Digital Commons Network^™

The Prostate Cancer Androgen Receptor Cistrome In African American Men Associates With Upregulation Of Lipid Metabolism And Immune Response, Jacob E Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K Dash, Jin Na Shin, Dallin Lowder, Collin Mccoll, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C Baca, Connor Bell, Heather M Mcclure, Talal El Zarif, Matthew P Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G Skapura, Sandra L Grimm, Christel M Davis, Erik A Ehli, Kaitlin M Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M Pomerantz, Massimo Loda, Michael Ittmann, Matthew L Freedman, Salma Kaochar

Faculty, Staff and Students Publications

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and …

Oropouche Orthobunyavirus Infection Is Mediated By The Cellular Host Factor Lrp1, Madeline M Schwarz, David A Price, Safder S Ganaie, Annie Feng, Nawneet Mishra, Ryan M Hoehl, Farheen Fatma, Sarah H Stubbs, Sean P J Whelan, Xiaoxia Cui, Takeshi Egawa, Daisy W Leung, Gaya K Amarasinghe, Amy L Hartman

2020-Current year OA Pubs

Oropouche orthobunyavirus (OROV;

Malic Enzyme 1 Absence In Synovial Sarcoma Shifts Antioxidant System Dependence And Increases Sensitivity To Ferroptosis Induction With Acxt-3102, Caitlyn B Brashears, Bethany C Prudner, Richa Rathore, Katharine E Caldwell, Sara E S Lange, Jennifer K Sehn, Dirk Spitzer, Regis O'Keefe, Jason M Held, William Hawkins, Brian A Van Tine, Carina A. Dehner, Et Al

2020-Current year OA Pubs

PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.

EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro …

Good Scientific Practice In Eeg And Meg Research: Progress And Perspectives, Guiomar Niso, Laurens R Krol, Etienne Combrisson, A Sophie Dubarry, Madison A Elliott, Clément François, Yseult Héjja-Brichard, Sophie K Herbst, Karim Jerbi, Vanja Kovic, Katia Lehongre, Steven J Luck, Manuel Mercier, John C Mosher, Yuri G Pavlov, Aina Puce, Antonio Schettino, Daniele Schön, Walter Sinnott-Armstrong, Bertille Somon, Anđela Šoškić, Suzy J Styles, Roni Tibon, Martina G Vilas, Marijn Van Vliet, Maximilien Chaumon

Faculty, Staff and Student Publications

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical …

Precision Dynamical Mapping Using Topological Data Analysis Reveals A Hub-Like Transition State At Rest, Manish Saggar, James M Shine, Raphaël Liégeois, Nico U F Dosenbach, Damien Fair

2020-Current year OA Pubs

In the absence of external stimuli, neural activity continuously evolves from one configuration to another. Whether these transitions or explorations follow some underlying arrangement or lack a predictable ordered plan remains to be determined. Here, using fMRI data from highly sampled individuals (~5 hours of resting-state data per individual), we aimed to reveal the rules that govern transitions in brain activity at rest. Our Topological Data Analysis based Mapper approach characterized a highly visited transition state of the brain that acts as a switch between different neural configurations to organize the spontaneous brain activity. Further, while the transition state was …

Technology-Delivered Adaptations Of Motivational Interviewing For The Prevention And Management Of Chronic Diseases: Scoping Review, Havisha Pedamallu, Matthew J Ehrhardt, Julia Maki, April Idalski Carcone, Melissa M Hudson, Erika A Waters

2020-Current year OA Pubs

BACKGROUND: Motivational interviewing (MI) can increase health-promoting behaviors and decrease health-damaging behaviors. However, MI is often resource intensive, precluding its use with people with limited financial or time resources. Mobile health-based versions of MI interventions or technology-delivered adaptations of MI (TAMIs) might increase reach.

OBJECTIVE: We aimed to understand the characteristics of existing TAMIs. We were particularly interested in the inclusion of people from marginalized sociodemographic groups, whether the TAMI addressed sociocontextual factors, and how behavioral and health outcomes were reported.

METHODS: We employed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews to conduct …

Online Randomised Factorial Trial Of Electronic Screening And Brief Intervention For Alcohol Use In Pregnancy: A Study Protocol, Steven J. Ondersma, Lisa Todd, Samantha Jablonski, Chaarushi Ahuja, Kathryn Gilstad-Hayden, Gregory Goyert, Amy M. Loree, Jaimee Heffner, Kimberly A. Yonkers

Center for Health Policy and Health Services Research Articles

INTRODUCTION: Approximately 1 in 7 pregnant women in the USA report past-month alcohol use. Strong evidence connects prenatal alcohol exposure with a range of adverse perinatal outcomes, including the spectrum of conditions known as fetal alcohol spectrum disorders. Screening and Brief Intervention (SBI) has been recommended for pregnant women but has proven difficult to implement. This study will test the efficacy of single-session technology-delivered SBI (electronic SBI) for alcohol use in pregnancy, while simultaneously evaluating the possible additional benefit of tailored text messages and/or booster sessions in a 3×2 factorial trial.

METHOD AND ANALYSIS: This full factorial trial will use …

The Use Of Objective Assessments In The Evaluation Of Technical Skills In Cardiothoracic Surgery: A Systematic Review, Nabil Hussein, Jef Van Den Eynde, Connor Callahan, Alvise Guariento, Can Gollmann-Tepeköylü, Malak Elbatarny, Mahmoud Loubani

2020-Current year OA Pubs

OBJECTIVES: With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula.

METHODS: Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological …

Risk Of Alzheimer’S Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching, Avram S Bukhbinder, Yaobin Ling, Omar Hasan, Xiaoqian Jiang, Yejin Kim, Kamal N Phelps, Rosemarie E Schmandt, Albert Amran, Ryan Coburn, Srivathsan Ramesh, Qian Xiao, Paul E Schulz

Faculty, Staff and Student Publications

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized.

OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years …

Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes In Using Elderly Donors, Shingo Shimada, Tayseer Shamaa, Tommy Ivanics, Toshihiro Kitajima, Kelly Collins, Michael Rizzari, Atsushi Yoshida, Marwan S. Abouljoud, Dilip Moonka, Mei Lu, Shunji Nagai

Surgery Articles

Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014-2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥ 70, 40-69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98-9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95-9.43); portal thrombus (aHR 1.87, 95%CI 1.26-2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34-6.20); and Karnofsky score 10-30% (aHR 2.03, 95%CI 1.13-3.65), 40-60% (aHR 1.65, 95%CI 1.08-2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss …

Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …

Informal And Incidental Learning In The Clinical Learning Environment: Learning Through Complexity And Uncertainty During Covid-19, Dimitrios Papanagnou, Karen E Watkins, Henriette Lundgren, Grace A Alcid, Deborah Ziring, Victoria J Marsick

Department of Emergency Medicine Faculty Papers

In the time of the COVID-19 pandemic, where clinical environments are plagued by both uncertainty and complexity, the importance of the informal and social aspects of learning among health care teams cannot be exaggerated. While there have been attempts to better understand the nuances of informal learning in the clinical environment through descriptions of the tacit or hidden curriculum, incidental learning in medical education has only been partially captured in the research. Understood through concepts borrowed from the Cynefin conceptual framework for sensemaking, the early stages of the pandemic immersed clinical teams in complex and chaotic situations where there was …

A Systematic Review And Meta-Analysis On Prevalence Of And Risk Factors Associated With Depression, Anxiety And Insomnia In Infectious Diseases, Including Covid-19: A Call To Action, Kai Yuan, Yong-Bo Zheng, Yi-Jie Wang, Yan-Kun Sun, Yi-Miao Gong, Yue-Tong Huang, Xuan Chen, Xiao-Xing Liu, Yi Zhong, Si-Zhen Su, Nan Gao, Yi-Long Lu, Zhe Wang, Wei-Jian Liu, Jian-Yu Que, Ying-Bo Yang, An-Yi Zhang, Meng-Ni Jing, Chen-Wei Yuan, Na Zeng, Michael V Vitiello, Vikram Patel, Seena Fazel, Harry Minas, Graham Thornicroft, Teng-Teng Fan, Xiao Lin, Wei Yan, Le Shi, Jie Shi, Thomas Kosten, Yan-Ping Bao, Lin Lu

Children’s Nutrition Research Center Staff Publications

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, …

State-Of-The-Art Review: Evidence On Red Meat Consumption And Hypertension Outcomes, Tara Shrout Allen, Harpreet S Bhatia, Alexis C Wood, Shabnam R Momin, Matthew A Allison

Children’s Nutrition Research Center Staff Publications

Hypertension (HTN) is a well-established risk factor for cardiovascular diseases (CVDs), including ischemic heart disease, stroke, heart failure, and atrial fibrillation. The prevalence of HTN, as well as mortality rates attributable to HTN, continue to increase, particularly in the United States and among Black populations. The risk of HTN involves a complex interaction of genetics and modifiable risk factors, including dietary patterns. In this regard, there is accumulating evidence that links dietary intake of red meat with a higher risk of poorly controlled blood pressure and HTN. However, research on this topic contains significant methodological limitations, which are described in …

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 …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients: Author Reply In Response To: “The Admission Serum Level Of Albumin Cannot Thoroughly Represent The Nutritional Status Of Trauma Patients”, Heather R Kregel, Patrick B Murphy, Mina Attia, David E Meyer, Rachel S Morris, Ezenwa C Onyema, Sasha D Adams, Charles E Wade, John A Harvin, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

BACKGROUND: Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS: This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI98). The primary outcome was mortality. Secondary outcomes …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

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 …

Antibody Evasion By Sars-Cov-2 Omicron Subvariants Ba2121, Ba4 And Ba5, Qian Wang, Yicheng Guo, Sho Iketani, Manoj S Nair, Zhiteng Li, Hiroshi Mohri, Maple Wang, Jian Yu, Anthony D Bowen, Jennifer Y Chang, Jayesh G Shah, Nadia Nguyen, Zhiwei Chen, Kathrine Meyers, Michael T Yin, Magdalena E Sobieszczyk, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D Ho

Faculty, Staff and Student Publications

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Factors Associated With Parental Acceptance Of Covid-19 Vaccination: A Multicenter Pediatric Emergency Department Cross-Sectional Analysis, Brigitte M Baumann, Robert M Rodriguez, Amy M Delaroche, David Rayburn, Stephanie A Eucker, Nicole L Nadeau, Lisa A Drago, Danielle Cullen, Sarah Dennis Meskill, Suzanne Bialeck, Michael Gillman

Faculty, Staff and Students Publications

STUDY OBJECTIVE: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients.

METHODS: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance.

RESULTS: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents …

Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, Sharon Pan, Lisa A Lai, Diane M Simeone, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall

Faculty, Staff and Students Publications

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE).

RESULTS: More than 1400 nonredundant proteins were identified …

Integrated Multi-Omic Characterization Of Congenital Heart Disease, Matthew C Hill, Zachary A Kadow, Hali Long, Yuka Morikawa, Thomas J Martin, Emma J Birks, Kenneth S Campbell, Jeanne Nerbonne, Kory Lavine, Lalita Wadhwa, Jun Wang, Diwakar Turaga, Iki Adachi, James F Martin

Faculty, Staff and Students Publications

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We …

Safety And Efficacy Of Voxelotor In Pediatric Patients With Sickle Cell Disease Aged 4 To 11 Years., Jeremie H. Estepp, Ram Kalpatthi, Gerald Woods, Sara Trompeter, Robert I. Liem, Kacie Sims, Adlette Inati, Baba P D Inusa, Andrew Campbell, Connie Piccone, Miguel R. Abboud, Kim Smith-Whitley, Sandra Dixon, Margaret Tonda, Carla Washington, Noelle M. Griffin, Clark Brown

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality.

PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization …

Novel Mitochondria-Targeting Compounds Selectively Kill Human Leukemia Cells, Svetlana B Panina, Jingqi Pei, Natalia Baran, Elissa Tjahjono, Shraddha Patel, Gheath Alatrash, Sergej Konoplev, Leonid A Stolbov, Vladimir V Poroikov, Marina Konopleva, Natalia V Kirienko

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive hematological malignancies commonly associated with treatment resistance, high risk of relapse, and mitochondrial dysregulation. We identified six mitochondria-affecting compounds (PS compounds) that exhibit selective cytotoxicity against AML cells in vitro. Structure-activity relationship studies identified six analogs from two original scaffolds that had over an order of magnitude difference between LD50 in AML and healthy peripheral blood mononuclear cells. Mechanistically, all hit compounds reduced ATP and selectively impaired both basal and ATP-linked oxygen consumption in leukemic cells. Compounds derived from PS127 significantly upregulated production of reactive oxygen species (ROS) in AML …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Fetal Loss In Pregnant Rhesus Macaques Infected With High-Dose African-Lineage Zika Virus, Lauren E. Raasch, Kevin K. Noguchi, Nicole A. Fuhler, Et Al

2020-Current year OA Pubs

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant …

Sexual Orientation And Gender Identity Data Collection In Oncology Practice: Findings Of An Asco Survey, Charles S Kamen, Mandi L Pratt-Chapman, Stephen C Meersman, Gwendolyn P Quinn, Matthew B Schabath, Shail Maingi, Janette K Merrill, Elizabeth Garrett-Mayer, Melinda Kaltenbaugh, Caroline Schenkel, Shine Chang

Faculty, Staff and Student Publications

Purpose: Lack of collection of sexual orientation and gender identity (SOGI) data in oncology practices limits assessment of sexual and gender minority (SGM) cancer patients' experiences and restricts opportunities to improve health outcomes of SGM patients. Despite national calls for routine SOGI data collection, individual-level and institutional barriers hinder progress. This study aimed to identify these barriers in oncology.

Methods: An online survey of ASCO members and others assessed SOGI data collection in oncology practices, institutional characteristics related to SOGI data collection, respondents' attitudes about SOGI data and SGM patients, and respondent demographics. Logistic regression calculated adjusted odds ratios (ORs) …

Patient Preferences For Strategies To Improve Tuberculosis Diagnostic Services In Zambia, Andrew D Kerkhoff, Lophina Chilukutu, Sarah Nyangu, Mary Kagujje, Kondwelani Mateyo, Nsala Sanjase, Ingrid Eshun-Wilson, Elvin H Geng, Diane V Havlir, Monde Muyoyeta

2020-Current year OA Pubs

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.

Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.

Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was …