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  1. Article ; Online: Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

    Mitchell, Aaron P / Kinlaw, Alan C / Peacock-Hinton, Sharon / Dusetzina, Stacie B / Winn, Aaron N / Sanoff, Hanna K / Lund, Jennifer L

    The oncologist

    2024  

    Abstract: Background: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs ... ...

    Abstract Background: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments.
    Materials and methods: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights.
    Results: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04).
    Conclusions: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.
    Language English
    Publishing date 2024-03-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1093/oncolo/oyae035
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  2. Article ; Online: Development of a Tool to Assess Surgical Resident Competence On-Call: The Western University Call Assessment Tool (WUCAT).

    Mitchell, Eric C / Ott, Michael / Ross, Douglas / Grant, Aaron

    Journal of surgical education

    2023  Volume 81, Issue 1, Page(s) 106–114

    Abstract: Background: A central tenet of competency-based medical education is the formative assessment of trainees. There are currently no assessments designed to examine resident competence on-call, despite the on-call period being a significant component of ... ...

    Abstract Background: A central tenet of competency-based medical education is the formative assessment of trainees. There are currently no assessments designed to examine resident competence on-call, despite the on-call period being a significant component of residency, characterized by less direct supervision compared to daytime. The purpose of this study was to design a formative on-call assessment tool and collect valid evidence on its application.
    Methods: Nominal group technique was used to identify critical elements of surgical resident competence on-call to inform tool development. The tool was piloted over six months in the Division of Plastic & Reconstructive Surgery at our institution. Quantitative and qualitative evidence was collected to examine tool validity.
    Results: A ten-item tool was developed based on the consensus group results. Sixty-three assessments were completed by seven staff members on ten residents during the pilot. The tool had a reliability coefficient of 0.67 based on a generalizability study and internal item consistency was 0.92. Scores were significantly associated with years of training. We found the tool improved the quantity and structure of feedback given and that the tool was considered feasible and acceptable by both residents and staff members.
    Conclusions: The Western University Call Assessment Tool (WUCAT) has multiple sources of evidence supporting its use in assessing resident competence on-call.
    MeSH term(s) Humans ; Internship and Residency ; Education, Medical, Graduate/methods ; Reproducibility of Results ; Universities ; Clinical Competence ; Educational Measurement/methods
    Language English
    Publishing date 2023-11-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2277538-9
    ISSN 1878-7452 ; 1931-7204
    ISSN (online) 1878-7452
    ISSN 1931-7204
    DOI 10.1016/j.jsurg.2023.10.001
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  3. Article: The Top 100 Most Cited Journal Articles on Hydrocephalus.

    Seltzer, Laurel A / Couldwell, Mitchell W / Tubbs, R Shane / Bui, C J / Dumont, Aaron S

    Cureus

    2024  Volume 16, Issue 2, Page(s) e54481

    Abstract: Hydrocephalus represents a significant burden of disease, with more than 383,000 new cases annually worldwide. When the magnitude of this condition is considered, a centralized archive of pertinent literature is of great clinical value. From a ... ...

    Abstract Hydrocephalus represents a significant burden of disease, with more than 383,000 new cases annually worldwide. When the magnitude of this condition is considered, a centralized archive of pertinent literature is of great clinical value. From a neurosurgical standpoint, hydrocephalus is one of the most frequently treated conditions in the field. The focus of this study was to identify the top 100 journal articles specific to hydrocephalus using bibliometric analysis. Using the Journal of Citation Report database, 10 journals were identified. The Web of Science Core Collection was then searched using each journal name and the search term "hydrocephalus." The results were ordered by "Times Cited" and searched by the number of citations. The database contained journal articles from 1976 to 2021, and the following variables were collected for analysis: journal, article type, year of publication, and the number of citations. Journal articles were excluded if they had no relation to hydrocephalus, mostly involved basic science research, or included animal studies. Ten journals were identified using the above criteria, and a catalog of the 100 most cited publications in the hydrocephalus literature was created. Articles were arranged from highest to lowest citation number, with further classification by journal, article type, and publication year. Of the 100 articles referenced, 38 were review articles, 24 were original articles, 15 were comparative studies, 11 were clinical trials, six were multi-center studies, three were cross-sectional, and three were case reports with reviews. Articles were also sorted by study type and further stratified by etiology. If the etiology was not specified, studies were instead subcategorized by treatment type. Etiologies such as aqueductal stenosis, tumors, and other obstructive causes of hydrocephalus were classified as obstructive (n=6). Communicating (n=15) included idiopathic, normal pressure hydrocephalus, and other non-obstructive etiologies. The category "other" (n=3) was assigned to studies that included etiologies, populations, and/or treatments that did not fit into the classifications previously outlined. Through our analysis of highly cited journal articles focusing on different etiologies and the surgical or medical management of hydrocephalus, we hope to elucidate important trends. By establishing the 100 most cited hydrocephalus articles, we contribute one source, stratified for efficient referencing, to facilitate clinical care and future research on hydrocephalus.
    Language English
    Publishing date 2024-02-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2747273-5
    ISSN 2168-8184
    ISSN 2168-8184
    DOI 10.7759/cureus.54481
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  4. Article ; Online: An extraordinary fossil captures the struggle for existence during the Mesozoic.

    Han, Gang / Mallon, Jordan C / Lussier, Aaron J / Wu, Xiao-Chun / Mitchell, Robert / Li, Ling-Ji

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 11221

    Abstract: Dinosaurs and mammals have coexisted for the last ~ 230 million years. Both groups arose during the Late Triassic and diversified throughout the Mesozoic and into the Cenozoic (the latter in the form of birds). Although they undoubtedly interacted in ... ...

    Abstract Dinosaurs and mammals have coexisted for the last ~ 230 million years. Both groups arose during the Late Triassic and diversified throughout the Mesozoic and into the Cenozoic (the latter in the form of birds). Although they undoubtedly interacted in many ways, direct fossil evidence for their interaction is rare. Here we report a new fossil find from the Lujiatun Member of the Lower Cretaceous Yixian Formation of China, showing a gobiconodontid mammal and psittacosaurid dinosaur locked in mortal combat. We entertain various hypothesized explanations for this association, but the balance of the evidence suggests that it represents a predation attempt on the part of the smaller mammal, suddenly interrupted by, and preserved within, a lahar-type volcanic debris flow. Mesozoic mammals are usually depicted as having lived in the shadows of their larger dinosaurian contemporaries, but this new fossil convincingly demonstrates that mammals could pose a threat even to near fully-grown dinosaurs. The Yixian Formation-and the Chinese fossil Jehol Biota more broadly-have played a particularly important role in revealing the diversity of small-bodied dinosaurs and other fauna. We anticipate that the volcanically derived obrution deposits specific to the Lujiatun Member will likewise continue to yield evidence for biotic interactions otherwise unknown from the rest of the fossil record.
    MeSH term(s) Animals ; Fossils ; Dinosaurs/anatomy & histology ; Birds ; Mammals ; Predatory Behavior ; Biological Evolution ; Phylogeny
    Language English
    Publishing date 2023-07-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-37545-8
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  5. Article ; Online: Targeted Genetic Changes in Candida albicans Using Transient CRISPR-Cas9 Expression.

    Huang, Manning Y / Cravener, Max C / Mitchell, Aaron P

    Current protocols

    2021  Volume 1, Issue 1, Page(s) e19

    Abstract: Candida albicans is an opportunistic fungal pathogen responsible for significant disease and mortality. Absent complete mating and other convenient methods, dissection of its virulence factors relies on robust tools to delete, complement, and otherwise ... ...

    Abstract Candida albicans is an opportunistic fungal pathogen responsible for significant disease and mortality. Absent complete mating and other convenient methods, dissection of its virulence factors relies on robust tools to delete, complement, and otherwise modify genes of interest in this diploid organism. Here we describe the design principles and use of CRISPR associated nuclease 9 (Cas9) and single-guide RNAs transiently expressed from PCR cassettes to modify genes of interest, generating homozygous mutants in a single transformation step. © 2021 Wiley Periodicals LLC. Basic Protocol 1: PCR amplification of CRISPR components Basic Protocol 2: Transformation of Candida albicans Basic Protocol 3: Selecting and genotyping transformants Alternate Protocol 1: Deletion with recyclable markers by CRISPR induced marker excision (CRIME) Alternate Protocol 2: Knock-in and combining multiple cassettes with overlapping homology.
    MeSH term(s) CRISPR-Cas Systems/genetics ; Candida albicans/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Homozygote ; RNA, Guide, CRISPR-Cas Systems/genetics
    Chemical Substances RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2021-01-21
    Publishing country United States
    Document type Journal Article
    ISSN 2691-1299
    ISSN (online) 2691-1299
    DOI 10.1002/cpz1.19
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  6. Article ; Online: Hyperpolarized Xenon-129 Chemical Exchange Saturation Transfer (HyperCEST) Molecular Imaging: Achievements and Future Challenges.

    Batarchuk, Viktoriia / Shepelytskyi, Yurii / Grynko, Vira / Kovacs, Antal Halen / Hodgson, Aaron / Rodriguez, Karla / Aldossary, Ruba / Talwar, Tanu / Hasselbrink, Carson / Ruset, Iulian C / DeBoef, Brenton / Albert, Mitchell S

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of ... ...

    Abstract Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP)
    MeSH term(s) Xenon Isotopes/chemistry ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Spectroscopy/methods ; Solubility ; Xenon/chemistry
    Chemical Substances Xenon-129 ; Xenon Isotopes ; Xenon (3H3U766W84)
    Language English
    Publishing date 2024-02-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031939
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  7. Article ; Online: Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network.

    Cravener, Max V / Do, Eunsoo / May, Gemma / Zarnowski, Robert / Andes, David R / McManus, C Joel / Mitchell, Aaron P

    PLoS pathogens

    2023  Volume 19, Issue 1, Page(s) e1011109

    Abstract: ... in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored ... of genetic variation in the C. albicans species. ...

    Abstract Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expression all depend upon the transcription factor Efg1. This transcription factor has been characterized extensively in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored in other clinical isolates. Here we define a principal set of Efg1-responsive genes whose expression is significantly altered by an efg1Δ/Δ mutation across 17 clinical isolates. This principal gene set includes 68 direct Efg1 targets, whose 5' regions are bound by Efg1 in five clinical isolates, and 42 indirect Efg1 targets, whose 5' regions are not detectably bound by Efg1. Three direct Efg1 target genes encode transcription factors-BRG1, UME6, and WOR3 -whose increased expression in an efg1Δ/Δ mutant restores expression of multiple indirect and direct principal targets, as well as biofilm formation ability. Although BRG1 and UME6 are well known positive regulators of hypha-associated genes and biofilm formation, WOR3 is best known as an antagonist of Efg1 in the sexual mating pathway. We confirm the positive role of WOR3 in biofilm formation with the finding that a wor3Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo biofilm model. Positive control of Efg1 direct target genes by other Efg1 direct target genes-BRG1, UME6, and WOR3 -may buffer principal Efg1-responsive gene expression against the impact of genetic variation in the C. albicans species.
    MeSH term(s) Candida albicans/genetics ; Candida albicans/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Biofilms ; Mutation ; Hyphae/genetics
    Chemical Substances Fungal Proteins ; Transcription Factors
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011109
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  8. Article ; Online: Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network.

    Max V Cravener / Eunsoo Do / Gemma May / Robert Zarnowski / David R Andes / C Joel McManus / Aaron P Mitchell

    PLoS Pathogens, Vol 19, Iss 1, p e

    2023  Volume 1011109

    Abstract: ... in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored ... of genetic variation in the C. albicans species. ...

    Abstract Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expression all depend upon the transcription factor Efg1. This transcription factor has been characterized extensively in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored in other clinical isolates. Here we define a principal set of Efg1-responsive genes whose expression is significantly altered by an efg1Δ/Δ mutation across 17 clinical isolates. This principal gene set includes 68 direct Efg1 targets, whose 5' regions are bound by Efg1 in five clinical isolates, and 42 indirect Efg1 targets, whose 5' regions are not detectably bound by Efg1. Three direct Efg1 target genes encode transcription factors-BRG1, UME6, and WOR3 -whose increased expression in an efg1Δ/Δ mutant restores expression of multiple indirect and direct principal targets, as well as biofilm formation ability. Although BRG1 and UME6 are well known positive regulators of hypha-associated genes and biofilm formation, WOR3 is best known as an antagonist of Efg1 in the sexual mating pathway. We confirm the positive role of WOR3 in biofilm formation with the finding that a wor3Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo biofilm model. Positive control of Efg1 direct target genes by other Efg1 direct target genes-BRG1, UME6, and WOR3 -may buffer principal Efg1-responsive gene expression against the impact of genetic variation in the C. albicans species.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Core Body Temperatures in Intermittent Sports: A Systematic Review.

    Henderson, Mitchell J / Grandou, Clementine / Chrismas, Bryna C R / Coutts, Aaron J / Impellizzeri, Franco M / Taylor, Lee

    Sports medicine (Auckland, N.Z.)

    2023  Volume 53, Issue 11, Page(s) 2147–2170

    Abstract: Background: Hyperthermia (and associated health and performance implications) can be a significant problem for athletes and teams involved in intermittent sports. Quantifying the highest thermal strain (i.e. peak core body temperature [peak T: ... ...

    Abstract Background: Hyperthermia (and associated health and performance implications) can be a significant problem for athletes and teams involved in intermittent sports. Quantifying the highest thermal strain (i.e. peak core body temperature [peak T
    Objective: The objective of this systematic review was to synthesise and characterise the available thermal strain data collected in competition from intermittent sport athletes.
    Methods: A systematic literature search was performed on Web of Science, MEDLINE, and SPORTDiscus to identify studies up to 17 April 2023. Electronic databases were searched using a text mining method to provide a partially automated and systematic search strategy retrieving terms related to core body temperature measurement and intermittent sport. Records were eligible if they included core body temperature measurement during competition, without experimental intervention that may influence thermal strain (e.g. cooling), in healthy, adult, intermittent sport athletes at any level. Due to the lack of an available tool that specifically includes potential sources of bias for physiological responses in descriptive studies, a methodological evaluation checklist was developed and used to document important methodological considerations. Data were not meta-analysed given the methodological heterogeneity between studies and therefore were presented descriptively in tabular and graphical format.
    Results: A total of 34 studies were selected for review; 27 were observational, 5 were experimental (2 parallel group and 3 repeated measures randomised controlled trials), and 2 were quasi-experimental (1 parallel group and 1 repeated measures non-randomised controlled trial). Across all included studies, 386 participants (plus participant numbers not reported in two studies) were recruited after accounting for shared data between studies. A total of 4 studies (~ 12%) found no evidence of hyperthermia, 24 (~ 71%) found evidence of 'modest' hyperthermia (peak T
    Conclusions: Practitioners and coaches supporting intermittent sport athletes are justified to seek interventions aimed at mitigating the high heat strain observed in competition. More research is required to determine the most effective interventions for this population that are practically viable in intermittent sports settings (often constrained by many competing demands). Greater statistical power and homogeneity among studies are required to quantify the independent effects of wet bulb globe temperature, competition duration, sport and level of competition on peak T
    Registration: This systematic review was registered on the Open Science Framework ( https://osf.io/vfb4s

    https://doi.org/10.17605/OSF.IO/EZYFA , 4 January 2021).
    Language English
    Publishing date 2023-08-01
    Publishing country New Zealand
    Document type Systematic Review
    ZDB-ID 605911-9
    ISSN 1179-2035 ; 0112-1642
    ISSN (online) 1179-2035
    ISSN 0112-1642
    DOI 10.1007/s40279-023-01892-3
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  10. Article ; Online: Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy.

    Sarkar, Omar S / Donninger, Howard / Al Rayyan, Numan / Chew, Lewis C / Stamp, Bryce / Zhang, Xiang / Whitt, Aaron / Li, Chi / Hall, Melissa / Mitchell, Robert A / Zippelius, Alfred / Eaton, John / Chesney, Jason A / Yaddanapudi, Kavitha

    Science advances

    2023  Volume 9, Issue 26, Page(s) eadg3736

    Abstract: Immune checkpoint inhibitor (ICI) therapy is effective against many cancers for a subset of patients; a large percentage of patients remain unresponsive to this therapy. One contributing factor to ICI resistance is accumulation of monocytic myeloid- ... ...

    Abstract Immune checkpoint inhibitor (ICI) therapy is effective against many cancers for a subset of patients; a large percentage of patients remain unresponsive to this therapy. One contributing factor to ICI resistance is accumulation of monocytic myeloid-derived suppressor cells (M-MDSCs), a subset of innate immune cells with potent immunosuppressive activity against T lymphocytes. Here, using lung, melanoma, and breast cancer mouse models, we show that CD73-expressing M-MDSCs in the tumor microenvironment (TME) exhibit superior T cell suppressor function. Tumor-derived PGE
    MeSH term(s) Animals ; Mice ; Myeloid-Derived Suppressor Cells ; Adenosine ; Immunotherapy ; Immunosuppression Therapy ; Immunosuppressive Agents
    Chemical Substances Adenosine (K72T3FS567) ; Immunosuppressive Agents
    Language English
    Publishing date 2023-06-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adg3736
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