Digital Commons Network^™

The Five Homologous Ciar-Controlled Ccn Srnas Of Streptococcus Pneumoniae Modulate Zn-Resistance, Nicholas R De Lay, Nidhi Verma, Dhriti Sinha, Abigail Garrett, Maximillian K Osterberg, Daisy Porter, Spencer Reiling, David P Giedroc, Malcolm E Winkler

Faculty, Staff and Student Publications

Zinc is a vital transition metal for all bacteria; however, elevated intracellular free Zn levels can result in mis-metalation of Mn-dependent enzymes. For Mn-centric bacteria such as Streptococcus pneumoniae that primarily use Mn instead of Fe as an enzyme cofactor, Zn is particularly toxic at high concentrations. Here, we report our identification and characterization of the function of the five homologous, CiaRH-regulated Ccn sRNAs in controlling S. pneumoniae virulence and metal homeostasis. We show that deletion of all five ccn genes (ccnA, ccnB, ccnC, ccnD, and ccnE) from S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) causes Zn …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

A Protein Expression Atlas On Tissue Samples And Cell Lines From Cancer Patients Provides Insights Into Tumor Heterogeneity And Dependencies, Jun Li, Wei Liu, Kamalika Mojumdar, Hong Kim, Zhicheng Zhou, Zhenlin Ju, Shwetha V Kumar, Patrick Kwok-Shing Ng, Han Chen, Michael A Davies, Yiling Lu, Rehan Akbani, Gordon B Mills, Han Liang

Faculty, Staff and Student Publications

The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our previous work to generate high-quality protein expression data for approximately 8,000 TCGA patient samples and around 900 CCLE cell line samples, covering 447 clinically relevant proteins, using reverse-phase protein arrays. These protein expression profiles offer profound insights into intertumor heterogeneity and cancer dependency and serve as sensitive functional readouts for somatic alterations. We develop a systematic protein-centered strategy …

Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, Lingzhi Hong, Sonia Patel, Leylah M Drusbosky, Yuanyuan Xiong, Rongrong Chen, Ruixuan Geng, Simon Heeke, Monique Nilsson, Jia Wu, John V Heymach, Yingyi Wang, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 …

Development Of An Engineered Extracellular Vesicles-Based Vaccine Platform For Combined Delivery Of Mrna And Protein To Induce Functional Immunity, Xin Luo, Kathleen M Mcandrews, Kent A Arian, Sami J Morse, Viktoria Boeker, Shreyasee V Kumbhar, Yingying Hu, Krishnan K Mahadevan, Kaira A Church, Sriram Chitta, Nicolas T Ryujin, Janine Hensel, Jianli Dai, Dara P Dowlatshahi, Hikaru Sugimoto, Michelle L Kirtley, Valerie S Lebleu, Shabnam Shalapour, Joe H Simmons, Raghu Kalluri

Faculty, Staff and Student Publications

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice …

High Throughput And Rapid Isolation Of Extracellular Vesicles And Exosomes With Purity Using Size Exclusion Liquid Chromatography, Kshipra S Kapoor, Kristen Harris, Kent A Arian, Lihua Ma, Beatriz Schueng Zancanela, Kaira A Church, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (< 20 min) EV isolation method termed size exclusion - fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.

Investigating The Effects Of Empathy On Implicit Race Bias, Macy Kisiel

Psychology Theses & Dissertations

Over the years there have been changes to social norms, which now discourage expressions of prejudice, and changes in many people’s self-reported attitudes, but prejudice is still a major issue in present-day American society. One important step toward addressing prejudice and social injustices is to understand the psychological processes that underlie and strengthen them. The current study aimed to use an empathy passage to positively prime the schema about a minority person of color and manipulate regulation of implicit bias. The study utilized a mixed 2 × 2 design. Sixty-four participants (Mage = 20.88 years, SD = 4.75 years) were …

A Theoretical Framework For Resilience In Complex System Governance (Csg), Susan A. Caskey

Engineering Management & Systems Engineering Theses & Dissertations

This dissertation addresses a critical gap in resilience research within complex systems by developing a theoretical framework for governance resilience—an underexplored area despite governance's crucial role in maintaining system resilience. Using the Complex System Governance (CSG) framework (Keating, Katina, Chesterman, et al., 2022; Keating & Katina, 2019), resilience is conceptualized as a system's ability to absorb disturbances while sustaining performance and enabling adaptive transformation. This involves three main capabilities: persistence, adaptability, and transformation in response to both internal and external pressures.

Through a constructivist grounded theory approach involving iterative coding, memoing, and theory development, this study inductively constructs a governance …

Symbolic Regression For Data-Driven Equation Discovery: A Physics-Informed Approach, Anusha Reddy Singireddy

Computer Science Theses & Dissertations

Symbolic Regression (SR) is a cutting-edge machine learning technique that discovers mathematical expressions representing the underlying patterns in data. Unlike traditional regression, SR explores a wide range of mathematical models, allowing for flexible and interpretable solutions. We utilize PySR, a highly customizable symbolic regression package, which combines genetic programming and modern optimization methods to efficiently search for interpretable equations. PySR balances model complexity with performance by penalizing overly complex expressions while optimizing accuracy. In this thesis, we apply Physics-informed Symbolic Regression through PySR to model the x and t dependence of the flavor isovector combination H_u − d( …

Feasibility Study Of Oyster Shell Filtration Media For Stormwater Pollutants Removal, Sadiq Omer

Civil & Environmental Engineering Theses & Dissertations

The depletion of resources has raised interest in reusing or incorporating by-products into alternative materials. In the effort for net zero emissions, waste reduction, and a circular economy, it is crucial to reinvent the alternative utilization strategy for by-products as construction materials sustainably. This research examines the alternative utilization strategy for oyster shell by-products in regular stormwater pollutant removal best management practices (BMPs).

Numerous research has examined the utilization of oyster shell waste as a construction material in Asia and Europe, specifically focusing on the physical properties of crushed oyster shells as alternatives for aggregates. No studies have been identified …

A Dendrochronological Analysis Of Longleaf And Associated Pines From The Blackwater Ecological Preserve In Southeastern Virginia, Sarah Durham

Biological Sciences Theses & Dissertations

The field of dendrochronology utilizes annual tree ring growth data to create chronologies, which function as proxies to measure the effect of climate on radial growth. In the southeastern United States, dendrochronological studies involving the effect of climate on the growth of Pinus species exist, but significant gaps persist. For this study, I: 1) created chronologies of earlywood, latewood, and total ring-width growth for longleaf pine (Pinus palustris Mill.), loblolly pine (P. taeda L.), and pond pine (P. serotina Michx.) and 2) conducted a climate analysis on each species to determine how climatic factors affected radial …

The Phenomenology Of Experiencing Critical Thinking In Vocational Higher Education, Sean Castleberry

Educational Leadership & Workforce Development Theses & Dissertations

This study investigated the role of critical thinking in vocational education within the Virginia Community College System by examining the lived experience of administrators, faculty, and students who are associated with vocational education. To complete this task, the researcher employed a phenomenological methodology primarily based on the philosophy of Martin Heidegger and other phenomenological philosophers including Edmund Husserl, Mark D. Vagle, and Karin Dahlberg. The goal of the research was to serve as a beginning and help close the gap in knowledge concerning how critical thinking is defined in vocational education, why it is seen as an important part of …

Does Job Satisfaction Take A Hit? The Relationships Between Employee Cannabis Use, Job Satisfaction, And Absenteeism, Caroline Jordan Moughan

Psychology Theses & Dissertations

Despite the frequency of cannabis use, limited research has examined how employees’ cannabis use relates to job attitudes and behaviors. This study responds to calls to examine the effects of employee cannabis use on work-relevant outcomes by exploring how employee cannabis use relates to job satisfaction and voluntary absenteeism by analyzing a sample of 526 employed young adults from the most recent three waves of the National Longitudinal Survey of Youth (NLSY) Child and Young Adult Cohort. Through estimating cross-lagged panel models, this study clarifies the direction of relationships between employee cannabis use and job satisfaction, and how these relate …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring

Biomedical Sciences Theses & Dissertations

The dynamic cellular microenvironment, made up of resident cells and various macromolecules, differs markedly across tissues in the body. The multidirectional signals that cells receive from this microenvironment, along with the signaling they send back, heavily influence their physiology and behavior. Recent important findings have further validated this notion as the mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) driving changes in metabolic reprogramming and cancer fate redirection is understudied. The work presented in this dissertation focuses on exploring the impact of …

Unveiling Resilience And Motivation Through Testimonios: Exploring The Influence Of Trio Student Services On Motivation And College Completion, Emily Leonard Garrison

Educational Leadership & Workforce Development Theses & Dissertations

This dissertation explores the impact of TRIO Student Support Services (TRIO SSS) on the motivation and college completion rates of first-generation rural community college students. Utilizing a qualitative approach centered on testimonios, this research captures the lived experiences of students at a rural community college in North Carolina, focusing on how TRIO SSS influences their educational journeys.

Through narrative inquiry, the study documents the personal stories of TRIO SSS graduates, highlighting the program's pivotal role in enhancing student retention and success. The findings demonstrate that TRIO SSS is essential in providing targeted support that aligns with the students' unique challenges …

The Role Of Policy Entrepreneurs In Understanding Oral Health Care Policy: A Case Study Approach Analyzing Multiple Streams Framework In Nc Oral Health Policy, Lori Gordon Hendrick

School of Public Service Theses & Dissertations

The United States Surgeon General has defined oral diseases as a “silent epidemic” that affects the most vulnerable citizens. More often, this includes those from low socio-economic backgrounds, children, elderly, and many members of ethnic minority groups. Although preventative and treatment modalities have improved over the past fifty years, some Americans continue to have little to no access to educational and preventative programs. The lack of access to dental care for all ages and oral health care literacy remains one of the largest health concerns for American citizens making it a “wicked problem”. Historically, raising Medicaid enrollment has failed to …

Pedestrian-Motorist Self-Reported Behavioral Intentions Toward Using Alternative And Standard Safety Infrastructure, Emma Sunshine Hood

Psychology Theses & Dissertations

The increasing trend in pedestrian-motorist incidents on American roadways warrants a novel solution for improving roadway safety. Alternative crosswalk designs have piqued communities both in the United States and abroad. Designs range from slight changes in colors to extravagant illusions of the roadway falling beneath users. These crosswalk designs are not novel, literature on their efficacy as safety infrastructure is modest with mixed results. The purpose of the study was to expand the current literature on alternative crosswalk designs. The author hypothesized that the differences in behavioral intentions at alternative and standard safety infrastructure would be greater for younger male …

The Anaerobic Rose Chamber (Arc): Novel Applications For Probing Clostridioides Difficile Dynamics, Tatiana Zvonareva

Chemistry & Biochemistry Theses & Dissertations

Clostridioides difficile infection (CDI) is an urgent public health threat with a high rate of recurrence and limited treatment options. Caused by the anaerobic intestinal pathogen C. difficile, this disease affects up to 500,000 Americans annually. Despite progress in our understanding of CDI pathophysiology, the lack of effective and accessible experimental platforms compatible with obligate anaerobe physiology hinders the advancement of treatment therapy. The application of in vivo models has been indispensable in understanding CDI pathophysiology, probing the complexity of the host response to the microbe, and establishing treatment protocols, and it continues to be essential in preclinical testing. …

Real-Time Synthesis Of A Nonuniformly Correlated, Partially Coherent Beam Using An Optical Coordinate Tansformation, Milo W. Hyde Iv

Faculty Publications

We design, build, and validate an optical system for generating light beams with complex spatial coherence properties in real time. Beams of this type self-focus and are resistant to turbulence degradation, making them potentially useful in applications such as optical communications. We begin with a general theoretical analysis of our proposed design. Our approach starts by generating a Schell-model (uniformly correlated or shift-invariant) source by spatially filtering incoherent light. We then pass this light through an optical coordinate transformer, which converts the Schell-model source into a nonuniformly correlated field. After the general analysis, we discuss system engineering, including trade-offs among …

Refinement Of Alphafold-Predicted Models Using Cryo-Em Density Maps And Enhancement Of Protein Secondary Structure Topologies With Residue Contacts, Maytha Naif Alshammari

Computer Science Theses & Dissertations

Proteins play an important role in almost every biological process. Understanding the mechanism of protein function requires knowledge of three-dimensional (3D) structures. Traditionally, the determination of 3D structures has presented significant challenges. However, Cryo-Electron Microscopy (Cryo-EM) has revolutionized the field of structural biology, providing a powerful technique for atomic structure determination. This dissertation delves into the potential of cryoEM in two ways. First, this dissertation presents a new flexible fitting approach, utilizing Normal Mode Analysis (NMA) and Elastic Network Models (ENMs) to refine AlphaFold-predicted models by optimizing the structures to match cryo-EM density maps. This approach identifies the optimal mode …

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Reimagining Supportive Approaches At The Intersection Of Mandatory Reporting Policies For The Mother–Infant Dyad Affected By Substance Use, Kelly Mcglothen-Bell, Diana Cartagena, Kathryn J. Malin, Dorothy Vittner, Jacqueline M. Mcgrath, Rebecca Koerner, Ashlee J. Vance, Allison Crawford

College of Nursing Faculty Research and Publications

Background: As rates of substance use during pregnancy persist, the health and optimal development of infants with prenatal substance exposure remain a key priority. Nurses are tasked with identifying and reporting suspected cases of child maltreatment, including abuse and neglect, which is often assumed to be synonymous with substance use during pregnancy. While policies aimed at protecting infants from child abuse and neglect are well intentioned, literature regarding the short- and long-term social and legal implications of mandatory reporting policies is emerging.

Purpose: In this article, we explore the intersections between the condition of substance use in pregnancy and policies …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

Investigating In Vivo Tumor Biomolecular Changes Following Radiation Therapy Using Raman Spectroscopy, Varsha Karunakaran, Sina Dadgar, Santosh K. Paidi, April Mordi, Whitney A. Lowe, Umme Marium Mim, Jesse D. Ivers, Joel Rodriguez Troncoso, Jared A. Mcpeake, Alric Fernandes, Sanidhya D. Tripathi, Ishan Barman, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

Treatment resistance is a major bottleneck in the success of cancer therapy. Early identification of the treatment response or lack thereof in patients can enable an earlier switch to alternative treatment strategies that can enhance response rates. Here, Raman spectroscopy was applied to monitor early tumor biomolecular changes in sensitive (UM-SCC-22B) and resistant (UM-SCC-47) head and neck tumor xenografts for the first time in in vivo murine tumor models in response to radiation therapy. We used a validated multivariate curve resolution-alternating least-squares (MCR-ALS) model to resolve complex multicomponent Raman spectra into individual pure spectra and their respective contributions. We observed …

Simultaneous Modulation Of Pulse Charge And Burst Period Elicits Two Differentiable Referred Sensations, T. R. Benigni, A. E. Pena, S. S. Kuntaegowdanahalli, J. J. Abbas, R. Jung

Biomedical Engineering Faculty Publications and Presentations

Objective. To investigate the feasibility of delivering multidimensional feedback using a single channel of peripheral nerve stimulation by complementing intensity percepts with flutter frequency percepts controlled by burst period modulation. Approach. Two dimensions of a distally referred sensation were provided simultaneously: intensity was conveyed by the modulation of the pulse charge rate inside short discrete periods of stimulation referred to as bursts and frequency was conveyed by the modulation of the period between bursts. For this approach to be feasible, intensity percepts must be perceived independently of frequency percepts. Two experiments investigated these interactions. A series of two alternative forced …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Three Classes Of Propofol Binding Sites On Gabaa Receptors, Zi-Wei Chen, Satyanarayana M Chintala, John Bracamontes, Yusuke Sugasawa, Spencer R Pierce, Balazs R Varga, Edward H Smith, Christopher J Edge, Nicholas P Franks, Wayland W L Cheng, Gustav Akk, Alex S Evers

2020-Current year OA Pubs

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator of gamma-aminobutyric acid type A (GABA

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.

EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: …

Adherence To Hygiene Protocols And Doxycycline Therapy In Ameliorating Lymphatic Filariasis Morbidity In An Endemic Area Post-Interruption Of Disease Transmission In Ghana, Linda Batsa Debrah, Philip J Budge, Et Al.

2020-Current year OA Pubs

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular …