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Pediatric Rheumatic Heart Disease Screening For Secondary Antibiotic Prophylaxis: An Explainable Shannon Energy Approach Using Heart Phonocardiogram In Northeast Brazil, Zhuohui Lin

Public Health Theses

Rheumatic Heart Disease (RHD), caused by Group A Streptococcus (GAS), remains a significant global health burden, particularly among children in low- and middle-income countries. Untreated GAS infection can lead to acute rheumatic fever and subsequent chronic valvular damage of RHD, such as mitral valve (MV) regurgitation. Hence, early detection is critical for the administration of Secondary Antibiotic Prophylaxis to prevent disease progression. Although deep learning models demonstrate high diagnostic accuracy, limited explainability restricts clinical adoption, especially in resource-limited settings. In this proof-of-concept study, we evaluated Shannon energy (SE) transformation as a proxy to differentiate holosystolic murmurs associated with RHD-related mitral …

Bulletin Of Yale University School Of Nursing 2026-2027, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 122, Number 16

September 5, 2026

Timbre — A Transcendent Paradox?, Eugenia Siegel Conte

Yale Journal of Music & Religion

Timbre, as ethnomusicologist Cornelia Fales writes, is “paradoxical” precisely because it is one of the most exacting processes in which the human body may sense and comprehend the source of a sound even as that comprehended sound is impossible to describe outside of metaphor or comparison. As one of the more recognizable qualities of sound but the most difficult to describe, timbre allows us to consider physical/emotional (affective) experiences of sound as a key aspect of faith and meditation. In this article, I examine physical-affective intersections of faith and meditation that often are key to praxes of worship, and show …

Kinetic And Thermodynamic Analysis Of Enpp1, Marisa Mary Michalchik

Yale Graduate School of Arts and Sciences Dissertations

The Ectonucleotide Pyrophosphatase Phosphodiesterase (ENPP) family members are promiscuous extracellular enzymes that play central roles in human physiology via catalysis of nucleotide and lipid substrates, but remain poorly characterized at the biochemical level. The founding member, ENPP1, is a glycosylated transmembrane enzyme with an extracellular catalytic domain that degrades nucleotide substrates (ATP and cGAMP) into their respective nucleotide monophosphates, playing a key role in both the regulation of biomineralization and innate immune system activation. The ENPP1 ATPase is the major source of extracellular pyrophosphate (PPi), the main chemical inhibitor of calcium phosphate crystal formation in physiology. ENPP1 deficiency lowers systemic …

Business As Usual: Organizational And Market Responses To The Natural Environment And Magnification Of Inequality, Taylor Martin Holdaway

Yale Graduate School of Arts and Sciences Dissertations

Climate change is a multifaceted and insidious grand challenge facing the world. Natural disasters and extreme weather conditions, made more common by climate change, will cause enormous ecological, human, and economic damage across the globe. Businesses, organizations, and markets are critically implicated in climate change due to their culpability for greenhouse gas emissions and their roles in building or hindering adaptive capacity and mediating transfers of wealth resulting from climate change. In my dissertation, I investigate how individuals, businesses, and markets respond to climate-related disasters and extreme weather conditions and how these processes contribute to patterns of inequality in the …

Uncovering Transkingdom Connectivity Through Mapping Host-Microbiota Interactions, Nicole Sonnert

Yale Graduate School of Arts and Sciences Dissertations

Our microbiota, the trillions of microbes that constitutively colonize every outward-facing surface of our bodies, have diverse impacts on human physiology, yet the molecular bases for these effects remain mostly unknown. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the ‘exoproteome’). Commensal microbes may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct microbiota-exoproteome interactions remain largely unexplored. We developed and validated a novel technology, BActerial Selection to Elucidate Host-microbe Interactions in high Throughput (BASEHIT), that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, …

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).

Environmental Exposures From The Local To The Global: A Comparison Of The Experiences And Consequences Of Exposure Among The Qom Of Formosa, Argentina, And Residents Of New Haven, Connecticut, Carlye Chaney

Yale Graduate School of Arts and Sciences Dissertations

Exposure to endocrine disrupting chemicals and other environmental contaminants is globally ubiquitous and can have adverse consequences on health throughout the lifespan. In this project, I investigated the experiences and consequences of environmental contaminant exposure for maternal and infant health in two places that differ environmentally, politically, and socioeconomically –Namqom in Formosa, Argentina, and New Haven, Connecticut. Specifically, I hypothesized that environmental contaminant exposure influences human well-being and physiology, as assessed from the human milk and urine metabolome, through changes in the hypothalamic-pituitary-gonadal (HPG) axis in both infancy and adulthood.I first investigated the local context, both historical and present, that …

Molecular Mechanisms Of Microbial Adaptation To The Host, Daniel G. Dumitrescu

Yale Graduate School of Arts and Sciences Dissertations

All host-associated microorganisms require mechanisms to adapt to stress encountered in the host. In particular, host immunity generates reactive oxygen species (ROS) as a measure to regulate microbial expansion in the gut and to kill invading pathogens. ROS are broadly toxic to cellular biomolecules, and consequently both microorganisms and the host employ molecular mechanisms to contend with their harmful properties. Accordingly, all life forms rely on low- molecular-weight (LMW) thiols, a family of ubiquitous small molecule antioxidants, to maintain intracellular redox homeostasis and resist oxidative damage caused by ROS. Chapter 1 reviews the molecular and biological functions of LMW thiols, …

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, …

Exploring The Perceptions Of Genetics, Genetics Testing, And Science In People Of African Descent, Maame-Owusua Boateng

Public Health Theses

Background: Historical injustices towards Black populations in the United States have impacted how communities interact with medicine and public health such as medical experimentations, scientific racism, medical racism, and eugenics. Black communities are underrepresented in human genomics projects compared to those that identify as white or of European ancestry. Prior research has demonstrated that Black people are less likely to know about the availability of genetic testing for diseases and have less confidence in the benefits of genetic testing. These disparities make it imperative to understand the perspectives of people of African descent. Methods: The Black Genome Project is an …

A Systematic Review Of The Effect Of Maternal Circadian Disruption During Pregnancy On Adverse Fetal Outcomes, Siyu Jiang

Public Health Theses

Exposure to a suboptimal pregnant environment can raise the risk of offspring experiencing a variety of diseases in later life. Circadian rhythms play an important role in endocrine system, physiological and psychological functions. Potentially, interruption of the circadian rhythm in pregnant women might impair fetal growth and lead to adverse effects on the children. In the modern world, millions of women experience circadian disruption during pregnancy due to night shift work, excessive light at night, and jet travel across time zones. However, the impact of maternal chrono-disruption during pregnancy on the health of the second generation remains largely unknown. The …

Functional Profiling Of Human Commensal Metabolites In Colorectal Cancer And Pain Sensation, Yiyun Cao

Yale Graduate School of Arts and Sciences Dissertations

The gastrointestinal tract contains the largest number and greatest diversity of microbes which are referred to collectively as the gut microbiota. Alterations in microbiota dysbiosis are associated with diverse disease states, including colorectal cancer (CRC), inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, the causative mechanisms mediated by the gut microbiota are still to be illustrated. Particularly, the gut commensals encode ~150 times more genes than the human genome and thousands of metabolites that mostly lack functional annotations or structural identification. Therefore, the functional profiling of human commensal metabolites is promising to reveal the molecular mechanisms of the …

Extracellular Elastin Assembly And Vascular Hyperproliferation: Connections For Treatment And Tissue Engineering, Matthew Ellis

Yale Graduate School of Arts and Sciences Dissertations

Elastin is the load-bearing extracellular matrix protein complex that endows the aorta with the recoil necessary to propagate blood to the peripheral circulation following systolic ejection from the heart. The assembly of the elastin complex occurs early in perinatal development and degrades over the course of a human lifetime, leading to arterial stiffening and elevated blood pressure. Although this complex assembly process occurs seamlessly in vivo, it has been a large obstacle in the field to replicate this process in vitro, hampering efforts to engineer elastin-rich grafts for transplantation and to study and develop curative treatments for elastin-associated pathologies. Herein, …

Cross-Kingdom Expression Of Synthetic Genetic Elements Promotes The Discovery Of A New Class Of Nucleotide Analogs From The Human Microbiome, Jaymin Patel

Yale Graduate School of Arts and Sciences Dissertations

The ability to mobilize functional genetic cargo into a versatile array of hosts is a defining challenge, as scientists increasingly reprogram diverse organisms as living therapeutics, for bioremediation, and as foundries for producing materials and molecules. However porting genetic material to diverse recipients is challenged by barriers to robust expression and mobilization. To address these challenges, we have developed an approach that integrates computer aided redesign of genetic sequences that are subsequently mobilized, expressed, and characterized cross-kingdom in diverse microbial hosts, including Gram negative and positive bacteria and yeast. Using the technology developed in this thesis, we were able to …

Mutations In Α And Β Subunits Of Voltage-Gated Sodium Channels In Neuropathic Pain: Functional Assessment In Rodent And Human Ipsc-Derived Sensory Neurons, Matthew Alsaloum

Yale Graduate School of Arts and Sciences Dissertations

Voltage-gated sodium (NaV) channels are key mediators of excitability in dorsal root ganglion (DRG) neurons, the primary afferents responsible for transmitting pain signals into the central nervous system. NaV channels are found as heterotrimeric complexes in humans, comprised of one pore-forming α-subunit and two non-ion conducting β-subunits. Gain-of-function mutations in NaV1.7, NaV1.8, and NaV1.9, the NaV channels preferentially expressed in the peripheral nervous system, confer hyperexcitability to DRG neurons and have been linked to the development of neuropathic pain. In this dissertation, I utilize dynamic clamp electrophysiology to precisely quantify the contribution of NaV1.8 and NaV1.9 to neuronal excitability. Furthermore, …

Decoding Gut Microbial Metabolites Through G-Protein Coupled Receptor (Gpcr) Activation, Phu Khat Nwe

Yale Graduate School of Arts and Sciences Dissertations

The microbiome encodes for a complex web of metabolites of which scientists are just starting to deconvolute. While a lot of focus has been on investigating the implications of the microbial metabolome on health and disease physiologies, we have merely uncovered the tip of the interactome of microbes and host G-Protein Coupled Receptors (GPCRs). Early literature has reported a plethora of short chain fatty acids fermented by dietary fibers acting as GPCR agonists. A few other studies have showcased that gut microbes produced N-acyl amides and secondary bile acids mimicking host ligands and therefore interacting with these GPCRs. Chapter 2 …

Macrophage Mechanosensing Of The Tissue Environment And Signal Integration Through The Cytoskeleton, Matthew Lowell Meizlish

Yale Graduate School of Arts and Sciences Dissertations

The extracellular matrix (ECM) is an organized assembly of proteins and polysaccharides that is produced by cells and forms the physical environment in which cells reside. Together, diverse cell types and their surrounding extracellular matrix form units of organization known as tissues, which make up organs. The ECM gives rise to the particular architecture and mechanical properties of each organ. During tissue repair, cells known as myofibroblasts deposit large quantities of ECM, in order to reconstruct the injured tissue. In normal tissue repair, that reparative phase is followed by a resolution phase, in which cells such as macrophages degrade and …

Discovery Of Host-Microbiota Interactions, Connor Rosen

Yale Graduate School of Arts and Sciences Dissertations

The microbiota, comprising the trillions of microorganisms that colonize barrier tissues, exert profound effects on host health and disease. Microbial effects on host physiology have been illuminated by a wealth of sequencing-based approaches that enumerate bacterial species, strains, genes, and products (collectively, “multi-omics” approaches) at different tissue sites and in different human populations. Microbes may influence local physiology at their site of residence, as well as having systemic effects including perturbation of organism-wide metabolism, with wide-ranging consequences. The molecular mechanisms by which microbes mediate both local and systemic effects, however, remain mostly unclear. This is in part due to technological …

Structural And Functional Characterization Of Lipid-Derived Molecules From The Human Microbiome, Woo Young Cho

Yale Graduate School of Arts and Sciences Dissertations

Scientific evidence for the contribution of the human microbiome to the promotion of human health and disease has been rapidly accumulating. With advances in sequencing technologies and bioinformatics, more specific correlations can be made between certain bacterial strains and/or their genes to specific disease phenotypes. However, the molecular mechanisms by which bacteria are able to influence human health remains largely elusive. Bacteria are known to interact with their environment by production and modulation of small molecules. Bacterially-produced lipid-derived molecules play important signaling roles and modulate eukaryotic cellular responses through the activation of various receptors.

Identification Of A Novel Disorder With Cholestasis, Liver Fibrosis And Congenital Diarrhea Due To Organic Solute Transporter Alpha Deficiency, Emily Gao

Yale Medicine Thesis Digital Library

BACKGROUND: Much of our understanding of normal liver pathophysiology comes from studying patients with liver disease who remain undiagnosed after a comprehensive workup. Searching for diagnoses among such cohorts has benefits both for the underserved patients with idiopathic liver disease, but also for science as a whole. Unbiased genomic analysis of patients with undiagnosed disease has yielded remarkable results, including clinically actionable diagnoses in children and adults, as well as the discovery of novel genetic diseases. Thus, we posit that among pediatric patients with undiagnosed liver disease, there may be previously unrecognized Mendelian causes.

METHODS: We report a 2.5 year …

Cerebral Autoregulation-Based Blood Pressure Management In The Neuroscience Intensive Care Unit: Towards Individualizing Care In Ischemic Stroke And Subarachnoid Hemorrhage, Andrew Silverman

Yale Medicine Thesis Digital Library

The purpose of this thesis is to review the concept of cerebral autoregulation, to establish the feasibility of continuous bedside monitoring of autoregulation, and to examine the impact of impaired autoregulation on functional and clinical outcomes following subarachnoid hemorrhage and ischemic stroke. Autoregulation plays a key role in the regulation of brain blood flow and has been shown to fail in acute brain injury. Disturbed autoregulation may lead to secondary brain injury as well as worse outcomes. Furthermore, there exist several methodologies, both invasive and non-invasive, for the continuous assessment of autoregulation in individual patients. Resultant autoregulatory parameters of brain …

Bulletin Of Yale University School Of Nursing 2020-2021, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 116, Number 15

September 5, 2020

Inhibition Of The Akt1-Mtorc1 Axis Alters Venous Remodeling To Improve Arteriovenous Fistula Patency, Arash Fereydooni

Yale Medicine Thesis Digital Library

Arteriovenous fistulae (AVF) are the most common access created for hemodialysis, but up to 60% do not sustain dialysis within a year, suggesting a need to improve AVF maturation and patency. In a mouse AVF model, Akt1 regulates fistula wall thickness and diameter. We hypothesized that inhibition of the Akt1-mTORC1 axis alters venous remodeling to improve AVF patency. Daily intraperitoneal injections of rapamycin reduced AVF wall thickness with no change in diameter. Rapamycin decreased smooth muscle cell (SMC) and macrophage proliferation; rapamycin also reduced both M1 and M2 type macrophages. AVF in mice treated with rapamycin had reduced Akt1 and …

Bulletin Of Yale University School Of Nursing 2019-2020, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 115, Number 15

September 5, 2019

Bulletin Of Yale University School Of Nursing 2018-2019, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 114, Number 15

September 5, 2018

Arterial And Venous Impacts Of Transdermally Administered Vasodilators On The Local Microvasculature, George Guo

Yale Medicine Thesis Digital Library

Microcirculatory function is an important component of cardiovascular pharmacology as related to cardiovascular dysfunction. We used photoplethysmography (PPG) to compare the microcirculatory effects of transdermal patches of rivastigmine (Exelon, Novartis), nicotine, nitroglycerin (NTG) and topically applied EMLA (eutectic mixture of lidocaine/prilocaine). We anticipate that this initial pilot comparison of single doses of each medication will catalyze future multi-dose comparisons of the various vasodilatory features of these and other drugs.

Methods: With IRB approval, 10 healthy volunteers were monitored with PPG at the time each transdermal patch was applied and every 8 minutes afterwards for a total of 40 minutes. 1x1 …

Bulletin Of Yale University School Of Nursing 2017-2018, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 113, Number 15

September 5, 2017

An Automated Temporal, Amplitude, And Complexity-Based Comparison Of Commercial Plethysmographs, Matthew Mikhail

Yale Medicine Thesis Digital Library

The study of plethysmographic physiology has been limited by a lack of standardized and open plethysmographic hardware in clinical use. Fundamental differences in the processing of output between various devices obfuscate direct comparison, and the role played by physiology versus that by technology in the final viewable plethysmogram (PPG). This study proposes a largely automated, unbiased method for quantitatively comparing the outputs from proprietary pulse oximeter devices along three metrics: temporal delay, amplification, and complexity. It then applies these methods to the deconstruction of Masimo and Nellcor pulse oximeters.

With IRB approval, twelve healthy, awake subjects were studied. Each individual …

Bulletin Of Yale University School Of Nursing 2016-2017, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 112, Number 15

September 5, 2016