizabeth E Gerard, Teneille E Gofton, Margaret T Gopaul, Matthew D Gruen, Anthony D Jimenez, Karnig Kazazian, Minjee Kim, Marwa Mansour, Lara Marcuse, Clémence Marois, Mikaela Morales, Lorenzo Muccioli, Elena Pasini, Michelle M Pham, Santiago Philibert Rosas, Aaron F Struck, Nathan Torcida, Mark S Wainwright, Ji Yeoun Yoo, Eyal Muscal, Vincent Navarro, Lawrence J Hirsch, Yichen Lai

Faculty, Staff and Students Publications

Objective: We investigated whether complete blood count (CBC) analyses during intensive care unit stay could predict 12-month outcomes in patients with cryptogenic febrile infection-related epilepsy syndrome (FIRES), a subset of new-onset refractory status epilepticus (NORSE).

Methods: Outcomes at 12 months were classified as "unfavorable" (Glasgow Outcome Score [GOS] 1-3) or "favorable" (GOS 4-5). Demographic, clinical, and serial CBC data were collected across treatment phases: (1) no immunotherapy (before initiation or no treatment), (2) first-line immunotherapy, and (3) second-line immunotherapy. For each treatment phase, predictive models stratified outcomes based on CBC features using decision tree regression, with separate models for adults …

How Well Can Commonly Used Anxiety Scales Detect Treatment Outcomes In The Context Of Autism?, Huilin Chen, Jeffrey J Wood, Connor M Kerns, Eric A Storch, Philip C Kendall, Gaia Scerif, Cathy Creswell

Faculty, Staff and Students Publications

Anxiety is one of the most prevalent mental health challenges in autistic children, yet there is limited evidence on effective tools to measure treatment outcomes. Previous research with non-autistic children has found that the Child Anxiety Impact Scale, Parent Version achieved good diagnostic accuracy when measuring treatment outcomes and performed better than a commonly used symptom measure. However, this has not been evaluated for autistic children. The present study examined the psychometric properties of the Child Anxiety Impact Scale, Parent Version in autistic children and compared its utility against other anxiety symptom measures, to detect treatment outcomes as assessed by …

Loss Of The Lysosomal Protein Cln3 Triggers C-Abl-Dependent Yap1 Pro-Apoptotic Signaling, Neuza Domingues, Alessia Calcagni', Sofia Freire, Joana Pires, Ricardo Casqueiro, Ivan L Salazar, Niculin Joachim Herz, Tuong Huynh, Katarzyna Wieciorek, Tiago Fleming Outeiro, Henrique Girão, Ira Milosevic, Andrea Ballabio, Nuno Raimundo

Duncan NRI Faculty and Staff Publications

Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protein. Currently, no therapies targeting disease progression are available, largely because its molecular mechanisms remain poorly understood. To understand how CLN3 loss affects cellular signaling, we generated human CLN3 knock-out cells (CLN3-KO) and performed RNA-seq analysis. Our multi-dimensional analysis reveals the transcriptional regulator YAP1 as a key factor in remodeling the transcriptome in CLN3-KO cells. YAP1-mediated pro-apoptotic signaling is also increased as a consequence of CLN3 functional loss in retinal pigment …

Surgical Removal Of Implanted Microchips To Correct Mri Susceptibility Artifacts In Mice, Elizabeth Hipskind, Nicole Hernandez, Sydney Fox, Tina Manirambona, Rita Schack, Brian Gibson, Robia G Pautler

Center on Aging Staff Publications

Purpose: Implanted microchips are becoming increasingly common in research for animal identification and have been adopted by commercial vendors for some mouse strains. However, they often contain metal components, which generate magnetic susceptibility artifacts on MR images. Despite this, some microchips are marketed as MR-compatible, even though they are likely to affect image quality.

Methods: We assessed the impact of a radiofrequency identification microchip on MR images of the mouse brain and present a method for precise surgical removal. A handheld magnet was used to locate and stabilize the microchips during removal. Mice were imaged before and after microchip removal. …

Ataxia-Telangiectasia Mutated Activation Mediates Transforming Growth Factor Beta Signaling In Acetaminophen-Induced Liver Injury In Mice, Matthew Mcmillin, Christopher S Chu, Elaina Williams, Juliet Venter, Kiersten Bell, Anca D Petrescu, Patrick Mireles, Sharon Demorrow

Faculty and Staff Publications

Acetaminophen (APAP) overdose is associated with increased transforming growth factor beta 1 (TGFβ1) signaling and elevated oxidative stress, which exacerbate DNA damage. TGFβ1 has been shown to regulate ataxia-telangiectasia mutated (ATM) signaling and DNA repair in other cell types. This study investigates the DNA damage response (DDR) during APAP-induced liver injury, focusing on ATM-mediated regulation of TGFβ1 signaling. APAP administration in vitro and in vivo resulted in DNA damage, increased ATM signaling, accumulation of γH2AX, and activation of phosphorylated ataxia telangiectasia mutated (pATM) and phosphorylated checkpoint kinase 2 (pChk2). Pretreatment with an ATM inhibitor, KU55933, attenuated APAP-induced hepatocyte damage and …