Digital Commons Network^™

Estimated Vaccine Effectiveness For Pediatric Patients With Severe Influenza, 2015-2020., Kelsey M. Sumner, Leila C. Sahni, Julie A. Boom, Natasha B. Halasa, Laura S. Stewart, Janet A. Englund, Eileen J. Klein, Mary A. Staat, Elizabeth P. Schlaudecker, Rangaraj Selvarangan, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Monica N. Singer, Parvin H. Azimi, Benjamin R. Clopper, Heidi L. Moline, Emma K. Noble, John V. Williams, Marian G. Michaels, Samantha M. Olson, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

OBJECTIVE: To investigate VE in children by severity of influenza illness.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020. Participants included children 6 months through 17 years of age who were hospitalized or presented to an emergency department (ED) with acute respiratory illness. …

Inherited Retinal Degenerations And Non-Neovascular Age-Related Macular Degeneration: Progress And Unmet Needs, Jacque L Duncan, Angela Bowman, Amy Laster, Claire Gelfman, David G Birch, Shannon E Boye, Stephen P Daiger, Lucian Del Priore, Donald J Zack, James T Handa

Faculty, Staff and Student Publications

Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD. The article outlines opportunities to address gaps and unmet needs that should lead to additional progress toward the development of treatments …

Rna Shielding Of P65 Is Required To Potentiate Oncogenic Inflammation In Tet2-Mutated Clonal Hematopoiesis, Nana Adjoa Ben-Crentsil, Wazim Mohammed Ismail, Maria E Balasis, Hannah Newman, Ariel Quintana, Moritz Binder, Traci Kruer, Surendra Neupane, Meghan C Ferrall-Fairbanks, Jenna Fernandez, Terra L Lasho, Christy M Finke, Mohammed L Ibrahim, Kathy L Mcgraw, Michael Wysota, Amy L Aldrich, Christopher B Ryder, Christopher T Letson, Joshua Traina, Amy F Mclemore, Nathalie Droin, Aditi Shastri, Seongseok Yun, Eric Solary, David A Sallman, Amer A Beg, Li Ma, Alexandre Gaspar-Maia, Mrinal M Patnaik, Eric Padron

Faculty, Staff and Student Publications

This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.

Myeloid Activation Clears Ascites And Reveals Il27-Dependent Regression Of Metastatic Ovarian Cancer, Brennah Murphy, Taito Miyamoto, Bryan S Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P Zhu, Daniel T Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang

Faculty, Staff and Student Publications

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of < 30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

Redesigning The Hospital Environment To Improve Restfulness, Caellagh D Catley, Kayla Paynter, Kendall Jackson, Ashley Huggins, Jenny Ji, Sai Anusha Sanka, Michelle Simkins, Thomas M Maddox, Patrick G Lyons

2020-Current year OA Pubs

IMPORTANCE: Hospital wards are often not conducive to patient sleep, negatively affecting patient health and experience.

OBJECTIVES: To assess determinants of in-hospital restfulness and to design and test rest-promoting interventions on the wards in partnership with clinicians, staff, and patients.

DESIGN, SETTING, AND PARTICIPANTS: This rapid-sequential mixed-methods quality improvement study was performed at a large urban academic hospital in St Louis, Missouri, from May 1, 2021, to December 31, 2022, with follow-up through hospitalization. Mixed-methods activities involved purposively selected hospitalized adults on the wards, nurses, hospitalists, and hospital staff. Interventions included all adult hospitalizations on the study wards.

INTERVENTIONS: Sequential …

Secure Messaging Use And Wrong-Patient Ordering Errors Among Inpatient Clinicians, Sunny S Lou, Daphne Lew, Linlin Xia, Laura Baratta, Elise Eiden, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Use of secure messaging for clinician-to-clinician communication has increased exponentially over the past decade, but its association with clinician work is poorly understood.

OBJECTIVE: To investigate the association between secure messaging use and wrong-patient ordering errors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included inpatient attending physicians, trainee physicians, and advanced practice practitioners (APPs) from 14 academic and community hospitals. Secure messaging volume was assessed over a 3-month period (February 1 to April 30, 2023).

EXPOSURE: Secure messaging volume per clinician-day, measured as the count of secure messages sent and received by a clinician on a given clinician-day.

MAIN …

Medical And Surgical Episodes Among Hospital Participants In The Bundled Payments For Care Improvement-Advanced Program, Keenan J Robbins, Jie Zheng, R J Waken, E John Orav, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Hospital participation in the Bundled Payments for Care Improvement-Advanced (BPCI-A) initiative has been associated with modest savings and stable clinical outcomes overall, but it is unknown whether the program performs differently for medical and surgical or procedural (henceforth, surgical) episodes.

OBJECTIVE: To assess the association of BPCI-A participation with Medicare spending and clinical outcomes for medical and surgical episodes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective difference-in-differences cohort study utilized 100% Medicare fee-for-service inpatient claims for episodes initiated between January 1, 2017, and September 30, 2019, and included 90 days of follow-up. The setting was hospitals participating in BPCI-A and …

Allostatic Load, Educational Attainment, And Risk Of Cancer Mortality Among Us Men, Cynthia Li, Sydney P Howard, Charles R Rogers, Sydney Andrzejak, Keon L Gilbert, Keith J Watts, Malcolm S Bevel, Myles D Moody, Marvin E Langston, Judah V Doty, Adetunji T Toriola, Darwin Conwell, Justin X Moore

2020-Current year OA Pubs

IMPORTANCE: Health disparities among racial and ethnic minoritized populations, particularly for cancer mortality rates, remain a major public health concern. Men from underrepresented backgrounds (Black and Hispanic men, specifically) face the pervasive effects of discrimination in their daily lives, which also contribute to the complex associations among allostatic load (a marker of chronic stress), educational opportunities, and elevated risks of cancer mortality.

OBJECTIVE: To elucidate the associations among educational attainment, allostatic load, and cancer mortality risk among men.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort analysis of data from the National Health and Nutrition Examination Survey, a nationally …

Neuroanatomical Variability And Substance Use Initiation In Late Childhood And Early Adolescence, Alex P Miller, David A A Baranger, Sarah E Paul, Hugh Garavan, Scott Mackey, Susan F Tapert, Kimberly H Leblanc, Arpana Agrawal, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood.

OBJECTIVE: To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, …

Major Depressive Disorder And Driving Behavior Among Older Adults, Ganesh M Babulal, Ling Chen, Jean-Francois Trani, David C Brown, David B Carr, Beau M Ances, Eric J Lenze, Drives Project

2020-Current year OA Pubs

IMPORTANCE: Depression and antidepressant use are independently associated with crash risk among older drivers. However, it is unclear what factors impact daily driving that increase safety risk for drivers with depression.

OBJECTIVE: To examine differences in naturalistic driving behavior and safety between older adults with and without major depressive disorder (MDD).

DESIGN, SETTING, AND PARTICIPANTS: A prospective longitudinal cohort study was conducted among older adults (≥65 years) from the Driving Real-World In-Vehicle Evaluation System Project collected from July 1, 2021, to December 30, 2023. The sample included 85 participants with MDD and 310 participants without. Neurological, clinical, mood, and neuropsychological …

Alcohol Use Disorder Polygenic Score Compared With Family History And Adh1b, Dongbing Lai, Michael Zhang, Marco Abreu, Tae-Hwi Schwantes-An, Grace Chan, Danielle M Dick, Chella Kamarajan, Weipeng Kuang, John I Nurnberger, Martin H Plawecki, John Rice, Marc Schuckit, Bernice Porjesz, Yunlong Liu, Tatiana Foroud

2020-Current year OA Pubs

IMPORTANCE: Identification of individuals at high risk of alcohol use disorder (AUD) and subsequent application of prevention and intervention programs has been reported to decrease the incidence of AUD. The polygenic score (PGS), which measures an individual's genetic liability to a disease, can potentially be used to evaluate AUD risk.

OBJECTIVE: To assess the estimability and generalizability of the PGS, compared with family history and ADH1B, in evaluating the risk of AUD among populations of European ancestry.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted between October 1, 2023, and May 21, 2024. A 2-stage design was used. …

Pediatric Covid-19 Vaccine Hesitancy Among Pregnant And Post-Partum Women: A Mixed-Method Study, Tasmiah Nuzhath, Brian Colwell, Timothy Callaghan, Peter Hotez, Sabrina Mousum, Ummul Wara Masud, Annette K Regan

Faculty, Staff and Students Publications

Background: This study aims to understand factors contributing to pediatric COVID-19 vaccine hesitancy among pregnant and postpartum adults.

Method: The study used targeted intercept advertising on Facebook, Twitter, and Instagram to recruit a panel of 3600 pregnant and postpartum US adults. Data were collected between December 2021 and April 2022 (i.e., before the introduction of pediatric COVID-19 vaccines in the U.S.). We used logistic regression to understand factors associated with pregnant and postpartum women's hesitancy towards getting children < 5 vaccinated against COVID-19. Poststratification weights were applied to analyses to promote the representativeness of the sample. We also conducted a qualitative thematic analysis to determine the reasons for pediatric vaccine hesitancy.

Results: Nearly half (45.6 %) of pregnant or postpartum women were hesitant to vaccinate their child against COVID-19. Vaccine hesitancy was lower …

Neurofeedback: New Territories And Neurocognitive Mechanisms Of Endogenous Neuromodulation, James Sulzer, T Dorina Papageorgiou, Rainer Goebel, Talma Hendler

Faculty, Staff and Students Publications

Neurofeedback (NF) is endogenous neuromodulation of circumscribed brain circuitry. While its use of real-time brain activity in a closed-loop system is similar to brain-computer interfaces, instead of controlling an external device like the latter, the goal of NF is to change a targeted brain function. In this special issue on NF, we present current and future methods for extracting and manipulating neural function, how these methods may reveal new insights about brain function, applications, and rarely discussed ethical considerations of guiding and interpreting the brain activity of others. Together, the articles in this issue outline the possibilities of NF use …

The Study Of The Epidemiology Of Pediatric Hypertension Registry (Superhero): Rationale And Methods, Andrew M South, Victoria C Giammattei, Kiri W Bagley, Christine Y Bakhoum, William H Beasley, Morgan B Bily, Shupti Biswas, Aaron M Bridges, Rushelle L Byfield, Jessica Fallon Campbell, Rahul Chanchlani, Ashton Chen, Lucy D'Agostino Mcgowan, Stephen M Downs, Gina M Fergeson, Jason H Greenberg, Taylor A Hill-Horowitz, Elizabeth T Jensen, Mahmoud Kallash, Margret Kamel, Stefan G Kiessling, David M Kline, John R Laisure, Gang Liu, Jackson Londeree, Caroline B Lucas, Sai Sudha Mannemuddhu, Kuo-Rei Mao, Jason M Misurac, Margaret O Murphy, James T Nugent, Elizabeth A Onugha, Ashna Pudupakkam, Kathy M Redmond, Sandeep Riar, Christine B Sethna, Sahar Siddiqui, Ashley L Thumann, Stephen R Uss, Carol L Vincent, Irina V Viviano, Michael J Walsh, Blanche D White, Robert P Woroniecki, Michael Wu, Ikuyo Yamaguchi, Emily Yun, Donald J Weaver

Faculty, Staff and Students Publications

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th …

Urinary Metal Levels, Cognitive Test Performance, And Dementia In The Multi-Ethnic Study Of Atherosclerosis, Arce Domingo-Relloso, Katlyn E Mcgraw, Susan R Heckbert, Jose A Luchsinger, Kathrin Schilling, Ronald A Glabonjat, Irene Martinez-Morata, Melanie Mayer, Yongmei Liu, Alexis C Wood, Jeff Goldsmith, Kathleen M Hayden, Mohamad Habes, Ilya M Nasrallah, R Nick Bryan, Tanweer Rashid, Wendy S Post, Jerome I Rotter, Priya Palta, Linda Valeri, Timothy M Hughes, Ana Navas-Acien

Faculty, Staff and Students Publications

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024.

EXPOSURE: Urine samples were collected at baseline …

Excess Mortality In Persons With Concurrent Hiv And Cancer Diagnoses: A Retrospective Cohort Study, Kamaria L Lee, Varada Sarovar, Jennifer O Lam, Wendy A Leyden, Stacey E Alexeeff, Alexandra N Lea, Rulin C Hechter, Haihong Hu, Julia L Marcus, Qing Yuan, Jennifer R Kramer, Lilie L Lin, Elizabeth Y Chiao, William J Towner, Michael A Horberg, Michael J Silverberg

Center for Medical Ethics and Health Policy Staff Publications

Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality among PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population.

Methods: We identified 39,000 PWH and 387,767 demographically matched PWoH in three integrated healthcare systems from 2000 to 2016. We estimated excess mortality among PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and …

Chlorthalidone Vs Hydrochlorothiazide And Kidney Outcomes In Patients With Hypertension: A Secondary Analysis Of A Randomized Clinical Trial, Areef Ishani, Cynthia Hau, Srihari Raju, Jessica K Wise, Peter A Glassman, Addison A Taylor, Ryan E Ferguson, William C Cushman, Sarah M Leatherman

Faculty, Staff and Students Publications

Importance: Hypertension is a risk factor for the development and progression of chronic kidney disease (CKD). It is unclear whether different thiazide diuretics have a differential impact on kidney outcomes.

Objective: To compare kidney outcomes in patients with hypertension taking chlorthalidone and hydrochlorothiazide.

Design, setting, and participants: This prespecified secondary analysis of the Diuretic Comparison Project, a randomized clinical trial comparing chlorthalidone and hydrochlorothiazide for the treatment of hypertension, was conducted between June 1, 2016, and June 1, 2022, through Veterans Affairs facilities nationwide. This analysis extended follow-up to December 31, 2023. Veterans 65 years or older with hypertension who …

A Framework For Sharing Of Clinical And Genetic Data For Precision Medicine Applications., Ahmed Elhussein, Ulugbek Baymuradov, Nygc Als Consortium, Noémie Elhadad, Karthik Natarajan, Gamze Gürsoy

Faculty Research 2024

Precision medicine has the potential to provide more accurate diagnosis, appropriate treatment and timely prevention strategies by considering patients' biological makeup. However, this cannot be realized without integrating clinical and omics data in a data-sharing framework that achieves large sample sizes. Systems that integrate clinical and genetic data from multiple sources are scarce due to their distinct data types, interoperability, security and data ownership issues. Here we present a secure framework that allows immutable storage, querying and analysis of clinical and genetic data using blockchain technology. Our platform allows clinical and genetic data to be harmonized by combining them under …

Investigating Impacts Of The Mycothiazole Chemotype As A Chemical Probe For The Study Of Mitochondrial Function And Aging., Naibedya Dutta, Joe A Gerke, Sofia F. Odron, Joseph D. Morris, Adam Hruby, Juri Kim, Toni Castro Torres, Sarah J. Shemtov, Jacqueline G. Clarke, Michelle C. Chang, Hooriya Shaghasi, Marissa N. Ray, Maxim Averbukh, Sally Hoang, Maria Oorloff, Athena Alcala, Matthew Vega, Hemal H Mehta, Max A Thorwald, Phillip Crews, Marc Vermulst, Gilberto Garcia, Tyler A. Johnson, Ryo Higuchi-Sanabria

Natural Sciences and Mathematics | Faculty Scholarship

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function. Similar to rotenone (Rote), MTZ, a newly employed ETC complex I inhibitor, exhibited higher cytotoxicity against cancer cell lines compared to certain non-cancer cell lines. Interestingly, 8-OAc demonstrated greater selectivity for cancer cells …

Improved Robustness For Deep Learning-Based Segmentation Of Multi-Center Myocardial Perfusion Cardiovascular Mri Datasets Using Data-Adaptive Uncertainty-Guided Space-Time Analysis., Dilek M Yalcinkaya, Khalid Youssef, Bobak Heydari, Janet Wei, C Noel Bairey Merz, Robert Judd, Rohan Dharmakumar, Orlando P Simonetti, Jonathan W Weinsaft, Subha V Raman, Behzad Sharif

Heart and Vascular Articles

BACKGROUND: Fully automatic analysis of myocardial perfusion cardiovascular magnetic resonance imaging datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge.

METHODS: Datasets from three medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models …

Assessment Of Gender Differences In Letters Of Recommendation For Physical Therapy Residency Applications, Darren Q Calley, Sunyang Fu, Marissa D Hamilton, Austin W Kalla, Christopher K Lee, Veronica A Rasmussen, John H Hollman, Hongfang Liu

Faculty, Staff and Student Publications

Introduction: Letters of recommendation (LOR) are an integral component of physical therapy residency applications. Identifying the influence of applicant and writer gender in LOR will help identify whether potential implicit gender bias exists in physical therapy residency application processes.

Review of literature: Several medical and surgical residency education programs have reported positive, neutral, or negative LOR female gender bias among applicants and writers. Little research exists on gender differences in LOR to physical therapy education programs or physical therapy residency programs.

Subjects: Seven hundred sixty-eight LOR were analyzed from 256 applications to 3 physical therapy residency programs (neurologic, orthopaedic, sports) …

A Graph Theoretical Approach To Experimental Prioritization In Genome-Scale Investigations., Stephen K Grady, Kevin A Peterson, Stephen A Murray, Erich J Baker, Michael A Langston, Elissa J Chesler

Faculty Research 2024

The goal of systems biology is to gain a network level understanding of how gene interactions influence biological states, and ultimately inform upon human disease. Given the scale and scope of systems biology studies, resource constraints often limit researchers when validating genome-wide phenomena and potentially lead to an incomplete understanding of the underlying mechanisms. Further, prioritization strategies are often biased towards known entities (e.g. previously studied genes/proteins with commercially available reagents), and other technical issues that limit experimental breadth. Here, heterogeneous biological information is modeled as an association graph to which a high-performance minimum dominating set solver is applied to …

The Mutant Mouse Resource And Research Center (Mmrrc) Consortium: The Us-Based Public Mouse Repository System., Yuksel Agca, James Amos-Landgraf, Renee Araiza, Jennifer Brennan, Charisse Carlson, Dominic Ciavatta, Dave Clary, Craig Franklin, Ian Korf, Cathleen Lutz, Terry Magnuson, Fernando Pardo-Manuel De Villena, Oleg Mirochnitchenko, Samit Patel, Dan Port, Laura G Reinholdt, K C Kent Lloyd

Faculty Research 2024

Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of …

Citation Bias, Diversity, And Ethics, Keisha S Ray, Perry Zurn, Jordan D Dworkin, Dani S Bassett, David B Resnik

Faculty and Staff Publications

How often a researcher is cited usually plays a decisive role in that person's career advancement, because academic institutions often use citation metrics, either explicitly or implicitly, to estimate research impact and productivity. Research has shown, however, that citation patterns and practices are affected by various biases, including the prestige of the authors being cited and their gender, race, and nationality, whether self-attested or perceived. Some commentators have proposed that researchers can address biases related to social identity or position by including a Citation Diversity Statement in a manuscript submitted for publication. A Citation Diversity Statement is a paragraph placed …

Reduction Of Overactive Bladder Medications In Spinal Cord Injury With Self-Administered Neuromodulation: A Randomized Trial, Argyrios Stampas, Radha Korupolu, Kyung Hyun Lee, Betsy Salazar, Rose Khavari

Faculty, Staff and Student Publications

Purpose: Our goal was to evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation could safely replace overactive bladder medications in people with spinal cord injury.

Materials and methods: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre/post Neurogenic Bladder Symptom Score and the Incontinence Quality of Life questionnaire, respectively. Secondary outcomes included changes in pre/post cystometrogram, 2-day …

The Primate Gut Microbiota Contributes To Interspecific Differences In Host Metabolism., Elizabeth K Mallott, Sahana Kuthyar, Won Lee, Derek Reiman, Hongmei Jiang, Sriram Chitta, E Alexandria Waters, Brian T Layden, Ronen Sumagin, Laura D Manzanares, Guan-Yu Yang, Maria Luisa Savo Sardaro, Stanton Gray, Lawrence E Williams, Yang Dai, James P Curley, Chad R Haney, Emma R Liechty, Christopher W Kuzawa, Katherine R Amato

Faculty Research 2024

Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known. Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variation in normal cross-vertebrate species differences in metabolism, including those associated with the brain's energetic requirements. By inoculating germ-free mice with the gut microbiota (GM) of three primate species - two with relatively larger brains and one with a smaller brain - we demonstrated that the GM of larger-brained primates shifts host metabolism towards …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Tumor Expression Of Cd83 Reduces Glioma Progression And Is Associated With Reduced Immunosuppression, Malcolm F Mcdonald, Rachel Naomi Curry, Isabella O'Reilly, Brittney Lozzi, Alexis Cervantes, Zhung-Fu Lee, Anna Rosenbaum, Peihao He, Carrie Mohila, Arif O Harmanci, Akdes Serin Harmanci, Benjamin Deneen, Ganesh Rao

Faculty, Staff and Student Publications

Immunosuppression in malignant glioma remains a barrier to therapeutic development. CD83 overexpression in human and mouse glioma increases survival. CD83+ tumor cells promote signatures related to cytotoxic T cells, enhanced activation of CD8+ T cells, and increased proinflammatory cytokines. These findings suggest that tumor-expressed CD83 could mediate tumor-immune communications.

Biomechanics And Clinical Implications Of Fontan Upsizing, Vijay Govindarajan, Akshita Sahni, Emily Eickhoff, Peter Hammer, David M Hoganson, Rahul H Rathod, Pedro J Del Nido

Faculty, Staff and Student Publications

Background: The Fontan operation, a palliative procedure for single ventricle patients, has evolved to improve outcomes and reduce complications. While extracardiac conduit (ECC) is favored for its simplicity and potential hemodynamic benefits, concerns arise about conduit size adequacy over time. Undersized ECC conduits may cause hemodynamic inefficiencies and long-term complications, while oversizing can lead to flow disturbances, stagnation, and thrombosis, necessitating surgical revision or upsizing to optimize hemodynamics.

Objectives: The study aimed to predict the impact of upsizing by developing a patient-specific workflow using cardiac magnetic resonance-based imaging and computational fluid dynamics to assess Fontan hemodynamic changes and determine the …

A Qualitative Exploration Of Barriers, Facilitators And Best Practices For Implementing Environmental Sustainability Standards And Reducing Food Waste In Veterans Affairs Hospitals, Bethany D Williams, Stephanie Jilcott Pitts, Stephen J Onufrak, Emma Sirois, Anne Utech, Michelle Wood, Jessi Silverman, Funke Ajenikoko, Meghan Murphy, Amy Lowry Warnock

Faculty, Staff and Students Publications

BACKGROUND: To improve the healthfulness of foods offered while accelerating the use of environmental sustainability practices, it is important to engage hospital food service operators in the adoption of such practices. The purpose of this study was to explore barriers, facilitators and best practices for implementing environmental sustainability standards in food service among veterans affairs (VA) hospitals in the United States.

METHODS: We conducted an online survey with 14 VA hospital food service directors and then 11 qualitative interviews. The survey assessed motivations for initiating sustainability standards and included a self-rating of implementation for each of five standards: increasing plant-forward …