Tim-3 Expression on Tumor-Infiltrating PD-1CD8 T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma.

Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8 T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry.

LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion.

Multiple imputation by chained equations for systematically and sporadically missing multilevel data.

In multilevel settings such as individual participant data meta-analysis, a variable is 'systematically missing' if it is wholly missing in some clusters and 'sporadically missing' if it is partly missing in some clusters. Previously proposed methods to impute incomplete multilevel data handle either systematically or sporadically missing data, but frequently both patterns are observed. We describe a new multiple imputation by chained equations (MICE) algorithm for multilevel data with arbitrary patterns of systematically and sporadically missing variables.

Identification of Multiple Gene Mutations Accounts for a new Genetic Architecture of Primary Ovarian Insufficiency.

Context: Idiopathic primary ovarian insufficiency (POI) is a major cause of amenorrhea and infertility. POI affects 1% of women before age 40 years, and several genetic causes have been reported. To date, POI has been considered a monogenic disorder.

Fluorescence in situ hybridization of Microcystis strains producing microcystin using specific mRNA probes.

Unlabelled: Cyanobacteria are ubiquitous micro-organisms that can produce toxic compounds, the cyanotoxins. The monitoring of such producers in the environment is of prime importance for human health. An attractive technology for such monitoring is fluorescence in situ hybridization (FISH), which allows the detection and enumeration of environmental micro-organisms.

Exclusion of Patients with a Severe T-Cell Defect Improves the Definition of Common Variable Immunodeficiency.

Background: In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients.

Objective: The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia.

Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.

Unlabelled: Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects.

Hepatitis E virus antibody prevalence, RNA frequency, and genotype among blood donors in Cambodia (Southeast Asia).

Background: Recent studies conducted in developed countries described hepatitis E virus (HEV) as an emerging infectious threat to blood safety. However, data on HEV among blood donors from southeast Asia are lacking.

Study Design And Methods: Between July and August 2014, we assessed the presence of HEV immunoglobulin (Ig)G and IgM in 301 Cambodian blood donors.

ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects.

Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex.

[Sinonasal fungal infections are not exclusively due to mucorales and Aspergillus!].

Rhino-sinusal infections are serious diseases and possibly lethal. When they are invasive, we easily discuss apergilloses and mucormycoses. The confirmation of the diagnosis of mucormycosis need an extensive surgery for precise histopathological and mycological evaluation.

Genomic Copy Number Profiling Using Circulating Free Tumor DNA Highlights Heterogeneity in Neuroblastoma.

Purpose: The tumor genomic copy number profile is of prognostic significance in neuroblastoma patients. We have studied the genomic copy number profile of cell-free DNA (cfDNA) and compared this with primary tumor arrayCGH (aCGH) at diagnosis.

Experimental Design: In 70 patients, cfDNA genomic copy number profiling was performed using the OncoScan platform.

Medical complications following splenectomy.

Splenectomy is attended by medical complications, principally infectious and thromboembolic; the frequency of complications varies with the conditions that led to splenectomy (hematologic splenectomy, trauma, presence of portal hypertension). Most infectious complications are caused by encapsulated bacteria (Meningococcus, Pneumococcus, Hemophilus). These occur mainly in children and somewhat less commonly in adults within the first two years following splenectomy.

Pseudopilin residue E5 is essential for recruitment by the type 2 secretion system assembly platform.

Type II secretion systems (T2SSs) promote secretion of folded proteins playing important roles in nutrient acquisition, adaptation and virulence of Gram-negative bacteria. Protein secretion is associated with the assembly of type 4 pilus (T4P)-like fibres called pseudopili. Initially membrane embedded, pseudopilin and T4 pilin subunits share conserved transmembrane segments containing an invariant Glu residue at the fifth position, E5.

[Chronic fatigue syndrome: A new disorder?].

More than 30 years after its individualization, chronic fatigue syndrome (CFS) remains a debilitating condition for the patient and a confusing one to the physicians, both because of diagnostic difficulties and poorly codified management. Despite the numerous work carried out, its pathophysiology remains unclear, but a multifactorial origin is suggested with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low grade inflammation, microglial activation…), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens…) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive…). The complexity of the problem and the sometimes contradictory results of available studies performed so far are at the origin of different pathophysiological and diagnostic concepts.

Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency.

Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries.

Unconventional High-Energy-State Contribution to the Cooper Pairing in the Underdoped Copper-Oxide Superconductor HgBa_{2}Ca_{2}Cu_{3}O_{8+δ}.

We study the temperature-dependent electronic B_{1g} Raman response of a slightly underdoped single crystal HgBa_{2}Ca_{2}Cu_{3}O_{8+δ} with a superconducting critical temperature T_{c}=122  K. Our main finding is that the superconducting pair-breaking peak is associated with a dip on its higher-energy side, disappearing together at T_{c}. This result reveals a key aspect of the unconventional pairing mechanism: spectral weight lost in the dip is transferred to the pair-breaking peak at lower energies.

[Negotiating knowledge and power: the National Policy for Comprehensive Men's Healthcare and the Brazilian Society of Urology].

The aim of this article is to demonstrate the negotiations and disputes between different kinds of knowledge and power in the history of the Brazilian National Policy for Comprehensive Men's Healthcare based on the creation in 2008 of the Technical Area for Men's Health within the Ministry of Health's Department of Strategic Programs. We observed the Brazilian Society of Urology's position as the policy was being drawn up, including the discourse adopted, based on interviews held with managers from the Ministry of Health and the assistant representative of the United Nations Population Fund in Brazil. We analyzed the visibility of the male body in signs of resistance to the interventions of biopower in the expression of the right to health.

Investigating covariate-by-centre interaction in survival data.

In survival analysis, assessing the existence of potential centre effects on the baseline hazard or on the effect of fixed covariates on the baseline hazard, such as treatment-by-centre interaction, is a frequent clinical concern in multicentre studies. Survival models with random effects on the baseline hazard and/or on the effect of the covariates of interest have been largely applied, for instance, to investigate potential centre effects. We aimed to develop a procedure to routinely test for multiple random effects in survival analyses.

Intertwined Multiple Spiral Fracture in Perforated Sheets.

We study multiple tearing of a thin, elastic, brittle sheet indented with a rigid cone. The n cracks initially prepared symmetrically propagate radially for n≥4. However, if n<4 the radial symmetry is broken and fractures spontaneously intertwine along logarithmic spiral paths, respecting order n rotational symmetry.