Digital Commons Network^™

Mhc Hammer Reveals Genetic And Non-Genetic Hla Disruption In Cancer Evolution, Clare Puttick, Thomas P Jones, Michelle M Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K Dijkstra, James R M Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A Quezada, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% …

Meta-Analysis Of Censored Adverse Events, Xinyue Qi, Shouhao Zhou, Christine B Peterson, Yucai Wang, Xinying Fang, Michael L Wang, Chan Shen

Faculty, Staff and Student Publications

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete reporting of adverse events (AEs) in published clinical studies is frequently encountered, especially if the observed number of AEs is below a pre-specified study-dependent threshold. Ignoring the censored AE information, often found in lower frequency, can significantly bias the estimated incidence rate of AEs. Despite its importance, this prevalent issue in meta-analysis has received little statistical or analytic attention in the literature. To address this challenge, we propose a Bayesian …

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …

Precision Imaging For Prostate Cancer Localization: How Multiparametric Ultrasound Stands Against Multiparametric Mri, Amr Mohammed, Priscilla Machado, Tania Siu Xiao, Aylin Tahmasebi, Mostafa Alnoury, Edouard Trabulsi, Ethan J. Halpern, John R. Eisenbrey, Flemming Forsberg

Department of Radiology Faculty Papers

Multiparametric MRI (mpMRI) is currently the standard imaging modality for the diagnosis of prostate cancer; however, studies have reported that targeted biopsy based on mpMRI may miss approximately 30% of clinically significant cases. Recent advances in ultrasound imaging have improved its accuracy for detection of prostate cancer. Newer techniques such as MicroUS, elastography, contrast-enhanced ultrasound (CEUS), and contrast ultrasound dispersion imaging (CUDI) have enabled a comprehensive, real-time, and relatively inexpensive approach to evaluate the prostate gland. Multiparametric ultrasound (mpUS) integrates multiple parameters from these techniques to generate multiparametric maps akin to those produced by mpMRI, to localize prostate cancer. This …

Implications Of Persistent Micro-Bioplastics On Biogeochemical Properties Across Soil Types, Casandra R. Leach

Master's Theses

Terrestrial microplastics are increasing in abundance and are an emerging contaminant of concern, particularly in agriculture ecosystems where plastic use and subsequent soil contamination are prevalent. Plastic film mulches make up a significant portion of the plasticulture industry and are directly linked to soil microplastic pollution where negative effects to soil biotic and abiotic functions have been observed. In response to this issue, biodegradable film mulches have been promoted as a sustainable alternative to conventional polyethylene-based mulches. These biodegradable mulches, composed of various bioplastics, are designed to be tilled back into the soil where they are expected to decompose. However, …

The Role Of The Basolateral Nuclear Complex & Central Nucleus Of The Amygdala In Fear-Conditioned Responses To External Stimuli And Anxiety Responses, Oluwaseyi A. Adelakun

Senior Theses

This thesis reviews the role of the amygdala, particularly the basolateral nuclear complex (BLA) and central nucleus (CeA), in fear-conditioned responses and generalized anxiety disorder (GAD). By investigating the neurological and physiological mechanisms that influence the amygdala’s fear and anxiety responses, further connections can be made between this region and other notable brain regions, like the prefrontal cortex (PFC). We review both human and rodent models to explore the overlap between the two and explore various therapeutic interventions that regulate amygdalar activity and therefore mitigate anxiety symptoms. Key research into the patient SM, who lacks fear responses due to bilateral …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Lukoye Atwoli

Internal Medicine, East Africa

Importance: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies’ findings are not very generalizable and have focused on different kinds of population groups.

Objective: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

Design, setting and participants: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …

Participant Engagement And Preference Study For Clinical Outcomes Associated With Atrial Fibrillation: The Pearl-Af Study, Shelby D. Reed, Josephine L. Harrington, Daniel P. Morin, Samir F. Saba, Jay Alan Montgomery, Robert W. Harrison, Daniel R. Frisch, Thomas Viethen, Miriam Tamm, Jessica Xiao, Hardi Mundl, Rosa Coppolecchia, Jui-Chen Yang, Matthew J. Wallace, Juan Marcos Gonzalez, Manesh R. Patel

Division of Cardiology Faculty Papers

Background: Quantifying patients’ preferences for health outcomes associated with atrial fibrillation (AF) and its treatments offers a replicable approach to considering the patient perspective in regulatory decision-making. Objective: The authors conducted a preference survey to estimate the relative importance of AF-related events for use in clinical trial analyses to estimate net health benefits with anticoagulants. Methods: The survey included nontechnical descriptions of three severities of stroke, systemic embolism, myocardial infarction (MI) with or without subsequent heart failure (HF), major bleeding, clinically relevant nonmajor bleeding, and death. A best-worst scaling question format was used in which patients were shown 10 sets …

El Campanario (Volume 1, Issue 1), St. Mary's University

Honors Program Newsletters

No abstract provided.

Blurring Boundaries: A Proposed Research Agenda For Ethical, Legal, Social, And Historical Studies At The Intersection Of Infectious And Genetic Disease, Seethal Jose, Juli Bollinger, Gail Geller, Jeremy Greene, Leslie Meltzer Henry, Brian Hutler, Eric Thomas Juengst, Jeffrey Kahn, Anna Mastroianni, Graham Mooney

Articles

Contemporary understanding of the mechanisms of disease increasingly points to examples of “genetic diseases” with an infectious component and of “infectious diseases” with a genetic component. Such blurred boundaries generate ethical, legal, and social issues and highlight historical contexts that must be examined when incorporating host genomic information into the prevention, outbreak control, and treatment of infectious diseases.

Strategies For Prevention And Management Of Non-Communicable Diseases Among Community Women In Nigeria: Insights For Family Social Welfare, Abiola Adiat Omokhabi Dr

Journal of Human Services: Training, Research, and Practice

In this study, modifiable risk factors, prevention and management plans for non-communicable diseases (NCDs) among women were examined. This study examined published and grey literature that was gathered from a number of sources, such as open data portals on the five major illness categories that make up the NCDs such as cardiovascular diseases (CVDs), diabetes, malignancies, chronic respiratory diseases, and mental health. Literature shows that the primary behavioural risk factors for NCDs, including CVDs, diabetes, and cancer(malignancies), can be largely avoided. Inactivity, tobacco use, alcohol use, and unhealthy eating habits (often high in processed sugar, fats, and salt) are a …

Voices From The Classroom: A Qualitative Study Of Teachers' Perspectives On Student Depression, Naomi Brinton, Jacqlyn Zarabba, Linda Mcwhorter, Linda Knauss

Journal of Human Services: Training, Research, and Practice

Rising levels of depression among adolescents is an important issue to teachers and school administrators, as teenagers spend the majority of their time in the school environment. By analyzing individual interviews with 15 public high school teachers using a modified grounded theory approach, this qualitative study examines the role high school teachers might play in identifying and referring students who exhibit signs and symptoms of depression. Results provide guidance for high school teachers in connecting students with appropriate services and identifying common barriers and facilitating factors in this process. Specific recommendations are outlined to help aid schools in the identification …

Outcome Of Vital Pulp Therapy Using Mta And Biodentine In Permanent First Molars With Or Without Pulpitis In Pediatric Patients, Daniel Nho Dmd, Ms, Susan Paurazas Dds, Ms, Mhsa, Mazin Askar Bds, Ms, Salwa Atwan Dds, Ms

The Journal of the Michigan Dental Association

Purpose: This study evaluated the outcome of vital pulp therapy (VPT) in permanent first molar teeth using Biodentine (Septodont, Saint Maur des Fosses, France) or ProRoot MTA (Dentsply Tulsa Dental Specialties, Johnson City, Tenn.) in pediatric patients. Methods: Permanent first molar teeth with or without a history of pulpitis from patients aged 7 to 14 years old were treated at the Graduate Endodontic Clinic from September 2007 to August 2022. A retrospective cohort clinical trial was conducted. VPT was performed on a total of 22 teeth. There were 13 teeth in the Biodentine (BD) group and nine teeth in the …

Venom Immunization: Igg/Ige Titers, Safety, Risk, And Methods Of The Viprbitem Cohort, Brian P. Hanley, Gustavo Gross

School of Medicine Publications

Background: This is the first study to examine a cohort that engages in the practice of immunization with snake venoms. In this practice, either fresh wet venom or venom reconstituted from freeze-dried form is used in vaccination protocols to produce hyper-immunity to venom.

Methods: This is a retrospective community-initiated collaborative research (CICR) project that collated the records of venom immunization. Records of schedules, formulations, photographs, medical records, and diaries were collated from existing practitioners and evaluated by inspection and interviews. One accidental bite was observed over 3 days, with vital signs, and photographic records of swelling taken to verify reality …

A Sophisticated Model Of Human Atherosclerosis On A Chip, Brandon J. Tefft

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Realtime And Noninvasive Assessment Of Endotracheal Tube Displacement Using Near-Infrared And Visible Cameras, Tongtong Lu, Pawjai Khampang, Ahmed Beydoun, Rebecca Rodhe, Wenzhou Hong, Joseph E. Kerschner, Bing Yu

Biomedical Engineering Faculty Research and Publications

Endotracheal tube (ETT) intubation is a medical procedure routinely used for achieving mechanical ventilation in critically ill patients. Appropriate ETT placement is crucial as undetected tube migration may cause multiple complications or even fatalities. Therefore, prompt detection of unplanned movement of the ETT and immediate action to restore proper placement are essential to ensure patient safety. Despite this necessity, there is not a widely adopted tool for real-time assessment of ETT displacement. We have developed a device, a dual-camera endotracheal tube or DC-ETT, to address this unmet clinical need. This device uses a near-infrared (NIR) LED and a side-firing optical …

Tracking Implementation Of Shark-Related Measures And Actions In The Mediterranean Region In The Context Of International Law, Jason Lowther, Lydia Koehler

School of Law, Humanities and Social Sciences

We present national implementation progress on international and regional legal obligations up to 2020 and discuss recent developments in shark conservation management in the region. This study provides insights into the complexity of implemented measures and actions related to shark conservation and fisheries management, governed by various legal instruments. Measures were primarily identified through regional fisheries management organisations (RFMO) reports, reports of Focal Point meetings under the Barcelona Convention, and national reports under the Convention on Biological Diversity (CBD) and the Convention on Migratory Species (CMS). A total of 208 implemented measures across different categories were found. The most common …

Pagbabalik-Tanaw Sa Maagang Malay Ni Jose Rizal Sa Kakanyahang Malay At Pagsipat Sa Kinahinatnang Pananangkapan At Retorikang Politikal Dito Noong Dantaon 20, Axle Christien J. Tugano

Journal Article

Batay sa isinusulong na mandato ng General Education (GE) Courses Program ng University of the Philippines (UP), kinakailangang maisingkaw sa pag-aaral at/o pagtuturo ng PI 10 (Philippine Institutions: The Life, Works, and Writings of Jose Rizal) ang panlipunang saysay (social utility) ni Jose Rizal tungo sa pagiging makatao at makabayan ng mga Pilipino. Kaakibat ng preskripsiyong ito ang integratibong paghuhugpong sa kaniyang kaisipan sa iba’t ibang disiplina at paksa. Layunin ng pag-aaral na ito ang integratibong pagsasalok sa katuturan ni Rizal sa iba pang kurso ng kasaysayan katulad ng HIST 1 (Philippine History) o KAS 1 (Kasaysayan ng Pilipinas) bilang …

Sex Differences In Active Avoidance And Neural Circuit Mechanisms In Contextual Fear Generalization, Carly Vincent

Theses and Dissertations

The current studies were aimed to investigate two behavioral hallmarks of anxiety and stress-related disorders, avoidance responses and the over-generalization of fear. In the first set of studies, active avoidance and extinction learning, that parallels exposure therapy in preclinical rodent models, were used. It is known that stress can influence aversive learning and extinction training, which can result in poor extinction retention. However, it is not well understood how the stress response is facilitating extinction resistance in active avoidance learning across sexes. Therefore, the first set of studies aimed to investigate the role of biological sex and glucocorticoid receptor (GR) …

Discovering Therapeutic Strategies In Colorectal Cancer Via Synthetic Lethal Genetic Screens On Patient-Derived Organoid Models, Sana Khalili

Theses and Dissertations

Precision medicine is a revolutionary approach of targeting genetic alterations that are present only in tumor cells to find vulnerabilities that can be targeted with therapy. Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens can reveal all genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs.

In this dissertation, I comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. I identified all somatic mutations, all expressed genes, and conducted a genome-wide CRISPR dropout screen to elucidate …

Impacts Of Ing4-Deficiency On Hematopoietic Stem And Progenitor Cells & Characterizing The Concerns Of Novice Stem Graduate Teaching Assistant, Georgina Alice Anderson

Theses and Dissertations

The hematopoietic compartment is tasked with the establishment and maintenance of the entire blood program in steady-state and in response to stress. Key to this process are hematopoietic stem cells (HSCs), which possess the unique ability to self-renew and differentiate to replenish blood cells throughout an organism’s lifetime. Recent work has illustrated the vast mechanisms involved in regulating stress-induced hematopoiesis, including cytokine-mediated lineage bias, gene signature changes in aged HSCs associated with chronic inflammation, the impact of clonal hematopoiesis and stress tolerance. Inhibitor of Growth 4 (Ing4) has been identified as a critical regulator of HSC homeostasis. We show that …

Mitochondrial Function In The Maternal Brain: A New Perspective On Gestational Stress And Pathology Of Postpartum Depression, Erin Rene Gorman-Sandler

Theses and Dissertations

Postpartum depression (PPD) is a major psychiatric complication of childbirth, affecting up to 20% of mothers, yet remains understudied. Mitochondria, dynamic organelles crucial for cell homeostasis and energy production, share links with many of the proposed mechanisms underlying PPD pathology. Brain mitochondrial function is affected by stress, a major risk factor for development of PPD, and is linked to avoidance and social behaviors. Considering the importance of mitochondria in regulating brain function and behavior, we hypothesized that mitochondrial dysfunction is associated with behavioral alterations in a chronic stress-induced rat model of PPD. Chronic mild unpredictable (CMUS) stress during late gestation …

Plankton Dynamics In A Temperate Estuary:Size Structure And Trophic Implications, Nayan Mallick

Theses and Dissertations

Estuarine ecosystems provide goods and services to around 45% of the entire human population. In recent times, these ecosystems have been severely affected by multiple stressors such as pollution, eutrophication, harmful algal blooms, sea level rise, and, most importantly, climate change. Increasing temperature associated with climate change can have pervasive impacts throughout the ecosystem’s functions and processes. Plankton, a conspicuous member of estuarine food web, are among the first to respond to the changes in temperature due to their high sensitivity to changing environmental conditions.

In this dissertation, I investigated the plankton dynamics in an estuarine ecosystem through a combination …

Multi-Scale Ai-Assisted Gene Expression Decoding, Fengyao Yan

Theses and Dissertations

Genes can be treated as a graph that can be mapped. Tremendous information is coded in genes to ensure a complex functioning organism. Decoding this information is critical to understanding our biology and developing treatments for various diseases including cancer. Deep learning, a new branch of computer science, has gained traction over the past decade. It offers more insight into the data that is processed by the deeplearning models. Our study has shown that deep-learning models can be an effective tool in decoding genetic data such as gene tissue-deconvolution, gene graph mapping and genomic imputation. In tasks such as tissue …

Assessing The Accuracy, Validity, And Application Of A New Method For Sex Estimation Using Isotopic Ratios Of Fe, Cu, And Zn In Human Bone, Elizabeth Anne Wakefield

Theses and Dissertations

This dissertation evaluates the accuracy, validity, and application of a novel sex determination method based on isotopic variations in copper (Cu) and iron (Fe) within human bone, initially developed by Jaouen et al. (2012). The primary aim of this research was to test the reproducibility of the method, expand the sample to include a broader age range and ethnically diverse groups, and assess its applicability in forensic contexts using contemporary skeletal samples. Bone samples were collected from 60 individuals across two curated skeletal collections: the George S. Huntington Skeletal Collection and the Texas State Forensic Anthropology Donated Skeletal Collection. The …

Creating A Quality Feedback System Between School Administrators And Teachers, Gerald Keith Price

Theses and Dissertations

After moving to a new school district as superintendent, I recognized early on that student achievement was low and intentional work needed to be done to bring about academic improvement. As the district leadership team began to explore causes and discuss possible solutions, we decided we needed to focus on changing the perception around instructional leadership. School administrators are much more likely to have mutual dialogue with their teachers when they assume the role of a coach rather than a superior. With open lines of communication, teachers and administrators are able to discuss ways to maximize learning time with students …

Engaging Students In The Scientific Process: An Examination Of Active Learning Strategies In Introductory Geoscience Labs, Meryssa Piper

Theses and Dissertations

High-quality instruction of introductory geoscience courses entices students to major in geoscience fields and ensures undergraduate students have opportunities to learn and apply scientific information and practices. Prior studies indicate that active learning strategies in higher education settings can increase student knowledge and interest. This dissertation explores the integration of two active learning strategies in introductory geoscience laboratory courses: inquiry and gamification The first study housed in Chapter 2 investigates the level of inquiry used in introductory geoscience lab activities across the United States. Through a comprehensive analysis of these activities, this chapter assesses: (1) the degree to which instructor …

Exploring The Impact Of Teacher Curiosity On Job Satisfaction And Self-Efficacy: A Quantitative Study In Stem Education, Christopher Jeffcoat

Theses and Dissertations

This dissertation presents a quantitative study involving 96 teachers of STEM subjects, aimed at investigating the relationship between teacher curiosity, job satisfaction, and teacher self-efficacy. The primary objective was to examine the significance of teacher curiosity in the context of educators' job satisfaction. The research findings indicate a moderate positive correlation between teacher curiosity and job satisfaction (r=0.57), suggesting that educators with higher curiosity tend to experience greater job satisfaction. Also, a moderate positive correlation (r=0.51) was identified between teacher curiosity and teacher self-efficacy, emphasizing the connection between curiosity and educators' belief in their ability to positively impact student learning. …

Providing A Social Emotional Learning Opportunity To Virtual Students Struggling With Social Anxiety: Group Counseling As An Intervention, Josie Kate White Ivey

Theses and Dissertations

The purpose of this mixed methods action research dissertation was to offer a social/emotional learning opportunity for virtual students struggling with social anxiety. A six-week group counseling experience was offered to on-campus high school students focused on social anxiety in order to determine is group counseling would be a beneficial intervention strategy for virtual students also dealing with social anxiety. An observer protocol was used to make note of participants responses and physical characteristics related to social anxiety and make reflective notes after each counseling session. Group participants also completed quick-check exit tickets to help the researcher determine the student’s …

In Search Of Cognitive Justice: One District’S Approach To Implementing Culturally Responsive Practices, Anne Marie Mancini

Theses and Dissertations

This action research study examined district leaders' approach to integrating culturally responsive practices into classrooms in a medium-sized urban Connecticut public school system. The framework for this study was supported by two theories: transformative learning and culturally responsive pedagogy. Following a case study model of design, the project focused on the work of the Supervisor of Professional Learning and the Department Supervisor for English Language Arts (ELA) as they provided training, support, and resources to the Grade 7 team. Two research questions guided this study: (1) What successes, if any, did district leaders experience in implementing culturally responsive teaching practices …