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Although acute promyelocytic leukemia (APL) is one of the most characterized forms of acute myeloid leukemia (AML), the molecular mechanisms involved in the development and progression of this disease are still a matter of study. APL is defined by the PML-RARA rearrangement as a consequence of the translocation t(15;17)(q24;q21). However, this abnormality alone is not able to trigger the whole leukemic phenotype and secondary cooperating events might contribute to APL pathogenesis. Additional somatic mutations are known to occur recurrently in several genes, such as FLT3, WT1, NRAS and KRAS, whereas mutations in other common AML genes are rarely detected, resulting in a different molecular profile compared to other AML subtypes. How this mutational spectrum, including point mutations in the PML-RARA fusion gene, could contribute to the 10%–15% of relapsed or resistant APL patients is still unknown. Moreover, due to the uncertain impact of additional mutations on prognosis, the identification of the APL-specific genetic lesion is still the only method recommended in the routine evaluation/screening at diagnosis and for minimal residual disease (MRD) assessment. However, the gene expression profile of genes, such as ID1, BAALC, ERG, and KMT2E, once combined with the molecular events, might improve future prognostic models, allowing us to predict clinical outcomes and to categorize APL patients in different risk subsets, as recently reported. In this review, we will focus on the molecular characterization of APL patients at diagnosis, relapse and resistance, in both children and adults. We will also describe different standardized molecular approaches to study MRD, including those recently developed. Finally, we will discuss how novel molecular findings can improve the management of this disease.

Emotional intelligence (EI) refers to the ability to perceive, express, understand, and manage emotions. Current research indicates that it may protect against the emotional burden experienced in certain professions. This article aims to provide an updated systematic review of existing instruments to assess EI in professionals, focusing on the description of their characteristics as well as their psychometric properties (reliability and validity). A literature search was conducted in Web of Science (WoS). A total of 2761 items met the eligibility criteria, from which a total of 40 different instruments were extracted and analysed. Most were based on three main models (i.e., skill-based, trait-based, and mixed), which differ in the way they conceptualize and measure EI. All have been shown to have advantages and disadvantages inherent to the type of tool. The instruments reported in the largest number of studies are Emotional Quotient Inventory (EQ-i), Schutte Self Report-Inventory (SSRI), Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT 2.0), Trait Meta-Mood Scale (TMMS), Wong and Law’s Emotional Intelligence Scale (WLEIS), and Trait Emotional Intelligence Questionnaire (TEIQue). The main measure of the estimated reliability has been internal consistency, and the construction of EI measures was predominantly based on linear modelling or classical test theory. The study has limitations: we only searched a single database, the impossibility of estimating inter-rater reliability, and non-compliance with some items required by PRISMA.

Purpose This study presents data on the feasibility and possible benefits of a psychological intervention that uses virtual reality to induce positive emotions on adult hospitalized patients with metastatic cancer. The patient’s satisfaction and perceived utility was also examined. Method The sample was composed of 19 patients (53 % men, aged from 29 to 85 years old; x  = 60.9; standard deviation = 14.54). The intervention consisted of four 30-min sessions during 1 week in which patients navigated through virtual environments designed to induce joy or relaxation. Mood was assessed before and after each session using the Visual Analog Scale. Patient satisfaction was assessed after each session and at the end of the intervention. Qualitative data were also collected with open-ended questions. Results There were no major difficulties with the use of devices, and any difficulties that did arise were solved through practice. There were adequate levels of pleasantness and perceived utility of the proposed intervention. The main perceived benefits were distraction, entertainment, and promotion of relaxation states. Regarding mood changes, an increase in positive emotions and a decrease in negative emotions were also detected. Conclusions The intervention was positively assessed and rated as minimally uncomfortable. Future actions are discussed as well as the need to implement brief interventions that take into account the patients’ medical state and physical discomfort level, especially with those in the advanced stages of disease.

Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and function of this gene as a result of germinal mutations underlie distinct clinical presentations, including childhood myelodysplastic syndrome and acute myeloid leukemia, in which the acquisition of additional molecular somatic abnormalities can lead to variable outcomes. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation, which should be performed before irreversible organ damage happens. In this review, we will examine the structural characteristics of the GATA2 gene, its physiological and pathological functions, how GATA2 genetic mutations contribute to myeloid neoplasms, and other potential clinical manifestations. Finally, we will provide an overview of current therapeutic options, including recent transplantation strategies.

We aim to clarify the ligninolytic capabilities of dye-decolorizing peroxidases (DyPs) from bacteria and fungi, compared to fungal lignin peroxidase (LiP) and versatile peroxidase (VP). With this purpose, DyPs from Amycolatopsis sp., Thermomonospora curvata, and Auricularia auricula-judae, VP from Pleurotus eryngii, and LiP from Phanerochaete chrysosporium were produced, and their kinetic constants and reduction potentials determined. Sharp differences were found in the oxidation of nonphenolic simple (veratryl alcohol, VA) and dimeric (veratrylglycerol-β- guaiacyl ether, VGE) lignin model compounds, with LiP showing the highest catalytic efficiencies (around 15 and 200 s−1·mM−1 for VGE and VA, respectively), while the efficiency of the A. auricula-judae DyP was 1–3 orders of magnitude lower, and no activity was detected with the bacterial DyPs. VP and LiP also showed the highest reduction potential (1.28–1.33 V) in the rate-limiting step of the catalytic cycle (i.e., compound-II reduction to resting enzyme), estimated by stopped-flow measurements at the equilibrium, while the T. curvata DyP showed the lowest value (1.23 V). We conclude that, when using realistic enzyme doses, only fungal LiP and VP, and in much lower extent fungal DyP, oxidize nonphenolic aromatics and, therefore, have the capability to act on the main moiety of the native lignin macromolecule.

RNA splicing and epigenetic gene mutations are the most frequent genetic lesions found in patients with myelodysplastic neoplasm (MDS). About 25% of patients present concomitant mutations in such pathways, suggesting a cooperative role in MDS pathogenesis. Importantly, mutations in the splicing factor ZRSR2 frequently associate with alterations in the epigenetic regulator TET2. However, the impact of these concurrent mutations in hematopoiesis and MDS remains unclear. Using CRISPR/Cas9 genetically engineered mice, we demonstrate that Zrsr2m/mTet2−/− promote MDS with reduced penetrance. Animals presented peripheral blood cytopenia, splenomegaly, extramedullary hematopoiesis, and multi-lineage dysplasia, signs consistent with MDS. We identified a myelo-erythroid differentiation block accompanied by an expansion of LT-HSC and MPP2 progenitors. Transplanted animals presented a similar phenotype, thus indicating that alterations were cell-autonomous. Whole-transcriptome analysis in HSPC revealed key alterations in ribosome, inflammation, and migration/motility processes. Moreover, we found the MAPK pathway as the most affected target by mRNA aberrant splicing. Collectively, this study shows that concomitant Zrsr2 mutation and Tet2 loss are sufficient to initiate MDS in mice. Understanding this mechanistic interplay will be crucial for the identification of novel therapeutic targets in the spliceosome/epigenetic MDS subgroup.

The first step in biomarkers discovery is to identify the best protocols for their purification and analysis. This issue is critical when considering peripheral blood samples (plasma and serum) that are clinically interesting but meet several methodological problems, mainly complexity and low biomarker concentration. Analysis of small molecules, such as circulating microRNAs, should overcome these disadvantages. The present study describes an optimal RNA extraction method of microRNAs from human plasma samples. Different reagents and commercially available kits have been analyzed, identifying also the best pre-analytical conditions for plasma isolation. Between all of them, the column-based approaches were shown to be the most effective. In this context, miRNeasy Serum/Plasma Kit (from Qiagen) rendered more concentrated RNA, that was better suited for microarrays studies and did not require extra purification steps for sample concentration and purification than phenol based extraction methods. We also present evidences that the addition of low doses of an RNA carrier before starting the extraction process improves microRNA purification while an already published carrier dose can result in significant bias over microRNA profiles. Quality controls for best protocol selection were developed by spectrophotometry measurement of contaminants and microfluidics electrophoresis (Agilent 2100 Bioanalyzer) for RNA integrity. Selected donor and patient plasma samples and matched biopsies were tested by Affymetrix microarray technology to compare differentially expressed microRNAs. In summary, this study defines an optimized protocol for microRNA purification from human blood samples, increasing the performance of assays and shedding light over the best way to discover and use these biomarkers in clinical practice.

Polyamines (PAs) are ubiquitous low molecular weight, molecules found in all living cells with participation in a variety of processes. The establishment of symbiotic interactions between soil nitrogen fixing bacteria (rhizobia) and leguminous plants, as well as the formation of the root nodules where the rhizobia are hosted, depends on the production of PAs by both partners. In the bacteria, PAs provide certain traits that facilitate the recognition between the symbionts, while in the plant, PAs participate in the production of signaling molecules like hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO), detected during the initial stages of the symbiosis. Once the symbiosis is established, the high amount and variety of PAs in the root nodules together to their participation in the metabolic reactions supporting nitrogen fixation, suggest their involvement in the nodule functioning. In addition, PAs are key players in the response to abiotic stresses contributing to the adaptation of the symbiosis to salinity, specially, by an increment in the production of PAs in the bacteroids and their interactions with other anti-stress plant hormones. Considering the importance of biological nitrogen fixation in soil fertility and agriculture productivity in a context of climate change, in this review we describe the participation of PAs to the rhizobia-legume interaction and the nitrogen fixation process, as well as its involvement in the response to salinity in the symbiosis.

Background and Objectives: The aim of this study is to evaluate the efficacy of an autologous dentin graft, via extracted teeth that are processed into bacteria-free particulate dentin in a Smart dentin grinder and then grafted immediately into alveolus post extraction or into bone deficiencies. Materials and Methods: Ten healthy, partially edentulous patients with some teeth in the mandible were recruited in the study. After their own teeth were grinded, particulate teeth were placed in empty sockets and bone defects after teeth extractions. Furthermore, after three, six, 12 and 24 months, core samples using a 3 mm trephine were obtained. Results: At three months, the particles of grinded tooth were immersed inside a new connective tissue with a small new bone formation (16.3 ± 1.98). At six months, we observed small particles of dentin integrated in new immature bone, without inflammation in the soft tissue (41.1 ± 0.76). At twelve months, we observed a high amount of bone formation surrounding tooth particles (54.5 ± 0.24), and at twenty-four months, new bone, a big structure of bone, was observed with dentin particles (59.4 ± 1.23), statistically different when compared it with at three months. Conclusions: A particulate dentin graft should be considered as an alternative material for sockets’ preservation, split technique, and also for sinus lifting. One of the special characteristics after 24 months of evaluation was the high resorption rate and bone replacement without inflammation. This material could be considered as an acceptable biomaterial for different bone defects due to its osteoinductive and osteoconductive properties

Acute Myeloid Leukemia (AML) is a genetically and clonally heterogeneous blood malignancy characterized by somatic gene mutations influencing disease biology. Despite advances in genomic analyses, splicing alterations associated with AML mutations remain underexplored. In this study, we systematically analyzed 914 single nucleotide variants previously found in 1540 AML patients and integrated DNA and RNA sequencing data from an additional 639 cases obtained from the BeatAML and TCGA-LAML cohorts. We identified 125 somatic variants in 32 genes with predicted splicing impact, including traditionally categorized missense/nonsense mutations. Among the 36 variants tested experimentally, 17 were validated through RNA-seq and/or minigene assays, with the latter providing support when RNA-seq evidence was limited. Validated splicing-associated variants (SAVs) frequently induced exon skipping or cryptic splice site activation in AML-associated genes such as EZH2 , FLT3 , ASXL1 , IDH1 , and U2AF1 . In several cases, these splicing changes altered conserved protein domains or were predicted to trigger nonsense-mediated decay. Our findings reveal a previously underappreciated contribution of cis -acting SAVs to AML pathogenesis, highlighting the need for integrative prediction–validation strategies to uncover their functional and potential therapeutic relevance.