Digital Commons Network^™

Implementation And Assessment Of The Openbci Platform As An Accessible Brain- Computer Interface, Jewell Norris

Honors Theses

OpenBCI is a low-cost, open-source platform for alternative brain-computer interface (BCI) software and hardware. This thesis evaluates OpenBCI’s electroencephalogram (EEG) and electromyography (EMG) capabilities by constructing and testing a 16-channel EEG system using the Ultracortex Mark IV headset and Cyton + Daisy biosensing board. The viability of the system was assessed through real-time BCI control and comparison to a clinical-grade EEG system. Real-time BCI control of an online falling-block game was tested via the use of eye blinks EMG (channels Fp1/Fp2) and head-tilt accelerometer inputs. The BCI game demonstrated reliable control despite minor latency and artifact sensitivity. For clinical comparison, …

Read The Data For Diverse Truths-And Quantitative Myocardial Perfusion Versus Angiography, Kenneth Lance Gould, Nils P Johnson

Faculty, Staff and Student Publications

No abstract provided.

Sex Differences In Atherosclerotic Coronary Artery Disease Patterns, Kazumasa Ikeda, Daniel Munhoz, Sofie Brouwers, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Domenico Galante, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Koshiro Sakai, Tatyana Storozhenko, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Thomas Johnson, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad Ali, Bernard De Bruyne, Frederic Bouisset, Takashi Kubo, Nobuhiro Tanaka, Kazuhiro Satomi, Nils P Johnson, Carlos Collet, Takuya Mizukami

Faculty, Staff and Student Publications

Background: Sex differences in coronary artery disease (CAD) have been increasingly recognized, as women present with distinct clinical characteristics and outcomes compared with men. This study investigated the impact of sex on pathophysiological CAD patterns (focal versus diffuse) in stable patients undergoing percutaneous coronary interventions (PCI).

Methods: We conducted a subanalysis of the PPG Global (Pullback Pressure Gradient Global Registry) study, a multicenter, prospective trial including 993 patients (236 [23.8%] women and 757 [76.2%] men) with hemodynamically significant CAD, defined as fractional flow reserve ≤0.80. The pullback pressure gradient metric categorized CAD patterns as focal or diffuse. Patient-reported outcomes were …

Vessel-Specific Myocardial Mass In Patients With Stable Coronary Artery Disease, Nikolaos Stalikas, Takuya Mizukami, Frederic Bouisset, Kazumasa Ikeda, Atomu Tajima, Daniel Munhoz, Thabo Mahendiran, Adriaan Wilgenhof, Koshiro Sakai, Bjarne Noorgard, Thomas Engstroem, Jonathon Leipsic, Giulio Stefanini, Antonio Bartorelli, Timothy Fairbairn, Alan Bagnall, Brian Ko, Nils P Johnson, Colin Berry, Divaka Perera, Evald Høj Christiansen, Toshiro Shinke, Hiromase Otake, Bon Kwon Koo, Emanuele Barbato, Salvatore Brugaletta, Damien Collison, Gianluca Campo, Eric Van Belle, Tommaso Goori, Lokien Van Nunen, Adam Witkowski, Patricio Astudillo, James Spratt, Tetsuya Amano, Hirohiko Ando, Georgios Sianos, Jeroen Sonck, Daniele Andreini, Bernard De Bruyne, Carlos Collet

Faculty, Staff and Student Publications

Background: Assessing the myocardial mass at risk is essential in evaluating patients with coronary artery disease. This study aims to establish reference values for vessel-specific myocardial mass derived from coronary computed tomography angiography, providing a quantitative assessment of the myocardial mass subtended by each epicardial vessel.

Methods: Left ventricular (LV) and vessel-specific myocardial mass were calculated from coronary computed tomography angiography using the Voronoi method in patients with stable coronary artery disease. Myocardial mass was quantified for each epicardial coronary artery with a diameter >1.5 mm.

Results: We included 948 patients with 9228 epicardial coronary artery branches. Mean age was …

Prognosis And Treatment Response Stratification According To Loss Of Proofreading (Lop), Giulia Maddalena, Fadl A Zeineddine, Saikat Chowdhury, Mohammad A Zeineddine, Abdelrahman M Yousef, Francesca Bergamo, Sara Lonardi, Timothy A Yap, Michael Geoffrey White, Michael J Overman, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Background: Only a subset of polymerase epsilon (POLE) mutations is associated with hypermutant phenotype; we hypothesized that only loss-of-proofreading (LOP) POLE mutations are associated with favorable immunotherapy response.

Methods: This retrospective cohort study included a pan-cancer cohort of 69,223 patients from cBioPortal and a cohort of patients with 41 POLE mutant metastatic colorectal (CRC) treated with immunotherapy at the MD Anderson Cancer Center between January 2017 and May 2023. We evaluated prognosis according to POLE mutation functionality.

Results: In the pan-cancer cBioPortal cohort (n=69,223) POLE was mutated in 2.8% (1,965) of tumors; of these, only 7.5% (n=148) had …

Improved Technical Outcomes With Converting Thrombectomy Techniques After Failed First Pass Recanalization, Hidetoshi Matsukawa, Charles Matouk, Kazutaka Uchida, Sami Al Kasab, Mohammad-Mahdi Sowlat, Sameh Samir Elawady, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Q Wolfe, Ansaar T Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Adam S Arthur, Hugo Cuellar, Brain M Howard, Daniele G Romano, Omar Tanweer, Justin R Mascitelli, Isabel Fragata, Adam Polifka, Joshua W Osbun, Roberto Javier Crosa, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Richard Williamson, Pedro Navia, Peter Kan, Reade Andrew De Leacy, Shakeel A Chowdhry, Mohamad Ezzeldin, Alejandro M Spiotta, Shinichi Yoshimura, Ali M Alawieh

Faculty, Staff and Students Publications

Background: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes.

Methods: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique …

Retinol Tracing Within Murine Neural Retina Reveals Cell Type-Specific Retinol Transport And Distribution, Zachary J Engfer, Grazyna Palczewska, Samuel W Du, Jianye Zhang, Zhiqian Dong, Carolline Rodrigues Menezes, Jun Wang, Jianming Shao, Budd A Tucker, Robert F Mullins, Rui Chen, Philip D Kiser, Krzysztof Palczewski

Faculty, Staff and Students Publications

11-cis-Retinal is essential for light perception in mammalian photoreceptors (PRs), and aberrations in retinoid transformations cause severe retinal diseases. Understanding these processes is crucial for combating blinding diseases. The visual cycle, operating within PRs and the retinal pigment epithelium (RPE), regenerates 11-cis-retinal to sustain light sensitivity. Retinoids are also present in Müller glia (MG), hypothesized to supply 11-cis-retinol to cone PRs and retinal ganglion cells (RGCs). To trace retinoid movement through retinal cell types, we used cell-specific knock-in of lecithin:retinol acyltransferase (LRAT), which converts retinols into stable retinyl esters (REs). Ectopic LRAT expression in murine PRs, MG, and RGCs resulted …

Elastic Cytomatrix Dynamics Influences Metabolic Rate And Tumor Microenvironment Formation, Tattym E Shaiken, Tulendy T Nurkenov, Meruyert S Kurmanbayeva, David Y Graham

Faculty, Staff and Students Publications

In healthy cells, the cytomatrix mechanics utilize mitochondrial respiration to control cytosolic motion and fine-tune the chemical processes. In cancer, the cytosolic motion is energized by glycolytic fermentation (the Warburg effect), which provides additional energy to supply the needs of the cytomatrix. Here, we describe the physical and chemical processes of the integrated and cooperative cytomatrix cytoarchitecture, in which structure and function are inseparable. The extracellular matrix is interconnected with the intracellular cytomatrix and functions as two integrated elastic solid phases. This finding led us to propose mechanisms of tumor microenvironment formation resulting from the mutational burden, in which altered …

Apathy Self-Awareness And Its Neural Correlates In Parkinson’S Disease, Hannah Conn, Hideo Suzuki, Zekai Jin, Ana Marin, Xi Zhu, Seonjoo Lee, Edward Huey, Ratko Radakovic, Sarah R Heilbronner, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy is a prevalent non-motor symptom in Parkinson's disease (PD) that negatively impacts quality of life. Impaired self-awareness of apathy (ISA-a) further impacts patient care by limiting engagement. While apathy has been associated with reduced fronto-striatal functional connectivity (FC), the neural basis of ISA-a remains unclear. We examined ISA-a in 52 individuals and the neural basis of ISA-a in 35 individuals with PD using a dimensional approach (i.e., initiation, executive, and emotional apathy) and resting-state fMRI (3T scanner). Apathetic PD patients (42%) showed poorer self-awareness than non-apathetic peers. Apathetic PD patients showed a trend towards reduced FC between the left …

Comparing Diagnostic Tools For Heart Failure With Preserved Ejection Fraction Across Community And Clinical Cohorts, Luca Monzo, Olivier Huttin, Biykem Bozkurt, Kévin Duarte, Cecilia Linde, Lars H Lund, Camilla Hage, Erwan Donal, Martin Magnusson, Peter Nilsson, Margret Leosdottir, Erwan Bozec, Guillaume Baudry, Faiez Zannad, Nicolas Girerd

Faculty, Staff and Students Publications

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, particularly in older adults. While the Heart Failure Association (HFA)-PEFF and H2FPEF Scores offer structured diagnostic approaches, their clinical utility is still debated. This study aims to compare the diagnostic accuracy of HFpEF Scores versus inclusion criteria used in sodium-glucose cotransporter-2 inhibitors (SGLT2i) trials, age-adjusted N-terminal pro B-type natriuretic peptide (NT-proBNP) thresholds and the universal definition of heart failure (HF).

Methods: Diagnostic tools were assessed using sex-weighted and age-weighted propensity score adjustment in individuals aged 60-80 years from two established HFpEF cohorts (MEtabolic Road to DIAstolic Heart Failure (MEDIA), …

Advancements In Understanding Spasticity: A Neuromusculoskeletal Modeling Perspective, Mohammad S Shourijeh, Argyrios Stampas, Shuo-Hsiu Chang, Radha Korupolu, Gerard E Francisco

Faculty, Staff and Student Publications

Spasticity, a complex consequence of upper motor neuron lesions, poses challenges for clinical assessment due to its neural and mechanical origins. Traditional scales like the Modified Ashworth and Tardieu Scales provide subjective, context-limited insights, often missing spasticity's dynamic nature. Neuromusculoskeletal (NMS) modeling offers objective, quantitative insights by integrating patient-specific muscle-tendon properties, reflex dynamics, and multi-joint biomechanics. This scoping review examines advancements in spasticity modeling, comparing mechanical, neurological, and integrated approaches, and their applications in conditions like cerebral palsy and stroke. We highlight barriers to clinical translation, including computational demands and regulatory challenges, and propose future directions, such as real-time simulation …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …

“For Haitian Culture, Being Older [Is] A Blessing”: Perceptions Of Aging, Elderhood, And Dementia In A Haitian Born Sample, Melissa K. Eustache

USF Tampa Graduate Theses and Dissertations

This thesis investigates how first-generation Haitian immigrants in the United States understand and interpret dementia within the intersecting contexts of culture, migration, and biomedicine. While dementia is constructed as a pathological “loss of self” and a public health epidemic, in American biomedical and popular discourse, this study examines how Haitian-born individuals—socialized within a non-Western cultural and spiritual framework—make sense of cognitive decline and impairment in ways that diverge from Western biomedical narratives. Guided by theoretical orientations from medical anthropology, including Mark Nichter’s idioms of distress, Margaret Lock’s local biologies, and neuroanthropology, this research explores how cultural models of illness, aging, …

The Unfolded Protein Response-Novel Mechanisms, Challenges, And Key Considerations For Therapeutic Intervention, P M Quan Mai, Tam-Anh Truong, Sai Kumar Samala, Bhoomika Muruvekere Lakshmisha, Prapannajeet Biswal, Khadijeh Koushki, Prudhvi Chand Mallepaddi, Geraldine Vijay, Sunil Krishnan

Faculty, Staff and Student Publications

Background: The unfolded protein response (UPR) is an evolutionarily conserved, synchronized, and orchestrated process triggered by eukaryotic cells in response to endoplasmic reticulum (ER) stress. UPR restores the ER's capacity to handle large protein loads within it, and still fold and process these proteins accurately. Many recent studies have documented the non-canonical roles of the UPR, outside of protein quality control, in the context of lipid metabolism and the immune system in cancer. Cancer cells have been known to hijack the UPR to promote survival and evade immune surveillance. However, the underlying mechanisms remain poorly understood.

Objectives: Here, we critically …

Immunogenomic Diversity Of Triple-Negative Breast Cancers In Obese And Non-Obese Black And White Women, Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Xiao-Cheng Wu, Luis Del Valle, Chindo Hicks, Jiande Wu, Jerneja Tomsic, Susan Neuhausen, Yuan Chun Ding, Kavitha Mukund, Zahra Mesrizadeh, Shankar Subramaniam, Augusto Ochoa, Victoria Seewaldt, Lucio Miele

School of Medicine Faculty Publications

Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like …

Genome-Wide Discovery Of Multiple Sclerosis Genetic Risk Variant Allelic Regulatory Activity, Marissa Granitto, Lois Parks, Molly S Shook, Carmy Forney, Xiaoting Chen, Lee E Edsall, Omer A Donmez, Sreeja Parameswaran, Kristen S Fisher, Aram Zabeti, Lucinda P Lawson, Matthew T Weirauch, Leah C Kottyan

Faculty, Staff and Students Publications

Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system with a complex etiology involving environmental and genetic factors. Numerous genetic risk loci for multiple sclerosis have been nominated through genome-wide association studies, with most associated variants residing in noncoding regions. However, further work is needed to understand how genetic variation contributes to disease-related alterations to gene expression. Here, we use Massively Parallel Reporter Assays to identify genetic risk variants with genotype-dependent enhancing or silencing activity within a set of 14,275 variants distributed among multiple sclerosis risk loci that have reached genome-wide or suggestive significance. We applied our …

Low Mutation Rate But High Male-Bias In The Germline Of A Short-Lived Opossum, Yadira Peña-García, Richard J Wang, Muthuswamy Raveendran, R Alan Harris, Paul B Samollow, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but the mechanisms underlying these factors are still unclear. One approach to distinguishing between alternative mechanisms is to study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns of mutation in these organisms. Here, we study the germline mutation rate in the gray short-tailed opossum, Monodelphis domestica, a laboratory model species that becomes reproductively mature at less than 6 mo of age. Whole-genome sequencing of 22 trios reveals one of the lowest mutation rates per generation …

Slc35g3 Is A Udp-N-Acetylglucosamine Transporter For Sperm Glycoprotein Formation And Underpins Male Fertility In Mice, Daisuke Mashiko, Shingo Tonai, Haruhiko Miyata, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter …

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Reprogramming Tumor Microenvironment Via Systemic Delivery Of Tlr3 Agonist And Manganese Nanoparticle, Young Seok Cho, Xingwu Zhou, Xiaoqi Sun, Ziye Wan, Julia Crowther, Mariko Takahashi, Swetha Kodamasimham, Qi Wu, May Thazin Phoo, Youngseo Na, Kai Han, Zaiye Li, Anna Schwendeman, Steven P Schwendeman, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Toll-like receptor (TLR) agonists, as potent immunostimulatory adjuvants, play a critical role in linking the innate and adaptive immune responses. However, their antitumor effects as cancer immunotherapeutic agents have been limited. Here, we report our finding that manganese ion (Mn2+) potentiates various TLR agonists, leading to robust activation of the TLR pathway and the stimulator of interferon genes (STING) pathway among innate immune cells. In particular, we have observed robust antitumor efficacy after intratumoral administration of a TLR3 agonist and Mn2+. To achieve systemic codelivery of TLR3 agonist and Mn2+, we have developed a low-molecular-weight poly(inosinic:cytidylic acid)-Mn2+ coordination lipid nanoparticle …

Development Of A Longitudinal, Small-Group Pocus Curriculum For Internal Medicine Residents, Shah N. Mahmud Do, Ammar W. Bhatti Do, Ariq Rahman Md, Omar Al Qassab Md, Fraser Mackay Md

The Lahey Journal

Development of a Longitudinal, Small-Group POCUS Curriculum for Internal Medicine Residents

Introduction

Point-of-Care Ultrasound (POCUS) is integral for clinicians to enhance their diagnostic and procedural skills. Unlike Emergency Medicine or Anesthesia training programs, Internal Medicine programs often lack a structured and standardized curriculum. We thus developed a longitudinal and multi-pronged POCUS curriculum aimed at building trainee competency when utilizing ultrasound for diagnostic and procedural work-up.

Methods

The curriculum encompasses the following: basics of ultrasound, ultrasound-guided procedures, thoracic ultrasound/Bed Lung Ultrasound in Emergency (BLUE), and cardiac ultrasound/Focus-Assessed Transthoracic Echocardiography (FATE). These modules were integrated into the residents’ clinic blocks. We utilized …

Peripheral Microvascular And Cerebral White Matter Dysfunction In Schizophrenia: Implications Of A Body-Brain Endothelial Pathophysiology, Eric L Goldwaser, Alexa Yuen, Wyatt Marshall, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Mark Kvarta, Yizhou Ma, Xiaoming Du, Si Gao, Heather Bruce, Patrick Donnelly, Braxton Mitchell, Charles Hong, Danny J J Wang, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

Background and hypothesis: Schizophrenia spectrum disorder (SSD) is a chronic neuropsychiatric illness accompanied by significant brain structural and functional abnormalities and higher rate of cardio- and cerebrovascular comorbidities. We hypothesized that genetic and environmental risk factors that led to SSD act throughout the body and demonstrated the association between lower integrity of peripheral vascular endothelium and white matter (WM) microstructure.

Study design: Microvascular endothelial function was evaluated using brachial artery post-occlusive reactive hyperemia (PORH), in which endothelial responses are measured under reduced blood flow and after blood flow is restored. White matter microstructure was assessed by multi-shell diffusion tensor imaging …

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Compadre: Combined Pedigree-Aware Distant Relatedness Estimation For Improved Pedigree Reconstruction, Grahame F Evans, James T Baker, Lauren E Petty, Alexander S Petty, Hannah G Polikowsky, Ryan J Bohlender, Hung-Hsin Chen, Che-Yu Chou, Kathryn Z Viljoen, Janet M Beilby, Shelly Jo Kraft, Wanying Zhu, Joshua M Landman, Autumn R Morrow, Dayi Bian, Alyssa C Scartozzi, Chad D Huff, Jennifer E Below

Faculty, Staff and Student Publications

Designing powerful and unbiased genomic studies requires accurate assessment of familial relatedness even when this information is not captured from participants. Characterization of pairwise degrees of relatedness from participants' genetic data enables reconstruction of pedigrees, and several pedigree reconstruction tools have emerged in the last decade. However, limitations of these tools include high computational burden in large datasets, reliance on external information, reduced accuracy in admixed populations, and most notably, an inability to accurately reconstruct pedigrees when only a subset of family members is represented in the genetic data. To improve pedigree reconstruction in large-scale data and in pedigrees with …

Menin Inhibitor Ds-1594b Drives Differentiation And Induces Synergistic Lethality In Combination With Venetoclax In Acute Myeloid Leukemia Cells With Rearranged Mixed-Lineage Leukemia And Mutated Nucleophosmin-1, Valerio Ciaurro, Vassilena Sharlandjieva, Anna Skwarska, Catherine Chahrour, Natalia Baran, Zhihong Zeng, Cassandra Ramage, Naval Daver, Bing Z Carter, Sovira Chaundhry, Palaniraja Thandapani, Maria Paola Martelli, Thomas A Milne, Marina Konopleva

Faculty, Staff and Student Publications

Mixed-lineage leukemia (MLL) rearrangements and Nucleophosmin-1 (NPM1) mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL. We hypothesized that targeting the menin-MLL interaction using DS-1594b and blocking the antiapoptotic BCL-2 protein using venetoclax may promote differentiation and enhance eradication of MLL-rearranged and NPM1-mutated leukemias models. We treated acute myeloid leukemia (AML) cell lines with MLL rearrangements, NPM1 mutations, other leukemias and primary samples from AML patients with venetoclax alone, DS- 1594b alone, and their combination. We measured proliferation, viability, apoptosis, and differentiation using a variety of cellular assays, Western blotting, and …

The Utility Of Ultra-Deep Rna Sequencing In Mendelian Disorder Diagnostics, Sen Zhao, Jefferson C Sinson, Shenglan Li, Jill A Rosenfeld, Gladys Zapata, Kristina Macakova, Mezthly Pena, Becky Maywald, Kim C Worley, Lindsay C Burrage, Monika Weisz-Hubshman, Shamika Ketkar, William Craigen, Lisa Emrick, Undiagnosed Diseases Network, Tyson Clark, Gila Yanai Lithwick, Zohar Shipony, Christine Eng, Brendan Lee, Pengfei Liu

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has emerged as a powerful tool for resolving variants of uncertain significance (VUSs), particularly those affecting gene expression and splicing. However, most reference datasets and diagnostic protocols employ relatively modest sequencing depths (∼50-150 million reads), which may fail to detect low-abundance transcripts and rare splicing events critical for accurate diagnosis. We evaluated the diagnostic and translational utility of ultra-high-depth (up to ∼1 billion unique reads) RNA-seq in four clinically accessible tissues using the Ultima sequencing platform. After validating the performance of Ultima RNA-seq, we investigated how increasing sequencing depth affects gene and isoform detection, splicing variant discovery, …

Effects Of Combining Traditional East Asian And Conventional Western Medicine On Acute Stroke Outcomes, Dong-Seok Gwak, Jong-Sik Lee, Dawid Schellingerhout, Jinyong Chung, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Hee-Joon Bae, Mikyung Kim, Dong-Jun Choi, Dong-Eog Kim

Faculty, Staff and Student Publications

Background: Traditional East Asian medicine (TM) is widely used in Korea and other East Asian countries. However, the effects of TM treatment on acute ischemic stroke (AIS) outcomes remain unclear, as previous studies lacked a sufficient sample size, a consecutive series design, or a prospective outcome capture approach. We aimed to investigate whether combining TM with conventional Western medicine (CM) treatments (C+TM) leads to better outcomes after AIS, relative to CM treatment alone.

Methods: We retrospectively analyzed 2157 consecutive patients with AIS from a prospectively collected registry (2011-2021) at our center and compared the CM and C+TM groups in terms …

Assessing The Impact Of A Semi-Structured Intraoperative Anaesthesia Handoff Cognitive Aid On Surgical Patient Outcomes: Study Protocol For A Cluster Randomised Trial, Aubrey Samost-Williams, Charles E Green, Lillian S Kao, Srikanth Sridhar, Daniel I Sessler, Alparslan Turan, Eric J Thomas

Faculty, Staff and Student Publications

Introduction: Intraoperative anaesthesia handoffs represent a risk point in the care of surgical patients. Although often necessary to prevent fatigue, improve vigilance and optimise operational efficiency, critical information can be lost, potentially leading to postoperative complications. Structured handoffs can increase the transfer of knowledge during intraoperative anaesthesia handoffs, improving their quality. We therefore propose to test the primary hypothesis that a semi-structured intraoperative anaesthesia handoff cognitive aid reduces the number of serious 30-day complications in surgical patients.

Methods and analysis: We will enrol adults having non-cardiac surgery who are scheduled to have an intraoperative anaesthesia handoff for operational reasons. We …

Large-Scale Profiling Of Antibody Reactivity To Glycolipids In Patients With Guillain-Barré Syndrome, Robin C M Thomma, Susan K Halstead, Laura C De Koning, Eveline J A Wiegers, Dawn S Gourlay, Anne P Tio-Gillen, Wouter Van Rijs, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A Barroso, Kathleen J Bateman, Luana Benedetti, Peter Van Den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, Efthimios Dardiotis, Amy Davidson, Thomas E Feasby, Janev Fehmi, Giuliana Galassi, Tania Garcia-Sobrino, Volkan Granit, Gerardo Gutiérrez-Gutiérrez, Robert D M Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, James K L Holt, Zhahirul Islam, Summer Karafiath, Hans D Katzberg, Noah Kolb, Susumu Kusunoki, Satoshi Kuwabara, Motoi Kuwahara, Helmar C Lehmann, Sonja E Leonhard, Lorena Martín-Aguilar, Soledad Monges, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo C Reisin, Simon Rinaldi, Paolo Ripellino, Rhys C Roberts, Olivier Scheidegger, Nortina Shahrizaila, Kazim A Sheikh, Nicholas J Silvestri, Soren H Sindrup, Beth Stein, Cheng Y Tan, Hatice Tankisi, Leo H Visser, Waqar Waheed, Ruth Huizinga, Bart C Jacobs, Hugh J Willison

Faculty, Staff and Student Publications

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, …

A Multiomics Approach To Defining Target-Organ Injury In Youths With Primary Hypertension: The Ship Ahoy Cohort, Kalyani Ananthamohan, Tammy M Brady, Mohammed Arif, Stephen R Daniels, Bonita Falkner, Michael Ferguson, Joseph T Flynn, Coral Hanevold, Stephen R Hooper, Julie R Ingelfinger, Marc Lande, Lisa J Martin, Kevin E Meyers, Mark Mitsnefes, Bernard Rosner, Joshua A Samuels, Gina Kuffel, Michael J Zilliox, Qin M Chen, Richard C Becker, Elaine M Urbina, Sakthivel Sadayappan

Faculty, Staff and Student Publications

Background: Primary hypertension in childhood tracks into adulthood and is associated with increased cardiovascular risk. Studies conducted in individuals aged < 18 years, an age group without many of the confounding comorbid cardiovascular disease risk factors in adults, provide an opportunity to explore early cardiovascular target-organ injury.

Methods: Youths (n=132, mean age, 15.8 years) were stratified by blood pressure (BP) as low-BP, mid-BP, and high-BP and by left ventricular mass index as low-and high left ventricular mass index. Systemic circulating RNA, microRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. In vitro cell culture experiments assessed angiotensin II- and microRNA-mediated Vash1 (vasohibin-1 protein) regulation and Vash1-mediated hypertrophic response.

Results: In high-BP youths, transcriptomics analysis identified …