Digital Commons Network^™

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Faculty, Staff and Student Publications

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Insights From A Large-Scale Whole-Genome Sequencing Study Of Systolic Blood Pressure, Diastolic Blood Pressure, And Hypertension, Tanika N Kelly, Xiao Sun, Karen Y He, Michael R Brown, Sarah A Gagliano Taliun, Jacklyn N Hellwege, Marguerite R Irvin, Xuenan Mi, Jennifer A Brody, Nora Franceschini, Xiuqing Guo, Shih-Jen Hwang, Paul S De Vries, Yan Gao, Arden Moscati, Girish N Nadkarni, Lisa R Yanek, Tali Elfassy, Jennifer A Smith, Ren-Hua Chung, Amber L Beitelshees, Amit Patki, Stella Aslibekyan, Brandon M Blobner, Juan M Peralta, Themistocles L Assimes, Walter R Palmas, Chunyu Liu, Adam P Bress, Zhijie Huang, Lewis C Becker, Chii-Min Hwa, Jeffrey R O'Connell, Jenna C Carlson, Helen R Warren, Sayantan Das, Ayush Giri, Lisa W Martin, W Craig Johnson, Ervin R Fox, Erwin P Bottinger, Alexander C Razavi, Dhananjay Vaidya, Lee-Ming Chuang, Yen-Pei C Chang, Take Naseri, Deepti Jain, Hyun Min Kang, Adriana M Hung, Vinodh Srinivasasainagendra, Beverly M Snively, Dongfeng Gu, May E Montasser, Muagututi'a Sefuiva Reupena, Benjamin D Heavner, Jonathon Lefaive, James E Hixson, Kenneth M Rice, Fei Fei Wang, Jonas B Nielsen, Jianfeng Huang, Alyna T Khan, Wei Zhou, Jovia L Nierenberg, Cathy C Laurie, Nicole D Armstrong, Mengyao Shi, Yang Pan, Adrienne M Stilp, Leslie Emery, Quenna Wong, Nicola L Hawley, Ryan L Minster, Joanne E Curran, Patricia B Munroe, Daniel E Weeks, Kari E North, Russell P Tracy, Eimear E Kenny, Daichi Shimbo, Aravinda Chakravarti, Stephen S Rich, Alex P Reiner, John Blangero, Susan Redline, Braxton D Mitchell, Dabeeru C Rao, Yii-Der Ida Chen, Sharon L R Kardia, Robert C Kaplan, Rasika A Mathias, Jiang He, Bruce M Psaty, Myriam Fornage, Ruth J F Loos, Adolfo Correa, Eric Boerwinkle, Jerome I Rotter, Charles Kooperberg, Todd L Edwards, Gonçalo R Abecasis, Xiaofeng Zhu, Daniel Levy, Donna K Arnett, Alanna C Morrison, Samoan Obesity, Lifestyle, And Genetic Adaptations Study (Olaga) Group,‡ Nhlbi Trans-Omics For Precision Medicine Topmed) Consortium

Faculty, Staff and Student Publications

BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

RESULTS: Two blood pressure signals …

Use Of Active Video Games With Or Without Videoconferencing On Health Outcomes In Adolescent And Young Adult Cancer Survivors: A Systematic Review, Ursela Christopherson, Stephanie J Wells, Nathan Parker, Elizabeth J Lyons, Michael D Swartz, Anna Blozinski, Karen Basen-Engquist, Susan Peterson, Maria C Swartz

Faculty, Staff and Student Publications

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience greater functional deficits compared to non-cancer peers or older survivors with a similar diagnosis. Physical activity (PA) is a key strategy for mitigating functional decline, and motivation and peer support are critical PA facilitators in AYA cancer survivors. Active video games (AVGs) may be a "gateway" method to promote PA. Further, integrating AVGs into group videoconferencing, a medium used by AYAs to socialize, can capitalize on peer support needed for PA motivation. Thus, we examined the use of AVGs and/or videoconferencing in PA interventions that included AYA survivors and the effect …

Racial And Ethnic Disparities In The Refusal Of Surgical Treatment In Women 40 Years And Older With Breast Cancer In The Usa Between 2010 And 2017, Pierre Fwelo, Zenab I Yusuf, Abigail Adjei, Gabriel Huynh, Xianglin L Du

Faculty, Staff and Student Publications

PURPOSE: Although surgical resection is the main modality of treatment for breast cancer, some patients elect to refuse the recommended surgery. We assessed racial and ethnic differences in women 40 years and older who received or refused to receive surgical treatment for breast cancer in the USA and whether racial disparities in mortality were affected by their differences in the prevalence of refusal for surgical treatment.

METHODS: We studied 277,127 women with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) data and performed multivariable logistic regressions to investigate the association between surgery status of breast cancer and race/ethnicity. …

A Systematic Review Up To 2018 Of Hiv And Associated Factors Among Criminal Justice-Involved (Cji) Black Sexual And Gender Minority Populations In The United States (Us), Russell Brewer, Santhoshini L Ramani, Aditya Khanna, Kayo Fujimoto, John A Schneider, Anna Hotton, Leo Wilton, Tania Escobedo, Nina T Harawa

Faculty, Staff and Student Publications

Black men who have sex with men (BMSM) and Black transgender women (BTW) are impacted by dual epidemics of HIV and incarceration. We advanced understanding of the relationship between criminal justice involvement, HIV, and other key HIV-related characteristics among these key populations in the US. We conducted a systematic review up to 2018 and 47 articles met the inclusion criteria of scientific publications involving quantitative findings of US-based HIV-related studies focused on criminal justice-involved (CJI) BMSM and BTW. Overall, there was a dearth of studies focused specifically on BTW. Criminal justice involvement was relatively high among BMSM and BTW and …

Impact Of Somatic Mutations On Survival Outcomes In Patients With Anaplastic Thyroid Carcinoma, Jennifer Rui Wang, Matthew Montierth, Li Xu, Maitrayee Goswami, Xiao Zhao, Gilbert Cote, Wenyi Wang, Priyanka Iyer, Ramona Dadu, Naifa L Busaidy, Stephen Y Lai, Neil D Gross, Renata Ferrarotto, Charles Lu, Gary Brandon Gunn, Michelle D Williams, Mark Routbort, Mark E Zafereo, Maria E Cabanillas

Faculty, Staff and Student Publications

PURPOSE: Anaplastic thyroid carcinoma (ATC) uniformly present with aggressive disease, but the mutational landscape of tumors varies. We aimed to determine whether tumor mutations affect survival outcomes in ATC.

MATERIALS AND METHODS: Patients who underwent mutation sequencing using targeted gene panels between 2005 and 2019 at a tertiary referral center were included. Associations between mutation status and survival outcomes were assessed using Cox proportional hazards models.

RESULTS: A total of 202 patients were included, where 122 died of ATC (60%). The median follow-up was 31 months (interquartile range, 18-45 months). The most common mutations were in

CONCLUSION: Mutation analysis provides …

Prediction Of Breast Cancer-Related Lymphedema By Dermal Backflow Detected With Near-Infrared Fluorescence Lymphatic Imaging, Melissa B Aldrich, John C Rasmussen, Sarah M Desnyder, Wendy A Woodward, Wenyaw Chan, Eva M Sevick-Muraca, Elizabeth A Mittendorf, Benjamin D Smith, Michael C Stauder, Eric A Strom, George H Perkins, Karen E Hoffman, Melissa P Mitchell, Carlos H Barcenas, Lynn E Isales, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL.

METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and …

A Cluster-Randomized Controlled Trial To Assess The Impact Of A Nutrition Intervention On Dietary Behaviors Among Early Care And Education Providers: The Create Healthy Futures Study, Dania Mofleh, Ru-Jye Chuang, Nalini Ranjit, Jill N Cox, Christine Anthony, Shreela V Sharma

Faculty, Staff and Student Publications

Create Healthy Futures is a self-paced, web-based intervention on improving healthy eating behaviors among Early Care and Education (ECE) providers. We examined the impact of web-based Create Healthy Futures on diet quality measured by the Alternative Healthy Eating Index (AHEI) 2010, dietary behaviors, and related psychosocial and environmental factors among ECE providers. A cluster randomized controlled trial (CRCT) was implemented with baseline surveys administered from October 2019-January 2020, intervention implementation from April-May 2020, and post-intervention from May 2020-August 2020. Centered-based ECE programs under the Pennsylvania Head Start Association (n = 12) were recruited and randomized to intervention (n = 5) …

Perceived Discrimination And Injury At Work: A Cross-Sectional Study Among Latino Day Laborers, Lynn N Ibekwe, John S Atkinson, Rosalia Guerrero-Luera, Yesmel A King, Maria L Rangel, Maria Eugenia Fernández-Esquer

Faculty, Staff and Student Publications

BACKGROUND: Given the stigma of their undocumented status and their high prevalence of workplace injury, understanding the impact of discrimination on Latino day laborers (LDLs) is a critical public health issue.

METHODS: We surveyed LDLs (N = 149) and assessed their sociodemographics, experiences of and perceived reasons for discrimination, and work-related injury. A logistic regression examined the association between discrimination and injury, adjusting for sociodemographics. Next, Chi-square tests identified perceived reasons for discrimination associated with injury which were then included in a second logistic regression to test their association with injury, adjusting for discrimination and sociodemographics.

RESULTS: Participants reported a …

Perceived Discrimination And Injury At Work: A Cross-Sectional Study Among Latino Day Laborers, Lynn N Ibekwe, John S Atkinson, Rosalia Guerrero-Luera, Yesmel A King, Maria L Rangel, Maria Eugenia Fernández-Esquer

Faculty, Staff and Student Publications

BACKGROUND: Given the stigma of their undocumented status and their high prevalence of workplace injury, understanding the impact of discrimination on Latino day laborers (LDLs) is a critical public health issue.

METHODS: We surveyed LDLs (N = 149) and assessed their sociodemographics, experiences of and perceived reasons for discrimination, and work-related injury. A logistic regression examined the association between discrimination and injury, adjusting for sociodemographics. Next, Chi-square tests identified perceived reasons for discrimination associated with injury which were then included in a second logistic regression to test their association with injury, adjusting for discrimination and sociodemographics.

RESULTS: Participants reported a …

Awareness Of Human Papillomavirus And Reported Human Papillomavirus Vaccine Uptake In A High-Risk Population, Trisha L Amboree, Jane R Montealegre, Paige Padgett Wermuth, Osaro Mgbere, Kayo Fujimoto, Charles Darkoh

Faculty, Staff and Student Publications

INTRODUCTION: Disparities in human papillomavirus (HPV) awareness and HPV vaccine uptake are likely exacerbated among racial/ethnic minority populations living in low-income areas. This study aims to determine the prevalence and correlates of HPV awareness and HPV vaccine uptake in an urban, low-income, racial/ethnic minority population.

METHODS: Secondary data analyses were performed in 2021 using 380 participants aged 18-45 years from the 2019 National HIV Behavioral Surveillance for high-risk heterosexuals, which monitors HIV risk behaviors among individuals living in high-poverty, high HIV prevalence neighborhoods. Prevalence estimates and modified Poisson regression models were used to assess the relationship between HPV awareness and …

Association Of Disease Outcomes With Physical Activity In Multiple Sclerosis: A Cross-Sectional Study, Trinh L T Huynh, Stephanie L Silveira, Brenda Jeng, Robert W Motl

Faculty, Staff and Student Publications

Purpose/Objective Research: This study examined combinations of disease outcomes (i.e., walking, cognition, and symptoms) as correlates of physical activity subgroups (insufficiently active vs. sufficiently active) in persons with multiple sclerosis (MS).

RESEARCH METHOD/DESIGN: This study included 213 participants who completed walking and cognitive function tests and self-report measures of symptoms and physical activity. Multivariate analysis of variance and discriminant function analysis identified combinations of MS outcomes associated with physical activity.

RESULTS: The sample had a mean age of 49.6 years (

CONCLUSION/IMPLICATIONS: The findings identified walking endurance and limitations, processing speed, depression, and fatigue as primary correlates of physical activity …

Mediating And Maintaining Methylation While Minimizing Mutation: Recent Advances On Mammalian Dna Methyltransferases, Xiaodong Cheng, Robert M Blumenthal

Faculty, Staff and Student Publications

Mammalian genomes are methylated on carbon-5 of many cytosines, mostly in CpG dinucleotides. Methylation patterns are maintained during mitosis via DNMT1, and regulatory factors involved in processes that include histone modifications. Methylation in a sequence longer than CpG can influence the binding of sequence-specific transcription factors, thus affecting gene expression. 5-Methylcytosine deamination results in C-to-T transition. While some mutations are beneficial, most are not; so boosting C-to-T transitions can be dangerous. Given the role of DNMT3A in establishing de novo DNA methylation during development, it is this CpG methylation and deamination that provide the major mutagenic impetus in the DNMT3A …

Assessing The Practicality Of Using A Single Knowledge-Based Planning Model For Multiple Linac Vendors, Raphael J Douglas, Adenike Olanrewaju, Lifei Zhang, Beth M Beadle, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Knowledge-based planning (KBP) has been shown to be an effective tool in quality control for intensity-modulated radiation therapy treatment planning and generating high-quality plans. Previous studies have evaluated its ability to create consistent plans across institutions and between planners within the same institution as well as its use as teaching tool for inexperienced planners. This study evaluates whether planning quality is consistent when using a KBP model to plan across different treatment machines.

Materials and methods: This study used a RapidPlan model (Varian Medical Systems) provided by the vendor, to which we added additional planning objectives, maximum dose limits, …

Love And Fear: A Special Issue, C Sue Carter, Robert Dantzer

Faculty, Staff and Student Publications

Love and fear were forged by the same fundamental evolutionary processes that permitted life on Earth. Both love and fear are deeply interwoven with the adaptive management of stress and disease. Love and fear share common roots and both can play a role in reproduction, survival, perceived safety and wellbeing. This special issue of Comprehensive Psychoneuroendocrinology focuses specifically on the causes and consequences of love from the interactive perspectives of evolution, neurobiology and culture.

Clinical Activity Of Mitogen-Activated Protein Kinase-Targeted Therapies In Patients With Non-V600 Braf-Mutant Tumors, Matthew Dankner, Yifan Wang, Rouhi Fazelzad, Benny Johnson, Caroline A Nebhan, Ibiayi Dagogo-Jack, Nathaniel J Myall, Georg Richtig, Jillian W P Bracht, Marco Gerlinger, Eiji Shinozaki, Takayuki Yoshino, Daisuke Kotani, Jason R Fangusaro, Oliver Gautschi, Julien Mazieres, Jeffrey A Sosman, Scott Kopetz, Vivek Subbiah, Michael A Davies, Anna L Groover, Ryan J Sullivan, Keith T Flaherty, Douglas B Johnson, Andrea Benedetti, David W Cescon, Anna Spreafico, George Zogopoulos, April A N Rose

Faculty, Staff and Student Publications

Purpose: Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.

Methods: We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, …

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Albiruni Abdul Razak, Neeta Somaiah, Sant Chawla, Javier Martin-Broto, Giovanni Grignani, Scott M Schuetze, Bruno Vincenzi, Andrew J Wagner, Bartosz Chmielowski, Robin L Jones, Richard F Riedel, Silvia Stacchiotti, Elizabeth T Loggers, Kristen N Ganjoo, Axel Le Cesne, Antoine Italiano, Xavier Garcia Del Muro, Melissa Burgess, Sophie Piperno-Neumann, Christopher Ryan, Mary F Mulcahy, Charles Forscher, Nicolas Penel, Scott Okuno, Anthony Elias, Lee Hartner, Tony Philip, Thierry Alcindor, Bernd Kasper, Peter Reichardt, Lore Lapeire, Jean-Yves Blay, Christine Chevreau, Claudia Maria Valverde Morales, Gary K Schwartz, James L Chen, Hari Deshpande, Elizabeth J Davis, Garth Nicholas, Stefan Gröschel, Helen Hatcher, Florence Duffaud, Antonio Casado Herráez, Roberto Diaz Beveridge, Giuseppe Badalamenti, Mikael Eriksson, Christian Meyer, Margaret Von Mehren, Brian A Van Tine, Katharina Götze, Filomena Mazzeo, Alexander Yakobson, Aviad Zick, Alexander Lee, Anna Estival Gonzalez, Andrea Napolitano, Mark A Dickson, Dayana Michel, Changting Meng, Lingling Li, Jianjun Liu, Osnat Ben-Shahar, Dane R Van Domelen, Christopher J Walker, Hua Chang, Yosef Landesman, Jatin J Shah, Sharon Shacham, Michael G Kauffman, Steven Attia

Faculty, Staff and Student Publications

Purpose: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

Methods: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Regulation And Function Of Id2 In Plasmacytoid Dendritic Cells, Rachel L Babcock, Yifan Zhou, Bhakti Patel, Taylor T Chrisikos, Laura M Kahn, Allison M Dyevoich, Yusra B Medik, Stephanie S Watowich

Faculty, Staff and Student Publications

Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-I) producing cells that promote anti-viral immune responses and contribute to autoimmunity. Development of pDCs requires the transcriptional regulator E2-2 and is opposed by inhibitor of DNA binding 2 (Id2). Prior work indicates Id2 is induced in pDCs upon maturation and may affect pDC IFN-I production via suppression of E2-2, suggesting an important yet uncharacterized role in this lineage. We found TLR7 agonists stimulate Id2 mRNA and protein expression in pDCs. We further show that transcriptional activation of Id2 is dependent on the E2 ubiquitin-conjugating enzyme Ubc13, but independent of IFN-I …

Probing The Structure And Function Of Polymerase Θ Helicase-Like Domain, Scott Vanson, Yuzhen Li, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

DNA Polymerase θ is the key actuator of the recently identified double-strand break repair pathway, theta-mediated end joining (TMEJ). It is the only known polymerase to have a 3-domain architecture containing an independently functional family A DNA polymerase tethered by a long central region to an N-terminal helicase-like domain (HLD). Full-length polymerase θ and the isolated HLD hydrolyze ATP in the presence of DNA, but no processive DNA duplex unwinding has been observed. Based on sequence and structure conservation, the HLD is classified as a member of helicase superfamily II and, more specifically, the Ski2-like family. The specific subdomain composition …

Mechanism Of Neonatal Hypoglycemia After Late Preterm Steroids: Are Fetal Metabolic Effects Responsible?, Ashley N Battarbee, Grecio J Sandoval, Cynthia Gyamfi-Bannerman, Sean C Blackwell, Alan T N Tita, Uma M Reddy, Lucky Jain

Faculty, Staff and Student Publications

OBJECTIVE:

Betamethasone administration in the late preterm period(340/7–365/7 weeks’ gestation) not only reduces neonatal respiratory morbidity but also increases neonatal hypoglycemia through an uncertain mechanism.¹ Based on data from pregnant individuals with diabetes, excessive amounts of maternal glucose can cross the placenta and cause fetal hyperinsulinemia, which can cause neonatal hypoglycemia at birth.² Given that betamethasone can also increase maternal glucose levels,³ our objective was to explore the potential mechanisms for late preterm steroid-induced neonatal hypoglycemia by measuring the fetal metabolic effects of antenatal late preterm betamethasone and assessing the relationship of the fetal metabolic effects with …

Detecting Cognitive Impairment And Dementia In The Emergency Department: A Scoping Review, Armin Nowroozpoor, Jeff Dussetschleger, William Perry, Mary Sano, Amy Aloysi, Michael Belleville, Alexandria Brackett, Jon Mark Hirshon, William Hung, Joan Michelle Moccia, Ugochi Ohuabunwa, Manish N Shah, Ula Hwang

Faculty, Staff and Student Publications

OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).

DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.

SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients.

METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and …

Association Of Gangrenous, Suppurative, And Exudative Findings With Outcomes And Resource Utilization In Children With Nonperforated Appendicitis, Shannon L Cramm, Aaron M Lipskar, Dionne A Graham, Shaun M Kunisaki, Cornelia L Griggs, Myron Allukian, Robert T Russell, Nicole M Chandler, Matthew T Santore, Danielle I Aronowitz, Martin L Blakely, Brendan Campbell, Devon T Collins, Sarah J Commander, Robert A Cowles, Jennifer R Defazio, Justice C Echols, Joseph R Esparaz, Christina Feng, Richard A Guyer, David N Hanna, Katherine He, Anastasia M Kahan, Olivia A Keane, Abdulraouf Lamoshi, Carla M Lopez, Sean E Mclean, Elizabeth Pace, Maia D Regan, Stefan Scholz, Elisabeth T Tracy, Sasha A Williams, Lucy Zhang, Shawn J Rangel

Faculty, Staff and Student Publications

IMPORTANCE: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis.

OBJECTIVE: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study …

Emergency Department Communication In Persons Living With Dementia And Care Partners: A Scoping Review, Christopher R Carpenter, Jesseca Leggett, Fernanda Bellolio, Marian Betz, Ryan M Carnahan, David Carr, Michelle Doering, Jennie Chin Hansen, Eric D Isaacs, Deborah Jobe, Kathleen Kelly, Nancy Morrow-Howell, Beth Prusaczyk, Bob Savage, Joe Suyama, Allan S Vann, Kristin L Rising, Ula Hwang, Manish N Shah

Faculty, Staff and Student Publications

OBJECTIVES: To synthesize published research exploring emergency department (ED) communication strategies and decision-making with persons living with dementia (PLWD) and their care partners as the basis for a multistakeholder consensus conference to prioritize future research.

DESIGN: Systematic scoping review.

SETTINGS AND PARTICIPANTS: PLWD and their care partners in the ED setting.

METHODS: Informed by 2 Patient-Intervention-Comparison-Outcome (PICO) questions, we conducted systematic electronic searches of medical research databases for relevant publications following standardized methodological guidelines. The results were presented to interdisciplinary stakeholders, including dementia researchers, clinicians, PLWD, care partners, and advocacy organizations. The PICO questions included: How does communication differ for …

Association Of Changes In Antithrombin Activity Over Time With Responsiveness To Enoxaparin Prophylaxis And Risk Of Trauma-Related Venous Thromboembolism, Laura E Vincent, Michael M Talanker, Dakota D Butler, Xu Zhang, Jeanette M Podbielski, Yao-Wei W Wang, Amber Chen-Goodspeed, Selina L Hernandez Gonzalez, Erin E Fox, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity < 80%).

Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis.

Design, setting, and participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January …

Predictors Of Disease Activity And Worsening In Relapsing-Remitting Multiple Sclerosis, Yinan Zhang, Stacey Cofield, Gary Cutter, Stephen Krieger, Jerry S Wolinsky, Fred Lublin

Faculty, Staff and Student Publications

Background and objectives: Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening.

Methods: The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of …

Event-Related Phase Synchronization Propagates Rapidly Across Human Ventral Visual Cortex, Oscar Woolnough, Kiefer J Forseth, Patrick S Rollo, Zachary J Roccaforte, Nitin Tandon

Faculty, Staff and Student Publications

Visual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression …

Complication Rates In Patients Using Intracavernosal Injection Therapy For Erectile Dysfunction With Or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study, Kyle A Blum, Justin P Mehr, Travis Green, Lauren Conroy, Vanessa Marino, Daniel Kim, Kailash Panchapakesan, Liam Murphy, Sravan Panuganti, Run Wang

Faculty, Staff and Student Publications

Background: Intracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI.

Aim: We sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use.

Methods: We reviewed our institutional electronic health record and identified 168 patients who were seen in …

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity In Human Sensory Neuron Somata Parallel Alterations Described In Spontaneously Active Rodent Nociceptors, Robert Y North, Max A Odem, Yan Li, Claudio Esteves Tatsui, Ryan M Cassidy, Patrick M Dougherty, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to …

3’Utr Shortening Of Has2 Promotes Hyaluronan Hyper-Synthesis And Bioenergetic Dysfunction In Pulmonary Hypertension, Victor Tseng, Scott D Collum, Ayed Allawzi, Kathryn Crotty, Samantha Yeligar, Aaron Trammell, M Ryan Smith, Bum-Yong Kang, Roy L Sutliff, Jennifer L Ingram, Soma S S K Jyothula, Rajarajan A Thandavarayan, Howard J Huang, Eva S Nozik, Eric J Wagner, C Michael Hart, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH. Herein, we identified HA synthase-2 (HAS2) in the pulmonary artery smooth muscle cell (PASMC) layer as a predominant locus of HA dysregulation. HA upregulation involves depletion of NUDT21, a master regulator of …

Covid-19: Perceived Infection Risk And Barriers To Uptake Of Pfizer-Biontech And Moderna Vaccines Among Community Healthcare Workers, Tolulope B Famuyiro, Abayomi Ogunwale, Jude Des Bordes, Mukaila Raji

Faculty, Staff and Student Publications

Background: The health and economic ramifications of the coronavirus pandemic have prompted the need for a timely and effective vaccine development. While the rollout of the COVID-19 vaccine in record time is being hailed as a scientific feat, skepticism about the safety, side effects, and even its long-term effects remain. Acceptance of the vaccine may therefore be a challenge among healthcare workers (HCWs), whose role is considered a proxy to determining the COVID-19 vaccine uptake response by the general population.

Methods: In December 2020, prior to the arrival and receipt of the Pfizer-BioNTech and Moderna COVID-19 vaccine, we conducted a …