Digital Commons Network^™

Targeting Aldh16a1 Mediated Thioredoxin Lysosomal Degradation To Enhance Ferroptosis Susceptibility In Smarca4-Deficient Nsclc, Guoshu Bi, Jiaqi Liang, Yunyi Bian, Guangyao Shan, Shencheng Ren, Xiaolong Huang, Qun Wang, Wei Jiang, Boyi Gan, Cheng Zhan

Faculty, Staff and Student Publications

Ferroptosis, an iron-dependent form of cell death, holds promise for cancer therapy. However, the intricate link between ferroptosis and oncogenic mutations remains unclear. Here we show that SMARCA4, a well-established tumour suppressor whose deficiency is associated with poor prognosis and resistance to treatments, sensitizes non-small cell lung cancer (NSCLC) cells to ferroptosis. Mechanistically, SMARCA4 promotes chromatin accessibility and expression of ALDH16A1. Surprisingly, ALDH16A1 lacks ALDH enzymatic activity, but binds to the anti-ferroptotic oxidoreductase thioredoxin (TXN), facilitating its translocation to the lysosome and subsequent degradation. Meanwhile, ALDH16A1 directly inhibits TXN's oxidoreductase function by occluding its active site. We also show that …

Trends In Radiation Use From 2004 To 2020 Among Adolescents And Young Adults With Hodgkin Lymphoma, Kelsey L Corrigan, Amy M Berkman, Jillian Gunther, Clark R Andersen, Susan Wu, Branko Cuglievan, Gohar Manzar, Penny Fang, Brian De, Sairah Ahmed, Cesar Nunez, Michelle A T Hildebrandt, David C Mccall, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Background: Hodgkin lymphoma has excellent survival rates in adolescents and young adults (AYA, diagnosed between ages 15 and 39 years). However, survivors are at risk of treatment-related late effects. Whereas radiotherapy (RT) de-escalation/omission has emerged as an approach to minimize late effects, no prior studies have evaluated RT use over time in AYAs with Hodgkin lymphoma.

Methods: Using the National Cancer Database, we identified 40,717 AYAs diagnosed with Hodgkin lymphoma between 2004 and 2020. Differences in sociodemographic and clinical variables were assessed using a two-sample two-sided t test or χ2 test. RT use was summarized per year by frequency with …

Efficacy Of Atr Kinase Inhibitor Elimusertib Monotherapy Or Combination In Tumors With Dna Damage Response Pathway And Other Genomic Alterations, Kaushik Varadarajan, Christian X Cruz Pico, Kurt W Evans, Maria Gabriela Raso, Yasmeen Qamar Rizvi, Dhruv Chachad, Bailiang Wang, Stephen M Scott, Ming Zhao, Argun Akcakanat, Antje M Wengner, Timothy A Yap, Funda Meric-Bernstam

Faculty, Staff and Student Publications

The ataxia telangiectasia and RAD3-related (ATR) kinase functions with ataxia telangiectasia-mutated (ATM) kinase as a modulator of DNA damage response (DDR). We assessed the antitumor effects of the ATR inhibitor elimusertib (BAY-1895344) in patient-derived xenograft (PDX) models with DDR alterations. Antitumor activity was assessed by change in tumor volume (TV) from baseline. Responses were categorized as follows: partial response (PR), ≥30% decrease in TV; ≥20% increase in TV, progressive disease; and non-PR/progressive disease, stable disease (SD). Event-free survival was defined as time for tumor doubling (EFS-2). Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. …

Identification Of An Rsph4a Founder Variant And Newborn Screening For Primary Ciliary Dyskinesia, Wilfredo De Jesús-Rojas, Katherine P Guerra-Torres, Alondra J Rosado-Ayala, Edwin L Acevedo-Soto, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

This cross-sectional study estimates the prevalence of an RSPH4A variant identified in Puerto Rico in an effort to evaluate the feasibility of targeted newborn screening for primary ciliary dyskinesia (PCD).

Functional Connectivity Predicting Transdiagnostic Treatment Outcomes In Internalizing Psychopathologies, Kai Zhang, Heide Klumpp, Jagan Jimmy, K Luan Phan, Mohammed R Milad, Zhenfu Wen

Faculty, Staff and Student Publications

Importance: Predicting treatment outcomes for internalizing psychopathologies (IPs), such as depression and anxiety, holds promise for advancing precision medicine. The extent to which whole-brain functional connectivity (FC) can predict treatment responses for patients with IPs across different therapeutic modalities remains unclear.

Objective: To examine whether pretreatment FC patterns predict multidimensional treatment outcomes in patients with IPs and whether predictive performance generalizes across diagnoses and treatment modalities.

Design, setting, and participants: This prognostic study analyzed baseline neuroimaging and clinical data from patients with IPs enrolled in 1 of 2 randomized clinical trials (conducted from December 2013 to February 2018 and September …

Adaptive Filters At The First Olfactory Synapse, Elizabeth H Moss, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The olfactory system is able to filter odor representations based on attention and learning. Two PLoS Biology studies reveal how short axon cells in the olfactory bulb integrate cholinergic input from the basal forebrain to dynamically regulate olfactory input.

Folliculin Deletion In The Mouse Kidney Results In Cystogenesis Of The Loops Of Henle Via Aberrant Tfeb Activation, Ola Shalaby, Tomoko Ohmori, Koichiro Miike, Shunsuke Tanigawa, Luh Ade Wilan Krisna, Alessia Calcagnì, Andrea Ballabio, Yoshiaki Kubota, Laura S Schmidt, W Marston Linehan, Takaaki Ito, Masaya Baba, Ryuichi Nishinakamura

Duncan NRI Faculty and Staff Publications

The mammalian kidney contains numerous nephrons connected to the collecting ducts, and each nephron consists of a glomerulus, a proximal tubule, the loop of Henle (LoH), and a distal tubule. Folliculin (FLCN) is a causative gene for Birt-Hogg-Dubé syndrome, which is characterized by a variety of manifestations, including renal cysts and cancer. Although deletion of Flcn in the mouse collecting duct and distal nephron leads to cyst formation, its precise role in the entire nephron remains unclear. Herein, nephron-specific Flcn knockout mice exhibited cystogenesis along the entire nephron segments, most prominent in the LoH, preceded by an irregularly shaped lumen …

Diagnostic Yield Of Exome Sequencing For Pregnancies With And Without Fetal Anomalies And For Stillbirth, Roni Zemet, Christian M Parobek, April D Adams, Mohamad Ali Maktabi, Lena Shay, Linyan Meng, Pengfei Liu, Hongzheng Dai, Fan Xia, Christine Eng, Ignatia B Van Den Veyver, Liesbeth Vossaert

Duncan NRI Faculty and Staff Publications

Objective: Exome sequencing (ES) benefits the genetic work-up for fetuses with structural anomalies, but data on its utility for fetuses without anomalies and stillbirths is more limited. We report our experience with prenatal ES for all three indications.

Method: We retrospectively reviewed results from 344 trio-ES performed for fetuses with structural anomalies (N = 262), stillbirths (N = 39), and fetuses without anomalies (N = 43), many of which had a relevant family history. We classified pathogenic variants (P), likely pathogenic variants (LP), or variants of uncertain significance (VUS) favoring pathogenicity in a gene consistent with the fetal phenotype as …

The Ethics Of Clinical Ethics, Matthew Shea

Center for Medical Ethics and Health Policy Staff Publications

The concept ethics defines health care ethics as a professional practice. Yet the meaning of "ethics" is often unclear in the theory and practice of clinical ethics. Clarity on this matter is crucial for understanding the nature of clinical ethics and for debates about the professional identity and proper role of ethicists, the sort of training and skills they should possess, and whether they have ethics expertise. This article examines two different ways the ethics of clinical ethics can be understood: Real Ethics, which consists of objective moral norms grounded in moral truth; and Conventional Ethics, which consists of conventional …

Microbiome Signatures And Inflammatory Biomarkers In Culture-Negative Neonatal Sepsis, Morcos Hanna, Shixia Huang, Matthew Ross, Anaid Reyes, Dimuthu Perera, Anil Surathu, Sara Javornik Cregeen, Joseph Hagan, Mohan Pammi

Faculty and Staff Publications

Overuse of antibiotics is a concern in 'culture-negative sepsis' but it is unclear whether this is due to infection with viruses, fungi or other microbes that are not easily cultured, or whether it results from inflammatory processes. In a prospective study, we enrolled 50 preterm neonates with culture-positive sepsis (CP), culture-negative sepsis (CN), and asymptomatic preterm controls (CO). The microbiome of stool, skin, and blood, including bacterial, viral and fungal components and serum cytokine profiles were evaluated. The microbiome alpha or beta diversity did not differ between CN and CO groups. A MaAsLin analysis revealed increased relative abundances of specific …

Synthetic Zfta Fusions Pinpoint Disordered Protein Domain Acquisition As A Mechanism Of Brain Tumorigenesis, A Arabzade, H K Shirnekhi, S Varadharajan, S M Ippagunta, A H Phillips, N Laboe, D W Baggett, Wahiduzzaman, M Jo, T Zheng, R Pathak, D Gee, D Bhimsaria, H Wu, X Gao, J Liu, E Emanus, A Bland, A Kardian, A Hancock, B Holcomb, T Wright, T Bugbee, H Sun, M Zhai, E Caesar, M Park, S Tripathi, A Shirinifard, K Lowe, A Khalighifar, R A Petersen, S King, D Stabley, A Pitre, G E Campbell, C-G Park, W T Freyaldenhoven, B Chandra, Y Xia, E Bonten, A Achari, S Kandikonda, A Carisey, S B Pounds, J Xu, D W Ellison, B Deneen, K C Bertrand, R W Kriwacki, S C Mack

Children’s Nutrition Research Center Staff Publications

Over 95% of ependymomas that arise in the cortex are driven by a gene fusion involving the zinc finger translocation-associated (ZFTA) protein. Here, using super-resolution and lattice light-sheet microscopy, we demonstrate that the most frequent fusion variant, ZFTA-RELA (ZR), forms dynamic nuclear condensates that are required for oncogene expression and tumorigenesis. Mutagenesis studies of ZR reveal a key intrinsically disordered region (IDR) in RELA that governs condensate formation. Condensate-modulating IDR mutations introduced into ZR impaired its genomic occupancy at oncogenic loci and inhibited the recruitment of transcriptional effector proteins, such as MED1, BRD4 and RNA polymerase II. Using nuclear magnetic …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

Genome-Wide Association Study Provides Novel Insight Into The Genetic Architecture Of Severe Obesity, Mohanraj Krishnan, Mohammad Yaser Anwar, Anne E Justice, Geetha Chittoor, Hung-Hsin Chen, Rashedeh Roshani, Alyssa Scartozzi, Rachel R Dickerson, Roelof A J Smit, Michael H Preuss, Nathalie Chami, Benjamin S Hadad, Esteban J Parra, Miguel Cruz, Qin Hui, Peter W F Wilson, Yan V Sun, Xiaoyu Zhang, Gregorio V Linchangco, Sharon L R Kardia, Jessica D Faul, David R Weir, Lawrence F Bielak, Heather M Highland, Kristin L Young, Baiyu Qi, Yujie Wang, Myriam Fornage, Christopher Haiman, Iona Cheng, Ulrike Peters, Charles Kooperberg, Steven Buyske, Joseph B Mccormick, Susan P Fisher-Hoch, Frida Lona-Durazo, Jesus Peralta, Jamie Gomez-Zamudio, Stephen S Rich, Kendra R Ferrier, Ethan M Lange, Christopher R Gignoux, Eimear E Kenny, Genevieve L Wojcik, Kelly Cho, Michael J Gaziano, Luc Djousse, Shuwei Liu, Dhananjay Vaidya, Renée De Mutsert, Navya S Josyula, Christopher R Bauer, Wei Zhao, Ryan W Walker, Jennifer A Smith, Leslie A Lange, Mariah C Meyer, Ching-Ti Liu, Lisa R Yanek, Miryoung Lee, Laura M Raffield, Ruth J F Loos, Penny Gordon-Larsen, Jennifer E Below, Kari E North, Mariaelisa Graff

The Brown Foundation: Institute of Molecular Medicine

Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution (≥95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI ≥ 40 kg/m2 and Obesity Class IV BMI ≥ 50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated three novel …

Utilization Of Outpatient Mental Health Services During And 2 Years After The Covid-19 Pandemic, Michelle A Hayek, Hye-Chung Kum, Sulki Park, Robert Ohsfeldt, Mark A Lawley, Michelle J Bovin

The Brown Foundation: Institute of Molecular Medicine

Objective: Analyze the impact of COVID-19 on outpatient mental health (OP-MH) utilization patterns, particularly telehealth, across eight different MH conditions with a 2-year follow-up.

Methods: This population-based cohort study uses a 5% random sample of Medicare beneficiaries aged ≥18 and newly diagnosed with one of the eight MH disorders: psychotic, depressive, bipolar, anxiety, trauma-related, substance-use, other MH disorders, and two or more MH disorders. Monthly OP-MH utilization patterns were compared among patients in 2020-2021 newly diagnosed in 2019 to comparable prepandemic cohorts newly diagnosed in 2017. Multiple logistic regression models were conducted to examine differences in telehealth utilization across MH …

Does Stem Design Affect Primary Stability Of Splined Tapered Fluted Stems? A Biomechanical Cadaver Study, Shuyang Han, Daniel C Mascarenhas, Camryn A Pletka, Jonathan E Gold, Sabir K Ismaily, Matthew Cao, Matthew W Brewer, Robert Frangie, Philip C Noble, David Rodriguez-Quintana

Faculty, Staff and Student Publications

Background: Tapered fluted stems are an excellent solution for revision hip arthroplasty following periprosthetic fractures. However, existing implant designs differ in terms of the number of splines, taper angle, and cross-sectional design, and there is a lack of knowledge on the biomechanical effect of these design variations. Therefore, the objective of this study was to compare the primary stability of two representative stem designs and the extent and distribution of stem-bone contact in a periprosthetic fracture model. It was hypothesized that a greater number of splines would lead to greater stability.

Methods: There were six pairs of cadaver femora included …

Drivers Of Frequent Emergency Department Use In Socioeconomically Disadvantaged Older Adults: A Qualitative Study, Elise Brickhouse, Mariana Rios, Aanand D Naik, Margaret Samuels-Kalow, Naomi George

Faculty, Staff and Student Publications

Background: The emergency department (ED) is the safety net for and a common point of healthcare access for socioeconomically disadvantaged older adults. Little is known about socioeconomically disadvantaged older ED patients' perspectives on their health, healthcare access, and ED use. Such insights could guide tailored interventions to address unmet clinical and health-related social needs (HRSN).

Methods: We performed a qualitative study with older adults in a single public safety net hospital ED. We interviewed patients age 60+ who had ≥ 4 ED 4 visits in the past year. Semi-structured interviews explored perceived health needs and motivations underlying ED visits. We …

Chest X-Ray Interpretation In The Epico Pediatric Covid-19 Study: Addressing Misconceptions, Daniela Duarte-Montero, María Margarita Rodriguez, Arianna Martinez, Paola Sanchez, Carolina Tovar, Gabriela Friedrich, Gustavo Adolfo Triana-Rodriguez, Mónica Royero-Arias, Jessica Echeverry, Tamara Gamo, Luz Ángela Moreno, Olga Lucía Baquero, Luz Marina Mejía, Sonia Restrepo-Gualteros, Sergio Moreno-Lopez, Juan Gabriel Piñeros, Carlos Álvarez-Moreno, Alejandro Díaz-Díaz, Clara Galvis-Diaz, José Manuel Nieto, Irati Gastesi, Cinta Moraleda, Alfredo Tagarro García, Andrea Ramirez Varela, Epico‐Colombia And Epico‐Aep Working Groups

Faculty, Staff and Student Publications

No abstract provided.

Steroid Hormone Biosynthesis And Dietary Related Metabolites Associated With Excessive Daytime Sleepiness, Robert Kaplan, Kent D Taylor, Peter Y Liu, Satu J Strausz, Hanna M Ollila, Tianyi Huang, Russell P Tracy, Craig Johnson, Stephen S Rich, Clary B Clish, Jerome I Rotter, Susan Redline, Tamar Sofer, Heming Wang

Faculty, Staff and Student Publications

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses.

Methods: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each …

A Metabolomics Study Of Cardiac Dysfunction In Hyperglycemia: Findings From The Atherosclerosis Risk In Communities (Aric) Study And The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Hicham Skali, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J Rodriguez, Qibin Qi, Susan Cheng, Bing Yu

Faculty, Staff and Student Publications

Objective: Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals.

Research design and methods: We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011-2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Critical Care Cadets: A Serious Game For Managing Mechanical Ventilation, Aarti Bavare, Moushumi Sur, Shelley Kumar, Thomas Reeves, Brian Rissmiller

Faculty, Staff and Students Publications

Background: Pediatric critical care medicine (PCCM) fellows require proficiency in mechanical respiratory support and ventilator management strategies. Traditional training methods have limitations, and there is a need to expedite the learning process. Serious games have emerged as effective supplements to traditional teaching methods, promoting knowledge acquisition through immersive and engaging experiences. However, there is a void in the context of complex decision making in mechanical ventilation management.

Objective: To develop a serious game to enhance the knowledge and practical strategies of PCCM fellows in mechanical ventilation management.

Methods: The game was designed on the basis of theory-informed design principles and …

Treatment Of Cutaneous Collagenous Vasculopathy With Pulsed Dye Laser

Faculty, Staff and Students Publications

Objectives: Cutaneous collagenous vasculopathy (CCV) is a rare, idiopathic microangiopathy marked by widespread telangiectasias and histologic vessel wall thickening. Due to its rarity and clinical overlap with other vascular conditions, CCV poses diagnostic and therapeutic challenges. This report highlights the successful use of pulsed dye laser (PDL) therapy in treating a case of extensive CCV.

Methods: A 40-year-old woman with a decade-long history of progressive telangiectasias involving the extremities, trunk, and forearms underwent treatment with a 595-nm PDL. Six treatment sessions were conducted over 14 months.

Results: The patient experienced significant improvement in erythema, telangiectasias, and associated discomfort, with sustained …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

2d Speckle Tracking Strain Echocardiography In Multisystem Inflammatory Syndrome In Children: A Multicenter Analysis From The Music Study, Dongngan T Truong, Sanjeev Aggarwal, Joseph R Block, Tamara T Bradford, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese M Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean M Lang, Carol A Mcfarland, Elizabeth C Mitchell, Elias Moussi Saad, Todd T Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie K Votava-Smith, Hunter C Wilson, Jane W Newburger, Kevin G Friedman

Faculty, Staff and Students Publications

Background: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes.

Methods: We performed an ambi-directional, 32-center cohort study on hospitalized patients with MIS-C (March 2020-November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant).

Results: Of 349 patients (median age, 8.7 years [interquartile …

Patient-Centered Management Of Heavy Menstrual Bleeding While On Anticoagulation: A Survey Study, Leben Tefera, Jordan K Schaefer, Ang Li, Alejandra Gutierrez Bernal, Shruti Chaturvedi, Anjlee Mahajan, Leslie Lake, Jori May, Anna L Parks

Faculty, Staff and Students Publications

Background: Nearly three-quarters of women experience heavy menstrual bleeding (HMB) during anticoagulation treatment for venous thromboembolism (VTE). HMB can lead to medical interventions, impact school or work and diminish quality of life (QOL). While there are several management options for HMB in patients with VTE, we lack information on how patients approach HMB treatment decisions.

Objectives: We examined patients' experience with, perceptions of, and preferences for treatment of HMB while on anticoagulation.

Methods: Clinicians and patient advocates developed a web-based survey that was distributed via patient advocacy organizations and social media between May and June 2024, targeting participants 18 years …

Ideal Navitor Implant Depth For Redo-Tavr Feasibility And Coronary Access: A Ct Simulation Study, Anoop N Koshy, Sneha Gudibendi, Megan Berdan, Lucy M Safi, Stamatios Lerakis, George D Dangas, Samin K Sharma, Annapoorna S Kini, Gilbert H L Tang

Faculty, Staff and Students Publications

Background: The impact of implant depth of the Abbott Navitor intra-annular, self-expanding valve on redo-transcatheter aortic valve replacement (TAVR) feasibility is unknown.

Objectives: The authors sought to determine the feasibility of redo-TAVR and coronary access with Edwards Sapien 3 (S3) valve after initial Navitor valve, based on various implant depths on computed tomography (CT) simulation.

Methods: Using 2050 pre-TAVR CTs of patients with native aortic stenosis, initial Navitor TAVR simulations were done at 3 implant depths (0 mm, 3 mm, and 5 mm), with frame expansion assumed at native annular dimensions and commissural alignment not achievable. Redo-TAVR with S3 was …

A Divergent Cyclic Nucleotide Binding Protein Promotes Plasmodium Ookinete Infection Of The Mosquito, Lijia Liu, Jennifer C Regan, Choel Kim, Nisha Philip

Faculty, Staff and Students Publications

Colonisation of mosquitos by the malarial parasite is critically reliant on the invasive ookinete stage. Ookinete invasion of mosquito is coordinated by the apical complex, a specialised parasite structure containing components for secretion, attachment and penetration. While studies have investigated cytoskeletal and secretory elements, it is currently unknown if signalling modules are present or functional at the apical complex. Here we elucidate the role of a cryptic cyclic nucleotide-binding protein which we name CBP-O. PbCBP-O showed a marked localisation to the ookinete apex and disruption of the protein severely compromised ookinete invasion of mosquitos. Domain dissection analysis revealed that the …

Experiences Of Emotional Support Among Parents Of Children And Adolescents With Type 1 Diabetes: A Qualitative Study, Deborah I Thompson, David G Marrero, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Parents of youth with type 1 diabetes (T1D) experience substantial disease-specific demands and distress, yet their perceptions about the emotional support they receive related to the challenges of caring for a child with diabetes have not been well described. This research aimed to characterize the types of emotional support parents of youth with T1D receive and how they experience emotional support.

Methods: As part of a larger qualitative study on diabetes health-related quality of life, 23 parents (96% mothers) of youth with T1D (M age = 10.9 ± 3.8 years; 35% female) completed semi-structured interviews about various aspects of …

One-Year Outcomes From The Pivotal Trial Of A Four-Branch Off-The-Shelf Solution To Treat Pararenal And Extent Iv Thoracoabdominal Aortic Aneurysms, Jon S Matsumura, Bernardo C Mendes, Gustavo S Oderich, Luis A Sanchez, Bjoern D Suckow, Carlos H Timaran

Faculty, Staff and Students Publications

Objective: To report 1-year primary-arm outcomes of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis pivotal trial.

Methods: The multicenter, nonrandomized, prospective study included patients with extent IV thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). All-cause and adjudicated lesion-related mortality were assessed at 12 months. Core-lab-reported, imaging-dependent outcomes included aneurysm size, endoleaks assessed through 1-year follow-up window, and target vessel instability (defined as occlusion, stenosis, type Ic/IIIc endoleak, or reintervention) at 1 year.

Results: One hundred two patients were treated; 59 patients had an extent IV TAAA and 43 had a PRAA. The mean maximum aneurysm diameter was 59.4 ± …

A Fascination With Gastrointestinal Viruses

Faculty, Staff and Students Publications

My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements …