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Abstract In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 106 PBSC/kg, 2.6% (n = 7) mobilized 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.

Abstract Different driver mutations and/or chromosomal aberrations and dysregulated signaling interactions between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand changes in the bone marrow microenvironment and signaling pathways in pediatric T-ALL, bone marrows collected at diagnosis (Dx) and end of induction therapy (EOI) from 11 patients at a single center were profiled by single cell transcriptomics (10 Dx, 5 paired EOI, 1 relapse). T-ALL blasts were identified by comparison with healthy bone marrow cells. T-ALL blast-associated gene signature included SOX4, STMN1, JUN, HES4, CDK6, ARMH1 among the most significantly overexpressed genes, some of which are associated with poor prognosis in children with T-ALL. Transcriptome profiles of the blast cells exhibited significant inter-patient heterogeneity. Post induction therapy expression profiles of the immune cells revealed significant changes. Residual blast cells in MRD+ EOI samples exhibited significant upregulation (P

Abstract Detection of Zn(II) in oil-polluted seawater via square-wave anodic stripping voltammetry (SW-ASV) utilizing thin gold electrodes sputtered onto nanoporous poly(acrylic acid)-grafted-poly(vinylidene difluoride) (PAA-g-PVDF) membrane is herein reported. Prior to SW-ASV, PAA grafted nanopores demonstrated to efficiently trap Zn(II) ions at open circuit. This passive adsorption followed a Langmuir law. An affinity constant of 1.41 L $$\upmu $$ μ mol $$^{-1}$$ - 1 and a maximum Zn(II) adsorbed mass q $$_{max}$$ max of 1.21 $$\upmu $$ μ mol g $$^{-1}$$ - 1 were found. Applied SW-ASV protocol implied an accumulation step (− 1.2 V for 120 s) followed by a stripping step (− 1.2 to 1 V; 25 Hz; step: 4 mV; amplitude: 25 mV; acetate buffer (pH 5.5)). It revealed a Zn redox potential at − 0.8 V (Ag/AgCl pseudo-reference). Multiple measurements in synthetic waters close to the composition of production waters exhibited a decreasing precision with the number of readings R (1.65 $$\%$$ % (R = 2) and 6.56 $$\%$$ % (R = 3)). These membrane-electrodes should be used as disposable. The intra-batch mean precision was 14 $$\%$$ % (n = 3) while inter-batches precision was 20 $$\%$$ % (n = 15). Linear and linear-log calibrations allow exploitation of Zn(II) concentrations ranging from 10 to 500 $$\upmu $$ μ g L $$^{-1}$$ - 1 and 100 to 1000 $$\upmu $$ μ g L $$^{-1}$$ - 1 respectively. The LOD was 4.2 $$\upmu $$ μ g L $$^{-1}$$ - 1 (3S/N). Thanks to obtained calibration, a detected Zn(II) content of 1 ppm in a raw production water from North Sea oil platform was determined.

Abstract The objective of this prospective study was to investigate the morphological changes of myopic choroidal neovascularization (mCNV) after treatment with anti-vascular endothelial growth factor and to identify potential features predictive of the final BCVA. OCT and OCTA features were evaluated at baseline and at 1, 6 and 12 months. Parameters investigated were the maturity pattern, presence of mCNV OCT activity signs, subretinal fibrosis and mCNV area. Forty patients (41 eyes) were included in the study. At the final visit, after a mean of 3.1 ± 1.4 injections, BCVA had improved significantly (p = 0.009) and subretinal hyperreflective exudation, subretinal fluid and intraretinal cysts nearly disappeared at 12 months. At baseline, 20 eyes had an immature CNV that were smaller, required less injections (2.5 ± 1.2 vs 3.8 ± 1.4, p = 0.002), they completely regressed in seven eyes and achieved a better BCVA (0.14 ± 0.15 vs 0.40 ± 0.26 logMAR, p

Abstract Plasminogen activator inhibitor-1 (PAI-1) is known to protect mice against cardiac fibrosis. It has been speculated that PAI-1 may regulate cardiac fibrosis by inactivating urokinase-type plasminogen activator (uPA) and ultimately plasmin (Pm) generation. However, the in vivo role of PAI-1 in inactivating uPA and limiting the generation of Pm during cardiac fibrosis remains to be established. The objective of this study was to determine if the cardioprotective effect of PAI-1 is mediated through its ability to directly regulate urokinase -mediated activation of plasminogen (Pg). An Angiotensin II (AngII)-aldosterone (Ald) infusion mouse model of hypertension was utilised in this study. Four weeks after AngII-Ald infusion, PAI-1-deficient (PAI-1−/−) mice developed severe cardiac fibrosis. However, a marked reduction in cardiac fibrosis was observed in PAI-1−/−/uPA−/− double knockout mice that was associated with reduced inflammation, lower expression levels of TGF-β and proteases associated with tissue remodeling, and diminished Smad2 signaling. Moreover, total ablation of cardiac fibrosis was observed in PAI-1−/− mice that express inactive plasmin (Pm) but normal levels of zymogen Pg (PAI-1−/−/PgS743A/S743A). Our findings indicate that PAI-1 protects mice from hypertension-induced cardiac fibrosis by inhibiting the generation of active Pm.