Digital Commons Network^™

Margetuximab In Her2-Positive Metastatic Breast Cancer, William J Gradishar, Ruth O'Regan, Mothaffar F Rimawi, Jeffrey L Nordstrom, Minori K Rosales, Hope S Rugo

Faculty, Staff and Students Publications

Several anti-HER2 agents are approved for third-line treatment and beyond (after first-line and second-line); however, no specific treatment strategy is recommended for third-line and beyond. Although these agents improve disease outcomes, HER2-positive metastatic breast cancer remains incurable and there is an unmet need for effective therapies in the later line setting. This review focuses on the development of margetuximab-cmkb, a novel, Fc-engineered, anti-HER2 monoclonal antibody, and its role in the systemic treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva

2020-Current year OA Pubs

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant …

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

State 4-H Horse Show Entry Packet, Mary Davis

UNH Cooperative Extension

No abstract provided.

Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby

2020-Current year OA Pubs

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, …

Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.

2020-Current year OA Pubs

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …

Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill

2020-Current year OA Pubs

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes …

Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi

2020-Current year OA Pubs

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, …

Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen

2020-Current year OA Pubs

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …

Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu

2020-Current year OA Pubs

Identifying complete response (CR) after rectal cancer preoperative treatment is critical to deciding subsequent management. Imaging techniques, including endorectal ultrasound and MRI, have been investigated but have low negative predictive values. By imaging post-treatment vascular normalization using photoacoustic microscopy, we hypothesize that co-registered ultrasound and photoacoustic imaging will better identify complete responders. In this study, we used

Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang

2020-Current year OA Pubs

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …

Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint

2020-Current year OA Pubs

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …

Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski

2020-Current year OA Pubs

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric …

Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman

2020-Current year OA Pubs

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD. Our screen identifies 15 genetic enhancers of αSyn-induced progressive locomotor dysfunction, including knockdown of fly homologs of GBA …

Assessment Of The Knowledge, Attitude, And Practice Towards Expired Drug Disposal Among The Community In Beirut City, Lebanon, Nada Khansa, Azza A. K. Gazy, Abdalla El-Lakany, Souraya Domiati

BAU Journal - Health and Wellbeing

The global increase in pharmaceutical spending has led to enhanced international awareness of the unused and expired drug issues due to improper drug disposal's harmful economic, environmental, and health effects. Consequently, the study was conducted to assess the knowledge, attitude, and practice toward expired drug disposal among the community in Beirut City, Lebanon. A cross-sectional, observational, questionnaire-based study was conducted. Data were analyzed using SPSS version 23. The fact that improper disposal of expired medicine affects the environment and health was acknowledged by 70.7% of the 450 participants. Even though 72.2% of the participants knew that the best method for …

The Family History Of Arin A. Pitcher, Arin Pitcher

Your Family in History: HIST 550/700

The Family History of

Arin A. Pitcher

30 April 2023

Arin Alicejean Pitcher authored this family history as part of the course requirements for HIST 550/700 Your Family in History offered online in Spring 2023 and was submitted to the Pittsburg State University Digital Commons. Please contact the author directly with any questions or comments: [email protected]

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Meeting, Moving, Mastering - A Text Analysis Of The Aesthetic Attractions Of 'Wild Swimming', Dagmar Dahl, Åsa I. Bäckström

International Journal of Aquatic Research and Education

Why are people fascinated by swimming in nature? This article addresses the aesthetic experiences of wild swimming as expressed by five wild swimming authors in their books. Drawing from aesthetic philosophy, we analyze the ways in which the appeal of wild swimming is described on three levels: the allure of water in the environment, the sensory encounter between water and the body, and the experience of moving in water. Furthermore, with reference to Seel’s concept of nature aesthetics (1996), the experience of wild swimming is analyzed in terms of contemplation, correspondence, and imagination. We can conclude that the special intensity …

Development And Implementation Of An Ultrasound-Guided Peripheral Intravenous Catheter Insertion Training Program For Student Registered Nurse Anesthetists, Nicholas Colangelo, Zachary Wise

Doctor of Nursing Practice Scholarly Projects

The American Association of Nurse Anesthetists (AANA) has defined the scope of nurse anesthesia practice to include services in acute, chronic, and interventional pain management, as well as the use of ultrasound (U/S) and other diagnostic technologies. However, there are no standard curriculum requirements in place that mandate graduate programs to educate student nurse anesthetists in U/S-related modalities. In addition to the AANA, the use of U/S in nurse anesthesia practice has recently been adopted by The Council on Accreditation of Nurse Anesthesia Educational Programs (COA), which characterizes U/S use by its clinical impact on the reduction in complications, increased …

A Comparative Analysis Of The European And American Child Advocacy Model To Address Violence Against Children, Abigail Champion

Undergraduate Research Symposium

This presentation attempts to explain how each of the child advocacy models in the United States and Europe are different and similar. In addition, the presentation demonstrates how each model addresses violence against children. The slideshow provides examples of tools and resources therapists, social workers, and other social scientists use in the field. Lastly, the slideshow offers solutions and references on how the audience can become advocates and learn more information about child advocacy, child advocacy centers, and the different careers people can work in the child advocacy area.

Investigating The Nectar Preferences Of Bumblebees While Foraging: Are Total Responses A Good Metric?, Alexander Entwistle, Becky Hansis-O'Neill, Aimee Dunlap Dr

Undergraduate Research Symposium

The declining population of bumblebees worldwide poses an unmistakable threat to ecological systems and biodiversity. Therefore, a deep understanding of the factors at play when bees are foraging is crucial to conservation efforts. This research aims to explore the energy that foraging bumblebees are willing to expend at a known food source after the food has stopped, and if these responses reveal sugar concentration preferences. In this experiment a novel approach was used, adapted from psychology research on addiction, to measure bee’s preferences for different concentration of sugar-water (nectar). First, how many rewards the bees earned if they were given …

Green Synthesis Of Glutethimide Intermediate Via Nash Reaction, Zahria Patrick

Undergraduate Research Symposium

The purpose of my research project is to utilize green chemistry principles to synthesize an intermediate for Glutethimide, a drug used to treat patients with insomnia. Many pharmaceutical processes require the use of halide-containing chemicals which are harmful to the environment when discarded as waste. Not only does this waste affect the quality of drinking water and aquatic life, but it affects the economy as well. The cost of waste disposal increases with the increasing difficulty of treating it and thus raises the cost of production for pharmaceutical companies.
The reaction of choice is a nucleophilic aromatic substitution of hydrogen, …

Does A Bumblebee’S Size Influence Foraging Behavior?, Alametta Thompson-Hinton, Becky Hansis-O'Neill, Aimee Dunlap Dr

Undergraduate Research Symposium

Current studies of Bumblebees (Bombus impatiens) have shown that they prefer plants that have a higher concentration of sugar over those that are of a lower concentration. However, there is little research analyzing the impact of the size difference amongst bumblebee foragers. During our experiment, we tested if larger bumblebees demonstrate a propensity to pursue nectar rewards more frequently compared to smaller bees. We hypothesized that the smaller bumblebees would forage less than the larger ones under a fixed ratio and three different sugar concentrations. We found that our hypothesis was partly correct: smaller bees initially earned fewer rewards, …

The Family History Of Jeff Clark 29 January 2023, Jeff Clark

Your Family in History: HIST 550/700

The Family History of Jeff Clark 29 January 2023

Family History Of Marissa Ramirez, Marissa Ramirez

Your Family in History: HIST 550/700

The data and research collected was to discover the history of the four generations of Marissa Ramirez. A graduate study that focused on learning about her past and searching into more of her family history.

Who To Host: Competition Interactions Between Parasitoid Wasp Species, Jailah Henderson, Becky Hansis-O’Neill

Undergraduate Research Symposium

The availability of resources plays an important role in the survival and fitness of all organisms, one's ability to find and utilize resources can impact interactions between them and their environments. The interaction between organisms for resources can lead to interspecific competition, amongst two different species, or intraspecific competition, amongst the same species. In an experiment to test for competitive interactions between the parasitoid wasp species of N. vitripennis and M. digitata that utilize a fresh fly papua as their host to aid in the reproduction of their offspring. Over a period of time testing for conditions of interspecific and …

Extracting Cultural Commonsense Knowledge At Scale, Tuan Phong Nguyen, Simon Razniewski, Aparna S. Varde, Gerhard Weikum

School of Computing Faculty Scholarship and Creative Works

Structured knowledge is important for many AI applications. Commonsense knowledge, which is crucial for robust human-centric AI, is covered by a small number of structured knowledge projects. However, they lack knowledge about human traits and behaviors conditioned on socio-cultural contexts, which is crucial for situative AI. This paper presents Candle, an end-to-end methodology for extracting high-quality cultural commonsense knowledge (CCSK) at scale. Candle extracts CCSK assertions from a huge web corpus and organizes them into coherent clusters, for 3 domains of subjects (geography, religion, occupation) and several cultural facets (food, drinks, clothing, traditions, rituals, behaviors). Candle includes judicious techniques for …

The Unheard Voices Of Al-Intifadah Al-Shabaaniyah: An Exploration Of The 1991 Uprising And America’S Betrayal Through The Testimonies Of Iraqi Participants Residing In America, Zainab Alhussainy

Honors College Theses

This thesis delves into the often-overlooked 1991 uprising in Iraq, a significant early instance of resistance against Middle Eastern dictatorship. Rooted in the experiences shared within Michigan's Iraqi community. Focusing on southern Iraq, the thesis investigates the catalysts and mechanisms that enabled oppressed individuals under Saddam Hussein's Ba’athist regime to unite and rebel. Through extensive oral history methodologies, this research engages with diverse survivors—mothers, youth, and children—across various southern Iraqi cities. Their narratives unveil the hardships endured before, during, and after the rebellion.

Remarkably, despite oppressive conditions and violent impediments, the southern Iraqi populace achieved a formidable mass uprising. This …

Only 2000 Psi Of Bottom-Time Air: A Case Study Of Diveheart Participant Social Capital, Kirk J. Williams

Nonprofit and NGO Studies Student Projects

Social capital development for many, but not all, is a relatively organic process, and as social creatures, people work together to reach collective goals. The defined interactions related to the practices of societal norms, taboos, and broad cultural acceptance are constructs of communal decisions lending deep credence to the value of any number of the social capital definitions. However, opportunities are not always readily available to individuals living with disabilities, so they can and do get left out to varied degrees. With unsurprising results, previous research relied on comparing survey data from individuals with and without disabilities to identify possible …

The Effect Of Abortion Rights’ Political Activity On Engagement With Planned Parenthood, Emma C. Hazen

Nonprofit and NGO Studies Student Projects

In 2022, Roe v. Wade was overturned by the Supreme Court of the United States. Abortion became a hot topic of debate. Activists turned their attention to the issue with new vigor, and countless nonprofits became involved as well. The purpose of this study serves to explore the influence of political activity pertaining to abortion rights on Planned Parenthood. The aim is to analyze the ways that Planned Parenthood, as a national nonprofit, is affected by changes in the political sphere, which in turn generates activity via abortion activists.

This study will evaluate the extent to which abortion activity in …

Herpetofauna And Tarantula Avoidance: A Missouri Glades Location Survey, Zach Pfeiffer, Becky Hansis-O'Neill, Aimee Dunlap Dr

Undergraduate Research Symposium

Missouri glades are home to a variety of herpetofauna and one species of tarantula: Aphonopelma hentzi (Texas brown tarantula). These animals traverse through their environment very differently. Herpetofauna tend to travel in search of food, while tarantulas are usually restricted to foraging in areas very close to their burrows. Due to this contrast, and because of potential predator-prey relationships, I wanted to see if there was a pattern in the distances between these two groupings. To do this I conducted a location survey to determine how far each individual was from the nearest spider. After analyzing the data, it was …