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Mechanisms Of Immunopathology Following Covid-19 And Vaccination In Children & Early Life Immunity In Neonates, Anjali Ramaswamy

Yale Graduate School of Arts and Sciences Dissertations

Children and babies have unique infectious and inflammatory susceptibilities and are at an increased risk for developing severe disease or autoinflammatory sequelae from infections. However, many pediatric autoinflammatory diseases are poorly understood, as are mechanisms by which humans mount immune defenses in early life. We uncovered novel immunopathologic mechanisms underlying two childhood inflammatory conditions linked to COVID-19 infection and vaccination: multisystem inflammatory syndrome in children (MIS-C) and vaccine-adjacent myopericarditis, respectively. We leveraged a systems approach to study these conditions, using multiomic single-cell RNA sequencing and serum profiling. We found key signatures of MIS-C that include innate immune triggering, and an …

Functionalized Dna Nanostructures For Membrane Engineering, Qiancheng Xiong

Yale Graduate School of Arts and Sciences Dissertations

DNA nanotechnology is a powerful tool for constructing precisely designed nanostructures with applications in diverse fields, including synthetic biology, nanomedicine, and biomolecular engineering. This dissertation explores the use of DNA nanotechnology in membrane engineering, focusing on developing DNA endoskeleton-supported membranes and large functionalized DNA-toxin nanopores. The first approach encountered challenges while constructing interlocked DNA nanostructures for endoskeleton-supported membranes. The negative results highlighted the need to optimize the interlocked DNA endoskeleton cage design further to ensure its practical application in templating fully exposed, continuous membranes. The second approach incorporated pneumolysins into DNA-origami channels to create large, functionalized DNA-toxin nanopores. These hybrid …

Statistical Methods In High-Throughput Biomedical Data With Application To Precision Medicine, Yunqing Liu

Yale Graduate School of Arts and Sciences Dissertations

Precision medicine has emerged as a critical approach in healthcare due to its potential to revolutionize patient care. Traditional medical practices often adopt a one-size-fits-all approach, treating patients based on generalized guidelines. However, individuals exhibit significant variations in their genetic makeup, lifestyle factors, and environmental exposures. Precision medicine recognizes and leverages these differences to deliver personalized treatment plans tailored to each patient's unique characteristics. Recent technological advancements have facilitated the generation of high-throughput data, such as single-cell RNA sequencing (scRNA-seq) data, spatial transcriptomics (ST) data, locomotor activity assays measuring behavior, which offers the potential to the development of precision medicine. …

Bacterial Cell Surface Characterization By Phage Display Coupled To High-Throughput Sequencing, Casey Grun

Yale Graduate School of Arts and Sciences Dissertations

Antimicrobial resistance is a looming threat that reflects the remarkable capacity of bacteria to adapt and change in response to selective pressures. The versatile pathogen P. aeruginosa is a model case---already intrinsically resistant to many antibiotics, it can establish decades-long chronic infections, during which it evolves to survive antimicrobial treatment and evade host defenses. Many changes occur on its cell surface, a key location for both virulence and antibiotic resistance, but our technologies for studying these adaptive phenotypes are limited. Here we combined phage display with high-throughput DNA sequencing to create a high throughput, highly multiplexed technology for surveying bacterial …

Outbreak Dynamics Of Emerging Sars-Cov-2 Variants In Human And Animal Populations, Rebecca Lynn Earnest

Yale Graduate School of Arts and Sciences Dissertations

The COVID-19 pandemic is characterized by cycles of SARS-CoV-2 viral variant emergence followed by surges of infections and deaths. In the United States, the most notable variants to date are Alpha (B.1.1.7), Delta (B.1.617.2 and AY.x sub-lineages), and Omicron (BA.1, BA.2, BA.4, BA.5, and various sub-lineages). Pandemic response evolved along with the virus, raising three overarching research questions with each new variant that correspond to the chapters of this dissertation. When a new variant emerges, how is it different from the previously dominant variant(s) in circulation? The set of mutations that define a SARS-CoV-2 variant can affect viral properties such …

Yale Medicine Magazine Autumn 2023, Issue 171, Yale University. School Of Medicine

Yale Medicine Magazine - alumni bulletin and magazine

This is the Autumn 2023 issue of Yale Medicine Magazine, issue 171. Prepared in cooperation with the alumni and development offices at the School of Medicine. Earlier volumes are called Yale School of Medicine alumni bulletins, dating from v.1 (1953) through v.13 (1965) and Yale Medicine: alumni bulletin of the School of Medicine, v.1 (1965) through v. 52, no.1. (Autumn 2017).

Use Of A Decision Aid In Medication Initiation Among Patients With Opioid Use Disorder And Hiv, Katrina Gateley

Yale School of Medicine Physician Associate Program Theses

Opioid use disorder refers to the maladaptive use of prescribed or illicit opioids. This condition can be treated using pharmacotherapy referred to as medications for opioid use disorder (MOUD), but they are underutilized. Opioid use disorder is more prevalent among people living with HIV (PLH), highlighting a target population for interventions to increase treatment. Patient decision aids have been successful in affecting decision-making in other populations. However, no decision aid for medication for opioid use disorder has been utilized among patients with comorbid HIV and OUD. In this randomized cluster trial, we will determine whether a patient decision aid affects …

Media Release Q1 23, Credit Suisse

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No abstract provided.

Credit Suisse Reports Pre-Tax Income Of Chf 12.8 Bn With A Cet1 Ratio Of 20.3% In 1q23; Results Reflect Write-Down Of Chf 15 Bn At1 Capital Notes, Credit Suisse

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No abstract provided.

Visualization Of Infection And Therapies For Sars-Cov-2 Variants Of Concern In Murine Models Of Infection, Kelly Symmes

Yale Graduate School of Arts and Sciences Dissertations

The declaration of the COVID-19 pandemic compelled urgent research into better understanding the causative agent, SARS-CoV-2, and the race for a vaccine and therapeutics for the severely ill. Since its emergence in late 2019, several variants of concern have arisen, characterized in part by their mutations in the spike glycoprotein, that have altered ACE-2 binding efficiency, disease progression and pathogenesis, and viral kinetics. These mutations can also allow for immune evasion from antibodies, highlighting the need to better understand the immune response to infection and a rapid modality to characterize emerging variant pathogenesis and screen potential therapeutics. Here, we introduce …

Signaling Between Intraepithelial T Cells And Villous Enterocytes In Celiac Disease, Justin Johnson

Yale Graduate School of Arts and Sciences Dissertations

Celiac disease (CeD) is a common autoimmune disorder triggered by HLA-DQ2/DQ8-restricted CD4 T cells responding to gluten-derived peptides that have been deamidated by tissue transglutaminase 2 (TG2). These activated CD4 T cells then provide help to B cells that produce IgA antibodies to deamidated gluten peptides (DPG) and TG2. Histologically, the epithelial lining of the small intestinal villi is destroyed by infiltrating cytotoxic T cells (CTLs) that replace the normal resident T cell populations, resulting in villous flattening and absorptive dysfunction. The link between the response of CD4+ T cells to DPGs and the generation, recruitment, and activation of intraepithelial …

Animation Before Anime, Jason Cody Douglass

Yale Graduate School of Arts and Sciences Dissertations

This dissertation asserts that animated media circulating into, within, and away from Japan during the mid-20th century stand to tell us much about how such texts shaped, and were shaped by, the cultural forces of class, gender, age, and race. The four chapters traverse intersecting, albeit disparate planes. Each uses a distinct critical lens to demonstrate how understudied archival materials can help to resolve some of the most pressing questions currently raised within animation studies. Chapter 1 focuses upon issues of socioeconomic class, forging a vital link between functional animation, such as television advertisements, and working-class animators who developed their …

Ship164 Is A Lipid Transfer Protein That Coordinates Membrane Trafficking In The Endolysosomal System, Patreece H. Suen

Yale Graduate School of Arts and Sciences Dissertations

A defining feature of cells are membrane bilayers that separate them from their environment and, in eukaryotic cells, delineate intracellular organelles with specialized functions. In eukaryotes, the lipid composition of different organellar membranes varies both in terms of bulk and signaling lipids, lending these membranes different biochemical and biophysical characteristics. Yet most lipids are synthesized in the endoplasmic reticulum (ER), then redistributed asymmetrically from there via mechanisms that remain poorly understood. Lipid redistribution is mediated in part by lipid transport proteins that operate at membrane contact sites, where organelles are closely apposed but do not fuse, moving lipids between their …

A Novel Microbial Source Of Stochasticity In Microbiota-Driven Diseases, Yi Yang

Yale Graduate School of Arts and Sciences Dissertations

Gut commensals with the capacity to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host, raising the possibility that changes in individual commensals themselves over time may impact their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of chronic inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found …

Helicobacter Pylori Catabolism Of Host Glutathione: An Emerging Mechanism Of Nutritional Virulence, Maia Joi Baskerville

Yale Graduate School of Arts and Sciences Dissertations

Mammalian cells synthesize the antioxidant glutathione (GSH) to shield cellular biomolecules from oxidative damage. Certain bacteria, including the gastric pathogen Helicobacter pylori, can perturb host GSH homeostasis. H. pylori infection significantly decreases GSH levels in host tissues, which has been attributed to the accumulation of reactive oxygen species in infected cells. However, the precise mechanism of H. pylori-induced GSH depletion remains unknown, and tools for studying this process during infection are limited. We developed an isotope-tracing approach to quantitatively monitor host-derived GSH in H. pylori-infected cells by mass spectrometry. Using this method, we determined that H. pylori catabolizes reduced GSH …

Human Cerebral Organoids For Modeling Neurodevelopmental And Infectious Disease, Ce Zhang

Yale Graduate School of Arts and Sciences Dissertations

Human cerebral organoids are three-dimensional cultures of brain-like tissue that model early human fetal cortical development. They recapitulate important neurodevelopmental events, including neural progenitor cell expansion, formation of a well-defined outer radial glia layer resembling the human outer subventricular zone, neurogenesis, and neuronal migration. In this study, I utilize cerebral organoids generated from induced pluripotent stem cells as a human-specific platform to investigate the mechanisms underlying neurodevelopmental and infectious central nervous system disease. The immediate application for cerebral organoids is to address the global healthpandemic of COVID-19 and its associated neurological manifestations. I demonstrate that exposure of cerebral organoids to …

Evaluating Novel Diagnostics In Covid-19 And Malaria, Jillian Armstrong

Yale Graduate School of Arts and Sciences Dissertations

Although there have been significant improvements in recent decades, emerging and established infections continue to represent a significant contribution to the global burden of disease. Diagnostics play a critical role at the population level for infectious disease surveillance and at the individual level for patient care decisions. However, adequate diagnosis can be challenging in high-risk populations and resource-limited settings. In my dissertation, I present work on repeat positive SARS-CoV-2 testing in nursing home residents and the detection and differentiation of hemozoin, a parasite-derived biomarker, produced by human malaria species. In the first year of the COVID-19 pandemic, little was known …

Yale Medicine Magazine Spring 2023, Issue 170, Yale University. School Of Medicine

Yale Medicine Magazine - alumni bulletin and magazine

This is the Spring 2023 issue of Yale Medicine Magazine, issue 170. Prepared in cooperation with the alumni and development offices at the School of Medicine. Earlier volumes are called Yale School of Medicine alumni bulletins, dating from v.1 (1953) through v.13 (1965) and Yale Medicine: alumni bulletin of the School of Medicine, v.1 (1965) through v. 52, no.1. (Autumn 2017).

Credit Suisse Group Takes Decisive Action To Pre-Emptively Strengthen Liquidity And Announces Public Tender Offers For Debt Securities, Credit Suisse

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No abstract provided.

Credit Suisse Announces Technical Delay Of Publication Of 2022 Annual Report, Credit Suisse

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No abstract provided.

Soil-Transmitted Helminthiases And Deworming Response In School-Aged Children In Retalhuleu, Guatemala, Rebeca Esther Vergara Greeno

Yale Medicine Thesis Digital Library

Background: Soil-transmitted helminthiases (STH) are amongst the most common diseases of poverty worldwide despite mass deworming campaigns. However, widespread use of benzimidazole anthelminthics in these campaigns has been associated with variable efficacy against three of the most common STHs, thus raising concerns regarding emerging resistance. Albendazole, in particular, has been shown to be least effective against Trichuris trichiura.

Methods: Our aim was to determine baseline prevalence and intensity of STH infections in rural school children living in Retalhuleu, Guatemala, and to evaluate the efficacy of single dose albendazole in infected children. We conducted a cross-sectional study with 557 children ages …

Comparison Of Clinical Study Results Reported In Medrxiv Preprints Vs Peer-Reviewed Journal Articles, Guneet Singh Janda

Yale Medicine Thesis Digital Library

The aim of this project was to evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies that are subsequently published in peer-reviewed journals (preprint-journal article pairs).

In this cross-sectional analysis, preprints posted on medRxiv in September 2020 were identified. Four evaluators determined how many preprints were subsequently published in peer-reviewed journals as of September 2022, calculating the time from preprint posting to publication. For preprints with multiple versions, the most recent version prior to journal acceptance was selected. Preprints updated after journal acceptance were excluded. For preprint-journal article pairs describing clinical trials, observational studies, …

Influence Of Stigma On Retention In Hiv Care And Adherence To Antiretroviral Therapy In Specialized Hiv Clinics Targeting Men Who Have Sex With Men And Transgender Women In Lima, Peru, David Oliveros Oliveros

Public Health Theses

HIV stigma is a social determinant of health that can influence adherence to antiretroviraltherapy (ART) and engagement in HIV care that impacts viral suppression levels for people with HIV (PWH). In Peru, a country which lags behind 95-95-95 targets for HIV outcomes, LGBTQ-affirming clinics have the potential to mitigate these negative health effects of stigma and discrimination among men who have sex with men (MSM) and transgender women (TGW), two populations that continue to be disproportionately affected by HIV. Using a validated HIV stigma scale and multivariate logistic regression models, this study assessed the magnitude and types of stigma present …

Intersectoral Responses To Climate Change And Waterborne Diseases In The Caribbean Region: Current Actions And Pathways Forward Using The One Health Framework, Sydney A. Steel

Public Health Theses

The Caribbean exists on the frontlines of climate change, and many climate-related threats are already felt throughout the region and projected to worsen in the coming decades. A critical climate-related threat is that of waterborne diseases, as extreme weather events, sea level rise, and temperature increases are shown to contribute to potable water inaccessibility and a more favorable environment for pathogen proliferation and transmission. The complexity of this challenge calls for increased regional and inter-sectoral collaboration in both preparedness and response efforts. Countries and territories across the Caribbean are currently displaying variable yet marked interest in One Health, yet there …

Does Environmental Testing Of C. Difficile Predict Whether A Patient Is Positive With C. Difficile?, David Caccese

Public Health Theses

Clostridioides difficile is a major public health threat and frequent cause of healthcare-associated infections. Hospitals have struggled to control C. difficile due in part to the challenge of identifying asymptomatic C. difficile carriers and because of C. difficile’s ability to survive on environmental surfaces for long periods. Asymptomatic carriers and environmental surfaces can contribute to C. difficile transmission. Screening of all patients for C. difficile upon hospital admission is not feasible and asymptomatic patients may not be accepting of surveillance testing. Thus, this study examines whether sampling the patient’s room environment once they have been admitted can indicate a patient …

Subcutaneous Lesions And Systemic Infections: A Scoping Review Of The Clinical Implications Of Illicit Xylazine Use, Fatimah Maiga

Public Health Theses

Xylazine, a clonidine analog, is a potent alpha-2 adrenergic agonist used as an analgesic sedative in veterinary medicine. Known to people who inject drugs (PWID) as “tranq”, xylazine has recently infiltrated the U.S. illicit opiate drug supply and has been associated with severe, necrotic lesions, sedation, and respiratory depression. Unlike opiates, xylazine has no human reversal agent or standardized withdrawal treatment protocol and its effects are unclear.

The objective of this study was to conduct a scoping review synthesizing the available clinical research and reporting on xylazine associated subcutaneous lesions and systemic infections. The study also sought to identify gaps …

Barriers To Help-Seeking For Minority College Students During The Covid-19 Pandemic, Jasminder Bains

Public Health Theses

Background: The COVID-19 pandemic has profoundly impacted US college student mental health, but it is unclear how racial/sexual/gender minority students have specifically been affected. Traditional barriers to help-seeking such as mental health stigma do not necessarily hold the same influence in college student populations, and there is mixed evidence on what barriers are the most significant in this population. Therefore, the present study aims to ascertain the effects of the COVID-19 pandemic on the mental health outcomes of racial/sexual/gender minority college students and identify the largest barriers to care for college students.

Methods: Data were obtained from the 2020-21 Healthy …

Social Vulnerability And Viral Respiratory Infections In Connecticut (2018-2021): A Modeling Approach To Identify Salient Measures, Sarah C. Katsandres

Public Health Theses

The social vulnerability index (SVI) measure was developed by the Centers for Disease Control and Prevention to characterize a community’s vulnerability level. Recently, SVI has been used to predict risk of COVID-19, in order to understand which communities may be most vulnerable. This analysis aims to understand what factors are driving the relationship between census tract-level vulnerability and risk of hospitalization with a viral respiratory pathogen. A statistical analysis and modeling study of surveillance data was conducted, analyzing the incidence of hospitalization with influenza, respiratory syncytial virus (RSV), and COVID-19, by census tract, in two counties in Connecticut between 2018–2021. …

Scoping Review On Gonorrhea Vaccines, Linyang Li

Public Health Theses

Gonorrhea infection is caused by Neisseria gonorrhoeae and it is the second most common bacterial sexually transmitted infection around the globe. Although gonorrhea infection is treatable with antibiotics, the level of antimicrobial resistance continues to increase and has become a major public health concern. As options of available treatments are reduced by the emergence of AMR, it has become urgent to develop effective vaccines against gonorrhea infection. The purpose of this scoping review is to describe existing epidemiological evidence in support of gonorrhea vaccine development, to discuss the current vaccine candidates in clinical stages, and to evaluate the theoretical impact …

Shiga Toxin Producing Escherichia Coli (Stec) In Connecticut, Usa, 2017-2021, Angelo Raymond Lodato

Public Health Theses

Introduction: Shiga-toxin producing Escherichia coli (STEC) is a common foodborne pathogen known to cause significant gastrointestinal illness in humans and often results after contact with animals and/or consumption of food that has been contaminated. STEC is a major contributor of foodborne outbreaks in the US. Understanding major contributors of infection is important to improving prevention. Methods: Cases of STEC reported in routine Connecticut FoodNet surveillance were included. Trends in demographic features, serotypes, and exposure histories were used to assess whether there was variation among cases between 2017 and 2021, and pre (2017-2019) and post (2020-2021) COVID-19 pandemic. CT respondents of …