Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause severe respiratory illness with high mortality. SARS-CoV-2 infection results in a massive inflammatory cell infiltration into the infected lungs accompanied by excessive pro-inflammatory cytokine production. The lung histology of dead patients shows that some areas are severely emphysematous, with enormously dilated blood vessels and micro-thromboses.

The β-carboline Harmine improves the therapeutic benefit of anti-PD1 in melanoma by increasing the MHC-I-dependent antigen presentation.

Harmine is a dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitor that displays a number of biological and pharmacological properties. Also referred to as ACB1801 molecule, we have previously reported that harmine increases the presentation of major histocompatibility complex (MHC)-I-dependent antigen on melanoma cells. Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells.

Is Sphingosine-1-Phosphate a Regulator of Tumor Vascular Functionality?

Increasing evidence indicates that tumor vasculature normalization could be an appropriate strategy to increase therapies' efficacy in solid tumors by decreasing hypoxia and improving drug delivery. We searched for a novel approach that reduces hypoxia and enhances chemotherapy efficacy in pancreatic adenocarcinoma which is characterized by disrupted blood vasculature associated with poor patient survival. Clinical significance of plasma levels of the angiogenic lipid sphingosine-1-phosphate (S1P) was assessed at baseline in 175 patients.

The Forgotten Health-Care Occupations at Risk of Burnout-A Burnout, Job Demand-Control-Support, and Effort-Reward Imbalance Survey.

Aims: We conducted a cross-sectional study on healthcare workers from the University Hospital in Clermont-Ferrand. They received a self-report questionnaire consisting of the Maslach Burnout Inventory, Job Demand Control Support, Effort-Reward Imbalance model, and questions about ethical conflict in order to investigate on burnout.

Results: We included 1774 workers.

Burnout Among Hospital Non-Healthcare Staff: Influence of Job Demand-Control-Support, and Effort-Reward Imbalance.

Objectives: To study the prevalence of burnout among non-health care workers (NHCW), the risk and protective factors and to quantify the risk of burnout.

Method: We conducted a cross-sectional study on the 3142 NHCW of the University Hospital of Clermont-Ferrand. They received a self-assessment questionnaire.

The 'Holy Grail' in Immuno-Oncology: AC BioScience SA is Aiming to Potentiate Anti-PD-1 Therapy Efficacy through Tumor Cell Conditioning Strategy.

AC BioScience is a Swiss biotech company based at the EPFL Innovation Park and Biopôle, dedicated to developing groundbreaking therapies to fight a range of cancers and infectious diseases. We are about to start clinical trials with two of four leading-edge cancer drugs mainly focusing on immune-oncology and tumor vascular normalization with multi-billion $ sales potential. Here, we present our strategy and one of our pioneering drug candidates that has already shown exceptional results with tumor cell conditioning to improve the efficacy of immune checkpoint inhibitors.

The β-Carboline Harmine Induces Actin Dynamic Remodeling and Abrogates the Malignant Phenotype in Tumorigenic Cells.

Numerous studies have shown that alteration of actin remodeling plays a pivotal role in the regulation of morphologic and phenotypic changes leading to malignancy. In the present study, we searched for drugs that can regulate actin polymerization and reverse the malignant phenotype in cancer cells. We developed a cell-free high-throughput screening assay for the identification of compounds that induce the actin polymerization in vitro, by fluorescence anisotropy.

Measuring the impact of the French version of The Whiplash Book on both treatment approach and fear-avoidance beliefs among emergency physicians. A cluster randomized controlled trial.

Background: Whiplash-associated disorders have been the subject of much attention in the scientific literature and remain a major public health problem.

Objective: Measure the impact of a validated information booklet on the fear-avoidance beliefs of emergency physicians and their approach to management regarding the treatment of whiplash-associated disorders.

Methods: A prospective cluster randomized controlled study conducted with a sample of emergency medicine physicians.

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial.

To assess masitinib in the treatment of ALS. Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.

A close relative of the Amazon river dolphin in marine deposits: a new Iniidae from the late Miocene of Angola.

Background: A few odontocetes (echolocating toothed cetaceans) have been able to independently colonize freshwater ecosystems. Although some extant species of delphinids (true dolphins) and phocoenids (porpoises) at least occasionally migrate upstream of large river systems, they have close relatives in fully marine regions. This contrasts with the three odontocete families only containing extant species with a strictly freshwater habitat (Iniidae in South America, the recently extinct Lipotidae in China, and Platanistidae in southeast Asia).

PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer.

Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer.

Improving image quality of mid-trimester fetal sonography in obese women: role of ultrasound propagation velocity.

Objective: The quality of ultrasound images is impaired in obese patients. All ultrasound scanners are calibrated for an ultrasound propagation velocity of 1540 m/s, but the propagation in fatty tissue is slower (in the order of 1450 m/s). The main objective of this study was to evaluate the quality of images obtained with different ultrasound propagation velocity settings during the mid-trimester fetal ultrasound examination in obese patients.

Targeting TCTP with Sertraline and Thioridazine in Cancer Treatment.

We have initially demonstrated in knocking down experiments that decreasing TCTP in cancer cells leads in some tissues to cell death while in others to a complete reorganization of the tumor into architectural structures reminiscent of normal ones. Based on these experiments and a series of other findings confirming the key role of TCTP in cancer, it became important to find pharmacological compounds to inhibit its function, and this became for us a priority. In the present text, we explain in detail the experiments that were performed and the perspectives of sertraline in cancer treatment, as this became today a reality with a clinical study that started in collaboration with Columbia University and Johns Hopkins University.

[Spouses' health-related quality of life evaluation of elderly patients with depression].

Objective: To assess and compare the health-related quality of life (HRQoL) of spouses living at home with a patient aged 65 years or more suffering from a major depressive disorder and that of matched controls. Secondly, to investigate whether the HRQoL of spouses was correlated with the assessment of their partner's depression, their own depression and the self-perceived level of care burden experienced by the caregiver partner.

Methods: Assessment of patients was based on the clinical diagnosis of a major depressive disorder as established by the criteria of the DSM-IV-TR, the geriatric depression scale GDS-15 and the LEIPAD questionnaire specific to subjects aged 65 or over living at home.

Psychometric properties of the French version of the Endometriosis Health Profile-30, a health-related quality of life instrument.

Introduction: The objectives were to evaluate the acceptability, reliability and validity of the cross-cultural adaptation of the Endometriosis Health Profile-30 instrument into French.

Methods: This cross-sectional study was conducted between July and October 2015. We created an online link (REDCap platform) with the questionnaires.

NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.

Despite effective targeted therapy acting on and tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST.

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study.

Background: Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.

Protein kinase C inhibitor Gö6976 but not Gö6983 induces the reversion of E- to N-cadherin switch and metastatic phenotype in melanoma: identification of the role of protein kinase D1.

Background: Melanoma is a highly metastatic type of cancer that is resistant to all standard anticancer therapies and thus has a poor prognosis. Therefore, metastatic melanoma represents a significant clinical problem and requires novel and effective targeted therapies. The protein kinase C (PKC) family comprises multiple isoforms of serine/threonine kinases that possess distinct roles in cancer development and progression.

Health-related quality of life, anxiety and depression in parents of adolescents with Gilles de la Tourette syndrome: a controlled study.

Our objectives were to assess health-related quality of life (HRQoL), anxiety, depression of Gilles de la Tourette syndrome (GTS) adolescents' parents compared to controls; to assess GTS adolescents' HRQoL compared to controls; to investigate which parental and adolescent variables are associated with poorer parental HRQoL. The controlled study involved GTS outpatients and their parents, adolescent healthy controls matched for gender and age and their parents. Parents' HRQoL was assessed using SF-36 and WHOQOL-BREF; anxiety, depression using HADS.

Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics.

The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected.

Osteopontin and thrombospondin-1 play opposite roles in promoting tumor aggressiveness of primary resected non-small cell lung cancer.

Background: Osteopontin (OPN) and thrombospondin-1 (TSP-1) are extracellular matrix proteins secreted by stromal and tumor cells. These proteins appear to have a key role in the tumor microenvironment for cancer development and metastasis. There is little information regarding the prognostic value of the combination of these two proteins in human cancers.

Amiodarone-Induced Thyrotoxicosis Recurrence After Amiodarone Reintroduction.

Reintroduction of amiodarone in patients with a history of amiodarone-induced thyrotoxicosis (AIT) is rarely used. To date, the risk of AIT recurrence after amiodarone reintroduction is unpredicted. The aim of the study was to evaluate the risk of AIT recurrence.

[Psychiatrists' decision making and monitoring of antipsychotic prescription for elderly schizophrenia patients].

Objective: Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients.

Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5.

KIT is a cell surface tyrosine kinase receptor whose ligand stem cell factor (SCF) triggers homodimerization and activation of downstream effector pathways involved in cell survival, proliferation, homing, or differentiation. KIT-activating mutations are major oncogenic drivers in subsets of acute myeloid leukemia (AML), in mast cell leukemia, and in gastrointestinal stromal tumors (GIST). The overexpression of SCF and/or wild-type (WT) KIT is also observed in a number of cancers, including 50% of AML and small cell lung cancer.