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Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

Contributions Of Brain Microstructures And Metabolism To Visual Field Loss Patterns In Glaucoma Using Archetypal And Information Gain Analyses, Yueyin Pang, Ji Won Bang, Anisha Kasi, Jeremy Li, Carlos Parra, Els Fieremans, Gadi Wollstein, Joel S. Schuman, Mengyu Wang, Kevin C Chan

Wills Eye Hospital Papers

PURPOSE: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures.

METHODS: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with …

Computational Insights Into Sars-Cov-2 Main Protease Mutations And Nirmatrelvir Efficacy: The Effects Of P132h And P132h-A173v, Yuan-Ling Xia, Wen-Wen Du, Yong-Ping Li, Yan Tao, Zhi-Bi Zhang, Song-Ming Liu, Yun-Xin Fu, Ke-Qin Zhang, Shu-Qun Liu

Faculty, Staff and Student Publications

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir’s efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the …

Predictors Of Aneurysm Obliteration In Patients Treated With The Web Device: Results Of A Multicenter Retrospective Study, Panagiotis Mastorakos, Kareem El Naamani, Nimer Adeeb, Mathews Lan, James Castiglione, Omaditya Khanna, Ritam Ghosh, Jose Danilo Bengzon Diestro, Mahmoud Dibas, Rachel M Mclellan, Oktay Algin, Sherief Ghozy, Nicole M Cancelliere, Assala Aslan, Hugo H Cuellar-Saenz, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin E Vranic, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Jay A Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Vincent M Tutino, Mohamed K Ibrahim, Marwa A Mohammed, James D Rabinov, Yifan Ren, Clemens M Schirmer, Mariangela Piano, Maria Bres Bullrich, Michael Mayich, Anna L Kühn, Caterina Michelozzi, Stéphanie Elens, Robert M Starke, Ameer E Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marios Psychogios, Christian Ulfert, Julian Spears, Brian T Jankowitz, Jan-Karl Burkhardt, Ricardo A Domingo, Thien Huynh, Rabih G Tawk, Boris Lubicz, Marie T Nawka, Pietro Panni, Ajit S Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberpfalzer, M Ozgur Ozates, Giyas Ayberk, Robert W Regenhardt, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Andrew F Ducruet, Felipe C Albuquerque, Nirav J Patel, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Frédéric Clarençon, Nicola Limbucci, Mario Zanaty, Juan Carlos Martinez-Gutierrez, Sunil Sheth, Gary Spiegel, Rawad Abbas, Abdelaziz Amllay, Stavropoula I Tjoumakaris, Michael R Gooch, Nabeel A Herial, Robert H Rosenwasser, Hekmat Zarzour, Richard F Schmidt, Vitor Mendes Pereira, Aman B Patel, Pascal M Jabbour, Adam A Dmytriw

Faculty, Staff and Student Publications

Background and purpose: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment.

Materials and methods: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up.

Results: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis …

Multi-Scale Signaling And Tumor Evolution In High-Grade Gliomas, Jingxian Liu, Song Cao, Kathleen J Imbach, Marina A Gritsenko, Tung-Shing M Lih, Jennifer E Kyle, Tomer M Yaron-Barir, Zev A Binder, Yize Li, Ilya Strunilin, Yi-Ting Wang, Chia-Feng Tsai, Weiping Ma, Lijun Chen, Natalie M Clark, Andrew Shinkle, Nataly Naser Al Deen, Wagma Caravan, Andrew Houston, Faria Anjum Simin, Matthew A Wyczalkowski, Liang-Bo Wang, Erik Storrs, Siqi Chen, Ritvik Illindala, Yuping D Li, Reyka G Jayasinghe, Dmitry Rykunov, Sandra L Cottingham, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Tyler Sagendorf, Vladislav A Petyuk, Michael Nestor, Lisa M Bramer, Kelly G Stratton, Athena A Schepmoes, Sneha P Couvillion, Josie Eder, Young-Mo Kim, Yuqian Gao, Thomas L Fillmore, Rui Zhao, Matthew E Monroe, Austin N Southard-Smith, Yang E Li, Rita Jui-Hsien Lu, Jared L Johnson, Maciej Wiznerowicz, Galen Hostetter, Chelsea J Newton, Karen A Ketchum, Ratna R Thangudu, Jill S Barnholtz-Sloan, Pei Wang, David Fenyö, Eunkyung An, Mathangi Thiagarajan, Ana I Robles, D R Mani, Richard D Smith, Eduard Porta-Pardo, Lewis C Cantley, Antonio Iavarone, Feng Chen, Mehdi Mesri, Maclean P Nasrallah, Hui Zhang, Adam C Resnick, Milan G Chheda, Karin D Rodland, Tao Liu, Li Ding, Philadelphia Coalition For A Cure, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream …

Intratumoral Immune Triads Are Required For Immunotherapy-Mediated Elimination Of Solid Tumors, Gabriel Espinosa-Carrasco, Edison Chiu, Aurora Scrivo, Paul Zumbo, Asim Dave, Doron Betel, Sung Wook Kang, Hee-Jin Jang, Matthew D Hellmann, Bryan M Burt, Hyun-Sung Lee, Andrea Schietinger

Faculty, Staff and Students Publications

Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. …

Broadcasters, Receivers, Functional Groups Of Metabolites, And The Link To Heart Failure By Revealing Metabolomic Network Connectivity, Azam Yazdani, Raul Mendez-Giraldez, Akram Yazdani, Rui-Sheng Wang, Daniel J Schaid, Sek Won Kong, M Reza Hadi, Ahmad Samiei, Esmat Samiei, Clemens Wittenbecher, Jessica Lasky-Su, Clary B Clish, Jochen D Muehlschlegel, Francesco Marotta, Joseph Loscalzo, Samia Mora, Daniel I Chasman, Martin G Larson, Sarah H Elsea

Faculty, Staff and Students Publications

Background and objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline.

Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. …

Dissociation Of Reading And Naming In Ventral Occipitotemporal Cortex, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Lesions in the language-dominant ventral occipitotemporal cortex (vOTC) can result in selective impairment of either reading or naming, resulting in alexia or anomia. Yet, functional imaging studies that show differential activation for naming and reading do not reveal activity exclusively tuned to one of these inputs. To resolve this dissonance in the functional architecture of the vOTC, we used focused stimulation to the vOTC in 49 adult patients during reading and naming, and generated a population-level, probabilistic map to evaluate if reading and naming are clearly dissociable within individuals. Language mapping (50 Hz, 2829 stimulations) was performed during passage reading …

Ai Driven Analysis Of Mri To Measure Health And Disease Progression In Fshd, Lara Riem, Olivia Ducharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A Jacobs, Doris G Leung, Seth D Friedman, Silvia S Blemker

Faculty, Staff and Student Publications

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image …

Reverse Phase Proteomic Array Profiling Of Asparagine Synthetase Expression In Newly Diagnosed Acute Myeloid Leukemia, Nisha Narayanan, Jennifer Marvin-Peek, Mohamad K Abouelnaaj, Dhabya Majid, Bofei Wang, Brandon D Brown, Yihua Qiu, Steven M Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower …

Genetic Diversity Of 1,845 Rhesus Macaques Improves Genetic Variation Interpretation And Identifies Disease Models, Jun Wang, Meng Wang, Ala Moshiri, R Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H O'Connor, Zach Johnson, Melween Martinez, Michael J Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M Thomasy, Jeffrey Rogers, Rui Chen

Faculty, Staff and Students Publications

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which …

Hur Controls Glutaminase Rna Metabolism, Douglas Adamoski, Larissa M Dos Reis, Ana Carolina Paschoalini Mafra, Felipe Corrêa-Da-Silva, Pedro Manoel Mendes De Moraes-Vieira, Ioana Berindan-Neagoe, George A Calin, Sandra Martha Gomes Dias

Faculty, Staff and Student Publications

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and …

O-Glcnacylation Of Mitf Regulates Its Activity And Cdk4/6 Inhibitor Resistance In Breast Cancer, Yi Zhang, Shuyan Zhou, Yan Kai, Ya-Qin Zhang, Changmin Peng, Zhuqing Li, Muhammad Jameel Mughal, Belmar Julie, Xiaoyan Zheng, Junfeng Ma, Cynthia X Ma, Min Shen, Matthew D Hall, Shunqiang Li, Wenge Zhu

2020-Current year OA Pubs

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or …

Task And Stimulus Coding In The Multiple-Demand Network, Sneha Shashidhara, Moataz Assem, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in …

Loss Of The Dna Repair Gene Rnase H2 Identifies A Unique Subset Of Ddr-Deficient Leiomyosarcomas, Michael S Nakazawa, Ian M Silverman, Victoria Rimkunas, Artur Veloso, Dominik Glodzik, Adrienne Johnson, Toshiro K Ohsumi, Shreyaskumar R Patel, Anthony P Conley, Christina L Roland, Pamela T Soliman, Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Rossana Lazcano, Dawon Song, Khalida M Wani, Alexander J Lazar, Timothy A Yap, Wei-Lien Wang, J Andrew Livingston

Faculty, Staff and Student Publications

Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR-targeted treatments. Therefore, we designed a protein- and genomic-based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS; 30%, 39/102). In …

Addressing Disparities In Pediatric Congenital Heart Disease: A Call For Equitable Health Care, Devyani Chowdhury, Pietro A Elliott, S Yukiko Asaki, Shahnawaz Amdani, Quang-Tuyen Nguyen, Christina Ronai, Seda Tierney, Victor Y Levy, Kriti Puri, Carolyn A Altman, Jonathan N Johnson, Julie S Glickstein

Faculty, Staff and Students Publications

While significant progress has been made in reducing disparities within the US health care system, notable gaps remain. This article explores existing disparities within pediatric congenital heart disease care. Congenital heart disease, the most common birth defect and a leading cause of infant death, has garnered substantial attention, revealing certain disparities within the US health care system. Factors such as race, ethnicity, insurance coverage, socioeconomic status, and geographic location are all commonalities that significantly affect health disparities in pediatric congenital heart disease. This comprehensive review sheds light on disparities from diverse perspectives in pediatric care, demonstrates the inequities and inequalities …

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository With Genomic And Pathologic Annotations Enables Deep Learning Analysis, Brian S White, Xing Yi Woo, Soner Koc, Todd Sheridan, Steven B Neuhauser, Shidan Wang, Yvonne A Evrard, Li Chen, Ali Foroughi Pour, John D Landua, R Jay Mashl, Sherri R Davies, Bingliang Fang, Maria Gabriela Raso, Kurt W Evans, Matthew H Bailey, Yeqing Chen, Min Xiao, Jill C Rubinstein, Brian J Sanderson, Michael W Lloyd, Sergii Domanskyi, Lacey E Dobrolecki, Maihi Fujita, Junya Fujimoto, Guanghua Xiao, Ryan C Fields, Jacqueline L Mudd, Xiaowei Xu, Melinda G Hollingshead, Shahanawaz Jiwani, Saul Acevedo, Pdxnet Consortium, Brandi N Davis-Dusenbery, Peter N Robinson, Jeffrey A Moscow, James H Doroshow, Nicholas Mitsiades, Salma Kaochar, Chong-Xian Pan, Luis G Carvajal-Carmona, Alana L Welm, Bryan E Welm, Ramaswamy Govindan, Shunqiang Li, Michael A Davies, Jack A Roth, Funda Meric-Bernstam, Yang Xie, Meenhard Herlyn, Li Ding, Michael T Lewis, Carol J Bult, Dennis A Dean, Jeffrey H Chuang

Faculty, Staff and Students Publications

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a …

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository With Genomic And Pathologic Annotations Enables Deep Learning Analysis, Brian S White, R Jay Mashl, Sherri R Davies, Ryan C Fields, Jacqueline L Mudd, Ramaswamy Govindan, Shunqiang Li, Li Ding, Et Al.

2020-Current year OA Pubs

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a …

In Search Of The Locus Coeruleus: Guidelines For Identifying Anatomical Boundaries And Electrophysiological Properties Of The Blue Spot In Mice, Fish, Finches, And Beyond, Amelien Vreven, Gary Aston-Jones, Anthony E Pickering, Gina R Poe, Barry Waterhouse, Nelson K Totah

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of …

Fasthpocr: Pragmatic, Fast, And Accurate Concept Recognition Using The Human Phenotype Ontology., Tudor Groza, Dylan Gration, Gareth Baynam, Peter N Robinson

Faculty Research 2024

MOTIVATION: Human Phenotype Ontology (HPO)-based phenotype concept recognition (CR) underpins a faster and more effective mechanism to create patient phenotype profiles or to document novel phenotype-centred knowledge statements. While the increasing adoption of large language models (LLMs) for natural language understanding has led to several LLM-based solutions, we argue that their intrinsic resource-intensive nature is not suitable for realistic management of the phenotype CR lifecycle. Consequently, we propose to go back to the basics and adopt a dictionary-based approach that enables both an immediate refresh of the ontological concepts as well as efficient re-analysis of past data.

RESULTS: We developed …

Reliable Detection Of Generalized Convulsive Seizures Using An Off-The-Shelf Digital Watch: A Multisite Phase 2 Study, Yash Shashank Vakilna, Xiaojin Li, Jaison S Hampson, Yan Huang, John C Mosher, Yuri Dabaghian, Xi Luo, Blanca Talavera, Sandipan Pati, Masel Todd, Ryan Hays, Charles Akos Szabo, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy.

Methods: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of …

Fedgmmat: Federated Generalized Linear Mixed Model Association Tests, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Increasing genetic and phenotypic data size is critical for understanding the genetic determinants of diseases. Evidently, establishing practical means for collaboration and data sharing among institutions is a fundamental methodological barrier for performing high-powered studies. As the sample sizes become more heterogeneous, complex statistical approaches, such as generalized linear mixed effects models, must be used to correct for the confounders that may bias results. On another front, due to the privacy concerns around Protected Health Information (PHI), genetic information is restrictively protected by sharing according to regulations such as Health Insurance Portability and Accountability Act (HIPAA). This limits data sharing …

In Vivo Validation Of Late-Onset Alzheimer's Disease Genetic Risk Factors., Michael Sasner, Christoph Preuss, Ravi S Pandey, Asli Uyar, Dylan Garceau, Kevin P Kotredes, Harriet M. Jackson, Adrian L Oblak, Peter Bor-Chian Lin, Bridget Perkins, Disha Soni, Cindy Ingraham, Audrey Lee-Gosselin, Bruce T Lamb, Gareth R Howell, Gregory W. Carter

Faculty Research 2024

INTRODUCTION: Genome-wide association studies have identified over 70 genetic loci associated with late-onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

METHODS: Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD-sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

RESULTS: We created new models for 11 coding and loss-of-function risk variants. …

Vaccine-Sensitive Allocation - Another Divide To Divide Us?, Joelle Robertson-Preidler, Olivia Schuman

Faculty and Staff Publications

No abstract provided.

A Longitudinal Evaluation Of Personalized Intrinsic Network Topography And Cognitive Decline In Parkinson's Disease, Renxi Li, Vincent Pozorski, Kevin Dabbs, Maureen Haebig, Christopher R. Cox, Colleen Pletcher, Alexandra Wey, Amy Barzgari, Frances Theisen, Ozioma Okonkwo, Catherine L. Gallagher

Faculty Publications

Resting state functional magnetic resonance imaging (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network-based statistics (NBS) and calculations of …

A Risk Is Not A Harm: Abortion Exceptions In State Laws, Trevor M Bibler, Alison Suen

Center for Medical Ethics and Health Policy Staff Publications

This letter responds to the article "Beneath the Sword of Damocles: Moral Obligations of Physicians in a Post-Dobbs Landscape," by Anne Drapkin Lyerly, Ruth R. Faden, and Michelle M. Mello, in the May-June 2024 issue of the Hastings Center Report.

The Effect Of Adamts13 On Graft-Versus-Host Disease, Dan Li, Min Soon Cho, Ricardo Gonzalez-Delgado, Xiaowen Liang, Jing-Fei Dong, Miguel A Cruz, Qing Ma, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed …

Trans-Ancestral Genetic Risk Factors For Treatment-Related Type 2 Diabetes Mellitus In Survivors Of Childhood Cancer, Cindy Im, Achal Neupane, Jessica L Baedke, Brian Lenny, Angela Delaney, Stephanie B Dixon, Eric J Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A Richard, M Monica Gramatges, Philip J Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Yutaka Yasui, Carmen L Wilson, Yadav Sapkota

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D.

Patients and methods: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic …

Data Consistency Of Two National Registries In Iran: A Preliminary Assessment To Health Information Exchange., Mohammad Dashtkoohi, Mohammad Poursalehian, Zahra Azadmanjir, Masoomeh Vaeidi, Mahdi Mohammadzadeh, Mahdi Sharif-Alhoseini, Khatereh Naghdi, Marzieh Moniri Asl, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

BACKGROUND: The National Spinal Cord Injury Registry of Iran (NSCIR-IR) and the National Trauma Registry of Iran (NTRI) were established to meet the data needs for research and assessing trauma status in Iran. These registries have a group of patients shared by both registries, and it is expected that some identical data will be collected about them. A general question arises whether the spinal cord injury registry can receive part of the common data from the trauma registry and not collect them independently.

METHODS: We examined variables captured in both registries based on structure and concept, identified the overlapping period …

Wide-Field Optical Coherence Tomography Imaging Improves Rate Of Change Detection In Progressing Glaucomatous Eyes Compared With Standard-Field Imaging, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Jost B. Jonas, Leslie Hyman, Robert N. Weinreb, Linda M. Zangwill

Wills Eye Hospital Papers

PURPOSE: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.

METHODS: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube …