Surrogate Modeling for Bayesian Optimization Beyond a Single Gaussian Process.

Bayesian optimization (BO) has well-documented merits for optimizing black-box functions with an expensive evaluation cost. Such functions emerge in applications as diverse as hyperparameter tuning, drug discovery, and robotics. BO hinges on a Bayesian surrogate model to sequentially select query points so as to balance exploration with exploitation of the search space.

Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.

Aims: Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation.

Disruption of GPR35 Signaling in Bone Marrow-Derived Cells Does Not Influence Vascular Inflammation and Atherosclerosis in Hyperlipidemic Mice.

G-protein-coupled receptor-35 (GPR35) has been identified as a receptor for the tryptophan metabolite kynurenic acid (KynA) and suggested to modulate macrophage polarization in metabolic tissues. Whether GPR35 can influence vascular inflammation and atherosclerosis has however never been tested. Lethally irradiated mice were randomized to receive or wild type (WT) bone marrow transplants and fed a high cholesterol diet for eight weeks to develop atherosclerosis.

Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans.

Background: The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this pathway is a major regulator of vascular inflammation and influences atherogenesis. Knowledge of the role of this pathway in human atherosclerosis remains incomplete.

Simultaneous Diagnosis of Emphysematous Osteomyelitis and Emphysematous Pyelonephritis in a Diabetic Patient.

BACKGROUND Emphysematous osteomyelitis of the spine is characterized by intravertebral or intraosseous air. Emphysematous pyelonephritis (EP) is the infection of the renal parenchyma and perirenal tissues caused by gas forming microorganisms and thus is characterized by gas formation. Prompt diagnosis and initiation of necessary treatment is crucial, as both entities are associated with high mortality rates.

3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr-/- mice.

Aims: Atherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism.

Clinical Influence of Ploidy and Cancer Stem Cells and Other Parameters in Stage IV Colorectal Cancer.

Background/aim: The aim of the present study was the evaluation of the influence of cancer stem cells and other parameters in stage IV colorectal cancer patients.

Materials And Methods: One hundred patients were retrospectively included in the study and 24 variables were examined for their relation with response to treatment and survival.

Results: A low ploidy score in the histology of colorectal cancer was associated with improvement of performance status and response to therapy.

Acute Loss of Apolipoprotein E Triggers an Autoimmune Response That Accelerates Atherosclerosis.

Objective- Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. Approach and Results- We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse.

Activation of the Regulatory T-Cell/Indoleamine 2,3-Dioxygenase Axis Reduces Vascular Inflammation and Atherosclerosis in Hyperlipidemic Mice.

T-cell activation is characteristic during the development of atherosclerosis. While overall T-cell responses have been implicated in disease acceleration, regulatory T cells (Tregs) exhibit atheroprotective effects. The expression of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), which catalyzes the degradation of tryptophan (Trp) along the kynurenine pathway, has been implicated in the induction and expansion of Treg populations.

Hypercholesterolemia Enhances T Cell Receptor Signaling and Increases the Regulatory T Cell Population.

Hypercholesterolemia promotes the inflammation against lipoproteins in atherosclerosis. Development of atherosclerosis is affected by the balance between pro-inflammatory effector T cells and anti-inflammatory regulatory T (Treg) cells. However, phenotype and function of T cell subpopulations in hypercholesterolemia remain to be investigated.

The inflammatory cytokine interferon-gamma inhibits sortilin-1 expression in hepatocytes via the JAK/STAT pathway.

Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear.

Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.

Rationale: The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T-cell differentiation remains unknown.

Gentamicin-Collagen Sponges for the Prevention of Surgical Site Infections: A Meta-Analysis of Randomized Controlled Trials.

Background: To study the effectiveness of gentamicin-collagen sponges (GCS) for the prevention of surgical site infections (SSIs).

Methods: A systematic search of the PubMed and Scopus databases was performed (up to April 2015) to identify randomized controlled trials evaluating the efficacy of GCS for the prevention of SSIs. A random effects model was applied.

Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells.

Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, HCMV infection increased the efflux of cellular cholesterol, despite reducing the abundance of ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association of actin with lipid rafts, and leading to a dramatic change in the abundance and/or structure of lipid rafts.

Atherosclerosis Susceptibility in Mice Is Independent of the V1 Immunoglobulin Heavy Chain Gene.

Objective: The V1 (VHS107.1.42) immunoglobulin heavy chain gene is thought to be critical in producing IgM natural antibodies of the T15-idiotype that protect against both atherosclerosis and infection from Streptococcus pneumoniae.

Maternal Influenza Vaccination and Risk for Congenital Malformations: A Systematic Review and Meta-analysis.

Objective: To systematically summarize the literature on maternal influenza vaccination and the risk for congenital malformations using the methodology of meta-analysis.

Data Sources: PubMed, Scopus, and Embase databases (up to December 2014) as well as ClinicalTrials.gov (May 2015) and references of relevant articles were searched.

Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis.

Infectious complications after cardiac implantable electronic device (CIED) implantation are increasing over time and are associated with substantial mortality and healthcare costs. The aim of this study was to systematically summarize the literature on risk factors for infection after pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantation. Electronic searches (up to January 2014) were performed in PubMed, Scopus, and Web of Science databases.

Antimicrobial-impregnated and -coated shunt catheters for prevention of infections in patients with hydrocephalus: a systematic review and meta-analysis.

OBJECT The aim of this study was to evaluate the effectiveness of antimicrobial-impregnated and -coated shunt catheters (antimicrobial catheters) in reducing the risk of infection in patients undergoing CSF shunting or ventricular drainage. METHODS The PubMed and Scopus databases were searched. Catheter implantation was classified as either shunting (mainly ventriculoperitoneal shunting) or ventricular drainage (mainly external [EVD]).

Inhibition of indoleamine 2,3-dioxygenase promotes vascular inflammation and increases atherosclerosis in Apoe-/- mice.

Aims: Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of low-density lipoprotein in the artery, leading to maladaptive response of cells from the immune system and vessel wall. Strong evidence implicates indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the kynurenine pathway of tryptophan (Trp) degradation, with immune regulation and anti-inflammatory mechanisms in different diseases. However, the role of IDO and the endogenous degradation of Trp have never been directly examined in atherosclerosis development.

The role of the kynurenine pathway of tryptophan metabolism in cardiovascular disease. An emerging field.

Coronary heart disease and stroke, the deadliest forms of cardiovascular disease (CVD), are mainly caused by atherosclerosis, a chronic inflammatory disease of the artery wall driven by maladaptive immune responses in the vessel wall. Various risk factors for CVD influence this pathogenic process, including diabetes mellitus, hypertension, dyslipidaemia, and obesity. Indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing the rate-limiting step in the kynurenine pathway of tryptophan degradation, is strongly induced by inflammation in several tissues, including the artery wall.

The level of endotoxemia in sepsis varies in relation to the underlying infection: Impact on final outcome.

Former studies of our group have shown that the innate and adaptive immune status may differ in relation with the causative infection. To this same end, it was investigated if kinetics of circulating lipopolysaccharide (LPS) leading to inflammatory response may differ. Blood was sampled from 189 patients with sepsis and 206 with severe sepsis/shock starting 24h from advent of sepsis and repeating on day 3.

Modified docetaxel-cisplatin in combination with capecitabine as first-line treatment in metastatic gastric cancer. a phase II study.

The combination of docetaxel, cisplatin and fluorouracil is considered to be one of the reference regimens for advanced gastric cancer, but due to its major myelotoxicity, its use in clinical practice has become limited. This prospective phase II study evaluated the activity and toxicity of a modified regimen with lower doses of docetaxel and cisplatin combined with oral capecitabine instead of fluorouracil for patients with advanced gastric cancer. Treatment consisted of docetaxel at 60 mg/m(2) i.

Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis.

Introduction: The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens.

Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence.

The objective of this review was to evaluate the frequency of treatment failure and recurrence of Clostridium difficile infection (CDI) following treatment with vancomycin or metronidazole in recently performed studies (last 10 years). Searches in PubMed and Scopus were performed by two reviewers independently. Data regarding treatment failure and recurrence following metronidazole and vancomycin treatment were extracted and analysed.