Digital Commons Network^™

Mutant P53 Confers Chemoresistance By Activating Kmt5b-Mediated Dna Repair Pathway In Nasopharyngeal Carcinoma, Haidan Luo, Mo-Fan Huang, An Xu, Donghui Wang, Julian A Gingold, Jian Tu, Ruoyu Wang, Zijun Huo, Yen-Ting Chiang, Kuang-Lei Tsai, Jie Su, Danielle A Bazer, Mien-Chie Hung, Canmao Xie, Yubiao Guo, Dung-Fang Lee, Huiling Yang, Ruiying Zhao

Faculty, Staff and Student Publications

Nasopharyngeal carcinoma (NPC), a malignancy arising from the nasopharyngeal epithelium, is common in the east and southeast area of Asia. Treatments for locally advanced and recurrent NPC include chemotherapy (usually combined with 5-Fluorouracil, 5-FU) and radiotherapy, but response is limited due to chemo-resistance. p53 mutation is a critical factor for 5-FU resistance in some cancers, but its role in NPC chemo-resistance remains unclear. Here, we demonstrate that p53(R280T), a common p53 somatic mutation found in multiple NPC tumor samples, induces gain-of-function upregulation of DNA repair genes which leads to 5-FU resistance in NPC. p53(R280T) specifically upregulates the expression of DNA …

Effects Of Mode And Transitioning To A Mixed-Mode (Web/Phone) Design On Categorical Survey Estimates: Do Question Characteristics Matter?, Mengyao Hu, Vicki A Freedman, Justin Kamens

Faculty, Staff and Student Publications

An increasing number of telephone surveys are introducing a web option. Limited experimental research has explored the implications of such design changes and how they vary by question characteristics. Using an experimental design and propensity score matching techniques, this study examines the effects of mode (web vs. telephone) and transitioning to a mixed-mode design (from telephone-only to the choice of web or telephone) on survey estimates and how effects differ by question characteristics. We draw upon an experiment embedded in the National Study of Caregiving (NSOC), in which half of NSOC-eligible caregivers were randomized to a telephone-only design and the …

Enhancing Digital Health Development Through Speech Act Theory: Application To Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Michael Truong, Sahiti Myneni

Faculty, Staff and Student Publications

The peripartum period is a time of complex transition into motherhood when women may develop peripartum depression (PPD). Digital information sources can help prevent and monitor symptoms through social support and mental health knowledge. However, few studies have characterized the content and form of peer interactions in PPD online forums to inform interventions. In this paper, we present preliminary work using a dataset of 55,301 interactions to inform our digital health development. We combine manual coding for speech acts, behavioral theory mapping, and user engagement modeling to conceptualize dynamic digital education modules for PPD. Results reveal "Expressive" speech act, where …

Towards Data-Driven Science Literacy: Extracting Psycholinguistic Markers In Vaping-Related Online Peer Interactions, Michael Truong, Ahmed Abdelhameed, Tavleen Singh, Kirk Roberts, Sahiti Myneni

Faculty, Staff and Student Publications

Social media debates on e-cigarettes raise public health concerns due to evolving evidence and conflicting guidelines. We analyzed 25,127 vaping-related comments to explore how users discuss vaping-related topics. Our analysis revealed 25 topics grouped into three parent topics: positive effects of vaping, negative effects of vaping, and vaping-related news & information. Significant differences were observed in psycholinguistic characteristics with high emotional exchanges as positive and negative effects of e-cigarettes are debated. Our results can inform interventions promoting science literacy and misinformation resistance.

Efficient Training Corpus Retrieval For Large Language Model Fine Tuning: A Case Study In Cancer., Avisha Das, Chiamaka Diala, Guocai Chen, Zhao Li, Rongbin Li, Omer Anjum, W Jim Zheng

Faculty, Staff and Student Publications

The objective is to create an automated knowledge extraction tool for cancer research that builds high-quality academic corpora for LLM fine-tuning while investigating its effectiveness in interleukin-6 and bladder cancer domains. To address the current gap in knowledge retrieval techniques for cancer research data collection, we propose KnowledgePipeline, a novel automated tool that incorporates diverse aspects of academic papers and metadata. Our tool integrates content, co-citations, and co-authorship networks to construct domain-specific academic corpora suitable for fine-tuning LLMs. We leverage two LLMs (GPTJ-6.7B and Galactica30B) trained on domain-specific question-answer pairs from the refined data. The system's evaluation focuses on both …

Generational Health Professional Perceptions About Artificial Intelligence Impact On Clinical Work, Karima Lalani, Kerryn Butler-Henderson, David T Marc, Susan H Fenton

Faculty, Staff and Student Publications

Whilst the evidence-base related to artificial intelligence (AI) has been growing in relation to its use and impact on healthcare, there is a lack of evidence related to the health workforce impact and no research examining the generational perceptions in relation to the health workforce and AI. This paper presents the results of a survey, which found generational differences in perceptions about the impact of AI on clinical jobs. Gen Z and Millennials were more likely to agree with statements that AI will improve their clinical decision-making skills/abilities, accomplish clinical tasks more quickly, and cause unemployment in their professional occupation. …

Proactive Planning For Contextual Fit: The Role Of The Implementation Premortem, Guillermo M Wippold, Kaylyn A Garcia, Ariel Domlyn, Dylan Wong, Maria E Fernandez

Faculty, Staff and Student Publications

Background: Implementation failure is a major barrier to program success. It is widely acknowledged that context matters-individual, community, and organizational norms, values, environment, and priorities influence successful program implementation. A mismatch between how the program was intended to be delivered and the constraints of the context in which it was delivered is a major cause of implementation failure. The barriers to implementation are usually understood after a program has failed. Although there are tools that can help accommodate for, or overcome, contextually-driven sources of implementation failure, there remains a significant gap - a tool and structured approach to analyze data …

Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

Methods: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts …

Sulfated Dietary Fiber Protects Gut Microbiota From Antibiotics, Fuqing Wu, Xiaoqian Annie Yu, David Angeles-Albores, Susan E Erdman, Eric J Alm

Faculty, Staff and Student Publications

Background: Antibiotics, while essential for combating pathogens, also disrupt commensal bacteria, leading to gut microbiota imbalance and associated diseases. However, strategies to mitigate such collateral damage remain largely underexplored.

Result: In this study, we found that fucoidan, a marine polysaccharide derived from brown seaweed, provides broad-spectrum growth protection against multiple classes of antibiotics for human gut microbial isolates in vitro and for fecal communities ex vivo. This protective effect is dependent on the structural integrity, molecular weight, and sulfur content of the polysaccharide. Transcriptomic analysis showed that while fucoidan had minimal impact on baseline gene expression, it counteracted about 60% …

Development Of A Customizable Web-Based Dashboard For Remote Blood Pressure Monitoring: Feasibility And Usability Implementation Study, Joshua Wollen, Thuy Nguyen, Charles Coton, Gina Dewildt, Gabretta Cooksey, Audrey Cohen, Nicholas Hoang, Munachi Okpala, Michael Gonzalez, Mengxi Wang, Chigozirim Izeogu, Elmer Bernstam, Charles Green, Sean Savitz, Jose-Miguel Yamal, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Effective blood pressure (BP) management is essential for several disease states, including secondary stroke prevention. Remote BP monitoring used in combination with an electronic data capture (EDC) system offers potential for improved BP control for patients. While such systems currently exist, there are many patient-, provider-, and system-specific challenges these systems currently do not address. In addition, such systems are rarely described transparently and comprehensively in the literature with enough detail to be reproduced by other clinicians.

Objective: This study aims to describe the development and design of a web-based EDC system tailored for remote BP monitoring and management …

Biomarkers In Renal Cell Carcinoma: A Systematic Review And Immunohistochemical Validation Study, Brett Berezowski, Robert Boothe, Billy Chaplin, Sharon J Del Vecchio, Zakariya Fares, Tyrone L R Humphries, Keng Lim Ng, Taylor Noonan, Hemamali Samaratunga, Aaron Urquhart, David A Vesey, Simon T Wood, Glenda C Gobe, Robert J Ellis

Faculty, Staff and Student Publications

The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management. Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential …

Immunomodulatory Effects Of Gold Nanoparticles: Impacts On Immune Cells And Mechanisms Of Action, Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Traditional anti-inflammatory medications-such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs-are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we …

Real-Time Experiences Of Racism And Stress In Association With Postpartum Weight Retention: A Longitudinal Ecological Momentary Assessment Study, Dara M Méndez, Amanda L Tapia, Sarah A Sanders, Andrea D Casas, Marquita Smalls, Esa M Davis, Stephen L Rathbun, Tiffany L Gary-Webb, Lora E Burke, Serwaa S Omowale, Linda A Adodoadji, John J Gianakas, Y Lai, Maisa Feghali, Meredith L Wallace

Faculty, Staff and Student Publications

Racial inequities in postpartum weight have been documented with limited studies on the influences of racism and other forms of discrimination. In a prospective longitudinal study applying ecological momentary assessment (EMA) and ambulatory assessment of weight, we measured the association between discrimination, stress, and postpartum weight change. The Postpartum Mothers Mobile Study is a cohort of 313 pregnant and birthing individuals who were followed during their second and third trimesters through 1 year postpartum. They were recruited in clinical settings between 2017 and 2020 in a major city center in Pennsylvania. Measures of racism and gender-based discrimination were collected via …

Association Between Allostatic Load And Accelerated White Matter Brain Aging: Findings From The Uk Biobank, Li Feng, Zhenyao Ye, Zewen Du, Yezhi Pan, Travis Canida, Hongjie Ke, Song Liu, Shuo Chen, L Elliot Hong, Peter Kochunov, Jie Chen, David K Y Lei, Edmond Shenassa, Tianzhou Ma

Faculty, Staff and Student Publications

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting, …

Gated Recurrent Unit With Decay Has Real-Time Capability For Postoperative Ileus Surveillance And Offers Cross-Hospital Transferability, Xiaoyang Ruan, Sunyang Fu, Heling Jia, Kellie L Mathis, Cornelius A Thiels, Schaeferle M Gavin, Patrick M Wilson, Curtis B Storlie, Hongfang Liu

Faculty, Staff and Student Publications

Background: Ileus, a postoperative complication after colorectal surgery, increases morbidity, costs, and hospital stays. Assessing risk of ileus is crucial, especially with the trend towards early discharge. Prior studies assessed risk of ileus with regression models, the role of deep learning remains unexplored.

Methods: We evaluated the Gated Recurrent Unit with Decay (GRU-D) for real-time ileus risk assessment in 7349 colorectal surgeries across three Mayo Clinic sites with two Electronic Health Record (EHR) systems. The results were compared with atemporal models on a panel of benchmark metrics.

Results: Here we show that despite extreme data sparsity (e.g., 72.2% of labs, …

Factors Influencing Covid-19 Vaccine Uptake Among Vulnerable Communities In Texas: Perceptions Of 2-1-1 Helpline Callers, Lara S Savas, Paula Cuccaro, Kehe Zhang, Rodrigo Hernandez, Meghan E Haffey, Belinda Reininger, Anais Mendiola, Olivia Dominguez, Maribel Sifuentes, Cici Bauer, Maria E Fernandez

Faculty, Staff and Student Publications

Background: Vaccination effectively and safely prevents serious illness from coronavirus disease 2019 (COVID-19). This study examines the complex factors associated with vaccination uptake among economically disadvantaged adults calling the Texas/United Way 2-1-1 helpline. Results informed the development of strategies to increase COVID-19 vaccine uptake among vulnerable populations disproportionately impacted by COVID-19-related morbidity and mortality.

Material and methods: We conducted a cross-sectional survey among 2-1-1 adult callers (May 2021-September 2022). The survey examined demographic, sociocultural, healthcare access, and psychosocial factors, as well as mistrust in health agencies. We used multivariable logistic regression models to examine factors associated with vaccination uptake, and …

Integrating Ctdna Analysis And Radiomics For Dynamic Risk Assessment In Localized Lung Cancer, Everett J Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B Hui, Barzin Y Nabet, Yufei Liu, Jacob J Chabon, Michael S Binkley, David M Kurtz, Emily G Hamilton, Aadel A Chaudhuri, Chih Long Liu, Zhe Li, Rene F Bonilla, Alice L Jiang, Brianna C Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J Ramchandran, Sukhmani K Padda, Joel W Neal, Heather A Wakelee, Michael F Gensheimer, Billy W Loo, Ruijiang Li, Steven H Lin, Ash A Alizadeh, Maximilian Diehn

Faculty, Staff and Student Publications

The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. Circulating tumor DNA (ctDNA) minimal residual disease after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. Here, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration …

Trauma Resuscitation With Low-Titer Group O Whole Blood Or Products: Study Protocol For A Randomized Clinical Trial (The Troop Trial), Jan O Jansen, Claudia Pedroza, Luis Leon Novelo, Tianyao Hao, Gina R Dewildt, Charles F Coton, Kiran Mansoor, Shannon W Stephens, Marisa B Marques, James R Stubbs, Jillian R Richter, Henry E Wang, John B Holcomb, Stacia M Desantis

Faculty, Staff and Student Publications

Background: Hemorrhage is the most common cause of potentially preventable death after injury. Balanced transfusion with red blood cells, plasma, and platelets (component therapy, CT) has been shown to reduce mortality, and is the standard of care. Low-Titer Group O Whole Blood (LTOWB) is an attractive alternative to CT, but existing evidence comprises observational studies, and a small single center pilot randomized controlled trial, which evaluated a type of whole blood that is no longer in use. The aim of the "Trauma Resuscitation with Low-Titer Group O Whole Blood Or Products" (TROOP) trial is to compare the effectiveness and safety …

Rsph4a-Pcdx: An Index To Predict Lung Function Decline In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with

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 …

A Comparative Study Of Recent Large Language Models On Generating Hospital Discharge Summaries For Lung Cancer Patients, Yiming Li, Fang Li, Na Hong, Manqi Li, Kirk Roberts, Licong Cui, Cui Tao, Hua Xu

Faculty, Staff and Student Publications

Objective: Generating discharge summaries is a crucial yet time-consuming task in clinical practice, essential for conveying pertinent patient information and facilitating continuity of care. Recent advancements in large language models (LLMs) have significantly enhanced their capability in understanding and summarizing complex medical texts. This research aims to explore how LLMs can alleviate the burden of manual summarization, streamline workflow efficiencies, and support informed decision-making in healthcare settings.

Materials and methods: Clinical notes from a cohort of 1,099 lung cancer patients were utilized, with a subset of 50 patients for testing purposes, and 102 patients used for model fine-tuning. This study …

Dp-Brem: Differentially-Private And Byzantine-Robust Federated Learning With Client Momentum, Xiaolan Gu, Ming Li, Li Xiong

Faculty, Staff and Student Publications

Federated Learning (FL) allows multiple participating clients to train machine learning models collaboratively while keeping their datasets local and only exchanging the gradient or model updates with a coordinating server. Existing FL protocols are vulnerable to attacks that aim to compromise data privacy and/or model robustness. Recently proposed defenses focused on ensuring either privacy or robustness, but not both. In this paper, we focus on simultaneously achieving differential privacy (DP) and Byzantine robustness for cross-silo FL, based on the idea of learning from history. The robustness is achieved via client momentum, which averages the updates of each client over time, …

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 …

Management Approaches To Spastic Gait Disorders, Sheng Li, Tulsi Pandat, Bradley Chi, Daniel Moon, Manuel Mas

Faculty, Staff and Student Publications

Spastic gait presents clinically as the net mechanical consequence of neurological impairments of spasticity, weakness, and abnormal synergies and their interactions with the ground reaction force in patients with upper motor neuron syndromes and with some neuromuscular diseases. It is critical to differentiate whether the primary problem is weakness or spasticity, thus better understanding different phenotypes of spastic gait disorders. Pelvic girdle abnormality plays a pivotal role in determining the clinical presentation of gait disorders, since it determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. Knee joint abnormality can be a mechanical compensation …

Patient-Specific Preoperative Plans Can Optimize Femoral Head Coverage And Range Of Motion After Periacetabular Osteotomies, Shuyang Han, Carey A Clark, Nicholas J Dunbar, Madison Brenner, Alexis H Aboulafia, Alfred A Mansour Iii, Philip C Noble

Faculty, Staff and Student Publications

Background: The goal of a periacetabular osteotomy is to increase the coverage of the femoral head, primarily in the antero-lateral region, through rotation of the acetabulum in three anatomical planes. The present study was undertaken to determine whether specific combinations of lateral rotation, anterior rotation, and anteversion of the acetabular fragment can be targeted to provide the best balance between femoral head coverage and joint motion.

Methods: Three-dimensional patient-specific hip models were reconstructed from preoperative computerized tomography scans of 15 patients diagnosed with hip dysplasia. Each model was placed in a standard coordinate system with neutral pelvic tilt and femoral …

A 65-Year-Old Man With Cough, Hypercalcemia, And Diffuse Opacities, Philip K Angelides, Oriana Salamo, Sujith V Cherian, Eduardo Yepez Guevara, Carlos A Jimenez, Saadia A Faiz

Faculty, Staff and Student Publications

Respiratory infections in patients with cancer are common. A low threshold for bronchoscopy with bronchoalveolar lavage (BAL) should be maintained in immunocompromised patients with pulmonary opacities on chest imaging to evaluate for opportunistic infections. In those with unresolving symptoms, transbronchial biopsies may add significant diagnostic value. Concomitant hypercalcemia in patients with cancer is typically related to underlying malignant disease. However, in those with persistent respiratory symptoms or atypical infiltrates then granulomatous inflammatory diseases should be considered. Diagnosing histoplasmosis in immunocompromised patients can be difficult. Antigen testing is often more sensitive, but tissue biopsy or culture may be needed. We describe …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

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 …