Digital Commons Network^™

A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1a (CK1a) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1a enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1a phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of …

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K. Russell, Chad J. Creighton, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box–binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small- molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic …

Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated …

Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss

Markey Cancer Center Faculty Publications

The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …

In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun

Markey Cancer Center Faculty Publications

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …

Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng

Markey Cancer Center Faculty Publications

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both …

The Influence Of Management On Health Status Of Festuca Rubra In Mountain Meadows, B. Voženílková, F. Klimeš, J. Květ, Z. Mašková, B. Čermák, K. Suchý

IGC Proceedings (1977-2023)

Snijders & Winkelhorst (1996) investigated swards in West Europe and showed that it was not the snow mould (Microdochium nivale) but other species of the genus Fusarium (F. cerealis (Cooke) Sacc., F. graminearum Schwabe, F. culmorum (Wm. G. Sm.) Sacc. and F. acuminatum Ellis & Everh.) that caused serious damage to grasslands where Lolium perenne L. and Festuca rubra L. were dominant components. In this study the spread and harmfulness of pathogeneous fungi involved in damage to and death of some species (Festuca rubra L., Holcus mollis L.) in grass swards was examined.

Adult Asthma Associated With Roadway Density And Housing In Rural Appalachia: The Mountain Air Project (Map)., W Jay Christian, John Flunker, Beverly May, Susan Westneat, Wayne T Sanderson, Nancy Schoenberg, Steven R Browning

UK CARES Faculty Publications

BACKGROUND: Appalachian Kentucky is a rural area with a high prevalence of asthma among adults. The relative contribution of environmental exposures in the etiology of adult asthma in these populations has been understudied.

OBJECTIVE: This manuscript describes the aims, study design, methods, and characteristics of participants for the Mountain Air Project (MAP), and focuses on associations between small area environmental exposures, including roadways and mining operations, and lifetime and current asthma in adults.

METHODS: A cohort of residents, aged 21 and older, in two Kentucky counties, was enrolled in a community-based, cross-sectional study. Stratified cluster sampling was used to select …

The Association Between Comorbidities And Self-Care Of Heart Failure: A Cross-Sectional Study, Kyoung Suk Lee, Debra K. Moser, Kathleen Dracup

Nursing Faculty Publications

Background Because heart failure (HF) is a debilitating chronic cardiac condition and increases with age, most patients with HF experience a broad range of coexisting chronic morbidities. Comorbidities present challenges for patients with HF to successfully perform self-care, but it is unknown what types and number of comorbidities influence HF patients’ self-care. The purpose of this study was to explore whether the number of cardiovascular and non-cardiovascular conditions are associated with HF self-care.

Methods Secondary data analysis was performed with 590 patients with HF. The number of cardiovascular and noncardiovascular conditions was calculated using the list of conditions in the …

Global Dna Adenine Methylation In Caenorhabditis Elegans After Multigenerational Exposure To Silver Nanoparticles And Silver Nitrate, Anye Wamucho, Jason M. Unrine, John May, Olga V. Tsyusko

UK CARES Faculty Publications

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO3 ). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-20 -deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO₃ . Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F₀) after two generations of exposure (F₂) and two generations of …

Role Of The Banyuls(Ban) Gene From Arabidopsis Thaliana In Transgenic Alfalfa Expression Of Anthocyanins And Proanthocyanidins, S. M. Hesamzadeh Hejazi, Sergio Arcioni, F. Paolocci

IGC Proceedings (1977-2023)

Condensed tannins (CTs) are flavonoid oligomers, many of which have beneficial effects on animal (bloat safe) and human health. The BAN gene encodes anthocyanidin reductase (ANR), an enzyme proposed to convert anthocyanidins to their corresponding 2,3-cis-flavan-3-ols (Xie et al., 2003). Ectopic expression of BAN in Alfalfa transgenic foliage results in accumulation of CTs. Thus, it has been assumed that the BAN gene also acts in starter units for the condensation of tannins in Alfalfa.

Child Traumatic Stress And Covid-19: The Impact Of The Pandemic On A Clinical Sample Of Children In Trauma Treatment, Ginny Sprang, Jessica G. Eslinger, Adrienne Whitt-Woosley, Stephanie Gusler, Tracy Clemans

Psychiatry Faculty Publications

Given the scope and duration of the COVID-19 pandemic, it is not surprising that research has documented negative effects to youth’s mental health. Yet, there is negligible research on the impact of the pandemic among clinical samples of youth receiving treatment for pre-existing trauma exposure and symptoms. The current study investigates COVID-19 as an index trauma, and if prior traumatic stress scores mediate the relationship between pandemic-related exposure and subsequent traumatic stress. Methods: This is a study of 130 youth ages 7–18 receiving trauma treatment at an academic medical center. The University of California Los Angeles Post-traumatic Stress Disorder-Reaction Index …

Magnetic Nanocomposites For The Remote Activation Of Sulfate Radicals For The Removal Of Rhodamine B, Pranto Paul, Marissa Nicholson, J. Zach Hilt

Chemical and Materials Engineering Faculty Publications

The widespread presence of numerous organic contaminants in water poses a threat to the ecological environment and human health. Magnetic nanocomposites exposed to an alternating magnetic field (AMF) have a unique ability for magnetically mediated energy delivery (MagMED) resulting from the embedded magnetic nanoparticles; this localized energy delivery and associated chemical and thermal effects are a potential method for removing contaminants from water. This work developed a novel magnetic nanocomposite—a polyacrylamide-based hydrogel loaded with iron oxide nanoparticles. For this magnetic nanocomposite, persulfate activation and the contamination removal in water were investigated. Magnetic nanocomposites were exposed to AMF with a model …

Eating Biodiversity: Investigating The Links Between Grassland Biodiversity And Quality Food Production, A. Hopkins, H. Buller, C. Morris, J. D. Wood

IGC Proceedings (1977-2023)

Modern food production systems are generally detrimental to biodiversity, and the widespread loss of species-diverse grassland as a consequence of intensive farming methods is well documented. Since the 1980s, a range of policy measures and financial incentives for farmers have been introduced in Europe to halt (and in some cases, reverse) this trend, primarily to meet environmental objectives of species and habitat conservation and landscape protection. Biodiversity, where associated with agricultural production, has largely been regarded as a positive 'externality' to the process of food production; a ‘product’ which benefits wider society without necessarily conferring an agricultural benefit to the …

Soil, Plant And Livestock Interactions In Australian Tropical Savannas, L. P. Hunt, T. Z. Dawes-Gromadzki

IGC Proceedings (1977-2023)

This paper considers the various soil, plant and livestock interactions occurring in Australia’s wet-dry savanna rangelands. These regions are relatively intact compared to most of the world’s rangelands. However there is increasing pressure for more intensive use of the landscape, especially from pastoralism. This potentially threatens landscape health, function and productivity through reduced soil health and a loss of digestible perennial plants, especially given the low soil fertility and highly variable rainfall characteristic of these regions. There is an obvious need for understanding these impacts to devise sustainable management practices that promote soil health and viable perennial plant communities, and …

Andean Pastures In The Fourth Region Of Chile: Marginal Lands And Vital Spaces For A Transhumance System, T. S. Koné, R. Osorio, J. -M. Fotsing

IGC Proceedings (1977-2023)

In the fourth region of Chile, the high Andean pastures between Chile and Argentina are the summer destination for transhumant shepherds and sustain a part of the regional livestock. Since 2000, Chile has prohibited the passage of livestock to Argentina for animal health reasons in spite of official registers indicating that 60 to 75% of the summer transhumance livestock had an Argentine destination. Under those conditions it is questionable whether the Andean Chilean grasslands can absorb the increased pastoral demand without suffering damage. The objective is to provide elements of an answer to this question regarding the distribution and availability …

Microcystin-Lr Removal From Water Via Enzymatic Linearization And Ultrafiltration, Abelline Fionah, Cannon Hackett, Hazim Aljewari, Laura Brady, Faisal Alqhtani, Isabel C. Escobar, Audie K. Thompson

Chemistry Faculty Publications

Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria that can bloom in freshwater supplies. This study describes a new strategy for remediation of MC-LR that combines linearization of the toxin using microcystinase A, MlrA, enzyme with rejection of linearized byproducts using membrane filtration. The MlrA enzyme was expressed in Escherichia coli (E. coli) and purified via a His-tag with 95% purity. Additionally, composite membranes made of 95% polysulfone and 5% sulfonated polyether ether ketone (SPEEK) were fabricated and used to filter a solution containing cyclic and linearized MC-LR. Tests were also performed to measure the adsorption and desorption of MC-LR …

Translational Genomics For Alfalfa Varietal Improvement, G. D. May

IGC Proceedings (1977-2023)

Key points

1. Medicago truncatula is a model legume with available mapping, genome, and RNA, protein and metabolite profiling databases and genetically diverse populations.
2. Genomics resources developed for M. truncatula have application in the study and improvement of alfalfa making it an excellent model for this forage legume.

Accumulation Of Polyphenols And Major Bioactive Compounds In Plantago Lanceolata L. As A Medicinal Plant For Animal Health And Production, Y. Tamura, K. Yamaki

IGC Proceedings (1977-2023)

Producing animals without the use of feed-grade antibiotic growth promoters and chemical medicines is sought. Scientific studies with this aim have focused on medicinal plants to identify and quantify any beneficial effects that they might have on animal production. Plantago lanceolata L. has been used in herbal medicines and is currently being evaluated as a potential pasture species because of its beneficial effects on animal health. In the present study, the accumulation of polyphenols in P. Lanceolata is compared to that in principal pasture species, and genetic variation and environmental changes in the major bioactive compounds in P. Lanceplata are …

Grass Silage: Factors Affecting Efficiency Of N Utilisation In Milk Production, P. Huhtanen, K. J. Shingfield

IGC Proceedings (1977-2023)

Key points

1. Low efficiency of N utilisation for milk production in cows fed grass silage-based diets is mainly due to excessive N losses in the rumen.
2. The type and extent of in silo fermentation can alter the balance of absorbed nutrients.
3. There is very little experimental evidence that the capture of N in the rumen can be improved by a better synchrony between energy and N release in the rumen. Nitrogen losses in the rumen can be reduced by decreasing the ratio between rumen degradable N and fermentable energy.
4. Rapeseed meal has increased milk protein output more than isonitrogenous soybean …

Decision Support For Grassland Systems In Developing Countries, P. K. Thornton

IGC Proceedings (1977-2023)

Key points

1. Information flows in complex systems are often themselves highly complex, and decision support approaches based on linear input-output processes may have only limited impact.

2. How decisions are made, and how they can be appropriately supported, is often incompletely understood, in part because of inadequate understanding of the objectives and attitudes of all the decision makers involved.

3. Much of the developing world faces daunting problems in the coming 30 years, and appropriate information could play a critical role in dealing with these.

4. System complexity, household variability, and institutional intricacies have to be embraced rather than …

Participant Engagement To Develop Report-Back Materials For Personal Air Monitoring, Patrick H. Ryan, Chris Wolfe, Allison Parsons, Cole Brokamp, Ashley Turner, Erin N. Haynes

Epidemiology and Environmental Health Faculty Publications

Background: Studies that measure environmental exposures in biological samples frequently provide participants their results. In contrast, studies using personal air monitors do not typically provide participants their monitoring results. The objective of this study was to engage adolescents who completed personal air sampling and their caregivers to develop understandable and actionable report-back documents containing the results of their personal air sampling.

Methods: Adolescents and their caregivers who previously completed personal air sampling participated in focus groups to guide the development of report-back materials. We conducted thematic analyses of focus group data to guide the design of the report-back …

Measuring Ground Surface Elevation Changes In A Slow-Moving Colluvial Landslide Using Combinations Of Regional Airborne Lidar, Uav Lidar And Uav Photogrammetric Surveys, Sarah E. Johnson, William C. Haneberg, L. Sebastian Bryson, Matthew M. Crawford

UK CARES Faculty Publications

Slow-moving, chronically destructive landslides are projected to grow in number globally in response to precipitation increases from climate change, and land disturbances from wildfire, mining and construction. In the Cincinnati and northern Kentucky metropolitan area, USA, landslides develop in colluvium that covers the steep slopes along the Ohio River and its tributaries. Here we quantify elevation changes in a slow-moving colluvial landslide over 14 years using county- wide lidar, uncrewed aerial vehicle (UAV) structure-from-motion (SfM) surveys and a UAV lidar survey. Because the technology and quality differ between surveys, the challenge was to calculate a threshold of detectable change for …

A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo

UK CARES Faculty Publications

Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …

Effect Of Lifestyle-Based Lipid Lowering Interventions On The Relationship Between Circulating Levels Of Per-And Polyfluoroalkyl Substances And Serum Cholesterol, Stephanie Morgan, M. Abdul Mottaleb, Maria P. Kraemer, Debra K. Moser, Jessica Worley, Andrew J. Morris, Michael C. Petriello

UK CARES Faculty Publications

Exposure to certain per-and polyfluoroalkyl substances (PFAS) has been shown to be positively associated with total and/or low-density lipoprotein cholesterol. Examining this association in lipid lowering interventions may provide additional evidence linking PFAS to cardiovascular risk. We examined the relationship of 6 PFAS with cholesterol in a 6-month lifestyle-based intervention. We quantitated PFAS in 350 individuals at baseline and post intervention and examined associations of PFAS with cholesterol before and after intervention. Food frequency questionnaires and GIS analyses were used to investigate PFAS hotspots and possible exposure routes. Cholesterol significantly decreased following intervention and in parallel, PFOS, PFOA, PFHxS, and …

Impact Of In Utero Drug Exposure On Neonates Requiring Ecmo: A Retrospective Cohort Study, Hallie Walther, Aric Schadler, Karen Garlitz, John Anthony Bauer, Lindsay Kohler, Erika Waldsmith, Hubert O. Ballard

UK CARES Faculty Publications

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children’s Hospital. A total of 56 neonatal patients were placed on ECMO …

Hpv Vaccination And Cervical Cancer Screening Promotion Among Black Individuals: Social Ecological Perspectives From Key Informants Interviews, Adebola Adegboyega, Desmennu Adeyimika, Obielodan Omoadoni, Dignan Mark

UK CARES Faculty Publications

Objectives: Rates of HPV infection and HPV-related cancers are elevated in the Black population of the US. Efforts to promote HPV vaccination and cervical cancer screening are important to reducing the cancer burden among Black populations. The purpose of this qualitative descriptive study guided by social ecological model (SEM) was to describe from the perspective of key informants, the challenges and opportunities for HPV vaccination and cervical cancer screening promotion among Black adults.

Design: Twenty-three key informants participated in individual interviews over zoom video conferencing. The sessions were audio- recorded, transcribed verbatim, and checked for accuracy prior to data analysis. …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

Magnetic Nanocomposites For The Remote Activation Of Sulfate Radicals For The Removal Of Rhodamine B, Pranto Paul, Marissa Nicholson, J. Zach Hilt

UK CARES Faculty Publications

The widespread presence of numerous organic contaminants in water poses a threat to the ecological environment and human health. Magnetic nanocomposites exposed to an alternating magnetic field (AMF) have a unique ability for magnetically mediated energy delivery (MagMED) resulting from the embedded magnetic nanoparticles; this localized energy delivery and associated chemical and thermal effects are a potential method for removing contaminants from water. This work developed a novel magnetic nanocomposite—a polyacrylamide-based hydrogel loaded with iron oxide nanoparticles. For this magnetic nanocomposite, persulfate activation and the contamination removal in water were investigated. Magnetic nanocomposites were exposed to AMF with a model …

Association Of Symptoms And Mode Of Transportation To Emergency Department In Patients With Acute Coronary Syndrome, Leslie L. Davis, Thomas P. Mccoy, Barbara Riegel, Sharon Mckinley, Lynn V. Doering, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with acute coronary syndrome (ACS) with symptoms matching their expectations of a heart attack are more likely to use emergency medical services (EMS) than not.

Objective: To determine whether presenting symptom clusters are associated with EMS use in ACS patients and if EMS use or symptom clusters are associated with prehospital delay.

Methods: This secondary analysis used data from the PROMOTION trial, a randomized clinical trial that enrolled 3522 subjects with a history of or at risk for ACS from 5 sites in the United States, Australia, and New Zealand. Subjects were randomized to usual care or an …