Digital Commons Network^™

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu

Faculty, Staff and Student Publications

Purpose: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios.

Methods: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson, Ambro Van Hoof

Faculty, Staff and Student Publications

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Body Image Mediating The Relationship Between Personality Factors, Emotionality And Extraversion, And Psychological Well-Being In A Gender-Diverse And Queer Sample, Rachel Jones

Senior Independent Study Theses

Research has examined the relationship between personality factors, body image, and psychological well-being. Some researchers look at how the three variables interact and relate to each other. Previous research shows how different levels of Emotionality and Extraversion influence one’s body image and psychological well-being (Allen & Celestino, 2018; Kokko et al., 2013; Lie et al., 2015; Swami et al., 2008). One’s body image also influences their psychological well-being. Additionally, personality factors, such as high Emotionality and low Extraversion can lead to someone having worse body image and worse well-being (Allen & Celestino, 2018). In a questionnaire that was made up …

Desperate Democrats In The Reagan Revolution: A Party Determined To Win The White House, Matthew Maxwell Akins

Senior Independent Study Theses

Bill Clinton’s 1992 election to the presidency as a Democrat ended a series of defeats for that party on the presidential level. Clinton may have won the White House, but he did not do it alone. In the decade before his victory, the “New Democrats” worked to moderate the Democratic Party from within, responding to the presidential losses of 1980, 1984, and 1988. Scholars have explored this topic from many angles, but none have explored it from the perspective of these “New Democrats” in a way that traces their story from Al From and Gillis Long to the DLC and …

Spiritual And Sexual Simultaneity: The Fourteenth-Century Psalter Of Bonne Of Luxembourg, Zoe Johnson

Senior Independent Study Theses

No abstract provided.

Stroke Clustering And Fitting In Vector Art, Khandokar Shakib

Senior Independent Study Theses

Vectorization of art involves turning free-hand drawings into vector graphics that can be further scaled and manipulated. In this paper, we explore the concept of vectorization of line drawings and study multiple approaches that attempt to achieve this in the most accurate way possible. We utilize a software called StrokeStrip to discuss the different mathematics behind the parameterization and fitting involved in the drawings.

Creating An Arcgis Dashboard For Climate Data Management And Visualization, Sydney Noel Case

Senior Independent Study Theses

The College of Wooster Department of Earth Sciences has collected over the past 12 years (and continues to collect) hourly local climate indicator data including stream level and temperature, air temperature and pressure, precipitation levels, and relative humidity. This data is collected at the College’s research station, Fern Valley, located in Holmes County, Ohio and serves as a storytelling component for regional climate change. Upon initial investigation, the extensive dataset revealed a fundamental data storage problem within Earth Sciences, as there lacked a singular location to store complex datasets. Several technological solutions were explored to create a long-term data storage, …

“What Does The Black Legend Have To Do With Cusco?”: Un Discurso De La Alteridad, La Evangelización, Y El Arte Religioso En El Cusco Colonial, Cammy Bly

Senior Independent Study Theses

Este trabajo considera las representaciones gráficas y artísticas de la conquista y la evangelización de las Américas en el contexto de la construcción del yo y del otro de Tzvetan Todorov y la reconceptualización de La Leyenda Negra de Walter Mignolo. Todorov propone que la conquista de las Américas es la conquista que “el yo hace del otro” (Todorov 13). Según Todorov, la construcción de la alteridad, u otherness, motivó las acciones de los conquistadores en las Américas y puso a los indígenas en una posición social inferior. Además de la teoría de Todorov, Walter Mignolo utiliza el …

Unearthing The Effects Of European-American Settlement On A Northeast Ohio Kettle Lake Through Diatom Stratigraphy, Justine Paul A. Berina

Senior Independent Study Theses

Recently, wetland conservation has highlighted the necessity for assessing limnological changes following European-American settlement. A prior study at Brown's Lake (northeast Ohio) identified a stratigraphic sequence that shows an abrupt transition from organic-rich muds to several centimeters of a bright loess layer, then a recovery to organic-rich sediments near the top. Based on ²¹⁰Pb dates, the loess deposition occurred before 1846 CE, when a growing population cleared trees and farmed intensively. Likewise, organics had recovered after 1950 CE, when people abandoned farmland and practiced conservation tillage. However, the effects of settlement on limnology are poorly known. Diatoms (microscopic algae; …

Backlog Burner: An Adventure Into Automated Scheduling, Anjolaoluwa J. Olubusi

Senior Independent Study Theses

The focus of this independent study is to explain the nurse scheduling problem (NSP) and use it as a basis to create an automated scheduling program. The nurse scheduling problem is an operational research problem that sets to find an optimal hospital schedule that fulfills the needs of the hospital and the personal requests of the nurses. The majority of solutions for the nurse scheduling problem are often designed within a hospital setting. The objective of this independent study is to use the solutions of the nurse scheduling problem to develop an automated scheduling program for the College of Wooster …

Puffins, The Charismatic Clowns Of The Sea: Examining The Relationship Between Community Identity And The Social Construction Of Animals, Megan Henry Tuennerman

Senior Independent Study Theses

This study analyzes the factors, internal and external, that affect the relationship between community identity and the social construction of animals, and the ways in which that social construction impacts the environment. Studied through the lens of the relationship between Atlantic Puffins and the human communities they live near, these questions situate our understanding of human societies as within, as opposed to above, the environment. Without this perspective, enacting environmental protections across the globe is ineffective. The study was conducted using ethnographic methods, including 11 formal interviews with community members and experts, along with observations in Iceland and Canada. Results …

Integrating Art History Into K-5 Social Studies Classrooms, Kate L. Schlegel

Senior Independent Study Theses

This independent study investigates the possibility for interaction between art and history in elementary school curriculum. An analysis of current education initiatives at the federal level establishes the need to create a more effective history—or, its counterpart at the elementary level, social studies--curriculum. Since other subjects–such as English, math, and science–are assessed at the national level, while history is not, this subject is often under-emphasized in order to meet learning targets in these other subjects. A study of educational theorists, such as Piaget and William Blake, establishes the potential for the study of history with students at lower stages of …

Sheltered: An Investigation Of Homelessness In The United States, Maya Renee Vasta

Senior Independent Study Theses

The purpose of this project is to investigate the connection between the social and statistical findings regarding the issue of homelessness in the United States. Because of the inconsistencies with how homelessness is tracked, two government-provided sources were used. The United States Interagency Council on Homelessness provides general data of homelessness, while the U.S. Department of Housing and Urban Development data shows the reported usage of homeless by the programs themselves. In addition, I also investigate the social impact and experiences of this issue to provide a more dynamic view of the problem of homelessness in the states. It was …

Visual Looming Cues Increases The Auditory Looming Bias, Maggie K. Mccracken

Senior Independent Study Theses

Looming objects have been environmentally relevant cues throughout human evolution due to potential danger. Observers integrate both auditory and visual signals emitted by moving objects. While visual arrival time estimates are relatively more accurate, auditory estimates are anticipatory as observers perceive a moving sound source as arriving before it actually does. In the present study, participants made loudness change judgments of sounds presented unimodally or with visual motion. The sounds consisted of two intensity ranges and conditions included both looming and receding motion. The results showed that listeners perceived looming sounds as changing more in loudness than equivalent receding sounds. …

Still Awaiting Justice: An Analysis On The Impact Of Anti-Immigrant Sentiment On The Reproductive Autonomy Of Migrant Women, Annays Esperanza Yacaman

Senior Independent Study Theses

My research aims to explain the impact of anti-immigrant sentiment on the reproductive autonomy of migrant women. Legislators typically act as their constituents feel on a certain issue, so I aimed to explore how legislators responded with legislation when their constituents held higher levels of anti-immigrant sentiment, hypothesizing that this would lead to more legislation limiting the reproductive autonomy of migrant women. I explore topics of eugenics and how anti-immigrant sentiment has led to modern day eugenics.

My hypothesis did not manifest itself in the expected way, but the results do provide evidence for a causal link between legislation meant …

"Not Liberating Women Means The Building Of A Socialist Society Is Only Half-Way Done": A Feminist Analysis Of Ho Chi Minh's Advocacy For The First Law On Marriage And Family In 1959 Vietnam, Hannah Nguyen

Senior Independent Study Theses

In October 1959, Ho Chi Minh attended and spoke before the North Vietnamese National Assembly at the “Meeting to Discuss the Draft of the Law on Marriage and Family.” The purpose of this study is to provide a feminist rhetorical analysis of this address to explicate the rhetorical strategies Ho employed to advocate for this law. I argue that Ho reframed the Marriage and Family Law into a policy that corresponded to the needs and demands of the National Assembly through methods of dissociation, association, and strategic repetition. I also found that Ho employed a dual leader/uncle first persona to …

Gaming The System: A Game Theoretic Approach To Risk Management And Cybersecurity, Abigail Breitenbucher

Senior Independent Study Theses

In this independent study, we detail two fields of game theory, traditional and evolutionary. After establishing foundational concepts in both, we explore risk management and cybersecurity through a game theoretic lens, focusing on some current applications in both fields. The research culminates in an application case of a game theoretic model for the 2017 Equifax data breach. To conclude, we discuss the implications of this model and future work involving evolutionary game theory in cybersecurity/risk management.

Setting The Stage For Representation: Women Candidates And Moderators' Impact On The Prevalence Of Women's Issues In Presidential Primary Debates, Hannah Groetsch

Senior Independent Study Theses

This Independent Study explores how women’s increased presence in presidential primary debates impacts the extent to which women’s issues are discussed in the debates. Prior research on political representation and critical mass theory indicates that women politicians can turn their identity as women (descriptive representation) into action that benefits their women constituents (substantive representation) by adding women’s voices and lived experiences into the political conversation. I capitalize on the 2020 election being the first where multiple women presidential candidates ran against each other, allowing me to see whether the increase in the number of women participating in the Democratic primary …

Deux Histoires De Meurtres Et D’Intrigues : L’Étude Et L’Application Pratique Des Techniques Courantes De La Traduction Française, Joseph Kalmar

Senior Independent Study Theses

Cette thèse vise à examiner les techniques courantes de la traduction littéraire et leur application pratique dans les contextes du thème et de la version. Le chapitre méthodologique explique d’abord les concepts qui sous-tendent les cinq techniques principales que j’ai utilisées pendant mon travail : les unités de traduction, la modulation, la transposition, l’équivalence, et l’adaptation. Chaque partie de ce chapitre comprend des exemples concrets tirés de mes traductions afin de démontrer comment et pourquoi un traducteur choisirait de profiter de ces procédés dans certains contextes. Pour la version, j’ai traduit une vingtaine de pages de Seule en sa Demeure, …

Are We Defined By Our Adversity? Examining The Relationship Between Childhood Trauma And Well-Being In Adulthood, Karabella Rose Hernandez

Senior Independent Study Theses

Much research has laid bare the significant negative impacts that childhood trauma can have on individuals’ lives; however, its relationships with other variables, including substance use, attachment, and self-esteem, are often unclear. Thus, the current study investigates the relationship between childhood trauma and psychological well-being in conjunction with the variables listed above. I predicted that childhood trauma would have significant relationships with well-being, substance use, attachment style, and self-esteem and also predicted that self-esteem would mediate the relationship between childhood trauma and well-being. Fifty-eighty (58) total participants, who were either clients or staff members of the mental health and substance …

Adaptive Npc Behavior In Maze Chase Game Using Genetic Algorithms, Karen Suzue

Senior Independent Study Theses

Difficulty adjustment, although an important aspect of game development, is a tedious and costly process that produces uncertain results due to the wide range of skill among players. Most of the current approaches to difficulty adjustment in video games include fixed incremental difficulty curves, data generalization, and extensive manual playtesting. In this study, we explore genetic algorithms as an alternative approach to difficulty balancing with a focus on adjusting NPC behavior. A maze-chase game is built for demonstration purposes. Additionally, a genetic algorithm based on previous theoretical techniques is developed for the game.

Women Of Appalachia: Common Ground, Different Matriarch, Cecelia A. Bagnoli

Senior Independent Study Theses

No abstract provided.