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  1. Article ; Online: XPF-ERCC1: Linchpin of DNA crosslink repair.

    McHugh, Peter J

    PLoS genetics

    2020  Volume 16, Issue 4, Page(s) e1008616

    MeSH term(s) DNA ; DNA Damage ; DNA Repair ; Homeostasis ; Liver
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2020-04-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1008616
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  2. Article: Editorial: Targeting DNA repair and the DNA damage response: Beyond the standard PI3 kinase-like kinases.

    Turchi, John J / Pawelczak, Katherine S / Weinfeld, Michael / McHugh, Peter J

    Frontiers in oncology

    2022  Volume 12, Page(s) 1023500

    Language English
    Publishing date 2022-09-27
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1023500
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Analysis of DNA Interstrand Cross-Links and their Repair by Modified Comet Assay.

    Swift, Lonnie P / Castle, Lianne / McHugh, Peter J

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2119, Page(s) 79–88

    Abstract: DNA interstrand cross-links (ICLs) are an extremely toxic form of DNA damage that cells experience upon exposure to natural metabolites. Moreover, ICLs are cytotoxic lesions produced by a range of clinically important anticancer agents. Therefore, ... ...

    Abstract DNA interstrand cross-links (ICLs) are an extremely toxic form of DNA damage that cells experience upon exposure to natural metabolites. Moreover, ICLs are cytotoxic lesions produced by a range of clinically important anticancer agents. Therefore, improving our understanding of ICL induction and processing has important implications in biology and medicine. The sensitive detection of ICLs in mammalian cells is challenging but has been aided by the development of a modified form of the single-cell gel electrophoresis (SCGE) assay, also known as the "comet assay." Here we describe this method and how it can be used to sensitively monitor the induction and removal of ICLs in single mammalian cells.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Cell Line ; Comet Assay ; DNA/analysis ; DNA/metabolism ; DNA Damage ; DNA Repair/drug effects ; Humans
    Chemical Substances Antineoplastic Agents ; DNA (9007-49-2)
    Language English
    Publishing date 2020-01-27
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0323-9_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: An enhanced phenomenological model to predict surface-based localised corrosion of magnesium alloys for medical use.

    Quinn, Conall / Van Gaalen, Kerstin / McHugh, Peter E / Kopp, Alexander / Vaughan, Ted J

    Journal of the mechanical behavior of biomedical materials

    2022  Volume 138, Page(s) 105637

    Abstract: This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the ... ...

    Abstract This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the role of β-phase components throughout the material volume to better predict spatial and temporal aspects of surface-based corrosion in magnesium alloys. This enhanced surface-based corrosion model offers many advantages as it (i) captures multi-directional pitting, (ii) captures various pit morphologies, (iii) eliminates mesh sizing effects, (iv) reduces computational cost through custom time controls (v) offers control of pit sizing and (vi) produces corrosion rates that are independent of pitting parameter values. The model was fully implemented in three dimensions within the finite element framework and shows excellent potential to enable robust predictions of the long-term performance of magnesium-based implants undergoing corrosion.
    MeSH term(s) Alloys ; Magnesium ; Corrosion ; Absorbable Implants ; Materials Testing
    Chemical Substances Alloys ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2022-12-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2378381-3
    ISSN 1878-0180 ; 1751-6161
    ISSN (online) 1878-0180
    ISSN 1751-6161
    DOI 10.1016/j.jmbbm.2022.105637
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  5. Article ; Online: Predicting localised corrosion and mechanical performance of a PEO surface modified rare earth magnesium alloy for implant use through in-silico modelling.

    van Gaalen, Kerstin / Quinn, Conall / Weiler, Marek / Gremse, Felix / Benn, Felix / McHugh, Peter E / Vaughan, Ted J / Kopp, Alexander

    Bioactive materials

    2023  Volume 26, Page(s) 437–451

    Abstract: In this study, the influence of a plasma electrolytic oxidation (PEO) surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion ... ...

    Abstract In this study, the influence of a plasma electrolytic oxidation (PEO) surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process. First, a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification, which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning, followed by uniaxial tensile testing. Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model. In-vitro, it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified. While corrosion rates were ∼50% lower in the WE43-PEO modified specimens, the local geometric features of corroding surfaces remained similar to the unmodified WE43 group, however evolving after almost the double amount of time. We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested, and not just in the early stages of corrosion. Using the results from the testing framework, the model parameters of the surface-based corrosion model were identified for both groups. This enabled, for the first time, in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens. This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.
    Language English
    Publishing date 2023-03-21
    Publishing country China
    Document type Journal Article
    ISSN 2452-199X
    ISSN (online) 2452-199X
    DOI 10.1016/j.bioactmat.2023.03.009
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  6. Article ; Online: An Effective Program to Reduce Malpractice Claims and Payments in a Large Orthopaedic Practice.

    Cooper, William O / Doub, Thomas W / Hickson, Gerald B / Casey, Virginia F / McHugh, Damian F / Nonken, Peter / Catron, Thomas F / Domenico, Henry J / Pichert, James W

    The Journal of bone and joint surgery. American volume

    2024  

    Abstract: Background: High reliability in health care requires a balance between intentionally designed systems and individual professional accountability. One element of accountability includes a process for addressing clinicians whose practices are associated ... ...

    Abstract Background: High reliability in health care requires a balance between intentionally designed systems and individual professional accountability. One element of accountability includes a process for addressing clinicians whose practices are associated with a disproportionate share of patient complaints. This study aimed to evaluate the impact of the Patient Advocacy Reporting System (PARS), a tiered intervention model to reduce patient complaints about clinicians.
    Methods: A retrospective cohort study was conducted involving a southeastern U.S. orthopaedic group practice. The study assessed the implementation of the PARS program and subsequent malpractice claims from 2004 to 2020.
    Results: The implementation of PARS was associated with an 83% reduction in malpractice claims cost per high-risk clinician after intervention (p = 0.05; Wilcoxon rank sum test). The overall practice group experienced an 87% reduction in mean annual claims cost per clinician (p = 0.007; segmented regression). The successful adoption required essential elements such as PARS champions, peer messengers, an Office of Patient Affairs, and a clear statement of practice values and professionalism expectations at the time of onboarding.
    Conclusions: The PARS program was successfully adopted within a surgical specialty group as a part of ongoing risk prevention and management efforts. The period following PARS was associated with a retrospectively measured reduction in malpractice claim costs. The PARS program can be effectively implemented in a large, single-specialty orthopaedic practice setting and, although not necessarily causal, was, in our case, associated with a period of reduced malpractice claim costs.
    Clinical relevance: We have learned in previous research that there are clear links between professionalism and patient outcomes (e.g., surgical complications), but agree that the focus here on medical malpractice is not directly clinical.
    Language English
    Publishing date 2024-04-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 220625-0
    ISSN 1535-1386 ; 0021-9355
    ISSN (online) 1535-1386
    ISSN 0021-9355
    DOI 10.2106/JBJS.23.00973
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  7. Article: N

    Emms, Vicki L / Lewis, Liam A / Beja, Lilla / Bulman, Natasha F A / Pires, Elisabete / Muskett, Frederick W / McCullagh, James S O / Swift, Lonnie P / McHugh, Peter J / Hopkinson, Richard J

    Chemical science

    2023  Volume 14, Issue 44, Page(s) 12498–12505

    Abstract: Formaldehyde is a pollutant and human metabolite that is toxic at high concentrations. Biological studies on formaldehyde are hindered by its high reactivity and volatility, which make it challenging to deliver quantitatively to cells. Here, we describe ... ...

    Abstract Formaldehyde is a pollutant and human metabolite that is toxic at high concentrations. Biological studies on formaldehyde are hindered by its high reactivity and volatility, which make it challenging to deliver quantitatively to cells. Here, we describe the development and validation of a set of
    Language English
    Publishing date 2023-09-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2559110-1
    ISSN 2041-6539 ; 2041-6520
    ISSN (online) 2041-6539
    ISSN 2041-6520
    DOI 10.1039/d3sc02867d
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  8. Article ; Online: Linking the effect of localised pitting corrosion with mechanical integrity of a rare earth magnesium alloy for implant use.

    van Gaalen, Kerstin / Quinn, Conall / Benn, Felix / McHugh, Peter E / Kopp, Alexander / Vaughan, Ted J

    Bioactive materials

    2022  Volume 21, Page(s) 32–43

    Abstract: This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide ... ...

    Abstract This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework
    Language English
    Publishing date 2022-08-12
    Publishing country China
    Document type Journal Article
    ISSN 2452-199X
    ISSN (online) 2452-199X
    DOI 10.1016/j.bioactmat.2022.08.004
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  9. Article ; Online: Linking the effect of localised pitting corrosion with mechanical integrity of a rare earth magnesium alloy for implant use

    Kerstin van Gaalen / Conall Quinn / Felix Benn / Peter E. McHugh / Alexander Kopp / Ted J. Vaughan

    Bioactive Materials, Vol 21, Iss , Pp 32-

    2023  Volume 43

    Abstract: This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide ... ...

    Abstract This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface-based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.
    Keywords Magnesium ; Localised corrosion ; Corrosion modelling ; Phenomenology ; FEM ; Materials of engineering and construction. Mechanics of materials ; TA401-492 ; Biology (General) ; QH301-705.5
    Subject code 669
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation.

    Dorel, Ruth / Sun, Dawei / Carruthers, Nicholas / Castanedo, Georgette M / Ung, Peter M-U / Factor, Daniel C / Li, Tianbo / Baumann, Hannah / Janota, Danielle / Pang, Jodie / Salphati, Laurent / Meklemburg, Robert / Korman, Allison J / Harper, Halie E / Stubblefield, Samantha / Payandeh, Jian / McHugh, Daniel / Lang, Bradley T / Tesar, Paul J /
    Dere, Edward / Masureel, Matthieu / Adams, Drew J / Volgraf, Matthew / Braun, Marie-Gabrielle

    Journal of medicinal chemistry

    2024  Volume 67, Issue 6, Page(s) 4819–4832

    Abstract: The inhibition of emopamil binding protein (EBP), a sterol isomerase within the cholesterol biosynthesis pathway, promotes oligodendrocyte formation, which has been proposed as a potential therapeutic approach for treating multiple sclerosis. Herein, we ... ...

    Abstract The inhibition of emopamil binding protein (EBP), a sterol isomerase within the cholesterol biosynthesis pathway, promotes oligodendrocyte formation, which has been proposed as a potential therapeutic approach for treating multiple sclerosis. Herein, we describe the discovery and optimization of brain-penetrant, orally bioavailable inhibitors of EBP. A structure-based drug design approach from literature compound
    MeSH term(s) Humans ; Brain ; Oligodendroglia/metabolism ; Drug Design ; Hydantoins/metabolism
    Chemical Substances Hydantoins
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c02396
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