Digital Commons Network^™

Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud

Faculty, Staff and Students Publications

Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.

Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.

Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …

Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith

Faculty, Staff and Students Publications

Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …

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, Staff and Students Publications

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 …

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker

2020-Current year OA Pubs

IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.

OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.

EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …

Ibrutinib Added To Standard Conditioning And As Maintenance Therapy Following Autologous Hematopoietic Stem Cell Transplantation For Relapsed Or Refractory Activated-B-Cell Type Diffuse Large B-Cell Lymphoma: Primary Analysis Of The Us Intergroup Double-Blind Randomized Phase Iii Study Alliance A051301/Bmt-Ctn 1201, Charalambos Andreadis, Brad S Kahl, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (

Microglia Regulate Gabaergic Neurogenesis In Prenatal Human Brain Through Igf1, Diankun Yu, Samhita Jain, Andi Wangzhou, Beika Zhu, Wenyuan Shao, Elena J Coley-O'Rourke, Stacy De Florencio, Jaeyeon Kim, Jennifer Ja-Yoon Choi, Mercedes F Paredes, Tomasz J Nowakowski, Eric J Huang, Xianhua Piao

2020-Current year OA Pubs

GABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans

A Modification To The Brand Transfer For Claw Hand: The Four-Tailed Extensor Carpi Radialis Brevis To Lateral Band Transfer, Lauren E Wessel, Nirbhay S Jain, Ambika E Paulson, Carrie Bettlach, Mitchell A Pet, Amy M Moore

2020-Current year OA Pubs

BACKGROUND: Claw deformity is a devastating consequence of low ulnar nerve palsy, resulting in loss of finger function. Traditionally, the Brand transfer is a favored intervention but requires lengthy grafts and bulky tenorrhaphies, risking adhesions in the lumbrical canal. We present a modified Brand tendon transfer, which extends the extensor carpi radialis brevis (ECRB) into 4 tails for individual grafting into the lateral band, decreasing adhesion risk and graft length need.

METHODS: Nine consecutive patients with claw hand were examined in detail to confirm the diagnosis and appropriateness for claw-correction surgery by the senior author. All patients underwent our modified …

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Jessie R Zhang, Liana M Valin, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Lisa Emrick, William J Craigen, Stephen M Sykes, Tim Schedl, Stephen C Pak, Et Al.

2020-Current year OA Pubs

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

Hemodynamic Characteristics Of Dilated Ascending Aorta In Patients With Bicuspid Aortic Valve, Yu Xia, Xuehuan Zhang, Shuai Zhu, Suwei Chen, Wentao Dong, Zhuo Chen, Nan Zhang, Jiafu Ou, Junming Zhu, Duanduan Chen, Tie Zheng

2020-Current year OA Pubs

BACKGROUND: The aim of this study is to investigate the influence of aortic diameter on hemodynamic environment characteristics in patient with the bicuspid aortic valve (BAV) and dilated ascending aorta (AAo).

METHOD: In this study, an MRI of one BAV patient with 4.5 cm AAo was collected and numerical model was constructed. Based on the images, three additional anatomical models were constructed with different AAo sizes of 4.0 cm, 5.0 cm and 5.5 cm respectively, while the size and the geometry of other parts were fixed. Then hemodynamics in these four models was simulated numerically and the flow patterns and …

Direct-To-Unit, Single-Visit, Curative-Intent Online Adaptive Stereotactic Ablative Radiotherapy For Early-Stage Lung Adenocarcinoma, Farnoush Forghani, Kendall Kiser, Eric Laugeman, Yao Hao, Robbie Beckert, Julie Rolfingsmeier, Clifford Robinson, Thomas Mazur, Pamela Samson

2020-Current year OA Pubs

BACKGROUND: Advancements in cone beam computed tomography (CBCT)-guided radiotherapy (RT) platforms have created new frontiers in adaptive radiotherapy (ART). This report describes the novel application of single-fraction adaptive stereotactic body radiotherapy (SBRT) for a 66-year-old woman with lung adenocarcinoma for whom a conventional RT workflow was impractical due to advanced Parkinson's disease with uncontrolled tremors.

CASE PRESENTATION: The patient presented with a 2.4 cm spiculated nodule in the left upper lobe (LUL) diagnosed as stage 1A3 lung adenocarcinoma. She declined surgery, and local radiation oncologists deemed SBRT unsafe due to her tremors. Our team proposed a direct-to-unit, single-visit SBRT treatment …

Dissecting Real-World Memory Clinical Cohort Heterogeneity: Analysis Of Neuroanatomical Subtypes Using Hydra, Gordon Zhaoqi An, Yunchang Xie, Tammie L S Benzinger, Brian A Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

BACKGROUND: There is significant evidence for neuroanatomical heterogeneity in neurodegenerative disorders, which has been demonstrated predominantly through analyses of well-characterized research cohorts. Despite the known diversity in clinical presentations among patients attending memory clinics, studies exploring neuroanatomical heterogeneity in such clinically diverse groups remain sparse.

METHODS: To address this gap, we applied the semi-supervised Heterogeneity through Discriminative Analysis (HYDRA) (Neuroimage 145:346-364 2017) machine learning method to magnetic resonance imaging (MRI) data from the Open Access Series of Imaging Studies (OASIS) (NeuroImage 26:102248 2020) to uncover patterns of neurostructural heterogeneity in memory clinic attendees. Cross-validation was used to assess clustering stability …

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Peroxisomal Metabolism Of Branched Fatty Acids Regulates Energy Homeostasis, Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N Finck, Mohamed Zayed, Jonathan R Brestoff, Ali Javaheri, Fong-Fu Hsu, Clay F Semenkovich, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1

Upper And Lower Airway Microbiota Across Infancy And Childhood, Ariel J Hernandez-Leyva, Anne L Rosen, Christopher P Tomera, Elaina E Lin, Elikplim H Akaho, Allison M Blatz, William R Otto, Joey Logan, Lisa R Young, Rebecca M Harris, Samantha A Whiteside, Andrew L Kau, Audrey R Odom John

2020-Current year OA Pubs

BACKGROUND: The upper and lower respiratory tracts feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the nasopharynx and trachea across childhood.

METHODS: We employed V4 16S rRNA gene sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 172 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures over the course of 20 weeks in 2020 from subjects enrolled in a cross-sectional study. After extraction, sequencing, and quality control, we studied the remaining 147 of …

Life-Moms: Effects Of Multicomponent Lifestyle Randomized Control Trial On Physical Activity During Pregnancy In Women With Overweight And Obesity, Hannah E Cabre, Debra Haire-Joshu, Alison G Cahill, Samuel Klein, Et Al.

2020-Current year OA Pubs

BACKGROUND: This report details the effect of LIFE-Mom's multicomponent lifestyle interventions on physical activity (PA) and inactivity time across pregnancy (2nd and 3rd trimesters) and their effect on gestational weight gain (GWG) and maternal/neonatal outcomes, a pre-specified secondary analysis.

METHODS: Pregnant people with BMI ≥ 25 kg/m

RESULTS: Although there were statistically significant differences in vigorous activity between the intervention and control group (p = .024), there were no clinically meaningful differences in PA. In the combined sample, moderate to vigorous PA (MVPA) significantly decreased across pregnancy (mean ± SD: 72.9 ± 29.1 min/day vs 63.9 ± 28.1 min/day; p …

Economics Of Corneal Cross-Linking For Keratoconus Treatment, Christopher J. Rapuano, Richard L. Lindstrom, Eric Donnenfeld, John P. Berdahl, Vance Thompson, David Kratochvil, John Carter

Wills Eye Hospital Papers

AIM: To optimize the real-world applicability of a health economic model estimating the cost-effectiveness of corneal cross-linking for the treatment of keratoconus in the United States.

MATERIALS AND METHODS: A previously reported discrete-event simulation (DES) model was adapted to reassess the cost-effectiveness of corneal cross-linking (CXL) from the US payer perspective. The simulation of keratoconus progression, which is a key driver of model outcomes, was remodeled to more accurately reflect the real-world relationship between age and the rate of disease progression. All costs were updated to reflect 2025 values. We simulated 4,000 eyes of 2,000 patients diagnosed with keratoconus to …

Motion Impact Score For Detecting Spurious Brain-Behavior Associations, Benjamin P Kay, David F Montez, Scott Marek, Joshua S Siegel, Babatunde Adeyemo, Timothy O Laumann, Athanasia Metoki, Roselyne J Chauvin, Andrew N Van, Vahdeta Suljic, Samuel R Krimmel, Ryland L Miller, Dillan J Newbold, Annie Zheng, Nicole A Seider, Kristen M Scheidter, Julia S Monk, Jarod L Roland, Evan M Gordon, Abraham Z Snyder, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without …

In Vivo Crispr Screening In Head And Neck Cancer Reveals Uchl5 As An Immunotherapy Target, Cong Fu, Zahra Alipour, Douglas R Adkins, Rebecca D Chernock, Et Al.

2020-Current year OA Pubs

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a significant unmet need for enhancing immunotherapy response given current modest efficacy. Here, we perform an in vivo CRISPR screen in an HNSCC mouse model to identify immune evasion genes. We identify several regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increases CD8

Effects Of Olfactory Enrichment On Perioperative Neurocognitive Disorders In Elderly Patients Undergoing Orthopedic Surgery: A Study Protocol Of A Multi-Center Randomized Controlled Trial, Xinchun Mei, Jiayi Wang, Zihan Ni, Yanyan Wang, Binglei Zhao, Daniel I Sessler, Zhongcong Xie, Yuan Shen

Faculty, Staff and Student Publications

Background: Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume …

Genetic Susceptibility To Oral And Atherosclerotic Cardiovascular Diseases Based On Dental And Heart Score Studies, Mariana Bezamat, Dylan J Baxter, Nandita Mukhopadhyay, Anum Saeed, Lei Liu, Lisa De Las Fuentes, Betsy Foxman, John R Shaffer, Daniel W Mcneil, Steven E Reis, Mary L Marazita

2020-Current year OA Pubs

Periodontal disease and dental caries are two oral conditions that have been associated with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if one of the key mechanisms involved in this association could be a shared genetic susceptibility. The goal of this study was to explore whether there is an intersection of genetic loci among individuals with comprehensive oral examinations and subclinical ASCVD screenings. We leveraged data from oral and medical examinations obtained from the Dental and Heart Strategies Concentrating on Risk Evaluation (Dental/Heart SCORE) projects. Genome-wide association studies (GWASs) were performed independently in 552 participants (aged 45-75 years). The …

Bedside Small-Bowel Challenge Vs. Fluoroscopic Series For Sbo: A Cost Effectiveness Analysis, Aravinda Krishna Ganapathy, Liam Cunningham, M Hunter Lanier, Selasi Nakhaima, Madelyn Thiel, Daniel Hoffman, Obeid Ilahi, David H Ballard, Vincent M Mellnick

2020-Current year OA Pubs

BACKGROUND: Small bowel obstruction (SBO) accounts for 12-16% of surgical hospital admissions and can lead to complications such as bowel ischemia. Traditional management requires transporting patients to the Radiology Department (RD) for a fluoroscopic small bowel series, occupying resources and time. This study evaluates the efficacy and efficiency of the Small Bowel Challenge Exam, a bedside alternative.

METHODS: A retrospective analysis was performed on 85 SBO patients from January 2018 to December 2023 at an academic tertiary care facility, comparing the traditional fluoroscopic series (37 patients) to the bedside Small Bowel Challenge Exam (48 patients). Key metrics analyzed included hospital …

Breaking The Silence: A Scoping Literature Review On Trauma-Informed Care For Black Women Navigating Sexual Health-Related Trauma, Ayanna Troutman, Funlola Are, Ashley Okoye, Sarah Chiang, Destiny Craig, Anthony Akande, Irene Stafford

Faculty, Staff and Student Publications

Black women disproportionately experience sexual health-related trauma, yet their mental health needs are often inadequately addressed due to systemic barriers and stigma. This literature review examines trauma-informed care (TIC) frameworks tailored to Black women, emphasizing culturally responsive practices in addressing sexual health-related trauma. By synthesizing findings from existing research, including the importance of intersectionality, culturally specific interventions, and community-centered approaches, this review highlights effective strategies for mental health providers. The review concludes with implications for enhancing TIC training and implementation in clinical settings which contributes to the advancement of equitable mental health services for Black women.

Association Of Chronic Conditions With Bladder Health In Women: Cross-Sectional Results From The Rise For Health Study, Camille P Vaughan, Gerald Mcgwin, Jean F Wyman, Siobhan Sutcliffe, Diane K Newman, Ariana L Smith, Colleen M Fitzgerald, Todd Rockwood, James Griffith, Sheila Gahagan, Alayne D Markland, Prevention Of Lower Urinary Tract Symptoms (Plus) Research Consortium

2020-Current year OA Pubs

INTRODUCTION: Women with multiple chronic conditions are more likely than women without them to report lower urinary tract symptoms (LUTS); understanding the association of common and coexisting chronic conditions with bladder health across adulthood may inform prevention efforts.

METHODS: Data were collected from May 2022 through December 2023 from a regionally representative cohort of community-dwelling adult women in the US. Chronic conditions were assessed by self-report and bladder health, and LUTS were measured using validated questionnaires. Analyses were limited to women aged 40 years or older and included multivariable linear and logistic regression models, adjusted for age, body mass index, …

Global, Regional, And National Burden Of Cardiovascular Diseases And Risk Factors In 204 Countries And Territories, 1990-2023, Global Burden Of Cardiovascular Diseases And Risks 2023 Collaborators, Mohammadreza Abbasian

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging.

OBJECTIVES: We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure.

METHODS: The Global Burden of Disease (GBD) 2023 study, a multinational …

Associations Between Adhering To 24-Hour Movement Guidelines And Anxiety Among Adolescents Across Intersectional Identities: Kyrbs 2020-2022., Suryeon Ryu, Eun Young Lee, Zan Gao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Identifying preventive measures for adolescent mental health is a global public health priority, as poor mental health heightens the risk of early death from related issues, including suicide. This study examined the associations between adherence to the 24-Hour Movement Guidelines and anxiety among a nationally representative sample of South Korean adolescents, using an intersectional identity framework.

METHODS: Data from the 2020-2022 Korea Youth Risk Behavior Surveys were analyzed. Adolescents aged 12-17 years were grouped based on adherence to guidelines: none, physical activity (PA), sedentary behavior (SB), sleep, two guideline combinations, and all three. Anxiety was the mental health outcome. …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Association Of Genetic Scores Related To Insulin Resistance With Neurological Outcomes In Ancestrally Diverse Cohorts From The Trans-Omics For Precision Medicine (Topmed) Program, Chloé Sarnowski, Yixin Zhang, Farah Ammous, Lincoln M P Shade, Daniel Dicorpo, Xueqiu Jian, Donna K Arnett, Thomas R Austin, Alexa Beiser, Joshua C Bis, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Charles S Decarli, Harsha Doddapaneni, Josée Dupuis, David W Fardo, Jose C Florez, Stacey Gabriel, Richard A Gibbs, David C Glahn, Namrata Gupta, Hector M González, Kevin A González, Konstantinos Hatzikotoulas, Kathleen M Hayden, Susan R Heckbert, Bertha Hidalgo, Alicia Huerta-Chagoya, Timothy M Hughes, Sharon L R Kardia, Charles L Kooperberg, Lenore J Launer, W T Longstreth, Ravi Mandla, Rasika A Mathias, Andrew P Morris, Thomas H Mosley, Ilya M Nasrallah, Paul Nyquist, Bruce M Psaty, Qibin Qi, Laura M Raffield, Nigel W Rayner, Alexander P Reiner, Claudia L Satizabal, Elizabeth Selvin, Magdalena D R Sevilla-Gonzalez, Albert V Smith, Jennifer A Smith, Kirk Smith, Beverly M Snively, Lorraine Southam, Tamar Sofer, Ken Suzuki, Henry J Taylor, Miriam S Udler, Karine A Viaud-Martinez, Sylvia Wassertheil-Smoller, Alexis C Wood, Lisa R Yanek, Xianyong Yin, Alisa K Manning, Jerome I Rotter, Stephen S Rich, James B Meigs, Myriam Fornage, Sudha Seshadri, Alanna C Morrison, Topmed Neurocognitive Working Group, Topmed Diabetes Working Group

The Brown Foundation: Institute of Molecular Medicine

To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P <  0.002) of the cross-population (P = 1.3 × 10-5) and European (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P <  0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.

A Community-Engaged Approach To Enhancing Participation In Genomic Research In Rare And Understudied Cancer Populations, Saira Khan, Bailey Martin-Giacalone, Kayla Wallace, Briana Wilson, Christine Marx, Erin Linnenbringer, Jessica Mozersky, Melinda Bachini, Nancy Chollet, Dionne Stalling, Li Ding, Ryan C Fields, Graham A Colditz, Bettina F Drake

2020-Current year OA Pubs

UNLABELLED: Few studies provide insights on how to incorporate community members' perspectives of genomic research during the early phases of study development. Engaging with community members early and consistently throughout the research lifecycle could help identify and mitigate barriers to genomic research participation, particularly among groups with rare and understudied cancers.

METHODS: The Washington University Participant Engagement and Cancer Genome Sequencing (WU-PE-CGS) study formed a Participant Engagement Advisory Board (PEAB) consisting of patients, patient advocates, and patient advocacy organizations who represented the three understudied cancer populations: cholangiocarcinoma, early-onset colorectal cancer in Black Americans, and multiple myeloma in Black Americans. PEAB …

Gata2 Mutation Is Associated With Immune Dysfunction And Increased Mycobacterium Haemophilum Susceptibility In Immunocompromised Individuals, Ananya Gupta, Shail B. Mehta, Abhimanyu, Bruce A. Rosa, John Martin, Mushtaq Ahmed, Shyamala Thirunavukkarasu, Farheen Fatma, Gaya K. Amarasinghe, Makedonka Mitreva, Thomas C. Bailey, David B. Clifford, Shabaana A. Khader

2020-Current year OA Pubs

Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by M. haemophilum (Mh, n = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in GATA2 gene, which was absent in healthy controls (HCs, n = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to Mh stimulation for IL-1β, IL-6, IL-8, MIP-1α and MIP-1β, but not to phytohemagglutinin (PHA) or another NTM, M. abscessus. Impaired …