Abstract: Disclosed is a method for the generation of a consciousness indicator for a non-communicating subject, including the steps of generating an auditory stimulation, receiving an electrocardiographic signal of the subject obtained from a recording during the generation of the auditory stimulation, extracting at least one feature from the electrocardiographic signal and deducing a consciousness indicator from an analysis of the electrocardiographic feature.

Abstract: The inventors initially participated to the identification of LPIN1 mutations as a cause for massive rhabdomyolysis episodes in children, triggered by febrile illness. The inventors have suggested that TLR9 antagonists would be suitable for the treatment of rhabdomyolysis (WO2017085115). The inventors thus treated 2 patients with lipin-1 disease by a TRL9 antagonist (hydroxychloroquine). They showed that the accumulation of mtDNA in plasma of the two patients before treatment decreases under treatment. When the treatment was stopped, the accumulation of mtDNA reappeared, then normalized when treatment was resumed. Accordingly, the present invention relates to a method for determining whether a patient suffering from rhabdomyolysis achieves a response with a TLR9 antagonist comprising determining the amount of mitochondrial DNA (mtDNA) in a blood sample obtained from the patient (e.g. by PCR).

Abstract: The inventors have developed a metastatic 4T1 breast tumor model in BALB/c mice. They have shown that the vaccination with xenogeneic embryonic stem cells in combination with valproic acid (VPA) generates a higher anti-tumoral response against breast cancer and inhibits metastasis development. They established that these responses are achieved only by the addition of valproic acid in the therapeutic regimen in comparison to the use ESCs or iPSCs alone. Thus, the inventors provide a new therapeutic strategy to treat cancers expressing embryonic antigens. Accordingly, the present invention relates to i) a population of pluripotent cells and ii) a compound selected from a group which activates MHC expression, as a combined preparation for use in a method for treating a subject suffering from a cancer, comprising a step of administering simultaneously, separately or sequentially to said subject a therapeutically amount thereof.

Abstract: The present invention relates to compounds of formula (I): for use as peripheral NMDA receptor antagonists.

Abstract: A method for providing cardioprotection in a subject who experienced a myocardial infarction, including administering a therapeutically effective amount of a Granzyme B inhibitor. Following acute MI in mice, CD8+ T lymphocytes are quickly recruited and activated in ischemic heart tissue, and release Granzyme B, leading to cardiomyocyte apoptosis and deterioration of myocardial function. Antibody-mediated depletion of CD8+ T lymphocytes decreases Granzyme B content and apoptotic within the myocardium and inflammatory response. mAb mediated-CD8 depletion limits myocardial injury and improves heart function. These effects are recapitulated in mice with CD8+ T cell selective Granzyme B deficiency in mice. Granzyme B is produced by other cell types (e.g., NK cells). Global Granzyme B deletion (GzmB-/- mice) decreases apoptotic within the myocardium, reduces local pro-inflammatory signature and ultimately limits infarct size after MI.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of tissue lesions. The inventors showed that CCR2 is expressed on FMCs, especially on a subpopulation of progenitor cells, that they call “fetal myeloid progenitor cells” (FMPCs), and mediates the recruitment of these cells to maternal wound tissue. Moreover, the inventors reported that recruited FMCs/FMPCs improve maternal skin wound healing by organizing blood vessel endothelium and secreting pro-angiogenesis peptides, particularly chemokine CXCL1, to enhance angiogenesis in wound. In particular, the present invention relates to CCR2 agonists for use in the treatment of tissue lesions in a subject in need thereof.

Abstract: A method of producing a monomer of a Shiga toxin B-subunit (STxB) protein or of a variant thereof by peptide chemical synthesis, as well as to a method of producing a pentamer of the STxB protein or of the variant thereof. The methods are particularly advantageous as they overcome major issues typically observed in peptide chemical synthesis, including solubility and purity issues.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: The present invention relates to methods for predicting the survival time of patients suffering from a lung cancer.

Abstract: The present invention relates to compounds of formula (I) for use as peripheral NMDA receptor antagonists.

Abstract: A compound of formula (I): wherein R1 is a (C1-C4) alkyl group, or a (C3-C6) cycloalkyl group, R2 is a phenyl or a substituted phenyl with one to three groups, with the proviso that when R2 is a phenyl then R1 is a (C3-C6) cycloalkyl group, or anyone of its pharmaceutically acceptable salt. Also, the compound of formula (I) as medicament for treating rare biliary diseases such as intrahepatic cholestatic diseases. A compound of formula (I): wherein R1 is a (C1-C4) alkyl group, or a (C3-C6) cycloalkyl group, R2 is a phenyl or a substituted phenyl with one to three groups, with the proviso that when R2 is a phenyl then R1 is a (C3-C6) cycloalkyl group, or anyone of its pharmaceutically acceptable salt. Also, the compound of formula (I) as medicament for treating rare biliary diseases such as intrahepatic cholestatic diseases.

Abstract: The present invention relates to the prognosis of the outcome of a cancer in a patient, which prognosis is based on the quantification of one or several biological markers that are indicative of the presence of, or alternatively the level of, the adaptive immune response of said patient against said cancer.

Abstract: A system to measure and monitor neurodegeneration of a subject, which includes: an acquisition module configured to acquire electroencephalographic signals with multiple EEG channels from a subject perceptually isolated; a calculation module configured to extract at least one EEG metric representative of neurodegeneration; and an evaluation module configured to evaluate the at least one EEG metric and extract a neurodegeneration index.

Abstract: Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the 5 CFTR Cl— channel and affects several organs, but the most severe consequences are observed in the lung. The inventors have now instigated the combination of Orkambi® and ANO1 TSB (SEQ ID NO:1) and show that said combination increases mucociliary clearance and chloride channel activity. Thus the combination represents an alternative treatment for CF subjects.

Abstract: An in-ear stimulation system including a first device configured to be worn at least partially in a first ear canal of a subject and a second device configured to be worn at least partially in a second ear canal of the subject. Each of the first device and the second device includes: at least one in-ear active electrode configured to receive a bio-signal and at least one in-ear reference electrode configured to receive a bio-signal; at least one stimulation device configured for emitting at least one electrical or sensory stimulus; and an electronic system configured to detect at least one bio-signal pattern from the bio-signals measured from the electrodes.

Abstract: The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

Abstract: Plasma levels of different sub-populations of microvesicles (endothelial, leukocyte, platelet and hepatocyte) were measured by flow cytometry or ELISA/filtration on blood samples from 125 patients with cirrhosis, for which 36 of them were diagnosed with HCC at inclusion. The inventors show that the levels of microvesicles of endothelial origin (CD62E+) could predict the occurrence of HCC in patients with cirrhosis. Therefore the present invention relates to a method for determining whether a patient suffering from cirrhosis is at risk of having or developing hepatocellular carcinoma comprising determining the level of endothelial-derived microvesicles (e.g. by flow cytometry) in a blood sample obtained from the patient.

Abstract: A method for the generation of a consciousness indicator for a non-communicating subject, including generating a sensory stimulation involving at least one of the five senses, the sensory stimulation having multiple consecutive stimuli including at least a first stimulus and a second stimulus relating to the same sense and different from one another, measuring an electrocardiographic signal of the subject during the generation of the sensory stimulation, extracting at least one EKG feature from the electrocardiographic signal associated to cognitive processes and generating a consciousness indicator using the EKG features as input of a classifier.

Abstract: The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 401 or 408 is mutated.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of acute myeloid leukemia. In particular, the present invention relates to a method for treating NPM-1-driven acute myeloid leukemia (AML) in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one arsenic compound and with a therapeutically effective amount of at least one retinoid.