Impaired Awareness in People with Severe Alcohol-Related Cognitive Deficits Including Korskoff's Syndrome: A Network Analysis.

Background: Impaired awareness of one's own functioning is highly common in people with Korsakoff's syndrome (KS). However, it is currently unclear how awareness relates to impairments in daily functioning and quality of life (QoL).

Methods: We assessed how impaired awareness relates to cognitive, behavioral, physical, and social functioning and QoL by applying a network analysis.

Penalized estimation of the Gaussian graphical model from data with replicates.

Gaussian graphical models are usually estimated from unreplicated data. The data are, however, likely to comprise signal and noise. These two cannot be deconvoluted from unreplicated data.

C1 Inhibitor Administration Reduces Local Inflammation and Capillary Leakage, Without Affecting Long-term Wound Healing Parameters, in a Pig Burn Wound Model.

Background: Burns induce a boost in local and systemic complement levels as well as immune cell infiltration in the burn wound, which may negatively affect wound healing.

Objective: In this study, the effects of long-term treatment with complement inhibitor C1 esterase inhibitor (C1inh) on post-burn inflammation and wound healing parameters were analyzed in time up to 60 days post-burn.

Methods: Burned pigs were treated either with or without C1inh up to 15 days post-burn.

Mechanical stress regulates bone regulatory gene expression independent of estrogen and vitamin D deficiency in rats.

Mechanical stress determines bone mass and structure. It is not known whether mechanical loading affects expression of bone regulatory genes in a combined deficiency of estrogen and vitamin D. We studied the effect of mechanical loading on the messenger RNA (mRNA) expression of bone regulatory genes during vitamin D and/or estrogen deficiency.

Identification of Deregulated Pathways, Key Regulators, and Novel miRNA-mRNA Interactions in HPV-Mediated Transformation.

Next to a persistent infection with high-risk human papillomavirus (HPV), molecular changes are required for the development of cervical cancer. To identify which molecular alterations drive carcinogenesis, we performed a comprehensive and longitudinal molecular characterization of HPV-transformed keratinocyte cell lines. Comparative genomic hybridization, mRNA, and miRNA expression analysis of four HPV-containing keratinocyte cell lines at eight different time points was performed.

NOX2 Expression Is Increased in Keratinocytes After Burn Injury.

Reepithelialization is crucial for effective wound repair in burn wounds. Reactive oxygen species (ROS) have shown to be important in this. Recent studies suggest that NOX proteins produce ROS in keratinocytes.

Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice.

Background: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model.

No Plasmatic Proteomic Signature at Clinical Disease Onset Associated With 11 Year Clinical, Cognitive and MRI Outcomes in Relapsing-Remitting Multiple Sclerosis Patients.

The clinical course of relapsing-remitting multiple sclerosis (RRMS) is highly heterogeneous and prognostic biomarkers at time of diagnosis are lacking. We investigated the predictive value of the plasma proteome at time of diagnosis in RRMS patients. The plasma proteome was interrogated using a novel aptamer-based proteomics platform, which allows to measure the levels of a predefined set of 1310 proteins.

Ridge estimation of network models from time-course omics data.

Time-course omics experiments enable the reconstruction of the dynamics of the cellular regulatory network. Here, we describe the means for this reconstruction and the downstream exploitation of the inferred network. It is assumed that one of the various vector-autoregressive models (VAR) models presented here serves as a reasonably accurate description of the time-course omics data.

Rscreenorm: normalization of CRISPR and siRNA screen data for more reproducible hit selection.

Background: Reproducibility of hits from independent CRISPR or siRNA screens is poor. This is partly due to data normalization primarily addressing technical variability within independent screens, and not the technical differences between them.

Results: We present "rscreenorm", a method that standardizes the functional data ranges between screens using assay controls, and subsequently performs a piecewise-linear normalization to make data distributions across all screens comparable.

Reconstruction of molecular network evolution from cross-sectional omics data.

Cross-sectional studies may shed light on the evolution of a disease like cancer through the comparison of patient traits among disease stages. This problem is especially challenging when a gene-gene interaction network needs to be reconstructed from omics data, and, in addition, the patients of each stage need not form a homogeneous group. Here, the problem is operationalized as the estimation of stage-wise mixtures of Gaussian graphical models (GGMs) from high-dimensional data.

Prognostic modeling of oral cancer by gene profiles and clinicopathological co-variables.

Accurate staging and outcome prediction is a major problem in clinical management of oral cancer patients, hampering high precision treatment and adjuvant therapy planning. Here, we have built and validated multivariable models that integrate gene signatures with clinical and pathological variables to improve staging and survival prediction of patients with oral squamous cell carcinoma (OSCC). Gene expression profiles from 249 human papillomavirus (HPV)-negative OSCCs were explored to identify a 22-gene lymph node metastasis signature (LNMsig) and a 40-gene overall survival signature (OSsig).

4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System.

4H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0-54) was developed to quantify hypomyelination and atrophy of different brain regions.

The Local and Systemic Inflammatory Response in a Pig Burn Wound Model With a Pivotal Role for Complement.

In patients with burns, a massive inflammatory response is induced which negatively affects the healing process of the burn wound and additionally exerts systemic effects. An important factor herein is the complement system. Here we analyzed the effects of burns on complement and inflammatory cells both locally and systemically after burn in time in a pig burn wound model.

Gene Network Reconstruction using Global-Local Shrinkage Priors.

Reconstructing a gene network from high-throughput molecular data is an important but challenging task, as the number of parameters to estimate easily is much larger than the sample size. A conventional remedy is to regularize or penalize the model likelihood. In network models, this is often done in the neighbourhood of each node or gene.

An empirical Bayes approach to network recovery using external knowledge.

Reconstruction of a high-dimensional network may benefit substantially from the inclusion of prior knowledge on the network topology. In the case of gene interaction networks such knowledge may come for instance from pathway repositories like KEGG, or be inferred from data of a pilot study. The Bayesian framework provides a natural means of including such prior knowledge.

Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.

Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with Re in prostate carcinoma cell lines.

Ridge estimation of the VAR(1) model and its time series chain graph from multivariate time-course omics data.

Omics experiments endowed with a time-course design may enable us to uncover the dynamic interplay among genes of cellular processes. Multivariate techniques (like VAR(1) models describing the temporal and contemporaneous relations among variates) that may facilitate this goal are hampered by the high-dimensionality of the resulting data. This is resolved by the presented ridge regularized maximum likelihood estimation procedure for the VAR(1) model.

Quantitative MRI in hypomyelinating disorders: Correlation with motor handicap.

Objective: To assess the correlation of tissue parameters estimated by quantitative magnetic resonance (MR) techniques and motor handicap in patients with hypomyelination.

Methods: Twenty-eight patients with different causes of hypomyelination (12 males, 16 females; mean age 10 years) and 61 controls (33 males, 28 females; mean age 8 years) were prospectively investigated. We quantified T2 relaxation time, magnetization transfer ratio, fractional anisotropy, mean, axial, and radial diffusivities, and brain metabolites.

Distinguishing Three Unprofessional Behavior Profiles of Medical Students Using Latent Class Analysis.

Purpose: Because unprofessional behavior of physicians is associated with unprofessional behavior in medical school, identifying unprofessional behavior in medical school is critical. Research has noted the difficulty in assessing professional behavior. Instead of identifying isolated behaviors, it could be more helpful to recognize behavioral patterns to evaluate students' professional behavior.

Transcriptomic Heterogeneity in Cancer as a Consequence of Dysregulation of the Gene-Gene Interaction Network.

Many pathways are dysregulated in cancer. Dysregulation of the regulatory network results in less control of transcript levels in the cell. Hence, dysregulation is reflected in the heterogeneity of the transcriptome: the more dysregulated the pathway, the more the transcriptomic heterogeneity.

Better prediction by use of co-data: adaptive group-regularized ridge regression.

For many high-dimensional studies, additional information on the variables, like (genomic) annotation or external p-values, is available. In the context of binary and continuous prediction, we develop a method for adaptive group-regularized (logistic) ridge regression, which makes structural use of such 'co-data'. Here, 'groups' refer to a partition of the variables according to the co-data.

tigaR: integrative significance analysis of temporal differential gene expression induced by genomic abnormalities.

Background: To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.