Nanopore adaptive sampling accurately detects nucleotide variants and improves the characterization of large-scale rearrangement for the diagnosis of cancer predisposition.

Background: Molecular diagnosis has become highly significant for patient management in oncology.

Methods: Here, 30 well-characterized clinical germline samples were studied with adaptive sampling to enrich the full sequence of 152 cancer predisposition genes. Sequencing was performed on Oxford Nanopore (ONT) R10.

Impact of scFv on Functionality and Safety of Third-Generation CD123 CAR T Cells.

Chimeric antigen receptor (CAR) T cells express an extracellular domain consisting of a single-chain fragment variable (scFv) targeting a surface tumor-associated antigen. scFv selection should involve safety profiling with evaluation of the efficacy/toxicity balance, especially when the target antigen also is expressed on healthy cells. Here, to assess differences in terms of efficacy and on-target/off-tumor effects, we generated five different CARs targeting CD123 by substituting only the scFv.

Crystalline restacking of 2D-materials from their nanosheets suspensions.

We report here the highly ordered restacking of the layered phosphatoantimonic dielectric materials HMSbPO, (where M = Li, Na, K, Rb, Cs and 0 ≤ ≤ 1), from their nanosheets dispersed in colloidal suspension, induced by a simple pH change using alkaline bases. HSbPO aqueous suspensions are some of the rare examples of colloidal suspensions based on 2D materials exhibiting a lamellar liquid crystalline phase. Because the lamellar period can reach several hundred nanometers, the suspensions show vivid structural colors and because these colors are sensitive to various chemicals, the suspensions can be used as sensors.

Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization.

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA.

Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes.

Background: Non-small cell lung cancer is a very poor prognosis disease. Molecular analyses have highlighted several genetic alterations which may be targeted by specific therapies. In clinical practice, progression-free survival on EGFR TKI treatment is between 12 and 14 months.

Exome-Based Genomic Markers Could Improve Prediction of Checkpoint Inhibitor Efficacy Independently of Tumor Type.

Immune checkpoint inhibitors (ICIs) have improved the care of patients in multiple cancer types. However, PD-L1 status, high Tumor Mutational Burden (TMB), and mismatch repair deficiency are the only validated biomarkers of efficacy for ICIs. These markers remain imperfect, and new predictive markers represent an unmet medical need.

Orchestrated translation specializes dinoflagellate metabolism three times per day.

Many cells specialize for different metabolic tasks at different times over their normal ZT cycle by changes in gene expression. However, in most cases, circadian gene expression has been assessed at the mRNA accumulation level, which may not faithfully reflect protein synthesis rates. Here, we use ribosome profiling in the dinoflagellate to identify thousands of transcripts showing coordinated translation.

Hematopoietic Prostaglandin D2 Synthase Controls Tfh/Th2 Communication and Limits Tfh Antitumor Effects.

T follicular helper (Tfh) cells are a subset of CD4+ T cells essential in immunity and have a role in helping B cells produce antibodies against pathogens. However, their role during cancer progression remains unknown. The mechanism of action of Tfh cells remains elusive because contradictory data have been reported on their protumor or antitumor responses in human and murine tumors.

T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19.

Background: T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated.

Methods: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID-19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40-parameter mass cytometry, targeted proteomics, and functional assays.

Single-cell proteomics defines the cellular heterogeneity of localized prostate cancer.

Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.

How are randomized clinical trials ethically justified? A systematic scoping review and thematic analysis of reasons that ethically justify randomized clinical trials.

Objectives: We set out to identify and count the types of reasons that are used in contemporary scholarship about the ethical permissibility of randomized trials, with the goal of developing a finer grained taxonomy of reasons than what is currently used by most participants in this literature. Because of its central role in justifying normative conclusions about randomized clinical trials (RCTs), we paid particular attention to both uses of the keyword "equipoise" and to the different concepts associated with it.

Methods: We conducted a scoping review to identify articles that included arguments that were likely to express reasons justifying RCTs.

MER4 endogenous retrovirus correlated with better efficacy of anti-PD1/PD-L1 therapy in non-small cell lung cancer.

Background: Endogenous retroviruses (ERVs) are highly expressed in various cancer types and are associated with increased innate immune response and better efficacy of antiprogrammed death-1/ligand-1 (anti-PD1/PD-L1)-directed immune checkpoint inhibitors (ICI) in preclinical models. However, their role in human non-small cell lung cancer (NSCLC) remains unknown.

Methods: We conducted a retrospective study of patients receiving ICI for advanced NSCLC in two independent cohorts.

Custom multi‑tumor next‑generation sequencing panel for routine molecular diagnosis of solid tumors: Validation and results from three‑year clinical use.

Molecular testing is extremely important in cancer care, starting as early as at diagnosis. In order to address the challenge of providing reliable results within the timeframe adapted to patient management and suitable to guide clinical decisions, a capture‑based next‑generation sequencing (NGS) panel focusing on ten genes known to harbor genetic variations which may be targeted by approved drugs in patients with cancer was designed and validated. Very favorable analytical performances were obtained for both solid and liquid biopsies.

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer.

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk.

A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota.

Unlabelled: Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC.

Clinical value of serology for the diagnosis of strongyloidiasis in travelers and migrants: A 4-year retrospective study using the Bordier IVD Strongyloides ratti ELISA assay.

Strongyloides stercoralis serology is a sensitive method for strongyloidiasis diagnosis, but it is prone to cross-reactions with other helminthiases. This four-year retrospective study aimed at estimating the performance of the Bordier IVD Strongyloides ratti ELISA assay in a non-endemic country (France). The study included all patients tested for strongyloidiasis in our center between 2015 and 2019, by both serology and stool examination.

Predictors of methacholine challenge testing results in subjects without airflow obstruction.

Objective: Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEV (PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry.

Does large NGS panel analysed using exome tumour sequencing improve the management of advanced non-small-cell lung cancers?

Introduction: Non-small-cell lung cancer (NSCLC) is one of the most common and deadly cancers. Several molecular drivers of oncogene addiction are now known to be strong predictive biomarkers for target therapies. Advances in large Next Generation Sequencing (LNGS) have improved the ability to detect potentially targetable mutations.

An Algorithm Combining Patient Performance Status, Second Hit Analysis, PROVEAN and Dann Prediction Tools Could Foretell Sensitization to PARP Inhibitors in Digestive, Skin, Ovarian and Breast Cancers.

PARP inhibitors yield interesting outcomes for patients with ovarian tumors harboring or mutation, but also with other tumors with homologous repair (HR) deficiency. About 40% of variants are variants of unknown significance (VUS), blocking the use of PARP inhibitors. In this study, we analyzed NGS data from 78 metastatic patients treated with PARP inhibitors.

Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID-19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill-defined in COVID-19.

A distinct innate immune signature marks progression from mild to severe COVID-19.

Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Here, we use mass cytometry and targeted proteomics to profile the innate immune response of patients with mild or severe COVID-19 and of healthy individuals. Sampling at different stages allows us to reconstruct a pseudo-temporal trajectory of the innate response.