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Träfflista för sökning "WFRF:(Axelsson Inge) srt2:(2020-2023)"

Sökning: WFRF:(Axelsson Inge) > (2020-2023)

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  • Bruschettini, Matteo, et al. (författare)
  • Många källor till problem i systematiska översikter
  • 2023
  • Ingår i: Lakartidningen. - 0023-7205. ; 120
  • Tidskriftsartikel (refereegranskat)abstract
    • A well-conducted systematic review requires a scrupulous assessment of the design of included studies. This may unveil major issues in how studies were planned, conducted and reported. This section presents a few examples. 1) A Cochrane review on pain and sedation management in the newborn identified a study described as a randomized trial, which later, following communication with authors and the editor-in-chief, turned out to be observational. 2) Poor evaluation of heterogeneity and active placebo when pooling studies on inhalation of saline solution for bronchiolitis led to clinical implementation of treatments later shown not to be effective. 3) A Cochrane review on methylphenidate for attention deficit hyperactivity disorder in adults did not identify problems with blinding and a »wash-out« period, resulting in erroneous conclusions. The review was therefore retracted. Although as important as benefits, harms of interventions are often given less attention in trials and systematic reviews.
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  • Rudd, Sean, et al. (författare)
  • Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy
  • 2020
  • Ingår i: EMBO Molecular Medicine. - : Blackwell Publishing Ltd. - 1757-4676 .- 1757-4684.
  • Tidskriftsartikel (refereegranskat)abstract
    • The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML. © 2020 The Authors. Published under the terms of the CC BY 4.0 license
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