RSS 1.0eScholarship@UMassChan
eScholarship@UMassChan is a digital repository for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA.
New! The recording and slides for our webinar "eScholarship@UMassChan: Share UMass Chan Research with the World" are available.
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Northeast Institutional Repository Day 2023: Links Mentioned in PresentationsThis document, compiled by conference organizers, is a list of links to resources mentioned by attendees in the chat during the 5th annual Northeast Institutional Repository Day (NIRD23) conference, held virtually on Thursday, November 30, 2023 and Friday, December 1, 2023.
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Second Time's the Charm ... (sort of): Lessons Learned from Two Attempts to Migrate from DSpace 6.3 to DSpace 7.6Members from Cornell University Library's IT department share lessons learned from two attempts to migrate their DSpace 6.3 repository to the new DSpace 7.6 infrastructure. Learn about performance tuning, customizations, streamlined and secure access, containerization, and more!
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Making Migration Less Mysterious: Developing a Migration Plan for ScholarWorks@UMassAmherstIn January 2023, after years of environmental scans, interviews with stakeholders and other IR managers, and platform investigations and pilots, the UMass Amherst Libraries made the decision to migrate its IR from bepress' Digital Commons to a combination of Janeway and Atmire-hosted DSpace 7.x. We all love a good migration presentation, but for most of us, migration remains a mysterious process that's difficult to envision. In this talk, I will walk through my process of creating a migration plan for our rather large and unwieldy IR -- from interviews with IR managers who have been through migration, the beginning stages of data cleanup and standardization, and the fun -- Excel column limits! Items uploaded multiple times!--discoveries made along the way. I will also discuss how the cleanup and discoveries are shaping our IR policies moving forward.
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Signs and Wonders: Integrating Multiple Systems to Digitize the Deaf Catholic ArchivesThe Archives and Distinctive Collections at the College of the Holy Cross is in the second half of a two-year CLIR "Digitizing Hidden Collections" grant project to preserve and provide access to key components of the Deaf Catholic Archives (DCA). Ideally, digital content would be accessible through both the institutional repository as well as the archival finding aids. Wonder how we did it? The project utilized three systems (Digital Commons, ArchivesSpace and Google) to efficiently upload thousands of items to our repository and link them to their respective finding aids. This presentation will discuss how we worked to build the repository structures and then developed workflows to create and populate an online collection that allows multiple access points for a large, complex, and growing archive. As this work continues, the next phase of the grant will use another tool to create exhibits using our IR, thus facilitating additional access, promotion and outreach efforts. These efforts, as well as the creation of metadata and description, will intentionally include input from members of the Deaf community here at Holy Cross and in partnership with others. Our experience offers suggestions for how to build out a large collection with several structures that require different technical treatments. We have already begun adapting them for other digitization projects. Though we used specific platforms, this presentation will demonstrate how different applications can be harnessed for a large, long-term project.
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Agility in Changing Institutional Repository PlatformsThe purpose of this presentation is that it is perfectly okay to instill flexibility to change an institutional repository (IR) platform that will improve the (IR) user experience. New to the IR landscape in 2019 this was the first IR at this academic institution. Even with an ambitious focus to make this a shiny IR resource it fell short in its mission. It was time to go back to the drawing board in 2022, post-Covid pandemic, to search the IR landscape for a new generation IR. The goal was to have an abundance of modern features in the IR that would survive past the expiration date of staleness. Agility to change is necessary and making the change in a timely matter can benefit both library users of the IR and the library staff overseeing the IR. After four years with an IR platform the change in 2023 to a new IR platform that became a successful launching pad for new IR experience.
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Kwalk: A Simple Program to Crosswalk Metadata for Repository UploadsUniversity of Chicago's Center for Digital Scholarship has been utilizing this program to better edit metadata for batch upload to Knowledge@UChicago. There are plans to share this software in the future as it is platform agnostic and has a potential wide range of use cases. Suppose you need to upload 1,000 items to TIND from a source like Lens.org or PLOS journals. You obtain informal metadata for the items by you or another person creating the spreadsheet from scratch, exporting the data, or web scraping each individual record. You might need to do the following after obtaining the data: Rename all the fields in the from the invented field names to TIND's field names; Add some fields that are missing; Leave out some fields you don't want; Combine several fields into one field; Modify the values of date formats or author names in a programmatic way; Generate syntactically correct upload URLs from a simple filename field. Kwalk is a program that lets us write a simple crosswalk that we can apply to each batch of metadata as we receive it and have multiple crosswalks for multiple projects as we work on them in an intermixed fashion. The program allows us to apply special functions to modify date formats, combine literal and field name text, generate uniform upload URLs, and much more.
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Increase Discoverability of IR Works by Utilizing SEO (Search Engine Optimization) ToolsThe University of Notre Dame Law School utilizes Digital Commons to maintain its institutional repository, known as NDLScholarship, which is overseen by a small team within the Kresge Law Library at the Law School. Upon conducting a content review of the repository in collaboration with the Bepress consultant, it became evident that the SEO tools and features are overlooked. The new manager initiated a project to enhance the discoverability of the repository's content, leveraging Digital Commons' built-in SEO tools and features. This presentation intends to outline the team's approach, including the methods employed to gather and prioritize metadata, as well as the creation of descriptive page titles and introductory text to be incorporated at various structural levels such as the site homepage, community page, and individual publication items.
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Northeast Institutional Repository Day 2023: NIRD23 Program and ScheduleSchedule and program for the 5th annual Northeast Institutional Repository Day (NIRD) conference, held virtually on Thursday, November 30, 2023 (1:00-4:00 pm ET) and Friday, December 1, 2023 (10:00 am - 12:00 pm ET).
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Curating Audiovisual Data in Data RepositoriesThis presentation reviews the practices of curating audiovisual data for submission into data repositories. As part of our Data Curation Network training program, we decided to write a primer on the topic of curating audiovisual data. Audiovisual materials are not a common form of research data in all fields, but is a burgeoning data type especially in the social sciences. Audiovisual data curation processes are not well documented, which motivated us to write a foundational and accessible guide for curators. We interviewed multiple experts in this field in order to learn more about their needs, challenges, and existing procedures. Our hope for this guide and presentation is to encourage further exploration of this fast developing topic. This presentation will cover our investigation of curation workflow, ethical issues, technical concerns, documentation, metadata, and special considerations.
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Journey into the Third Dimension: Extending IRs to Support 3D Model DataFor the last 2 years, Florida State University Libraries' Technology and Digital Scholarship department has been exploring ways to incorporate 3D model data into DigiNole, FSU's digital repository built on the open source Islandora 7 platform. In August 2023 we finally reached a major milestone with a publicly viewable demo open for review and testing by internal stakeholders. This represents the culmination of much collaborative work between 3D modeling subject experts and developers, and a lot of hard lessons learned along the way that we are ready to share with others trodding a similar path. Join us for a summary of our journey into the unfamiliar realm of 3D modeling, and learn how you can extend your IR to handle 3D model data as well! This session covers the specific requirements for supporting 3D model data as scholarly research outputs stored in an institutional repository, and is aimed at an audience familiar with standard scholarly content in an institutional repository but with little to no prior knowledge of 3D modeling. Topics covered will include the production and use of scholarly 3D model data by students and faculty, unique metadata elements for 3D model data, how to create a 3D model test suite, tips for integrating a 3D model viewer like the Online 3D Viewer (https://3dviewer.net/) into your repository, an overview of the most popular 3D model file formats, and a discussion about the complexities of building a system that creates a consistent user experience for ingesting and displaying 3D models with surprisingly inconsistent data structures.
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Surveying and Editing the Metadata of Our Marathon: The Boston Bombing Digital ArchiveIn this talk, I will discuss my experience surveying and editing the metadata of a large crowdsourced public history archive. The Our Marathon collection includes nearly 8,000 items, with materials ranging from letters to collages to oral histories and other first-person accounts collected in the wake of the 2013 Boston Marathon bombing. Along the way, collaborations were established between Northeastern University and the NPR radio station, WBUR, the Boston Globe, and the Boston Public Library. This archive bears some resemblance to other projects that used crowdsourced materials in response to a public trauma, such as the September 11 Digital Archive and the Hurricane Digital Memory Bank relating the experiences of Katrina and Rita. I added to and edited the Metadata Object Description Schema (or MODS) records from this collection, in order to clarify the copyright status, associated names and subjects of these materials, as well as the languages used in certain items, so as to improve discoverability for researchers viewing the collection through Northeastern University Library's Digital Repository Service. One of the biggest issues with these records initially was their lack of standardization and authorities, and in order to address these problems I needed to develop new ways of searching and surveying this collection. In working with this collection, I have realized that it presents some challenges that are perhaps unique to such a large, crowdsourced response to a shared trauma. Because this is a kind of memorial, with a goal of both community building and healing, it is important for users to be able to access this material on their own terms. Yet the large number of items in this collection require organization to allow for meaningful access.
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Approaching Accessibility For Your IRAccessibility standards are commonplace. While this progress is something to be championed, it can leave an institutional repository in a difficult situation. How do you uphold accessibility standards when you are not in creating the materials that are being added to your IR? This session will start by looking at the policy and potentially political considerations, as well as the practical aspects of implementing the policy. How do you implement the standards? What stake-holder buy in do you need? Is there technology that can help? Are you actually able to acquire the technology? Who is going to pay for the technology? Will AI truly save us all? And, because of the inevitable way that things like this usually go, how do you formulate Plans B-D just in case things do not go according to plan/take longer to implement? This presentation is coming from librarians who are currently working through this process and will outline what we've done so that others (hopefully) don't have to experience the same. Commiseration and comments from the audience will be highly encouraged.
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Rethinking Institutional RepositoriesOver the past twenty years, institutional repositories (IRs) have become commonplace across most colleges and universities. While IRs were originally conceived as a means to collect and disseminate faculty scholarship, in recent years it has become apparent that this may not be the most effective use case for the modern IR. In light of this changing landscape, how should IR managers think about the IR today? This session will provide an overview of the forthcoming book Rethinking Institutional Repositories, published by ACRL, which seeks to answer this question through contributions from IR managers at a wide range of institutions. The session will also briefly highlight several case studies from the book that provide practical suggestions for managing the modern IR, developing innovative projects and use cases for the IR, and using the IR as a means to highlight and showcase diverse voices and viewpoints and to provide an inclusive platform for all members of the community.
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POINT-OF-CARE TECHNOLOGY CLINICIAN-FACING SURVEY Dataset for Sampling of Healthcare Professionals’ Perspective on Point-of-Care Technologies from 2019-2021: a survey of benefits, concerns, and developmentPoint-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice.
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Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy [preprint]The rational combination of anticancer agents is critical to improving patient outcomes in cancer. Nonetheless, most combination regimens in the clinic result from empirical methodologies disregarding insight into the mechanism of action and missing the opportunity to improve therapy outcomes incrementally. Deciphering the genetic dependencies and vulnerabilities responsible for synergistic interactions is crucial for rationally developing effective anticancer drug combinations. Hence, we screened pairwise pharmacological interactions between molecular-targeted agents and conventional chemotherapeutics and examined the genome-scale genetic dependencies in gastric adenocarcinoma cell models. Since this type of cancer is mainly chemoresistant and incurable, clinical situations demand effective combination strategies. Our pairwise combination screen revealed SN38/erlotinib as the drug pair with the most robust synergism. Genome-wide CRISPR screening and a shRNA-based signature assay indicated that the genetic dependency/vulnerability signature of SN38/erlotinib is the same as SN38 alone. Additional investigation revealed that the enhanced cell death with improved death kinetics caused by the SN38/erlotinib combination is surprisingly due to erlotinib's off-target effect that inhibits ABCG2 but not its on-target effect on EGFR. Our results confirm that a genetic dependency signature different from the single-drug application may not be necessary for the synergistic interaction of molecular-targeted agents with conventional chemotherapeutics in gastric adenocarcinoma. The findings also demonstrated the efficacy of functional genomics approaches in unveiling biologically validated mechanisms of pharmacological interactions.
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Addressing Bottlenecks of Prime Editing Through Improved pegRNA Designs and Rationally Engineered Prime Editor VariantsPrime editing systems have enabled the incorporation of precise edits within a genome without introducing double strand breaks. With the versatile ability to introduce point mutations, deletions and insertions, prime editors have the ability to correct around 89% of known genetic variants associated with human diseases. However, there are several bottlenecks currently restricting prime editing activity that need to be addressed to further their use as therapeutics. In the first half of this thesis, we address the auto-inhibitory interaction between the PBS and the spacer sequence that affects pegRNA binding efficiency and target recognition. We show that destabilizing this auto-inhibitory interaction by reducing the complementarity between the PBS-spacer region enhances prime editing efficiency. These design parameters were initially fueled by our goal to improve prime editor ribonucleoprotein activity where the auto-inhibitory interaction of the pegRNA is more prominent, but we show that they can be applied to multiple prime editing formats to increase editing rates. In the case of end-protected pegRNAs, we discover that a shorter PBS length with a PBS-target strand melting temperature near 37°C is optimal in mammalian cells. Additionally, we show that a transient cold shock treatment of the cells post PE-pegRNA delivery further increases prime editing outcomes for pegRNAs with optimized PBS lengths. In the first study, we noticed that the prime editor protein had the tendency to aggregate during purification procedures and that the editing rates were still modest in primary cells. MMLV-reverse transcriptase - the prime editor polymerase subunit - requires high intracellular dNTPs levels for efficient polymerization. Prior optimization of the system has been performed in rapidly dividing cell lines like HEK293Ts where dNTP concentration is not a limiting factor. Primary cells that are quiescent or slowly proliferating have tightly regulated intracellular dNTP levels that could limit the reverse transcription process. Therefore, in the second half of this thesis, we address two more bottlenecks of prime editing - solubility of the prime editor protein and the intracellular dNTP concentration. To address that, in the reverse transcriptase domain, we introduced the L435K mutation that improves the solubility of the protein. Additionally, we introduced a V223M mutation that changes the active site of the reverse transcriptase to resemble a lentiviral enzyme that is more efficient in non-dividing cells. We show that this rationally engineered prime editor variant with increased solubility and lower Km to dNTPs, increases editing rates across diverse cell types and in vivo. Finally, we show that targeted SAMHD1 degradation by co-delivery of VPX to increase dNTP concentration in the cell further increases prime editing rates. We believe that addressing these bottlenecks, with the recommendations we describe in this thesis, will contribute to the advancement of prime editor ribonucleoproteins and mRNA for in vivo and ex vivo therapeutics.
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Charting the Course to Meaningful Community-Academic Research Partnerships: A roadmap and tools to advance heath equity through community partnership on Patient Centered Outcomes Research /Comparative Effectiveness Research (PCOR/CER) StudiesRecent calls to advance pathways towards health equity highlight the need for greater investment in multi-sectoral and community partnerships. Efforts to advance health equity research require meaningful participation of individuals and communities underrepresented in research partnerships. Meaningful participation provides a foundation critical for creating and sustaining the structural changes required to advance health equity. Accordingly, this Roadmap provides an overview of tools that aim to promote the meaningful engagement of individuals underrepresented in research partnerships.
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A Targeted Approach for Evaluating DUX4-Regulated Proteins as Potential Serum Biomarkers for Facioscapulohumeral Muscular Dystrophy Using Immunoassay ProteomicsBackground: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by misexpression of the double homeobox 4 (DUX4) embryonic transcription factor in skeletal muscle. Identifying quantitative and minimally invasive FSHD biomarkers to report on DUX4 activity will significantly accelerate therapeutic development. Objective: The goal of this study was to analyze secreted proteins known to be induced by DUX4 using the commercially available Olink Proteomics platform in order to identify potential blood-based molecular FSHD biomarkers. Methods: We used high-throughput, multiplex immunoassays from Olink Proteomics to measure the levels of several known DUX4-induced genes in a cellular myoblast model of FSHD, in FSHD patient-derived myotube cell cultures, and in serum from individuals with FSHD. Levels of other proteins on the Olink Proteomics panels containing these DUX4 targets were also examined in secondary exploratory analysis. Results: Placental alkaline phosphatase (ALPP) levels correlated with DUX4 expression in both cell-based FSHD systems but did not distinguish FSHD patient serum from unaffected controls. Conclusions: ALPP, as measured with the Olink Proteomics platform, is not a promising FSHD serum biomarker candidate but could be utilized to evaluate DUX4 activity in discovery research efforts.
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Distinct members of the C. elegans CeMbio reference microbiota exert cryptic virulence and infection protection [preprint]Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. A key aspect is the ability of each distinct community member to promote or impair host health, alone or in the context of the community, in hosts with varied levels of immune competence. Understanding such interactions is limited by the complexity and experimental accessibility of current systems and models. Recently, a reference twelve-member microbiota for the model organism C. elegans, known as CeMbio, was defined to aid the dissection of conserved host-microbiota interactions. Understanding the physiological impact of the CeMbio bacteria on C. elegans is in its infancy. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh/WNT, and HLH-30/TFEB pathways. Using immunodeficient animals, we uncovered several examples of bacterial 'cryptic' virulence, or virulence that was masked by the host defense response. The ability to activate the PMK-1/p38 pathway did not correlate with bacterial virulence in wild type or immunodeficient animals. In contrast, ten out of twelve species activated HLH-30/TFEB, and most showed virulence towards hlh-30-deficient animals. In addition, we identified Pseudomonas lurida as a pathogen in wild type animals, and Acinetobacter guillouiae as avirulent despite activating all three pathways. Moreover, short pre-exposure to A. guillouiae promoted host survival of infection with P. lurida, which was dependent on PMK-1/p38 MAPK and HLH-30/TFEB. These results suggest that the microbiota of C. elegans is rife with "opportunistic" pathogens, and that HLH-30/TFEB is a fundamental and key host protective factor. Furthermore, they support the idea that bacteria like A. guillouiae evolved the ability to induce host innate immunity to improve host fitness when confronted with pathogens, providing new insights into how colonization order impacts host health.
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Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfmentEngulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluorescence (AF) likely due to lipofuscin (lipo-AF) and typically associated with aging, can also be detected within microglial lysosomes in the young mouse brain by light microscopy. This lipo-AF signal accumulates first within microglia and it occurs earliest in white versus gray matter. Importantly, in gray matter, lipo-AF signal can confound the interpretation of antibody-labeled synaptic material within microglia in young adult mice. We further show that there is an age-dependent accumulation of lipo-AF inside and outside of microglia, which is not affected by amyloid plaques. We finally implement a robust and cost-effective strategy to quench AF in mouse, marmoset, and human brain tissue.
