Publications by authors named "Tina Wagner"

5 Publications

  • Page 1 of 1

An Analysis of the Safety of Medication Ordering Using Typo Correction within an Academic Medical System.

Appl Clin Inform 2021 May 2;12(3):655-663. Epub 2021 Aug 2.

Department of Information Technology, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin, United States.

Objectives:  Spelling during medication ordering is prone to error, which can contribute to frustration, confusion, and, ultimately, errors. Typo correction can be utilized in an effort to mitigate the effects of misspellings by providing results even when no exact matches can be found. Although, typo correction can be beneficial in some scenarios, safety concerns have been raised when utilizing the functionality for medication ordering. Our primary objective was to analyze the effects of typo correction technology on medication errors within an academic medical system after implementation of the technology. Our secondary objective was to identify and provide additional recommendations to further improve the safety of the functionality.

Methods:  We analyzed 8 months of post-implementation data obtained from staff-reported medication errors and search query information obtained from the electronic health record. The reports were analyzed by two pharmacists in two phases: retrospective identification of errors occurring as a result of typo correction and prospective identification of potential errors with continued use of the functionality.

Results:  In retrospective review of 2,603 reported medication-related errors, 26 were identified as potentially involving typo correction as a contributing factor. Six of these orders invoked typo correction, but none of the errors could be attributed to typo correction. In prospective review, a list of 40 error-prone words and terms were identified to be added as stop words and 407 medication synonyms were identified for removal from their associated medication records.

Conclusion:  Our results indicate, when properly implemented, typo correction does not cause additional medication errors. However, there may be benefit in implementing further precautions for preventing future errors.
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http://dx.doi.org/10.1055/s-0041-1731745DOI Listing
May 2021

Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.

PLoS Genet 2020 12 28;16(12):e1008603. Epub 2020 Dec 28.

Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, Mainz, Germany.

Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence.
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http://dx.doi.org/10.1371/journal.pgen.1008603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793543PMC
December 2020

Inactivation of folylpolyglutamate synthetase Met7 results in genome instability driven by an increased dUTP/dTTP ratio.

Nucleic Acids Res 2020 01;48(1):264-277

DNA Repair Mechanisms and Cancer, German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.

The accumulation of mutations is frequently associated with alterations in gene function leading to the onset of diseases, including cancer. Aiming to find novel genes that contribute to the stability of the genome, we screened the Saccharomyces cerevisiae deletion collection for increased mutator phenotypes. Among the identified genes, we discovered MET7, which encodes folylpolyglutamate synthetase (FPGS), an enzyme that facilitates several folate-dependent reactions including the synthesis of purines, thymidylate (dTMP) and DNA methylation. Here, we found that Met7-deficient strains show elevated mutation rates, but also increased levels of endogenous DNA damage resulting in gross chromosomal rearrangements (GCRs). Quantification of deoxyribonucleotide (dNTP) pools in cell extracts from met7Δ mutant revealed reductions in dTTP and dGTP that cause a constitutively active DNA damage checkpoint. In addition, we found that the absence of Met7 leads to dUTP accumulation, at levels that allowed its detection in yeast extracts for the first time. Consequently, a high dUTP/dTTP ratio promotes uracil incorporation into DNA, followed by futile repair cycles that compromise both mitochondrial and nuclear DNA integrity. In summary, this work highlights the importance of folate polyglutamylation in the maintenance of nucleotide homeostasis and genome stability.
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http://dx.doi.org/10.1093/nar/gkz1006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145683PMC
January 2020

SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition.

Cell Death Differ 2018 06 11;25(6):1131-1145. Epub 2017 Dec 11.

Department of Biomedical Sciences, University of Padova, Padova, Italy.

Contact sites are discrete areas of organelle proximity that coordinate essential physiological processes across membranes, including Ca signaling, lipid biosynthesis, apoptosis, and autophagy. However, tools to easily image inter-organelle proximity over a range of distances in living cells and in vivo are lacking. Here we report a split-GFP-based contact site sensor (SPLICS) engineered to fluoresce when organelles are in proximity. Two SPLICS versions efficiently measured narrow (8-10 nm) and wide (40-50 nm) juxtapositions between endoplasmic reticulum and mitochondria, documenting the existence of at least two types of contact sites in human cells. Narrow and wide ER-mitochondria contact sites responded differently to starvation, ER stress, mitochondrial shape modifications, and changes in the levels of modulators of ER-mitochondria juxtaposition. SPLICS detected contact sites in soma and axons of D. rerio Rohon Beard (RB) sensory neurons in vivo, extending its use to analyses of organelle juxtaposition in the whole animal.
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http://dx.doi.org/10.1038/s41418-017-0033-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988678PMC
June 2018

Cancer-associated TERT promoter mutations abrogate telomerase silencing.

Elife 2015 Jul 21;4. Epub 2015 Jul 21.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

Mutations in the human telomerase reverse transcriptase (TERT) promoter are the most frequent non-coding mutations in cancer, but their molecular mechanism in tumorigenesis has not been established. We used genome editing of human pluripotent stem cells with physiological telomerase expression to elucidate the mechanism by which these mutations contribute to human disease. Surprisingly, telomerase-expressing embryonic stem cells engineered to carry any of the three most frequent TERT promoter mutations showed only a modest increase in TERT transcription with no impact on telomerase activity. However, upon differentiation into somatic cells, which normally silence telomerase, cells with TERT promoter mutations failed to silence TERT expression, resulting in increased telomerase activity and aberrantly long telomeres. Thus, TERT promoter mutations are sufficient to overcome the proliferative barrier imposed by telomere shortening without additional tumor-selected mutations. These data establish that TERT promoter mutations can promote immortalization and tumorigenesis of incipient cancer cells.
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http://dx.doi.org/10.7554/eLife.07918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507476PMC
July 2015
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