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Analysis of Tumor Methylation Quantitative Trait Loci in Pediatric Cancer Patients with Central Nervous System Tumors
Get PDFWhile many adult cancers are characterized by a large number of somatic mutations, pediatric cancers tend to be associated with a greater prevalence of germline mutations in cancer predisposition genes. However, the mechanisms through which these germline variants impact tumor progression remain poorly understood. The goal of this project is to uncover the genetic basis for epigenetic changes potentially impacting tumor development by integrating germline genotypic data with tumor methylation data through a tumor methylation quantitative trait loci (tumor meQTLs) framework. Tumor meQTLs are germline genomic loci at which different genotypes are associated with differences in methylation levels at nearby sites in the tumor sample. To map the QTLs, I used pre-processed and normalized methylation data and merged genotype files from 528 pediatric cancer patients with central nervous system tumors. Ultimately, 5,889 significant tumor meQTL associations were identified. A couple of these QTLs were found to be within known medulloblastoma predisposition genes, however more work must be done to contextualize this list of associations.No embargoAcademic Major: Data Analytic
Examining the Predictors of White-throated Sparrow (Zonotrichia albicollis) Spring Departure Date
Get PDFMigratory birds encounter a variety of obstacles while migrating that can have profound negative effects on breeding success. These obstacles and their effects are exacerbated by anthropogenic climate change in addition to novel obstacles arising, such as advancing producer phenology. As such, migratory decisions have the capacity to impact breeding success and therefore population dynamics which in turn have serious implications for conservation. At present, most studies of migratory and phenological decisions by migratory birds have focused on long-distance migrants. Here, I focus on examining the predictors of spring departure date for a boreal-breeding, short-distance migrant, the White-throated Sparrow. I determined the departure date for 42 motus-tagged White-throated Sparrows and qualitatively investigated spring departure date’s relationship with a common spring phenology indicator, common lilac flowering, and winter weather. I found that sex best predicted spring departure date with male sparrows departing earlier. Additionally, departure date and winter weather remained stagnant while lilac phenology advanced. These results align with previous work regarding White-throated Sparrow migratory and phenological decisions and emphasize the occurrence of male migratory birds departing and arriving earlier than females in the spring. Furthermore, advancing producer phenology and stagnant White-throated Sparrow phenology highlight the need for future research to increase statistical power and identify phenological mismatches and associated conservation implications.No embargoAcademic Major: Forestry, Fisheries and Wildlif
Echoes of the Past: Han's Insights into Polish Authenticity, Identity, and Education
Get PDFSession 3-D: Identity and Educational Practices in Central and Eastern Europe. Presenter: Aneta Sobieraj-Skórski, Pomeranian School. - "Echoes of the Past: Han's Insights into Polish Authenticity, Identity, and Education"
Exploring an Online Training Program for Caregivers of Children with ASD Post-pandemic
No full textRural caregivers of children with autism spectrum disorder (ASD) face many challenges accessing support, and these challenges increased during the COVID-19 pandemic. Online parent-training programs have been proven to support caregivers of children with ASD, especially for those residing in rural areas. This is a sub-study of a pilot study that examined the effects of a web-based parent training program for caregivers of rural children with ASD post- pandemic. This sub-study used a post-intervention qualitative design to gather caregivers’ perspectives on the online intervention and compare it to resources they received prior to the pandemic. Rural caregivers of children with ASD participated in the study. Participants were invited to complete an online parent training program (Attend Behavior) for 12 weeks. After 12 weeks, participants were encouraged to provide feedback through a 1:1 interview. 7 participants completed the interview and answered questions that addressed the study’s content and their experiences in relation to the pandemic. All the participants found this program to be helpful considering the recent changes due to the COVID-19 pandemic. Many caregivers did not receive any resources prior to the pandemic and those that had resources received limited information and access due to living in a rural area. Based on these findings, the web-based parent training program, Attend Behavior, has addressed the needs of caregivers of children with ASD post- pandemic. This program can be beneficial for caregivers living in rural areas with limited access to resources and seeking support for their child with ASD.A five-year embargo was granted for this item.Academic Major: Nursin
Immune Checkpoint Inhibitor Clearance in a Genetically Engineered Mouse Model of Inducible Pancreatic Adenocarcinoma Associated Cachexia
Get PDFOver the past decade, immune checkpoint inhibitors (ICIs) have emerged as an efficacious type of anticancer therapeutics across a variety of diseases. Yet, despite the efficacy seen in these biologics, less than half of patients indicated for a given ICI respond to therapy. Further investigation has uncovered a strong correlation between rapid baseline ICI drug clearance and decreased overall survival in these patients, independent of drug exposure and dose. Of these high clearance patients, the majority fell into the diagnostic criteria of cancer cachexia, a wasting condition that sees involuntary skeletal muscle loss with or without the loss of adipose tissue. This cancer cachexia, antibody drug clearance, and decreased efficacy relationship phenomenon in patients has since been replicated in injected allograft murine cancer models. However, a common criticism of the injected allograft models is the artificiality of tumor induction, possibly misrepresenting the patient phenomenon. Thus, this project tries to address those concerns through utilizing a more translational, previously reported tamoxifen-induced transgenic mouse model (RAS_Bact) of pancreatic ductal adenocarcinoma (PDAC), resulting in rapid cachectic decline after tumor induction. We characterized the cachectic response to tumor induction (utilizing metrics of longitudinal body weight, tissue weight, etc) in this model and performed a pharmacokinetic experiment with pembrolizumab (an ICI therapeutic antibody) in PDAC mice vs uninduced RAS_Bact controls. This thesis reports a significantly higher clearance within cachectic mice relative to tumor free controls, consistent with previously reported allogeneic xenograft models.The Ohio State University College of Pharmacy (SURF Fellowship)The James Comprehensive Cancer Center (CREATES Fellowship)No embargoAcademic Major: Pharmaceutical Science
Zbtb16 as novel transcription factor in metabolism
No full textThe rapid rise in obesity and its associated co-morbidities has amplified the importance of understanding exercise-induced metabolic adaptations, particularly within adipose tissue. While previous studies have characterized macro-level tissue responses, the specific molecular and cellular mechanisms remain incompletely defined. Using single-cell RNA sequencing (scRNA-seq) of subcutaneous white adipose tissue (scWAT), our lab identified Zbtb16 as the only gene upregulated across multiple progenitor cell types following exercise. This study investigates the functional significance of Zbtb16 through both in vitro and in vivo models. We demonstrate that Zbtb16 expression increases in male adipose tissue post-exercise, but not in females, indicating a sex-specific response. Overexpression of Zbtb16 in mice via AAV8 leads to a reduction in respiratory exchange ratio (RER) in high-fat-diet-fed males, suggesting enhanced lipid metabolism. Additionally, Zbtb16 expression appears to be modulated via β-adrenergic signaling, as B3-adrenergic receptor blockade suppressed its exercise-induced upregulation. Immune markers typically elevated post-exercise, such as IL6, were also increased with Zbtb16 overexpression, supporting its role in mediating inflammatory adaptations. These findings highlight Zbtb16 as a novel regulator of adipose tissue metabolism and immune signaling in response to physical activity, with implications for future therapeutic strategies targeting metabolic disease.A three-year embargo was granted for this item.Academic Major: Biomedical Scienc
Synthesis and Characterization of Cobalt PPXP Complexes and Catalytic Investigation
Get PDFRecent studies have shown a divergence in reactivity between (PPRP)CoI2 precatalysts (R = H, Cl, CF3), appearing to be contingent on the central phosphorus substituent. This study reports the synthesis and characterization of a manifold of PPXP and (PPXP)CoI2 complexes (X = NEt2, NiPr2, OEt, OiPr, OCH2CF3, OCH(CF3)2, (-)-mentholate, and Me) to probe the impact of substituent (X) on electronic character of the metal complex. A combination of spectroscopic techniques, including NMR, Cyclic Voltammetry, Electron Paramagnetic Resonance, and DFT-simulated IR allowed for further understanding of the electronic environment of the cobalt center as a function of central phosphorus substituent. Preliminary kinetic studies allowed for a direct comparison of catalytic activity towards hydroboration of styrene via kobs. This work serves as a holistic approach to understanding precise ligand tuning to optimize catalytic activity for this PPXP system.NSF Grant CHE-2349302No embargoAcademic Major: Chemistr
Seasonal Influenza Vaccine Intention among College Students: Testing the Impact of an Implementation Intentions Intervention
Get PDFDespite known benefits of vaccines, vaccine uptake falls short of current goals. People may not vaccinate due to vaccine-relevant fears. The Reasoned Action Approach understands an individual’s behaviors as due to their intent and perceived behavioral control. Intention is predicted by attitudes, subjective norms, and perceived behavioral control. Implementation intentions are an intervention to support behavior and use a goal statement with an “if-then” statement structure. The current study included two research aims. The first aim is to test associations among the Reasoned Action Approach variables and intention to get the flu vaccine among college students. The second aim was to test the effect of an implementation intention intervention addressing vaccine-relevant fears and their effect on the Reasoned Action Approach variables predicting intention to get the seasonal flu vaccine. Participants completed an online, self-report survey. Participants in the intervention reviewed coping strategies and created an implementation intention while the control group only saw the coping strategies. Results showed that most Reasoned Action Approach variables were correlated in the expected direction. A trend was present for an association between vaccine-relevant fears and experiential attitudes. The intervention group saw a small effect size for positive change in experiential attitudes and capacity. The control group significantly decreased fear and had a trend for decreasing injunctive norms. Future research regarding implementation intentions and vaccine uptake is warranted.No embargoAcademic Major: Psycholog
The Implementation of an Evidence-Based Patient Decision Aid for Lumbar Epidural Procedures: A Quality Improvement Project
No full textBackground: The standard benchmark for outpatient procedure cancellation is less than 5%. Most procedure cancellations are avoidable and can be prevented with thorough patient evaluations and proper preparation, highlighting the critical role of standardizing patient education to help increase compliance with pre-procedure instruction.
Purpose: This project aimed to improve patient understanding of the lumbar epidural steroid injection procedure and reduce the number of procedure cancellations by 25%.
Methods: A quality improvement project using the Plan-Do-Study-Act (PDSA) framework was conducted to implement an evidence-based patient decision aid for lumbar epidural steroid injections (LESI). Outcome measures included (a) the number of cancellations for LESI procedures, (b) the frequency of decision-aid usage and patient-reported helpfulness, and (c) provider feedback on the decision-aid intervention.
Results: Twelve health providers participated in this project. The evidence-based patient decision aid was utilized for approximately 50% of patients. Among the patients who reported receiving the evidence-based decision aid, 97.1% found it helpful. The physical medicine and rehabilitation (PM&R) team experienced a 24.8% reduction in lumbar epidural procedure cancellations.
Conclusion: The data from this project suggest that an evidenced-based lumbar epidural patient decision aid should continue to enhance verbal patient education when scheduling a lumbar epidural procedure.A three-year embargo was granted for this item
Mechanism Underlying Astrocytic Uptake of Sulforhodamine 101 (SR101)
No full textHealth Under the Microscope (The Ohio State University Denman Undergraduate Research
Forum)Sulforhodamine 101 (SR101) is a commonly used chemical marker for astrocytes and is particularly useful in functional in vivo and in situ studies. However, the mechanism underlying the astrocytic uptake of SR101 remains elusive. Serendipitously, we found that SR101 uptake can be fully inhibited by meclofenamic acid (MFA). The MFA-mediated SR101 uptake inhibition is characterized by a non-competitive binding of MFA to the SR101 uptake pathway, a rapid inhibitory time course (T50, 0.4925 min), and high efficacy (IC50, 4.428 µM). Therefore, MFA emerges as a useful inhibitor to further explore the mechanism of SR101 uptake in astrocytes. In a transcriptome study, the slco1c1 mRNAs, a gene encoding L-thyroxine (T4) transporter (OATP1C1), showed high astrocyte expression. To explore slco1c1 as a potential SR101 uptake pathway, we pre-incubated acute hippocampal slices with 10 µM T4 for 20 min. This resulted in a 95% inhibition of SR101 uptake. Inhibition of OATP1C1 should lead to a buildup of ambient T4. To examine if T4 could affect neuronal excitability, we examine the electrophysiological responses of CA1 pyramidal neurons to 10 µM T4. Elevated ambient T4 appeared to attenuate the excitability of CA1 pyramidal neurons. Thus, our study has identified MFA as a potent SR101 uptake inhibitor in astrocytes. Additionally, we show that L-thyroxine competitively inhibits SR101 uptake in astrocytes, implying that slco1c1 is likely the transporter that mediates the SR101 uptake in astrocytes. Potentially, inhibition of OATP1C1 has an inhibitory impact on the excitability of CA1 pyramidal neurons.Career Accelerator Fund, 1,250 (Ohio State University, 2023 autumn)Undergraduate Research Apprenticeship Program (Ohio State University, 2024 summer)Academic Enrichment Grant, $400 (Ohio State University, 2024 fall)National Institute of Neurological Disorders and Stroke (RO1NS116059)A one-year embargo was granted for this item.Academic Major: Biolog