Digital Commons Network^™

Epidemiology Of Diagnostic Errors In Pediatric Emergency Departments Using Electronic Triggers, Prashant Mahajan, Emily White, Kathy Shaw, Sarah J Parker, James Chamberlain, Richard M Ruddy, Elizabeth R Alpern, Jacqueline Corboy, Andrew Krack, Brandon Ku, Daphne Morrison Ponce, Asha S Payne, Elizabeth Freiheit, Gregor Horvath, Giselle Kolenic, Michele Carney, Nicole Klekowski, Karen J O'Connell, Hardeep Singh

Faculty, Staff and Students Publications

Objectives: We applied three electronic triggers to study frequency and contributory factors of missed opportunities for improving diagnosis (MOIDs) in pediatric emergency departments (EDs): return visits within 10 days resulting in admission (Trigger 1), care escalation within 24 h of ED presentation (Trigger 2), and death within 24 h of ED visit (Trigger 3).

Methods: We created an electronic query and reporting template for the triggers and applied them to electronic health record systems of five pediatric EDs for visits from 2019. Clinician reviewers manually screened identified charts and initially categorized them as "unlikely for MOIDs" or "unable to rule …

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen

Faculty, Staff and Student Publications

Background: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.

Objective: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with …

Patient Consent And The Right To Notice And Explanation Of Ai Systems Used In Health Care, Meghan E Hurley, Benjamin H Lang, Kristin Marie Kostick-Quenet, Jared N Smith, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Given the need for enforceable guardrails for artificial intelligence (AI) that protect the public and allow for innovation, the U.S. Government recently issued a Blueprint for an AI Bill of Rights which outlines five principles of safe AI design, use, and implementation. One in particular, the right to notice and explanation, requires accurately informing the public about the use of AI that impacts them in ways that are easy to understand. Yet, in the healthcare setting, it is unclear what goal the right to notice and explanation serves, and the moral importance of patient-level disclosure. We propose three normative functions …

A Multicenter Training And Interrater Reliability Study Of The Based Score For Infantile Epileptic Spasms Syndrome, John R Mytinger, Dara V F Albert, Shawn C Aylward, Christopher W Beatty, Sonam Bhalla, Sonal Bhatia, Guy N Brock, Micheal A Ciliberto, Purva R Choudhari, Daniel J Clark, Jennifer Madan Cohen, Theresa M Czech, Megan M Fredwall, Ernesto Gonzalez-Giraldo, Chellamani Harini, Senyene E Hunter, Amanda G Sandoval Karamian, Akshat Katyayan, Isaac Kistler, Neil Kulkarni, Virginia B Liu, Corinne Mccabe, Thomas Murray, Kerri Neville, Shital H Patel, Spriha Pavuluri, Donald J Phillips, Debopam Samanta, Deepa Sirsi, Emily M Spelbrink, Carl E Stafstrom, Maija Steenari, Danielle S Takacs, Tyler Terrill, Linh Tran, Jorge Vidaurre, Daniel W Shrey

Faculty, Staff and Students Publications

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE).

METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 …

Comprehensive Normalization And Binary Classification Methods For Enhanced Sensitivity And Reproducibility In Luminex Assay Quantitation, B A Burns, C A Shaw, M Chandra, C S Forconi, A M Moormann, V Konduri, V N Tubman, W K Decker

Faculty, Staff and Students Publications

The Luminex assay is a powerful tool for large-scale quantitation of antibody levels and cytokines, but its utility can be limited by issues of specificity, sensitivity, and reproducibility. The corrections for background fluorescence and machine drift are essential steps in the normalization process. However, traditional methods often oversimplify these steps, failing to account for the complexity of the data, leading to the introduction of error and decreasing the sensitivity and reproducibility of the analysis. Furthermore, conventional methods to determine cut-points in binary measures do not consider the true distribution of the data, leading to arbitrary cut-points that compromise the integrity …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

Tau Oligomers Resist Phase Separation, Lathan Lucas, Phoebe S Tsoi, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Tau is a microtubule-associated protein that undergoes liquid-liquid phase separation (LLPS) to form condensates under physiological conditions, facilitating microtubule stabilization and intracellular transport. LLPS has also been implicated in pathological Tau aggregation, which contributes to tauopathies such as Alzheimer's disease. While LLPS is known to promote Tau aggregation, the relationship between Tau's structural states and its phase separation behavior remains poorly defined. Here, we examine how oligomerization modulates Tau LLPS and uncover key distinctions between monomeric, oligomeric, and amyloidogenic Tau species. Using dynamic light scattering and fluorescence microscopy, we monitored oligomer formation over time and assessed oligomeric Tau's ability to …

Developing Evaluation Metrics To Measure The Us National Institute Of Health Plans To Enhance Diverse Perspectives: A Protocol For A Consensus-Based Study, Yulia A Levites Strekalova, Sanjay Jain, Pinaki Sarder

2020-Current year OA Pubs

INTRODUCTION: The diversity of participating investigators representing diverse disciplines, career stages, stakeholder groups, regions and types of institutions is essential for the success of large-scale research programmes. In 2021, the National Institutes of Health introduced a requirement for some of its large grants to include a separate section that describes the project's plan for enhancing diverse perspectives (PEDPs). Our project aims to develop consensus-based PEDP evaluation metrics and instruments that can be systematically and sustainably collected across the projects.

METHODS AND ANALYSIS: Evaluation work is organised into three objectives. First, shared knowledge about PEDP infrastructures, activities and outcomes will be …

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Human Intestinal Enteroids For Evaluating The Persistence Of Infectious Human Norovirus In Raw Surface Freshwater, Malak A Esseili, Revati Narwankar, Riya Hooda, Veronica Costantini, Mary K Estes, Jan Vinjé, Issmat I Kassem

Faculty, Staff and Students Publications

Globally, human norovirus (HuNoV) is the leading cause of foodborne illnesses. Norovirus transmission to fresh produce can occur via several sources, including contaminated irrigation water. HuNoV RNA has been detected in freshwater resources, but knowledge about virus infectivity is limited due to a historical lack of a HuNoV cell culture. Recently, HuNoV was shown to replicate in human intestinal enteroids (HIE). The objective of this study was to use HIE to evaluate the persistence of infectious HuNoV in raw (i.e. biologically active) surface freshwater. The virus was spiked into freshwater microcosms sampled from three freshwater ponds and then incubated inside …

Conformational Flexibility Is A Critical Factor In Designing Broad-Spectrum Human Norovirus Protease Inhibitors, Son Pham, Boyang Zhao, Neetu Neetu, Banumathi Sankaran, Ketki Patil, Sasirekha Ramani, Yongcheng Song, Mary K Estes, Timothy Palzkill, B V Venkataram Prasad

Faculty, Staff and Students Publications

UNLABELLED: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein. Thus, it is an ideal target for developing antiviral small-molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. …

Characterization Of Factors Associated With Death In Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey, Alina Ivaniuk, Irina A Anselm, Aaron Bowen, Bruce H Cohen, Fatma Tuba Eminoglu, Jane Estrella, Renata C Gallagher, Rebecca D Ganetzky, Jennifer Gannon, Grainne S Gorman, Carol Greene, Andrea L Gropman, Richard H Haas, Michio Hirano, Seema Kapoor, Amel Karaa, Mary Kay Koenig, Cornelia Kornblum, Engin Kose, Austin Larson, Uta Lichter-Konecki, Piervito Lopriore, Michelangelo Mancuso, Robert Mcfarland, Aye Myat Moe, Eva Morava, Yi Shiau Ng, Russell P Saneto, Fernando Scaglia, Carolyn M Sue, Mark Tarnopolsky, Melissa A Walker, Sumit Parikh, Fung Cheuk-Wing, Tsz-Sum Wong, Kiran Belaramani, Chun-Kong Chan, Wing-Ki Chan, Wai-Lun Larry Chan, Hon-Wing Cheung, Ka-Yin Cheung, Shek-Kwan Chang, Sing-Ngai Cheung, Tsz-Fung Cheung, Yuk-Fai Cheung, Shuk-Ching Josephine Chong, Chi-Kwan Jasmine Chow, Hon-Yin B Chung, Sin-Ying Florence Fan, Wai-Ming Joshua Fok, Ka-Wing Fong, Tsui-Hang Sharon Fung, Kwok-Fai Hui, Ting-Hin Hui, Joannie Hui, Chun Hung Ko, Min-Chung Kwan, Mei-Kwan Anne Kwok, Sung-Shing Jeffrey Kwok, Moon-Sing Lai, Yau-On Lam, Ching-Wan Lam, Ming-Chung Lau, Chun-Yiu Eric Law, Hiu-Fung Law, Wing-Cheong Lee, Han-Chih Hencher Lee, Kin-Hang Leung, Kit-Yan Leung, Siu-Hung Li, Tsz-Ki Jacky Ling, Kam-Tim Timothy Liu, Fai-Man Lo, Colin Lui, Ching-On Luk, Ho-Ming Luk, Che-Kwan Ma, Karen Ma, Kam-Hung Ma, Yuen-Ni Mew, Alex Mo, Sui-Fun Hg, Wing-Kit Grace Poon, Bun Sheng, Cheuk-Ling Charing Szeto, Shuk-Mui Tai, Jing-Liang Tang, Choi-Ting Alan Tse, Li-Yan Lilian Tsung, Ho-Ming June Wong, Wing-Yin Winnie Wong, Kwok-Kui Wong, Suet-Na Sheila Wong, Chun-Nei Virginia Wong, Wai-Shan Sammy Wong, Chi-Kin Felix Wong, Shun-Ping Wu, Hiu-Fung Jerome Wu, Man-Mut Yau, Kin-Cheong Eric Yau, Wai-Lan Yeung, Hon-Ming Jonas Yeung, Kin-Keung Edwin Yip, Hui-Jun Wu, Pui-Hong Terence Young, Gao Yuan, Yuet-Ping Liz Yuen, Chi-Lap Yuen

Faculty, Staff and Student Publications

Background and objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based …

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Aberrant Choroid Plexus Formation Drives The Development Of Treatment-Related Brain Toxicity, Tamara Bender, Esther Schickel, Celine Schielke, Jürgen Debus, David R Grosshans, Marco Durante, Insa S Schroeder

Faculty, Staff and Student Publications

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1+/AQP1+/CLDN3+-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

The Effects Of Major Abdominal Surgery On Skeletal Muscle Mitochondrial Respiration In Relation To Systemic Redox Status And Cardiopulmonary Fitness, Jia L. Stevens, Daniel Martin, Helen Mckenna, Magdalena Minnion, Andrew Murray, Martin Feelisch

Peninsula Medical School

More complex surgeries are being performed in increasingly sicker patients, resulting in a greater burden of postoperative morbidity. Delineating the metabolic and bioenergetic changes that occur in response to surgical stress may further our understanding about how humans respond to injury and aid the identification of resilient and frail phenotypes. Skeletal muscle biopsies were taken from patients undergoing hepato-pancreatico-biliary surgery at the beginning and end of the procedure to measure mitochondrial respiration and thiol status. Blood samples were taken at the same timepoints to measure markers of inflammation and systemic redox state. A sub-group of patients underwent cardiopulmonary exercise testing …

At-Home Stroke Neurorehabilitation: Early Findings With The Neuroexo Bci System, Juan José González-España, Lianne Sánchez-Rodríguez, Maxine Annel Pacheco-Ramírez, Jeff Feng, Kathryn Nedley, Shuo-Hsiu Chang, Gerard E Francisco, Jose L Contreras-Vidal

Faculty, Staff and Student Publications

Background: Democratized access to safe and effective robotic neurorehabilitation for stroke survivors requires innovative, affordable solutions that can be used not only in clinics but also at home. This requires the high usability of the devices involved to minimize costs associated with support from physical therapists or technicians.

Methods: This paper describes the early findings of the NeuroExo brain-machine interface (BMI) with an upper-limb robotic exoskeleton for stroke neurorehabilitation. This early feasibility study consisted of a six-week protocol, with an initial training and BMI calibration phase at the clinic followed by 60 sessions of neuromotor therapy at the homes of …

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …

Post-Traumatic Growth And Influencing Factors Of Parents With Children With Duchenne Muscular Dystrophy: A Cross-Sectional Survey Study, Li Xu, Meili Liu, Yuewei Chen, Liwen Wu, Siyi Gan, Jianhui Xie, Jos M. Latour

School of Nursing and Midwifery

Background: The aim of the study was to identify the post-traumatic growth status and influencing factors of parents with children with Duchenne muscular dystrophy (DMD). Methods: We adopted a cross-section survey study. Between February and December 2022, 181 parents responded to the survey including a participants’ characteristics section, post-traumatic growth assessment scale, caregiver burden scale, and social support assessment scale. Multiple linear regression analysis was used to investigate influencing factors of post-traumatic growth. Results: The mean score of post-traumatic growth of parents was 56.66 (SD ± 18.67). Post-traumatic growth was positively correlated with social support (r = 0.452, P < 0.01) and negatively correlated with care burden (r = -0.207, P < 0.01). Multiple linear regression showed that the child’s age, course of disease, self-care ability, parent’s working condition, residence, education, number of children, and health status were the main influencing factors for the post-traumatic growth of parents (P < 0.001). Conclusion: The post-traumatic growth of parents with children with DMD was at a moderate level. Healthcare professionals should pay attention to the psychological state of parents with children with this rare disease and promote post-traumatic growth through psychological mindfulness interventions, strengthening family and social support, and providing care knowledge and skills.

Reneu: A Pivotal, Phase Iib Trial Of Mirdametinib In Adults And Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma, Christopher L Moertel, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

METHODS: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m

RESULTS: Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term …

Clinician Experiences With Ambient Scribe Technology To Assist With Documentation Burden And Efficiency, Matthew J. Duggan, Julietta Gervase, Anna Schoenbaum, William Hanson, John T. Howell, Michael Sheinberg, Kevin B. Johnson

SKMC Student Presentations and Publications

IMPORTANCE: Timely evaluation of ambient scribing technology is warranted to assess whether this technology can lessen the burden of clinical documentation on clinicians.

OBJECTIVE: To investigate the association of ambient scribing technology with efficiency, quality, and perceived burden of clinical documentation in the outpatient setting.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-group pre-post quality improvement study was conducted between April and June 2024 in the outpatient setting of an academic health system in Philadelphia, Pennsylvania. Participants included physicians, nurse practitioners, and physician assistants. Data were analyzed from July to August 2024.

EXPOSURE: Access to an artificial intelligence-driven ambient scribing tool …

Benefits Of Equilibrium Between Microbiota- And Host-Derived Ligands Of The Aryl Hydrocarbon Receptor After Stroke In Aged Male Mice, Pedram Peesh, Maria P Blasco-Conesa, Ahmad El Hamamy, Romeesa Khan, Gary U Guzman, Parisa Honarpisheh, Eric C Mohan, Grant W Goodman, Justin N Nguyen, Anik Banerjee, Bryce E West, Kyung Ae Ko, Janelle M Korf, Chunfeng Tan, Huihui Fan, Gabriela D Colpo, Hilda Ahnstedt, Lucy Couture, Solji Roh, Julia K Kofler, Jose F Moruno-Manchon, Michael E Maniskas, Jaroslaw Aronowski, Rodney M Ritzel, Juneyoung Lee, Jun Li, Robert M Bryan, Anjali Chauhan, Venugopal Reddy Venna, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in …

Reward Responses To Vicarious Feeding Depend On Body Mass Index, Lili Järvinen, Severi Santavirta, Vesa Putkinen, Henry K Karlsson, Kerttu Seppälä, Lihua Sun, Matthew Hudson, Jussi Hirvonen, Pirjo Nuutila, Lauri Nummenmaa

School of Psychology

Eating is inherently social for humans. Yet, most neuroimaging studies of appetite and food-induced reward have focused on studying brain responses to food intake or viewing pictures of food alone. We used functional magnetic resonance imaging (fMRI) to measure haemodynamic responses to “vicarious” feeding. The subjects (n = 97) viewed series of short videos representing naturalistic episodes of social eating intermixed with videos without feeding/appetite-related content. Viewing the vicarious feeding (versus control) videos activated motor and premotor cortices, thalamus, and dorsolateral prefrontal cortices, consistent with somatomotor and affective engagement. Responses to the feeding videos were negatively correlated with the participants’ …

Single-Cell Analysis Of Neoplastic Plasma Cells Identifies Myeloma Pathobiology Mediators And Potential Targets, Luz Yurany Moreno Rueda, Hua Wang, Keiko Akagi, Minghao Dang, Amishi Vora, Li Qin, Hans C Lee, Krina K Patel, Pei Lin, David E Mery, Fenghuang Zhan, John D Shaughnessy, Qing Yi, Yang Song, Bo Jiang, Maura L Gillison, Sheeba K Thomas, Donna M Weber, Lixia Diao, Jing Wang, Isere Kuiatse, Elisabet E Manasanch, David E Symer, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models. Moreover, functional studies show a …

An Integrative Multiparametric Approach Stratifies Putative Distinct Phenotypes Of Blast Phase Chronic Myelomonocytic Leukemia, Kristian Gurashi, Yu-Hung Wang, Fabio M R Amaral, Katherine Spence, Rachel Cant, Chi-Yuan Yao, Chien-Chin Lin, Christopher Wirth, David C Wedge, Guillermo Montalban-Bravo, Simona Colla, Hwei-Fang Tien, Tim C P Somervaille, Kiran Batta, Daniel H Wiseman

Faculty, Staff and Student Publications

Approximately 30% of patients with chronic myelomonocytic leukemia (CMML) undergo transformation to a chemo-refractory blastic phase (BP-CMML). Seeking novel therapeutic approaches, we profiled blast transcriptomes from 42 BP-CMMLs, observing extensive transcriptional heterogeneity and poor alignment to current acute myeloid leukemia (AML) classifications. BP-CMMLs display distinctive transcriptomic profiles, including enrichment for quiescence and variability in drug response signatures. Integrating clinical, immunophenotype, and transcriptome parameters, Random Forest unsupervised clustering distinguishes immature and mature subtypes characterized by differential expression of transcriptional modules, oncogenes, apoptotic regulators, and patterns of surface marker expression. Subtypes differ in predicted response to AML drugs, validated ex vivo in …

Mitochondrial Defects And Metabolic Vulnerabilities In Lynch Syndrome-Associated Msh2-Deficient Endometrial Cancer, Mikayla Borthwick Bowen, Brenda Melendez, Qian Zhang, Diana Moreno, Leah Peralta, Wai Kin Chan, Collene Jeter, Lin Tan, M Anna Zal, Philip L Lorenzi, Kenneth Dunner, Richard K Yang, Russell R Broaddus, Joseph Celestino, Nisha Gokul, Elizabeth Whitley, Deena M Scoville, Tae Hoon Kim, Jae-Wook Jeong, Rosemarie Schmandt, Karen Lu, Hyun-Eui Kim, Melinda S Yates

Faculty, Staff and Student Publications

Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes, including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC (LS-EC) remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By 8 months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 50% of Msh2KO mice exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO …

Machine Learning-Enhanced Surface-Enhanced Spectroscopic Detection Of Polycyclic Aromatic Hydrocarbons In The Human Placenta, Oara Neumann, Yilong Ju, Andres B Sanchez-Alvarado, Guodong Zhou, Weiwu Jiang, Bhagavatula Moorthy, Melissa A Suter, Ankit Patel, Peter Nordlander, Naomi J Halas

Faculty, Staff and Students Publications

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, polycyclic aromatic compounds (PACs), are essential for environmental and health monitoring, for assessing toxicological exposure and their associated health risks. PAHs/PACs are the most dangerous chemicals found in tobacco smoke, and cigarette use during pregnancy can convey these molecules to the developing fetus through the placenta. This exposure is associated with many negative health outcomes, from premature birth to sudden infant death syndrome and adverse neurodevelopmental disorders. This study demonstrates the use of surface-enhanced Raman and surface-enhanced infrared absorption spectroscopies for direct detection of PAHs/PACs in human placental …

Unveiling The Genetic Landscape Of Coronary Artery Disease Through Common And Rare Structural Variants, Kruthika R Iyer, Erica P Young, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. …