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Library Opportunities for Increasing Engagement: Educating Users about Questionable and Predatory Publishing
Get PDFThe Technologist Will See You Now: How re-establishing a computer class curriculum through a library-led initiative known as Orlando Health UpSkill met the tech literacy needs of hospital team members
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Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia
Get PDFDespite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched evolution in response to selective pressure exerted by therapy; relapse founder clones emerge from pre-leukemic clones or minor subclones present at diagnosis. It is hence crucial to develop biomarkers capable of tracking subclones throughout therapy. Current practices for monitoring disease response in leukemia rely on the analysis of BM biopsy sample at specific time points throughout therapy. Not only the invasiveness of the BM biopsy hinders the sequential sampling, but also, the currently implied techniques are associated with a lack of sensitivity to detect subclones other than the major diagnostic clone. Somatic mutation detection in circulating-tumor DNA (Ct-DNA) offers a new venue for non-invasive studying of genetic heterogeneity and tracking clonal dynamics throughout therapy. Here, we employ targeted Next-Generation Sequencing (NGS) using a specifically designed ALL custom gene panel for Ct-DNA analysis of sequential plasma samples of 14 pediatric ALL during remission induction therapy. Utilizing 1 ml of plasma, Ct-DNA successfully captured all the clinically relevant somatic single nucleotide variants (SNVs) detected by whole exome sequencing (WES) in bone marrow (BM) biopsy samples at diagnosis. Moreover, we were able to show the ability of Ct-DNA analysis to track the change in the mutant allele fraction (MAF) across multiple time points as well as, to detect mutations in Flowcytometry (FC) MRD-negative patients. Taken together, sequential analysis of Ct-DNA in plasma demonstrates a role, as a non-invasive technique, for detecting the clonal composition as well as, tracking clonal dynamics in pediatric ALL
Targeting the Colchicine Binding Site on Tubulin to Overcome Multidrug Resistance and Anticancer Efficacy of Selective Survivin Inhibitors
Get PDFTubulin inhibitors are widely used as chemotherapeutic agents, and their successis attributed to their ability to target microtubule dynamics and disrupt critical cellular functions including cell signaling, motility, intracellular trafficking, and mitosis. Interference with microtubule dynamics consequently disrupts mitotic progression and ultimately leads to apoptosis, validating microtubule dynamics as an excellent target for anticancer agents. While this class of drug has proven to be effective against many cancer types, the clinical efficacy of current tubulin inhibitors is often limited by the development of multidrug resistance. The most common form of resistance to these agents arises from the overexpression of drug efflux transporters. Extensive research efforts have attempted to develop colchicine binding site inhibitors, which are reported to be significantly less susceptible to multidrug resistance and have therapeutic advantages over agents that target the taxane and vinca alkaloid site. Herein, we evaluated the anticancer activity of novel small-molecules that target the colchicine binding site, focusing on the most promising compounds from several structural scaffolds including indolyl-imidazopyridines (DJ95 and DJ101), VERU-111 analogs with a modified indole moiety (10ab and 10bb) or 3,4,5-trimethoxyphenyl moiety (13f), and heterocyclic pyrimidines (4a, 6a, 5a, and 5b). We demonstrated the cytotoxic potency of these compounds against a variety of cancer cell lines, including malignant melanomas, taxaneresistant prostate cancer cells, and drug efflux pump-overexpressing cell lines. Their mechanism of action was revealed through tubulin polymerization inhibition, disruption of microtubule networks and mitotic spindle formation, and confirmed through X-ray crystallography, which detailed their specific molecular interactions with tubulin in the colchicine binding pocket. Furthermore, these compounds exhibited hallmark characteristics of colchicine binding site agents, such as arresting cells in the G2/M phase of the cell cycle, inducing apoptosis in a concentration-dependent manner, and impeding cancer cell proliferation and migration. Finally, the compounds were efficacious in vivo against melanoma and taxane-resistant prostate cancer xenograft tumors. Several agents were evaluated for ability to prevent melanoma metastases to the lungs in experimental mouse models, and they potently inhibited the development metastatic foci. Safety assessment by pharmacological profiling demonstrated minimal interactions to physiologically important targets and pathophysiological analysis of major organs from the in vivo treatment groups did not expose apparent drug-related injury. Several of the investigated compounds also demonstrated vascular disrupting properties by targeting tumor vasculature and inhibiting capillary-like network formation of endothelial cells. Ultimately, these compounds exhibit strong anticancer efficacy, specifically target the colchicine binding site, and have great potential as cancer therapeutics, particularly for multidrug resistance phenotypes.
Another target we explored for anticancer intervention was survivin. Survivin is the smallest member the inhibitor of apoptosis protein family and its overexpression in tumor cells is been positively correlated with the development of multidrug resistance and radiation resistance. Because it is differentially expressed in healthy tissues and tumors, it is an attractive therapeutic target. Using the scaffold of UC-112, which was previously identified through virtual screening, we evaluated a series of analogs designed to optimize potency and improve selectivity to survivin over other inhibitor of apoptosis proteins. We identified compound 10f, which was highly cytotoxic to melanoma and Pglycoprotein overexpressing cell lines, induced apoptotic cascades in a concentrationdependent manner, specifically downregulated survivin protein levels, and significantly inhibited tumor growth in vivo. Ultimately, these results validated our in-depth biological investigation of novel scaffolds of survivin inhibitors and verified the anticancer efficacy of 10f
Speeding Ahead: Assessing Trends in Distance Librarian Services for Advanced Practice Nursing Programs
Get PDFWith the increasing popularity of distance education among universities and busy students, many Advanced Practice Nursing (APN) programs have shifted to become either online or hybrid programs. To meet the research and instruction needs of these students, some nursing librarians are using technology for virtual research and instruction. This study was designed to assess the extent to which nursing librarians in North America are providing virtual research and instruction services for APN students
Handwriting and Occupational Therapy in the Schools
Get PDFHandwriting is an important life skill, and handwriting tasks take up a significant amount of time during the school day. Research suggests that writing by hand influences reading skills, recall, academics, and motor and composition skills. Pediatric occupational therapists evaluate and treat children who are struggling with handwriting; therefore, it is important for practitioners to be aware of a variety of treatment strategies for addressing handwriting challenges. After participating in this session, the learner will be able to discuss the research on typical and atypical pencil grasps, identify and name 5 common handwriting errors, and explain 3 techniques for increasing handwriting legibility
Redesigning a Hospital’s Evidence-Based Practice Course
Get PDFThe Medical University of South Carolina (MUSC) Value Institute, which falls under the hospital’s Quality Department, has contributed to evidence-based practice (EBP) culture through education, evidence synthesis services, and the development of clinical decision support tools. Three members of the Value Institute -- a librarian, Clinical Evidence-Based Analyst, and Senior Value Specialist -- have taught a variety of EBP courses to clinicians over the years. However, because of increasing course dropout rates, the Value Institute conducted focus groups to identify ways to redesign the course. Two focus groups consisted of 6-8 previous course participants each. The focus groups started with an introduction, challenge statement, and problem statement. Participants silently brainstormed answers to four questions then posted answers to wall-mounted paper. A group discussion followed
