Medical Specialties Commons^™

Dengue Outbreak Response During Covid-19 Pandemic, Key Largo, Florida, Usa, 2020, Devin Rowe, Catherine Mcdermott, Ysla Veliz, Alison Kerr, Mark Whiteside, Mikki Coss, Chad Huff, Andrea Leal, Edgar Kopp, Alexis Lacrue, Lea A Heberlein, Laura E Adams, Gilberto A Santiago, Jorge L Munoz-Jordan, Gabriela Paz-Bailey, Andrea M Morrison

Faculty, Staff and Student Publications

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Fibroblast-Derived Pi16 Sustains Inflammatory Pain Via Regulation Of Cd206+ Myeloid Cells, Rachelle Garrity, Neha Arora, Md Areeful Haque, Drew Weis, Ronnie T Trinh, Sanjay V Neerukonda, Susmita Kumari, Ibdanelo Cortez, Eroboghene E Ubogu, Rajasekaran Mahalingam, Diana Tavares-Ferreira, Theodore J Price, Annemieke Kavelaars, Cobi J Heijnen, Andrew J Shepherd

Faculty, Staff and Student Publications

Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund’s Adjuvant inflammatory pain model, we show that Pi16-/- mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain. In contrast to neuropathic pain models, we did not observe any changes in blood-nerve barrier permeability due to PI16 deletion. Instead, Pi16-/- mice display reduced macrophage density …

Barriers And Determinants Of Consistent Offering Of Hpv Vaccination By Healthcare Facilities, Ikponmwosa Osaghae, Onyema Greg Chido-Amajuoyi, Banda A A Khalifa, Sanjay Shete

Faculty, Staff and Student Publications

Expanding access to HPV vaccination is critical to increasing HPV vaccine uptake. We assessed the determinants and barriers to consistent offering of HPV vaccine among healthcare facilities. This was a cross-sectional survey of healthcare providers (HCPs) in Texas. Prevalence of the reasons healthcare practices do not consistently offer HPV vaccination was estimated. Multivariable regression analyses were conducted. Of 1169 HCPs included in the study, 47.5% (95% CI: 44.6-50.3%) reported their practices do not provide HPV vaccination or do not offer it consistently. Compared to physicians, nurses had 77% lower odds (Adjusted Odds Ratio (AOR): 0.23, 95% CI: 0.16-0.32, p-value: < .001), and physician assistants had 89% lower odds (AOR: 0.11, 95% CI: 0.07-0.16, p-value: < .001) of their healthcare practices consistently offering HPV vaccination. Compared to university/teaching hospitals, the odds of healthcare practices consistently offering HPV vaccination were 44% lower (AOR: 0.56, 95% CI: 0.35-0.91, p-value: 0.019) in solo practices but 266% higher (AOR: 3.66, 95% CI: 2.04-6.58, p-value: < .001) in FQHC/public facilities. The common reasons healthcare practices do not consistently offer HPV vaccination were; HPV vaccination is not within the scope of the practice (48.1%), referrals to other clinics (27.7%), and limited personnel (11.4%). Non-physicians were more likely to report that HPV vaccination was not in their scope and to refer patients than physicians. Moreover, solo practices were more likely to report challenges with acquisition and storage of the vaccine and referral of patients as reasons for not consistently offering HPV vaccination than university/teaching hospitals, FQHC/public facilities, or group practices. System-level interventions including training of non-physicians and expansion of practice enrollment in programs that support HPV vaccine acquisition and storage are needed.

The Influence Of Political Ideology On Awareness Of Hpv And Hpv Vaccine Among Adults In The United States, Onyema Greg Chido-Amajuoyi, Henry Onyeaka, Hermioni Amonoo, Sanjay Shete

Faculty, Staff and Student Publications

This study aimed to investigate the association between political ideology and awareness of HPV and HPV vaccine among US adults. Study data were derived from Health Information National Trends Survey 5 Cycle 4, a 2020 cross-sectional survey of US adults. Multivariable logistic regressions were conducted to examine the association between political ideology with HPV and HPV vaccine awareness. A total of 3418 adults participated in the study, with the majority being non-Hispanic White individuals and women. The results showed that 66.1% and 62.3% of the participants were aware of HPV and HPV vaccine, respectively. A total of 36.9%, 29.7% and …

Mpla Case: I Didn't Realize Those Were The Expectations!, Samantha J Simiele, Serdar Charyyev, Liyong Lin, Leonard Kim, Dongxu Wang, Mary P Gronberg

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of how students and advisors can better communicate expectations and navigate difficult conversations. In this case, a fourth-year Ph.D. student Emma learns that her advisor Dr. So is leaving the institution and has not arranged to bring any students with him. As Emma and Dr. So meet to discuss Emma's next steps, the conversation reveals misunderstandings and miscommunications of expectations, including a specific publication requirement for graduation from Dr. So. Having just learned of …

Hazard Testing To Reduce Risk In The Development Of Automated Planning Tools, Kelly A Nealon, Raphael J Douglas, Eun Young Han, Stephen F Kry, Valerie K Reed, Samantha J Simiele, Laurence E Court

Faculty, Staff and Student Publications

PURPOSE: Hazard scenarios were created to assess and reduce the risk of planning errors in automated planning processes. This was accomplished through iterative testing and improvement of examined user interfaces.

METHODS: Automated planning requires three user inputs: a computed tomography (CT), a prescription document, known as the service request, and contours. We investigated the ability of users to catch errors that were intentionally introduced into each of these three stages, according to an FMEA analysis. Five radiation therapists each reviewed 15 patient CTs, containing three errors: inappropriate field of view, incorrect superior border, and incorrect identification of isocenter. Four radiation …

Cardiovascular Risk Factor Disparities In Adult Survivors Of Childhood Cancer Compared With The General Population, David H Noyd, Qi Liu, Yutaka Yasui, Eric J Chow, Smita Bhatia, Paul C Nathan, Andrew P Landstrom, Emily Tonorezos, Jacqueline Casillas, Amy Berkman, Kirsten K Ness, Daniel A Mulrooney, Wendy M Leisenring, Carrie R Howell, Jamie Shoag, Anne Kirchhoff, Rebecca M Howell, Todd M Gibson, Leah L Zullig, Gregory T Armstrong, Kevin C Oeffinger

Faculty, Staff and Student Publications

BACKGROUND: It is unknown whether a history of childhood cancer modifies the established disparities in cardiovascular risk factors (CVRFs) observed in the general population.

OBJECTIVES: We sought to determine if disparities in CVRFs by race/ethnicity are similar among childhood cancer survivors compared with the general population.

METHODS: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort with a longitudinal follow-up of 24,084 5-year survivors diagnosed between 1970 and 1999. Multivariable piecewise exponential regression estimated incidence rate ratios (IRRs) for hypertension, hyperlipidemia, diabetes, obesity, and ≥2 CVRFs by race/ethnicity. The CCSS sibling cohort and the National Health and Nutrition Examination …

Outcomes In Anca-Associated Vasculitis In Scotland: Validation Of The Renal Risk Score In A Complete National Cohort, Dominic P Mcgovern, Jennifer S Lees, Jamie P Traynor, Bruce Mackinnon, Samira Bell, Robert W Hunter, Neeraj Dhaun, Wendy Metcalfe, Dana Kidder, Michelle Lim, Nicola Joss, Michael Kelly, Alison Taylor, Zoe Cousland, Vishal Dey, Kate Buck, Silke Brix, Colin C Geddes, Emily P Mcquarrie, Kathryn I Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach.

METHODS: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD.

RESULTS: A total of 288 patients were eligible for inclusion in the study (low risk

CONCLUSION: The ARRS better discriminates …

Evaluation Of The Clinical And Radiographic Effectiveness Of Treating Peri-Implant Bone Defects With A New Biphasic Calcium Phosphate Bone Graft: A Prospective, Multicenter Randomized Controlled Trial, Jae-Hong Lee, Hyun-Wook An, Jae-Seung Im, Woo-Joo Kim, Dong-Won Lee, Jeong-Ho Yun

Faculty, Staff and Student Publications

PURPOSE: Biphasic calcium phosphate (BCP), a widely used biomaterial for bone regeneration, contains synthetic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), the ratio of which can be adjusted to modulate the rate of degradation. The aim of this study was to evaluate the clinical and radiographic benefits of reconstructing peri-implant bone defects with a newly developed BCP consisting of 40% β-TCP and 60% HA compared to demineralized bovine bone mineral (DBBM).

METHODS: This prospective, multicenter, parallel, single-blind randomized controlled trial was conducted at the periodontology departments of 3 different dental hospitals. Changes in clinical (defect width and height) and radiographic (augmented …

Diverse Clonal Fates Emerge Upon Drug Treatment Of Homogeneous Cancer Cells, Yogesh Goyal, Gianna T Busch, Maalavika Pillai, Jingxin Li, Ryan H Boe, Emanuelle I Grody, Manoj Chelvanambi, Ian P Dardani, Benjamin Emert, Nicholas Bodkin, Jonas Braun, Dylan Fingerman, Amanpreet Kaur, Naveen Jain, Pavithran T Ravindran, Ian A Mellis, Karun Kiani, Gretchen M Alicea, Mitchell E Fane, Syeda Subia Ahmed, Haiyin Li, Yeqing Chen, Cedric Chai, Jessica Kaster, Russell G Witt, Rossana Lazcano, Davis R Ingram, Sarah B Johnson, Khalida Wani, Margaret C Dunagin, Alexander J Lazar, Ashani T Weeraratna, Jennifer A Wargo, Meenhard Herlyn, Arjun Raj

Faculty, Staff and Student Publications

Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1-7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7-9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and …

Cell-Type-Specific Prediction Of 3d Chromatin Organization Enables High-Throughput In Silico Genetic Screening, Jimin Tan, Nina Shenker-Tauris, Javier Rodriguez-Hernaez, Eric Wang, Theodore Sakellaropoulos, Francesco Boccalatte, Palaniraja Thandapani, Jane Skok, Iannis Aifantis, David Fenyö, Bo Xia, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of cell-type-specific chromatin organization using DNA sequence and two cell-type-specific genomic features-CTCF binding and chromatin accessibility. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. We further developed an in silico genetic screening approach to assess how individual DNA elements may contribute to chromatin organization and …

Clinical, Endoscopic, And Histopathologic Gastrointestinal Disease In An American Cohort With Behçet's Disease, Bryan F Curtin, Kareen L Hill, Sumona Bhattacharya, Astin Powers, Aradhana Venkatesan, Preet Bagi, Elizabeth Joyal, Meghna Alimchandani, Raphaela Goldbach-Mansky, Peter Grayson, Martha Quezado, Cailin Sibley, Theo Heller

Faculty, Staff and Student Publications

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD.

METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent.

RESULTS: Eighty-three patients …

Prospective Evaluation Of In Vivo And Phantom Repeatability And Reproducibility Of Diffusion-Weighted Mri Sequences On 15 T Mri-Linear Accelerator (Mr-Linac) And Mr Simulator Devices For Head And Neck Cancers, Brigid A Mcdonald, Travis Salzillo, Samuel Mulder, Sara Ahmed, Alex Dresner, Kathryn Preston, Renjie He, John Christodouleas, Abdallah S R Mohamed, Marielle Philippens, Petra Van Houdt, Daniela Thorwarth, Jihong Wang, Amita Shukla Dave, Michael Boss, Clifton D Fuller

Faculty, Staff and Student Publications

INTRODUCTION: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck cancers (HNC) but requires extensive validation. We performed technical validation to compare six total DWI sequences on an MR-linac and MR simulator (MR sim) in patients, volunteers, and phantoms.

METHODS: Ten human papillomavirus-positive oropharyngeal cancer patients and ten healthy volunteers underwent DWI on a 1.5 T MR-linac with three DWI sequences: echo planar imaging (EPI), split acquisition of fast spin echo signals (SPLICE), and turbo spin echo (TSE). Volunteers were also imaged on a 1.5 T …

Multi-Parametric Mri For Radiotherapy Simulation, Tian Li, Jihong Wang, Yingli Yang, Carri K Glide-Hurst, Ning Wen, Jing Cai

Faculty, Staff and Student Publications

Magnetic resonance imaging (MRI) has become an important imaging modality in the field of radiotherapy (RT) in the past decade, especially with the development of various novel MRI and image-guidance techniques. In this review article, we will describe recent developments and discuss the applications of multi-parametric MRI (mpMRI) in RT simulation. In this review, mpMRI refers to a general and loose definition which includes various multi-contrast MRI techniques. Specifically, we will focus on the implementation, challenges, and future directions of mpMRI techniques for RT simulation.

Outcomes Of Young Adults (Aged ≤ 40 Years) With Newly Diagnosed Multiple Myeloma After Up-Front Autologous Stem Cell Transplant, Oren Pasvolsky, Curtis Marcoux, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Priti Tewari, Lindsay Crawford-Suber, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22-40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9-238.0), median PFS and OS were 43.1 months (95% CI 31.2-65.0) and 146.6 months (95% CI 100.0-208.1) respectively. …

A Review Of A Strategic Roadmapping Exercise To Advance Clinical Translation Of Photoacoustic Imaging: From Current Barriers To Future Adoption, Hisham Assi, Rui Cao, Madhura Castelino, Ben Cox, Fiona J Gilbert, Janek Gröhl, Kurinchi Gurusamy, Lina Hacker, Aoife M Ivory, James Joseph, Ferdinand Knieling, Martin J Leahy, Ledia Lilaj, Srirang Manohar, Igor Meglinski, Carmel Moran, Andrea Murray, Alexander A Oraevsky, Mark D Pagel, Manojit Pramanik, Jason Raymond, Mithun Kuniyil Ajith Singh, William C Vogt, Lihong Wang, Shufan Yang, Members Of Ipasc, Sarah E Bohndiek

Faculty, Staff and Student Publications

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of …

Long-Term Patient-Reported Outcomes In A Population-Based Cohort Following Radiotherapy Vs Surgery For Oropharyngeal Cancer, Michael J Dohopolski, Kevin Diao, Katherine A Hutcheson, Neil S Akhave, Ryan P Goepfert, Weiguo He, Xiudong Jennifer Lei, Susan K Peterson, Yu Shen, Baran D Sumer, Benjamin D Smith, David J Sher

Faculty, Staff and Student Publications

IMPORTANCE: Oncologic outcomes are similar for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery or radiotherapy. However, comparative differences in long-term patient-reported outcomes (PROs) between modalities are less well established.

OBJECTIVE: To determine the association between primary surgery or radiotherapy and long-term PROs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the Texas Cancer Registry to identify survivors of OPSCC treated definitively with primary radiotherapy or surgery between January 1, 2006, and December 31, 2016. Patients were surveyed in October 2020 and April 2021.

EXPOSURES: Primary radiotherapy and surgery for OPSCC.

MAIN OUTCOMES AND MEASURES: Patients completed …

Prame And Lef1 In Combined Deep Penetrating Nevus And Combined Blue Nevus: Utility And Pitfall, Kaitlin Vanderbeck, Aimi T Rothrock, Woo Cheal Cho, Priyadharsini Nagarajan, Phyu P Aung, Courtney Hudgens, Roland L Bassett, Doina Ivan, Victor G Prieto, Jonathan L Curry, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME …

The Initial Age-Associated Decline In Early T-Cell Progenitors Reflects Fewer Pre-Thymic Progenitors And Altered Signals In The Bone Marrow And Thymus Microenvironments, Jayashree Srinivasan, Anusha Vasudev, Carolyn Shasha, Hilary J Selden, Encarnacion Perez, Bonnie Lafleur, Shripad A Sinari, Andreas Krueger, Ellen R Richie, Lauren I R Ehrlich

Faculty, Staff and Student Publications

Age-related thymus involution results in decreased T-cell production, contributing to increased susceptibility to pathogens and reduced vaccine responsiveness. Elucidating mechanisms underlying thymus involution will inform strategies to restore thymopoiesis with age. The thymus is colonized by circulating bone marrow (BM)-derived thymus seeding progenitors (TSPs) that differentiate into early T-cell progenitors (ETPs). We find that ETP cellularity declines as early as 3 months (3MO) of age in mice. This initial ETP reduction could reflect changes in thymic stromal niches and/or pre-thymic progenitors. Using a multicongenic progenitor transfer approach, we demonstrate that the number of functional TSP/ETP niches does not diminish with …

Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites In Treg-Deficient Scurfy Mice, Yuying Liu, Shabba A Armbrister, Beanna Okeugo, Tingting W Mills, Rhea C Daniel, Jee-Hwan Oh, Jan-Peter Van Pijkeren, Evelyn S Park, Zeina M Saleh, Sharmistha Lahiri, Stefan Roos, Jmarc Rhoads

Faculty, Staff and Student Publications

Probiotic Limosilactobacillus reuteri DSM 17938 (DSM 17938) prolongs the survival of Treg-deficient scurfy (SF) mice and reduces multiorgan inflammation by a process requiring adenosine receptor 2A (A2A) on T cells. We hypothesized that L. reuteri-derived ecto-5'-nucleotidase (ecto-5'NT) activity acts to generate adenosine, which may be a central mediator for L. reuteri protection in SF mice. We evaluated DSM 17938-5'NT activity and the associated adenosine and inosine levels in plasma, gut, and liver of SF mice. We examined orally fed DSM 17938, DSM 17938Δ5NT (with a deleted 5'NT gene), and DSM 32846 (BG-R46) (a naturally selected strain derived from DSM 17938). …

Low-Grade Intestinal Inflammation Two Decades After Pelvic Radiotherapy, Sravani Devarakonda, Annika Thorsell, Per Hedenström, Azar Rezapour, Lisen Heden, Sanghita Banerjee, Malin E V Johansson, George Birchenough, Amelie Toft Morén, Karin Gustavsson, Viktor Skokic, Victor L Pettersson, Fei Sjöberg, Marie Kalm, Mohammad Al Masri, Michaela Ekh, Henrik Fagman, Mats Wolving, Rosie Perkins, Rodrigo A Morales, Francisca Castillo, Eduardo J Villablanca, Ulf Yrlid, Karin Bergmark, Gunnar Steineck, Cecilia Bull

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.

METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag …

Role Of Circulating Mitochondria In Venous Thrombosis In Glioblastoma, Ricardo Gonzalez-Delgado, Nina M Muñoz, Wendolyn Carlos-Alcalde, Min Soon Cho, Hani Lee, Jeff Jin, Victoria Serpas, Olga Gorlova, Rahul A Sheth, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

Background: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy.

Objectives: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state.

Methods: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis.

Results: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: …

Identification Of Genetic Variation Influencing Metformin Response In A Multiancestry Genome-Wide Association Study In The Diabetes Prevention Program (Dpp), Josephine H Li, James A Perry, Kathleen A Jablonski, Shylaja Srinivasan, Ling Chen, Jennifer N Todd, Maegan Harden, Josep M Mercader, Qing Pan, Adem Y Dawed, Sook Wah Yee, Ewan R Pearson, Kathleen M Giacomini, Ayush Giri, Adriana M Hung, Shujie Xiao, L Keoki Williams, Paul W Franks, Robert L Hanson, Steven E Kahn, William C Knowler, Toni I Pollin, Jose C Florez, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide …

Metabolomic Profile Of The Healthy Eating Index-2015 In The Multiethnic Study Of Atherosclerosis, Meghana D Gadgil, Alexis C Wood, Ibrahim Karaman, Goncalo Graça, Ioanna Tzoulaki, Victor W Zhong, Philip Greenland, Alka M Kanaya, David M Herrington

Children’s Nutrition Research Center Staff Publications

Background: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version) are limited.

Objectives: The goal was to determine a pattern of metabolites associated with the Healthy Eating Index (HEI)-2015, which measures adherence to the Dietary Guidelines for Americans.

Methods: The analysis examined 3557 adult men and women from the longitudinal cohort Multiethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens and diet and demographic questionnaires were assessed at baseline. Untargeted 1H 1-dimensional nuclei magnetic …

Factors Associated With Choice Of Behavioural Weight Loss Program By Adults With Obesity, Yasaman Jamshidi-Naeini, Susan B Roberts, Stephanie Dickinson, Arthur Owora, Jon Agley, Roger S Zoh, Xiwei Chen, David B Allison

Children’s Nutrition Research Center Staff Publications

We assessed the preference for two behavioural weight loss programs, Diabetes Prevention Program (DPP) and Healthy Weight for Living (HWL) in adults with obesity. A cross-sectional survey was fielded on the Amazon Mechanical Turk. Eligibility criteria included reporting BMI ≥30 and at least two chronic health conditions. Participants read about the programs, selected their preferred program, and answered follow-up questions. The estimated probability of choosing either program was not significantly different from .5 (N = 1005, 50.8% DPP and 49.2% HWL, p = .61). Participants' expectations about adherence, weight loss magnitude, and dropout likelihood were associated with their choice (p <  .0001). Non-White participants (p = .040) and those with monthly income greater than $4999 (p = .002) were less likely to choose DPP. Participants who had postgraduate education (p = .007), did not report high serum cholesterol (p = .028), and reported not having tried losing weight before (p = .025) were more likely to choose DPP. Those who chose HWL were marginally more likely to report that being offered two different programs rather than one would likely affect their decision to enrol in one of the two (p = .052). The enrolment into DPP and HWL was balanced, but race, educational attainment, income, previous attempt to lose weight, and serum cholesterol levels had significant associations with the choice of weight loss program.

Undisclosed Outcome Switching, Undisclosed Analysis Switching, Inappropriate Rounding, And Selective Reporting Render Paper “Effectiveness Of A Minimally Processed Food-Based Nutritional Counselling Intervention On Weight Gain In Overweight Pregnant Women: A Randomized Controlled Trial” Unreliable, Armando Peña, Mike Gibney, Kevin Hall, Theodore K Kyle, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

T-Cell Receptor Beta Variable Gene Polymorphism Predicts Immune-Related Adverse Events During Checkpoint Blockade Immunotherapy, Bettzy Stephen, Joud Hajjar, Shrutii Sarda, Dzifa Yawa Duose, Jeffrey M Conroy, Carl Morrison, Anas Alshawa, Mingxuan Xu, Abdulrazzak Zarifa, Sapna P Patel, Ying Yuan, Evan Kwiatkowski, Linghua Wang, Jordi Rodon Ahnert, Siqing Fu, Funda Meric-Bernstam, Geoffrey M Lowman, Timothy Looney, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the …

Age Dependency Of Cardiovascular Outcomes With The Amyloidogenic Pv142i Transthyretin Variant Among Black Individuals In The Us, Senthil Selvaraj, Brian L Claggett, C Cristina Quarta, Bing Yu, Riccardo M Inciardi, Joel N Buxbaum, Thomas H Mosley, Amil M Shah, Sharmila Dorbala, Rodney H Falk, Scott D Solomon

Faculty, Staff and Student Publications

IMPORTANCE: Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.

OBJECTIVE: To estimate age-dependent risks for cardiovascular events with the variant.

DESIGN, SETTINGS, AND PARTICIPANTS: This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up …

The Development Of Artificial Intelligence-Based To Ols For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations and Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …

Auto-Segmentation In Pancreatic And Liver Radiation Therapy, Cenji Yu

Dissertations and Theses (Open Access)

Background

Gastrointestinal cancers exhibit a high mortality rate compared to other cancer types. Among these, pancreatic cancer ranks as the fourth leading cause of cancer-related deaths worldwide. The five-year survival rate remains alarmingly low at a mere 9%. Hepatocellular carcinoma (HCC), another aggressive form of cancer, is rapidly becoming the primary cause of cancer-related deaths in the United States. The treatment of both liver cancer and pancreatic cancer heavily relies on a multidisciplinary approach. Innovative treatment strategies involving dose-escalated regimens, such as stereotactic body radiation therapy (SBRT), are emerging as an important pillar of the management of liver and pancreatic …