Digital Commons Network^™

Dexmedetomidine On Supraventricular Tachycardia In Critical Illness: A Time-Dependent Propensity Score Matching Study, Qiaonan Zhong, Marin H Kollef, Patrick G Lyons, Andrew P Michelson

2020-Current year OA Pubs

BACKGROUND: Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults. METHODS: This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48 h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate > 100 …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …

Integrative Multiomic Classification Reveals Distinct Origins And Evolutionary Trajectories Of Thymic Epithelial Tumors., Seongyeol Park, Kijong Yi, Jieun Lee, Myung Jin Yang, Joo-Hye Song, Joonoh Lim, Taewoo Kim, Seokhwi Kim, Su Yeon Kim, Hyung-Don Kim, Yoon Ho Kim, Sae Bom Lee, Yoo Jin Jung, Hansol Park, Jake June-Koo Lee, Yohan An, Jeonghwan Youk, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Chang Hyun Kang, Eui-Cheol Shin, Tae Min Kim, Won Do Heo, Charles Lee, Gou Young Koh, Sung-Yup Cho, Young Seok Ju, Young Tae Kim

Faculty Research 2026

Thymic epithelial tumors (TET), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TEC). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. In this study, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases, combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages were incorporated to further …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUND. Gut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.

METHODS. In a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUNDGut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.METHODSIn a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were held constant. Serum …

Integrative Multiomic Classification Reveals Distinct Origins And Evolutionary Trajectories Of Thymic Epithelial Tumors., Seongyeol Park, Kijong Yi, Jieun Lee, Myung Jin Yang, Joo-Hye Song, Joonoh Lim, Taewoo Kim, Seokhwi Kim, Su Yeon Kim, Hyung-Don Kim, Yoon Ho Kim, Sae Bom Lee, Yoo Jin Jung, Hansol Park, Jake June-Koo Lee, Yohan An, Jeonghwan Youk, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Chang Hyun Kang, Eui-Cheol Shin, Tae Min Kim, Won Do Heo, Charles Lee, Gou Young Koh, Sung-Yup Cho, Young Seok Ju, Young Tae Kim

Faculty Research 2026

Thymic epithelial tumors (TET), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TEC). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. In this study, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases, combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages were incorporated to further …

Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.

METHODS: Using

RESULTS: We identified …

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Cell Type-Specific Enhancers Regulate Il-22 Expression In Innate And Adaptive Type 3 Lymphoid Cells, Ankita Saini, Leone S Hopkins, Vanida A Serna, Matthew V D Mccullen, Nicholas G Selner, Bishan Bhattarai, José L Fachi, Rebecca A Glynn, Katharina E Hayer, Craig H Bassing, Marco Colonna, Eugene M Oltz

2020-Current year OA Pubs

IL-22, a signature cytokine for type 3 lymphoid cells, including T helper 17/22 (Th17/22) and type 3 innate lymphoid cells (ILC3), mediates epithelial homeostasis and protective pathogen responses in barrier tissues. Upon dysregulation, IL-22 can drive chronic inflammatory diseases, yet little is known about transcriptional elements modulating its expression. Here, we identify two enhancers, E22-1 and E22-2, with distinct capacities for regulating Il22 expression in type 3 lymphoid cells. Both enhancers are necessary for protection from Citrobacter rodentium infection and for the onset of IL-22-mediated psoriasis. E22-2 is specifically required for IL-22 expression in ILC3s, while E22-1 functions in both …

Gastrointestinal Symptoms After Sport-Related Concussion In Irish Athletes, Emma Finnegan, Ed Daly, Katherine Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Sport-related concussion (SRC) elicits multi-systemic symptoms, including nausea, fatigue, and cognitive changes. Gastrointestinal (GI) symptoms are not well captured in current concussion assessments and may be under-recognised in clinical follow-up. GI disturbances may influence intake tolerance and day-to-day fuelling during post-SRC recovery. This study investigated the prevalence and severity of self-reported GI symptoms in Irish athletes after their most recent SRC, examined sex-based patterns, and evaluated the rationale for integrating GI symptom checks into standard concussion tools (e.g., SCAT6) and post-injury monitoring. Methods: An online survey was completed by recreational, competitive, and elite athletes who retrospectively self-reported concussion history, …

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …

Cannabis Stigma And Symptom Management Considerations In Cancer Survivors: A Mixed-Methods Exploration Of Patient Perspectives, Sera Levy, Salimah Meghani, Brooke Worster, Colleen Kilanowski, Danielle Smith, Amy A. Case, Rebecca L. Ashare

Department of Medical Oncology Faculty Papers

PURPOSE: This study aims to assess for indications of stigma and attitudes toward cannabis among cancer survivors (CS) who use or consider the use of cannabis.

METHODS: This study employed a convergent, parallel mixed methods design utilizing focus group and questionnaire data to assess the presence of stigma among a sample of CS (n = 23) who use (n = 10) and do not use (n = 13) cannabis to manage symptoms. CS were recruited from a multi-site observational study in the Northeast U.S. region that assesses cannabis use among oncology patients.

RESULTS: A total of 23 CS participated in …

The Efficacy And Safety Of Serratus Anterior Plane Block In Patients Undergoing Cardiac Surgery: A Systematic Review And Meta-Analysis, Xu-Bo Cui, Ming-Zhu Cui, Qiu-Ju Yang, Yang Liu, Meng-Qi Yi, Xiao-Yang Zhang, Yun-Tai Yao

Faculty, Staff and Student Publications

Background: Serratus anterior plane block (SAPB) is a widely used fascial block that reduces postoperative pain and perioperative opioid consumption. This meta-analysis assessed the efficacy and safety of SAPB in cardiac surgery patients.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases on May 10, 2024. Pooled relative risks and mean differences (MD) with 95% confidence intervals (CI) were calculated for dichotomous and continuous outcomes, respectively. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using Egger test. Subgroup analyses were stratified by study design (randomized controlled trials …

Mechanism-Informed Transition From Pediatric To Adult Care In Sickle Cell Disease: A Case Study, Jane S Hankins, Tarun Aurora, Rachel Matsumoto, Sara Malone, Ana A Baumann

2020-Current year OA Pubs

BACKGROUND: Healthcare transition (HCT) refers to the shift from a child-centered to an adult-centered model of care, a process that, when well-functioning, can reduce disengagement and improve satisfaction with care. The Six Core Elements (6CE) framework structures HCT services; however, its implementation process remains understudied, limiting its broader applicability. Learning how to effectively implement the 6CE strategies can enhance their application in real clinical contexts. This case study describes the successful implementation of a 6CE-informed transition program for adolescents and young adults with sickle cell disease (SCD), a genetic condition associated with reduced life expectancy. We also propose a mechanism-informed …

Interim Estimates Of 2025-26 Seasonal Influenza Vaccine Effectiveness - United States, September 2025-February 2026., Patrick Maloney, Emily L. Reeves, Kristina Wielgosz, Ashley M. Price, Karthik Natarajan, Malini B. Desilva, Kristin Dascomb, Nicola P. Klein, Sara Y. Tartof, Stephanie A. Irving, Shaun J. Grannis, Toan C. Ong, Zachary A. Weber, Jennifer E. Schuster, Danielle M. Zerr, Marian G. Michaels, Julie A. Boom, Natasha B. Halasa, Mary A. Staat, Geoffrey A. Weinberg, Stacey L. House, Elie A. Saade, Krissy Moehling Geffel, Manjusha Gaglani, Karen J. Wernli, Vel Murugan, Emily T. Martin, Natalie A B Bontrager, Marie K. Kirby, Amanda B. Payne, Fatimah S. Dawood, Ayzsa Tannis, Heidi L. Moline, Sifang Kathy Zhao, Katherine Adams, Jennifer Decuir, Samantha M. Olson, Jessie R. Chung, Nathaniel Lewis, Brendan Flannery, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025-26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness-associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025-26 influenza season, using a test-negative case-control design. Among children and adolescents aged < 18 years, VE was 38%-41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%-34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)-associated outpatient visits was 35% and against influenza A(H3N2)-associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%-71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025-26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

Publication Productivity Among International Medical Graduates And U.S. Medical Graduates In Neurosurgery: A Comparative Assessment Using The Arms Race Control Score, Joanna M. Roy, Omar M. M. Mansoor, Samit Sen, Aaron C. Segura, Rithvik Naga Ganti, Basel Musmar, Gilberto Perez Rodriguez Garcia, Brett Henshey, Saarang Patel, Sruthi Ranganathan, Victor Gabriel El-Hajj, Stavropoula I. Tjoumakaris, M. Reid Gooch, Robert H. Rosenwasswer, Christian Bowers, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The Arms Race Control Score (ARCS) was developed to provide a quantitative assessment of publications among residency applicants. International medical graduates (IMGs) often have higher numbers of publications compared to U.S medical graduates (US MDs). However, there is limited knowledge of publication quality and effort among IMGs and US MDs. Our study analyzes publication productivity among IMGs and US MDs using the ARCS.

METHODS: Applicants were selected from ACGME-accredited training programs that enrolled both IMG and US MD residents over the 2018-2024 match cycle. Programs without IMG residents in a given year were excluded from the analysis. …

Mist: A Hierarchical Bayesian Framework For Detecting Differential Dna Methylation Dynamics In Single-Cell Data, Daoyu Duan, Wenjing Ma, Wen Tang, Hao Wu, Liangliang Zhang, Hao Feng

Faculty, Staff and Student Publications

Recent advancements in single-cell DNA methylation (scDNAm) sequencing technologies have enabled the profiling of epigenetic landscapes at unprecedented resolution, offering insights into cellular heterogeneity, differentiation and evolution. Trajectory inference, which orders cells along pseudotime, allows researchers to track genomics changes across continuous cell states and identify key loci exhibiting differential methylation. However, no methods currently exist to model methylation changes along pseudotime in scDNAm data. Here, we present a hierarchical Bayesian framework for scDNAm data analysis. Our method, named mist (methylation inference for single-cell along trajectory), models stage-specific biological variations, identifies genomic features with significant methylation changes along pseudotime, and …

Cost-Effectiveness And Implementation Strategies For Hypertension Management Using Non-Physician Healthcare Workers In Low- And Middle-Income Countries: A Systematic Review, Gabriel Lamkur Shedul, Olutobi Adekunle Sanuade, Emmanuel Iroboudu Okpetu, Molly Beestrum, Dike Bevis Ojji, Lisa R Hirschhorn, Mark D Huffman, Dustin D French

2020-Current year OA Pubs

BACKGROUND: This review assessed the cost-effectiveness and implementation strategies of hypertension management by non-physician healthcare workers (NPHCWs) in low- and middle-income countries (LMICs).

METHODS: A systematic search (inception-May 2024) included adults ≥18 years managed by NPHCWs LMICs, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Economic evaluations were assessed using Drummond's checklist and ROBINS-I.

RESULTS: Seven studies (2002-2022) conducted across eight countries enrolled 96-10,000 participants and included randomized, modeling, observational, and quasi-experimental designs. NPHCWs included pharmacists, community and village health workers, and nurses. Patients' mean age ranged 58-71 years, with 57-82% female. Outcomes assessed included cost per …

Cortical-Limbic Circuit Dynamics Of Approach-Avoidance Conflict In Humans, Brooke R Staveland, Julia Oberschulte, Barbara Berger, Tamas Minarik, Olivia Kim-Mcmanus, Jon T Willie, Peter Brunner, Mohammad Dastjerdi, Jack J Lin, Elizabeth L Johnson, Michelle Paff, Ming Hsu, Robert T Knight

2020-Current year OA Pubs

Choosing to approach or avoid is common in everyday life and excessive avoidance is a cardinal feature of anxiety disorders. We use intracranial EEG to define a prefrontal-limbic circuit supporting approach and avoidance. Presurgical epilepsy patients (n = 20) performed an approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where patients trade off rewards against losses from ghost attack. During approach, theta power increases across a limbic circuit including the hippocampus, amygdala, orbitofrontal cortex and anterior cingulate cortex, which drops during avoidance. Theta connectivity between this circuit and lateral prefrontal cortex increases during approach and falls during avoidance. …

Spatial Transcriptomic Landscape Of Invasion Patterns In Human Papillomavirus-Associated Endocervical Adenocarcinoma, Margaret L Axelrod, Ruiwen Zhou, Lulu Sun

2020-Current year OA Pubs

Human papillomavirus (HPV)-associated endocervical adenocarcinoma is the second-most common cancer of the uterine cervix. HPV-associated endocervical adenocarcinoma can be classified into histologic Silva patterns of invasion, which are associated with clinical outcome. However, the mechanisms underlying these patterns of invasion are incompletely understood. We used whole transcriptome spatial transcriptomics to examine gene expression differences separately in the tumor epithelium and the surrounding stromal immune microenvironment (SIME). Seven cases were evaluated, focusing on cases with two distinct patterns of invasion within the same tumor, to control for inter-patient heterogeneity. The most strongly upregulated pathways in both higher-risk tumor epithelium and SIME …

Longitudinal Profiles Of Executive Function In Autistic And Non-Autistic Children At High Likelihood Of Autism, Tanya St John, Neva M Corrigan, Ariel Rokem, Annette M Estes, Heather C Hazlett, Juhi Pandey, Robert T Schultz, Natasha Marrus, Lonnie Zwaigenbaum, Chimei M Lee, Stephen R Dager, Joseph Piven, Ibis Network

2020-Current year OA Pubs

BACKGROUND: Executive functioning (EF) difficulties are common in autistic children and may aggregate in families. Longitudinal studies examining EF development in autistic children and their siblings are limited. In the current study, we characterized EF development from later infancy through school-age in autistic and non-autistic high likelihood (HL; with an older autistic sibling) and low likelihood (LL; without older autistic sibling) children. METHODS: Participants were 83 autistic and 235 non-autistic HL children, and 132 LL children from the Infant Brain Imaging Study. EF was assessed at ages 12 and 24 months using the A-not-B task and ages 5–14 years (school-age) …

Molecular Insights Into The Regulation Of Gnptαβ By Lyset, Xi Yang, Balraj Doray, Danielle Henn, Varsha Venkatarangan, Benjamin C Jennings, Zhongzheng Dong, Jiaxuan Liang, Weichao Zhang, Bokai Zhang, Linchen Yu, Liang Chen, Stuart Kornfeld, Ming Li

2020-Current year OA Pubs

In vertebrates, newly synthesized lysosomal enzymes traffic to lysosomes through the mannose-6-phosphate (M6P) pathway. The Golgi membrane protein LYSET was recently discovered to regulate lysosome biogenesis by controlling the level of GlcNAc-1-phosphotransferase (GNPT). However, its working mechanism remained unclear. In this study, we demonstrate that LYSET is a two-transmembrane protein essential for GNPT stability, cleavage by Site-1 Protease (S1P), and enzymatic activity. We reconcile conflicting models by showing that LYSET enhances GNPT cleavage and prevents its mislocalization to lysosomes for degradation. We further establish that LYSET achieves this by interacting with GOLPH3 and retromer complexes to anchor the LYSET-GNPT complex …

Get Social Media And Risk-Reduction Training (Get Smart) To Improve Infant Safe Sleep Practices Through A Mobile Text Message-Delivered Video Safe Sleep Intervention For New Parents: Study Protocol For A Type 3 Hybrid Implementation-Effectiveness Cluster Randomized Trial In 20 Us Birth Hospitals, Rachel Y Moon, Sunah S Hwang, Fern R Hauck, Ann L Kellams, Paul R Shafer, Bryanne N Colvin, Hannah Karpman, Rebecca F Carlin, Michael J Corwin, Eve Colson, Margaret G Parker

2020-Current year OA Pubs

BACKGROUND: Annually, more than 3500 US infants die suddenly and unexpectedly. Many sudden unexpected infant deaths (SUID) are preventable with greater adherence to safe infant sleep guidelines. There are racial and socioeconomic disparities, both in adherence to these guidelines and in SUID rates. In the original Social Media and Risk-Reduction Training for Infant Care Practices (SMART) study in which 1600 mothers were randomized to receive short educational videos, focused on safe sleep vs. control, those receiving the safe sleep intervention had ~ 10% point higher rates of following safe sleep practices, with elimination of racial and socioeconomic disparities in safe …

Leveraging Patient Data To Detect Systematic Shifts In Daptomycin Susceptibility Testing Associated With Reduced Prescribing, Mark A Zaydman, Laurel Glaser, Daniel S Herman, Mason Kressloff, Vahid Azimi, Christine R Lockowitz, Rebekah E Dumm

2020-Current year OA Pubs

UNLABELLED: Systemic shifts in antimicrobial resistance rates can be due to epidemiologic shifts in microbial susceptibility patterns or artifactual shifts introduced by technical biases in antimicrobial susceptibility testing (AST)-both ultimately leading to changes in antimicrobial prescribing. To reduce technical variability, quality control (QC) criteria for AST are published by manufacturers and standards organizations. However, traditional QC metrics, in isolation, are fallible. In this study, we describe a systematic shift in daptomycin AST results between 2022 and 2025 in isolates tested in two independent health systems. Comprehensive analysis of clinical isolate AST results and retrospective mining of QC data from this …

The Use And Utility Of Wearable Devices For Tracking Sleep And Activity In Inpatient Mental Health Settings: Protocol For A Rapid Review, Gillian Strudwick, Hwayeon Danielle Shin, Iman Kassam, Karishini Ramamoorthi, Benjamin Rosen, Michelle A Patriquin, Justin Baker, Nicholas Neufeld

Faculty, Staff and Student Publications

Background: Wearable devices offer an opportunity to objectively monitor and capture sleep and activity in psychiatric inpatient settings, where traditional approaches often rely on subjective reporting or staff observation, both of which have inherent flaws. Technologies such as Fitbit, Garmin, Oura Ring, GENEActiv, Empatica, and WHOOP (among others) have been used to passively collect physiological data that may inform care planning and clinical decision-making. Despite growing interest, the extent to which these wearables are feasible, acceptable, and useful in inpatient mental health settings remains unclear. Synthesizing this evidence is essential to inform their potential integration into psychiatric care.

Objective: This …

International Consensus-Driven Recommendations For Patient-Reported Outcome Research Objectives In Early Phase Dose-Finding Oncology Trials: Optimise-Ror, Emily Alger, Olalekan Lee Aiyegbusi, Amylou C Dueck, Anna Minchom, Madeline Pe, John D Peipert, Claire Snyder, Stefan N Symeonides, Roger Wilson, Ethan Basch, Yu Qiao, Susan E Bates, Helen Bulbeck, Lizzie Dean, Massimo Di Maio, Aaron R Hansen, Olga Kholmanskikh, Ken Kobayashi, Dónal Landers, Christophe Le Tourneau, J Jack Lee, Brigette B Y Ma, Lynley V Marshall, Sheetal Patel, Joan Petrie, Gregory R Pond, Kieran Prior, Khadija R Rantell, John F Reeve, Olga Solovyeva, Nolan A Wages, Harald A Weber, Melanie J Calvert, Christina Yap

Faculty, Staff and Student Publications

Purpose: There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.

Methods: Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) …

Virtual Reality For The Management Of Postoperative Pain And Anxiety In Children And Adolescents Undergoing Nuss Repair Of Pectus Excavatum: Randomized Controlled Trial, Charlotte M. Walter, Dillon Froass, Nora Bell, Lauren Haack, Chloe Boehmer, Claudia Bruguera Torres, Rachel Spivak, Max Chou, Kristie Geisler, Keith O'Conor, Sara E. Williams, Lili Ding, Christopher D. King, Vanessa A. Olbrecht

Department of Medicine Faculty Papers

BACKGROUND: Virtual reality (VR) is a novel technology with implications for pain and sensory processing. VR may serve as a novel, scalable method to deliver clinically validated therapy for pain management as an alternative or adjunct to opioids for acute pain. Given that psychological factors and pain perception are both components of postoperative pain, it may also be beneficial to incorporate modalities that decrease anxiety, such as active relaxation and guided meditation with VR. Unfortunately, these therapies are not widely available due to multiple barriers. VR has the potential to deliver pain-reducing, psychologically based therapy to children, thereby enhancing multimodal …

Recommendations For The Diagnosis And Management Of Cln3 Disease (Batten Disease) Using The Delphi Consensus Methodology, Jonathan W Mink, Jonathan D Cooper, Et Al.

2020-Current year OA Pubs

BACKGROUND: CLN3 disease, also called Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is an ultra‑rare, neurodegenerative lysosomal storage disorder generally affecting individuals during the first decade of life. There can be a delay in diagnosis or misdiagnosis due to a lack of awareness, and when the most common presenting symptom of visual loss is attributed to more common conditions affecting vision. METHODS: We used a previously published Expert Mapping Tool (EMT) to identify multidisciplinary professionals with diagnostic or clinical management expertise, as well as patient advocates with experience of CLN3 disease. A systematic literature review of published evidence using …

Ultrasound-Guided Skeletal Muscle Biopsy Technique Permits Measurement Of Structural, Functional, Cellular And Biochemical Properties, Addison Barber, Amber Willbanks, Guadalupe Meza, Jeremie L A Ferey, Gretchen A Meyer, Sudarshan Dayanidhi, W David Arnold, Richard L Lieber, Ishan Roy

2020-Current year OA Pubs

Human muscle biopsies are often required to study or diagnose diseases. However, traditional approaches are challenging due to limited sample size, quality, or participant discomfort. Fine-gauge needle biopsies (≥ 14-gauge), present an alternative but may yield insufficient tissue for comprehensive analysis. Ultrasound guidance, coupled with vacuum-assisted, single needle-insertion multiple sampling addresses these challenges. In 19 healthy participants (mean age: 30.1 ± 10 years, 42% male), 2-3 samples were collected from a single needle insertion into the vastus lateralis (VL) and tibialis anterior (TA). Summed VL and TA sample masses averaged 148 ± 38 mg and 166 ± 64 mg, with …