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Objective: To investigate current HCP stillbirth aftercare practices and use findings to inform suggestions for stillbirth aftercare guidelines. Study Design: Participants (n=18) were HCPs (MDs, DOs, or NPs) in the field of Obstetrics and Gynecology or Maternal Fetal Medicine. Focus groups and surveys were conducted. A phenomenological approach was used

Objective: To investigate current HCP stillbirth aftercare practices and use findings to inform suggestions for stillbirth aftercare guidelines. Study Design: Participants (n=18) were HCPs (MDs, DOs, or NPs) in the field of Obstetrics and Gynecology or Maternal Fetal Medicine. Focus groups and surveys were conducted. A phenomenological approach was used to explore and understand current stillbirth aftercare practices and thoughts about protocols for stillbirth aftercare. Descriptive statistics were used to analyze demographics of participants and prevalence of references to stillbirth aftercare topics. Results: Sixteen obstetric HCPs (medical doctors and nurse practitioners in the fields of obstetrics and gynecology and/or maternal and fetal medicine) participated in Focus Groups and two obstetric HCPs alternatively completed surveys. Current stillbirth aftercare practices and perceptions related to stillbirth aftercare protocols and guidelines were clustered around the following themes: recommendations made to mothers after stillbirth, subsequent pregnancy care, perceptions and use of protocols for stillbirth aftercare, and responsibilities of nurses and nurse practitioners after stillbirth. Conclusion: Findings were used to develop a list of stillbirth aftercare practice suggestions and may be used to help design future research related to HCPs' stillbirth aftercare practices and the need for training on existing guidelines and development of further protocols or guidelines.
ContributorsMartinez, Lauren Ann (Author) / Huberty, Jennifer (Thesis director) / Coursen, Cristi (Committee member) / Leiferman, Jennifer (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Background: The purpose of this study was to determine the acceptability of a survey for MPN patients about: a) how patients with MPN cancer perceive information relayed from their healthcare providers in regards to integrative medicine and b) how patients use integrative medicine modalities to cope with their symptom burden

Background: The purpose of this study was to determine the acceptability of a survey for MPN patients about: a) how patients with MPN cancer perceive information relayed from their healthcare providers in regards to integrative medicine and b) how patients use integrative medicine modalities to cope with their symptom burden (i.e. fatigue, headaches, abdominal discomfort). Additionally, we assessed what MPN patients thought about the survey (i.e., questions asked, how it could be modified, acceptability). This paper presents the patient's assessment of the survey. This information will be used to finalize the survey and distribute nationally to address integrative medicine and symptom burden in MPN patients. Methods: The survey was taken by 366, English speaking patients previously diagnosed with essential thrombocythemia, polycythemia vera, or myelofibrosis (primary and post polycythemia vera/post essential thrombocythemia) and ages 18 or older. The survey had XX questions and took approximately 20 minutes to complete. Acceptability questions were qualitatively analyzed and used to construct recurring themes and modifications for the final MPN Integrative Survey. Results: The following themes were recurrent in the acceptability responses; MPN symptom burden comments, views on healthcare, comments about demographics, and requests for survey modifications. When asked which Integrative Therapies have been used to treat symptom burden, participants most commonly named guidance therapy (i.e. counseling, prayer), physiotherapy ,and supplements administered orally, intravenously, intramuscularly, and topically. Conclusions: These results suggest this survey is an acceptable and feasible tool for MPN patients to assess how patients with MPN cancer perceive information relayed from their healthcare providers in regards to integrative medicine, and how patients use integrative medicine modalities to cope with their symptom burden. These findings also provide a better understanding of what facilitates and prevents MPN patients from using Integrative Medicine to treat MPN symptoms, as well as suggests useful survey modifications to inform the final MPN Integrative Survey.
ContributorsLebowitz, Nicole (Author) / Huberty, Jennifer (Thesis director) / Gowin, Krisstina (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Objective: The purpose of this study was to determine the feasibility (i.e., acceptability) of a yoga intervention implemented within a preschool with typically and atypically developing children.
Participants: 29 children between the ages of three and five years that are currently attending the Mary Lou Fulton Teacher’s College Preschool.

Methods: Children

Objective: The purpose of this study was to determine the feasibility (i.e., acceptability) of a yoga intervention implemented within a preschool with typically and atypically developing children.
Participants: 29 children between the ages of three and five years that are currently attending the Mary Lou Fulton Teacher’s College Preschool.

Methods: Children participated in eight ~15-20-minute yoga sessions consisting of an opening circle, breathing, mindful movement, and a closing circle with relaxation time. Parents completed weekly homework assignments and surveys about the homework. Parents and teachers both completed daily behavior logs to track their child’s number of outbursts, mention of yoga, and use of yoga. Additionally, parents completed a post-intervention survey to determine overall satisfaction.

Results: The Preschool Behavior Questionnaire paired t-test results did not demonstrate any significant differences in pre-intervention (M=13.00, SD±7.55) and post-intervention (M=11.95, SD±6.92) scores, t(17)=0.94, p=0.36. There were no visible correlations between outbursts and use of yoga as reported by parents, but the use of yoga increased with the number of outbursts as reported by parents. Overall, parents felt the sessions had a positive effect on their child’s behavior and felt their children enjoyed the sessions.

Conclusion: Implementing classroom-based yoga programs could be an acceptable, realistic option to manage and prevent negative behaviors in preschool children.
ContributorsColeman, Lindsey Katlin (Author) / Huberty, Jennifer (Thesis director) / Rotheram-Fuller, Erin (Committee member) / Mullady, Allison (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Background: The purpose of this study was to determine the feasibility of using Facebook as compared to a discussion board in an online, web-based intervention, Fit Minded College Edition-Podcasts (FMCEP), to improve physical activity and self-worth in female college students.
Methods: Participants (n=55) were randomly assigned to either a private

Background: The purpose of this study was to determine the feasibility of using Facebook as compared to a discussion board in an online, web-based intervention, Fit Minded College Edition-Podcasts (FMCEP), to improve physical activity and self-worth in female college students.
Methods: Participants (n=55) were randomly assigned to either a private Facebook group (FB) or the Fit Minded discussion board (DB) to participate in discussion of health and wellness related podcasts. FMCEP was a 6-week intervention guided by the self-determination theory (SDT) to target autonomy, relatedness and competence. Each week participants were instructed to complete three tasks: (1) listen to an assigned podcast, (2) complete a workbook assignment, and (3) participate in FB or DB online discussion. Participants completed assessments at baseline and post-intervention (6-weeks).
Results: Self-reported physical activity (p=0.032, η2= 0.193) and physical self-worth (p<0.001, η2=0.747) increased significantly over time, but no difference was seen between the groups for both physical activity (p=0.266, η2= 0.056) and physical self-worth (p=0.485, η2=0.024). Website use (measured by mean number of engagements per day, each week) declined across the 6-week intervention in the DB group but was consistent in the FB group.
Conclusion: These findings suggest web-based interventions, guided by SDT, can improve physical activity and physical self-worth among female college students, and the Facebook group may be more feasible and effective. Future studies are needed to optimize web-based physical activity interventions in college females.
ContributorsSorteberg, Samantha Fern (Author) / Huberty, Jennifer (Thesis director) / Bruening, Meg (Committee member) / Mailey, Emily (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Nucleic acid polymers have numerous applications in both therapeutics and research to control gene expression and bind biologically relevant targets. However, due to poor biological stability their clinical applications are limited. Chemical modifications can improve both intracellular and extracellular stability and enhance resistance to nuclease degradation. To identify a potential

Nucleic acid polymers have numerous applications in both therapeutics and research to control gene expression and bind biologically relevant targets. However, due to poor biological stability their clinical applications are limited. Chemical modifications can improve both intracellular and extracellular stability and enhance resistance to nuclease degradation. To identify a potential candidate for a highly stable synthetic nucleic acid, the biostability of α-L-threofuranosyl nucleic acid (TNA) was evaluated under simulated biological conditions. TNA contains a four-carbon sugar and is linked by 2’, 3’ phosphodiester bonds. We hypothesized that this distinct chemical structure would yield greater nuclease resistance in human serum and human liver microsomes, which were selected as biologically relevant nuclease conditions. We found that TNA oligonucleotides remained undigested for 7 days in these conditions. In addition, TNA/DNA heteropolymers and TNA/RNA oligonucleotide duplexes displayed nuclease resistance, suggesting that TNA has a protective effect over DNA and RNA. In conclusion TNA demonstrates potential as a viable synthetic nucleic acid for use in numerous clinical and therapeutic applications.
ContributorsCulbertson, Michelle Catherine (Author) / Maley, Carlo (Thesis director) / Mangone, Marco (Committee member) / Larsen, Andrew (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including

Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
The splicing of precursor messenger RNAs (pre-mRNAs) plays an essential role in dictating the mature mRNA profiles of eukaryotic cells. Mis-regulation of splicing, due to mutations in pre-mRNAs or in components of the splicing machinery, is associated with many diseases. Therefore, knowledge of pre-mRNA splicing mechanisms is required to understand

The splicing of precursor messenger RNAs (pre-mRNAs) plays an essential role in dictating the mature mRNA profiles of eukaryotic cells. Mis-regulation of splicing, due to mutations in pre-mRNAs or in components of the splicing machinery, is associated with many diseases. Therefore, knowledge of pre-mRNA splicing mechanisms is required to understand gene expression regulation during states of homeostasis and disease, and for the development of therapeutic interventions.Splicing is catalyzed by the spliceosome, a dynamic and protein-rich ribozyme composed of five small nuclear ribonucleoproteins (snRNPs) and ~170 auxiliary factors. Early interactions that occur in prespliceosomal complexes formed by the 5′- and 3′-splice-site bound U1 and U2 snRNPs are responsible for committing introns for removal. However, the mechanisms underlying these early interactions remain to be fully characterized for understanding the influence of alternative splicing factors and the impact of recurrent disease-associated mutations in prespliceosomal proteins. The goal of my dissertation research was to delineate the role of the U1 small nuclear RNA (snRNA) during prespliceosome assembly. By applying a cellular minigene reporter assay and a variety of in vitro techniques including cell-free protein expression, UV-crosslinking, electrophoretic mobility shift assays, surface plasmon resonance, and RNA affinity purification, my work establishes critical roles for the U1 snRNA stem-loops 3 (SL3) and 4 (SL4) in formation of intron definition interactions during prespliceosome assembly. Previously, the SL4 of the U1 snRNA was shown to form a molecular bridge across introns by contacting the U2-specific splicing factor 3A1 (SF3A1). I identified the Ubiquitin-like domain of SF3A1 as a non-canonical RNA binding domain responsible for U1-SL4 binding. I also determined a role for the SL3 region of the U1 snRNA in splicing and characterized the spliceosomal RNA helicase UAP56 as an SL3 interacting protein. By knocking-down the SL3- and SL4-interacting proteins, I confirmed that U1 splicing activity in vivo relies on UAP56 and SF3A1 and that their functions are interdependent. These findings, in addition to the observations made using in vitro splicing assays, support a model whereby UAP56, through its interaction with U1-SL3, enhances the cross-intron interaction between U1-SL4 and SF3A1 to promote prespliceosome formation.
ContributorsMartelly, William (Author) / Sharma, Shalini (Thesis advisor) / Mangone, Marco (Thesis advisor) / Gustin, Kurt (Committee member) / Chen, Julian (Committee member) / Arizona State University (Publisher)
Created2021
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Meditation app usage is associated with decreases in stress, anxiety, and depression symptoms. Many meditation app subscribers, however, quickly abandon or reduce their app usage. This dissertation presents three manuscripts which 1) determined the behavioral, demographic, and socioeconomic factors associated with the abandonment of a meditation app, Calm, during the

Meditation app usage is associated with decreases in stress, anxiety, and depression symptoms. Many meditation app subscribers, however, quickly abandon or reduce their app usage. This dissertation presents three manuscripts which 1) determined the behavioral, demographic, and socioeconomic factors associated with the abandonment of a meditation app, Calm, during the COVID-19 pandemic, 2) determined which participant characteristics predicted meditation app usage in the first eight weeks after subscribing, and 3) determined if changes in stress, anxiety, and depressive symptoms from baseline to Week 8 predicted meditation app usage from Weeks 8-16. In Manuscript 1, a survey was distributed to Calm subscribers in March 2020 that assessed meditation app behavior and meditation habit strength, and demographic information. Cox proportional hazards regression models were estimated to assess time to app abandonment. In Manuscript 2, new Calm subscribers completed a baseline survey on participants’ demographic and baseline mental health information and app usage data were collected over 8 weeks. In Manuscript 3, new Calm subscribers completed a baseline and Week 8 survey on demographic and mental health information. App usage data were collected over 16 weeks. Regression models were used to assess app usage for Manuscripts 2 and 3. Findings from Manuscript 1 suggest meditating after an existing routine decreased risk of app abandonment for pre-pandemic subscribers and for pandemic subscribers. Additionally, meditating “whenever I can” decreased risk of abandonment among pandemic subscribers. No behavioral factors were significant predictors of app abandonment among the long-term subscribers. Findings from Manuscript 2 suggest men had more days of meditation than women. Mental health diagnosis increased average daily meditation minutes. Intrinsic motivation for meditation increased the likelihood of completing any meditation session, more days with meditation sessions, and more average daily meditation minutes. Findings from Manuscript 3 suggest improvements in stress increased average daily meditation minutes. Improvements in depressive symptoms decreased daily meditation minutes. Evidence from this three-manuscript dissertation suggests meditation cue, time of day, motivation, symptom changes, and demographic and socioeconomic variables may be used to predict meditation app usage.
ContributorsSullivan, Mariah (Author) / Stecher, Chad (Thesis advisor) / Huberty, Jennifer (Committee member) / Buman, Matthew (Committee member) / Larkey, Linda (Committee member) / Chung, Yunro (Committee member) / Arizona State University (Publisher)
Created2022
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Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the

Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the last decade there has been considerable interest in using HDAC inhibitors (HDACi) for the treatment of malignant primary brain tumors. However, to date most HDACi tested in clinical trials have failed to provide significant therapeutic benefit to patients with GBM. This is because current HDACi have poor or unknown pharmacokinetic profiles, lack selectivity towards the different HDAC isoforms, and have narrow therapeutic windows. Isoform selectivity for HDACi is important given that broad inhibition of all HDACs results in widespread toxicity across different organs. Moreover, the functional roles of individual HDAC isoforms in GBM are still not well understood. Here, I demonstrate that HDAC1 expression increases with brain tumor grade and is correlated with decreased survival in GBM. I find that HDAC1 is the essential HDAC isoform in glioma stem cells and its loss is not compensated for by its paralogue HDAC2 or other members of the HDAC family. Loss of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner and leads to significant suppression of tumor growth in vivo. While no HDAC isoform-selective inhibitors are currently available, the second-generation HDACi quisinostat harbors high specificity for HDAC1. I show that quisinostat exhibits potent growth inhibition in multiple patient-derived glioma stem cells. Using a pharmacokinetics- and pharmacodynamics-driven approach, I demonstrate that quisinostat is a brain-penetrant molecule that reduces tumor burden in flank and orthotopic models of GBM and significantly extends survival both alone and in combination with radiotherapy. The work presented in this thesis thereby unveils the non-redundant functions of HDAC1 in therapy- resistant glioma stem cells and identifies a brain-penetrant HDACi with higher selectivity towards HDAC1 as a potent radiosensitizer in preclinical models of GBM. Together, these results provide a rationale for developing quisinostat as a potential adjuvant therapy for the treatment of GBM.
ContributorsLo Cascio, Costanza (Author) / LaBaer, Joshua (Thesis advisor) / Mehta, Shwetal (Committee member) / Mirzadeh, Zaman (Committee member) / Mangone, Marco (Committee member) / Paek, Andrew (Committee member) / Arizona State University (Publisher)
Created2022
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Advances in sequencing technology have generated an enormous amount of data over the past decade. Equally advanced computational methods are needed to conduct comparative and functional genomic studies on these datasets, in particular tools that appropriately interpret indels within an evolutionary framework. The evolutionary history of indels is complex and

Advances in sequencing technology have generated an enormous amount of data over the past decade. Equally advanced computational methods are needed to conduct comparative and functional genomic studies on these datasets, in particular tools that appropriately interpret indels within an evolutionary framework. The evolutionary history of indels is complex and often involves repetitive genomic regions, which makes identification, alignment, and annotation difficult. While previous studies have found that indel lengths in both deoxyribonucleic acid and proteins obey a power law, probabilistic models for indel evolution have rarely been explored due to their computational complexity. In my research, I first explore an application of an expectation-maximization algorithm for maximum-likelihood training of a codon substitution model. I demonstrate the training accuracy of the expectation-maximization on my substitution model. Then I apply this algorithm on a published 90 pairwise species dataset and find a negative correlation between the branch length and non-synonymous selection coefficient. Second, I develop a post-alignment fixation method to profile each indel event into three different phases according to its codon position. Because current codon-aware models can only identify the indels by placing the gaps between codons and lead to the misalignment of the sequences. I find that the mouse-rat species pair is under purifying selection by looking at the proportion difference of the indel phases. I also demonstrate the power of my sliding-window method by comparing the post-aligned and original gap positions. Third, I create an indel-phase moore machine including the indel rates of three phases, length distributions, and codon substitution models. Then I design a gillespie simulation that is capable of generating true sequence alignments. Next I develop an importance sampling method within the expectation-maximization algorithm that can successfully train the indel-phase model and infer accurate parameter estimates from alignments. Finally, I extend the indel phase analysis to the 90 pairwise species dataset across three alignment methods, including Mafft+sw method developed in chapter 3, coati-sampling methods applied in chapter 4, and coati-max method. Also I explore a non-linear relationship between the dN/dS and Zn/(Zn+Zs) ratio across 90 species pairs.
ContributorsZhu, Ziqi (Author) / Cartwright, Reed A (Thesis advisor) / Taylor, Jay (Committee member) / Wideman, Jeremy (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022