Survival and quality of life in patients with lower risk myelodysplastic syndromes exposed to erythropoiesis-stimulating agents: an observational cohort study.

Background: In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes.

Methods: The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms.

Background: Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear.

Case report: Development of clonal hematologic disorders from inherited bone marrow failure.

Introduction: Inherited bone marrow failure (IBMF) syndromes are caused by mutations forming pathologic germline variants resulting in the production of defective hematopoietic stem cells (HSC) and in congenital failure in the production of one or more blood lineages. An acquisition of subsequent somatic mutations is determining further course of the disease. Nevertheless, a certain number of patients with IBMF may escape correct diagnosis in childhood, especially those with mild cytopenia and minimal clinical features without non-hematologic symptoms.

Inflammatory profile of lower risk myelodysplastic syndromes.

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs).

The role of thoracic surgery in the management of complicated acute and post-acute COVID-19 pneumonia (PASC).

Introduction: COVID-19 is considered a respiratory virosis in its classic form, although it may present with heterogeneous symptoms. Thoracic complications occur in a small percentage of patients. Our objective was to evaluate existing experience with this disease and its thoracic manifestations and to determine the real-world status of care of these patients.

Attenuated cell cycle and DNA damage response transcriptome signatures and overrepresented cell adhesion processes imply accelerated progression in patients with lower-risk myelodysplastic neoplasms.

Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower-risk MDS patients (LR-MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed to uncover the mechanisms of this accelerated progression at the transcriptome level.

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation.

Absolute energy levels in nanodiamonds of different origins and surface chemistries.

Nanodiamonds (NDs) are versatile, broadly available nanomaterials with a set of features highly attractive for applications from biology over energy harvesting to quantum technologies. synthesis and surface chemistry, NDs can be tuned from the sub-micron to the single-digit size, from conductive to insulating, from hydrophobic to hydrophilic, and from positively to negatively charged surface by simple annealing processes. Such ND diversity makes it difficult to understand and take advantage of their electronic properties.

Design and Synthesis of New Sulfonic Acid Functionalized Ionic Liquids as Catalysts for Esterification of Fatty Acids with Bioethanol.

In this study, three types of sulfonic acid group functionalized ionic liquids (SAILs) with a different number of catalytic groups and lipophilicity were synthesized and characterized by FT-IR, NMR, and MS analyses. Their catalytic activities were studied in a model esterification of oleic acid with ethanol; heating in a microwave reactor was also used. The experimental results indicated that SAIL, with the lipophilic alkyl chain, performed the best due to its increased solubility in the reaction mixture.

Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1.

Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells.

A multi-institutional epidemiologic study evaluating environmental risk factors for feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive cancer in domestic cats that has no effective treatment option when advanced. Preventative or early diagnostic measures are thus crucial. FOSCC is also a model for human head and neck SCC (HNSCC); strong risk factors in HNSCC include exposure to alcohol, tobacco, areca nut, and high-risk human papillomavirus.

Influence of Fe on the Hydrogen Storage Properties of LaCeNi Alloys.

LaNi intermetallic compounds with a hexagonal CaCu type structure can react reversibly with hydrogen. The element substitutions in LaNi can significantly change the hydrogenation properties, allowing to tune them to a large extent. It could be very advantageous to partially replace Ni or La with other elements to reduce the cost of this alloy as well as the equilibrium pressure of absorption and desorption.

Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations.

Introduction: Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making complement inhibition the best approach to manage PNH. Three complement inhibitors are approved by the European Medicines Agency as targeted therapy for PNH: eculizumab and ravulizumab, two humanized monoclonal antibodies targeting the same complement 5 (C5) epitope, approved in 2007 and 2019, respectively, and the more recently approved cyclic peptide, the complement 3 (C3) inhibitor pegcetacoplan. Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial evidence.

Highly Regular LIPSS on Thin Molybdenum Films: Optimization and Generic Criteria.

A systematic experimental study was performed to determine laser irradiation conditions for the large-area fabrication of highly regular laser-induced periodic surface structures (HR-LIPSS) on a 220 nm thick Mo film deposited on fused silica. The LIPSS were fabricated by scanning a linearly polarized, spatially Gaussian laser beam at 1030 nm wavelength and 1.4 ps pulse duration over the sample surface at 1 kHz repetition rate.

An Observational Pilot Study using a Digital Phenotyping Approach in Patients with Major Depressive Disorder Treated with Trazodone.

This 8-week study was designed to explore any correlation between a passive data collection approach using a wearable device (i.e., digital phenotyping), active data collection (patient's questionnaires), and a traditional clinical evaluation [Montgomery-Åsberg Depression Rating Scale (MADRS)] in patients with major depressive disorder (MDD) treated with trazodone once a day (OAD).

Cause of death and excess mortality in patients with lower-risk myelodysplastic syndromes (MDS): A report from the European MDS registry.

Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS (LR-MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR-MDS. We prospectively collected data on patients with LR-MDS in the European MDS registry from 2008 to 2019.

Missense mutation in RPS7 causes Diamond-Blackfan anemia via alteration of erythrocyte metabolism, protein translation and induction of ribosomal stress.

Diamond-Blackfan anemia (DBA) is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25 % of patients. We previously reported a novel heterozygous RPS7 mutation hg38 chr2:g.3,580,153G > T p.

RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS.

Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, a small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive of LR-MDS progression and to uncover cellular pathways contributing to malignant transformation. The mutational landscape was analyzed in 214 LR-MDS patients, and at least one mutation was detected in 137 patients (64%).

Mass spectrometry, data re-analysis, and homology modelling predict posttranslational modifications of leucine-rich alpha-2-glycoprotein as a marker of myelodysplastic syndrome.

Background: Leucine-rich alpha-2-glycoprotein (LRG) has been repeatedly proposed as a potential plasma biomarker for myelodysplastic syndrome (MDS).

Objective: The goal of our work was to establish the total LRG plasma level and LRG posttranslational modifications (PTMs) as a suitable MDS biomarker.

Methods: The total plasma LRG concentration was determined with ELISA, whilst the LRG-specific PTMs and their locations, were established using mass spectrometry and public mass spectrometry data re-analysis.

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes.

Background/aim: Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs).

Materials And Methods: RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers.

Opportunistic experiments to constrain aerosol effective radiative forcing.

Aerosol-cloud interactions (ACIs) are considered to be the most uncertain driver of present-day radiative forcing due to human activities. The nonlinearity of cloud-state changes to aerosol perturbations make it challenging to attribute causality in observed relationships of aerosol radiative forcing. Using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently.