Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted.

Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.

Research Question: Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections.

An integrated cell atlas of the lung in health and disease.

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population.

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis.

Background: Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.

Methods: Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease.

Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles' pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics' efficacy.

An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.

Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale.

A Single-Cell Atlas of the Human Healthy Airways.

The respiratory tract constitutes an elaborate line of defense that is based on a unique cellular ecosystem. We aimed to investigate cell population distributions and transcriptional changes along the airways by using single-cell RNA profiling. We have explored the cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling.

Liver X receptors are required for thymic resilience and T cell output.

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)-a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity-critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire.

[The age of artificial intelligence in lung cancer pathology: Between hope, gloom and perspectives].

Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility.

[Standard of care of carcinomas on cancer of unknown primary site in 2016].

Patients with Cancer of unknown primary (cup) represent 2-10%, and have disseminated cancers for which we cannot find the primary site despite the clinical, pathological and radiological exams at our disposal. Diagnosis is based on a thorough clinical and histopathologic examination as well as new imaging techniques. Several clinicopathologic entities requiring specific treatment can be identified.

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC.