Functional changes in prefrontal cortex following frequency-specific training

Altres ajuts: European ANR (COEN4007-18, COEN-0003-01); PHRC grants from the French Ministry of Health and research funding; France Parkinson and ARSLA charity.Numerous studies indicate a significant role of pre-frontal circuits (PFC) connectivity involving attentional and reward neural networks within attention deficit hyperactivity disorder (ADHD) pathophysiology. To date, the neural mechanisms underlying the utility of non-invasive frequency-specific training systems in ADHD remediation remain underexplored. To address this issue, we created a portable electroencephalography (EEG)-based wireless system consisting of a novel headset, electrodes, and neuro program, named frequency specific cognitive training (FSCT). In a double-blind, randomized, controlled study we investigated the training effects in N = 46 school-age children ages 6-18 years with ADHD. 23 children in experimental group who underwent FCST training showed an increase in scholastic performance and meliorated their performance on neuropsychological tests associated with executive functions and memory. Their results were compared to 23 age-matched participants who underwent training with placebo (pFSCT). Electroencephalogram (EEG) data collected from participants trained with FSCT showed a significant increase in 14-18 Hz EEG frequencies in PFC brain regions, activities that indicated brain activation in frontal brain regions, the caudate nucleus, and putamen. These results demonstrate that FSCT targets specific prefrontal and striatal areas in children with ADHD, suggesting a beneficial modality for non-invasive modulation of brain areas implicated in attention and executive functions

3D-in-2D Displays for ATC.

This paper reports on the efforts and accomplishments of the 3D-in-2D Displays for ATC project at the end of Year 1. We describe the invention of 10 novel 3D/2D visualisations that were mostly implemented in the Augmented Reality ARToolkit. These prototype implementations of visualisation and interaction elements can be viewed on the accompanying video. We have identified six candidate design concepts which we will further research and develop. These designs correspond with the early feasibility studies stage of maturity as defined by the NASA Technology Readiness Level framework. We developed the Combination Display Framework from a review of the literature, and used it for analysing display designs in terms of display technique used and how they are combined. The insights we gained from this framework then guided our inventions and the human-centered innovation process we use to iteratively invent. Our designs are based on an understanding of user work practices. We also developed a simple ATC simulator that we used for rapid experimentation and evaluation of design ideas. We expect that if this project continues, the effort in Year 2 and 3 will be focus on maturing the concepts and employment in a operational laboratory settings

Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score.

To support the global restart of elective surgery, data from an international prospective cohort study of 8492 patients (69 countries) was analysed using artificial intelligence (machine learning techniques) to develop a predictive score for mortality in surgical patients with SARS-CoV-2. We found that patient rather than operation factors were the best predictors and used these to create the COVIDsurg Mortality Score (https://covidsurgrisk.app). Our data demonstrates that it is safe to restart a wide range of surgical services for selected patients

Secado a presión reducida de naranjas (<i>Cv. Valencia Late</i>) pre-tratadas osmóticamente

Se ha estudiado la deshidratación de naranjas (cv. Valencia Late) empleando técnicas de osmosis (DO) y secado a presión reducida (SPR) –individuales y combinadas (DO seguida de SPR) – bajo diferentes condiciones: DO: tipo de agente osmótico (sacarosa, glucosa), concentración (20, 40, 60% p/p), temperatura del jarabe (20, 40, 60ºC), tiempo (rango: 0-240 min), con relación fruta:jarabe constante de 1:10 sin agitación; SPR: temperatura (20, 40, 60ºC), tiempo de SPR (0-240 min), vacío constante de 40 mmHg. En primer lugar se evaluó el proceso individual de DO mediante la metodología de superficie de respuesta a fin de establecer las mejores condiciones para obtener la máxima pérdida de agua (WL) con una moderada incorporación de sólidos solubles (SG). El análisis de optimización de respuestas múltiple permitió establecer que tanto en solución de sacarosa como en glucosa a una concentración de 60% p/p a 20ºC es posible obtener una WL máxima de 40.2% y una SG de 17.3% en un tiempo de proceso de 221.7 minutos. En el mismo sentido, se determinaron las condiciones óptimas para el tratamiento individual de SPR que resultaron 60|C a un tiempo. En el estudio de los procesos combinados, se evaluó el efecto de un pre-tratamiento por DO en condiciones óptimas de proceso (sacarosa, 20% p/p, 20 ºC) sobre el SPR. El proceso combinado (DO+SPR) redujo los tiempos de tratamiento del tratamiento individual por SPR para alcanzar un determinado contenido de humedad final. Por otro lado, basándose en un modelo difusional fueron calculadas las difusividades efectivas de humedad para las diferentes temperaturas de SPR de las frutas frescas y pre-deshidratadas por ósmosis, observándose que los coeficientes de difusión del agua fueron mayores para las muestras DO+SPR: 1,0523×10⁻⁹ m²/s (20ºC); 2,1553×10⁻⁹ m²/s (40ºC) y 6,8613×10⁻⁹ m²/s (60ºC) frente a los siguientes valores de difusividad para el SPR: 4,1330×10⁻¹² m²/s (20°C); 3,5427×10⁻¹¹ m²/s (40°C) y 1,3503×10⁻¹⁰ m²/s (60°C). Sobre la base de estos resultados, mediante una ecuación tipo Arrhenius se determinó la energía de activación para la deshidratación de las naranjas predeshidratadas por ósmosis.Centro de Investigación y Desarrollo en Criotecnología de Alimento

miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden

Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

Timed degradation of the cyclin-dependent kinase inhibitor p27^(Kip1) by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leukemia models, with little effect on normal tissues. We also demonstrate a novel feed forward feedback loop by which Notch and IL-7 signaling cooperatively converge on SKP2 induction and cell cycle activation. These studies show that the Notch/SKP2/p27^(Kip1) pathway plays a unique role in T-ALL development and provide a proof-of-concept for the use of SKP2 as a new therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL)

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

Anaplastic large cell lymphomas (ALCLs) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to the nucleophosmin (NPM) gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo and that ALK activity is strictly required for the survival of ALK-positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK-positive ALCL cell lines, abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell-permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBP\u3b2 and the antiapoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK-positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions

Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score

To support the global restart of elective surgery, data from an international prospective cohort study of 8492 patients (69 countries) was analysed using artificial intelligence (machine learning techniques) to develop a predictive score for mortality in surgical patients with SARS-CoV-2. We found that patient rather than operation factors were the best predictors and used these to create the COVIDsurg Mortality Score (https://covidsurgrisk.app). Our data demonstrates that it is safe to restart a wide range of surgical services for selected patients.Laura Bravo ... COVIDSurg Collaborative : (Royal Adelaide Hospital, N. N. Dudi-Venkata, H. M. Kroon, T. Sammour) ... et al.