Neurosciences Commons^™

Subpial Resection Of Epileptogenic Tubers: Operative Nuances And Lessons Learned, Nisha Giridharan, Collin W English, Marcus Wong, Howard L Weiner

Faculty, Staff and Students Publications

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder. Tubers of the central nervous system are a hallmark of the disorder and often cause epilepsy. Many TSC patients fail to achieve seizure control with medication alone. Several case series have demonstrated high seizure freedom rates after resective surgery. However, the technique for the resection of epileptogenic tubers has largely been unreported. Here the authors present 2 cases to illustrate their multistage approach for localizing and resecting the seizure onset zone in patients with TSC. At their institution, they have excellent seizure outcomes and a low complication rate with this …

Resting State Electroencephalographic Brain Activity In Neonates Can Predict Age And Is Indicative Of Neurodevelopmental Outcome, Amir Ansari, Kirubin Pillay, Emad Arasteh, Anneleen Dereymaeker, Gabriela Schmidt Mellado, Katrien Jansen, Anderson M. Winkler, Gunnar Naulaers, Aomesh Bhatt, Sabine Van Huffel

School of Medicine Publications

Objective: Electroencephalography (EEG) can be used to estimate neonates' biological brain age. Discrepancies between postmenstrual age and brain age, termed the brain age gap, can potentially quantify maturational deviation. Existing brain age EEG models are not well suited to clinical cot-side use for estimating neonates' brain age gap due to their dependency on relatively large data and pre-processing requirements.

Methods: We trained a deep learning model on resting state EEG data from preterm neonates with normal neurodevelopmental Bayley Scale of Infant and Toddler Development (BSID) outcomes, using substantially reduced data requirements. We subsequently tested this model in two independent datasets …

A Multimodal Deep Learning Tool For Detection Of Junctional Ectopic Tachycardia In Children With Congenital Heart Disease, Yilong Ju, Jamie L S Waugh, Satpreet Singh, Craig G Rusin, Ankit B Patel, Parag N Jain

Faculty, Staff and Students Publications

BACKGROUND: Junctional ectopic tachycardia (JET) is a prevalent life-threatening arrhythmia in children with congenital heart disease. It has a marked resemblance to normal sinus rhythm, often leading to delay in diagnosis and management.

OBJECTIVE: The study sought to develop a novel multimodal automated arrhythmia detection tool that outperforms existing JET detection tools.

METHODS: This is a cohort study performed on 40 patients with congenital heart disease at Texas Children's Hospital. Electrocardiogram and central venous pressure waveform data produced by bedside monitors are captured by the Sickbay platform. Convolutional neural networks (CNNs) were trained to classify each heartbeat as either normal …

Perinatal Mental Healthcare Utilization Among Patients With Placenta Accreta Spectrum, Sarah R Casey, Alison N Goulding, Christina C Reed, Amir A Shamshirsaz, Hennie A Lombaard, Michael A Belfort, Lisa M Noll, Karin A Fox

Faculty, Staff and Students Publications

No abstract provided.

The Relationship Between Diet, Depression, And Alzheimer's Disease: A Narrative Review, Hilal Salim Said Al Shamsi, Stephanie R. Rainey-Smith, Samantha L. Gardener, Hamid R. Sohrabi, Rodrigo Canovas, Ralph N. Martins, Warnakulasuriya Mary Ann Dipika Binosha Fernando

Research outputs 2022 to 2026

Purpose of Review: This narrative review evaluates the role of diet in the relationship between depression and Alzheimer's disease (AD). Recent Findings: AD and depression are often comorbid, and depression appears to independently increase the future risk of AD. Evidence suggests diet influences the risk of both conditions directly and indirectly. Diet impacts neurochemical and biological processes that may affect the development and progression of depression and cognitive dysfunction. The dietary components offering the greatest protection against depression and AD are yet to be determined. Current evidence highlights the importance of polyphenolic compounds, folate, B vitamins, and polyunsaturated fatty acids, …

Verbal Learning And Memory Deficits Across Neurological And Neuropsychiatric Disorders: Insights From An Enigma Mega Analysis, Eamonn Kennedy, Spencer W Liebel, Hannah M Lindsey, Shashank Vadlamani, Pui-Wa Lei, Maheen M Adamson, Martin Alda, Silvia Alonso-Lana, Tim J Anderson, Celso Arango, Robert F Asarnow, Mihai Avram, Rosa Ayesa-Arriola, Talin Babikian, Nerisa Banaj, Laura J Bird, Stefan Borgwardt, Amy Brodtmann, Katharina Brosch, Karen Caeyenberghs, Vince D Calhoun, Nancy D Chiaravalloti, David X Cifu, Benedicto Crespo-Facorro, John C Dalrymple-Alford, Kristen Dams-O'Connor, Udo Dannlowski, David Darby, Nicholas Davenport, John Deluca, Covadonga M Diaz-Caneja, Seth G Disner, Ekaterina Dobryakova, Stefan Ehrlich, Carrie Esopenko, Fabio Ferrarelli, Lea E Frank, Carol E Franz, Paola Fuentes-Claramonte, Helen Genova, Christopher C Giza, Janik Goltermann, Dominik Grotegerd, Marius Gruber, Alfonso Gutierrez-Zotes, Minji Ha, Jan Haavik, Charles Hinkin, Kristen R Hoskinson, Daniela Hubl, Andrei Irimia, Andreas Jansen, Michael Kaess, Xiaojian Kang, Kimbra Kenney, Barbora Keřková, Mohamed Salah Khlif, Minah Kim, Jochen Kindler, Tilo Kircher, Karolina Knížková, Knut K Kolskår, Denise Krch, William S Kremen, Taylor Kuhn, Veena Kumari, Junsoo Kwon, Roberto Langella, Sarah Laskowitz, Jungha Lee, Jean Lengenfelder, Victoria Liou-Johnson, Sara M Lippa, Marianne Løvstad, Astri J Lundervold, Cassandra Marotta, Craig A Marquardt, Paulo Mattos, Ahmad Mayeli, Carrie R Mcdonald, Susanne Meinert, Tracy R Melzer, Jessica Merchán-Naranjo, Chantal Michel, Rajendra A Morey, Benson Mwangi, Daniel J Myall, Igor Nenadić, Mary R Newsome, Abraham Nunes, Terence O'Brien, Viola Oertel, John Ollinger, Alexander Olsen, Victor Ortiz García De La Foz, Mustafa Ozmen, Heath Pardoe, Marise Parent, Fabrizio Piras, Federica Piras, Edith Pomarol-Clotet, Jonathan Repple, Geneviève Richard, Jonathan Rodriguez, Mabel Rodriguez, Kelly Rootes-Murdy, Jared Rowland, Nicholas P Ryan, Raymond Salvador, Anne-Marthe Sanders, Andre Schmidt, Jair C Soares, Gianfranco Spalleta, Filip Španiel, Scott R Sponheim, Alena Stasenko, Frederike Stein, Benjamin Straube, April Thames, Florian Thomas-Odenthal, Sophia I Thomopoulos, Erin B Tone, Ivan Torres, Maya Troyanskaya, Jessica A Turner, Kristine M Ulrichsen, Guillermo Umpierrez, Daniela Vecchio, Elisabet Vilella, Lucy Vivash, William C Walker, Emilio Werden, Lars T Westlye, Krista Wild, Adrian Wroblewski, Mon-Ju Wu, Glenn R Wylie, Lakshmi N Yatham, Giovana B Zunta-Soares, Paul M Thompson, Mary Jo Pugh, David F Tate, Frank G Hillary, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest …

Assessing The Effects Of Repetitive Mild Traumatic Brain Injury On Risk/Reward Decision Making And Catecholamine Associated Proteins, Christopher Knapp

Theses and Dissertations

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior; however, the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific are unknown. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. Here, we exposed rats to sham (no injury), single, or three closed-head controlled cortical impact (CH-CCI) injuries to characterize the effects of rmTBI on 1) risk/reward decision making behavior using a probabilistic discounting task (PDT) and 2) levels …

Physiological And Circadian Outcomes Of Fkbp5 Imbalance: Insights From Two Models, Niat Tsegai Gebru

USF Tampa Graduate Theses and Dissertations

Circadian rhythms are crucial in regulating various physiological processes, including mood regulation, and disruptions in these rhythms have been linked to several neuropsychiatric disorders, such as depression, bipolar disorder, and schizophrenia. FKBP51, a protein involved in stress responses and glucocorticoid receptor function has emerged as a potential regulator of the circadian clock. FKBP51’s interaction with glucocorticoid receptors impacts the transcriptional regulation of circadian-related genes. In recent years, FKBP51 has been associated with genetic and epigenetic alterations in neuropsychiatric disorders, highlighting its potential as a target for intervention. The heterogeneity associated with neuropsychiatric disorders arises from a combination of genetic, environmental, …

Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee

USF Tampa Graduate Theses and Dissertations

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2T61I mutation being the most widely studied. We generated the first transgenic mouse models expressing human CHCHD2WT and the PD-linked CHCHD2T61I mutation driven by the mPrP promoter. CHCHD2T61I Tg, but not CHCHD2WT Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, …

The Role Of Spontaneous Activity In Maturation Of The Calyx Of Held Nerve Terminal And Its Synaptic Target In The Medial Nucleus Of The Trapezoid Body, Daniel Tatsuo Heller

USF Tampa Graduate Theses and Dissertations

Neural circuit formation is a complex process involving synergistic roles between neurons and glial cells regulated by coordinated genetic and molecular cues and activity-dependent mechanisms. The canonical pathway for synapse formation begins with neurogenesis and migration followed by axonal outgrowth and dendritic arborization allowing for the capture and formation of nascent synapses. These initial synaptic contacts are exuberant in nature ensuring proper neural connectivity and undergo a period of pruning of superfluous inputs followed by maturation and strengthening of the remaining contacts. This maturation includes pre- and postsynaptic specialization of the active zone, localization and clustering of ion channels, and …

Gait Initiation Alone May Be Insufficient To Identify A Neuromuscular Mechanism Underlying Concussion-Related Kinematic Alterations, Tyler A. Wood, Rafael Casas, Chris Hill, Nicholas E. Grahovec

Internet Journal of Allied Health Sciences and Practice

Purpose: Concussions create significant long-term health consequences, such as kinematic alterations, which may contribute to lower extremity musculoskeletal injury, dexterity limitations, disability, and declines in quality of life. A potential movement test that may identify neuromuscular mechanisms underlying these kinematic alterations is gait initiation. Gait initiation can assess preparatory postural adjustments as an individual transitions from static balance to voluntary movement. Thus, this study aims to examine muscle activation latency of individuals who sustained a concussion 3 to 24 months prior to testing, compared to healthy controls, during gait initiation tasks. Methods: This case-control study included 32 individuals who sustained …

The Crosstalk Between Amyloid-Β, Retina, And Sleep For The Early Diagnosis Of Alzheimer's Disease: A Narrative Review, Isaiah Lorenzo De Guia, Shaun Eslick, Sharon L. Naismith, Swathi Kanduri, Tejal M. Shah, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-β (Aβ) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. …

Ephrin-B2 Promotes Nociceptive Plasticity And Hyperalgesic Priming Through Ephb2-Mnk-Eif4e Signaling In Both Mice And Humans, Eric David, Muhammad Saad Yousuf, Hao-Ruei Mei, Ashita Jain, Sharada Krishnagiri, Hajira Elahi, Rupali Venkatesan, Kolluru Srikanth, Gregory Dussor, Matthew Dalva, Theodore Price

Department of Neuroscience Faculty Papers

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines …

Neuroimaging Of Vermiform Giant Arachnoid Granulations In Children, Oswaldo A Guevara Tirado, Livja Mertiri, Stephen F Kralik, Nilesh K Desai, Thierry A G M Huisman, Maarten H Lequin, Huy Brandon D Tran

Faculty, Staff and Students Publications

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed 'giant' arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus' lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, …

Riluzole For Degenerative Cervical Myelopathy: A Secondary Analysis Of The Csm-Protect Trial, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Jetan H. Badhiwala, Henry Ahn, H. Francis Farhadi, Christopher I. Shaffrey, Ahmad Nassr, Praveen Mummaneni, Paul M. Arnold, Bradley Jacobs, K. Daniel Riew, Michael Kelly, Darrel S. Brodke, Alexander R. Vaccaro, Alan S. Hilibrand, Jason Wilson, James S. Harrop, S. Timm Yoon, Kee D. Kim, Daryl R. Fourney, Carlo Santaguida, Eric M. Massicotte, Peng Huang

School of Medicine Faculty Publications

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical …

Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …

Protocol For Preclinical Evaluation Of Locoregionally Delivered Car T Cells In Patient-Derived Xenograft Models Of Brain Tumors, Benjamin Draper, Chantelle Bowers, Eleni Vassalou, Ailsa Greppi, John Anderson, Nabil Ahmed, Michael D Taylor, Laura K Donovan

Faculty, Staff and Students Publications

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Antidepressant Effect Of Enzymatic Porcine Placenta Hydrolysate In Repeated Immobilization Stress-Induced Ovariectomized Female Mice, Minsook Ye, Sharon Nguyen, Min Ju Kim, Jee Sun Hwang, Gun Won Bae, Keun-Hang Susan Yang, Insop Shim

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic …

Association Of Basal Forebrain Atrophy With Cognitive Decline In Early Alzheimer Disease, Ying Xia, Vincent Dore, Jurgen Fripp, Pierrick Bourgeat, Simon M. Laws, Christopher J. Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff

Research outputs 2022 to 2026

Background and Objectives: In early Alzheimer disease (AD), β-amyloid (Aβ) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD.

Methods: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aβ-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aβ status, yielding groups …

Cannabis Exposure During Pregnancy And Neural Mechanisms Of Parenting: Assessing Neural Responses To Infant Cues And Parenting Outcomes, Shannon Powers

Electronic Theses and Dissertations

As legalization of cannabis and cannabinoids spreads in the United States, access and use of cannabis during the prenatal period has increased. There is limited knowledge on the effects of prenatal cannabis use on the parental brain. One way to identify potential effects of cannabis on parenting is through studying parenting brain functions and behavior. Cannabis use disorder (CUD) has been shown to be associated with lower positive parenting and lower sensitivity to infants, but it is unclear by what mechanisms. The following two studies address this gap in knowledge by examining the association between cannabis use during the prenatal …

In-Silico Analysis Of Tmem2 As A Pancreatic Adenocarcinoma And Cancer-Associated Fibroblast Biomarker, And Functional Characterization Of Nsc777201, For Targeted Drug Development, Prateeti Srivastava, Vijesh Kumar Yadav, Tzu-Hao Chang, Emily Chia-Yu Su, Bashir Lawal, Alexander Th Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Pancreatic adenocarcinoma (PAAD), known as one of the deadliest cancers, is characterized by a complex tumor microenvironment, primarily comprised of cancer-associated fibroblasts (CAFs) in the extracellular matrix. These CAFs significantly alter the matrix by interacting with hyaluronic acid (HA) and the enzyme hyaluronidase, which degrades HA - an essential process for cancer progression and spread. Despite the critical role of this interaction, the specific functions of CAFs and hyaluronidase in PAAD development are not fully understood. Our study investigates this interaction and assesses NSC777201, a new anti-cancer compound targeting hyaluronidase. This research utilized computational methods to analyze gene expression data …

Sars-Cov-2 Neurotropism: Understanding Effects At The Blood-Brain Barrier And Hematogenous Neuroinvasiveness, Taylor E. Martinez

USF Tampa Graduate Theses and Dissertations

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has provisional counts of over 110 million documented cases and 1.218 million deaths (as of February 2024) in the United States since January 2020. SARS-CoV-2 is an airborne respiratory virus that primarily infects the lungs via the ACE2 receptor but has well-documented secondary target organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it …

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …

Rigor And Reproducibility In Human Brain Organoid Research: Where We Are And Where We Need To Go, Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Cross-Iddrc Human Stem Cell Consortium, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao

Faculty, Staff and Students Publications

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

Ethical, Legal, And Policy Challenges In Field-Based Neuroimaging Research Using Emerging Portable Mri Technologies: Guidance For Investigators And For Oversight, Francis X. Shen, Susan M. Wolf, Frances P. Lawrenz, Donnella S. Comeau, Kafui Dzirasa, Barbara J. Evans, Damien A. Fair, Martha J. Farah, Duke Han, Judy Illes, Jonathan D. Jackson, Eran Klein, Karen S. Rommelfanger, Matthew S. Rosen, Efraín Torres, Paul Tuite, J. Thomas Vaughan, Michael Garwood

UF Law Faculty Publications

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG’s consensus recommendations. These recommendations address technology quality control, design …

Cost-Effectiveness And Threshold Analysis Of Deep Brain Stimulation Vs Treatment-As-Usual For Treatment-Resistant Depression, Katherine E Kabotyanski, Ricardo A Najera, Garrett P Banks, Himanshu Sharma, Nicole R Provenza, Benjamin Y Hayden, Sanjay J Mathew, Sameer A Sheth

Faculty, Staff and Students Publications

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare …

Fine-Tuning Gene Expression: A Novel Therapeutic Approach For Rett Syndrome, Yewon Rhee

Master's Theses

Rett Syndrome (RTT) is a neurodevelopmental disorder that is characterized by a myriad of debilitating symptoms impacting nearly every aspect of life, including motor and gait impairment, social and cognitive deficits, as well as seizures and breathing abnormalities. RTT is caused by X-linked de novo loss-of-function mutations in the methyl-CpG binding protein 2 gene (MECP2), which is an essential epigenetic modulator. Any cure for RTT must directly target MECP2, a highly dosage-sensitive gene. This thesis developed a novel MECP2-targeted therapeutic approach using site-blocking antisense oligonucleotides to prevent microRNA-induced repression of MECP2, allowing fine-tuned control of gene expression. Here we report …

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

A Process To Reanalyze Clinical Dna Sequencing Data For Biomarker Matching In The Lung-Map Master Protocol, Joel W Neal, Katherine Minichiello, Ryan Brennick, Richard S P Huang, Matthew C Hiemenz, Cornel Amler, Jyoti Patel, Roy Herbst, Karen L Reckamp, Hossein Borghaei, Louise Highleyman, Mary W Redman, Lincoln W Pasquina, David E Kozono

Faculty, Staff and Student Publications

For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.7%) using GDR for Lung-MAP, with a median time from request to result of 9 days. During the same period, 691 of 791 (87.4%) …