Optimizing therapeutic targets for breast cancer using boolean network models.

Studying gene regulatory networks associated with cancer provides valuable insights for therapeutic purposes, given that cancer is fundamentally a genetic disease. However, as the number of genes in the system increases, the complexity arising from the interconnections between network components grows exponentially. In this study, using Boolean logic to adjust the existing relationships between network components has facilitated simplifying the modeling process, enabling the generation of attractors that represent cell phenotypes based on breast cancer RNA-seq data.

Altered innate immune profile in blood of systemic mastocytosis patients.

Background: Mast cells (MC) from systemic mastocytosis (SM) patients release MC mediators that lead to an altered microenvironment with potential consequences on innate immune cells, such as monocytes and dendritic cells (DC). Here we investigated the distribution and functional behaviour of different populations of blood monocytes and DC among distinct diagnostic subtypes of SM.

Methods: Overall, we studied 115 SM patients - 45 bone marrow mastocytosis (BMM), 61 indolent SM (ISM), 9 aggressive SM (ASM)- and 32 healthy donors (HD).

Immunophenotypic Analysis of Acute Megakaryoblastic Leukemia: A EuroFlow Study.

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL.

Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid.

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months.

Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study.

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel.

Low-beta repetitive transcranial magnetic stimulation to human dorsolateral prefrontal cortex during object recognition memory sample presentation, at a task-related frequency observed in local field potentials in homologous macaque cortex, impairs subsequent recollection but not familiarity.

According to dual-process signal-detection (DPSD) theories, short- and long-term recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to these processes, but frequency-specific neuronal activities are considered to play a key role. In Experiment 1, nonhuman primate (NHP) local field potential (LFP) electrophysiological recordings in macaque left dorsolateral PFC (dlPFC) revealed performance-related differences in a low-beta frequency range during the sample presentation phase of a visual object recognition memory task.

Data-Driven Modeling of Breast Cancer Tumors Using Boolean Networks.

Cancer is a genomic disease involving various intertwined pathways with complex cross-communication links. Conceptually, this complex interconnected system forms a network, which allows one to model the dynamic behavior of the elements that characterize it to describe the entire system's development in its various evolutionary stages of carcinogenesis. Knowing the activation or inhibition status of the genes that make up the network during its temporal evolution is necessary for the rational intervention on the critical factors for controlling the system's dynamic evolution.

Flow Cytometry Immunophenotyping for Diagnostic Orientation and Classification of Pediatric Cancer Based on the EuroFlow Solid Tumor Orientation Tube (STOT).

Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination-solid tumor orientation tube, STOT-for diagnostic screening of pediatric cancer by MFC.

Microclimate of grass canopies and biomass accumulation are influenced by the use of caged exclosures in grazing research.

Exclosure cages are often used for estimating biomass accumulation on continuously stocked pastures in grazing experiments. The microclimate inside the cages may affect the estimates of biomass accumulation, but this has not been previously identified or quantified. We evaluated how the exclusion from grazing for 21 days in Mulato II brachiariagrass (Brachiaria brizantha × Brachiaria decumbens × Brachiaria ruziziensis) pastures affected canopy air temperature (T) and relative humidity (RH) and how this related to biomass accumulation.

Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays.

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response.

Automated identification of leukocyte subsets improves standardization of database-guided expert-supervised diagnostic orientation in acute leukemia: a EuroFlow study.

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant classification panel and final diagnosis. In this study, we designed and validated an algorithm for automated (database-supported) gating and identification (AGI tool) of cell subsets within samples stained with ALOT.

Age Distribution of Multiple Functionally Relevant Subsets of CD4+ T Cells in Human Blood Using a Standardized and Validated 14-Color EuroFlow Immune Monitoring Tube.

CD4+ T cells comprise multiple functionally distinct cell populations that play a key role in immunity. Despite blood monitoring of CD4+ T-cell subsets is of potential clinical utility, no standardized and validated approaches have been proposed so far. The aim of this study was to design and validate a single 14-color antibody combination for sensitive and reproducible flow cytometry monitoring of CD4+ T-cell populations in human blood to establish normal age-related reference values and evaluate the presence of potentially altered profiles in three distinct disease models-monoclonal B-cell lymphocytosis (MBL), systemic mastocytosis (SM), and common variable immunodeficiency (CVID).

Maturation-associated gene expression profiles during normal human bone marrow erythropoiesis.

Erythropoiesis has been extensively studied using in vitro and in vivo animal models. Despite this, there is still limited data about the gene expression profiles (GEP) of primary (ex vivo) normal human bone marrow (BM) erythroid maturation. We investigated the GEP of nucleated red blood cell (NRBC) precursors during normal human BM erythropoiesis.

The Exact VC Dimension of the WiSARD -Tuple Classifier.

The Wilkie, Stonham, and Aleksander recognition device (WiSARD) -tuple classifier is a multiclass weightless neural network capable of learning a given pattern in a single step. Its architecture is determined by the number of classes it should discriminate. A target class is represented by a structure called a discriminator, which is composed of RAM nodes, each of them addressed by an -tuple.

BOLD mapping of human epileptic spikes recorded during simultaneous intracranial EEG-fMRI: The impact of automated spike classification.

Objectives: Simultaneous intracranial EEG and functional MRI (icEEG-fMRI) can be used to map the haemodynamic (BOLD) changes associated with the generation of IEDs. Unlike scalp EEG-fMRI, in most patients who undergo icEEG-fMRI, IEDs recorded intracranially are numerous and show variability in terms of field amplitude and morphology. Therefore, visual marking can be highly subjective and time consuming.

Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up and is associated with a poorer outcome.

Low-count monoclonal B-cell lymphocytosis is defined by the presence of very low numbers of circulating clonal B cells, usually phenotypically similar to chronic lymphocytic leukemia cells, whose biological and clinical significance remains elusive. Herein, we re-evaluated 65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemia-like) followed-up for a median of seven years, using high-sensitivity flow cytometry and interphase fluorescence hybridization. Overall, the clone size significantly increased in 69% of low-count monoclonal B-cell lymphocytosis cases, but only one subject progressed to high-count monoclonal B-cell lymphocytosis.

A novel scheme for the validation of an automated classification method for epileptic spikes by comparison with multiple observers.

Objective: To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data.

Method: Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs.

A universal multilingual weightless neural network tagger via quantitative linguistics.

In the last decade, given the availability of corpora in several distinct languages, research on multilingual part-of-speech tagging started to grow. Amongst the novelties there is mWANN-Tagger (multilingual weightless artificial neural network tagger), a weightless neural part-of-speech tagger capable of being used for mostly-suffix-oriented languages. The tagger was subjected to corpora in eight languages of quite distinct natures and had a remarkable accuracy with very low sample deviation in every one of them, indicating the robustness of weightless neural systems for part-of-speech tagging tasks.

Lot-to-lot stability of antibody reagents for flow cytometry.

The fluorescence detected using fluorochrome-labelled monoclonal antibodies depends not only on the abundance of the target antigen, but amongst many other factors also on the effective fluorochrome-to-antibody ratio. The diagnostic approach of the EuroFlow consortium relies on reproducible fluorescence intensities over time. A capture bead system for mouse immunoglobulin light chains was utilized to compare the mean fluorescence intensity of 1323 consecutive antibody lots to the currently used lot of the same monoclonal antibody.

Maturation-associated gene expression profiles along normal human bone marrow monopoiesis.

Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis.

Adverse perinatal outcomes for advanced maternal age: a cross-sectional study of Brazilian births.

Objectives: To investigate the risk of adverse perinatal outcomes in women aged ≥41 years relatively to those aged 21-34.

Methods: Approximately 8.5 million records of singleton births in Brazilian hospitals in the period 2004-2009 were investigated.

Past, present and future of spike sorting techniques.

Spike sorting is a crucial step to extract information from extracellular recordings. With new recording opportunities provided by the development of new electrodes that allow monitoring hundreds of neurons simultaneously, the scenario for the new generation of algorithms is both exciting and challenging. However, this will require a new approach to the problem and the development of a common reference framework to quickly assess the performance of new algorithms.