Fine Arts

Authors: Logan McMaster, Joshua Sponbeck, Malorie Wilwand, A. Wayne Johnson. Mentors: A Wayne Johnson. Insitution: Brigham Young University. In the dynamic game of professional football, where split-second decisions and explosive movements often determine the outcome, players train all year round for optimal athletic performance. Paramount to this performance are the hamstring muscles including the semimembranosus (SM), semitendinosus (ST), and both the long and short head of the biceps femoris (BFLH and BFSH). They play pivotal roles in sprints, agility, jumping, and overall lower-body strength. Because of the critical nature of the hamstrings during functional activity, this study sought to determine which of these three muscles contributes the most to eccentric hamstring strength. Recognizing the correlation between muscle volume and muscle strength, this study compared maximal eccentric hamstring strength with the proportion of each isolated hamstring muscle's volume relative to the total hamstring muscle group volume. Doing so would identify which specific muscle contributes the most to eccentric hamstring strength. This study incorporated 74 male, collegiate football players representing all positions on the team. Maximal strength was assessed through Nordic hamstring curls and overall muscle volume was quantified using magnetic resonance imaging (MRI). Our results show no correlation (R^2<0.2) between maximal force output and proportional muscle volume for the ST, and the BFSH. Additionally, the correlations for these muscles were not statistically significant (P>0.05). The SM muscles had a weak negative correlation (R^2= -0.25) with eccentric hamstring strength that was statistically significant (P = 0.03). The BFLH proportional volume was positively weakly correlated (R^2= 0.22) with eccentric hamstring strength. This correlation was statistically non-significant (P = 0.06). This information shows that no hamstring muscle contributes more to eccentric hamstring strength than any other. Knowledge of this can be invaluable for clinicians and researchers to design comprehensive strength training programs that enhance the collective strength of the entire hamstring muscle group, ultimately optimizing the performance of football players.

Authors: Spencer Jezek, Malorie Wilwand, Joshua Sponbeck, Hunter Jack, Kaden Kennard, A Wayne Johnson. Mentors: A Wayne Johnson. Insitution: Brigham Young University. Hamstring injuries are one of the most common injuries sustained in professional football with 800+ hamstring injuries per year. These hamstring injuries often occur between late swing (eccentric contraction) and early ground contact.PURPOSE: To investigate the correlation of eccentric hamstring strength to muscle volume across positional groups.METHODS:Athletes were divided into three homogeneous groups based on position (big (e.g., linemen), skill (e.g., receivers), combo (e.g., linebackers)). Seventy-three NCAA Division I football players participated (24 big, 37 skill, and 12 combo). Hamstring strength was collected for each leg while performing 3 Nordic curls on a Nordbord device. The peak force of each leg was summed for our data analysis. Collective hamstring volume for each athlete was found through MRI. RESULTS:A Pearson’s product correlation demonstrated an overall moderate correlation (r = 0.52, p < 0.0001) between hamstring muscle volume and strength, with skill players demonstrating a strong correlation (r = 0.66, p < 0.0001), combo players demonstrating a moderate correlation (r = 0.49, p < 0.0001), and big players demonstrating a weak correlation (r = 0.39, p < 0.0001). An ANOVA showed no statistically significant difference of hamstring strength between positional groups (p = 0.1074) relative to hamstring volume (p < 0.0001). CONCLUSION:The observed overall moderate correlation between hamstring strength and muscle volume across positional groups indicates that factors outside of muscle volume contribute to muscle strength. Our data also suggests that, regardless of position, hamstring muscle strength was similar when accounting for volume. Muscle volume was the best predictor of strength for the skill group. However, other factors should be considered, such as motor control factors. In the combo and big groups, these additional factors play a larger role.

Authors: Lizzie Stewart, Hayden Underwood, Dallas Goolsby, Spencer Sears. Mentors: Camilla Hodge. Insitution: Brigham Young University. Social connection is critical to understanding how individuals interact with one another and form social bonds in groups. Our research evaluates the effects on social connection based on the Ecology of Family Experiences framework, which considers the interplay between three domains: family, activity, and time. We believe that the EFE is a transferable framework that will have important social implications for understanding interpersonal relationships and designing experiences intended to increase social connection. In this study, we examine the relationship between social connection and two variables: 1) social interaction, or the behavior between two or more people crossing paths. Social interaction considers joint or parallel interaction styles between people; 2) self-disclosure, or interaction where one intends to willfully and deliberately divulge something personal to another. We hypothesize that social interaction and self-disclosure influence social connections outside the family context. We seek to shed light on the mechanisms that shape and alter the quality and depth of interpersonal connection. In our experiment, we used a 2x2 quasi-experimental design. Participants were assigned to one of four conditions varying in self-disclosure (high vs. low) and social interaction (joint vs. parallel). Self-disclosure questions asked participants to answer prescribed questions, including highly personalized questions (high disclosure) and non-personalized information (low disclosure). Participants either interacted with a partner (joint) or wrote responses next to a partner without verbal communication (parallel). Social connection was measured using the Inclusion of Others and Self Scale. The sample consisted of 148 university students. The average participant was a white, unmarried, 20-year-old from a middle- to high-class economic background. Data analysis was conducted using mixed model techniques that took into account the unique dyadic relationship of each pairing. Results suggested a significant interaction between self-disclosure and social interaction (t = 2.354, p < 0.05). With high self-disclosure and joint activity having a mean of 4.54, high self-disclosure and parallel activity having a mean of 2.33, low self-disclosure and joint activity having a mean of 3.47, and low disclosure parallel activity having a mean of 2.01. These findings highlight the importance of self-disclosure and social interaction styles in influencing social connection, extending the applicability of the EFE framework beyond the family unit.

Authors: Ramon Zabriskie, Erica Miller, Felicia Korth, Anna Taylor. Mentors: Ramon Zabriskie. Insitution: Brigham Young University. Implicit bias occurs automatically and unintentionally based on a person’s lifetime experience and cultural history (National Institutes of Health, 2022; Handelsman & Sakraney, 2015). In this study, implicit bias is evaluated through the lens of a transformative diversity, equity, inclusion, and belonging business course. DEIB originated in the 1960s in response to equal employment and affirmative action laws (Sarrett, 2022). Studies show that Millennials and Gen Z generations are the most diverse populations ever in the United States (Stamps & Foley, 2023). Benefits of DEIB include the creation of a more unified, diverse, and successful workplace, less biases in hiring, team development, promotions, and who companies do business with (El-Amin, 2022). This study’s theoretical framework is based on the transformative learning theory which seeks to understand and promote human development through learning. Transformation is more than "knowing more" through time; when a learner is transformed by education they undergo a shift in perspective, and after that shift, they cannot go back to see the world the way they once did, at least in some small way (Wichita State University). The class was designed with experiential learning approaches and introduces a variety of DEIB concepts such as privilege, unconscious bias, assumptions, and intersectionality. Students interacted with a variety of experiential components such as DEIB events, panels, and interviews which addressed various minority groups. At the beginning of the DEIB course, students completed an IAT test focused on racial bias. The IAT test is known as the Implicit Association Test that uses positive and negative connotative words in association with pictures of minority groups to measure automatic reactions targeting an individual's level of implicit bias towards one minority group versus another. After students completed the racial IAT test, scores were recorded representing the level of implicit racial bias students held towards white people vs. black people. At the conclusion of the 14-week-long course, students completed the same IAT test on racial bias. Scores were recorded once again, comparative with previous IAT scores, to evaluate whether the amount of racial implicit bias had changed as a result of participating in the DEIB course and its curriculum. Data was then analyzed visually comparing the means from the pre to post test results. The data was analyzed using this method because the sample size was not large enough to return what the researchers considered to be reliable results. More data is available for this study, but has not been cleaned and matched, this process is currently taking place. Once the data is available, the researchers will use paired sample T-tests to conduct a full analysis. Additionally, descriptive analysis will be represented in the form of histograms of pre and post test scores observing the progression towards less implicit bias. The mean for the pre-test was .78 (sdv=1.34, n=171) and the post-test was .63 (std=1.38, n=144). Our sample size was 181 participants with 25 that chose not to answer. Demographics of participants consisted of 66% Caucasian, 3% Hispanic, 2% Asian, 2% Native Hawaiian, 1% other, and 26% who chose not to respond. The average age of participants was 21. Gender of participants consisted of 121 females and 34 males. Visual examinations of the means suggest there was migration toward 0, which would represent little to no bias and the class was making a difference in participants’ implicit bias scores. This study underscores the utility of DEIB instruction in promoting changes in bias. The impact of changes in implicit bias through this learning coupled with DEIB principles in a transformative way will greatly influence the workforce for generations to come.

Authors: Joseph Holmes. Mentors: Jared Nielsen. Insitution: Brigham Young University. BACKGROUND Anosognosia is characterized by a stroke victim’s inability to acknowledge their acquired physical deficits. Such patients could believe they can operate their limbs normally even when they cannot. Patients will often attribute other reasons to explain their deficit (unwillingness to move, a sprain, arthritis, etc).Previous research has reported damage from various brain areas, including several fronto-temporal-parietal areas, insula, and subcortical regions. Many studies suggest that the deficit is caused from impaired sensory feedback coupled with spared motor intentions, which involves premotor, sensory-motor regions, basal ganglia, temporal-parietal junction, insular cortex, and prefrontal cortex. The objective of this study is to confirm the involvement of these brain areas. It is also to identify other possible networks that could contribute to the development of AHP. METHODSWe performed a literature review for case studies of patients presenting with anosognosia for hemiplegia (n=17). The majority of cases were attributed to ischemic stroke (n=15) while the others resulted from hemorrhagic stroke. Lesion network mapping analysis was performed on the 17 lesions with a large cohort of healthy control resting-state scans (n=1000). RESULTSThe main regions to which the lesions were functionally connected included the right transverse temporal gyrus (n=17) and the anterior left insula (n=17). It is also important to note that the lesion networks were found to be negatively correlated with a few areas in the prefrontal cortex. CONCLUSIONFurther research should be done to investigate the involvement of specific areas of the prefrontal cortex in AHP. Some regions in the prefrontal cortex may be negatively correlated; however, past research suggests a positive correlation of other prefrontal regions. It is important that clinicians understand the lesion networks of AHP, as it will guide them to treat patients more effectively. Interventions such as transcranial brain stimulation could become more beneficial to patients, as clinicians will know specific areas of the brain to stimulate to mitigate symptoms of AHP.

Authors: Amanda Carlson. Mentors: Bradford Berges. Insitution: Brigham Young University. Human Immunodeficiency Virus (HIV) causes AIDS and is one of the most studied viruses in history. HIV is a retrovirus that has two copies of a single stranded RNA genome. While there is in-depth understanding of the virus and its pathogenesis, no completely effective treatment or vaccine exists. One potential target for therapeutic treatment of HIV is Viral Protein R (Vpr). Vpr is a multi-functional accessory protein encoded by the HIV genome. While HIV is a quickly mutating virus, the vpr gene remains relatively conserved. Mutations in this protein dramatically impact the rate of AIDS progression compared to the wild type (WT) version of Vpr. The Vpr polymorphism R77Q is associated with the Long Term Non Progressor (LTNP) phenotype. Regular AIDS onset is 5-7 years for WT virus and 10 or more years for R77Q. These differences in AIDS progression have been observed in vivo by following people with HIV over time. We have successfully shown that R77Q activates G2 cell cycle arrest more efficiently than WT followed by apoptosis, a death mechanism with less inflammation compared to necrosis. While the molecular mechanism of Vpr-induced apoptosis is known, it is not yet determined why point mutations in Vpr are changing levels of apoptosis. With further experimentation, we have shown that R77Q has decreased expression of pro-inflammatory cytokines compared to WT virus, which may explain why it is associated with the LTNP phenotype. The functions of Vpr come from binding and modifying cellular proteins and enzymes. The focus of our research is to determine what molecular interactions change between Vpr mutants to better understand the shifts in apoptotic levels. Vpr can be found intracellularly in the nucleus, cytoplasm, and mitochondria and extracellularly in secreted proteins and within virions. We will determine Vpr concentration in these various locations for both WT Vpr and the R77Q mutant, starting by measuring extracellular Vpr. To quantify virion-associated Vpr, we have designed a research plan. We will use WT-Vpr plasmids tagged by GFP to create GFP-tagged plasmids with either WT, R77Q or null mutations using site-directed mutagenesis. We will use Sanger sequencing for confirmation of the proper Vpr mutations tagged by GFP. We will then digest the plasmid DNA, leaving only the Vpr-GFP component and use PCR to amplify the sequences. We will transfect null virus plasmid (NL4-3) and Vpr-GFP plasmids into HEK cells to package the null virus and Vpr-GFP plasmids together to create active HIV particles. Using these virus particles, we will infect Hut-78 cells for a short time to allow the virion to enter the cells. We will then measure GFP fluorescence via flow cytometry, allowing us to quantify virion Vpr. This will be run alongside a mock infection as a control. We hypothesize that differences in virion Vpr concentrations exist among Vpr mutants. Through these experiments, we aim to discover more about the role Vpr plays in cell death by apoptosis and contribute to the existing literature exploring the importance of Vpr in HIV-1.

Authors: Hunter Morrill, Ryley Parrish. Mentors: Ryley Parrish. Insitution: Brigham Young University. Spreading depolarizations (SDs) are slow propagating waves of depolarization that move through the brain and have been associated with a wide variety of neuropathologies including the termination of seizures, the cellular correlate of aura in migraines, traumatic brain injury, and ischemic stroke. Though first characterized by Aristides Leão in the 1940s, only a very limited understanding of the mechanisms of SD induction has been achieved. SDs have been induced in mouse models using a variety of techniques, however regardless of the method of induction, high extracellular potassium and/or a strong cellular depolarization have been largely hypothesized as necessary conditions for SD induction. Interestingly, we have recently demonstrated that using a light-induced chloride pump (Halorhodopsin) to drive chloride ions into the neurons can reliably induce SDs even in the absence of high extracellular potassium levels (Parrish, 2023). It was also demonstrated that the triggering of archaerhodopsin, which removes protons from the cell and therefore hyperpolarizes the neuronal membrane without affecting chloride levels, did not induce SDs, suggesting the implication of chloride loading as a primary mechanism in SD induction. This challenges the prevalent hypothesis regarding the induction of SDs and results in a novel method of induction that allows for more characterization of the mechanisms involved. The use of genetically expressed light-gated ion channels or pumps is referred to as optogenetics. Using zebrafish, a common model for electrophysiology recordings that is also cost-effective to genetically manipulate, we have established an optogenetically induced model of SD induction. We are currently characterizing mechanisms that result in optogenetically induced SDs with pharmacology to further our understanding of SD initiation and propagation.Parrish, R. R.-G.-T. (2023). Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization. The Journal of neuroscience: the official journal of the Society for Neuroscience, 43(5), 685-692.

Authors: Noah Bezzant, Mikayla Kimball, Ashley Allan. Mentors: Brent Feland. Insitution: Brigham Young University. BACKGROUND: General knee pain is a common complaint among both athletes and older adults. Osteoarthritis is a common etiology for knee pain that can interfere with function during aging and can be assessed by validated questionnaires. It remains unclear whether there exists a dose–response relationship between cartilage loss and pain worsening. Articular cartilage thickness of the femoral condyles can be measured by ultrasound imaging and few studies utilizing this form of measurement exist. It is currently unknown if articular cartilage thickness measured ultrasonographically correlates with pain related ratings in aging athletes. PURPOSE: The aim of this study was to assess whether articular cartilage thickness at the femoral condyles as measured by ultrasound imaging has any relationship to knee pain as rated by the modified KOOS (Knee Injury and Osteoarthritis Outcome Score) survey in senior athletes over the age of 50.METHODS: Data was collected from 35 volunteers (participants in the Huntsman World Senior Games) in St. George, Utah, 2023. All subjects (22 females: mean age = 64.9 ± 6.6 yrs, Ht = 158.7 ± 35.6 cm, Wt= 66.3 ± 10.0 kg; 13 males: mean age = 67.3 ± 8.3 yrs, Ht = 179.3 ± 10.7 cm, Wt= 84.3 ± 13.4 kg) signed an approved consent and completed a modified KOOS survey before being seated on a table, with their back flattened against the wall directly behind them. They were then asked to bring either knee as deeply into flexion against their torso as possible; approximating 120°-140° of knee flexion, depending on the range of motion the subject was capable of. In flexion, the patella was shifted inferiorly enough to expose the femoral condyles so that a short axis image of the articular cartilage was obtained and the thickness of the cartilage was assessed at 3 points.ANALYSIS: All data were analyzed using JMP ver16.2 with a Pearson product pairwise correlations to determine if a relationship between average cartilage thickness correlates with pain subscale scoring from the KOOS in males and females. Correlation between age and thickness was also examined.RESULTS AND CONCLUSION: There were no significant correlations between the pain subscale score and cartilage thickness in males (p=.6998, r=0.1316), females (p=.8733, r=0.0392), or combined (p=.7308, r=0.0655) in this group of senior athletes. Age and thickness was not significantly correlated (p=.1232, r= -0.2877), but did show a trend of decreasing cartilage thickness with age. The addition of more subjects should show age and thickness to be negatively correlated with each other.

Authors: Ishmael Elliott Molina-Zepeda, Brandt Jones, Myke Madsen, Douglas Sborov, Brian Avery, Nicola J. Camp . Mentors: Nicola J. Camp. Insitution: University of Utah. Multiple Myeloma (MM) is a malignancy of plasma cells and one of the more common hematological malignancies (6.3/100,000 new cases/year). Although treatments have improved, most patients fail their first line of treatment and ultimately do not survive beyond 5 years. Identifying patients at high risk of failing treatment early is a critical need. SPECTRA is a statistical technique developed by the Camp Lab to characterize global gene expression (the transcriptome) by representing it as multiple quantitative tumor variables. Spectra variables allow gene expression to be incorporated into predictive modeling to identify high-risk groups.Transcriptome data for myeloma cells was available from 768 patients in the international CoMMpass study where 39 spectra variables were derived. Each patient has a value for each of the 39 variables (their spectra “barcode”); patients can be compared for each bar in the barcode. Predictive modeling using spectra variables was successful in identifying risk groups for time to treatment failure, such that a patient’s tumor transcriptome can be used to predict whether they are at high risk of having their treatment fail earlier.To replicate the CoMMpass data findings, we collect and process local biological samples from MM patients at the Huntsman Cancer Institute (HCI). We collect bone marrow samples, which are then cell-sorted to identify tumor (CD138+) cells. RNA is extracted from these cells and sequenced to generate transcriptome data. Then the spectra barcode is calculated.Utilizing the SPECTRA technique provides a more complete understanding of MM by better characterizing the tumor. Each spectra is a tumor characteristic. Our future research includes an investigation of whether inherited variations (in normal DNA from saliva or whole blood) are associated with the transcriptome risk score. We are also pursuing the SPECTRA technique in several other cancers.

Authors: Sofia Denise Flowers. Mentors: Lauri Linder. Insitution: University of Utah. Background and Purpose: In the year 2023, roughly 9,000 children will be diagnosed with cancer each year in the United States. Dealing with a potentially fatal diagnosis is already difficult for many grown adults, let alone a young child. The aim of this project is to describe caregiving experiences of parents and children with cancer as related through feedback comments within written and oral feedback to proposed items to measure self-efficacy for managing their child’s symptoms and behaviors used to manage their child’s symptoms.Methods: This project involved a secondary analysis of qualitative data from 21 parents (19 mothers; mean age 38 years) of school-age children with cancer who participated in a study to establish the content validity of instruments to measure aspects of symptom management. Data consisted of interview transcripts and free responses to the content review surveys. The data were then uploaded to Dedoose. My mentor and I worked independently to identify statements pertaining to parents’ experiences in managing their child’s symptoms and responding to the child’s cancer diagnosis. We then met together to reconcile content and then organize parents’ statements into categories and subcategories. Results: 101 excerpts were extracted from the transcripts and included for the secondary analysis. Excerpts were grouped into four main categories: informational resources, social support, emotional support, and medication management Within these four main categories, subthemes of professional staff support, managing child attitude and mood changes, and balancing between being a parent and their child’s medical advocate were present. Conclusion: The insights gained from this project can guide the information healthcare providers need to provide better care to the child and additional support to parents. This can allow professional staff to get a stronger understanding of not just the family’s medical needs but their informational, social, and emotional needs as well.

Authors: Isaac Stubbs, Skyler Russell, Melissa Blotter, Maxwell Holmes. Mentors: Ryley Parrish. Insitution: Brigham Young University. Status Epilepticus (SE) is a severe medical condition marked by continuous seizures lasting over 5 minutes. When SE becomes resistant to anticonvulsant drugs, the condition is known as Refractory Status Epilepticus (RSE), which lacks effective treatments and has a mortality rate of 38%. RSE lacks effective treatments partially due to our limited understanding of the mechanisms that lead to patient drug resistance to commonly used anticonvulsants. This study aims to address this knowledge gap in two pivotal ways.First, we have employed a high-density multi-electrode array (HD-MEA) with acute mouse brain slices to better understand RSE propagation patterns and various seizure states with unparalleled spatial precision. The HD-MEA allows us to record from the entire brain slice with 4096 electrodes sampling electrophysiological activity at every 60 micrometers for many hours at a time. Our data demonstrates that different seizure states, such as phasic seizure-like events, short duration epileptic discharges, or RSE itself, occur within both the same brain region and in different brain regions simultaneously. With our novel data visualization software, we can visualize the unique propagation of this phenomenon. These findings indicate that RSE might be a progressive event, challenging conventional understanding of RSE. Second, we are currently exploring a potential pharmacoresistance mechanism that may contribute to the patient entering RSE, which suggests that changes in the chloride reversal potential may lead to a phenomenon known as depolarizing GABA. Depolarizing GABA may negate the effectiveness of the currently used antiepileptic drugs that rely on standard physiological chloride conductance to effectively limit seizure activity. We are studying this drug resistant mechanism with the HD-MEA by introducing anticonvulsant drugs to acute mouse brain slices during the evolution of RSE to locate a critical point at which the slice becomes resistant to these compounds.We hope this study will illuminate the complexities of RSE by revealing its progressive nature and drug resistant properties.

Authors: Mikayla Kimball, Noah Bezzant, Ashley Allan, Josh Sponbeck. Mentors: Brent Feland. Insitution: Brigham Young University. Ultrasonic analysis of patellar tendon thickness in active older athletesBACKGROUND: Recent research has suggested that patellar tendon loading through exercise and resistance training can help maintain and increase patellar tendon thickness in older adults. Limited research exists that identifies the average thickness of patellar tendons in younger athletes, however, it is unknown if this thickness remains or is maintained in older adult athletes who have maintained a very active lifestyle.PURPOSE: This study aimed to determine how gender correlates to patellar tendon thickness in the proximal and middle patellar tendon of active older athletes participating in sporting events at the Huntsman World Senior Games.METHODS: Data was collected from 59 volunteers (participants in the Huntsman WorldSenior Games) in St. George, Utah, 2022. All subjects (34 females: mean age = 61.09 ± 7.00 yrs, Ht = 162.41 ± 25.73 cm, Wt= 66.29 ±11.38 kg; 25 males: mean age = 68.68 ± 7.03 yrs, Ht = 178.21 ± 8.63 cm, Wt= 84.42±10.90 kg) signed an approved consent form and then sat on a treatment table with their legs relaxed and dangling off. The probe was placed vertically below the kneecap and an ultrasonic image was taken. Each image showed a small section of the patellar for reference. Each ultrasonic measurement showed the middle and proximal thickness of the patellar tendon. ANALYSIS: All data were analyzed using JMP ver16.2 with a stepwise multiple regression analysis to determine the effect of age, height, wt and gender on patellar tendon thickness. A sex*location mixed model was used to determine differences in middle and proximal thickness between gender. Data were normally distributed, not requiring transformation.RESULTS & CONCLUSIONS: Proximal tendon measurements were thicker than middle tendon measurements on both sides (p=0.0001). There was no significant difference either proximal tendon thickness (p=0.9323) or middle tendon thickness (p= 0.3993) between left and right sides. No significant difference between male and female tendon thickness at either location (p=0.7700). Proximal tendon thickness was greater and this has been found to be greater in younger athletes with a history of patellar tendinopathy. Aging athletes may also have a history of knee pain episodes that could have contributed to this finding. The lack of gender differences in thickness measures was surprising, but may be a result of the level of activity of senior athletes. In the future studies should look to compare active vs non-active aging athletes, more specific age range differences, and how knee replacements and other injuries affect patellar tendon thickness.

Authors: Caroline Cowley, Megan Jewell, Brenda Mendoza, Aubrey Cluff, Ryan Summerhays, Jason Hansen. Mentors: Jason Hansen. Insitution: Brigham Young University. Approximately 8 million newborns manifest a birth defect every year worldwide. One of the most common birth defects involve disruptions in musculoskeletal development. Oxidative stress has been found to propagate teratogenesis. Thioredoxin-1 (Trx1), an oxidoreductase, is an important antioxidant regulator required for proper embryonic development. Trx1 knockouts have been found to be embryolethal prior to implantation. A preliminary study to assess osteogenesis was conducted using mouse embryonic fibroblasts (MEFs) originating from transgenic conditional Trx1 knockout embryos. Upon confluence, MEFs were stimulated to undergo osteogenesis via commercially available media. A subset of cells were treated with doxycycline (DOX) prior to and throughout the culture period. MEFs were maintained over a 21 day period in a reduced oxygen environment. MEFs were then fixed in formalin and stained with Alizarin red to determine the degree of osteogenesis. MEFs treated with DOX were unable to undergo proper osteogenesis. While this would suggest that osteogenesis is regulated through proper functions of Trx1, it is unknown how Trx1 regulates osteogenesis in utero. Because Trx1 deletion is lethal prior to implantation it has been historically difficult to study the role of Trx1 during organogenesis. With the development of the DOX-inducible Trx1 conditional knockout mouse, we can now target specific developmental periods and evaluate post-implantation processes like osteogenesis. Using proper transgenic mice and breeding schemes, DOX-inducible Trx1 conditional knockout embryos were treated in utero with DOX through the dam’s drinking water, starting on gestational day (GD) 8.5. The embryos were collected on GD 16.5, fixed in 95% ethanol, and then skinned. To visualize bone and cartilage, the embryos were placed in ethanol and subsequently stained with Alizarin red and Alcian blue. The staining showed that embryos lacking Trx1 were significantly stunted in their skeletal maturation. With this data, we are the first to show that during organogenesis, the musculoskeletal system is affected by deletions of Trx1 at specific periods of development. Under oxidizing conditions which exceed the capacity of the oxidoreductase pathway of Trx1, Trx1 exists primarily in its oxidized form and can no longer reduce proteins that have been turned off by oxidation. Our Trx1 deletions model a highly oxidized state in which Trx1 is dysfunctional. Because regulatory redox control of protein activity is required for proper embryonic development, exposure to oxidizing environmental conditions specifically affecting Trx1 redox state may target the disruption of the musculoskeletal system.

Authors: Drew Allred, Vern Hart. Mentors: Vern Hart. Insitution: Utah Valley University. Surgery remains one of the most common and effective treatments for a variety of cancers, especially those that form solid, localized tumors such as breast and colorectal cancers. During these treatments, the palpable lesion is surgically resected with the assumption that cancerous cells have metastasized to nearby tissues. As such, surgeons will excise a tissue margin surrounding the tumor in hopes of removing any additional cancer, thus preventing further spread of the disease. However, this process is time-consuming and requires specialized expertise from a trained pathologist to verify that all cancer has been removed. Furthermore, if the pathology report indicates that not all cancerous cells have been extracted, additional follow-up visits and surgeries are typically required. In recent years a number of non-invasive technologies have been developed which seek to map cancerous cells in whole tissues. Training and validating these methods still requires a reliable ground truth, typically provided by an annotated pathology report. We propose a simpler model in which two cell species were co-cultured to provide a heterogeneous training sample. One of these species (PANC-1) was transfected with a vector coding for a fluorescent marker to represent healthy tissue, while the other species (COS-7) remained untreated, representing cancerous cells. An experiment was then conducted using a coherent diffraction imaging (CDI) system, in which laser light incident on the cells was used to quantify phase shifts produced by each cell type. Fluorescent microscopy was then used to create a map of transfected and non-transfected cells for comparison. Results will be presented demonstrating a correlation between the phase shifts produced by the two cell types and the corresponding fluorescent images, potentially facilitating optical cell identification without the need for pathology.

Authors: Maddy Howard, Brooke Dension, Shanna Groesbeck. Mentors: Sandy Wilson. Insitution: Utah Valley University. AbstractThere are many systemic diseases that are linked to oral health. This literature review specifically examines different studies and academic journals that have studied the relationship between oral health, obesity, heart disease, and diabetes. Obesity is linked to the patient's oral health in many ways. When patients are consuming large quantities of food more often than normal, this results in a more acidic environment along with energy for bacteria to grow. One study found a correlation between obesity and risk factors such as “frequency of brushing teeth, smoking, tooth loss, gingivitis, and dental caries (Yilmax & Somay, 2021). This article discusses the strong correlation between oral health and heart disease. Several studies emphasize the importance of dental hygienists educating their patients about the link between their oral and cardiovascular health. The articles conclude that treating periodontal disease more effectively and aggressively could lead to a marked reduction in coronary heart disease rates and vice versa.Diabetes and periodontal disease is also examined at length in this literature review. Diabetes and periodontitis is described as a ‘two-way relationship’. Evidence shows that individuals with diabetes, type 1 or type 2, are 34% more likely to develop periodontal disease. On the other hand, individuals experiencing periodontal disease are 53% more likely to develop diabetes (Wu, et al., 2020). This literature review will explore the importance of oral health in keeping your entire body healthy.ReferencesArora, A., Rana, K., Manohar, N., Li, L., Bhole, S., & Chimoriya, R. (2022). Perceptions and practices of oral health care professionals in preventing and managing childhood obesity. Nutrients, 14(9), 1809. 10.3390/nu14091809.Batty, G. D., Jung, K. J., Mok, Y., Lee, S. J., Back, J. H., Lee, S., & Jee, S. H. (2018). Oral health and later coronary heart disease: Cohort study of one million people. European Journal of Preventive Cardiology, 25(6), 598-605. 10.1177/2047487318759112Centers for Disease Control and Prevention. (2022). Defining adult overweight & obesity. Centers for Disease Control and Prevention. Deraz, O., Rangé, H., Boutouyrie, P., Chatzopoulou, E., Asselin, A., Guibout, C., Van Sloten, T., Bougouin, W., Andrieu, M., Vedie, B., Thomas, F., Danchin, N., Jouven, X., Bouchard, P., & Empana, J. P. (2022). Oral condition and incident coronary heart disease: A clustering analysis. Journal of Dental Research, 101(5), 526-533. 10.1177/00220345211052507Sanchez, P., Everett, B., Salamonson, Y., Ajwani, S., Bhole, S., Bishop, J., Lintern, K., Nolan, S., Rajaratnam, R., Redfern, J., Sheehan, M., Skarligos, F., Spencer, L., Srinivas, R., & George, A. (2017). Perceptions of cardiac care providers towards oral health promotion in Australia. Collegian, 25(5), 471-478. https://doi.org/10.1016/j.colegn.2017.11.006Preshaw, P. M., Alba, A. L., Herrera, D., Jepsen, S., Konstantinidis, A., Makrilakis, K., & Taylor, R. (2012). Periodontitis and diabetes: A two-way relationship. Diabetologia, 55(1), 21-31. 10.1007/s00125-011-2342-yWu, C.-Z., Yuan, Y.-H., Liu, H.-H., Li, S.-S., Zhang, B.-W., Chen, W., An, Z.-J., Chen, S.-Y., Wu, Y.-Z., Han, B., Li, C.-J., & Li, L.-J. (2020). Epidemiologic relationship between periodontitis and type 2 diabetes mellitus. BMC oral health, 20, 204. 10.1186/s12903-020-01180-wYilmax, Busra. & Somay, Efsun. (2021). Is obesity a problem that threatens oral health in adults? Cukurova Medical Journal, 46(3), 1215-1221. DOI: 10.17826/cumj.950243

Authors: Danielle Terry, Seth Helton, Michael Creer. Mentors: Austin M Green. Insitution: University of Utah. With anthropogenic influence increasing worldwide, it is important to understand how wildlife behavior changes in response to urbanized landscapes. Urban ecosystems represent relatively novel landscapes with unique threats and opportunities that can completely restructure species’ population composition and dynamics. Mule deer (Odocoileus hemionus) have been shown to alter their temporal activity in response to urbanization across their range of the Intermountain West of the United States. In this study, we will investigate the effects of anthropogenic influence on mule deer temporal activity behavior across two distinct life stages: fawning and non-fawning. Data for this study will come from the citizen science camera trapping project, Wasatch Wildlife Watch. The full project area is separated into two study sites: “Rural” and “Urban”. This study will be based around the wild-to-urban interface of the Central Wasatch Mountain Range and the Bear River Mountain Range, which composes some of the most highly recreated portions of the Uinta-Wasatch-Cache National Forest, receiving approximately 9,000,000 visitors annually (U.S Forest Service). We will investigate the proposed differential effects of anthropogenic influence and urbanization on mule deer diel activity patterns in the fawning vs. non-fawning life stages. Also, we will inquire whether intraspecific responses in mule deer diel activity alter interspecific interactions, especially with fawning predators, and how these responses might interact with environmental factors. We predict that anthropogenic influence and urbanization alter the diel activity patterns of fawning mule deer more than non-fawning deer and that the presence and activity of fawn predators (e.g., coyote [Canis latrans]) would have a stronger effect on fawning deer activity than non-fawning deer activity.

Authors: Marie Gibb. Mentors: Francine Jensen. Insitution: Utah Valley University. Maternal mortality, also known as maternal death, is defined as the death of a woman during pregnancy and up to one year postpartum. (MacDorman et al., 2021; Spelke & Werner, 2018). The United States is the only developed nation where the rates of maternal mortality are rising, and they have been rising for twenty years (Simpson, 2019; Spelke & Werner, 2018). This incidence represents a maternal health crisis in the United States. On average, 700 women in the United States die each year from pregnancy-related complications. This equates to 17.2 maternal deaths for every 100,000 live births (Simpson, 2019). Currently, the maternal mortality rate for Utah is higher than the national average at 21.5 maternal deaths per 100,000 live births (Utah Department of Health and Human Services, 2023). According to More than 60% of these deaths are preventable (MacDorman et al., 2021; Simpson, 2019).The leading causes of maternal death in the United States are hemorrhage, preeclampsia, eclampsia, hypertension, embolisms, and cardiomyopathy, which often lead to cardiovascular disorders (MacDorman et al., 2021; Simpson, 2019). The Utah Health and Human Services (2023) reported that increases in heart disease, hypertension, diabetes, mental health disorders, and other chronic conditions complicate pregnancies and are contributing to maternal mortality in Utah. The American Heart Association has cautioned that pregnancy complications like preeclampsia, gestational diabetes, and preterm delivery are linked to maternal heart disease later in life (Parikh et al., 2021). Research suggests that each episode has a cumulative effect (Marill, 2021), meaning, the more pregnancies women have, and the more complications women have during pregnancy, the more elevated their risks are in general for cardiovascular disorders as they age. A qualitative survey was sent out using snowball sampling to women over the age of 18 in Utah asking about their understanding of cardiovascular risk factors and current health conditions. Findings showed that women were unaware of their potential cardiovascular risks associated with pregnancy. Raising awareness regarding these cardiovascular risks may be the number one preventative strategy, as women are the ones who bear the personal and physical risks. If pregnant women are aware of their cardiovascular risk factors, they can be empowered to raise concerns when necessary. Future interventions may include educating all women of childbearing years about cardiovascular risks prior to pregnancy, as well as more frequent screening of women during and after delivery (Marill, 2021). ReferencesMacDorman, M. F., Thoma, M., Declcerq, E., & Howell, E. A. (2021). Racial and ethnic disparities in maternal mortality in the United States using enhanced vital records, 2016‒2017. American Journal of Public Health, 111(9), 1673–1681. https://doi.org/10.2105/ajph.2021.306375Marill, M. C. (2021). Getting to the heart of America's maternal mortality crisis. Health Affairs, 40(12), 1824-1829. https://doi.org/10.1377/hlthaff.2021.01702Parikh, N. I., Gonzalez, J. M., Anderson, C. A. M., Judd, S. E., Rexrode, K. M., Hlatky, M. A., Gunderson, E. P., Stuart, J. J., & Vaidya, D. (2021, May 4). Adverse pregnancy outcomes and cardiovascular disease risk: Unique opportunities for cardiovascular disease prevention in women: A scientific statement from the American Heart Association. Circulation, 143(18), e902-e916. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000961Simpson, K. (2019). Maternal mortality in the United States. MCN, The American Journal of Maternal/Child Nursing, 44 (5), 249-249. doi: 10.1097/NMC.0000000000000560.Spelke, B., & Werner, E. (2018). The fourth trimester of pregnancy: Committing to maternal health and well-being postpartum. Rhode Island Medical Journal (2013), 101(8), 30–33.Utah Department of Health and Human Services. (2023, March 16). Complete health indicator report of maternal mortality. Retrieved Sat, 09 September 2023 from the Utah Department of Health and Human Services, Indicator-Based Information System for Public Health website: http://ibis.health.utah.gov. https://ibis.health.utah.gov/ibisph-view/indicator/complete_profile/MatMort.html

Authors: Isaac Gillins, Zoe Thompson. Mentors: . Insitution: Utah Valley University. The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and is cleaved into several peptide hormones. One of these is melanocyte-stimulating hormone (MSH), which is involved in food intake and energy expenditure. A mutation in the POMC gene can result in a rare condition in which the subject displays early-onset obesity characterized by severe hyperphagia (i.e. excess hunger). Affected subjects may also show a lack of pubertal development. In this experiment, we will study mice with a mutation in the POMC gene. They show some of the same symptoms as humans with a POMC mutation, including hyperphagia, obesity & infertility. Specifically, we will investigate the estrous cycle in female mice to determine if they are cycling normally. The estrous cycle, similar to the menstrual cycle in humans, is characterized by changes in reproductive hormones, and can be divided into four stages: proestrus, estrus, metestrus, and diestrus. Cells lining the surface of the vagina have been previously collected using a pipette smear technique. Each stage can be characterized by the proportion of three cell types: epithelial cells, cornified cells, and leukocytes. These cells correspond to the fluctuating hormone levels during the estrous cycle. Images of these samples will be assessed for the composition of cells to determine the stage of the estrus cycle, and whether or not the cycle displays normal patterning. Because POMC-deficient mice are infertile, we hypothesize their estrous cycles may be atypical. For example, the estrous cycle of the POMC-deficient mice may appear in irregular order or with one stage being predominant over the rest. If the estrous cycle is atypical, then we will measure the hormones directly to confirm that the infertility is caused by changes in hormonal regulation. This will help us to understand more about how the POMC gene affects reproductive function.

Authors: Quinn Gerber, Lucas Carpenter, Jacob Clemons, Cindy Kin. Mentors: Cindy Kin. Insitution: Brigham Young University. Introduction: It is vital that patients are adequately prepared for surgical intervention. To meet this need, many medical centers have adopted prehabilitation protocols. The aim of this study was to establish an in-depth comprehension of the attitudes towards surgery and barriersand preferences to prehabilitation for patients identifying as Latino, in order to develop a preliminary framework for adapting prehab programs to best meet the needs of this specific patient population.Methods: We conducted qualitative semi-structured in-person one-on-one interviews with Latino patients who had recently undergone major abdominal surgery. The interviews, conducted at an academic medical center, were audio-recorded, transcribed verbatim, translated into English (as needed), iteratively coded, and discussed by four researchers to reach consensus. We used thematic analysis to identify shared attitudes held by patients and common barriers to the adoption of prehabilitation programs. Analysis of these attitudes and barriers, along with stated patient preferences, led to the development of several ideas that physicians can implement to increase prehab adoption among Latino patients.Results: We interviewed 16 patients, at which point we reached thematic saturation. The patients were on average 52 years old (range 20 to 79) and 50% were women. Our pooled kappa score was .92, indicating a very high degree of concordance among the coding researchers. We identified five common attitudes held by Latino patients regarding surgery: anxiety associated with hospitalizations and surgical procedures, deep trust in physicians, reliance on positivity, tight-knit families/communities, and prominent religious and cultural beliefs. A lack of understanding, physical limitations, a reactive/delayed approach to healthcare, dietary barriers, and mental barriers emerged as obstacles to prehabilitation adoption. These attitudes and barriers, along with direct patient feedback, led us to identify several programmatic priorities that may increase adherence to prehab. These components consist of face-to-face interaction, increased communication, patient and physician collaboration in program development, and family/support group engagement in surgical preparation.Conclusion: Our study provides physicians preliminary insight into customizing prehabilitation programs to best meet the needs and customs of the Latino community, including anxiety associated with hospitalizations, strong social support, and a dominant role of religious faith in coping with illness. We identified several critical components that may make prehab more culturally competent and thus more likely to be adopted by patients. These include in-person coaching, increased information about the upcoming operation and recovery, and engagement of family members. We recommend that healthcare teams committed to prehabilitation consider these needs to make their programs more attractive and accessible to their Latino patients.

Authors: Brock Sheehan, Bryson Edwards, Ivanna Soto, Justice Vance, Tyler Haywood, Jefferey Goddard, Logan Seegmiller, Mohammed A. El Saidi, Wissam R Zaidan , Asmahan El-Ezzi , Dr. Ruhul Kuddus. Mentors: Dr. Ruhul Kuddus. Insitution: Utah Valley University. Association of Cyclooxygenase 1 (COX-1) rs4648298 and Cyclooxygenase 2 (COX-2) rs20417 Polymorphisms and Prostatic diseases Among Lebanese MalesBrock J Sheehan1*, Bryson Edwards1, Ivanna Soto Medrano1, Justin Vance1, Tyler Haywood1, Jeffrey Goddard1, Logan Seegmiller1, Mohammed A. El Saidi2, Wissam R. Zaidan3, Asmahan A. El-Ezzi3, 4, Ruhul Kuddus11Department of Biology, 2Department of Strategic Management and Operations, Utah Valley University, Orem UT; 3Radioimmunoassay Laboratory, Lebanese Atomic Energy Commission, Beirut Lebanon; 4Department of Chemistry and Biochemistry, Lebanese University, Hadath, Lebanon. *- presenting author.Background: COX-1 and COX-2 genes encode prostaglandin-endoperoxide synthases (PTGS) isoenzymes, involved in inflammation and possibly neoplasms. The genes are expressed in the prostate gland. Both genes have several polymorphisms. Here we examine the association of rs4648298 (A-G transition) and rs20417 (G-C transversion) polymorphisms and prostatic diseases. This research was approved by the Utah Valley University IRB.Materials and Methods: DNA was extracted from a blood sample of 56 healthy volunteers, 51 volunteers with benign prostate hyperplasia (BPH), and 61 volunteers with clinical prostate cancer (PCa). Genotyping was conducted through PCR-RFLP analyses. The restriction enzymes used were BaeGI (for rs4648298) and AciI (rs20417), respectively. Alleles with the restriction site were considered recessive. The association was inferred through statistical analyses of the distribution of the genotypes (BB, Bb, and bb or AA, Aa and aa), and allele frequencies among the controls and the affected groups. A p-value of ≤0.05 was considered significant.Results: The distribution of the genotypes is in Hardy-Weinberg equilibrium for all three groups. The b allele of the COX-1 gene is extremely rare (less than 3%), and no significant association between the B or b allele or BB, Bb, and bb genotypes and prostatic disease was observed. The a allele of the COX-2 gene is more common in the BPH group (p=0.011), but not the PCa group (p= 0.472) or the combined affected group (p=0.068) compared to the control group.Conclusions: There is no association between the rs4648298 polymorphisms of the COX-1 gene and prostatic diseases. The a allele of the rs20417 polymorphisms of the COX-2 gene is associated with higher risks of BPH and possibly PCa. The small sample size, sampling from one ethnic group, and the low distribution of the b allele in the Lebanese population are limitations of this study.

Authors: Aljexi Olsen, Hali Lukacs. Mentors: Eddy Cadet. Insitution: Utah Valley University. Utah Lake is the third-largest freshwater body west of the Mississippi River and serves as a vital resource for just over 600,000 Utah Valley residents through agriculture, residential and recreational purposes. In addition to its utility, Utah Lake provides a haven for biodiversity for numerous species within its wetlands. Despite its utility and importance, the lake faces two significant challenges in the form of Trace Metal (TM) pollution and the encroachment of invasive plant species known as Phragmites australis (P. australis). Despite considerable investments of time, money, and resources by various state agencies to address these concerns, their success has been limited due to the agency’s isolated efforts for these large multifaceted issues. TM, though naturally occurring in the environment, has been found to be toxic to both people and the ecosystem when at elevated levels. P. australis, is a robust and fast-growing macrophyte, possessing remarkable adaptability to and tolerance for poor soils, enabling it to rapidly outcompete native species. Due to P. australis resilience and aggressive nature, many colonies have grown around the lake regardless of soil conditions. Studies have shown that P. australis has been utilized for remediation purposes around water bodies by extracting TMs from sediment. While P. australis must be addressed, can it be used as part of the solution by identifying TM polluted areas? This study aims to discern the variety in TM absorption by P. australis in both unpolluted and polluted sites in the wetlands surrounding the hyper-eutrophic Utah Lake. We selected nine sites around Utah Lake, considering their land use and proximity to pollution sources. At each site, three replicate samples encompassing P. australis, soil, and water were collected. These samples underwent a meticulous process, including washing, weighing, grounding, sieving, acid digesting using a CEM MARS 6, and analysis for TM content within an ICP-MS. Our preliminary findings reveal that in both unpolluted and polluted sites, soil concentrations of As and Cd exceeded background levels (11.73, 1.53 in unpolluted sites, and 27.47, 6.63 in polluted sites, respectively). Notably, in select polluted sites, such as UVU, P. australis displayed a remarkable capacity to hyper-accumulate As, with a transfer factor of 167.14% compared to the lowest unpolluted sites, like Lindon, which showed a rate of about 10%. Across all sites, the accumulation of Cr was relatively consistent (ranging from 17.13 to 19.7 ppm), irrespective of biomass. The examination of TM concentrations, transfer factor rates, and TM accumulation based on biomass suggests that P. australis may serve as a valuable biomarker for identifying TM-polluted sites. This research holds significant relevance, as it could offer state agencies a swift and effective means to pinpoint TM-polluted areas. Moreover, the areas where P. australis is thriving may be leveraged for phytoremediation efforts in TM-contaminated sites, providing an environmentally friendly solution to address this pressing concern.

Authors: Porter Bischoff, Kody Garrett, Clayton Rawson. Mentors: Britt Wyatt, Josh Premo. Insitution: Utah Valley University. This research delves into the underexplored territory of medical experiences and their potential impact on undergraduate students' motivation in STEM courses. While prior studies have focused on factors like gender and ethnicity in STEM, little attention has been given to the influence of medical experiences and chronic conditions on STEM students, despite evidence suggesting that students with medical conditions face unique challenges in completing their degrees.Our study specifically investigates the effects of medical experiences and chronic conditions on students enrolled in science classes at an open enrollment institution. We hypothesize that increased academic interruptions due to medical experiences may lead to decreased science motivation, reduced sense of belonging, self-efficacy, and self-determination.Data was collected from 390 students across 14 biology courses, including non-majors, at a teaching-focused institution, both before and after the courses. Surprisingly, 57% of surveyed students reported having a medical experience, and 22% reported having a chronic condition, highlighting the significance of this identity within the student population.As anticipated, students experiencing more medical interruptions exhibited a notable decrease in their sense of belonging and self-efficacy, albeit with a small effect size. Intriguingly, students with medical experiences who engaged more with science demonstrated significantly higher levels of science immersion and motivation. This suggests that medical experiences can influence student engagement with science, both positively and negatively. The impact of these interruptions on a student's academics is closely linked to their sense of belonging and self-efficacy. However, if medical experiences drive increased engagement with science, students may find themselves more motivated to explore these experiences within the context of scientific inquiry.Understanding how medical experiences can shape students' motivation is essential as science instructors adapt their course content and pedagogy to be more inclusive, embracing the diverse identities within their student population.

Authors: Brett Pickett, Lincoln Sutherland, Jacob Lang. Mentors: Brett Pickett. Insitution: Brigham Young University. Introduction: Breast cancer is one of the most prevalent types of cancer present in society today, and is the second leading cause of cancer death for women. Approximately 13% (1 in 8) of women will develop invasive breast cancer, with 3% of women (1 in 39) dying from this type of cancer. Three important classifications used when formulating a treatment plan for breast cancer are the presence or absence of Estrogen Receptor (ER), Progesterone Receptor (PR), or Hormone Receptor (HR). Treating Estrogen Receptor Positive (ER+) breast cancer with aromatase inhibitors, such as Letrozole, is the current standard treatment for all postmenopausal women. A prior study by Lee et. al. identified PRR11 as the only gene that was significantly overexpressed in resistant vs non-resistant cancers among the 51 genes in chromosome arm 17q23. The goal of the current study is to perform a secondary analysis of this valuable dataset to identify genes, signaling pathways, and biomarkers across the whole human transcriptome that are significantly associated with treatment resistance in ER+ patients.Methods: We retrieved, preprocessed and analyzed 58 ER+ breast cancer samples from patients who had been treated with Letrozole, which are publicly available in the NCBI Gene Expression Omnibus (GEO) database. The Automated Reproducible MOdular Workflow for Preprocessing and Differential Analysis of RNA-seq Data (ARMOR) was used to process our data downloaded from NCBI. This workflow trimmed low quality reads from the RNA-sequence reads, mapped and quantified our data to generate a DEG list. Gene ontology enrichment with camera was also performed. Next, the genes were mapped to common gene identifiers and input to the signaling pathway impact analysis (SPIA) algorithm to identify intracellular signaling pathways that were enhanced by our DEGs. With that information, Pathway2Target was used to identify known drug targets within our identified pathways. Finally, a decision tree-based machine learning approach was used to predict features/expressed genes that could be used to most accurately classify responders vs nonresponders to Letrozole. Results: Our comparison of 36 responders versus 22 non-responders detected a total of 18,735 genes and identified 105 that were statistically significant (p-value < 0.05) after applying a false-discovery rate (FDR) correction, including SOX11, S100A8/S100A8, and IGLV3-25. We then used the Signaling Pathway Impact Analysis (SPIA) algorithm to determine whether any known intracellular signaling pathways were significantly enriched in DEGs (Bonferroni-adjusted p-value < 0.05). This analysis identified 4 pathways that were statistically significant in Non-Responders to Letrozole Treatment. We then used the pathway results to predict 60 existing therapeutic targets that could be repurposed to treat the resistance phenotype. Notably, the predicted targets for the non-response phenotype included VEGFA, a current target for solid tumors as well as ESR1, an Estrogen Receptor. We next wanted to determine whether we could predict transcriptional biomarkers that could aid with identifying patients that do not respond to treatment. To do so, we used the read counts for all samples as the input for this analysis and identified 278 transcriptional biomarkers. Performance metrics for all biomarkers identified yielded an area under the receiver-operator characteristic (AUROC) curve of 0.972 (Figure 2), indicating an exceptional ability to classify Letrozole responders vs non-responders by the transcriptional profile. Sensitivity for all transcriptional biomarkers was measured at 100%, and specificity at 94%. We used the top two biomarkers from our first analysis as input for a second analysis to determine the performance of a smaller subset. Our second analysis determined that PRDX4 and E2F8 together yielded an AUROC of 0.823 and an overall accuracy of 88.2%. Discussion:Our results identify additional DEGs, pathways, targets and biomarkers for further exploration in the treatment and categorization of ER+ breast cancer.

Authors: Eden Beazer, Aubree Bench, Ethan Jones, Jared Carter. Mentors: Jeffrey Tessem. Insitution: Brigham Young University. Incidence of diabetes worldwide has grown from 108 million people in 1980 to 422 million people in 2014, nearly tripling in just thirty-four years. Type 2 diabetes (T2D) is characterized by the loss of pancreatic beta cell mass and the failure of the remaining beta cells to provide adequate insulin. Contributing to the development of T2D is glucolipotoxicity (GLT), a condition characterized by the harmful elevation of glucose and fatty acid levels within beta cells. While there are existing treatments for symptoms of diabetes, much remains to be understood about its underlying causes and effective preventative measures. Flavonoids are naturally occurring phenolic compounds found in many fruits and vegetables that have various anti-inflammatory health benefits. Previous studies suggest that epicatechin, a flavonoid present in cocoa, can reduce the effects of diabetes by diminishing insulin desensitization and increasing glucose stimulated insulin secretion (GSIS). Interestingly, the bioavailability of epicatechin is poor, while its metabolites are more easily absorbed in the small intestine. Further studies demonstrated that under non-stressed conditions in beta-cells, hippuric acid, homovanillic acid, and 5-phenylvaleric acid, metabolites of epicatechin, stimulate insulin secretion at concentrations more realistically found in the body. However, the effects of these metabolites in glucolipotoxic conditions are unknown. Here, we present the effects of epicatechin and its metabolites hippuric acid, homovanillic acid, and 5-phenylvaleric acid on beta cell insulin secretion and mitochondrial respiration under GLT culture conditions. This study aimed to contribute to the limited body of knowledge on the bioactivity of flavonoid metabolites on beta cell function under damaging conditions observed with T2D, offering crucial insights for developing effective strategies to harness the health benefits associated with flavonoids.