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Prognostic value of angiography-based fractional flow reserve of left anterior descending artery in orthotopic heart transplant recipients
No full textKnowledge and awareness of cervical cancer and prevention measures among female students in Poland : a cross-sectional, decade apart study
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Lead optimization of a butyrylcholinesterase inhibitor for the treatment of Alzheimer’s disease
No full textOn friendship in stylistics : stylistic "conspiracy" in the Swedish translation of Witold Gombrowicz's "Trans-Atlantyk"
No full textInotuzumab therapy resulted in molecular remission of relapsed/resistant B-cell acute lymphoblastic leukemia with BCR::ABL1 Lys404Glu mutation
Get PDFThe Philadelphia positive acute lymphoblastic leukemia (ALL BCR::ABL1 positive) is characterized by the presence of the t(9;22)(q34;q11) resulting in the formation of the BCR::ABL1 fusion, constant high cellular BCR-ABL1 tyrosine kinase activity, abnormal lymphoid cell proliferation and genetic instability of leukemic cells. Recently, great progress has been made due to the incorporation of tyrosine kinase inhibitors (TKI’s) into the treatment algorithms. Despite this, a significant number of patients experienced therapy resistance mainly due to disease evolution and/or acquisition of TKI resistant BCR::ABL1 mutation(s). Herein, we report the therapy outcome in a 65 year old woman with high-risk BCR::ABL1 positive ALL treated with the PALG ALL7 (including imatinib, IM) protocol, who obtained complete hematologic remission (CHR) and complete molecular remission (CMR) after treatment with induction,consolidation I and II. Despite the fully matched donor identification, the patient refused to continue with intensive chemotherapy. Therefore, only IM therapy was continued, with periodic drug dose reduction due to hematological toxicity. CHR loss with the absence of BCR::ABL1 KD mutation was noticed 10 months later. The treatment with dasatinib (DAS) 140mg/d and dexamethasone resulted in a second CMR. Due to gastrointestinal toxicity, the DAS dose was reduced to 100mg/d. The second disease relapse was diagnosed 3 months later. BCR::ABL1 KD mutation screening showed the Lys404Glu (K404E) substitution. The 3-week long treatment with ponatinib in the dose of 45mg/d resulted in disease progression. The reinduction therapy with anti-CD22 MoAb (Inotuzumab ozogamycin) led to the 3rd CMR (duration time 9 months). According to our knowledge, it is the first report on the emergence of a BCR::ABL1 Lys404Glu mutation in an ALL patient receiving TKI treatment. Due to the mutation emergence on DAS, and disease progression on subsequent ponatinib treatment, the impact of the mutation acquisition on the 3D structure of ABL1 molecule and the process of TKI’s binding to ATP-binding site were additionally studied. The results of the study indicate that the TKI resistance observed in the presented case is probably the result of the impossibility of the formation of stable complexes between ATP-competitive inhibitors and mutant Lys404Glu BCR-ABL1 tyrosine kinase due to conformational molecule changes
Status of "Bitcoin" virtual currency transactions in the VAT system : introduction and judgment of the Court of Justice of 22 October 2015, C-264/14, Skatteverket v David Hedqvist
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From donor‐acceptor ligands to smart coordination polymers : cyanothiazole‐Cu(I) complexes for multifunctional electronic devices
Get PDFCyanothiazoles, small and quite overlooked molecules, possess remarkable optical properties that can be fine-tuned through coordination with transition metals. In this study, we investigate a promising application of cyanothiazoles, where their combination with copper(I) iodide forms a new class of complexes exhibiting outstanding optical properties. X-ray crystallography of copper(I) iodide complexes with isomeric cyanothiazoles revealed key structural features, such as π─π stacking, hydrogen bonding, and rare halogen⋅⋅⋅chalcogen I⋅⋅⋅S interactions, enhancing stability and reactivity. Advanced spectroscopy and computational modeling allowed precise identification of spectral signatures in Fourier-transform infrared (FTIR), nuclear magnetic resonance (NMR), and ultraviolet-visible (UV–Vis) spectra. Fluorescence studies, along with X-ray absorption near edge structure (XANES) synchrotron analyses, highlighted their unique thermal and electronic properties, providing a solid foundation for further research in the field
RouteRL: Multi-agent reinforcement learning framework for urban route choice with autonomous vehicles
No full textRouteRL is a novel framework that integrates multi-agent reinforcement learning (MARL) with a microscopic traffic simulation for the development of efficient collective route choice strategies for autonomous vehicles (AVs). The proposed framework models the daily urban route choices of driver agents of two types: human drivers, emulated using behavioral route choice models, and AVs, modeled as MARL agents optimizing their policies for a predefined objective. RouteRL aims to advance research in MARL, transport modeling, and human–AI interaction for transportation applications. This study presents a technical report on RouteRL, outlines its potential research contributions, and showcases its impact via illustrative examples. Initial findings show that human travel times could increase following the introduction of AVs in urban environments, highlighting the importance of future studies to support efficient urban mobility