Digital Commons Network^™

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Marisa W Friederich, Daniella H Hock, Jessie R Zhang, Liana M Valin, Jill A Rosenfeld, Kevin T A Booth, Natasha J Brown, Rocio Rius, Tanavi Sharma, Liana N Semcesen, Kim C Worley, Lindsay C Burrage, Kayla Treat, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Farah A Ladha, Roxanne A Van Hove, Cole R Michel, Richard Reisdorph, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Claudia Soler-Alfonso, Erin Conboy, Francesco Vetrini, Lisa Emrick, William J Craigen, Undiagnosed Diseases Network, Stephen M Sykes, David A Stroud, Johan L K Van Hove, Tim Schedl, Stephen C Pak

Faculty, Staff and Students Publications

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

Nonexposed Endoscopic Full Thickness Resection Of Residual Disease After Definitive Chemoradiation For Locally Advanced Gastric Cancer, Brennan W Gioe, Bryan C Luu, Michael M Ittmann, George Chen, Yvonne H Sada, Wasseem Skef

Faculty, Staff and Students Publications

Salvage endoscopic resection of residual esophageal neoplasia for patients that prefer to avoid surgery or are poor surgical candidates has been reported. We report a case of gastric signet ring cell carcinoma with residual disease after definitive chemoradiotherapy, that was treated with nonexposed endoscopic full thickness resection. This endoscopic resection achieved negative margins, with postresection surveillance endoscopy and imaging showing no evidence of disease. This case highlights the potential use of salvage endoscopic resection as a therapy for residual gastric cancer after chemoradiation in patients where surgery is not an option.

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Clinical Profiles And Outcomes Of Adult Congenital Heart Disease Patients In The Cardiac Intensive Care Unit, Luke J Burchill, Viral K Desai, Maan Jokhadar, Cameron Dezfulian, Heidi M Connolly, Alexander C Egbe, William R Miranda, C Charles Jain, Jacob C Jentzer

Faculty, Staff and Students Publications

Background: There is limited evidence to guide care and improve outcomes among critically ill adult congenital heart disease (ACHD) patients.

Objectives: The purpose of this study was to examine the clinical profile and outcomes of ACHD patients admitted to an academic cardiac intensive care unit (CICU).

Methods: Retrospective cohort study of Mayo Clinic CICU admissions (2007-2018), including those who had been evaluated in our ACHD clinic. Critical care diagnoses (CCD) at the time of admission and critical care therapies (CCT) during the CICU stay were examined. Logistic regression and Cox proportional hazards regression were used to evaluate in-hospital and 1-year …

From Assistance To Autonomy: Evaluating Procedural Competency In Pediatric Emergency Medicine, Richard Barber, Marideth Rus, Elizabeth Moran, Esther M Sampayo, Deborah Hsu, Corrie E Chumpitazi, Elizabeth A Camp, Nidhi V Singh

Faculty, Staff and Students Publications

Objective: Pediatric emergency medicine (PEM) physicians require expertise in numerous procedural skills to manage emergencies in children. Fellows require hands-on experience, expert supervision, and standardized feedback to build procedural competency. Our objective was to develop and gather validity evidence for an evaluation tool to assess PEM fellows' ability to perform procedures.

Methods: We conducted a retrospective study of PEM fellows' procedural performance within a children's hospital system. Faculty evaluated fellows using a one-item, five-point entrustment/level of supervision scale. We focused on three frequently performed procedures: laceration repair, intubation, and procedural sedation. To assess changes in supervision scores by training year, …

A Narrative Review Of The Ileal Pouch In Pediatric Inflammatory Bowel Disease And Familial Adenomatous Polyposis, Anitta Philip, Allyson Wyatt, Jose R Rodriguez, Brad Pasternak, Lisa Mcmahon, Kalyani Patel, Richard Kellermayer

Faculty, Staff and Students Publications

Ileal pouch-anal anastomosis is a surgical intervention in patients with medically refractory inflammatory bowel disease and familial adenomatous polyposis syndrome. Reported outcomes in children have been limited by both the retrospective nature and sample size of the investigations. In addition, there is a lack of consensus on surveillance guidelines in this patient population. Delay or lack of surveillance may increase the risk of complications (pouchitis, Crohn's disease-like inflammation, dysplasia, etc.). This narrative review aims to summarize the most recent literature (2013-2023) on short-term, long-term, and quality of life (QoL) outcomes in pediatric ileal pouch (J-pouch) patients. A proposed surveillance guidance …

Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez

Faculty, Staff and Students Publications

Importance: Investments in emergency care systems are vital to ensuring universal health coverage and improving health outcomes in low- and middle-income countries.

Objective: To assess whether a package of emergency care interventions is associated with improved patient mortality and clinical care quality.

Design, setting, and participants: This pre-post quality improvement study was conducted at a single urban referral hospital emergency unit (EU) in Monrovia, Liberia, to assess clinical and educational outcomes resulting from the implementation of a package of interventions from January 1, 2018, through June 30, 2019. Final analysis was performed in November 2023. Data from a random subset …

Natriuretic Peptide Cut Points For Heart Failure Classification In Individuals With And Without Obesity, Mandana Chitsazan, Juhi K Parekh, Leah B Kosyakovsky, Sophie M Nemeth, Emily S Lau, James L Januzzi, Thomas J Wang, Daniel Levy, Chiadi E Ndumele, Elizabeth Selvin, Christie M Ballantyne, Bruce M Psaty, John S Gottdiener, Jorge R Kizer, Christopher R Defilippi, Norrina B Allen, Rudolf A De Boer, Sanjiv J Shah, Jennifer E Ho

Faculty, Staff and Students Publications

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines introduced elevated natriuretic peptide (NP) levels as a criterion for defining stage B heart failure (HF), or pre-HF, to identify individuals at greatest risk for future HF. Given the known NP deficiency in obesity, we aimed to assess whether a single NP cut point would disproportionately up-classify individuals with versus without obesity to stage B HF.

Methods: Participants free of HF from 5 community-based cohorts were included. We examined the reclassification of individuals to stage B HF using the 2022 versus 2013 guidelines, stratified by obesity …

Lp(A) Testing For The Primary Prevention Of Cardiovascular Disease In High-Income Countries: A Cost-Effectiveness Analysis, Jedidiah I Morton, Florian Kronenberg, Magdalena Daccord, Nicola Bedlington, Marius Geanta, Tobias Silberzahn, Zhenyue Chen, Jean-Luc Eisele, Bogi Eliasen, Mariko Harada-Shiba, Marc Rijken, Albert Wiegman, George Thanassoulis, Pia R Kamstrup, Iñaki Gutierrez-Ibarluzea, Pablo Coral, Raul D Santos, Erik Stroes, Michal Vrablik, Gerald F Watts, Christie M Ballantyne, Samia Mora, Børge G Nordestgaard, Kausik K Ray, Stephen J Nicholls, Zanfina Ademi, Lp(A) International Taskforce (Itf) Initiative

Faculty, Staff and Students Publications

Background and aims: Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives.

Methods: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of …

Visual And Quantitative Interstitial Lung Abnormality Progression In Copdgene, Rachel K Putman, Jonathan A Rose, Ruben San José Estepar, Ann-Marcia C Tukpah, Claire C Cutting, Takuya Hino, Akinori Hata, Mizuki Nishino, Stephen M Humphries, David A Lynch, Edwin K Silverman, Michael H Cho, Ivan O Rosas, George R Washko, Hiroto Hatabu, Raúl San José Estepar, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: Interstitial lung abnormalities (ILAs) are visually identified changes on chest computed tomography (CT) scans that may represent early or mild pulmonary fibrosis. Quantitative interstitial abnormalities (QIAs) measure potential parenchymal lung injury on chest CT scans using an automated algorithm. It is not known if combining these visual and quantitative assessments improves prediction of imaging progression.

Objectives: To assess the utility of quantitative imaging to predict imaging progression of ILAs and adverse clinical outcomes in a cohort of smokers.

Methods: ILA presence, subtypes, and progression, as well as QIAs, were assessed on chest CT scans from participants ∼5 years apart …

Lac-Phe Induces Hypophagia By Inhibiting Agrp Neurons In Mice, Hailan Liu, Veronica L Li, Qingzhuo Liu, Yao Liu, Cunjin Su, Hueyxian Wong, Na Yin, Hesong Liu, Xing Fang, Kristine M Mcdermott, Hueyzhong Wong, Meng Yu, Longlong Tu, Jonathan C Bean, Yongxiang Li, Mengjie Wang, Yue Deng, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Junying Han, Megan E Burt, Sanika V Jossy, Chunmei Wang, Yongjie Yang, Benjamin R Arenkiel, Dong Kong, Yang He, Jonathan Z Long, Yong Xu

Faculty, Staff and Students Publications

Lactate-derived N-lactoyl-phenylalanine (Lac-Phe) was recently identified as an lactate-derived circulating metabolite that reduces feeding and obesity, but mechanisms that underlie the metabolic benefits of Lac-Phe remain unknown. Here we demonstrated that Lac-Phe directly inhibits hypothalamic neurons that express Agouti-related protein (AgRP), resulting in an indirect activation of anorexigenic neurons in the paraventricular nucleus of the hypothalamus (PVH). We also found that both AgRP inhibition and PVH activation are required to mediate Lac-Phe-induced hypophagia. Further, we show that Lac-Phe inhibits AgRP neurons via activating the ATP-sensitive potassium (KATP) channel, and inhibition of the KATP channel blunts effects of Lac-Phe to suppress …

High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies

Faculty, Staff and Students Publications

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …

Transdiagnostic Correlates Of Family Accommodation In Anxious Youth, Whitney S Shepherd, Erika S Trent, Orri Smarason, Hannah N Sansone, Daphne M Ayton, Amanda Palo, Abigail E Candelari, Wayne K Goodman, Andrew G Guzick, Eric A Storch

Faculty, Staff and Students Publications

Anxiety disorders are common in children and cause significant impairment. Family accommodation, which refers to behavioral changes that family members make to temporarily alleviate a child’s anxiety, has been linked to child anxiety symptom severity. Although emotional vulnerabilities for anxiety such as emotion dysregulation, anxiety sensitivity, and distress intolerance have been associated with family accommodation, research concerning the relationship between these constructs among anxious youth is limited. We hypothesized that these variables would be uniquely and positively associated with family accommodation and would moderate the relationship between anxiety symptom severity and family accommodation. Treatment-seeking child–parent dyads (N = 90; …

Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough

Faculty, Staff and Students Publications

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.

Methods: A double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n …

Characterizing Measurement-Based Care In The Texas Youth Depression And Suicide Research Network (Tx-Ydsrn), Holli Slater, Yasmin Alzubi, Afsaneh Rezaeizadeh, Jennifer L Hughes, April Gorman, Taryn L Mayes, Joshua S Elmore, Eric A Storch, Sarah M Wakefield, Madhukar H Trivedi

Faculty, Staff and Students Publications

Integration of measurement-based care (MBC) into clinical practice has shown promise in improving treatment outcomes for depression. Yet, without a gold standard measure of MBC, assessing fidelity to the MBC model across various clinical settings is difficult. A central goal of the Texas Youth Depression and Suicide Research Network (TX-YDSRN) was to characterize MBC across the state of Texas through the development of a standardized tool to assess the use of MBC strategies when assessing depression, anxiety, side effects, and treatment adherence. A chart review of clinical visits indicated standardized depression measures (71.2%) and anxiety measures (64%) were being utilized …

Sustained Response To Pan-Braf Inhibitor Plixorafenib (Fore8394, Plx8394) In A Young Adult With Neurodegenerative Langerhans Cell Histiocytosis, Joanna S Yi, Kathleen S Mccarthy, Kate Mazur, Rebecca Kudlaty, Terry Armstrong, Nilesh Desai, Stacie Peacock Shepherd, Daniel Zinn, Jessica Velazquez, Brooks Scull, Carl Allen, Kenneth Mcclain

Faculty, Staff and Students Publications

No abstract provided.

Shrimp Allergy-Distinct Allergen Sensitization Profiles Between Intercontinental Cohorts, Shaymaviswanathan Karnaneedi, Sara Anvari, Shea Brunner, Karen S Tuano, Brenda Bin Su, Saachi Hira, Sahel Heidari, Diamond Hira, Carla M Davis, Andreas L Lopata

Faculty, Staff and Students Publications

No abstract provided.

Cytokine Variations After Positive Oral Food Challenges In Adult-Onset Food Protein-Induced Enterocolitis, Purificacion Gonzalez-Delgado, Sara Anvari, Ana I Jimenez, Paulina Gallego-Velez, Cristina Sanchez-Fortun, Teodorikez-Wilfox Jimenez-Rodriguez, Francisco Marco De La Calle, Javier Fernandez, Jordi Barrachina

Faculty, Staff and Students Publications

No abstract provided.

Post-Deployment Monitoring Of Ai Performance In Intracranial Hemorrhage Detection By Chatgpt, Eric Rohren, Mohadese Ahmadzade, Sofia Colella, Nina Kottler, Sriyesh Krishnan, Jason Poff, Neelesh Rastogi, Walter Wiggins, Joyce Yee, Carlos Zuluaga, Phil Ramis, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Rationale and objectives: To evaluate the post-deployment performance of an artificial intelligence (AI) system (Aidoc) for intracranial hemorrhage (ICH) detection and assess the utility of ChatGPT-4 Turbo for automated AI monitoring.

Materials and methods: This retrospective study evaluated 332,809 head CT examinations from 37 radiology practices across the United States (December 2023-May 2024). Of these, 13,569 cases were flagged as positive for ICH by the Aidoc AI system. A HIPAA (Health Insurance Portability and Accountability Act) -compliant version of ChatGPT-4 Turbo was used to extract data from radiology reports. Ground truth was established through radiologists' review of 200 randomly selected …

Nrf2 Hyperactivation As A Driver Of Radiotherapy Resistance And Suppressed Antitumor Immunity In Head And Neck Squamous Cell Carcinoma, Rutulkumar Patel, Kalil Saab, Lixia Luo, Yan Ma, Rashid Abdullah Osman, Nerissa T Williams, Jeffrey Everitt, Maciej J Zelazowski, Patricia Castro, William K Decker, William H Hudson, Jeffrey N Myers, Vlad C Sandulache, Mitchell J Frederick, Yvonne M Mowery, David G Kirsch

Faculty, Staff and Students Publications

Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ∼20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well studied.

Experimental design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed by Western …

Dysphoric Milk Ejection Reflex: Prevalence And Associations With Self-Reported Mental Health History, Megan Howard, Alison N Goulding, Anitha Muddana, Terri L Fletcher, Nicole Cirino, Alison M Stuebe

Faculty, Staff and Students Publications

This study sought to determine prevalence of Dysphoric Milk Ejection Reflex (D-MER) and mental health correlates in a cohort of patients from a breastfeeding medicine clinic. We determined prevalence of D-MER symptoms and performed bivariate analyses to explore associations between D-MER symptoms, demographics, and self-reported mental health history. Among 271 patients, 42 (15.5%) reported D-MER. Women with D-MER symptoms were more likely to report a history of panic attacks (28.6 vs. 12.2%, OR 2.87, 95% CI 1.23-6.25).

Strongyloides Seropositivity Among Children Utilizing A Mobile Clinic, Lynda Aririguzo, Aditi Gupta, Norma Castillo, Cassandra Duran, Eva H Clark, Ankona Banerjee, Sanghamitra Misra

Faculty, Staff and Students Publications

Experts recommend screening for or presumptively treating strongyloidiasis in foreign-born immigrant children, though prevalence is unknown. Health care providers encounter barriers to following this recommendation. We aimed to describe Strongyloides seropositivity and risk factors among pediatric patients on a mobile clinic. Participants completed a written survey and provided blood for absolute eosinophil count (AEC) and Strongyloides IgG enzyme-linked immunosorbent assay (ELISA). From October 2022 to June 2023, 206 patients participated; 201 (97.6%) were born outside the United States; 97.1% (n = 200) were Hispanic. Most (68.9%) arrived less than 1 year before study enrollment. Four (1.9%) and 3 (1.5%) had …

Clinically Significant Neuroimaging Findings Among Pediatric Patients Presenting To The Emergency Department With Symptoms Of Psychosis: A Multicenter Retrospective Study, Jennifer A Hoffmann, Tapan K Parikh, Doug Lorenz, Michael P Goldman, Emily M Powers, Shilpa J Patel, Ilana S Lavina, Theodore W Heyming, Jasmin T England, Mohsen Saidinejad, Ilene Claudius, Pallavi Ghosh, Daniel J Shapiro, Tricia B Swan, Kamali L Bouvay, Eileen Murtagh Kurowski, Nadine M Smith, Justin R Davis, Alexander B Moxam, Eli J Muhrer, Rohit P Shenoi, Elyse N Portillo, Ron L Kaplan, Neil G Uspal, Robert M Lapus, Andrea T Vo, Daniel B Fenster, Danielle B Barrocas, Deborah R Liu, Pradip P Chaudhari, Rachel Cafferty, Stephen B Freedman, Jerri A Rose, Megan F Evers, Ashley M Metcalf, Fareed Saleh, Jennifer Dunnick, Raymond D Pitetti, Yashas R Nathani, Muhammad Waseem, Todd A Florin

Faculty, Staff and Students Publications

Background: The clinical utility of diagnostic neuroimaging for pediatric patients presenting to the emergency department (ED) for psychosis remains unclear. We sought to estimate the prevalence of and characteristics associated with clinically significant neuroimaging findings among pediatric patients presenting to the ED with symptoms of psychosis who had neuroimaging performed.

Methods: This retrospective cross-sectional study included visits by patients 5 to < 18 years old presenting with symptoms of psychosis to 28 EDs affiliated with the Pediatric Emergency Medicine Collaborative Research Committee from 2016 to 2019 and had neuroimaging performed. We estimated the rate of clinically significant neuroimaging findings, defined as those resulting in further testing, treatment, or medical admission, overall and by imaging modality. Multivariable logistic regression models examined presenting features associated with clinically significant findings.

Results: Clinically significant neuroimaging findings were identified in 5.4% (95% CI 4.2%, 6.9%) of 1118 ED visits (54% male, median [IQR] 14 [11-16] years old). Clinically significant findings occurred in 4.9% (34/699) of head computed tomography scans and 7.5% …

Social Disparities, Delirium Occurrence, And Related Outcomes Among Hospitalized Older Adults, Alan P Pan, Kathryn Agarwal, Thomas Potter, Karim Borei, Sara Nowakowski, Courtenay R Bruce, George E Taffet, Farhaan S Vahidy

Faculty, Staff and Students Publications

Background: Underlying socio-economic and health burden may variably impact delirium presentation among older adults. We characterized differences in patient factors related to social marginalization and studied their effects on delirium occurrence and hospital outcomes.

Methods: We conducted a 7-year retrospective analysis of older adults (aged ≥ 70 years) who systematically underwent screening for delirium at an 8-hospital healthcare system. Our primary exposure included patient characteristics related to demographics and social marginalization. Multivariable logistic regression models were built to identify factors associated with increased odds of delirium occurrence, either (1) present-on-admission (D-POA) or (2) hospital-acquired (HAD). Secondary outcomes included hospital length …

Engineered Exosomes With Krasg12d Specific Sirna In Pancreatic Cancer: A Phase I Study With Immunological Correlates, Valerie S Kalluri, Brandon G Smaglo, Krishnan K Mahadevan, Michelle L Kirtley, Kathleen M Mcandrews, Mayela Mendt, Sujuan Yang, Ana S Maldonado, Hikaru Sugimoto, Maria E Salvatierra, Luisa M Solis Soto, Cara Haymaker, Rick Finch, Mihai Gagea, Adam C Fluty, Steven J Ludtke, J Jack Lee, Abhinav K Jain, Gauri Varadhachary, Rachna T Shroff, Anirban Maitra, Elizabeth Shpall, Shubham Pant, Raghu Kalluri

Faculty, Staff and Students Publications

Oncogenic KRAS is amongst the key genetic drivers for initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC). Here, we show that engineered exosomes with KrasG12D specific siRNA (iExoKrasG12D) reveal a biodistribution in pancreas with negligible toxicity in preclinical studies in mice and Rhesus macaques. Clinical testing of iExoKrasG12D in the iEXPLORE (iExoKrasG12D in Pancreatic Cancer) Phase I study employed a non-randomized single-arm classical 3 + 3 dose escalation design (Phase Ia), followed by an accelerated titration design (Phase Ib) (NCT03608631). The primary outcomes included safety, tolerability and target engagement, and the secondary outcomes aimed to assess disease control. …

Cookie-Pro: Covalent Inhibitor Binding Kinetics Profiling On The Proteome Scale, Hanfeng Lin, Bin Yang, Lang Ding, Yen-Yu Yang, Matthew V Holt, Sung Yun Jung, Bing Zhang, Meng C Wang, Jin Wang

Faculty, Staff and Students Publications

Covalent inhibitors are an emerging class of therapeutics, but methods to comprehensively profile their binding kinetics and selectivity across the proteome have been limited. Here we introduce COOKIE-Pro (COvalent Occupancy KInetic Enrichment via Proteomics), an unbiased method for quantifying irreversible covalent inhibitor binding kinetics on a proteome-wide scale. COOKIE-Pro uses a two-step incubation process with mass spectrometry-based proteomics to determine kinact and KI values for covalent inhibitors against both on-target and off-target proteins. We validated COOKIE-Pro using BTK inhibitors spebrutinib and ibrutinib, accurately reproducing known kinetic parameters and identifying both expected and unreported off-targets. The method revealed that …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …

Observational Activation Of Anterior Cingulate Cortical Neurons Coordinates Hippocampal Replay In Social Learning, Xiang Mou, Daoyun Ji

Faculty, Staff and Students Publications

Social learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are reactivated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during …

Functional Outcomes In Pediatric Patients On Renal Replacement Therapy In A Worldwide Registry, Kristin J Dolan, Katja M Gist, Abby Basalely, Gabriella Bottari, Abhishek Chakraborty, Mihaela Damian, Dana Fuhrman, Denise C Hasson, Catherine Joseph, Dave Kwiatkowski, Susan Martin, Jenn Nhan, Nicolas Ollberding, David T Selewski, Danielle Soranno, Michelle C Starr, Amy Strong, Sameer Thadani, Huaiyu Zang, Ayse Akcan Arikan

Faculty, Staff and Students Publications

Background and hypothesis: Mortality rates of children supported with continuous renal replacement therapy (CRRT) have improved, yet morbidity remains high. We aimed to evaluate the functional outcomes of children receiving CRRT using Functional Status Scale (FSS). We hypothesized that children receiving CRRT will have worse FSS compared with their baseline and acquire new morbidity at hospital discharge and 6 and 12 months post-discharge, and that lack of renal recovery will contribute to worsening functional status.

Methods: This is a retrospective chart review from The Worldwide Exploration of Renal Replacement Outcomes Collaborate in Kidney Disease (WE-ROCK), an international multi-center registry. Twenty-eight …

Microtia, Peng You, Yi-Chun Liu, Caitlin Symonette

Faculty, Staff and Students Publications

No abstract provided.