Digital Commons Network^™

Differential Relationship Between Meditation Methods And Psychotic-Like And Mystical Experiences, Timothy Palmer, Kenza Kadri, Eric Fakra, Jacqueline Scholl, Elsa Fouragnan

School of Psychology

Much work has investigated beneficial effects of mindfulness-based meditation methods, but less work has investigated potential risks and differences across meditation methods. We addressed this in a large pre-registered online survey including 613 mediators where we correlated participants' experience with fifty meditation techniques to psychotic-like experiences (PLEs) and mystical experiences. We found a positive correlation for both PLEs and mystical experiences with techniques aiming at reducing phenomenological content ('null-directed', NDM) or classified as non-dual or less embodied. In contrast, methods aiming at achieving an enhanced cognitive state (CDM), also described as 'attentional' or strongly embodied, showed negative correlations with PLEs. …

A Review Of The Association Between Dietary Intake And Brain Iron Levels In Older Adults: Preliminary Findings And Future Directions., Valentinos Zachariou, Christopher E. Bauer, Colleen A. Pappas, Brian T. Gold

Behavioral Science Faculty Publications

Background/Objectives: Non-heme iron is essential for critical neuronal functions such as ATP generation, synaptogenesis, neurotransmitter synthesis, and myelin formation. However, as non-heme iron accumulates with age, excessive levels can contribute to oxidative stress, potentially disrupting neuronal integrity and contributing to cognitive decline. Despite growing evidence linking high brain iron with poorer cognitive performance, there are currently no proven methods to reduce brain iron accumulation in aging or to protect cognitive function from iron’s negative effects. Recent studies suggest that nutrition may influence brain iron levels, though the evidence remains limited and mixed. Methods: In this review, we explore recent findings, …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

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 …

Individualized Functional Magnetic Resonance Imaging Neuromodulation Enhances Visuospatial Perception: A Proof-Of-Concept Study, Anthony Allam, Vincent Allam, Sandy Reddy, Eric M Rohren, Sameer A Sheth, Emmanouil Froudarakis, T Dorina Papageorgiou

Duncan NRI Faculty and Staff Publications

This proof-of-concept study uses individualized functional magnetic resonance imaging neuromodulation (iNM) to explore the mechanisms that enhance BOLD signals in visuospatial perception (VP) networks that are crucial for navigation. Healthy participants (n = 8) performed a VP up- and down-direction discrimination task at full and subthreshold coherence through peripheral vision, and superimposed direction through visual imagery (VI) at central space under iNM and control conditions. iNM targets individualized anatomical and functional middle- and medial-superior temporal (MST) networks that control VP. We found that iNM engaged selective exteroceptive and interoceptive attention (SEIA) and motor planning (MP) networks. Specifically, iNM increased …

Systemic Administration Of A Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits And Neuroinflammation In Mice, Amit Kumar Madeshiya, Brandi Quintanilla, Carl Whitehead, Stephen Tomlinson, Anilkumar Pillai

Faculty, Staff and Student Publications

Chronic stress, a risk factor for many neuropsychiatric conditions, causes dysregulation in the immune system in both humans and animal models. Additionally, inflammation and synapse loss have been associated with deficits in social behavior. The complement system, a key player of innate immunity, has been linked to social behavior impairments caused by chronic stress. However, it is not known whether complement inhibition can help prevent neuroinflammation and behavioral deficits caused by chronic stress. In this study, we investigated the potential of a site-targeted complement inhibitor to ameliorate chronic stress-induced changes in social behavior and inflammatory markers in the prefrontal cortex …

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 …

Onset And Progression Of Disease In Nonhuman Primates With Pde6c Cone Disorder, Monica Ardon, Lily Nguyen, Rui Chen, Jeffrey Rogers, Tim Stout, Sara Thomasy, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: The California National Primate Research Center contains a colony of rhesus macaques with a homozygous missense mutation in PDE6C (R565Q) which causes a cone disorder similar to PDE6C achromatopsia in humans. The purposes of this study are to characterize the phenotype in PDE6C macaques in detail to determine the onset of the cone phenotype, the degree to which the phenotype progresses, if heterozygote animals have an intermediate phenotype, and if rod photoreceptor function declines over time.

METHODS: We analyzed spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and electroretinography (ERG) data from 102 eyes of 51 macaques (aged 0.25 …

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, …

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 …

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 …

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 …

Heterozygous Btnl8 Variants In Individuals With Multisystem Inflammatory Syndrome In Children (Mis-C), Evangelos Bellos, Erica G Schmitt, Et Al.

2020-Current year OA Pubs

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

Chemogenetic Neuronal Silencing Decouples C-Jun Activation From Cell Death In The Temporal Cortex, Caleb A Wood, Preethi Somasundaram, Jacob M Dundee, Melissa A Rudy, Trent A Watkins, Joanna L Jankowsky

Faculty, Staff and Students Publications

Initial symptoms of neurodegenerative diseases are often defined by the loss of the most vulnerable neural populations specific to each disorder. In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology. We previously found that entorhinal neurons in the temporal cortex undergo cell death following transient suppression of electrical activity, suggesting a causal role for activity disruption in neurodegeneration. Here we demonstrate that electrical arrest of this circuit stimulates the injury-response transcription …

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 …

Metabolic Shifts In Ratio Of Ucocn To Cocn Toward Bone Resorption Contribute To Age-Dependent Bone Loss In Male Mice, Matthew Bernhard, Obinna Okorie, Wei-Ju Louis Tseng, Mengcun Chen, Julia Danon, Mingshu Cui, Elisabeth Lashbrooks, Yanmei Yang, Bin Wang

Center for Translational Medicine Faculty Papers

The study of the senile osteoporosis in men still lags significantly behind that in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 mo to delineate the mechanisms of aging effects on bone loss. We used the microcomputed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with the ratios of ucOcn-to-cOcn in mice from different age groups. The results showed …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Excellent Registry: A Prospective, Multicenter, Global Registry Of Endovascular Stroke Treatment With The Embotrap Device., Raul G Nogueira, Tommy Andersson, Diogo C Haussen, Albert J Yoo, Ricardo A Hanel, Osama O Zaidat, Werner Hacke, Tudor G Jovin, Jens Fiehler, Simon F De Meyer, Waleed Brinjikji, Karen M Doyle, David F Kallmes, David S Liebeskind, Renu Virmani, Malgosia A Kokoszka, Violiza Inoa, William Humphries, Keith B Woodward, Pascal M Jabbour, Olivier François, Elad I Levy, Hormozd Bozorgchami, Stephan Boor, Jose E Cohen, Shervin R Dashti, Muhammad A Taqi, Ronald F Budzik, Clemens M Schirmer, M Shazam Hussain, Laurent Estrade, Reade A De Leacy, Ajit S Puri, Rohan V Chitale, Caspar Brekenfeld, Adnan H Siddiqui

Neuroscience Articles

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, …

Genetic Architecture Of Cerebrospinal Fluid And Brain Metabolite Levels And The Genetic Colocalization Of Metabolites With Human Traits, Ciyang Wang, Chengran Yang, Daniel Western, Muhammad Ali, Yueyao Wang, Chia-Ling Phuah, John Budde, Lihua Wang, Priyanka Gorijala, Jigyasha Timsina, Agustin Ruiz, Pau Pastor, Maria Victoria Fernandez, Dominantly Inherited Alzheimer Network (Dian), Alzheimer’S Disease Neuroimaging Initiative (Adni), Daniel J Panyard, Corinne D Engelman, Yuetiva Deming, Merce Boada, Amanda Cano, Pablo Garcia-Gonzalez, Neill R Graff-Radford, Hiroshi Mori, Jae-Hong Lee, Richard J Perrin, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated …

Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Natalie Mccormick, Amit D Joshi, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.

Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization.

Results: …

Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans, Jesús-Daniel Zazueta-Borboa, Rafael Samper-Ternent, Rebeca Wong, Neil Mehta

Faculty, Staff and Student Publications

OBJECTIVES: Diabetes prevalence has increased markedly in Mexico. We examined the individual and joint contributions of economic disadvantage during childhood (EDDC) and elevated body weight on diabetes prevalence in 3 cohorts of Mexican adults.

METHODS: Data on those 60-69 years old from the 1930-1939, 1940-1949, and 1950-1959 birth cohorts in Waves 1 (2001), 3 (2012), and 5 (2018) of the Mexican Health and Aging Study were used. EDDC was defined as the absence of a toilet in the household before age 10. Body mass status was defined using self-reported perceived body image at age 50. Diabetes was based on respondent …

Anxiety-Like Behaviors In Mice Unmasked: Revealing Sex Differences In Anxiety Using A Novel Light-Heat Conflict Test, Sydney E Lee, Sung-Hoon Park, John C Aldrich, Laura K Fonken, Andrew D Gaudet

The Brown Foundation: Institute of Molecular Medicine

Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark-Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely …

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …

Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.

Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.

Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) …

Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Shuai Liu, Jingjing Zhu, Hua Zhong, Chong Wu, Haoran Xue, Burcu F Darst, Xiuqing Guo, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Loïc Le Marchand, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu

Faculty, Staff and Student Publications

Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were …

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

Faculty, Staff and Student 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

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 …

Azacitidine As Epigenetic Priming For Chemotherapy Is Safe And Well-Tolerated In Infants With Newly Diagnosed Kmt2a-Rearranged Acute Lymphoblastic Leukemia: Children's Oncology Group Trial Aall15p1, Erin M. Guest, John A Kairalla, Meenakshi Devidas, Emily Hibbitts, Andrew J. Carroll, Nyla A. Heerema, Holly R. Kubaney, Margaret A. August, Sidharth Ramesh, Byunggil Yoo, Midhat S. Farooqi, Melinda G. Pauly, Daniel S. Wechsler, Rodney R. Miles, Joel M. Reid, Cynthia D. Kihei, Lia Gore, Elizabeth A. Raetz, Stephen P. Hunger, Mignon L. Loh, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of failure to achieve remission, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children's Oncology Group trial AALL15P1 tested the safety and tolerability of 5 days of azacitidine treatment immediately prior to the start of chemotherapy on day 6, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was well-tolerated, with only …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …