Management of acute promyelocytic leukemia in the setting of acute COVID-19 infection

Acute promyelocytic leukemia (APL) often presents with significant coagulopathy which may result in both hemorrhagic and thrombotic complications. The emergence of the COVID-19 pandemic has complicated the initial treatment and diagnosis of APL owing to the viral infection\u27s own associated coagulopathy. Here we report two cases of APL newly diagnosed in the setting of COVID-19 infection and considerations in their management. Included is a discussion of strategies for the dosing of arsenic trioxide in patients with significant obesity and renal insufficiency. The case series submitted does not represent a study on patients and thus no specific informed consents or permissions were required. All images included in our manuscript have been deidentified and all authors certify that personal details that could potentially be used to identify the patients in the cases described have been removed. The corresponding author has personally confirmed that both patients included in this study have given verbal permission to present their cases in the de-identified manner as described above

The FORUM end-to-end simulator project: architecture and results

FORUM (Far-infrared Outgoing Radiation Understanding and Monitoring) will fly as the ninth ESA's Earth Explorer mission, and an end-to-end simulator (E2ES) has been developed as a support tool for the mission selection process and the subsequent development phases. The current status of the FORUM E2ES project is presented together with the characterization of the capabilities of a full physics retrieval code applied to FORUM data. We show how the instrument characteristics and the observed scene conditions impact on the spectrum measured by the instrument, accounting for the main sources of error related to the entire acquisition process, and the consequences on the retrieval algorithm. Both homogeneous and heterogeneous case studies are simulated in clear and cloudy conditions, validating the E2ES against appropriate well-established correlative codes. The performed tests show that the performance of the retrieval algorithm is compliant with the project requirements both in clear and cloudy conditions. The far-infrared (FIR) part of the FORUM spectrum is shown to be sensitive to surface emissivity, in dry atmospheric conditions, and to cirrus clouds, resulting in improved performance of the retrieval algorithm in these conditions. The retrieval errors increase with increasing the scene heterogeneity, both in terms of surface characteristics and in terms of fractional cloud cover of the scene

IMC-Denoise: A content aware denoising pipeline to enhance Imaging Mass Cytometry

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background noise removal, with significant image quality improvement in modeled data and datasets from multiple pathologies. This includes in technically challenging human bone marrow; we achieve noise level reduction of 87% for a 5.6-fold higher contrast-to-noise ratio, and more accurate background noise removal with approximately 2 × improved F1 score. Our approach enhances manual gating and automated phenotyping with cell-scale downstream analyses. Verified by manual annotations, spatial and density analysis for targeted cell groups reveal subtle but significant differences of cell populations in diseased bone marrow. We anticipate that IMC-Denoise will provide similar benefits across mass cytometric applications to more deeply characterize complex tissue microenvironments

Measurements of iodine monoxide at a semi polluted coastal location

Point source measurements of IO by laser induced fluorescence spectroscopy were made at a semi-polluted coastal location during the Reactive Halogens in the Marine Boundary Layer (RHaMBLe) campaign in September 2006. The site, on the NW French coast in Roscoff, was characterised by extensive intertidal macroalgae beds which were exposed at low tide. The closest known iodine active macroalgae beds were at least 300 m from the measurement point. From 20 days of measurements, IO was observed above the instrument limit of detection on 14 days, of which a clear diurnal profile was observed on 11 days. The maximum IO mixing ratio was 30.0 pptv (10 s integration period) during the day, amongst the highest concentrations ever observed in the atmosphere, and 1–2 pptv during the night. IO concentrations were strongly dependent on tidal height, the intensity of solar irradiation and meteorological conditions. An intercomparison of IO measurements made using point source and spatially averaged DOAS instruments confirms the presence of hot-spots of IO caused by an inhomogeneous distribution of macroalgae. The co-incident, point source measurement of IO and ultra fine particles (2.5 nm≥<i>d</i>≥10 nm) displayed a strong correlation, providing evidence that IO is involved in the production pathway of ultra fine particles at coastal locations. Finally, a modelling study shows that high IO concentrations which are likely to be produced in a macrolagae rich environment can significantly perturb the concentrations of OH and HO<sub>2</sub> radicals. The effect of IO on HO<sub>x</sub> is reduced as NO<sub>x</sub> concentrations increase

Direct nitrogen fixation at the edges of graphene nanoplatelets as efficient electrocatalysts for energy conversion

Nitrogen fixation is essential for the synthesis of many important chemicals (e.g., fertilizers, explosives) and basic building blocks for all forms of life (e.g., nucleotides for DNA and RNA, amino acids for proteins). However, direct nitrogen fixation is challenging as nitrogen (N2) does not easily react with other chemicals. By dry ball-milling graphite with N2, we have discovered a simple, but versatile, scalable and eco-friendly, approach to direct fixation of N2 at the edges of graphene nanoplatelets (GnPs). The mechanochemical cracking of graphitic C-C bonds generated active carbon species that react directly with N2 to form five- and six-membered aromatic rings at the broken edges, leading to solution-processable edge-nitrogenated graphene nanoplatelets (NGnPs) with superb catalytic performance in both dye-sensitized solar cells and fuel cells to replace conventional Pt-based catalysts for energy conversion.open302

Neratinib protects pancreatic beta cells in diabetes

The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Leprdb/db) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes

New evidence for habitat specific selection in Wadden Sea Zostera marina populations revealed by genome scanning using SNP and microsatellite markers

Eelgrass Zostera marina is an ecosystem-engineering species of outstanding importance for coastal soft sediment habitats that lives in widely diverging habitats. Our first goal was to detect divergent selection and habitat adaptation at the molecular genetic level; hence, we compared three pairs of permanently submerged versus intertidal populations using genome scans, a genetic marker-based approach. Three different statistical approaches for outlier identification revealed divergent selection at 6 loci among 46 markers (6 SNPs, 29 EST microsatellites and 11 anonymous microsatellites). These outlier loci were repeatedly detected in parallel habitat comparisons, suggesting the influence of habitat-specific selection. A second goal was to test the consistency of the general genome scan approach by doubling the number of gene-linked microsatellites and adding single nucleotide polymorphism (SNP) loci, a novel marker type for seagrasses, compared to a previous study. Reassuringly, results with respect to selection were consistent among most marker loci. Functionally interesting marker loci were linked to genes involved in osmoregulation and water balance, suggesting different osmotic stress, and reproductive processes (seed maturation), pointing to different life history strategies. The identified outlier loci are valuable candidates for further investigation into the genetic basis of natural selection