Inhibition Of Epithelial Cell Yap-Tead/Lox Signaling Attenuates Pulmonary Fibrosis In Preclinical Models, Darcy Elizabeth Wagner, Hani N Alsafadi, Nilay Mitash, Aurelien Justet, Qianjiang Hu, Ricardo Pineda, Claudia Staab-Weijnitz, Martina Korfei, Nika Gvazava, Kristin Wannemo, Ugochi Onwuka, Molly Mozurak, Adriana Estrada-Bernal, Juan Cala-Garcia, Katrin Mutze, Rita Costa, Deniz Bölükbas, John Stegmayr, Wioletta Skronska-Wasek, Stephan Klee, Chiharu Ota, Hoeke A Baarsma, Jingtao Wang, John Sembrat, Anne Hilgendorff, Jun Ding, Andreas Günther, Rachel Chambers, Ivan Rosas, Stijn De Langhe, Naftali Kaminski, Mareike Lehmann, Oliver Eickelberg, Melanie Königshoff

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX …

Pain Acceptance In Chronic Postoperative Pain: Concept Analysis, Sajini M Thekkel, Constance M Johnson, Meagan Whisenant, Deniz Dishman

Faculty, Staff and Student Publications

Purpose: Chronic postoperative pain (CPOP) is a potential outcome of otherwise successful surgery that can persist for months, with its prevalence varied by surgical type, genetic predispositions, and psychosocial factors. Pain acceptance offers better outcomes to these patient populations by fostering a willingness to experience pain without resistance. This analysis examines how pain acceptance contributes to psychological well-being, helps reduce opioid misuse, and enhances quality of life, even in the presence of CPOP.

Design: The concept analysis approach follows Walker and Avant's framework (2019).

Methods: A literature search across PubMed, Web of Science, and CINAHL yielded 276 articles, of which …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Rowan Saloner, Jacob W Vogel, Varsha Krish, Gamal Abdel-Azim, Muhammad Ali, Lijun An, Federica Anastasi, David Bennett, Alexa Pichet Binette, Adam L Boxer, Martin Bringmann, Jeffrey M Burns, Carlos Cruchaga, Jeff L Dage, Amelia Farinas, Luigi Ferrucci, Caitlin A Finney, Mark Frasier, Oskar Hansson, Timothy J Hohman, Erik C B Johnson, Mika Kivimaki, Roxanna Korologou-Linden, Agustin Ruiz Laza, Allan I Levey, Inga Liepelt-Scarfone, Lina Lu, Niklas Mattsson-Carlgren, Lefkos T Middleton, Kwangsik Nho, Hamilton Se-Hwee Oh, Ronald C Petersen, Eric M Reiman, Oliver Robinson, Jeffrey D Rothstein, Andrew J Saykin, Artur Shvetcov, Chad Slawson, Bart Smets, Marc Suárez-Calvet, Betty M Tijms, Maarten Timmers, Fernando Vieira, Natalia Vilor-Tejedor, Pieter Jelle Visser, Keenan A Walker, Laura M Winchester, Tony Wyss-Coray, Chengran Yang, Niranjan Bose, Simon Lovestone, The Global Neurodegeneration Proteomics Consortium (Gnpc)

Faculty, Staff and Student Publications

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Dissecting The Heterogeneous Effects Of Opioid Prescribing Limit Laws On Pediatric Mortality: A Multidimensional And Negative Binomial Modeling Approach, Francine R. Vega

Dissertations and Theses (Open Access)

Opioid prescribing for children and adolescents continues to be a significant health crisis in the United States. Early naïve exposure to opioid prescriptions has been linked to later misuse, opioid use disorder, and death. In response to the crisis, many states have implemented opioid prescribing limit laws (OPLLs) aimed at reducing exposure to opioids. These laws vary widely in their approach, including differences in dosage restrictions, prescription duration limits, informed consent requirements, educational provisions, and whether they offer explicit protections specifically for minors. Despite their widespread adoption, there is limited understanding of how heterogeneity in legal regulations affects outcomes for …

Rethinking Health Systems Responsiveness In Low–And Middle-Income Countries, Meesha Iqbal

Dissertations and Theses (Open Access)

Health systems responsiveness (HSR) refers to a health system’s ability to meet legitimate non-health expectations of the population. Traditionally, HSR has been conceptualized across eight domains: respect for dignity, autonomy, confidentiality, prompt attention to health needs, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. However, as the expectations of populations in high-income countries (HICs) and low- and middle-income countries (L&MICs) differ significantly due to diverse social and cultural contexts, the conceptualization of HSR also varies. We conducted a systematic review of literature to adapt and contextualize the HSR framework for L&MICs based …

De Novo And Inherited Variants In Ddx39b Cause A Novel Neurodevelopmental Syndrome, Kevin T A Booth, Sharayu V Jangam, Martin M C Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Yao Ruan, Jeffrey Wan-Hei Hui, Kerry White, Celanie K Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy H Y Tsang, Sally A Lynch, Sureni V Mullegama, Julia Baptista, Daniela Iancu, Shelagh K Joss, Sandra Y Y Wong, Christopher C Y Mak, Anna K Y Kwong, Hugo J Bellen, Erin Conboy, Remo Sanges, Anskar Yu-Hung Leung, Michael F Wangler, Brian H Y Chung, Francesco Vetrini

Duncan NRI Faculty and Staff Publications

DDX39B is a conserved member of the DEAD-box family of ATP-dependent RNA helicases, critical in mRNA metabolism across eukaryotes. DDX39B is also a core component of the TRanscription-EXport (TREX) super protein complex, and recent studies have highlighted the important role of its subunits in neurodevelopmental disorders. Here, we describe six individuals from five families, four harbouring de novo missense variants in DDX39B and one with an inherited splicing variant, presenting with variable developmental delay, congenital hypotonia, epilepsy, short stature, skeletal abnormalities, dysmorphic features and microcephaly in three patients.

3D molecular modelling predicts these variants would alter protein structure. In vitro …

Evaluating What Works: A Comparison Of Five Diabetes Prevention Programs For Latino Children, Ruchi Patel

Doctor of Nursing Practice Final Project Abstract

Background: Children in the Rio Grande Valley (RGV) are at increased risk of diabetes due to limited access to effective, culturally appropriate prevention programs. Existing programs are often time-intensive, require transportation, and lack cultural relevance, reducing participation and impacting outcomes. This project aimed to evaluate diabetes prevention programs (DPPs) in the literature and identify five that may benefit children in the RGV by reducing diabetes risk.

Methodology: The Eightfold Path policy analysis approach guided this project. A literature review identified DPPs for children, and the Critical Appraisal Skills Programme (CASP) was used to assess study quality. Limitations included difficulty finding …

Anxiety During Perimenopause: A Narrative Qualitative Study Of The Women’S Lived Experiences, Kayla Mcelhany

Dissertations and Theses (Open Access)

Abstract

Objectives: Perimenopause has been associated with increased anxiety symptoms. However, data is lacking regarding the experiences of women with perimenopausal anxiety and the contributing factors to worsening anxiety symptoms. We explored the experiences of women with self-reported new onset or worsening of anxiety symptoms during perimenopause to better understand contributing factors.

Study design: Twenty women participated in one-on-one interviews to explore experiences of perimenopausal anxiety in the context of their daily lives and perimenopausal physical changes. Inductive thematic analysis was used to develop codes and themes from the transcribed interview data. Analysis was done using MAXQDA software.

Main …

Multicenter Span Trial Of Fasudil In Ischemic Stroke, Takahiko Imai, Andreia Lopes De Morais, Xuyan Jin, Tao Qin, Jessica Lamb, Karisma A Nagarkatti, Mu-Hsun Chen, Ligia S B Boisserand, Rakesh B Patel, Mariia Kumskova, Anjali Chauhan, Krishnan M Dhandapani, Mohammad B Khan, Pradip K Kamat, Yanrong Shi, Suyi Cao, Basavaraju G Sanganahalli, Joseph B Mandeville, Patrick D Lyden, David C Hess, Enrique C Leira, Anil K Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Raymond C Koehler, Lauren H Sansing, Márcio A Diniz, Cenk Ayata

Children’s Nutrition Research Center Staff Publications

Background: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial.

Methods: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and …

Family-Level Factors That Influence Physical Activity Among Hispanic Adolescents At Risk For Type 2 Diabetes, Sandra Mihail, Ayleen A Hernandez, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Objective: Family-based health promotion and disease prevention strategies are recommended as best practice; however, there is limited knowledge regarding the family-level factors that influence modifiable behavior risk factors like physical activity (PA) among Latinx adolescents. This study addressed this knowledge gap by using qualitative methods to identify perceptions of family-level factors that influence PA among Hispanic youth.

Methods: We conducted semistructured, open-ended interviews with 20 Latinx adolescents (14-16 years) with obesity (body mass index ≥95th percentile) to identify their perceptions of how family influences PA. Content analysis was used to identify emergent themes, which were then compared across demographic factors, …

Human Salivary Gland Stem/Progenitor Cells For Tissue Engineering, Sars-Cov-2 Susceptibility, And Neurointegration, Caitlynn Barrows

Dissertations and Theses (Open Access)

Salivary glands and the saliva they secrete are important for digestion, chewing, and maintaining oral health. Reduced saliva production leads to a decreased quality of life for patients experiencing hyposalivation as a result of disease or injury, thus a large effort has been dedicated to developing materials and medium to recapitulate the structure of the gland for regenerative medicine. In doing so, we have come closer to developing a more complex model to study disease. These models, however, do not yet fully recapitulate the gland. In this dissertation, we describe a new cell source that can be used to develop …

Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo

Dissertations and Theses (Open Access)

Cancers are heterogeneous mixtures of tumor and surrounding cells, where each component comprises multiple distinct sub-types and/or states. Understanding the cell-type-specific contributions is critical for advancing cancer biology, yet high-throughput expression profiles from tumor tissues only represent combined signals from all diverse cellular sources. Bulk deconvolution with single-cell/nucleus (sc/sn) RNA-seq data has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns, yet the technological discrepancy across sequencing platforms limits accuracy.

To systematically evaluate the impact of platform discrepancies on bulk deconvolution, we first generated a benchmark dataset of 24 healthy retinas with paired bulk and …

Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression During Immunotherapy, Er-Yen Yen

Dissertations and Theses (Open Access)

Tumors are dynamic ecosystems that evolve under selective pressures, shaping their ability to either elicit or evade immune responses. In pancreatic ductal adenocarcinoma (PDAC), where immunotherapy has yet to become an effective treatment option, we investigated the role of intratumoral heterogeneity in influencing immune interactions. Using orthotopic clonal replica tumors, we tracked clonal dynamics in response to anti-PD1 therapy and found that while treatment had limited impact on overall tumor volume, it induced profound shifts in clonal composition. Spatial lineage analysis of treatment-naïve tumors revealed that clones with distinct immunotherapy sensitivities occupy unique tumor microenvironments, a pattern that remained stable …

National Immunization Awareness Month, Sandra Yvette Desjardins

TMC Library Newsletter (2015-)

August marks National Immunization Awareness Month (NIAM)—a time to spotlight the vital role vaccines play in protecting people of all ages.

Explore the Power of Vaccines with Trusted Resources from the TMC Library

Genetic Study Of Von Willebrand Factor Antigen Levels ≤ 50 Iu/Dl Identifies Variants Associated With Increased Risk Of Von Willebrand Disease And Bleeding, Rachel K Friedman, Adam S Heath, Jennifer E Huffman, James T Baker, Natalie R Hasbani, Sarah A Gagliano Taliun, Ming-Huei Chen, Tom E Howard, Joshua P Lewis, Nathan Pankratz, Snehal Patil, Alex P Reiner, Florian Thibord, Lisa R Yanek, Jie Yao, Hung-Hsin Chen, Joanne E Curran, Nauder Faraday, Xiuqing Guo, Marsha M Wheeler, Kathleen A Ryan, Xiang Zhou, Kelly Cho, Laura Almasy, Paul L Auer, Lewis C Becker, Peter W F Wilson, Eric Boerwinkle, Jeffrey R O'Connell, Stephen S Rich, David C Samuels, National Heart, Lung And Blood Institute (Nhlbi) Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology & Hemostasis Working Group, Va Million Veteran Program, John Blangero, Myriam Fornage, Charles Kooperberg, Rasika A Mathias, Braxton D Mitchell, Jerome I Rotter, Andrew D Johnson, Nicholas L Smith, Zeynep H Coban-Akdemir, Jennifer E Below, Alanna C Morrison, Jill M Johnsen, Paul S De Vries

Faculty, Staff and Student Publications

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤ 50 IU/dL) in the general population is underexplored.

Objectives: To identify genetic variants influencing VWF:Ag levels ≤ 50 IU/dL.

Methods: We performed a genome-wide association study in 926 cases with VWF:Ag levels ≤ 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with …

Impaired Rest-Activity Rhythm Characteristics Predict Higher Risk Of Incident Type 2 Diabetes In Uk Biobank Participants, Chris Ho Ching Yeung, Alison K Wright, Daniel P Windred, Angus C Burns, Andrew J K Phillips, Sean W Cain, Martin K Rutter, Qian Xiao

Faculty, Staff and Student Publications

Objective: Circadian rhythms play a key role in metabolic health. Rest-activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest-activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes.

Research design and methods: In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest-activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models …

Linking Chronic Kidney Disease To Incident Heart Failure And Adverse Cardiac Remodeling Through The Plasma Proteome: The Aric Study, Leo F Buckley, Pranav Dorbala, Victoria Lamberson, Brian L Claggett, Yue Ren, Morgan E Grams, Josef Coresh, Kunihiro Matsushita, Ryan T Demmer, Ruth F Dubin, Rajat Deo, Peter Ganz, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study. Relative plasma concentrations of 4,697 unique proteins were measured with the use of an aptamer assay (Somalogic). Each protein was tested for associations with estimated glomerular filtration rate (eGFR), log-transformed urine albumin-to-creatinine ratio (UACR), and incident HF by …

Trends In Glucagon-Like Peptide 1 Receptor Agonist Prescribing Patterns, Maria Ukhanova, Joseph S Wozny, Chau N Truong, Lopita Ghosh, Trudy M Krause

Faculty, Staff and Student Publications

Objective: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes.

Study design: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other …

Computational Frameworks To Unravel The Immune Landscape, Shan He

Dissertations and Theses (Open Access)

Recent advances in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, face challenges such as resistance and immune-related adverse events, partly due to our limited understanding of the immune signaling pathways. While high- throughput genomic data provide unprecedented resolution into these immune pathways, their full potential is limited by the lack of well-annotated, context-specific immune gene sets. To address this need, I developed a workflow to construct immune gene sets by integrating RNA- seq datasets and performing decomposition. Using this approach, I constructed 28 immune- specific gene sets from 83 bulk RNA-seq datasets and 12 Natural Killer (NK) …

Resolving Intra-Tumoral Heterogeneity Of Breast Cancer Using Single-Cell Multi-Omics, Yun Yan

Dissertations and Theses (Open Access)

Breast cancer is a highly heterogeneous disease characterized by diverse genetic, transcriptional, and epigenetic landscapes. Understanding how intra-tumoral heterogeneity (ITH) influences therapeutic response and drives tumor evolution remains a central challenge in cancer biology. Here, we leverage single-cell multi-omics technologies to dissect the cell states and gene expression programs underlying breast cancer heterogeneity, with a focus on triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER+) breast cancer.

In the first part, we applied single-cell RNA sequencing and spatial transcriptomics to profile over 400,000 cells from 101 treatment-naïve TNBC patients. We identified 4 archetypes at the patient level and 13 metaprograms …

Use Of The Protein Misfolding Cyclic Amplification For Food Safety And Drug Discovery, Maria R. Benavente Garcia-Huidobro

Dissertations and Theses (Open Access)

Prion diseases are fatal neurodegenerative disorders caused by the misfolding of the normal prion protein (PrP^C) into its infectious form (PrP^Sc). While the zoonotic potential of chronic wasting disease (CWD) remains uncertain, the presence of prions in food products raises public health concerns. Additionally, therapeutic strategies for prion diseases remain limited. This thesis presents a methodological exploration of the Protein Misfolding Cyclic Amplification (PMCA) technique to address these challenges in two key areas: (1) detecting CWD prions in processed meats subjected to common cooking procedures, and (2) identifying potential anti-prion compounds through a high-throughput PMCA adaptation. …

Structural Functional Investigation Of Hap40, Amanda M. Solbach

Dissertations and Theses (Open Access)

STRUCTURAL FUNCTIONAL INVESTIGATION OF HAP40

Amanda Marie Solbach

Dissertation Advisor: Sheng Zhang, Ph.D.

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene, resulting in a mutant huntingtin (mHTT) protein with an elongated polyglutamine tract. While the genetic basis of HD is well established, the mechanisms underlying mHTT toxicity and its impact on cellular function remain incompletely understood. Recent discoveries implicate Huntingtin-associated protein 40 (HAP40) as a critical regulator of HTT stability and intracellular function. However, the physiological and pathological significance of this interaction has not been fully explored.

This …

Modeling Renal Anomalies Associated With Li-Fraumeni Patients: A Novel Role For P53 In Kidney Development, Alejandra Davilavaladez

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a heritable disorder caused by germline mutations in the TP53 gene that result in an increased risk of cancer. The TP53 tumor suppressor gene regulates cell division and prevents the accumulation of cells that may become cancerous. LFS patients are susceptible to various types of cancers, including osteosarcoma, soft tissue sarcoma, acute leukemia, and adrenal cortical tumors, as well as breast and brain cancer. Additionally, these patients have an increased risk of developing kidney, stomach, colon, pancreas, esophagus, lung, and gonadal germ cell cancers. Prior studies indicate that p53 is involved in kidney development. However, there …

Effects Of Sex And Aging In The Response To Global Cerebral Hypoperfusion, Alexis Mcalister

Dissertations and Theses (Open Access)

Introduction

The prevalence of dementia worldwide is projected to double by the year 2030 and triple by 2050. Vascular cognitive impairment and dementia (VCID) encompasses diseases that lead to cognitive decline and dementia due to cerebrovascular disease. VCID is the second most common form of dementia after Alzheimer’s disease, accounting for approximately 15- 40% of all dementia cases. Reductions in cerebral blood flow from intracranial and extracranial atherosclerosis increase VCID risk, even in the absence of overt clinical or imaging evidence of stroke/embolization. The pathology seen in patients with chronic cerebral hypoperfusion, such as inflammation, neuronal loss, white matter abnormalities, …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Autoantibody Profiling To Predict Response To The Anti-Pd-1 Therapy, Pembrolizumab, In Rare Tumors, M H Derbala, J Hajjar, B Stephen, S A Gurses, E Kwiatkowski, P Budde, H-D Zucht, M Bräutigam, A-S Lindemann, B A Abhari, M A Gouda, L Castillo, A Zarifa, J A How, E Rodriguez, J T Moyers, D S Hong, S Fu, F Meric-Bernstam, A Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have limited response rates in selected patients and can cause potentially life-threatening immune-related adverse events (irAEs). This underscores the urgent need for the development of biomarkers predictive of ICI response. Pre-existing autoantibodies (AAbs) have been linked with responses to ICIs and the development of irAEs. We conducted AAb profiling to assess associations between baseline AAbs and clinical benefit (CB) in patients with rare tumors treated with anti-programmed cell death protein 1-based therapy.

Patients and methods: We conducted AAb profiling using Oncimmune's SeroTag multiplex antibody discovery technology and immune oncology array containing 1168 antigens. The study …

Racial Disparities In The Receipt Of Therapies For Cancer, Hypertension, And Diabetes, And In Mortality In A Large Population-Based Cohort Of Older Men With Prostate Cancer, Zhuoyun Li, Xianglin L Du

Faculty, Staff and Student Publications

Background: Racial disparities in treatment and mortality were widely studied among prostate cancer patients; however, few studies considered the prevalence of hypertension and diabetes and their treatment status.

Objectives: To determine whether there are racial discrepancies in the use of anti-cancer, antihypertensive, and antidiabetic drugs in a cohort of long-term survivors of prostate cancer diagnosed in 2007-2015; and to examine racial disparities in mortality after adjustments for their differences in those treatments.

Methods: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database and included records for patients with prostate cancer at age 65 years or older diagnosed from …

Fold-And-Fuse Neurulation In Zebrafish Requires Vangl2, Jacalyn Macgowan, Mara Cardenas, Margot Kossmann Williams

Faculty, Staff and Students Publications

Shaping of the future brain and spinal cord during neurulation is an essential component of early vertebrate development. In amniote embryos, primary neurulation occurs through a "fold-and-fuse" mechanism by which the edges of the neural plate fuse into the hollow neural tube. Failure of neural fold fusion results in neural tube defects (NTDs), which are among the most devastating and common congenital anomalies worldwide. Unlike amniotes, the zebrafish neural tube develops largely via formation of a solid neural keel that later cavitates to form a midline lumen. Although many aspects of primary neurulation are conserved in zebrafish, including neural fold …

The Psychiatric Genomics Consortium: Discoveries And Directions, Arpana Agrawal, Cynthia M Bulik, Dawit Shawel Abebe, Ole A Andreassen, Elizabeth G Atkinson, Karmel W Choi, Aiden Corvin, Helena L Davies, Lea K Davis, Anna R Docherty, Howard J Edenberg, Barbara Franke, Joel Gelernter, Paola Giusti-Rodríguez, John M Hettema, Jens Hjerling-Leffler, Hailiang Huang, Emma C Johnson, Cathryn M Lewis, Yi Lu, Mary-Ellen Lynall, Joanna Martin, Andrew M Mcintosh, Janitza L Montalvo-Ortiz, Niamh Mullins, Caroline M Nievergelt, Kevin S O'Connell, Michael C O'Donovan, Adeniran Okewole, Roseann E Peterson, Danielle Posthuma, Jonathan Sebat, Jordan W Smoller, Reeteka Sud, Biju Viswanath, James T R Walters, Hyejung Won, Naomi R Wray, Patrick F Sullivan, Coordinating Committee Of The Psychiatric Genomics Consortium

Faculty, Staff and Students Publications

The Psychiatric Genomics Consortium (PGC) has fueled discoveries of common and rare genetic variation contributing to liability to many psychiatric and neurodevelopmental conditions. This narrative review reflects on major findings from the past half decade of research by this international group of investigators in five priority areas: discovery of common variants using GWAS; rare variation and its interplay with polygenic risk; leveraging genetics to go beyond diagnostic boundaries; ascribing functional attributes to genomic discoveries; and developing and implementing processes for data sharing, outreach to various communities, and training. The insights gained in these domains frame the agenda for the next …

Mood And Sleep In Young Adults With Type 1 Diabetes, Samantha A Carreon, Marissa N Baudino, Charles G Minard, Sarah K Lyons, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sara Nowakowski, Ashley M Butler, Sridevi Devaraj, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Depression is associated with sleep problems, and both are associated with higher HbA1c in people with type 1 diabetes (T1D). However, little is known about depressed mood and sleep in young adults with T1D. The aims of this secondary analysis were to provide descriptive statistics of multiple aspects of mood and sleep in young adults with T1D and evaluate associations of depressed mood, diabetes distress, and sleep quality and duration.

Methods: At baseline of a behavioral intervention trial, young adults with T1D completed self-report measures of sleep, diabetes distress, and depressive symptoms. We described sleep metrics across racial/ethnic groups …