Kara Graves, Hannah Kiesling, Ellie Boyer, Brandon Alvarez-Serrano

Behind the Burqa” covers various topics about the current state of women’s rights in Afghanistan. These topics include women’s access to education, the drug trade, women being forced into marriages, and domestic violence. To achieve this, the main focus of the zine was to highlight the voices of women within Afghanistan and those that are fighting for their rights.https://digitalcommons.butler.edu/spring_2023/1009/thumbnail.jp

Fluorescence-Guided Stereotactic Biopsy: A Proof-of-Concept Study

Introduction: Histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in approximately 10% of cases. This can delay initiation of treatment and may result in further invasive procedures for patients. Here, we evaluate if coupling in vivo optical imaging with a STB system can identify diagnostic tissue at the time of biopsy. Methods: A minimally invasive fiber optic imaging system was developed by coupling a 0.65mm diameter fiber optic fluorescence microendoscope to a STB system. Human glioma cells were transduced for stable expression of blue fluorescent protein (U251-BFP) and utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by sodium fluorescein (FNa) was quantified with fluorescence microscopy. Rodent xenografts implanted with U251-BFP cells (n=4) were utilized for in vivo experiments. Five weeks post-implantation, xenografts received 5-10mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest (ROI) ipsilateral and contralateral to tumor implantation were analyzed. Results: Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2=0.91, p\u3c0.001). Normalized to background, in vivo FNa fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (60.65± 17.35 %, p\u3c0.001). Fluorescein fluorescence was not significantly greater from the tumor margin compared to normal brain (p =0.096). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor. Conclusion: We found in vivo fluorescence imaging with a STB needle containing a submillimeter diameter fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. This was confirmed in vivo and by post-hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies

ALTERNATIVE METHODS OF DESALINATION FOR SUB-SAHARAN AFRICA: A REVIEW OF PREFILTRATION AND MICROBIAL DESALINATION CELL TECHNOLOGY

Gemstone Team NOSALTOur research project has addressed the global need for greater accessibility to potable drinking water, specifically within the regions of sub-Saharan Africa. Initially, we planned to design a unique desalination system that was composed of a pre-filtration unit, a microbial desalination cell (MDC) and a post-desalination treatment unit. When in-person lab work was no longer feasible due to COVID-19 guidelines, we refocused our project to review the construction, efficiency, and cost effectiveness of the different designs of potential prefiltration units and MDC configurations. Our review of potential prefiltration systems included both chemical and physical separation methods, and the review of the MDC included the air cathode, biocathode and stacked configurations. While researching the technical details of the prefiltration and MDC systems, we also considered the cultural and societal impacts of introducing a technology such as the MDC into our project region. Our project started as an analysis of an emerging technology, but as the team has grown, the project has transformed into a comprehensive review of the emerging microbial desalination technology and the societal impacts of implementing it into some of the water scarce regions of coastal sub-Saharan Africa

Comparison of F(ab') versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. METHODS: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. RESULTS: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. CONCLUSIONS: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation

Safety and Efficacy of Ixoberogene Soroparvovec in Neovascular Age-Related Macular Degeneration in the United States (OPTIC): A Prospective, Two-Year, Multicentre Phase 1 Study

Background Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD. Methods In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to antiVEGF were assigned to four cohorts differing by ixo-vec dose (2 × 1011 vs 6 × 1011 vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784. Findings Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 1011 dose group and in 7 participants in the 2 × 1011 dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 1011 vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 1011 vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 1011 vg/eye cohorts. Interpretation Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions

Comparison of Four ChIP-Seq Analytical Algorithms Using Rice Endosperm H3K27 Trimethylation Profiling Data

Chromatin immunoprecipitation coupled with high throughput DNA Sequencing (ChIP-Seq) has emerged as a powerful tool for genome wide profiling of the binding sites of proteins associated with DNA such as histones and transcription factors. However, no peak calling program has gained consensus acceptance by the scientific community as the preferred tool for ChIP-Seq data analysis. Analyzing the large data sets generated by ChIP-Seq studies remains highly challenging for most molecular biology laboratories

Geometric, kinematic, and erosional history of the central Andean Plateau, Bolivia (15–17°S)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95425/1/tect1910.pd

Identifying generalised segmental acceleration patterns that contribute to ground reaction force features across different running tasks

Objective: To support future developments of field-based biomechanical load monitoring tools, this study aimed to identify generalised segmental acceleration patterns and their contribution to ground reaction forces (GRFs) across different running tasks. Design: Exploratory experimental design. Methods: A multivariate principal component analysis (PCA) was applied to a combination of segmental acceleration data from all body segments for fifteen team-sport athletes performing accelerated, decelerated and constant low-, moderate- and high-speed running, and 90° cutting trials. Segmental acceleration profiles were then reconstructed from each principal component (PC) and used to calculate their specific GRF contributions. Results: The first PC explained 48.57% of the acceleration variability for all body segments and was primarily related to the between-task differences in the overall magnitude of the GRF impulse. Magnitude and timing of high-frequency acceleration and GRF features (i.e. impact related characteristics) were primarily explained by the second PC (12.43%) and also revealed important between-task differences. The most important GRF characteristics were explained by the first five PCs, while PCs beyond that primarily contained small contributions to the overall GRF impulse. Conclusions: These findings show that a multivariate PCA approach can reveal generalised acceleration patterns and specific segmental contributions to GRF features, but their relative importance for different running activities are task dependent. Using segmental acceleration to assess whole-body biomechanical loading generically across various movements may thus require task identification algorithms and/or advanced sensor or data fusion approaches

Alternative Splicing in the Differentiation of Human Embryonic Stem Cells into Cardiac Precursors

The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation