Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations.

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype.

Immune recovery and the role of recent thymic emigrated T lymphocytes after pediatric hematopoietic stem cell transplantation.

Background Aims: Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3CD31CD45RA cells.

Methods: We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT.

ASCL1 promotes Scrt2 expression in the neural tube.

ASCL1 is a transcription factor that directs neural progenitors towards lineage differentiation. Although many of the molecular mechanisms underlying its action have been described, several of its targets remain unidentified. We identified in the chick genome a putative enhancer (cE1) upstream of the transcription factor () locus with a predicted heterodimerization motif for ASCL1 and POU3F2.

Pluripotency factors are repurposed to shape the epigenomic landscape of neural crest cells.

Yamanaka factors are essential for establishing pluripotency in embryonic stem cells, but their function in multipotent stem cell populations is poorly understood. Here, we show that OCT4 and SOX2 cooperate with tissue-specific transcription factors to promote neural crest formation. By assessing avian and human neural crest cells at distinct developmental stages, we characterized the epigenomic changes that occur during their specification, migration, and early differentiation.

Breast Implant-Associated Anaplastic Large-Cell Lymphoma in Brazil: What Are We Missing?

Background: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) has been diagnosed in more than 1000 patients in more than 30 countries, although only a few cases have been reported in Latin America and the Caribbean to date. As the second-largest global market for breast implants with a predominance of textured-surface implants, Brazil is a major global market for cosmetic augmentations, making it unlikely that cases of BIA-ALCL are actually scarce.

Methods: A local and voluntary registry of patients with BIA-ALCL was initiated in 2018.

Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease-a report from a highly complex hospital in Brazil.

Introduction: Lymphopenia is a laboratory marker of poor prognosis and severity of disease in the SARS-CoV-2 infection. This study aims to describe the immune profile of a Brazilian population.

Methods: A total of 121 consecutive patients with severe acute respiratory syndrome (SARS) were analyzed between April and June 2020.

Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial.

Background: COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease.

Survival benefit of pediatric-based regimen for adults with acute lymphoblastic leukemia: A single-center retrospective cohort.

Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens.

Use of flow cytometry and cytology to differentiate breast implant-associated anaplastic large cell lymphoma from reactive seromas in Brazilian patients.

Introduction: The combination of cytology and multiparametric flow cytometry (MFC) may be useful in the diagnosis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and may be a practical way to differentiate lymphoma from benign and reactive seromas. Although the Brazilian breast implant market is the second largest in the world, with several manufacturers and the almost exclusive use of textured implants, the occurrence of BIA-ALCL in Brazil is underreported.

Methods: One hundred seventeen sequential collections of suspicious periprosthetic fluid (PF) from 105 Brazilian patients registered between March/2018 and March/2021 were evaluated by routine cytomorphology and flow cytometry.

Analysis of baseline characteristics, disease burden and long-term follow-up of 167 patients with Paroxysmal Nocturnal Hemoglobinuria at a single center in Brazil.

Unlabelled: Paroxysmal nocturnal hemoglobinuria (PNH) can occur as a hemolytic form or small PNH clone found in a patient with bone marrow failure.

Methods: Describe Brazilian retrospective PNH cohort and identify the impact of disease burden on long-term follow-up.

Results: 167 patients, mean age at diagnosis 28.

Combined Use of Tocilizumab and Mesenchymal Stromal Cells in the Treatment of Severe Covid-19: Case Report.

The coronavirus pandemic is one of the most significant public health events in recent history. Currently, no specific treatment is available. Some drugs and cell-based therapy have been tested as alternatives to decrease the disease's symptoms, length of hospital stay, and mortality.

The connectome of neural crest enhancers reveals regulatory features of signaling systems.

Cell fate commitment is controlled by cis-regulatory elements often located in remote regions of the genome. To examine the role of long-range DNA interactions in early development, we generated a high-resolution contact map of active enhancers in avian neural crest cells. This analysis uncovered a diverse repertoire of enhancers that are part of the gene regulatory network underlying specification.

A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation.

The process of cell fate commitment involves sequential changes in the gene expression profiles of embryonic progenitors. This is exemplified in the development of the neural crest, a migratory stem cell population derived from the ectoderm of vertebrate embryos. During neural crest formation, cells transition through distinct transcriptional states in a stepwise manner.

Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation.

Introduction: The minimal residual disease (MRD) status plays a crucial role in the treatment of acute lymphoblastic leukemia (ALL) and is currently used in most therapeutic protocols to guide the appropriate therapeutic decision. Therefore, it is imperative that laboratories offer accurate and reliable results through well standardized technical processes by establishing rigorous operating procedures.

Method: Our goal is to propose a monoclonal antibody (MoAb) panel for MRD detection in ALL and provide recommendations intended for flow cytometry laboratories that work on 4-color flow cytometry platforms.

Metabolic Reprogramming Promotes Neural Crest Migration via Yap/Tead Signaling.

The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination.

3D Telomere Structure Analysis to DetectGenomic Instability and Cytogenetic Evolutionin Myelodysplastic Syndromes.

The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cytogenetics in 50% of patients with MDS, such distinguishing patterns are lacking in the other 50%. Despite the increase in the prognostic value of some biomarkers, none of them is specific and able to discriminate between stable and unstable patients that subsequently progress to acute myeloid leukemia.

Identifying Protein-DNA and Protein-Protein Interactions in Avian Embryos.

The chick embryo is a powerful model for experimental embryology due to its accessibility, sturdiness, and ease of manipulation. Here we describe protocols for analysis of protein-DNA and protein-protein interactions in tissues and cells isolated from the developing chick. These assays are aimed at the identification of interactions between transcription factors and regulatory elements in the genome, and, in combination with functional assays, can be used for the delineation of gene regulatory circuits.

Control of neural crest multipotency by Wnt signaling and the Lin28/ axis.

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells.

Cohort profile: the Baependi Heart Study-a family-based, highly admixed cohort study in a rural Brazilian town.

Purpose: Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits.