Digital Commons Network^™

Genetic Underpinnings Of The Heterogeneous Impact Of Obesity On Lipid Levels And Cardiovascular Disease, Daeeun Kim, Heather M Highland, Roelof A J Smit, Micah R Hysong, Victoria L Buchanan, Kristin L Young, Chi Zhao, Cassandra N Spracklen, Tuomas O Kilpeläinen, Boya Guo, Burcu F Darst, Yanwei Cai, Zhe Wang, Jessica Lundin, Sonja I Berndt, Joann E Manson, Eirini Marouli, Leslie Lange, Ethan Lange, Myriam Fornage, Christopher R Gignoux, Christopher A Haiman, Stephen S Rich, Steven Buyske, Ruth J F Loos, Charles Kooperberg, Ulrike Peters, Christy L Avery, Penny Gordon-Larsen, Mariaelisa Graff, Laura M Raffield, Kari E North

Faculty, Staff and Student Publications

Background: Obesity is thought to increase cardiovascular disease (CVD) risk partly through dyslipidemia. Yet, obesity's effects on dyslipidemia are not uniform. Understanding the shared genetic basis between obesity and lipid traits can provide insight into this heterogeneity and its implications for CVD risk.

Methods: We examined local genetic correlations between three lipid measures [high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG)] and body mass index (BMI) using genome-wide association study summary statistics from European ancestry UK Biobank participants. We identified genomic loci with opposing genetic effects on obesity and dyslipidemia risk (protective BMI-lipid loci) and those with …

Inflammation And Mutational Burden Differentially Associated With Nivolumab Or Ipilimumab Combination Efficacy In Colorectal Cancer, Ming Lei, Michael J Overman, Jin Yao, Thierry André, Sara Lonardi, Heinz-Josef Lenz, Massimo Aglietta, Fabio Gelsomino, Ray Mcdermott, Ka Yeung Mark Wong, Michael A Morse, Eric Van Cutsem, Alain Hendlisz, Dana B Cardin, Bart Neyns, Andrew Hill, Anuradha Krishnamurthy, Franklin Chen, Samith Kochuparambil, Robert R Jenq, Sandzhar Abdullaev, Beilei He, Ruslan Novosiadly, Scott Kopetz

Faculty, Staff and Student Publications

Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator …

Assessing A Community Health Worker-Facilitated, Digitally Delivered, Family-Centered Diabetes Management Program: Single-Arm Quasi-Experimental Study, Zenong Yin, Vanessa L Errisuriz, Heather Cuevas, Bertha E Flores, Laura Delfausse, Christina Galvan, Jing Wang, Chengdong Li, Renata Morfin, Shiyu Li, Maysa Sapargeldiyeva, Giliane Yza Muyna, Minyu Zhang, Vanessa Sweet, Deborah Parra-Medina

Faculty, Staff and Student Publications

Background: The high prevalence of type 2 diabetes (T2D) and associated complications disproportionately affect low-income Latino populations, who also experience disparities in diabetes self-management (DSM), including poor medication adherence, physical activity, diet, and glycemic control.

Objective: This study examined, through an academic-community partnership, the effectiveness of ¡Salud, Salud! (an evidence-based, family-centered diabetes self-management education and support [DSMES] program) on primary (glycemic control and quality of life) and secondary (social, psychological, and behavioral factors related to T2D management) outcomes among low-income Latino adults with T2D or prediabetes.

Methods: In total, 81 adults (mean age 48.90 years, SD 12.57; n=57, 70.4%, female; …

Rescue Epilepsy Medication And Training: A Comparison Between Midazolam Use, Guidelines, Clinical Practice, And Possibilities In The Uk And Norway, Rohit Shankar

Peninsula Medical School

Objectives: Status epilepticus (SE) is a prolonged epileptic seizure carrying significant risk of long-term disability and death. Rescue therapies are prescribedfor prehospital administration to terminate SE. This study compared prescribingpractices of rescue therapies of midazolam in the UK and Norway.Methods: A cross-sectional, online, 21-item Likert-style survey was administeredto epilepsy professionals in the UK circulated via ILAE/ESNA and in Norway viaILAE/Epilepsinet using a non-discriminatory exponential snowballing techniqueleading to non-probability sampling. Data were collected anonymously and analyzed using descriptive statistics, Mann–Whitney, Chi-square, and Fisher's exact tests. Significance was accepted at p<0.05.Results: All 86 UK and 53 Norway respondents identified buccal midazolam as the first-line rescue medication choice in the community for prolonged and/or generalized tonic–clonic seizures. Norwegian respondents had significantly more experience in epilepsy-related work (p=0.002), were more likely to have a larger caseload on buccal midazolam (p<0.001), prescribed higher midazolam doses (p<0.001), and provided training yearly (p<0.001). UK respondents were more likely to delegate rescue medication prescribing to primary care (p=0.006) and reviewed emergency management plans more frequently (p=0.006). There was an inter-country difference in the period of midazolam non-use that respondents required before withdrawing from treatment plans (p<0.001). Concern about inappropriate use of buccal midazolam was similarly high in both countries.Significance: This study compared epilepsy professionals in two neighboringhigh-income countries. Findings suggest an urgent need for international guidelines to recommend best practices on prescribing doses and withdrawal of buccal midazolam. The potential abuse of buccal midazolam by patients and carers warrants further investigation.

Understanding The Role Of Street Medicine In Harm Reduction: A Case Study Of Street Medicine St. Louis, Ari Gzesh, Jeremiah S Truel, Danielle R Adams, Luke Zabotka, Sara Malone, Nathanial S Nolan

2020-Current year OA Pubs

BACKGROUND: Homelessness results from, and exacerbates, various social determinants of health, including poverty, racism, and inadequate healthcare access, which are further compounded by physical and mental health challenges. The street medicine movement seeks to address these disparities by providing direct medical care and harm reduction services to unsheltered homeless in low-barrier settings. The development of trust is critical to providing this form of care. Few studies have sought to understand the factors influencing trust development in street medicine encounters.

METHODS: This case study of Street Medicine St. Louis aims to explore the factors that influence trust and how trust development …

Temporal Trends In The Epidemiology Of Hip Osteoarthritis In The Usa, 1990-2019: A Cross-Sectional Time-Series Study Using Gbd Data., Arsalaan Sayyed, Gabrielle Lucia Dykhouse, Taylor J Manes, Cameron Sabet, Minali Gautami Nemani, Ambrose Loc Ngo, Ayah A Ibrahim, Phillip C Mckegg, Jignesh N Patel

Ambulatory and Primary Care Articles

OBJECTIVES: To evaluate temporal trends in the epidemiology of hip osteoarthritis (OA) in the USA from 1990 to 2019, with stratification by sex and geographic region.

DESIGN: Cross-sectional time-series analysis using secondary data from the Global Burden of Disease (GBD) study.

SETTING: US population-based analysis, stratified by the four US Census Bureau regions: Northeast, Midwest, South and West.

PARTICIPANTS: De-identified, aggregate population-level data representing all adults in the USA from 1990 to 2019, drawn from the GBD database.

PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised rates per 100 000 population for years lived with disability (YLDs), prevalence and incidence of hip …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Robotic Ureteral Reconstruction For Endometriosis-Induced Strictures: Insights From A Multi-Institutional Experience, Matthew Lee, Sonam Saxena, Kelley Zhao, Cameron Dodd, Randall Lee, Michael Stifelman, Lee Zhao, Daniel D. Eun

Department of Surgery Faculty Papers

PURPOSE: To investigate outcomes of robotic ureteral reconstruction (RUR) in female patients with ureteral strictures caused by peri-ureteral endometriosis lesions.

METHODS: We retrospectively reviewed our multi-institutional Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database to identify all consecutive patients undergoing RUR for surgical management of endometriosis-induced ureteral strictures between 2017 and 2022. Indications for surgery included female patients with radiographic evidence of ureteral strictures and/or decreasing renal function on renal scan. We performed a descriptives analysis of perioperative outcomes in patients who met inclusion criteria. Surgical success was defined as freedom from additional interventions for recurrent ureteral stenosis.

RESULTS: Overall, …

Motivation And Experiences Of Individuals With Opioid Use Disorder And Chronic Pain Using Medical Cannabis For 12 Months., Michelle R. Lent, Karen L Dugosh, Kartik Varsani, Andrea Jonsson, Tyler Kung, Katherine E. Galluzzi

PCOM Scholarly Works

BACKGROUND: The objective of this qualitative study was to better understand the experiences of individuals living with opioid use disorder (OUD) and chronic pain using medical cannabis (MC) for 12 months.

METHODS: Perspectives were captured via 10 key informant interviews conducted after 12 months of treatment with MC RESULTS: Key themes identified regarding the reasons for initially pursuing MC included: (1) cannabis supply safety; (2) a desire to reduce or eliminate prescription medication usage for pain, OUD and mood; (3) to induce feelings of calm or relaxation; and (4) to improve levels of chronic pain. At 12 months, key themes …

Ambient Fine Particulate Matter, Residential Greenness, And Childhood Cancer Risk By Trimester Of Exposure In Minnesota 2000 To 2014: A Case-Control Study, Cassandra J Clark, David Haynes, Zhanni Lu, Jeannette M Sample, Laura A Mcguinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer, Erin L Marcotte, Lindsay A Williams

Faculty, Staff and Students Publications

Background: Outdoor air pollution is a suspected risk factor for childhood cancer, and there is some evidence that greenness may reduce cancer risk. We examined relationships between prenatal exposure to ambient fine particle air pollution [particulate matter < 2.5 µg/m3 (PM2.5)], greenness, and childhood cancer risk in Minnesota.

Methods: Cases included individuals born in the state of Minnesota and reported to the Minnesota Cancer Reporting System between 2000 and 2014 (n = 1272, ages 0-14 years at diagnosis) and birth year-matched cancer-free controls (n = 5245). We used Network Common Data Form to estimate monthly PM2.5 exposure and the normalized difference vegetation index for census tract-level greenness. We estimated ORs and …

All-Optical Voltage Interrogation For Probing Synaptic Plasticity In Vivo, Jacques Carolan, Michelle A Land, Xiaoyu Lu, Maxime Beau, Dimitar Kostadinov, François St-Pierre, Beverley A Clark, Michael Häusser

Faculty, Staff and Students Publications

Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) …

Genome-Wide Analysis Of Dna Methylation Signatures Linking Prenatal Exposure To The Chinese Great Famine And Blood Lipids In Late Adulthood: The Genomic Research Of The Chinese Famine (Grecf) Study, Huan Wang, Luqi Shen, Tingting Liu, Ruiyuan Zhang, Zhenghe Wang, Jingkai Wei, Ye Shen, Jinzhen Guo, Toni Miles, Changwei Li, Zhiyong Zou

Faculty, Staff and Student Publications

Background/objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959-1961) on human epigenome and the subsequent influence on blood lipids.

Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation …

A Mast Cell Receptor Mediates Post-Stroke Brain Inflammation Via A Dural-Brain Axis, Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim, Justin M Caplan, Fernanado L Gonzalez, Christopher M Jackson, Chetan Bettegowda, Judy Huang, Bhanu P Ganesh, Chunfeng Tan, Raymond C Koehler, Rafael J Tamargo, Louise D Mccullough, Risheng Xu, Xinzhong Dong

Faculty, Staff and Student Publications

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal …

Rare Variants In Prkci Cause Van Der Woude Syndrome And Other Features Of Peridermopathy, Kelsey Robinson, Sunil K Singh, Rachel B Walkup, Dorelle V Fawwal, Kendra M Vilfort, Amanda Koloskee, Azeez Fashina, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Wendy K Chung, David J Cutler, Michael P Epstein, Brooklynn Gasser, Lord J J Gowans, Jacqueline T Hecht, Anuj Mankad, Lina Moreno Uribe, Daryl A Scott, Gary M Shaw, Mary Ann Thomas, Seth M Weinberg, Eric C Liao, Harrison Brand, Mary L Marazita, Robert J Lipinski, Jeffrey C Murray, Robert A Cornell, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of ∼1 in 35,000 live births, it is the most common form of syndromic clefting. Most VWS is attributed to variants in IRF6 (∼70%) or GRHL3 (∼5%), leaving up to 25% of individuals without a molecular diagnosis. Both IRF6 and GRHL3 function in a transcriptional regulatory network (TRN) governing differentiation of periderm, a single epithelial cell layer preventing pathological adhesions during palatogenesis. Periderm disruption can elicit a spectrum of phenotypes, including lip pits and OFCs, pterygia, and severe …

Preclinical Models Of Melanoma Leptomeningeal Disease To Assess Intrathecal Checkpoint Blockade, Renato A Guerrieri, Grant M Fischer, Jacob R Cortez, Barbara G Knighton, Debora A Ledesma, Courtney W Hudgens, Yimmy F Delcid, Qianghua Hu, Christian Y B Onana, Fernando C L Carapeto, Michael T Tezlaff, Jason T Huse, Patrick Hwu, Elizabeth M Burton, Isabella C Glitza Oliva, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, …

The 10-Year Functional Outcome Of Ponseti Treatment Of Idiopathic And Arthrogrypotic Clubfeet With An Age-Matched Control, Chris Church, Nicole Wang, Stephanie Butler, Jose J Salazar-Torres, John Henley, Freeman Miller, Nancy Carlin, Maureen Donohoe, L Reid Nichols

Faculty and Staff Publications

Background: The Ponseti method is accepted as an effective primary conservative treatment for idiopathic clubfoot (IC) using serial casting, percutaneous Achilles tenotomy, and prolonged bracing. The outcomes of its use in treating rigid clubfoot in arthrogryposis are unclear. This study assesses the outcomes of the Ponseti method in children with IC and arthrogrypotic clubfoot at an average age of 10 years.

Methods: Outcomes of the Ponseti method were retrospectively studied in ambulatory children ages 8.0 to 12.9 years in the gait lab between 2004 and 2024. Children were excluded due to the presence of nonidiopathic or nonarthrogryposis-related clubfoot and history …

Exploring The Transformative Effects Of Calorie Restriction On The Lacrimal Gland In Adult Mice., Olivier Mauduit, Prashant Kumar, Kaitlin K Scholand, Emre Aksan, Laura Schaefer, Anmar Abu-Romman, Vanessa Delcroix, Zhiyuan Yu, Aude I Sindikubwabo, Ron Korstanje, Helen P Makarenkova, Cintia S De Paiva

Faculty Research 2025

Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months and continuing until 10-11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva, and cornea subjected …

A Program For The Occupational Needs Of Women With Urinary Incontinence In Independent/Assisted Living Facilities, Blair Riddell, Rebecca King

Fall 2025 OTD Capstone Symposium

The purpose of this capstone project was to develop a multimedia educational program for women with UI living in an independent living facility(ILF)/assisted living facility (ALF) to foster engagement in health management behaviors for enhanced overall quality of life.

What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam

Department of Medicine Faculty Papers

INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …

Concurrent Local Therapy Extends Clinical Benefit Of Tebentafusp In Metastatic Uveal Melanoma Patients, Tristan L. Lim, Kamaneh Montazeri, Eric Wehrenberg-Klee, Antoine Desilets, Rino S. Seedor, Marlana Orloff, Takami Sato, Michael Caplan, Mariam El-Ashmawy, Benjamin Izar, Shaheer Khan, Inderjit Mehmi, Aleigha Lawless, Theodore S. Hong, Omid Hamid, Richard D. Carvajal, Alexander Shoushtari, Ryan J. Sullivan

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that …

Occupational Therapy's Role In Maternal Health: Empowering Mothers Experiencing Postpartum Depression And Anxiety Through Education On Child Development, Phoebe Spernal, Keisa Boykin

Fall 2025 OTD Capstone Symposium

To empower mothers experiencing postpartum depression and anxiety by strengthening their maternal knowledge and self-efficacy in supporting their baby’s development through an occupational therapy-based educational program.

Escape Of Kdm6a From X Chromosome Is Detrimental To Ischemic Brains Via Irf5 Signaling, Conelius Ngwa, Afzal Misrani, Kanaka Valli Manyam, Yan Xu, Shaohua Qi, Romana Sharmeen, Juneyoung Lee, Long-Jun Wu, Louise Mccullough, Fudong Liu

The Brown Foundation: Institute of Molecular Medicine

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia, respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17–20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the …

Concussion Knowledge, Attitudes, And Behaviors: A Comparison Study Of Youth Athletes And Their Parents, Summer D Ott, Sukhnandan K Cheema, Holden Axel, Seema S Aggarwal, Natalie R Parks, Nikhil Gattu, Philip Schatz

Faculty, Staff and Student Publications

Objective: Given the rising participation in high school athletics and the concerning trend of underreporting concussions, this study aims to identify and compare factors influencing sports-related concussion (SRC) awareness and reporting among youth athletes to their parents.'

Methods: Surveys were completed by 239 student-athletes (ages 13-19) and their parents, using a modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) and demographic questionnaires. Statistical analyses, including paired sample t-tests, ANOVAs, and Spearman's correlations, compared knowledge and attitudes between groups and examined demographic influences.

Results: Parents showed significantly higher concussion knowledge (CKI: t(230) = 5.18, p < .001) and safer attitudes (CAI: t(230) = 10.62, p < .001) than their children. Knowledge scores varied significantly by race and socioeconomic status, with White parents scoring higher than Hispanic and African American parents (F(3,224) = 8.97, p < .001). Child knowledge scores also differed by race (F(4,223) = 3.73, p = .006) …

Hydrogen Sulfide Inhibits Recruitment Of Monocyte-Derived Tumor Associated Macrophages In Glioblastoma By Downregulating Cxcl12, Joseph Camarano, Morgan Roque, Gabrielle Gahn, Stephen Garrett Whipple, Danielle Terrell, Charles Ronkon, Jamie Toms, Anthony Sin, Bharat Guthikonda, Khatri Latha, Yuhui Yang, Xinggui Shen, Christopher G Kevil, Ganesh Rao, Sungho Lee

Faculty, Staff and Students Publications

Tumor associated macrophages (TAMs) directly contribute to the dismal prognosis of glioblastoma by preventing anti-tumor immunity and promoting tumor invasion and angiogenesis. Inhibiting TAM infiltration is a potential therapeutic strategy in glioblastoma, with several chemokine antagonists in early clinical development. Hydrogen sulfide, a gasotransmitter that regulates microglial accumulation in a wide range of CNS diseases, may be a novel therapeutic target to prevent TAM recruitment in glioblastoma. In this study, hydrogen sulfide concentrations were directly measured from 14 isocitrate dehydrogenase (IDH)-wildtype glioblastoma surgical samples and compared against overall survival as well as expression of TAM markers and chemokines. Effects of …

A New Multisystem Ercc1-Hepatorenal Syndrome: Insights From A Clinical Cohort, Molecular Pathogenesis, And Management Guidelines., Susan M. White, Annelotte P. Wondergem, Isa Breet, Maren Dittmaier, Katrina Bell, Christopher M. Richmond, Winita Hardikar, Kanika Bhatia, Catherine Quinlan, David Orchard, Areetha D'Souza, Walter J. Chazin, Christopher Smith, Rebecca Sparkes, Simon Lam, Alexandra Carter, Robert J. Hopkin, Leticia Khendek, Bonnie Sullivan, Naja Becher, Anne Katrine W. Simonsen, Helene Kvistgaard, Katherine Dempsey, Alexander G. Miethke, Pernille Axél Gregersen, Eliza Phillips, Martijn S. Luijsterburg

Manuscripts, Articles, Book Chapters and Other Papers

DNA repair disorders are a group of conditions characterized by progressive, multisystem phenotypes. Defining new clinical presentations of these disorders is essential for optimizing patient care. ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair. We sought to define a novel multisystem phenotype associated with biallelic ERCC1 variants and impaired DNA repair. Through international collaboration, we identified seven individuals from five families carrying biallelic ERCC1 variants, including p.Arg156Trp and p.Ala266Pro, who exhibited a distinct clinical phenotype. All individuals presented with growth restriction, photosensitivity, and kidney and liver dysfunction. Notably, three children required liver …

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Associations Among Human Milk Polyunsaturated Fatty Acids And Infant Sleep Patterns: A Cross-Sectional Study, Ana M Palacios, Dominick J Lemas, Bridget E Young, Erik Parker, Stephanie Dickinson, Nandi Marshall, Kelly L Sullivan, Haley Wilt, Michelle I Cardel, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

Methods: This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, …

All-Cause And Cause-Specific Mortality Among Patients With Narcolepsy., Chih-Wei Hsu, Yen-Shan Yang, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Importance: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

Objective: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

Design, setting, and participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 …

Menopause Factors And Alterations In Gut Microbiota And Insulin Homeostasis: A Cross-Sectional Analysis Of The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Vincent J Maffei, Alain G Bertoni, Alexis C Wood, Jerome I Rotter, Osa Crago, Yii-Der I Chen, Joseph F Petrosino, Kristi L Hoffman, Mark O Goodarzi, Elizabeth T Jensen

Children’s Nutrition Research Center Staff Publications

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, …

Hydroxocobalamin For Vasoplegia In Cardiac Surgery: A Retrospective Cohort Analysis, Luai Zakaria, Karan Shah, Dongsheng Yang, Marta Kelava, Haytham Elgharably, Ashish K Khanna, Sanchit Ahuja, Benjamin Hohlfelder, Andrej Alfirevic, Andra E Duncan, Nikolaos J Skubas, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Vasoplegia during cardiac surgery is common and associated with perioperative mortality. Hydroxocobalamin is a catecholamine-sparing approach for treating vasoplegia. However, there is currently limited evidence to inform its use.

Methods: We conducted a single-centre retrospective propensity-matched cohort study of patients who developed vasoplegia after cardiopulmonary bypass. Our primary outcome was vasopressor requirement, expressed as norepinephrine equivalents (NEE), at 1, 4, 24, and 48 h after treatment. Our secondary outcome was a collapsed composite of in-hospital complications comprising stroke, sternal wound infection, mesenteric ischaemia, renal failure, and death.

Results: We identified 2727 (11%) patients with vasoplegia from 2018 to 2024. …