Model and method to predict the turbulent kinetic energy induced by tidal currents, application to the wave-induced turbulence

A prediction model for the turbulent kinetic energy (TKE) induced by tidal-currents is proposed as a function of the barotropic velocity only, along with a robust method evaluating the different parameters involved using Acoustic Doppler Current Profiler (ADCP) measurements from Alderney Race. We find that the model is able to reproduce correctly the TKE profiles with coefficients of correlation on average higher than 0.90 and normalised root-mean-square errors (NRMSE) less than 14%. Different profiles are also tested for the mean velocity, no satisfactory prediction model is found but we are able to have decent estimates of the velocity shear and friction velocity. Two applications are then carried out. First the turbulent budget terms are estimated and discussed. We identify the turbulent production and dissipation of TKE as the most important mechanisms, then we discuss the validity of several theoretical results derived for isotropic turbulence for this application. A strong departure for the estimation of the turbulent dissipation is notably found and explained by the turbulent anisotropy. At last the prediction model for the TKE is used to infer the wave-induced TKE. We show the importance of removing the tidal component, waves can have a strong influence down to mid-depth

Graph-based multimodal multi-lesion DLBCL treatment response prediction from PET images

Diffuse Large B-cell Lymphoma (DLBCL) is a lymphatic cancer involving one or more lymph nodes and extranodal sites. Its diagnostic and follow-up rely on Positron Emission Tomography (PET) and Computed Tomography (CT). After diagnosis, the number of nonresponding patients to standard front-line therapy remains significant (30-40%). This work aims to develop a computer-aided approach to identify high-risk patients requiring adapted treatment by efficiently exploiting all the information available for each patient, including both clinical and image data. We propose a method based on recent graph neural networks that combine imaging information from multiple lesions, and a cross-attention module to integrate different data modalities efficiently. The model is trained and evaluated on a private prospective multicentric dataset of 583 patients. Experimental results show that our proposed method outperforms classical supervised methods based on either clinical, imaging or both clinical and imaging data for the 2-year progression-free survival (PFS) classification accuracy

Interest of FDG-PET in the Management of Mantle Cell Lymphoma

FDG-PET changed response assessment and therapy strategy in diffuse large B-cell lymphoma and Hodgkin disease lymphoma. The value of FDG-PET evaluation in MCL has not been extensively studied and a recent expert consensus highlighted the need for more studies addressing this question. Data of the literature show the value of FDG-PET at baseline in patients with MCL, underlining the good sensitivity of this examination for the initial staging of this pathology, but also the potential impact of semi-quantitative analysis in this indication. The determination of SUVmax at diagnosis might indeed provide important prognostic information. Some studies also suggest the potential value of early and end-of-treatment metabolic assessment in MCL, but these results need to be validated in standardized prospective studies. These results also underlie the need to integrate FDG-PET results into MCL treatment strategy to improve disease management in identifying patients who might benefit from more intensive therapy

Genome Expression Dynamics Reveal the Parasitism Regulatory Landscape of the Root-Knot Nematode Meloidogyne incognita and a Promoter Motif Associated with Effector Genes.

Root-knot nematodes (genus Meloidogyne) are the major contributor to crop losses caused by nematodes. These nematodes secrete effector proteins into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effector genes. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands, providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus, and we name it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode and identify a new set of candidate effector genes that will guide future functional analyses

Interest of Pet Imaging in Multiple Myeloma

The interest of 18Fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging in the management of patients with multiple myeloma (MM) for the workup at diagnosis and for therapeutic evaluation has recently been demonstrated. FDG-PET is a powerful imaging tool for bone lesions detection at initial diagnosis with high sensitivity and specificity values. The independent pejorative prognostic value on progression-free survival (PFS) and overall survival (OS) of baseline PET-derived parameters (presence of extra-medullary disease (EMD), number of focal bone lesions (FLs), and maximum standardized uptake values [SUVmax]) has been reported in several large independent prospective studies. During therapeutic evaluation, FDG-PET is considered as the reference imaging technique, because it can be performed much earlier than MRI which lacks specificity. Persistence of significant FDG uptake after treatment, notably before maintenance therapy, is an independent pejorative prognostic factor, especially for patients with a complete biological response. So FDG-PET and medullary flow cytometry are complementary tools for detection of minimal residual disease before maintenance therapy. However, the definition of PET metabolic complete response should be standardized. In patients with smoldering multiple myeloma, the presence of at least one hyper-metabolic lytic lesions on FDG-PET may be considered as a criterion for initiating therapy. FDG-PET is also indicated for initial staging of a solitary plasmacytoma so as to not disregard other bone or extra-medullary localizations. Development of nuclear medicine offer new perspectives for MM imaging. Recent PET tracers are willing to overcome limitations of FDG. (11)C-Methionine, which uptake reflects the increased protein synthesis of malignant cells seems to correlate well with bone marrow infiltration. Lipid tracers, such as Choline or acetate, and some peptide tracers, such as (68) Ga-Pentixafor, that targets CXCR4 (chemokine receptor-4, which is often expressed with high density by myeloma cells), are other promising PET ligands. 18F-fludarabine and immuno-PET targeting CD138 and CD38 also showed promising results in preclinical models

TWISTED DWARF1 mediates the action of auxin transport inhibitors on actin cytoskeleton dynamics

Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity

Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.

[en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice

New Biomarkers in Multiple Myeloma Imaging

Malgré d’importants progrès lors de cette dernière décennie, le myélome multiple reste encore une maladie incurable et l’identification de nouveaux biomarqueurs permettant de toujours mieux sélectionner les patients de mauvais pronostic éligibles à une thérapie plus intensive demeure d’actualité. L’imagerie en médecine nucléaire s’inscrit parfaitement dans cette démarche en permettant d’observer in vivo, de façon non invasive, l’expression et la distribution des biomarqueurs accessibles dans les cibles tumorales. Cette hétérogénéité de signatures moléculaires peut être appréciée qualitativement ou quantitativement, par l’intermédiaire de multiples traceurs apportant des informations phénotypiques, métaboliques, complémentaires ou en explorant les distributions et fixations de chaque traceur individuellement. La première partie de ce travail a été consacrée à l’évaluation pré-clinique d’anticorps ciblant le syndecan-1 ou CD138, une protéoglycane utilisée comme marqueur standard par de nombreux laboratoires pour l’identification et la purification de cellules myélomateuses. La seconde partie a évalué des paramètres quantitatifs d’analyse de l’imagerie TEP caractérisant l’hétérogénéité intra-tumorale afin de les corréler aux données histologiques. La troisième partie de ce travail a consisté en l’évaluation de la pertinence des paramètres quantitatifs d’analyse de l’imagerie TEP-FDG en clinique sur les données de la cohorte IMAJEM.Despite significant progress over the past decade, multiple myeloma remains an incurable disease and the identification of new biomarkers to better select patients with poor prognosis who are eligible for more intensive therapy remains a priority. Nuclear medicine imaging fits perfectly into this approach by allowing non-invasive in vivo observation of the expression and distribution of accessible biomarkers in tumor targets. This heterogeneity of molecular signatures can be assessedqualitatively or quantitatively, through multiple tracers providing complementary, phenotypic and metabolic, information or by exploring the distributions and uptakes of each tracer. The first .part of this work was devoted to the pre-clinical evaluation of antibodies targeting syndecan-1 or CD138, a proteoglycan used as a standard marker by many laboratories for the identification and purification of myeloma cells. The second part evaluated quantitative parameters for the analysis of PET imaging characterizing intra-tumor heterogeneity in order to correlate them with histological data.The third part of this work consisted in evaluating the relevance of quantitative parameters for the analysis of PET-FDG imaging in the clinic using the data of the IMAJEM cohort

PET Imaging for Initial Staging and Therapy Assessment in Multiple Myeloma Patients

Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using 18F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology. This paper reviews the recent advances as well as the potential place of a more specific radiopharmaceutical in MM