Digital Commons Network^™

Current Directions In The Treatment Of Classical Hodgkin Lymphoma, Frank G Keller, Brad Kahl, Jonathan W Friedberg

2020-Current year OA Pubs

Optimal management of patients who present with Hodgkin lymphoma continues to evolve. Most patients are cured with current treatment strategies, some but both short and long-term morbidity and mortality from treatment have particular relevance given the youth of the patient population. Combininations of targeted agents together with conventional chemotherapy have recently been investigated in phase 3 cliniial trials for advanced-stage Hodkgkin lymphoma, and have demonstrated improved efficacy compared with chemotherapy alone. These include both antibody-drug conjugates and PD-1 blockade. Treatment approaches have historically differed between pediatric and adult groups, but recent collaborations between adullt and pediatric groups via the NCTN …

Multi-Omics Analysis Of Circulating Exosomes In Adherent Long-Term Treated Osa Patients, Abdelnaby Khalyfa, Jose M. Marin, David Sanz-Rubio, Zhen Lyu, Trupti Joshi, David Gozal

Biomedical Sciences

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP …

An Empowerment Evaluation Of Colorado Mountain College’S Mountain Scholars Program Via Latino Alumni Aspirational Goals And Outcomes, Laura Anne Bruch

Electronic Theses and Dissertations

This qualitative inquiry evaluated Colorado Mountain College’s (CMC) in-house Mountain Scholars Program (MSP) via semi-structured interviews with five of its Latino alumni. This study’s assets-based social justice/transformative philosophical framework included David Fetterman’s methodological empowerment evaluation and Tara Yosso’s conceptual community cultural wealth (CCW) theory. This dissertation in practice examined the gap in literature with regards to an in-house student support services program evaluation that partners with the community and focuses on Latinos’ aspirations and aspirational outcomes. I wanted to be a worthy witness to the student demographic group at CMC, as well as at most American postsecondary institutions, considered the …

Mothers In Law: A Critical Discourse Analysis Of Mothers In Law School, Sarah M. Jordon

Electronic Theses and Dissertations

Mothers are an increasing student population in higher education but an extensively under-researched population. While research examining motherhood is limited, the dearth of studies examining motherhood in higher education is especially limited, with even less available in the legal field and the institutions that provide legal education. This study examined how mothers in law school made meaning of their experiences utilizing a postmodernist epistemological framework, postmodernism and performance as a theoretical framework, and critical discourse analysis as a methodology. Data collection took place over the 2022-2023 academic year. Eight mothers participated in this qualitative study representing a range of ability …

Increasing Hub Disruption Parallels Dementia Severity In Autosomal Dominant Alzheimer Disease, Jiaxin Cindy Tu, Peter R Millar, Jeremy F Strain, Andrew Eck, Babatunde Adeyemo, Alisha Daniels, Celeste Karch, Eric Mcdade, Jason Hassenstab, John Morris, Jorge J Llibre-Guerra, Laura Ibanez, Randell J Bateman, Richard J Perrin, Tammie Benzinger, Beau M Ances, Adam T Eggebrecht, Brian A Gordon, Muriah D Wheelock, Et Al.

2020-Current year OA Pubs

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels-a phenomenon termed "activity-dependent degeneration". Yet, two critical …

Epigenetic Regulation During Cancer Transitions Across 11 Tumour Types, Nadezhda V Terekhanova, Alla Karpova, Wen-Wei Liang, Siqi Chen, Yize Li, Austin N Southard-Smith, Michael D Iglesia, Michael C Wendl, Reyka G Jayasinghe, Jingxian Liu, Yizhe Song, Song Cao, Andrew Houston, Xiuting Liu, Matthew A Wyczalkowski, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Shinkle, Nataly Naser Al Deen, John M Herndon, Jacqueline Mudd, Kazuhito Sato, Omar M Ibrahim, Chia-Kuei Mo, Sara E Chasnoff, Jason M Held, Russell Pachynski, Julie K Schwarz, William E Gillanders, Albert H Kim, Ravi Vij, John F Dipersio, Sidharth V Puram, Milan G Chheda, Katherine C Fuh, David G Denardo, Ryan C Fields, Feng Chen, Li Ding, Et Al.

2020-Current year OA Pubs

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis

The Association Between Reasons For First Using Cannabis, Later Pattern Of Use, And Risk Of First-Episode Psychosis: The Eu-Gei Case-Control Study, Edoardo Spinazzola, Emma C Johnson, Et Al.

2020-Current year OA Pubs

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status.

RESULTS: Controls (86.1%) …

Modeling The Normal:Abnormal Spectrum Of Early Childhood Internalizing Behaviors: A Clinical-Developmental Approach For The Multidimensional Assessment Profiles Internalizing Dimensions, Lauren S Wakschlag, Phillip Sherlock, Courtney K Blackwell, James L Burns, Sheila Krogh-Jespersen, Richard C Gershon, David Cella, Kristin A Buss, Joan L Luby

2020-Current year OA Pubs

BACKGROUND: We expanded the Multidimensional Assessment Profiles (MAPS) Scales developmental specification model to characterize the normal:abnormal spectrum of internalizing (anxious and depressive) behaviors in early childhood via the MAPS-Internalizing (MAPS-INT) scale.

METHODS: The MAPS-INT item pool was generated based on clinical expertise and prior research. Analyses were conducted on a sub-sample of families (n = 183) from the diverse When to Worry early childhood sample.

RESULTS: Normal:abnormal descriptive patterns for both anxious and depressive behaviors were consistent with prior work: (1) extremes of normative variation are abnormal when very frequent; and (2) pathognomonic indicators that most children do not engage …

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …

Disrupting Actin Filaments Enhances Glucose-Stimulated Insulin Secretion Independent Of The Cortical Actin Cytoskeleton, Alexander J Polino, Xue Wen Ng, Rebecca Rooks, David W Piston

2020-Current year OA Pubs

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic β cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating β cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to …

The Structure Of Nad+ Consuming Protein Acinetobacter Baumannii Tir Domain Shows Unique Kinetics And Conformations, Erik Klontz, Kow Essuman, Jeffrey Milbrandt, Aaron Diantonio, Et Al.

2020-Current year OA Pubs

Toll-like and interleukin-1/18 receptor/resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of the Acinetobacter baumannii TIR domain protein (AbTir-TIR) with confirmed NAD

Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López

2020-Current year OA Pubs

Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in …

Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.

METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, …

Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.

2020-Current year OA Pubs

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2

DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.

RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …

Experimentally Induced Active And Quiet Sleep Engage Non-Overlapping Transcriptional Programs In Drosophila, Niki Anthoney, Lucy Tainton-Heap, Hang Luong, Eleni Notaras, Amber B Kewin, Qiongyi Zhao, Trent Perry, Philip Batterham, Paul J Shaw, Bruno Van Swinderen

2020-Current year OA Pubs

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly

Gelation Of Cytoplasmic Expanded Cag Rna Repeats Suppresses Global Protein Synthesis, Yuyin Pan, J Lu, Xinran Feng, S Lu, Y Yang, G Yang, Shudan Tan, Liang Wang, Pilong Li, Shouqing Luo, B Lu

Peninsula Medical School

RNA molecules with the expanded CAG repeat (eCAGr) may undergo sol–gel phase transitions, but the functional impact of RNA gelation is completely unknown. Here, we demonstrate that the eCAGr RNA may form cytoplasmic gel-like foci that are rapidly degraded by lysosomes. These RNA foci may significantly reduce the global protein synthesis rate, possibly by sequestering the translation elongation factor eEF2. Disrupting the eCAGr RNA gelation restored the global protein synthesis rate, whereas enhanced gelation exacerbated this phenotype. eEF2 puncta were significantly enhanced in brain slices from a knock-in mouse model and from patients with Huntington’s disease, which is a CAG …

Maternal Exposure To Ssris Or Snris And The Risk Of Congenital Abnormalities In Offspring: A Systematic Review And Meta-Analysis, Weiyi Huang, Robin Page, Theresa Morris, Susan Ayres, Alva Ferdinand, Samiran Sinha

Faculty Scholarship

Background

The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.

Methods

A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.

Results

Twenty-one cohort studies and seven case-control …

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

2020-Current year OA Pubs

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …

A Consortium Of Microalgae And Wastewater Activated Sludge To Generate Biohydrogen, Muhammad Asad Javed

Dissertations

Hydrogen is a clean source and carbon-free source of energy that can be generated photobiologically using green microalgae with 122 kJ/g of energy output which is 2.75 times that of hydrocarbon-based fuels. However, challenges, such as presence of molecular oxygen (O₂) within the cells, hinder their practical application. Molecular O₂, emanating from the activity of photosynthesis, acts as a powerful and effective switch that turns off bioH₂ production activity. The objective of this research was to develop an innovative approach to increase the yield and sustain bioH₂ photoproduction. For this purpose, a consortium of …

Our Authors

Gathered Fragments

No abstract provided.

Pedagogy In Times Of Crisis, James Daria, Abigail Wightman, Shelly Yankovskyy, Amanda J. Reinke

Southern Anthropologist

Editors’ note: With this issue, we launch a new feature of the journal, drawing from a panel discussion or roundtable at SAS, which sparked important discussion for panelists and conference participants. This panel, which took place on April 9, 2022, in Raleigh, NC, was part of the 55th Annual Meeting of the Southern Anthropological Society with the theme “Public Interest and Professional Anthropology in the South.” The roundtable was organized and moderated by Amanda J. Reinke. The transcript was created by Helen Regis and the conversation was lightly edited by the authors, who also had an opportunity to include references …

Building The Soil Carbon Sponge At Murray Wells Farm, Tambellup, Western Australia, Wendy Bradshaw

Natural resources published reports

Peter and Wendy Bradshaw farmed at Murray Wells Farm about 25 km west of Tambellup for around 46 years until they sold and retired in 2022. They produced barley, oats, merino and prime lambs on an annual rainfall of 450 mm over 1,000 arable hectares. The farm was on a moderately undulating landscape with a mix of soils including sandy duplex, well-drained sand over gravel over clay, shallow sandy or loamy gravel over cemented laterite and red to brown loamy soils.Their farming philosophy was to view agriculture as an ecological enterprise that included them as part of the ecosystem, and …

Challenges And Responses : The Impact Of Classification Methods Of Policies On First-Generation College Students In China And The Us, Ken Cheng

SOC 605 Comparative Social Policy Research Project - Student Works

In China and the United States, with the expansion of higher education, more and more people have become the first-generation of college students in their families. However, while gaining opportunities for social upward mobility, they also face many challenges, and the formation of these challenges is related to their multiple identities. In China, these challenges are more related to regional development differences, while in the United States, they are more impacted by identities such as immigrants and ethnic minorities. At the same time, the governments, universities, and society of both countries have introduced various policies to support first-generation college students, …

Citizenship Outside The Courts, Catherine Y. Kim

Faculty Scholarship

No abstract provided.

Big Boned: How Fat Storage And Other Adaptations Influenced Large Theropod Foraging Ecology, Cameron Pahl, Luis A. Ruedas

Biology Faculty Publications and Presentations

Dinosaur foraging ecology has been the subject of scientific interest for decades, yet much of what we understand about it remains hypothetical. We wrote an agent-based model (ABM) to simulate meat energy sources present in dinosaur environments, including carcasses of giant sauropods, along with living, huntable prey. Theropod dinosaurs modeled in this environment (specifically allosauroids, and more particularly, Allosaurus Marsh, 1877) were instantiated with heritable traits favorable to either hunting success or scavenging success. If hunter phenotypes were more reproductively successful, their traits were propagated into the population through their offspring, resulting in predator specialists. If selective pressure favored scavenger …

Drivers Of Plankton Community Structure In Intermittent And Continuous Coastal Upwelling Systems–From Microbes And Microscale In-Situ Imaging To Large Scale Patterns, Moritz Schmid, Su Sponaugle, Anne W. Thompson, Kelly T. Sutherland, Robert Cowen

Biology Faculty Publications and Presentations

Eastern Boundary Systems support major fisheries whose early life stages depend on upwelling production. Upwelling can be highly variable at the regional scale, with substantial repercussions for new productivity and microbial loop activity. Studies that integrate the classic trophic web based on new production with the microbial loop are rare due to the range in body forms and sizes of the taxa. Underwater imaging can overcome this limitation, and with machine learning, enables fine resolution studies spanning large spatial scales. We used the In-situ Ichthyoplankton Imaging System (ISIIS) to investigate the drivers of plankton community structure in the northern California …

Germ Cell Recovery, Cryopreservation And Transplantation In The California White Sturgeon, Acipenser Transmontanus, Amie L. Romney, Danielle M. Myers, Fatima R. Martin, Tawney N. Scanlan, Stuart A. Meyers

Biology Faculty Publications and Presentations

The white sturgeon (Acipenser transmontanus) is the largest freshwater fish in North America. Because of the unique life history characteristics of sturgeon, including longevity, late maturation and long spawning intervals, their aquaculture can be a significant investment of resources. As a result of habitat loss and overharvesting, natural populations of white sturgeon are threatened and there is a growing effort to improve conservation aquaculture programs. Germ cell transplantation is an innovative technology previously demonstrated in a variety of fish species to be able to produce a surrogate broodstock. The technique relies upon optimal donor germ cell recovery and transplantation into …

Characterization And Evaluation Of Bioactivity Of Dry Edible Bean And Bean Derived Small Peptides, Bikram Prasad Upadhyaya

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Obesity, diabetes, and their metabolic complications continue to be one of the major global public health concerns with a few effective treatment options. Although regular exercise and a well-balanced diet that includes calories from pulses can be recommended, much remains to be elucidated about the health effects of the various bioactive compounds including peptides and polyphenols present in pulses. Most of the previous studies have focused on individual dietary compounds and only a few investigated the synergistic effect of active compounds in modulating human health. Hence this dissertation aimed first, to provide a comparative evaluation of the overall therapeutic value …

Biomimetic Approach To Elucidate The Role Of Microenvironment In Regulating Cell Communications In Liver Diseases, Youra Moeun

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Liver is a complex organ but often underappreciated for its functions to remove toxins and fight infection in the body. Despite the ongoing prevalence of patients contracting chronic liver diseases, coupled with a global healthcare investment of approximately $70 billion, there is still no effective treatment for chronic liver diseases including alcoholic liver disease. The purpose of this dissertation was to understand the interactions of parenchymal and non-parenchymal liver cells in physiological and pathological like environments. This allowed us to recreate a healthy and the diseased microenvironments to observe the stages of the liver diseases development and apply appropriate treatments …

Modeling Overdraft-Driven Nitrate Transport In Shallow Wells For Mitigation And Scenario Planning, Jonathan Cronk

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

In Nebraska, average nitrate concentrations in groundwater have doubled since 1974, making water quality management more important than ever. As droughts, heat waves, and floods become more common climate events, understanding their impacts will be necessary to make informed management decisions. Emerging literature describes that drought correlates to an increase in the concentration of nitrate-N at domestic and irrigation wells, however the relative contributions of the mechanisms thought to be responsible is currently unknown.

This research assessed the impact of recharge and pumping rate changes as two mechanisms affecting nitrate-N concentration during drought, assessed the relationship between well depth and …