Digital Commons Network^™

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …

Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus

Dissertations

MLL-rearranged (MLL-r) leukemia is an aggressive subset of acute leukemia, accounting for up to 10% of adult and 70% of infant AML and ALL cases. These leukemias are driven by MLL fusion proteins, which recruit epigenetic cofactors to dysregulate gene expression, leading to poor prognosis and resistance to conventional chemotherapy. Previous lab work identified EYA1’s role in leukemogenesis, establishing it as a therapeutic target in MLL-r leukemia. EYA1, is a transcriptional coactivator and protein tyrosine phosphatase (PTP). Originally a gout medication, benzbromarone (BBR), was identified in an NCI Diversity Set screen as an EYA1-specific PTP inhibitor. BBR provides a tool …

Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler

School of Environmental Sustainability: Faculty Publications and Other Works

The COVID-19 pandemic disrupted food systems with disproportionate impacts on marginalized social groups, which in the USA included racial and ethnic minorities, working class families, immigrants, seniors, and people with disabilities, among others. The pandemic also greatly affected the operations of nonprofit organizations, which play important roles in disaster response. We explored how social networks supported non-profit organizations’ efforts to address increased food insecurity and food-related business disruptions during the pandemic in the Chicago region, IL, USA. We used mixed methods including a Social Network Analysis (SNA) of 48 organizations and their reported partners plus focus group discussions with representatives …

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …

Audiological Characteristics And Associations With Psychological Inflexibility, Karen Muñoz, Bailey Sorensen, Aryn Kamerer, Michael P. Twohig

Psychology Faculty Publications

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Method:

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The Acute Impact Of Game-Based Physical Education On The Mood States Of Middle School Students, John Nemeth

Doctorate in Kinesiology

Mental health disorders represent a massive global health burden, with close to one billion people currently affected. Access to treatment and medical care remains low, especially among children. Increased physical activity (PA) is a widely recognized and accessible method for improving mental health, with substantial evidence supporting its benefits. Physical education (PE) is a structured, school-based environment that promotes PA and increased movement, but research examining its impact on mood is limited. This study examined mood changes in middle school students following PE participation in two game-based activities: handball (team sports) and badminton (partner games). A quasi-experimental design was used …

Moderating Role Of Locus Of Control On The Relationship Between Self-Efficacy And Trust In Ai, Amelia Gillies

Walden Dissertations and Doctoral Studies

The rapid integration of artificial intelligence (AI) into essential sectors, including healthcare, customer services, and defense, has underscored the importance of user trust in AI systems. Psychological traits such as locus of control (the extent to which individuals attribute outcomes to internal or external factors) and self-efficacy (individuals’ confidence in their ability) have been identified as significant factors influencing trust in these automated systems. Previous studies have independently linked these psychological traits to trust in technology; however, there has been limited exploration of potential moderating effects of locus of control on the relationship between digital technology self-efficacy and trust in …

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …

Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Background: NLRP2 is a subcortical maternal complex (SCMC) protein of mammalian oocytes and preimplantation embryos. SCMC proteins are encoded by maternal effect genes and play a pivotal role in the maternal-to-zygotic transition (MZT), early embryogenesis, and epigenetic (re)programming. Maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans, but the underlying molecular mechanisms for the diverse functions of SCMC proteins, and specifically the role of NLRP2, are incompletely understood.

Results: We profiled the DNA methylome of pre-ovulatory germinal-vesicle (GV) oocytes from Nlrp2-null, heterozygous (Het), and wild-type (WT) female mice and assessed the …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …

Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh

Faculty, Staff and Students Publications

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Methods: Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins.

Results: SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of …

Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir

Faculty, Staff and Students Publications

No abstract provided.

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone

Faculty, Staff and Students Publications

Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …

An Antibody Biomarker Associated With Onchocerca Volvulus Microfilariae Identified By Proteomic Analysis Of Parasite Tissues Isolated From Paraffin Embedded O. Volvulus Nodules By Laser Capture Microdissection, Sarah E Greene, Kerstin Fischer, Lucia S Di Maggio, Bruce A Rosa, Yuefang Huang, Irina Diekmann, Byoung-Kyu Cho, Jessica Lukowski, Young A Goo, Makedonka Mitreva, Nicholas Opoku, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

Onchocerciasis (river blindness), a neglected tropical disease caused by the filarial nematode Onchocerca volvulus, impacts millions of people in sub-Saharan Africa. The WHO coordinates global efforts to eliminate onchocerciasis and has prioritized development of improved diagnostic tests to aid these efforts. To find new microfilarial-associated diagnostic targets to help identify active infections, we used laser capture microdissection to isolate embryonic stages from histologic sections of O. volvulus worms in subcutaneous nodules excised from onchocerciasis patients. Proteomic analysis identified 2,512 O. volvulus proteins in those tissues, including 264 found only in the microfilariae (Mf). From this pool of diagnostic candidates, we …

Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map Of The Human Kidney Across The Lifespan, Liam Mclaughlin, Bo Zhang, Siddharth Sharma, Amanda L Knoten, Madhurima Kaushal, Jeffrey M Purkerson, Heidie L Huyck, Gloria S Pryhuber, Joseph P Gaut, Sanjay Jain

2020-Current year OA Pubs

The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through "mother glomeruli" that serve as control centers, creating a repeating pattern …

Perceptions Of Spirituality And Of God: A Psychological Qualitative Study, Christopher E. Peck, Timothy B. Smith, Jamila Mastny

Faculty Publications

The majority of people living in the U.S. report that spirituality is an important part of their life that is influential to their well-being. However, individuals vary widely in how they conceptualize spirituality, which often stems from and overlaps with their conceptualizations of God or so-called “God image”. Examination of people’s experiences of spirituality and conceptualization of God can enable psychologists to improve their understanding of individuals’ core personal experiences. This study evaluates both spirituality and God image, as well as the relationship between these two constructs, using qualitative hermeneutic analysis of interviews with 63 adults (51% women, 49% men, …

Core Grade 7: Principles For Moving From Evidence To Recommendations And Decisions, Gordon Guyatt, Per Olav Vandvik, Alfonso Iorio, Arnav Agarwal, Liang Yao, Prashanti Eachempati, Linan Zeng, Derek K. Chu, Rohan D'Souza, Thomas Agoritsas, M. Hassan Murad, Stefan Schandelmaier, Jamie Rylance, Benjamin Djulbegovic, Victor M. Montori, Monica Hultcrantz, Romina Brignardello-Petersen

Peninsula Dental School

This seventh article in a seven part series presents the Core GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for moving from evidence to recommendations or policy decisions. Core GRADE users make strong recommendations for an intervention versus a comparator when the desirable consequences clearly outweigh the undesirable consequences, and a conditional (weak) recommendation when the balance is less clear. Primary considerations in deciding on recommendations considering an individual patient perspective include balance of benefits, harms, and burdens; the certainty of evidence; and values and preferences. Secondary considerations, most important from a population perspective, include costs, feasibility, acceptability, and …

Enhanced Heater For 3d Asic Chip Design, Na

Defensive Publications Series

This disclosure describes techniques to thermally characterize three-dimensional integrated circuits (IC). Per the techniques, logic is incorporated into the IC (chip-under-test) that can generate random data, e.g., pseudorandom binary sequence (PRBS), at controllable toggle rates. The random data toggles across the entire die. A power-control mechanism controls the toggle rate in a fine-grained manner. Thermal and voltage sensors integrated into the chip-under-test enable real-time monitoring of temperature and voltage and generate data that can be used to analyze the power consumption, thermal characteristics, and overall health of the chip.

A Century Of Servant Leadership: Jimmy Carter, Jeffrey H. Coats

Servant Leadership: Theory & Practice

This paper describes the servant leadership characteristics of Jimmy and Rosalyn Carter.

Enhancing Team Effectiveness: A Study On The Efficacy Of Servant Leadership Experiential Training As An Intervention, Jason R. Weber

Servant Leadership: Theory & Practice

Purpose: This paper aims to identify the impact of servant-leadership training on team effectiveness. It proposes using a perceptive behavior assessment tool (team effectiveness questionnaire (TEQ)), along with six servant leadership themes will increase a team’s effectiveness. This study aims to expand the literature on methods used when seeking to improve operational effectiveness of work teams.

Design/methodology/approach: This intervention study followed the two-group pre-test-post-test design. 18 teams were randomly assigned to either a control or experimental group. Each team completed the TEQ and identified one to two domains to focus their development on over an 8-week period. Experimental group teams …

Organizational Change, Servant Leadership, And Christian Perspective, David Macauley, Randall Trent Stevenson, Helen Mitchell, David S. Fowler

Servant Leadership: Theory & Practice

In today’s dynamic business environment, organizational change is inevitable, yet with a failure rate of more than 70%, successfully navigating change remains elusive for the majority of business leaders. Effective change management requires more than just strategy, it demands a leadership approach that fosters trust, engagement, and resilience among employees. Servant leadership, with its focus on humility, empathy, and support, offers a powerful framework for guiding leaders and the organizations they serve through transformative periods, and can increase the effectiveness of organizational change efforts. By putting the needs of others first, and aligning leadership actions with values such as patience, …

The Servant Leader's Influence, Kevin J. Hurt

Servant Leadership: Theory & Practice

No abstract provided.

Contributor Biographies, Editors Of Suurj

SUURJ: Seattle University Undergraduate Research Journal

No abstract provided.

Maghrebi Identity & Integration In France: Colonial Legacies And Contemporary Realities, Mariam Gohar

SUURJ: Seattle University Undergraduate Research Journal

Historical ties between France and the Maghreb continue to shape and inform the experiences of the Maghrebi population in contemporary French society. There is an extensive Maghrebi population in France as a result of France’s colonial history in the region and subsequent migration. The Maghrebi populations face structural and social barriers in French society, including employment and education disparities, spatial segregation, and social Otherization. Maghrebi communities are only one example of France’s structural discrimination against non-European populations. This work aims to unpack the historical, political, and economic factors that resulted in French colonization of the Maghreb and relate these to …

“This Is One Moment In Time, Sealed In Amber”: A Structural And Content Analysis Of Queer Characters And Themes In The Audio Drama Eos 10, Emma Renn

SUURJ: Seattle University Undergraduate Research Journal

Queer horror and science fiction (sf) audio dramas populate many podcasting platforms, from explicit calls for and queries about Queer representation to general forums discussing horror and sf audio dramas (or podcasts). In this study, I used the principles of a case study to explore the queer nature of EOS 10 (an sf audio drama). I listened to the podcast EOS 10 and coded transcriptions which focused on Queer themes, in reference to sexuality or in relationship to heteronormativity more generally. I focused primarily on the trope of found family, as well as how audio dramas can push back against …