Automated Database and Pattern-guided Immunophenotypic Classification of Acute Leukaemia Using Next Generation Flow Cytometry

Acute leukaemia is a heterogeneous group of disorders characterized by clonal expansion of abnormal haemopoietic cells arrested at early stages of maturation. Appropriate management of these disorders requires accurate diagnosis and classification based on the WHO classification of tumors of haemopoietic and lymphoid tissues. Despite several advances in molecular pathology, flow cytometry still remains an essential tool for diagnosis of this group of haematological disorders. The aim of this study was to validate the EuroFlow acute leukaemia orientation tube (ALOT) and its corresponding database-guided interpretation tool using the FACS Canto II flow cytometer and following in-house cytometer settings, compensation and staining procedures. The study also aimed to use the principal component analysis (PCA) and automated population separator (APS) tools on the Infinicyt software to merge the standard flow cytometry files (FCS) from the in-house acute leukaemia panel in order to create and compare immunophenotypic profiles of acute leukaemia cases in this study. A total of 24 specimens from 16 acute leukaemia cases were tested using both the in-house acute panel as well as the ALOT tube under validation. Results showed 100% agreement between the two methods as well as the ALOT automated database-guided interpretation tool compared to the conventional hematopathologist (expert-based) approach of results interpretation. Furthermore, the flow cytometry merged files and immunophenotypic profiles were successfully used to build in-house ALOT and acute leukaemia database-guided interpretation tools. Results of these newly developed tools showed 100% agreement II between the in-house database-guided tools and the conventional expert-based interpretation of flow cytometry results. Unsupervised comparison of the immunophenotypic profiles of B- acute lymphoblastic leukaemia (B-ALL) cases in this study showed some overlap between some cases with similar immunophenotypic profile and subsequent cytogenetic translocations as well as cases presented with CNS involvement. Further analysis confirmed that all the cases with CNS involvement in this study were CD34 negative. Limitations of this new approach were discussed in more detail, including the additional costs of the ALOT tube and the automated database interpretation tool. In conclusion, results of this study confirmed the validity of ALOT tube and its corresponding database using local cytometer settings and procedures. Results also showed that using next generation flow cytometry with automated database-guided interpretation tools is a promising approach that can facilitate standardised interpretation of flow cytometry results in future

Lateral orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases

Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected sequential effects, including increased willingness to take risks following risky wins, and spatial ‘win-stay/lose-shift’ biases. Recordings from lateral orbitofrontal cortex (lOFC) revealed encoding of reward history and receipt, and optogenetic inhibition of lOFC eliminated rats’ increased preference for risk following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and the lOFC’s role in adaptive behavior promotes learning of more abstract biases (here, biases for the risky option), but not spatial ones

Why sex hormones matter for neuroscience: A very short review on sex, sex hormones, and functional brain asymmetries

Biological sex and sex hormones are known to affect functional cerebral asymmetries (FCAs). Men are generally more lateralized than women. The effect size of this sex difference is small but robust. Some of the inconsistencies in the literature may be explained by sex-related hormonal differences. Most studies focusing on neuromodulatory properties of sex hormones on FCAs have investigated women during the menstrual cycle. Although contradictions exist, these studies have typically shown that levels of estradiol and/or progesterone correlate with the degree of FCAs, suggesting that sex differences in FCAs partially depend on hormonal state and day of testing. The results indicate that FCAs are not fixed but are hormone dependent, and as such they can dynamically change within relatively short periods throughout life. Many issues raised in this Mini-Review refer not only to FCAs but also to other aspects of functional brain organization, such as functional connectivity within and between the cerebral hemispheres. Our understanding of sex differences in brain and behavior as well as their clinical relevance will improve significantly if more studies routinely take sex and sex hormones into account

Photochemistry of single optically trapped oleic acid droplets

We report the photodegradation of optically trapped oleic acid droplets by visible light in the absence of additional reactive gaseous species. The temporal evolution of the droplet's chemical composition and size is monitored by Raman spectroscopy and elastic light scattering, respectively. The dependencies on the oxygen amount in the surrounding gas phase (~0–20%), the droplet size (~500–3000 nm in radius), and the laser power and wavelength are investigated. The oxygen amount and the droplet size have only a very minor influence on the reaction rate, if at all. By contrast, the reaction becomes substantially faster at higher laser power and shorter wavelength. The experimental observations indicate that mechanisms involving the photoexcitation of oleic acid are the dominant pathways. Our study reveals that direct photodegradation has to be accounted for when using optical traps or applying spectroscopic and light scattering characterization methods to study aerosol particles that contain fatty acids. © 2020 Elsevier LtdISSN:0021-8502ISSN:1879-196

Lateral orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases

Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected sequential effects, including increased willingness to take risks following risky wins, and spatial 'win-stay/lose-shift' biases. Recordings from lateral orbitofrontal cortex (lOFC) revealed encoding of reward history and receipt, and optogenetic inhibition of lOFC eliminated rats' increased preference for risk following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and the lOFC's role in adaptive behavior promotes learning of more abstract biases (here, biases for the risky option), but not spatial ones

Comment formuler les éléments de connaissances sous forme d'objectifs /

La couv. porte en outre: Méthode cadre, guide pratiqu