MAPK mutations and cigarette smoke promote the pathogenesis of pulmonary Langerhans cell histiocytosis.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare smoking-related lung disease characterized by dendritic cell (DC) accumulation, bronchiolocentric nodule formation, and cystic lung remodeling. Approximately 50% of patients with PLCH harbor somatic BRAF-V600E mutations in cells of the myeloid/monocyte lineage. However, the rarity of the disease and lack of animal models have impeded the study of PLCH pathogenesis.

The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence.

Background: Participation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e.

Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee.

We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies.

Nonionotropic Action of Endothelial NMDA Receptors on Blood-Brain Barrier Permeability via Rho/ROCK-Mediated Phosphorylation of Myosin.

Increase in blood-brain barrier (BBB) permeability is a crucial step in neuroinflammatory processes. We previously showed that N Methyl D Aspartate Receptor (NMDARs), expressed on cerebral endothelial cells forming the BBB, regulate immune cell infiltration across this barrier in the mouse. Here, we describe the mechanism responsible for the action of NMDARs on BBB permeabilization.

Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia.

Background: In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti-CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy.

Procedure: This international, multicenter, phase 2 study enrolled children with relapsed/refractory B-cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21-day cycle.

Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children.

Background: Montelukast, a potent oral selective leukotriene-receptor antagonist, inhibits the action of cysteinyl-leukotriene in patients with asthma. Although pharmacokinetic studies of montelukast have been reported in Caucasian adults and children, and showed large inter-individual variability on pharmacokinetics, none of these studies has been explored in Chinese children. Given the potential inter-ethnic difference, the purpose of the present study was to evaluate the effects of developmental factors and pharmacogenetics of CYP2C8 and SLCO2B1 on montelukast clearance in Chinese pediatric patients.

Perceptions of artificial intelligence in healthcare: findings from a qualitative survey study among actors in France.

Background: Artificial intelligence (AI), with its seemingly limitless power, holds the promise to truly revolutionize patient healthcare. However, the discourse carried out in public does not always correlate with the actual impact. Thus, we aimed to obtain both an overview of how French health professionals perceive the arrival of AI in daily practice and the perception of the other actors involved in AI to have an overall understanding of this issue.

Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients.

Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012.

Blinatumomab vs historic standard-of-care treatment for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukaemia.

Objectives: Survival outcomes from a single-arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set.

Methods: The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10 ). Relapse-free survival (RFS) and overall survival (OS) were compared between blinatumomab- and SOC-treatment groups.

Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib monotherapy: Analysis from phase 2 and 3 clinical trials.

Background: Previous analyses of BREAK-2 and BREAK-3 showed that durable outcomes lasting ≥3 years are achievable with dabrafenib in some patients with BRAF V600-mutant metastatic melanoma (MM); however, additional follow-up is needed to fully characterise the long-term impact of dabrafenib in these patients.

Methods: BREAK-2 was a single-arm phase 2 study evaluating dabrafenib in treatment-naive or previously treated BRAF V600E/K-mutant MM. BREAK-3, a randomised (3:1) phase 3 study, assessed dabrafenib versus dacarbazine in previously untreated unresectable or metastatic BRAF V600E-mutant melanoma.

ShiF acts as an auxiliary factor of aerobactin secretion in meningitis Escherichia coli strain S88.

Background: The neonatal meningitis E. coli (NMEC) strain S88 carries a ColV plasmid named pS88 which is involved in meningeal virulence. Transcriptional analysis of pS88 in human serum revealed a strong upregulation of an ORF of unknown function: shiF, which is adjacent to the operon encoding the siderophore aerobactin.

The flanking peptides issue from the maturation of the human islet amyloid polypeptide (hIAPP) slightly modulate hIAPP-fibril formation but not hIAPP-induced cell death.

Type 2 diabetes mellitus is a disease characterized by the formation of amyloid fibrillar deposits consisting mainly in human islet amyloid polypeptide (hIAPP), a peptide co-produced and co-secreted with insulin. hIAPP and insulin are synthesized by pancreatic β cells initially as prehormones resulting after sequential cleavages in the mature peptides as well as the two flanking peptides (N- and C-terminal) and the C-peptide, respectively. It has been suggested that in the secretory granules, the kinetics of hIAPP fibril formation could be modulated by some internal factors.

Physical and Functional Cross Talk Between Endo-Sarcoplasmic Reticulum and Mitochondria in Skeletal Muscle.

The physiological relevance of contacts between the sarcoplasmic reticulum (SR), a specialized domain of the endoplasmic reticulum (ER) in skeletal muscle, and mitochondria is still not clear. An extensive close proximity of these two organelles is a late developmental event, which suggests that it does not have an essential function. The intimate association of SR/mitochondria develops during murine postnatal differentiation and the recovery of denervated atrophic muscle, which suggests that this is a highly regulated process with a specific function.

Quantification of hepatic steatosis with ultrasound: promising role of attenuation imaging coefficient in a biopsy-proven cohort.

Objectives: To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis.

Methods: One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S0 < 5%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S3 > 66%); liver fibrosis was graded from F0 to F4.

Environmental mitigation hierarchy and biodiversity offsets revisited through habitat connectivity modelling.

Biodiversity loss is accelerating because of unceasing human activity and land clearing for development projects (urbanisation, transport infrastructure, mining and quarrying …). Environmental policy-makers and managers in different countries worldwide have proposed the mitigation hierarchy to ensure the goal of "no net loss (NNL) of biodiversity" and have included this principle in environmental impact assessment processes. However, spatial configuration is hardly ever taken into account in the mitigation hierarchy even though it would greatly benefit from recent developments in habitat connectivity modelling incorporating landscape graphs.

REVIEW: MR elastography of brain tumors.

MR elastography allows non-invasive quantification of the shear modulus of tissue, i.e. tissue stiffness and viscosity, information that offers the potential to guide presurgical planning for brain tumor resection.

Rare Solid Tumor of the Exocrine Pancreas: A Pictorial Review.

Numerous other solid primary neoplasms may arise from the pancreas besides primary ductal adenocarcinomas and neuroendocrine tumors. Although diagnosis can be difficult because of the very low incidence of these tumors, knowledge of several, typical, epidemiologic, biological, and imaging features can help obtain a correct diagnosis. This pictorial review describes the features of solid rare primary pancreatic neoplasms on computed tomography and magnetic resonance imaging focusing on characteristics that can help radiologists differentiate them from classical forms of ductal pancreatic adenocarcinoma and neuroendocrine tumors.

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.

Background: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.

Complications of hepatic echinococcosis: multimodality imaging approach.

Hydatid disease is a worldwide zoonosis endemic in many countries. Liver echinococcosis accounts for 60-75% of cases and may be responsible for a wide spectrum of complications in about one third of patients. Some of these complications are potentially life-threatening and require prompt diagnosis and urgent intervention.

Role of the intestinal microbiome in colorectal cancer surgery outcomes.

Objectives: Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery.

Methods: A systematic review was conducted according to the 2009 PRISMA guidelines.