Evaluation of the role of and in the dominant multidrug-resistant clone B0/W148.

Unlabelled: Multidrug-resistant (MDR) strains of represent an obstacle to eradicating tuberculosis (TB) due to the low treatment success rate of MDR TB. Among them, the MDR B0/W148 clone has recently evolved from the Beijing lineage 2 and is widely disseminated in Russia and Europe. To get more insights into the genetic factors underlying the evolutionary success of the MDR B0/W148 clone in addition to environmental and patient-related features, we focused on two mutations specific to this clone that are found in the transcriptional regulators WhiB6 and KdpDE and investigated in a H37Rv strain background the transcriptional profile associated with these mutations and their impact on the and growth characteristics.

Evaluation of High-Dose Isoniazid in Multidrug-Resistant Tuberculosis Treatment.

High-dose isoniazid is recommended to treat multidrug-resistant tuberculosis (MDR TB). Among 958 MDR TB isolates identified in France during 2008-2022, 93.1% exhibited high-level isoniazid resistance, and molecular testing showed limited diagnostic accuracy in predicting resistance.

Src kinase slows collective rotation of confined epithelial cell monolayers.

Collective cell migration is key during development, wound healing, and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a key signalling protein for the physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its overactivation is associated with cancer aggressiveness.

Clinical, biological, prognostic characteristics of patients with immune-mediated thrombotic thrombocytopenic purpura and Sjögren's disease.

Objectives: The association between immune-mediated thrombotic thrombocytopenic purpura (iTTP) and Sjögren disease (SjD) has been poorly investigated. This study presents the first retrospective cohort of iTTP-SjD aiming to identify risk factors for iTTP occurrence in SjD patients and examine their clinical course.

Methods: Patients with iTTP-SjD were identified within the French TTP Registry based on American College of Rheumatology/European League Against Rheumatism 2016 criteria.

Active tuberculosis screening among the displaced population fleeing Ukraine, France, February to October 2022.

Persons fleeing Ukraine since February 2022 have potentially higher risk of tuberculosis (TB) vs all European Union countries. Interest of active TB screening among this population is debated and not widely adopted. In this screening intervention by a network of TB centres in France, the number needed to screen (NNS) was 862 to find one case.

Actomyosin contractility in olfactory placode neurons opens the skin epithelium to form the zebrafish nostril.

Despite their barrier function, epithelia can locally lose their integrity to create physiological openings during morphogenesis. The mechanisms driving the formation of these epithelial breaks are only starting to be investigated. Here, we study the formation of the zebrafish nostril (the olfactory orifice), which opens in the skin epithelium to expose the olfactory neurons to external odorant cues.

TALASUR trial: a single arm phase II trial assessing efficacy and safety of TALazoparib and Avelumab as maintenance therapy in platinum-Sensitive metastatic or locally advanced URothelial carcinoma.

Background: Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients with advanced UC.

Use of a bDMARD or tsDMARD for the management of inflammatory arthritis under checkpoint inhibitors: an observational study.

Objective: There is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting.

Methods: Using the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi.

Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer According to Somatic Damage DNA Repair Gene Alterations.

(1) Background: In literature, approximately 20% of mCRPC present somatic DNA damage repair (DDR) gene mutations, and their relationship with response to standard therapies in mCRPC is not well understood. The objective was to evaluate outcomes of mCRPC patients treated with standard therapies according to somatic DDR status. (2) Methods: Eighty-three patients were recruited at Caen Cancer Center (France).

atpE Mutation in Mycobacterium tuberculosis Not Always Predictive of Bedaquiline Treatment Failure.

We report the emergence of an atpE mutation in a clinical Mycobacterium tuberculosis strain. Genotypic and phenotypic bedaquiline susceptibility testing displayed variable results over time and ultimately were not predictive of treatment outcome. This observation highlights the limits of current genotypic and phenotypic methods for detection of bedaquiline resistance.

Intertissue mechanical interactions shape the olfactory circuit in zebrafish.

While the chemical signals guiding neuronal migration and axon elongation have been extensively studied, the influence of mechanical cues on these processes remains poorly studied in vivo. Here, we investigate how mechanical forces exerted by surrounding tissues steer neuronal movements and axon extension during the morphogenesis of the olfactory placode in zebrafish. We mainly focus on the mechanical contribution of the adjacent eye tissue, which develops underneath the placode through extensive evagination and invagination movements.

A Comprehensive Evaluation of GeneLEAD VIII DNA Platform Combined to Deeplex Myc-TB Assay to Detect in 8 Days Drug Resistance to 13 Antituberculous Drugs and Transmission of Complex Directly From Clinical Samples.

The GeneLEAD VIII (Diagenode, Belgium) is a new, fully automated, sample-to-result precision instrument for the extraction of DNA and PCR detection of complex (MTBC) directly from clinical samples. The Deeplex Myc-TB assay (Genoscreen, France) is a diagnostic kit based on the deep sequencing of a 24-plexed amplicon mix allowing simultaneously the detection of resistance to 13 antituberculous (antiTB) drugs and the determination of spoligotype. We evaluated the performance of a strategy combining the both mentioned tools to detect directly from clinical samples, in 8 days, MTBC and its resistance to 13 antiTB drugs, and identify potential transmission of strains from patient-to-patient.

CABOCOL-01 trial: a single-arm phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure.

Background: Cervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor.

Rapid Molecular Diagnosis of Tuberculosis and Its Resistance to Rifampicin and Isoniazid with Automated MDR/MTB ELITe MGB Assay.

The MDR/MTB ELITe MGB kit (ELITech) carried on the ELITe InGenius platform is a new real-time PCR assay allowing automated extraction and detection of DNA of the complex (MTB) and mutations in the and genes and promoter region (pro-) associated to resistance to rifampicin and isoniazid, the two markers of multidrug-resistant TB (MDR). We assessed the performances of the test on a collection of strains ( = 54) and a set of clinical samples ( = 242) from routine practice, comparatively to TB diagnosis and genotypic drug susceptibility testing (gDST) as references. Regarding the 242 clinical samples, the sensitivity and specificity of MTB detection by ELITe were 90.

A Multitubular Kidney-on-Chip to Decipher Pathophysiological Mechanisms in Renal Cystic Diseases.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major renal pathology provoked by the deletion of or genes leading to local renal tubule dilation followed by the formation of numerous cysts, ending up with renal failure in adulthood. , renal tubules are tightly packed, so that dilating tubules and expanding cysts may have mechanical influence on adjacent tubules. To decipher the role of this coupling between adjacent tubules, we developed a kidney-on-chip reproducing parallel networks of tightly packed tubes.

Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis.

Objective: Peripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series aimed to evaluate the efficacy of rituximab (RTX) for PUK occurring in patients with RA.

Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage.

Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses. A way to decipher the mechanisms of such pleiotropic signaling activity is to directly manipulate the decision-making activity that supports the selection between distinct cellular responses. We developed an optogenetic probe (optoSRC) to control SRC signaling, an example of a pleiotropic signaling node, and we demonstrated its ability to generate different acto-adhesive structures (lamellipodia or invadosomes) upon distinct spatio-temporal control of SRC kinase activity.

Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study.

Background: The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR-based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4-5 h. We performed this study to evaluate the concordance between the multiplex PCR-based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP.