Digital Commons Network^™

Feasibility Of Large Language Models For Ceus Li-Rads Categorization Of Small Liver Nodules In Patients At Risk For Hepatocellular Carcinoma, Jiayan Huang, Rui Yang, Xiaotong Huang, Keyu Zeng, Yan Liu, Jun Luo, Andrej Lyshchik, Qiang Lu

Department of Radiology Faculty Papers

BACKGROUND: Large language models (LLMs) offer opportunities to enhance radiological applications, but their performance in handling complex tasks remains insufficiently investigated.

PURPOSE: To evaluate the performance of LLMs integrated with Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) in diagnosing small (≤20mm) hepatocellular carcinoma (sHCC) in high-risk patients.

MATERIALS AND METHODS: From November 2014 to December 2023, high-risk HCC patients with untreated small (≤20mm) focal liver lesions (sFLLs), were included in this retrospective study. ChatGPT-4.0, ChatGPT-4o, ChatGPT-4o mini, and Google Gemini were integrated with imaging features from structured CEUS LI-RADS reports to assess their diagnostic performance for sHCC. …

Achieving Inter- And Transdisciplinarity In Ecohealth: Insights From A Rodent-Borne Disease Project In A Polycrisis Era, Isabelle Arpin, Clémence Massart, Vincent Bourret, Guillaume Castel, Valeria Carolina Colombo, Jana Eccard, Jasmin Firozpoor, Maciej Grzybek, Heikki A. Henttonen, Herwig Leirs, Andrew Mcmanus, Ben Roche, Tarja Sironen, Vincent Sluydts, Peter Stuart, Annetta Zintl, Nathalie Charbonnel

Publications

Introduction: Inter- and transdisciplinary research (ITDR) is increasingly promoted to address “wicked problems”, particularly in health sectors adopting approaches like Ecohealth. Our Ecohealth-inspired project on rodent-borne diseases, initiated just before the COVID-19 pandemic, provided an opportunity to evaluate ITDR implementation.

Methods: We employed a recently developed semi-quantitative evaluation method to measure our project’s success in achieving ITDR and analyzed factors influencing this achievement.

Results: The project showed strengths in system description, team task allocation, and data sharing, but had lower scores in engaging societal actors throughout the project cycle.

Discussion: We identified the underexplored influence of problem wickedness as a …

Unraveling The Relationship Between Sleep Behaviors And Physical Activity In The United States: Insights From 2015 To 2020 Nhanes Data, Deepali K Ernest, Bipin Singh, Fathimath Shamna, Elizabeth A Onugha, Shreela V Sharma

Faculty, Staff and Student Publications

Background: Physical activity is an important component of metabolic health. However, little is known about the impact of specific types/intensities of physical activity on sleep health, especially among ethnically diverse populations. We examined the association of various sleep behaviors with moderate to vigorous work/recreational activity.

Methods: Self-reported data from the National Health and Nutrition Examination Survey 2015-2020 were cross-sectionally analyzed for a sample of 11,039 participants in the United States (U.S.). Weighted univariate logistic regressions determined unadjusted associations, while weighted multivariable regression models adjusting for age, sex, ethnicity, BMI categories, and socio-economic status assessed the multivariable associations with moderate and …

Embolic Stroke In A Patient With Left Atrial Myxoma, Muhammad Sabri, Sheraz Qamar, Naila Ijaz, Mark Decaro

Division of Cardiology Faculty Papers

We present a case of a patient with a left atrial myxoma who presented with an ischemic stroke. Her cardiac myxoma had an irregular contour and was highly mobile, both features that have been associated with a greater risk of thrombo- embolism. She was treated with prompt surgical resection

Functional Properties Of Corticothalamic Circuits Targeting Paraventricular Thalamic Neurons, Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte

Faculty, Staff and Student Publications

Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. …

Deceased Donor Renal Allograft Utility In Adult Single And Multi-Organ Transplantation In The United States, Peter J. Altshuler, Adam S. Bodzin, Kenneth A. Andreoni, Pooja Singh, Anju Yadav, Jaime M. Glorioso, Ashesh P. Shah, Carlo B. Ramirez, Warren R. Maley, Adam M. Frank

Department of Surgery Faculty Papers

BACKGROUND: Deceased donor multiorgan transplants utilizing kidneys (MOTs) can improve outcomes for multiorgan recipients but reduces kidneys for chronic renal failure patients.

METHODS: We reviewed the Organ Procurement and Transplantation Network database from 2015 through 2019, for adult deceased donor kidney transplants. Recipients were classified as kidney transplant alone (KTA) (n = 62,252) or MOTs pancreas-kidney, simultaneous pancreas-kidney (n = 3,976), liver-kidney, simultaneous liver-kidney (n = 3,212), heart-kidney, simultaneous heart-kidney (n = 808), and "other"-kidney, simultaneous "other" kidney (n = 73).

RESULTS: Liver, heart, and lung-alone transplants were at least 7 times more frequent than their MOT correlate, whereas the …

Gene Expression Regulation By Au-Rich Elements And Au-Rich Element Binding Proteins, Courtney Fay Jungers

Arts & Sciences Graduate Student Theses and Dissertations

The regulation of messenger RNA (mRNA) splicing, stability, and translation efficiency are major modes for controlling gene expression – which is essential for life. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are trans-acting factors that bind to cis-elements influencing the stability and translation of the mRNA transcript. AU-rich elements (AREs) are cis-elements that are targeted by AU-rich element binding proteins (ARE-BPs). Here, I show a novel role for AREs and AU-rich element binding protein 1 (AUF1) during alternative splicing and report on interactions of RBPs and miRNAs to design a new treatment for breast cancer by interrupting these interactions in the …

Sensitivity And Application Of Frequency Domain High-Density Diffuse Optical Tomography (Fd Hd-Dot), Weihao Fan

Arts & Sciences Graduate Student Theses and Dissertations

Functional near-infrared spectroscopy (fNIRS) is a non-invasive imaging technique that measures hemodynamic responses in the brain, similar to functional magnetic resonance imaging (fMRI) but with distinct advantages. By utilizing near-infrared light, fNIRS can penetrate biological tissues and detect changes in oxygenated and deoxygenated hemoglobin. Additionally, fNIRS is portable, noninvasive and inexpensive. Within the realm of fNIRS, several measurement techniques exist, including Continuous Wave (CW), Frequency Domain (FD), and Time Domain (TD) methods. In this dissertation, we focused on the effects, fundamental principles and applications of FD designs. We provided the introduction in Chapter 1, and discussed the background theory and …

Centering Autonomy And Choice To Support Oral Prep Utilization Among People Who Inject Drugs: Qualitative Lessons From Hptn 094 Integra, Amaya Perez-Brumer, Rose Schmidt, Rebecca Kennedy, Jordan E Lake, Yolanda R Villarreal, Sydney Bornstein, Irene Kuo, Omar Nieto, Julie Franks, Cecile Denis, Nabila El-Bassel, Steve Shoptaw, Peter Davidson, Laramie R Smith

Faculty, Staff and Student Publications

Background: Oral Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, despite high rates of HIV risk behaviors among people who inject drugs (PWID), this population remains underserved by current HIV prevention efforts in the United States. To address this challenge, we conducted an in-depth exploration of perspectives on using oral PrEP among PWID engaged in the HIV Prevention Trials Network (HPTN) 094 INTEGRA Study.

Methods: Guided by the Practical, Robust, Implementation, and Sustainability Model (PRISM), our qualitative study drew on semi-structured interviews conducted as part of the embedded implementation science evaluation of HPTN 094 INTEGRA. Seventy-seven PWID participants …

Targeting Corticotropin-Releasing Hormone Receptor Type 1 (Crhr1) Neurons: Validating The Specificity Of A Novel Transgenic Crhr1-Flpo Mouse, Mason Hardy, Yuncai Chen, Tallie Z Baram, Nicholas J Justice

Faculty, Staff and Student Publications

Corticotropin-releasing hormone (CRH) signaling through its cognate receptors, CRHR1 and CRHR2, contributes to diverse stress-related functions in the mammalian brain. Whereas CRHR2 is predominantly expressed in choroid plexus and blood vessels, CRHR1 is abundantly expressed in neurons in discrete brain regions, including the neocortex, hippocampus and nucleus accumbens. Activation of CRHR1 influences motivated behaviors, emotional states, and learning and memory. However, it is unknown whether alterations in CRHR1 signaling contribute to aberrant motivated behaviors observed, for example, in stressful contexts. These questions require tools to manipulate CRHR1 selectively. Here we describe and validate a novel Crhr1-FlpO mouse. Using bacterial artificial …

Characterization Of An Inorganic Powder-Based Scintillation Detector Under A Uhdr Electron Beam, Daline Tho, Sam Beddar

Faculty, Staff and Student Publications

Background: Ultra-high dose rate (UHDR) radiation therapy needs a reliable dosimetry solution and scintillation detectors are promising candidates. In this study, we characterized an inorganic powder-based scintillation detector under a 9 MeV UHDR electron beam.

Methods: A mixture of ZnS:Ag powder and optic glue was coupled to an 8 m Eska GH-4001-P polymethyl methacrylate (PMMA) optical fiber. We evaluated the dependence of the detector on dose per pulse (DPP), pulse repetition frequency (PRF), and pulse width (PW). Additionally, we determined the stability and the reproducibility of the detector.

Results: The signal ratio between the PMMA clear optical fiber and the …

How Do Female Arab International Students Negotiate Their Identities In The Esl Classroom In The Mid-Southern United States?, Sinaria Elmardi Hassan

Electronic Theses and Dissertations Archive

This dissertation explores how women of Islamic faith, as international students, negotiate their identities within the ESL classrooms in the mid-southern United States. Students in such categories face singular challenges at each juncture of gender, religion, and cultural background, especially in an educational system that does not always recognize or accommodate particular needs and experiences. The qualitative research design involved in-depth interviews with female Muslim students from various countries. This study aimed to determine how these students balanced their cultural and religious lives amidst the demands of the American academic environment, particularly in ESL settings where language acquisition was a …

Schedulability Analysis Of Multi-Phase Limited-Preemption Tasks, Benjamin Standaert

McKelvey School of Engineering Graduate Student Theses & Dissertations

This work addresses hard real-time systems, in which tasks must be scheduled so that they are guaranteed to meet deadlines. In particular, when tasks execute across multiple domains with high preemption costs, the combined cost of these preemptions can cause the system to become unschedulable. The number of preemptions must therefore be bounded to limit the overall task execution time, while ensuring that task blocking times are small enough to allow the system to be schedulable. Prior work introduces the Multi-Phase Secure model, which describes a more exact version of this scenario, and an algorithm to determine schedulability of sporadic …

Codifying Domesticity: The Story Of The Recommended Minimum Requirements For Small Dwelling Construction Of 1923, The Housing Policy Of The Hoover Secretariat, And The Impact On American Residential Architecture, Noah Morris

Graduate School of Architecture & Urban Design Theses & Dissertations

During the nineteenth and twentieth centuries, fire disasters and health-safety issues led to the widespread adoption of building codes. While the National Board of Fire Underwriters published the National Building Code in 1905, the code did not maintain regulatory consistency across the nation. This lack of consistency across the nation and socio-economic factors contributed to a nation-wide housing shortage of a million units by 1919. During World War I, the government addressed the housing crisis through the United States Housing Corporation and Emergency Fleet Corporation, building public housing based on the ideals of the Garden City Movement.[1] Following the …

The Relation Between Design Practice And Academic Pedagogy In The Architecture And Teaching Of John Hejduk, Jimin Kim

Graduate School of Architecture & Urban Design Theses & Dissertations

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Recollective Features In The Natural Language Used To Justify Memory Decisions, Xinran Zhang, Ian G. Dobbins

Arts & Sciences Graduate Student Theses and Dissertations

The natural language people use to justify memory decisions predicts recognition accuracy, in part, because it conveys recollection. This study compared a traditional bag-of-words (BOW) classifier to one using BERT embeddings, and newly tests whether classifier recognition scores also predict the later recall of individual recognition probes. During both training and testing, the BERT classifier outperformed the BOW classifier. Nonetheless, a BOW approach was important for explaining the BERT classifier, accounting for a sizeable portion of its variance and confirming that the BERT classifier was also recollection sensitive. The BERT classifier’s recognition scores predicted future recall and mediated the tendency …

Patterns Of Grief And Bereavement Following A Covid Death, Karuna Thomas

Arts & Sciences Graduate Student Theses and Dissertations

The large number of deaths due to COVID-19 has resulted in a similarly high number of people experiencing grief. The aim of this qualitative study was to understand patterns of grief and bereavement following a COVID death. Semi-structured interviews were conducted with individuals who had lost someone close to them to COVID (N = 32). Thematic analysis was used to identify themes and patterns. Participants described specific features of COVID as well as the interdependence within the community that shaped their unique experiences of grieving a COVID death. These unique experiences, in turn, led to disruptions in coping and …

Technology Development Of High-Resolution Single-Cell Lineage Tracing For Cell Reprogramming Systems, Sadie Vanhorn

Arts & Sciences Graduate Student Theses and Dissertations

A critical element of cell identity is the cell that created the observed cell. This parent cell dictates many aspects of its identity, whether measured by function, phenotype, or specific assays. The cell’s lineage impacts the ability of the cell to differentiate into final cell types in development or successfully reprogram in direct cell reprogramming. Here, we evolve molecular barcoding techniques to increase the resolution of lineage recording at single-cell resolution. Using single-cell RNA-sequencing as the readout for this measurement, polyadenylated reporter gene transcripts with engineered 3’ untranslated regions were designed to initially label and then record lineage information. While …

Synthesis Of Higher-Order Catenanes And Catenane-Based Materials, Gray Harlan

Arts & Sciences Graduate Student Theses and Dissertations

Catenanes are a subset of mechanically interlocked molecules (MIMs) and are composed of interlocked rings that can be oriented linearly, radially, or branched. A defining feature of all MIMs is that they are bound through their architectures consisting of mechanical bonds, leading to unique topologies. Catenanes have attracted interest due to their stimuli-responsive behavior and the degrees of freedom afforded by the mechanical bond, a feature which is absent with standard covalent bonds. The stimuli responsiveness of catenanes arises from their templated syntheses, where two or more pre-macrocycles are brought together by a driving force. Various templation strategies rely on …

Multi-Omic Analysis Of Phototrophic Extracellular Electron Uptake In Novel Rhodovulum Spp. Isolated From A Marine Estuary, Emily J. Davenport

Arts & Sciences Graduate Student Theses and Dissertations

Microbial metabolisms are incredibly versatile and dynamic, allowing adaptive strategies for growth in even the most limiting environments. For an ever-increasing number of microbes, this includes utilizing soluble or insoluble inorganic mineral species as electron donors, driving geochemical cycles and microbial metabolisms. This metabolic function of transporting electrons derived from the extracellular environment across cell membranes is called extracellular electron uptake (EEU). Within (photo)autotrophs, (p)EEU also sustains CO2 fixation to cell biomass, implicating a potentially fundamental role of microbial carbon cycling in aquatic and soil ecosystems. A model metabolic scheme of pEEU occurring in natural environments is photoferrotrophy, which pairs …

A Filter-Based Model Of Visual Recognition, Olivia Rose Bockler

Arts & Sciences Graduate Student Theses and Dissertations

Visual recognition, a key perceptual process, enables primates to identify faces, food, tools, and potential threats in their environment. Cortical neurons along the ventral visual stream—spanning from early visual cortex (V1) through inferotemporal cortex (IT), with long-range projections to ventrolateral prefrontal cortex (vlPFC)—are essential for visual recognition. Traditional models propose that neuronal representations increase in complexity in each stage of this pathway, culminating in object-specific representations in higher-order cortex. However, this hypothesis remains debated, particularly as artificial visual models have countered that individual neurons along this pathway may function more as filters contributing to distributed representations of objects. Thus, this …

A Computational And Mathematical Approach To The Preclinical Development Of Alpha Emitting Radiopharmaceutical Therapies, Abdulaziz Said

McKelvey School of Engineering Graduate Student Theses & Dissertations

Numerous candidate nuclides have been undergoing rigorous preclinical development in the pursuit of novel targeted therapies. Successful development of these drugs relies on the understanding of physiological impacts at the macro and micro scales, in addition to a scalable process for their production. Here, mathematical and computerized approaches have been developed to guide this preclinical development. In this report, two alpha emitting nuclides Pb-212 and Ra-223 are modeled. Radium-223 dichloride citrate a newly approved ion indicated for treatment of bone metastatic castrate resistant prostate cancer, irradiates lesions through targeted uptake in bone at sites of disease. We have undertaken the …

Aging, Fast And Slow: Gene Expression Signatures Of Physiological Age Vs. Future Lifespan In Caenorhabditis Elegans, Matthew Mosley

Arts & Sciences Graduate Student Theses and Dissertations

An outstanding question in the field of aging biology is the origin of variability in lifespans among members of the same species. Traditional wisdom dictates that differences in one individual’s genes or environment, “nature” and “nurture,” could predispose that individual to a long or short life. However, these explanations are radically incomplete. Even in a model system as homogenous as C. elegans, using an isogenic population in a lab-controlled environment, we observe a distribution in lifespans comparable to that seen in outbred human populations. The first part of this dissertation focuses on characterizing this non-genetic, non-environmental variability in the aging …

Brazilian Instrumental Music, U.S. Jazz, And Transnationalism: A Study Of National Identity In The Twentieth Century And Present, Felipe Guz Tinoco

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation considers the relationship between Brazilian instrumental music, U.S. jazz, and Brazilian national identity from the early twentieth century to the present. Though the time frame is broad, the present work uses nationalism as an anchoring point through which I analyze multiple musical genres. Previous works have primarily examined songs and lyrics, particularly during the military dictatorship (1964-85), when words against the regime were censored and songwriters persecuted. However, listeners and musicians of instrumental music also engaged with discourses of national identity in profound terms before, during, and after this period, posing ideals of Brasilidade against cultural productions abroad, …

Safety And Optimality Monitors For Learning-Enabled Systems Using Conformal Prediction, Jackson Cox

McKelvey School of Engineering Graduate Student Theses & Dissertations

The use of machine learning to create data-driven plant models and controllers has led to an increased need for safety and optimality monitors for model-based systems. System plant models are subject to uncertainty due to learning constraints such as unseen data and overfitting or physical constraints such as unknown dynamics and noise. This uncertainty is detrimental to safety-critical systems and must be properly regulated. To curb this uncertainty, we create prediction sets using the guarantees provided by Conformal Prediction. With a user-specified high probability, these prediction sets contain the true plant system states for an entire prediction horizon, which we …

Oculomotor Nerve Palsy Recovery Following Microsurgery Vs. Endovascular Treatment Of Posterior Communicating Artery Aneurysms: A Comparative Meta-Analysis Of Short- And Long-Term Outcomes, Rahim Abo Kasem, Conor Cunningham, Sameh Samir Elawady, Mohammad Mahdi Sowlat, Sofia Babool, Saad Hulou, Zachary Hubbard, Atakan Orscelik, Basel Musmar, Alejandro Spiotta

Department of Neurosurgery Faculty Papers

Recent advancements in endovascular treatment (EVT) and different views on optimal management for posterior communicating artery (PComA) aneurysms with oculomotor nerve palsy (ONP) highlight a need to compare recovery timelines between microsurgery and EVT; heterogeneous outcomes and influencing factors may also affect results. A comprehensive systematic review and meta-analysis were conducted by searching PubMed, Embase, Scopus, and Web of Science databases. The extracted data encompassed patient demographics, details on treatment modalities and timing, and characteristics of PComA aneurysms ONP caused by either unruptured or ruptured aneurysms. The primary outcome was ONP favorable recovery, defined as the resolution of admission symptoms, …

Sensitivity Of Difficult-To-Control Palmer Amaranth Accessions To Fluridone And Diflufenican, Maria Carolina Souza, Matthew Coleman Woolard, Jason K. Norsworthy, Tristen H. Avent, Tristen H. Avent, Tom Barber, Rodrigo Botelho

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Palmer amaranth (Amaranthus palmeri S. Watson) has evolved resistance to herbicides targeting nine sites of action. Phytoene desaturase-inhibiting herbicides remain among the few sites of action that are still effective in controlling Palmer amaranth. Greenhouse experiments were conducted to evaluate the effectiveness of fluridone and diflufenican in controlling difficult-to-control Palmer amaranth accessions collected in Arkansas from 2016 to 2022, to quantify the response of three accessions that exhibited low sensitivity to both herbicides, and to evaluate the effectiveness of photosystem II inhibitors alone and with fluridone or diflufenican on three accessions. At 14 days after a preemergence application, Palmer …

Macrowire For Intracranial Thrombectomy: An Early Experience Of A New Device And Technique For Anterior Circulation Large Vessel Occlusion Stroke, Kaustubh Limaye, Sami Al Kasab, Jaidevsinh Dolia, Mohamad Ezzeldin, Daniel Vela Duarte, Vinodh Doss, Sourabh Lahoti, David Hasan, Alejandro Spiotta, Khaled Asi, Vasu Saini, Tapan Mehta, Ameer Hassan, Diogo Haussen, Dileep Yavagal, Jesse Jones, Omar Tanweer, Waleed Brinjikji

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has become the standard of care for treatment of acute ischemic stroke secondary to large vessel occlusion up to 24 h from the last known normal time. With ADAPT and SOLUMBRA techniques, classically, a large bore aspiration catheter is delivered over a microcatheter and microwire crossing the clot to perform thrombectomy. Recently, a novel macrowire (Colossus 035 in.) has been introduced as a potential alternative to the use of microwire-microcatheter to allow the delivery of the aspiration catheter (ID = 0.070 in. up to 0.088 in.) over a macrowire alone.

OBJECTIVE: To test the …

Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Jesse D Bengtsson, Sameer S Bajikar, Christopher M Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J Trostle, Holly K Harris, Bernhard Suter, Sukru Aras, Melissa B Ramocki, Haowei Du, Michele G Mehaffey, Kyunghee Park, Ellen Wilkey, Cemal Karakas, Jesper J Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S Shinawi, Virginia E Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M Vianna-Morgante, Alberto S Cornier, Ahmed Abdelmoity, James P Hwang, Shalini N Jhangiani, Donna M Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G Glaze, Jawid M Fatih, Richard A Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J Sedlazeck, James R Lupski, Huda Y Zoghbi, Claudia M B Carvalho

Faculty, Staff and Students Publications

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …