Medicine and Health Sciences Commons^™

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Nuclear Receptor Subfamily 4 Group A Member 2 Induces A Warburg-Like Effect And Promotes Phospholipids Synthesis In The Mouse Heart, Sadia Ashraf, Dorcas Odogwu, David D Mcpherson, Romain Harmancey

Faculty, Staff and Student Publications

Myocardial metabolic flexibility is critical to ensuring the heart's capacity to maintain contraction and cellular functions under rapidly evolving environmental conditions. Although it is a tightly regulated process, loss of metabolic flexibility is often regarded as a contributing factor to heart failure. This study aims to determine the effects of the early response transcription factor nuclear receptor subfamily 4 group A member 2 (NR4A2) on cardiac metabolism and the resulting impact on left ventricular function. A multiomics approach combining the analysis of global ventricular gene expression, genome-wide NR4A2 binding, and untargeted metabolomics was used to track the molecular effects of …

Distinct Effects Of Complement C4a And C4b Copy Numbers In Systemic Sclerosis Serological And Clinical Subtypes, Javier Martínez-López, Carlos Rangel-Peláez, Inmaculada Rodriguez-Martin, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José L Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Gianluca Moroncini, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcon-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera, Martin Kerick

Faculty, Staff and Student Publications

Objective: Complement component 4 (C4), encoded by C4A and C4B within the major histocompatibility complex (MHC) on chromosome 6, regulates the immune response and clears immune complexes. The variable copy number (CN) of C4 genes and retroviral human endogenous retrovirus K (HERV-K) element influence its function. Given the relationship of C4 CN with systemic sclerosis (SSc) risk, we assessed associations with SSc clinical and serologic subtypes.

Methods: We compared imputed C4 CNs across SSc subgroups (4,049 anticentromere positive [ACA+]; 2,200 anti-topoisomerase I [ATA+]; 577 anti-RNA polymerase [ARA+]; 1,078 triple-negative [TN] patients; 6,295 limited cutaneous SSc [lcSSc]; and 2,946 diffuse cutaneous …

Growth Failure And Early Recurrence In Congenital Diaphragmatic Hernia: An International Cohort Study, Rachel C Bordelon, Kylie I Holden, Charles C Miller, Ashley H Ebanks, Kevin P Lally, Matthew T Harting, Allison L Speer, Representing The Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

Purpose: The primary objective was to determine whether growth failure (GF) is associated with early recurrence in congenital diaphragmatic hernia (CDH). The secondary objective was to characterize the prevalence and severity of GF in CDH survivors.

Background: GF is common among CDH survivors, yet it is unclear how growth challenges affect overall morbidity, including hernia recurrence. CDH-specific nutritional guidelines include high calorie and protein targets during periods of acute illness but may benefit from clarifying the relationship between growth and adverse outcomes in this population.

Methods: This multicenter cohort study retrospectively analyzed prospectively collected data from the CDH Study Group …

A Topic Modeling Analysis Of Stigma Dimensions, Social, And Related Behavioral Circumstances In Clinical Notes Among Patients With Hiv, Ziyi Chen, Yiyang Liu, Mattia Prosperi, Krishna Vaddiparti, Robert L Cook, Jiang Bian, Yi Guo, Yonghui Wu

Faculty, Staff and Student Publications

Objective: To characterize stigma dimensions, social, and related behavioral circumstances in people living with HIV (PLWHs) seeking care, using natural language processing methods applied to a large collection of electronic health record (EHR) clinical notes from a large integrated health system in the southeast United States.

Methods: We identified a cohort of PLWHs from the University of Florida (UF) Health Integrated Data Repository and performed topic modeling analysis using Latent Dirichlet Allocation (LDA) to uncover stigma-related dimensions and related social and behavioral contexts. Domain experts created a seed list of HIV-related stigma keywords, then applied a snowball strategy to iteratively …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

Dyadic Associations Between Stress And Sleep Quality And Moderating Effects Of Emotional Intimacy And In Survivors Of Young Adult Cancer And Their Spouses: An Observational Study, Haejeong An, Seokhun Kim, Michael Roth, Kathrin Milbury, Dalnim Cho

Faculty, Staff and Student Publications

Background: Survivors of young adult (YA) cancer often experience substantial stress during the transition to survivorship, which may impair sleep. Although the stress-sleep link is well established, its role within survivor-spouse dyads remains unclear. Emotional intimacy may influence how couples regulate stress and affect sleep. This study examined dyadic associations between stress and sleep among survivors of YA cancer and their spouses and significant others (hereafter spouses) and tested emotional intimacy as a moderator.

Methods: A total of 103 survivor of YA cancer-spouse dyads completed self-reported measures of stress, emotional intimacy, and sleep quality. An actor-partner interdependence moderation model was …

Associations Between Sociodemographic Predictors And Age Of Referral For Autism Spectrum Disorder (Asd) Diagnosis Since The Beginning Of The Covid-19 Pandemic, Mallika Mathur, Ruosha Li, Sandra Mckay, Christine Markham, Deepali K Ernest, Shreela Sharma

Faculty, Staff and Student Publications

Purpose: Sociodemographic characteristics, such as race and ethnicity, are associated with delays in ASD diagnosis. However, limited literature has examined the characteristics associated with delayed diagnosis since the start of the COVID-19 pandemic. This study aimed to identify the individual and aggregate sociodemographic characteristics associated with the age at which a child receives a referral for a diagnosis (from March 2020 to May 2023) and evaluate the impacts of the pandemic on this association.

Methods: Using cross-sectional data obtained from patients' electronic health records and the U.S. Census Bureau, we examined associations using linear regressions (N = 507). A subgroup …

Physical Activity For Public Health In The 21st Century, Deborah Salvo, Inacio Crochemore-Silva, Andrea Wendt, Jakob Tarp, Eric J Shiroma, Richard J Simpson, I-Min Lee, Ulf Ekelund, Ester Cerin, Youssouf Keita, Adrian Bauman, Pedro C Hallal, Andrea Ramirez Varela, Michael Pratt, Rodrigo Reis, Erica Hinckson, Ding Ding, Harold W Kohl, James Sallis

Faculty, Staff and Student Publications

With over 5 million attributed deaths per year, physical inactivity is a major global public health issue. Although the importance of physical activity is well recognized within the scope of obesity and cardiometabolic disease prevention and control, its broader benefits for the health of individuals and societies are yet to be fully harnessed. Furthermore, the role of active leisure, active transport and active labor-primary domains of physical activity-in supporting or hindering social and health equity has been largely overlooked. Here we (1) used a health equity lens to describe global domain-specific physical activity inequalities through an analysis of World Health …

Outcomes After Pulmonary Artery Flow Reducer Implantation In High-Risk Neonates With Congenital Heart Disease And Pulmonary Overcirculation, Cihangir Buyukgoz, Shyam Sathanandam, Neil Tailor, Ashley Molloy, Thomas Spentzas, Karthik Ramakrishnan, Christopher Knott-Craig, Umar Boston

Faculty, Staff and Student Publications

Background: Surgical outcomes in neonates with complex congenital heart disease (CHD) and pulmonary overcirculation (POC) initially palliated with pulmonary flow reducers (PFRs) were evaluated.

Methods: This was a retrospective study conducted between January 1, 2020 and December 31, 2023. Eleven neonates underwent PFR palliation. Fenestrated Medtronic microvascular plugs (PFRs) were delivered into the branch pulmonary artery (PA). The target surgical procedure involved the removal of PFRs and biventricular repair (n = 9) or single-ventricle palliation (n = 2).

Results: Patients were deemed high risk on the basis of prematurity (n = 5), early gestational age (n = 5), heterotaxy (n …

Probability Of Fentanyl Adulteration In Cocaine Selectively Decreases Cocaine Demand, Cecilia Nunez, Jin H Yoon, James Mackillop, Margaret C Wardle

Faculty, Staff and Student Publications

Fentanyl-related, cocaine-overdose deaths have drastically increased, yet research on how people who use cocaine perceive fentanyl adulteration is limited. This study developed the novel Adulterated Cocaine Purchasing Task (ACocPT), a modification of the original Cocaine Purchasing Task, to quantify how people respond to fentanyl adulteration in cocaine. In the ACocPT, participants indicated how much cocaine they would purchase when cocaine had no (0%) vs. some (10%) probability of fentanyl adulteration. Study aims were: 1) determine how possible fentanyl adulteration affects cocaine demand, and 2) determine which individual characteristics predict continued demand for cocaine despite fentanyl adulteration. This Amazon Mechanical Turk …

A Treat-To-Target Approach For Obesity Management: A Post Hoc Analysis Of The Surmount-5 Trial., Carel W Le Roux, Luca Busetto, Louis Aronne, Deborah Bade Horn, Georgios K Dimitriadis, Beverly Falcon, Luis-Emilio Garcia-Perez, Elisa Gomez Valderas, Theresa Hunter Gibble, Cagri Senyucel, Julia P Dunn

Faculty, Staff and Student Publications

Introduction: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide.

Methods: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) < 0.53, body mass index (BMI) < 27 kg/m2, or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored.

Results: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR < 0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS.

Conclusion: In this …

Confessions In Cases Of Child Physical Abuse-A Capnet Study., Margaret R. Russell, Antoinette L. Laskey, Henry T. Puls, Suzanne P. Starling, Joanne N. Wood, Daniel M. Lindberg, Nancy S. Harper, Caitlin R. Mcnamara, Angela W. Bachim, Farah W. Brink, Lori D. Frasier, James Anderst, Porcia Vaughn, Kristine A. Campbell

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

METHODS: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

RESULTS: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

CONCLUSIONS: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Initial Site Of Metastasis Influences Prognosis In Pancreatic Ductal Adenocarcinoma, Eleanor Mancheski, David Baek, Wilbur Bowne, Harish Lavu, Charles Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

METHODS: This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was …

Bridging Gaps: Enhancing Sleep And Health Disparities In Latino Families With Young Adults With Autism Using A Culturally Adapted Intervention, Antonio F Pagán, Alejandro L Pagán, Linda Hernandez, Matthew R Cribbet, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study examined the effects of a culturally adapted intervention, ¡Iniciando! la Adultez, on sleep and health-related quality of life (HRQoL) in Latino young adults with autism spectrum disorder (ASD) and their Spanish-speaking parents. The intervention targeted the transition to adulthood, a period associated with increased challenges in sleep and HRQoL, particularly for underserved Latino populations. Participants included 26 young adults and 38 parents who completed assessments at baseline and post-treatment. The results indicated significant improvements in several HRQoL domains for both groups, with young adults reporting enhanced emotional well-being, social functioning, and general health. Parents experienced notable improvements …

Visual Recognition Of The Anteroposterior Female Body Axis Drives Spatial Elements Of Male Courtship In Drosophila, Ross M Mckinney, Christian Monroy Hernandez, Yehuda Ben-Shahar

2020-Current year OA Pubs

Drosophila males exhibit a highly stereotypic courtship ritual toward virgin females, which is comprised of a sequence of specific behavioral elements that depend on inputs from diverse sensory modalities. Particularly, the visual system of the male plays an important role in detecting salient patterns, colors, and motion cues from conspecifics, which can promote or inhibit specific aspects of male courtship such as chase and song production. Here, we use a computer vision and machine learning-based approach, with a simplified courtship paradigm, to show that males also depend on visual cues to determine the anterior-posterior body axis of females, which drives …

Intracranial Mesenchymal Tumor, Fet::Creb Fusion-Positive: An Integrative Analysis Of 81 Cases, Sharika Rajan, Robert Schmidt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1, or CREM). The methylation signature(s), gene expression characteristics, and clinical behavior of this important tumor type require further characterization.

METHODS: We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available.

RESULTS: ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified …

Lyplal1 Rare Loss-Of-Function Variants In Humans And Deletion In Human Hepatoma Cells Protect Against Masld, Rawdat Hussain, Chinmay Raut, Ponnandy Prabhu, Akram Irshaid, Yash Hegde, Yue Chen, Asmita Pant, Antonino Oliveri, Xiaochao Wei, Lishi Yin, Tiffany L Russell, Brian Halligan, Clay F Semenkovich, Elizabeth K Speliotes

2020-Current year OA Pubs

Genetic variants near LYPLAL1 are associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in humans, but their impact on LYPLAL1 function is unknown. We identified LYPLAL1 loss-of-function variants from UK BioBank (UKBB) whole-exome sequencing data that had AlphaMissense or GPN-MSA scores in the top 20% of LYPLAL1 variants for being disruptive. We aggregated these variants and carried out burden analysis for effects on MRI Proton Density-Fat Fraction (MRI-PDFF) and ICD-based MASLD in UKBB. Rare loss-of-function LYPLAL1 variants were associated with reduced MRI-PDFF and ICD diagnosed MASLD across sexes. We used CRISPR to knockout and overexpress LYPLAL1 in human hepatoma cells …

The Femoral Head Edema Zone: A Novel Classification Scheme To Better Predict Osteonecrosis Progression, Deniz C Ince, Vivek P Shah, Kenichi Kikuchi, Kyle P O'Connor, Elizabeth L Yanik, John C Clohisy, Cecilia Pascual-Garrido

2020-Current year OA Pubs

BACKGROUND: This study proposed a new classification, the Edema Zone classification, that uses magnetic resonance imaging images to grade the extent of edema in osteonecrosis of the femoral head. The purpose of the study was (1) to examine how the Edema Zone classification compared to the Japanese Investigation Committee (JIC) classification's prognostic ability for early conversion to total hip arthroplasty (THA), and (2) to determine how accurately and reliably the Edema Zone classification performed as a classification system.

METHODS: This was a retrospective study of hips that converted to THA from a core decompression within 26 months compared to hips …

Alterations In Ascending Aortic Hemodynamics And Aortic Length Correlate With Sex-Specific Thoracic Aortic Aneurysm Dilation And Lifespan In A Mouse Model Of Severe Marfan Syndrome, Krashn Kr Dwivedi, Yufan Wu, Marisa S Bazzi, Hadi Wiputra, Jacob Rother, James D Quirk, Victor H Barocas, Jessica E Wagenseil

2020-Current year OA Pubs

Thoracic aortic aneurysm (TAA) is a dilation of the aorta that may eventually dissect and/or rupture. It is associated with genetic disorders such as Marfan syndrome (MFS) and is a life-threatening cardiovascular condition if left untreated. Current clinical guidelines for TAA management are primarily based on maximum diameter thresholds that are often inadequate, particularly in MFS patients. Moreover, the diameter thresholds are not sex-specific, despite growing evidence that TAA outcomes in MFS are influenced by sex. The aim of this study was to identify non-invasive biomarkers for better management of TAA using male and female mice that are a genetic …

Promoting Community And Social Participation In Chronic Stroke: A Pilot Study Of The Engage Intervention, Elizabeth Skidmore, Carolyn Baum, Jessica Kersey, Emily Kringle, Kelsey Voltz-Poremba, Sular Gordon, Tina Harris, Heidi Fischer, Maureen Gecht, Michelle Furman, Joy Hammel

2020-Current year OA Pubs

BACKGROUND: Survivors of stroke report low levels of community and social participation, even years after stroke. ENGAGE is a community-based intervention that merges social learning, guided problem solving, and supervised practice to collaboratively identify, generate, and apply solutions to challenges with community and social participation after stroke.

OBJECTIVE: We examined the feasibility, acceptability, and safety of ENGAGE and characterized within group changes in community and social participation outcomes.

METHODS: Community-dwelling survivors of stroke, occupational therapy providers, and occupational therapy scientists partnered to co-design the essential and structural elements of ENGAGE, as well as to evaluate ENGAGE using a multi-site single-arm …

Acute Myocardial Infarction In Medicare Beneficiaries During And After The Covid-19 Pandemic, Jonah M Graves, R J Waken, Fengxian Wang, Rishi K Wadhera, Jose F Figueroa, E John Orav, Osvaldo J Laurido-Soto, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: During early months of the COVID-19 pandemic, presentations for acute myocardial infarction (AMI) declined significantly, and outcomes worsened. However, the full extent and long-term sequelae of changes in AMI epidemiology during the pandemic remain uncertain, as does whether these patterns differed by rurality.

OBJECTIVE: To describe the epidemiology of AMI-related hospitalizations, interventions, and outcomes among Medicare beneficiaries throughout the COVID-19 pandemic, focusing on differences in urban and rural populations.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included all Medicare fee-for-service beneficiaries with AMI between January 1, 2018, and December 31, 2023, in the analysis. Data were analyzed from …

Performance Of Multiple Multi-Cancer Detection Tests Using A Large Independent Reference Set (Alliance A212102), Marie E Wood, Mark Watson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials.

METHODS: Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect ("targeted"), plus additional "non-targeted" and control samples. Companies reported …

Hepatitis C Virus Testing In Perinatally Exposed Children, Rachel L Epstein, Sarah Munroe, Elizabeth A Erdman, Amy Bettano, Megan R Curtis, Laura White, Elisha M Wachman, Anthony Osinski, Alexander Y Walley, Benjamin P Linas

2020-Current year OA Pubs

IMPORTANCE: Despite rising hepatitis C virus (HCV) incidence in pregnant people, studies demonstrate that fewer than 50% of perinatally exposed infants receive HCV testing. Few studies report treatment of infected infants or factors affecting testing.

OBJECTIVE: To identify birthing parent and child factors associated with appropriate HCV testing for perinatally exposed infants and characterize HCV care for children with HCV.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included records on testing, care, and treatment for Massachusetts children perinatally exposed to HCV between 2014 and 2021 from a statewide health database linking statewide vital statistics, infectious disease surveillance data, substance use …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …