Comparison of the hemoglobin variability in non-chronic kidney disease or end-stage renal disease participants and patients with CKD and ESRD.

Introduction: Hemoglobin (Hb) variability occurs frequently in hemodialysis (HD) patients during erythropoietin (EPO) therapy. Guidelines define a narrow target range for the anemia treatment in these patients that is difficult to adhere to in practice. Our aim was to evaluate whether the Hb variability in HD patients is higher compared to non-chronic kidney disease or end-stage renal disease (ESRD) participants and patients with CKD stage I or II.

Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.

The leukotriene (LT) pathway is positively correlated with the progression of solid malignancies, but the factors that control the expression of 5-lipoxygenase (5-LO), the central enzyme in LT biosynthesis, in tumors are poorly understood. Here, we report that 5-LO along with other members of the LT pathway is up-regulated in multicellular colon tumor spheroids. This up-regulation was inversely correlated with cell proliferation and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways.

Knock-out of 5-lipoxygenase in overexpressing tumor cells-consequences on gene expression and cellular function.

5-Lipoxygenase (5-LO), the central enzyme in the biosynthesis of leukotrienes, is frequently expressed in human solid malignancies even though the enzyme is not present in the corresponding healthy tissues. There is little knowledge on the consequences of this expression for the tumor cells regarding gene expression and cellular function. We established a knockout (KO) of 5-LO in different cancer cell lines (HCT-116, HT-29, U-2 OS) and studied the consequences on global gene expression using next generation sequencing.

Predicting genes associated with RNA methylation pathways using machine learning.

RNA methylation plays an important role in functional regulation of RNAs, and has thus attracted an increasing interest in biology and drug discovery. Here, we collected and collated transcriptomic, proteomic, structural and physical interaction data from the Harmonizome database, and applied supervised machine learning to predict novel genes associated with RNA methylation pathways in human. We selected five types of classifiers, which we trained and evaluated using cross-validation on multiple training sets.

Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia.

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity.

Novel Insights into Quantitative Proteomics from an Innovative Bottom-Up Simple Light Isotope Metabolic (bSLIM) Labeling Data Processing Strategy.

Simple light isotope metabolic labeling (SLIM labeling) is an innovative method to quantify variations in the proteome based on an original labeling strategy. Heterotrophic cells grown in U-[C] as the sole source of carbon synthesize U-[C]-amino acids, which are incorporated into proteins, giving rise to U-[C]-proteins. This results in a large increase in the intensity of the monoisotope ion of peptides and proteins, thus allowing higher identification scores and protein sequence coverage in mass spectrometry experiments.

Evaluation of dried blood spots as alternative sampling material for serological detection of anti-SARS-CoV-2 antibodies using established ELISAs.

Objectives: During the current pandemic, antibody testing based on venous serum helps to determine whether the tested person has been previously infected with SARS-CoV-2. Alternatively, capillary blood can be taken via a finger prick (dried blood spots, DBS). In this study, paired DBS and venipuncture samples were tested using two serological assays to evaluate the usability of DBS for the detection of anti-SARS-CoV-2 antibodies.

Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites.

Red blood cell (RBC) invasion by merozoites requires multiple steps that are regulated by signaling pathways. Exposure of merozoites to the physiological signal of low K, as found in blood plasma, leads to a rise in cytosolic Ca, which mediates microneme secretion, motility, and invasion. We have used global phosphoproteomic analysis of merozoites to identify signaling pathways that are activated during invasion.

Genome-wide investigation of gene-cancer associations for the prediction of novel therapeutic targets in oncology.

A major cause of failed drug discovery programs is suboptimal target selection, resulting in the development of drug candidates that are potent inhibitors, but ineffective at treating the disease. In the genomics era, the availability of large biomedical datasets with genome-wide readouts has the potential to transform target selection and validation. In this study we investigate how computational intelligence methods can be applied to predict novel therapeutic targets in oncology.

A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry.

The field of epitranscriptomics continues to reveal how post-transcriptional modification of RNA affects a wide variety of biological phenomena. A pivotal challenge in this area is the identification of modified RNA residues within their sequence contexts. Mass spectrometry (MS) offers a comprehensive solution by using analogous approaches to shotgun proteomics.

Evaluation of a Dual Isolation Width Acquisition Method for Isobaric Labeling Ratio Decompression.

Isobaric labeling is a highly precise approach for protein quantification. However, due to the isolation interference problem, isobaric tagging suffers from ratio underestimation at the MS2 level. The use of narrow isolation widths is a rational approach to alleviate the interference problem; however, this approach compromises proteome coverage.

Targeted Feature Detection for Data-Dependent Shotgun Proteomics.

Label-free quantification of shotgun LC-MS/MS data is the prevailing approach in quantitative proteomics but remains computationally nontrivial. The central data analysis step is the detection of peptide-specific signal patterns, called features. Peptide quantification is facilitated by associating signal intensities in features with peptide sequences derived from MS2 spectra; however, missing values due to imperfect feature detection are a common problem.

Flexible Data Analysis Pipeline for High-Confidence Proteogenomics.

Proteogenomics leverages information derived from proteomic data to improve genome annotations. Of particular interest are "novel" peptides that provide direct evidence of protein expression for genomic regions not previously annotated as protein-coding. We present a modular, automated data analysis pipeline aimed at detecting such "novel" peptides in proteomic data sets.

OpenMS: a flexible open-source software platform for mass spectrometry data analysis.

High-resolution mass spectrometry (MS) has become an important tool in the life sciences, contributing to the diagnosis and understanding of human diseases, elucidating biomolecular structural information and characterizing cellular signaling networks. However, the rapid growth in the volume and complexity of MS data makes transparent, accurate and reproducible analysis difficult. We present OpenMS 2.

Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow.

Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models.

Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants.

Expression Atlas (http://www.ebi.ac.

Prediction of colorectal cancer diagnosis based on circulating plasma proteins.

Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins.

Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis.

Phosphoproteomics studies have unraveled the extent of protein phosphorylation as a key cellular regulation mechanism, but assigning functionality to specific phosphorylation events remains a major challenge. TORC1 (target of rapamycin complex 1) is a kinase-containing protein complex that transduces changes in nutrient availability into phosphorylation signaling events that alter cell growth and proliferation. To resolve the temporal sequence of phosphorylation responses to nutritionally and chemically induced changes in TORC1 signaling and to identify previously unknown kinase-substrate relationships in Saccharomyces cerevisiae, we performed quantitative mass spectrometry-based phosphoproteomic analyses after shifts in nitrogen sources and rapamycin treatment.

Surgical intervention of pilonidal sinus: impact on patients' postoperative satisfaction and return to work time.

Background: Pilonidal sinus (PS) is a chronic inflammatory process accompanied by psychological strain and a high rate of work incapacity.

Objectives: To analyze the impact of PS surgery on individual patients' satisfaction (SAT) and economic impacts on work capability.

Patients And Methods: We retrospectively analyzed 40 PS patients regarding SAT and return to work time (RTW) in relation to various factors, using multivariate analysis and Pearson's correlation test.

An automated pipeline for high-throughput label-free quantitative proteomics.

We present a computational pipeline for the quantification of peptides and proteins in label-free LC-MS/MS data sets. The pipeline is composed of tools from the OpenMS software framework and is applicable to the processing of large experiments (50+ samples). We describe several enhancements that we have introduced to OpenMS to realize the implementation of this pipeline.

Streptococcus pyogenes in human plasma: adaptive mechanisms analyzed by mass spectrometry-based proteomics.

Streptococcus pyogenes is a major bacterial pathogen and a potent inducer of inflammation causing plasma leakage at the site of infection. A combination of label-free quantitative mass spectrometry-based proteomics strategies were used to measure how the intracellular proteome homeostasis of S. pyogenes is influenced by the presence of human plasma, identifying and quantifying 842 proteins.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

Background: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin.

Methods: Consecutive patients scheduled for surgery were prospectively enrolled in this study.

Intracranial impalement with entrance site in the mandibular region: postmortem elucidation of an accidental fall on a wooden plant stick.

A 78-year-old woman with a history of transient ischemic attacks was found in the doorway of her house in a somnolent and unresponsive condition. In the right mandibular region, a small skin wound was localized, which was surgically treated. Six days after admission to the hospital, an exploratory craniotomy was performed because of abnormal CT findings.

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment.