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Sökning: WFRF:(Reda Francesco)

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1.
  • Hedman, Åsa, et al. (författare)
  • IEA EBC Annex83 Positive Energy Districts
  • 2021
  • Ingår i: Buildings. - : MDPI AG. - 2075-5309. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • At a global level, the need for energy efficiency and an increased share of renewable energy sources is evident, as is the crucial role of cities due to the rapid urbanization rate. As a consequence of this, the research work related to Positive Energy Districts (PED) has accelerated in recent years. A common shared definition, as well as technological approaches or methodological issues related to PEDs are still unclear in this development and a global scientific discussion is needed. The International Energy Agency’s Energy in Buildings and Communities Programme (IEA EBC) Annex 83 is the main platform for this international scientific debate and research. This paper describes the challenges of PEDs and the issues that are open for discussions and how the Annex 83 is planned and organized to facilitate this and to actively steer the development of PEDs major leaps forward. The main topics of discussion in the PED context are the role and importance of definitions of PEDs, virtual and geographical boundaries in PEDs, the role of different stakeholders, evaluation approaches, and the learnings of realized PED projects.
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2.
  • Bonfiglio, Silvia, et al. (författare)
  • BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib
  • 2023
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:12, s. 2794-2806
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital polymerase chain reaction (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32 of 49 relapsing cases (65%) carried at least 1 hotspot BTK and/or PLCG2 mutation(s); in 6 of 32, BTK mutations were only detected by ddPCR (variant allele frequency [VAF] 0.1% to 1.2%). BTK/PLCG2 mutations were also identified in 6 of 49 responding patients (12%; 5/6 VAF <10%), of whom 2 progressed later. Among the relapsing patients, the BTK-mutated (BTKmut) group was enriched for EGR2 mutations, whereas BTK-wildtype (BTKwt) cases more frequently displayed BIRC3 and NFKBIE mutations. Using an extended capture-based panel, only BRAF and IKZF3 mutations showed a predominance in relapsing cases, who were enriched for del(8p) (n = 11; 3 BTKwt). Finally, no difference in TP53 mutation burden was observed between BTKmut and BTKwt relapsing cases, and ibrutinib treatment did not favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance.
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