Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study

Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelatio

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision

Multicenter randomized phase III trial of Epirubicin plus Paclitaxel vs Epirubicin followed by Paclitaxel in metastatic breast cancer patients: focus on cardiac safety

The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mgm(-2) plus Paclitaxel 200 mgm(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mgm(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mgm(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel

Search for Two-Neutrino Double Electron Capture of 124^{124}Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr.Comment: 6 pages, 4 figure

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

COHERENT Collaboration data release from the measurements of CsI[Na] response to nuclear recoils

Description of the data release 10.13139/OLCF/1969085 (https://doi.ccs.ornl.gov/ui/doi/426) from the measurements of the CsI[Na] response to low energy nuclear recoils by the COHERENT collaboration. The release corresponds to the results published in "D. Akimov et al 2022 JINST 17 P10034". We share the data in the form of raw ADC waveforms, provide benchmark values, and share plots to enhance the transparency and reproducibility of our results. This document describes the contents of the data release as well as guidance on the use of the data

Monitoring the SNS basement neutron background with the MARS detector

We present the analysis and results of the first dataset collected with the MARS neutron detector deployed at the Oak Ridge National Laboratory Spallation Neutron Source (SNS) for the purpose of monitoring and characterizing the beam-related neutron (BRN) background for the COHERENT collaboration. MARS was positioned next to the COH-CsI coherent elastic neutrino-nucleus scattering detector in the SNS basement corridor. This is the basement location of closest proximity to the SNS target and thus, of highest neutrino flux, but it is also well shielded from the BRN flux by infill concrete and gravel. These data show the detector registered roughly one BRN per day. Using MARS' measured detection efficiency, the incoming BRN flux is estimated to be $1.20~\pm~0.56~\text{neutrons}/\text{m}^2/\text{MWh}$ for neutron energies above $\sim3.5$~MeV and up to a few tens of MeV. We compare our results with previous BRN measurements in the SNS basement corridor reported by other neutron detectors.Comment: Submitted to JINS

First Probe of Sub-GeV Dark Matter Beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS

The COHERENT collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220~MeV/c$^2$ using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9~keV$_\text{nr}$. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6~kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants $\alpha_D<0.64$, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios

Measurement of scintillation response of CsI[Na] to low-energy nuclear recoils by COHERENT

We present results of several measurements of CsI[Na] scintillation response to 3-60 keV energy nuclear recoils performed by the COHERENT collaboration using tagged neutron elastic scattering experiments and an endpoint technique. Earlier results, used to estimate the coherent elastic neutrino-nucleus scattering (CEvNS) event rate for the first observation of this process achieved by COHERENT at the Spallation Neutron Source (SNS), have been reassessed. We discuss corrections for the identified systematic effects and update the respective uncertainty values. The impact of updated results on future precision tests of CEvNS is estimated. We scrutinize potential systematic effects that could affect each measurement. In particular we confirm the response of the H11934-200 Hamamatsu photomultiplier tube (PMT) used for the measurements presented in this study to be linear in the relevant signal scale region.Comment: The version accepted by JINST. The changes made as a result of the peer review process: 1. Section 8 "Global CsI[Na] QF data fit" is expanded. The main fit result and its uncertainty is NOT CHANGED. An alternative fit is now shown in Figure 14, Figure 15 is added to further validate the assumptions in the main fit. 2. The Appendix B is restructured for clarit