Digital Commons Network^™

The Evolving Paradigm Of Antibody-Drug Conjugates Targeting The Erbb/Her Family Of Receptor Tyrosine Kinases, Peyton High, Cara Guernsey, Shraddha Subramanian, Joan Jacob, Kendra S Carmon

The Brown Foundation: Institute of Molecular Medicine

Current therapies targeting the human epidermal growth factor receptor (HER) family, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs), are limited by drug resistance and systemic toxicities. Antibody-drug conjugates (ADCs) are one of the most rapidly expanding classes of anti-cancer therapeutics with 13 presently approved by the FDA. Importantly, ADCs represent a promising therapeutic option with the potential to overcome traditional HER-targeted therapy resistance by delivering highly potent cytotoxins specifically to HER-overexpressing cancer cells and exerting both mAb- and payload-mediated antitumor efficacy. The clinical utility of HER-targeted ADCs is exemplified by the immense success of HER2-targeted ADCs including trastuzumab …

Fourth Grade Teachers’ Experiences Addressing Low Reading Achievement, Sametria S. Alexander

Walden Dissertations and Doctoral Studies

The research problem addressed in this study was the low reading achievement scores of fourth grade students and fourth grade reading teachers’ struggles raising reading achievement. The purpose of the study was to explore fourth grade reading teachers’ experiences of finding strategies and interventions to improve reading achievement. The theoretical frameworks were Gough and Tunmer’s simple view of reading and Chall’s stages of reading development. The research questions addressed fourth grade reading teachers’ use of strategies and approaches and fourth grade reading teachers’ beliefs about school support. The study used a basic qualitative approach with semistructured interviews from 10 U.S. …

The Lived Experience Of Stigmatization Due To Chemotherapy-Induced Hair Loss For Young Women With Cancer Who Attend College, Challna Blair

Walden Dissertations and Doctoral Studies

This study investigated the stigmatization experienced by young women in college due to chemotherapy-induced hair loss. Previous research primarily focused on older women, adolescents, and men, leaving a gap in understanding the impact on young college-age women. Using Goffman’s theory of stigma and Giorgi’s descriptive phenomenological method, six young women were interviewed confidentially. The primary research question asked what is the experience of stigma in young women in college who have hair loss during or following chemotherapy cancer treatment? The study revealed that these women often faced being ostracized by peers, received minimal family support, and experienced distressing scrutiny from …

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository With Genomic And Pathologic Annotations Enables Deep Learning Analysis, Todd Sheridan, Steven B Neuhauser, Shidan Wang, Yvonne A Evrard, Li Chen, Ali Foroughi Pour, John D Landua, R Jay Mashl, Sherri R Davies, Bingliang Fang, Maria Gabriela Raso, Kurt W Evans, Matthew H Bailey, Yeqing Chen, Min Xiao, Jill C Rubinstein, Brian J Sanderson, Michael W Lloyd, Sergii Domanskyi, Lacey E Dobrolecki, Maihi Fujita, Junya Fujimoto, Guanghua Xiao, Ryan C Fields, Jacqueline L Mudd, Xiaowei Xu, Melinda G Hollingshead, Shahanawaz Jiwani, Saul Acevedo, Pdxnet Consortium, Brandi N Davis-Dusenbery, Peter N Robinson, Jeffrey A Moscow, James H Doroshow, Nicholas Mitsiades, Salma Kaochar, Chong-Xian Pan, Luis G Carvajal-Carmona, Alana L Welm, Bryan E Welm, Ramaswamy Govindan, Shunqiang Li, Michael A Davies, Jack A Roth, Funda Meric-Bernstam, Yang Xie, Meenhard Herlyn, Li Ding, Michael T Lewis, Carol J Bult, Dennis A Dean, Jeffrey H Chuang

Faculty, Staff and Students Publications

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a …

A Mechanistic Lnk Between Inflammation And Atrial Fibrillation?

Faculty, Staff and Students Publications

No abstract provided.

Assessment Of Patient-Derived Xenograft Growth And Antitumor Activity: The Nci Pdxnet Consensus Recommendations, Funda Meric-Bernstam, Ramaswamy Govinden, Li Ding, Ryan Fields, Et Al.

2020-Current year OA Pubs

Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification …

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository With Genomic And Pathologic Annotations Enables Deep Learning Analysis, Brian S White, R Jay Mashl, Sherri R Davies, Ryan C Fields, Jacqueline L Mudd, Ramaswamy Govindan, Shunqiang Li, Li Ding, Et Al.

2020-Current year OA Pubs

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a …

Identification Of Unique Cell Type Responses In Pancreatic Islets To Stress, Marlie M Maestas, Matthew Ishahak, Punn Augsornworawat, Daniel A Veronese-Paniagua, Kristina G Maxwell, Leonardo Velazco-Cruz, Erica Marquez, Jiameng Sun, Mira Shunkarova, Sarah E Gale, Fumihiko Urano, Jeffrey R Millman

2020-Current year OA Pubs

Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress. Through comprehensive pair-wise analysis of stress responses across pancreatic endocrine and exocrine cell types, we define changes in gene expression for each cell type under different diabetes-associated stressors. We find that …

Validating A Curvature-Based Marker Of Cervical Carotid Tortuosity For Risk Assessment In Heritable Aortopathies, Jin Vivian Lee, Anna L Huguenard, Ralph G Dacey, Alan C Braverman, Joshua W Osbun

2020-Current year OA Pubs

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies.

METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). …

Individual And Joint Associations Of High-Sensitivity Troponin I And High-Sensitivity Troponin T With Cardiac Phenotypes And Outcomes In The General Population: An Analysis From The Dallas Heart Study, Anand Rohatgi, Vijay Nambi, Christie M Ballantyne, Torbjorn Omland, Christopher R De Filippi, James De Lemos

Faculty, Staff and Students Publications

Background: High-sensitivity troponin I (hs-cTnI) and T (hs-cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood.

Methods and results: hs-cTnI and hs-cTnT were measured in Dallas Heart Study participants. Associations of hs-cTnI and hs-cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all-cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs-cTnI and hs-cTnT was modest (Spearman rho=0.35). Variables associated with hs-cTnI but …

Addressing Disparities In Pediatric Congenital Heart Disease: A Call For Equitable Health Care, Shahnawaz Amdani, Quang-Tuyen Nguyen, Christina Ronai, Seda Tierney, Victor Y Levy, Kriti Puri, Carolyn A Altman, Jonathan N Johnson, Julie S Glickstein

Faculty, Staff and Students Publications

While significant progress has been made in reducing disparities within the US health care system, notable gaps remain. This article explores existing disparities within pediatric congenital heart disease care. Congenital heart disease, the most common birth defect and a leading cause of infant death, has garnered substantial attention, revealing certain disparities within the US health care system. Factors such as race, ethnicity, insurance coverage, socioeconomic status, and geographic location are all commonalities that significantly affect health disparities in pediatric congenital heart disease. This comprehensive review sheds light on disparities from diverse perspectives in pediatric care, demonstrates the inequities and inequalities …

Characterization Of The Glyoxal Response In Pseudomonas Aeruginosa, Christopher James Corcoran

Dissertations

The toxic dialdehyde glyoxal is found in all domains of life and results as a by-product from a variety of metabolic activities such as DNA oxidation, lipid peroxidation, and autoxidation of sugars such as glucose. If allowed to accumulate, the reactive aldehyde groups of glyoxal have the ability to react with a plethora of molecules including, DNA, lipids, and protein side chains. Most notably, glyoxal can react with arginine, lysine, and cysteine residues, forming irreversible covalent modifications known as advanced glycation end products (AGEs). These glyoxal-derived AGEs can impair protein function, leading to cellular toxicity and eventual cell death. Due …

Peatmoss: A Dataset And Initial Analysis Of Pre-Trained Models In Open-Source Software, Wenxin Jiang, Jerin Yasmin, Jason Jones, Nicholas Synovic, Jiashen Kuo, Nathaniel Bielanski, Yuan Tian, George K. Thiruvathukal, James C. Davis

Computer Science: Faculty Publications and Other Works

The development and training of deep learning models have become increasingly costly and complex. Consequently, software engineers are adopting pre-trained models (PTMs) for their downstream applications. The dynamics of the PTM supply chain remain largely unexplored, signaling a clear need for structured datasets that document not only the metadata but also the subsequent applications of these models. Without such data, the MSR community cannot comprehensively understand the impact of PTM adoption and reuse. This paper presents the PeaTMOSS dataset, which comprises metadata for 281,638 PTMs and detailed snapshots for all PTMs with over 50 monthly downloads (14,296 PTMs), along with …

Esta Carta De Amor Es Para Ti: An Autoethnography Of An Undocumented Student’S Survival In Higher Education, Cuauhtemoc Salinas Martell

LMU Theses and Dissertations

This dissertation shed light on the need for higher education institutions to design support systems for undocumented students inside and outside of the classroom, especially when they apply to or attend prestigious universities. In addition, this study highlighted how I survived higher education, my home, and U.S. society through my multiple identities. The goal was to use my life experiences to show how powerful it is to be an undocumented student and how such students continue to influence laws, policies, and institutional change to make higher education more accessible and attainable. This study added to the literature on subaltern undocumented …

Influential Individuals Can Promote Prosocial Practices In Heterogeneous Societies: A Mathematical And Agent-Based Model, Stefani A. Crabtree, Colin D. Wren, Avinash Dixit, Simon A. Levin

Environment and Society Faculty Publications

In this paper, we examine how different governance types impact prosocial behaviors in a heterogenous society. We construct a general theoretical framework to examine a game-theoretic model to assess the ease of achieving a cooperative outcome. We then build a dynamic agent-based model to examine three distinct governance types in a heterogenous population: monitoring one's neighbors, despotic leadership, and influencing one's neighbors to adapt strategies that lead to better fitness. In our research, we find that while despotic leadership may lead towards high prosociality and high returns it does not exceed the effects of a local individual who can exert …

Rigorous Verification Of Stability Of Ideal Gas Layers, Damian Anderson

Theses and Dissertations

In this thesis we develop tools for carrying out computer assisted proof of the stability of traveling wave solutions of the spatially one-dimensional compressible Navier-Stokes equations with an ideal gas equation of state. In particular, we obtain rigorous, tight error bounds on a high-accuracy numerical approximation of the traveling wave profile for parameters corresponding to air, and we obtain rigorous representations in a neighborhood of positive and negative infinity of the solution to the first order ODE associated with linearizing the PDE equations about the traveling wave solution. We also develop supporting tools for rigorous verification of wave stability.

The Fishing Cat: New Insights On Distribution In The Northern Sector Of Chitwan National Park, Nepal, Rupesh Maharjan, Rama Mishra, Jhamak Bahadur Karki

School of Earth, Environmental, & Marine Sciences Faculty Publications

Fishing cat Prionailurus viverrinus (Bennett, 1833) is an elusive and medium-sized feline species with distinguished marking patterns on their head and body separating them from other feline species. Despite being distributed widely among diverse geographic locations, their abundance has declined due to significant habitat loss and human disturbances. There exists a substantial research gap regarding their abundance and distribution in Nepal. In this article, we presented the updated documentation of the fishing cat distribution in the northern sector of Chitwan National Park through our species-focused camera trapping survey. The study was carried out between April and May 2021 with a …

Celecoxib-Tramadol Co-Crystal In Patients With Moderate-To-Severe Pain Following Bunionectomy With Osteotomy: Secondary Analyses By Baseline Pain Intensity And Use Of Rescue Medication Of A Phase 3, Randomized, Double-Blind, Factorial, Active- And Placebo-Controlled Trial, Eugene R. Viscusi, Oscar De Leon-Casasola, Jesús Cebrecos, Adam Jacobs, Adelaida Morte, Esther Ortiz, Mariano Sust, Anna Vaqué, Ira Gottlieb, Stephen Daniels, Derek Muse, Michael E. Kuss, Sebastián Videla, Neus Gascón, Carlos Plata-Salamán

Department of Anesthesiology Faculty Papers

BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs).

METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of …

Influence Of Polypyrrole On Phosphorus- And Tio2-Based Anode Nanomaterials For Li-Ion Batteries, Yejin Kim, Keun-Young Shin, Byung Hyo Kim

Faculty, Staff and Student Publications

Phosphorus (P) and TiO2 have been extensively studied as anode materials for lithium-ion batteries (LIBs) due to their high specific capacities. However, P is limited by low electrical conductivity and significant volume changes during charge and discharge cycles, while TiO2 is hindered by low electrical conductivity and slow Li-ion diffusion. To address these issues, we synthesized organic–inorganic hybrid anode materials of P–polypyrrole (PPy) and TiO2–PPy, through in situ polymerization of pyrrole monomer in the presence of the nanoscale inorganic materials. These hybrid anode materials showed higher cycling stability and capacity compared to pure P and TiO2. The enhancements are attributed …

A/B Testing Of User Enrollment Forms To Enhance Diversity In The Biomedical Workforce Via The National Research Mentoring Network: User-Centered Design Case Study, Nan Kennedy, Damaris Javier, Katie Stinson, Jamboor K Vishwanatha

Faculty, Staff and Student Publications

BACKGROUND: The National Research Mentoring Network (NRMN) is a National Institutes of Health-funded program for diversifying the science, technology, engineering, math, and medicine research workforce through the provision of mentoring, networking, and professional development resources. The NRMN provides mentoring resources to members through its online platform-MyNRMN.

OBJECTIVE: MyNRMN helps members build a network of mentors. Our goal was to expand enrollment and mentoring connections, especially among those who have been historically underrepresented in biomedical training and the biomedical workforce.

METHODS: To improve the ease of enrollment, we implemented the split testing of iterations of our user interface for platform registration. …

Towards An Interdisciplinary “Science Of The Mind”: A Call For Enhanced Collaboration Between Philosophy And Neuroscience, Alessandra Buccella, Uri Maoz, Liad Mudrik

Psychology Faculty Articles and Research

In recent decades, the neuroscientific community has moved from describing the neural underpinnings of mental phenomena—as characterized by experimental psychology and philosophy of mind—to attempting to redefine those mental phenomena based on neural findings. Nowadays, many are intrigued by the idea that neuroscience might provide the “missing piece” that would allow philosophers (and, to an extent, psychologists, too) to make important advances, generating new means that these disciplines lack to close knowledge gaps and answer questions like “What is Free Will?” and “Do humans have it?.” In this paper, we argue that instead of striving for neuroscience to replace philosophy …

Nectarine Tree Named ‘A-783cn’, John R. Clark, Margaret L. Worthington

Patents Granted

Description and specification of a new and distinct nectarine tree cultivar named ‘A-783CN’ which originated from a hand-pollinated cross of ‘A-699N’ nectarine (female parent) x ‘A-717’ peach (male parent) in 2004. This new nectarine cultivar can be distinguished by its white, mid-acid, non-melting flesh, mid-season ripening, medium size, attractive appearance, and resistance to bacterial spot disease.

Waste Reduction And Recycling: Schweizer-Sklar Aggregation Operators Based On Neutrosophic Fuzzy Rough Sets And Their Application In Green Supply Chain Management, Zeeshan Ali, Hajra Bibi

Neutrosophic Systems with Applications

Green supply chain management (GSCM) is a valuable application that is used to reduce the overall environmental impact of the supply chain. Waste reduction and recycling are crucial components of sustainable technique that aims to reduce ecological impact and encourage reserve effectiveness. In this manuscript, we initiate the technique of Schweizer-Sklar (SS) operational laws based on neutrosophic fuzzy rough (NFR) values for SS t-norm (SSTN) and SS t-conorm (SSTCN). Further, we derive the NFR SS weighted averaging (NFRSSWA) operator and the NFR SS weighted geometric (NFRSSWG) operator. Some basic properties for the above-initiated techniques are derived. Additionally, we describe the …

Barriers And Facilitators To Healthy Eating In Disadvantaged Adults Living In The Uk:: A Scoping Review, R Briazu, F Masood, Louise Hunt, Clare Pettinger, Carol Wagstaff, R Mccloy

School of Health Professions

In the UK people living in disadvantaged communities are less likely than those with higher socio-economic status to have a healthy diet. To address this inequality, it is crucial scientists, practitioners and policy makers understand the factors that hinder and assist healthy food choice in these individuals. In this scoping review, we aimed to identify barriers and facilitators to healthy eating among disadvantaged individuals living in the UK. Additionally, we used the Theoretical Domains Framework (TDF) to synthesise results and provide a guide for the development of theory-informed behaviour change interventions. Five databases were searched, (CINAHL, Embase, MEDLINE, PsycINFO, and …

What Teams Need: Leading Digital Creatives, Matthew Dyet

Staff Scholarship - Australia & Dubai

What Teams Need: Leading Digital Creatives was a talk at the Revelations Conference. Based on my book Great Games Need Great Leaders, this talk was focused more broadly on leadership in the creative industries due to the audience being primarily from film.

Experimental Design For Scientific Discovery, Quan Minh Nguyen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Experimental design offers an elegant model of many problems where one navigates within a vast search space seeking data points with certain characteristics. A multitude of applications in science and engineering fall under this umbrella, with drug and materials discovery being prime examples. The experimental design approach maintains a probabilistic model of the search space, and uses Bayesian decision theory accounting for this model to guide the accumulation of observed data to maximize an experimentation objective of interest. This dissertation explores Bayesian optimization and active search, two realizations of the experimental design framework that model discovery tasks. While existing solutions …

Evaluating Artificial Intelligence On The Efficacy Of Preference Assessments For Preservice Speech-Language Pathologists, Brenna Griffin, Elizabeth R. Lorah, Christine Holyfield, Nicolette Caldwell, John Nosek

Curriculum and Instruction Faculty Publications and Presentations

Individuals with intellectual and developmental disabilities (IDD) face many barriers to meaningful inclusion, including limited language and communication skills. Professionals, such as speech-language pathologists (SLPs), can provide personalized instruction to promote skill development and inclusion. Providing opportunities for individuals to express preferences and choice, such as the multiple stimulus without replacement preference assessment (MSWO; DeLeon & Iwata 1996), within these programs, further increases skill acquisition and social interaction. However, limitations in professionals’ knowledge and skills in performing assessments can be another barrier to meaningful inclusion for individuals with IDD and traditional training methods can be challenging and time consuming. …

Predicting Distance Learning Counselor Education Doctoral Students’ Research Self-Efficacy, Jennifer Patrice Edwards

Walden Dissertations and Doctoral Studies

Distance learning is a growing educational delivery method for Counselor Education and Supervision (CES) doctoral students. At the time of this study, no research existed regarding the research self-efficacy (RSE) of distance learning CES doctoral students. Historically, the lack of RSE among counselor educators has been a chronic issue. However, research addressing contributors to improving RSE among distance learning CES doctoral students is unknown. The purpose of this study was to assess and provide data on current perceptions and predictors of RSE among distance learning CES doctoral students. Two theories were used to conceptualize the key variables which were Lent …

Ecological Factors And Minority Young Adults’ Trust In Law Enforcement, Jason Boswell

Walden Dissertations and Doctoral Studies

Throughout the past decade, studies have shown that the relationship between police organizations and community members has developed mistrust as more citizens begin to document misconduct by law enforcement officers. Studies have also proven that community members trust the police when they feel the police are fair and just. Distrust of law enforcement undermines the legitimacy of police officers, and without this trust legitimacy, police officers lose their ability and authority to perform their jobs effectively. To help bridge the gap between minority communities and law enforcement agencies, this qualitative phenomenological study was conducted to examine the trust within law …

Exploration Of The Implementation Of The Workforce Innovation And Opportunity Act By Vocational Rehabilitation Programs Through Collaboration With Education Officials, Elyse Leinani Luke

Walden Dissertations and Doctoral Studies

Despite public policies intended to achieve employment equity for students with disabilities, compared to students without disabilities, transition-age students with disabilities are less likely to be in the workforce even after receiving public vocational rehabilitation (VR) services. The purpose of this qualitative, multicase study was to explore implementation of the Workforce Innovation and Opportunity Act (WIOA) by VR programs through collaboration with state education officials to deliver pre-employment transition services (pre-ETS) to students with disabilities. The Integration Continuum was used to conceptually frame this study because the model provides a hierarchical scale with definitions about how organizations work together at …