Ultrasensitive sequencing of STR markers utilizing unique molecular identifiers and the SiMSen-Seq method.

Massively parallel sequencing (MPS) is increasingly applied in forensic short tandem repeat (STR) analysis. The presence of stutter artefacts and other PCR or sequencing errors in the MPS-STR data partly limits the detection of low DNA amounts, e.g.

Realization of either physisorption or chemisorption of 2H-tetraphenylporphyrin on the Cu(111) from density functional theory.

The adsorption of organic molecules to surfaces is a central issue to achieve fully-functional molecular devices, for which porphyrins are well-studied due to their chemical stability and functional diversity. Herein, we investigate both the physical and the chemical adsorption of the free-base tetraphenylporphyrin 2H-TPP on the Cu(111) surface within the framework of density functional theory and find that the most stable physisorbed configuration is more weakly bound by -0.31 eV than the chemisorbed configuration.

Risk factors for and consequences of positive valve cultures in patients who undergo cardiac surgery while receiving antimicrobial treatment for infective endocarditis.

Introduction: Cardiac surgery is required in up to half of the patients with infective endocarditis (IE). Positive valve cultures have been associated with higher in-hospital mortality. The aims were to identify risk factors for positive valve cultures and its relation to outcome.

Clinical Significance of a 16S-rDNA Analysis of Heart Valves in Patients with Infective Endocarditis: a Retrospective Study.

A substantial proportion of patients with infective endocarditis (IE) are subjected to heart valve surgery. Microbiological findings on valves are important both for diagnostics and for tailored antibiotic therapy, post-operatively. The aims of this study were to describe microbiological findings on surgically removed valves and to examine the diagnostic benefits of 16S-rDNA PCR and sequencing (16S-analysis).

UMIErrorCorrect and UMIAnalyzer: Software for Consensus Read Generation, Error Correction, and Visualization Using Unique Molecular Identifiers.

Background: Targeted sequencing using unique molecular identifiers (UMIs) enables detection of rare variant alleles in challenging applications, such as cell-free DNA analysis from liquid biopsies. Standard bioinformatics pipelines for data processing and variant calling are not adapted for deep-sequencing data containing UMIs, are inflexible, and require multistep workflows or dedicated computing resources.

Methods: We developed a bioinformatics pipeline using Python and an R package for data analysis and visualization.

Oxygen-vacancy-induced magnetism in anti-perovskite topological Dirac semimetal BaSnO.

The thermodynamic, structural, magnetic and electronic properties of the pristine and intrinsic vacancy-defect-containing topological Dirac semimetal BaSnO are studied using first-principles density functional theory calculations. The thermodynamic stability of BaSnO has been evaluated with reference to its competing binary phases BaSn, BaSn and BaO. Subsequently, valid limits of the atomic chemical potentials derived from the thermodynamic stability were used for assessing the formation of Ba, Sn and O vacancy defects in BaSnO under different synthesis environments.

Monitoring Circulating Tumor DNA During Surgical Treatment in Patients with Gastrointestinal Stromal Tumors.

The majority of patients diagnosed with advanced gastrointestinal stromal tumors (GISTs) are successfully treated with a combination of surgery and tyrosine kinase inhibitors (TKIs). However, it remains challenging to monitor treatment efficacy and identify relapse early. Here, we utilized a sequencing strategy based on molecular barcodes and developed a GIST-specific panel to monitor tumor-specific and TKI resistance mutations in cell-free DNA and applied the approach to patients undergoing surgical treatment.

Differential role of cytosolic Hsp70s in longevity assurance and protein quality control.

70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones.

A MALT1 inhibitor suppresses human myeloid DC, effector T-cell and B-cell responses and retains Th1/regulatory T-cell homeostasis.

The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) regulates nuclear-factor-kappa-B (NF-κB) activation downstream of surface receptors with immunoreceptor tyrosine-based activation motifs (ITAMs), such as the B-cell or T-cell receptor and has thus emerged as a therapeutic target for autoimmune diseases. However, recent reports demonstrate the development of lethal autoimmune inflammation due to the excessive production of interferon gamma (IFN-ɣ) and defective differentiation of regulatory T-cells in genetically modified mice deficient in MALT1 paracaspase activity. To address this issue, we explored the effects of pharmacological MALT1 inhibition on the balance between T-effector and regulatory T-cells.

Ultrasensitive DNA Immune Repertoire Sequencing Using Unique Molecular Identifiers.

Background: Immune repertoire sequencing of the T-cell receptor can identify clonotypes that have expanded as a result of antigen recognition or hematological malignancies. However, current sequencing protocols display limitations with nonuniform amplification and polymerase-induced errors during sequencing. Here, we developed a sequencing method that overcame these issues and applied it to γδ T cells, a cell type that plays a unique role in immunity, autoimmunity, homeostasis of intestine, skin, adipose tissue, and cancer biology.

Corrigendum to "Considerations and quality controls when analyzing cell-free tumor DNA" [Biomol. Detect. Quantif. 17 (2019) 100078].

[This corrects the article DOI: 10.1016/j.bdq.

Considerations and quality controls when analyzing cell-free tumor DNA.

Circulating cell-free tumor DNA (ctDNA) is a promising biomarker in cancer. Ultrasensitive technologies enable detection of low (< 0.1%) mutant allele frequencies, a pre-requisite to fully utilize the potential of ctDNA in cancer diagnostics.

Clinical decision support for stroke prevention in atrial fibrillation (CDS-AF): Rationale and design of a cluster randomized trial in the primary care setting.

Background: Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains a significant undertreatment. The main aim of the current study is to investigate whether a clinical decision support tool for stroke prevention (CDS) integrated in the electronic health record can improve adherence to guidelines for stroke prevention in patients with AF.

Patient stratification and the unmet need in asthma.

Asthma is often described as an inflammatory disease of the lungs and in most patients symptomatic treatment with bronchodilators or inhaled corticosteroids is sufficient to control disease. Unfortunately there are a proportion of patients who fail to achieve control despite treatment with the best current treatment. These severe asthma patients have been considered a homogeneous group of patients that represent the unmet therapeutic need in asthma.

Declines in predatory fish promote bloom-forming macroalgae.

In the Baltic Sea, increased dominance of ephemeral and bloom-forming algae is presently attributed to increased nutrient loads. Simultaneously, coastal predatory fish are in strong decline. Using field data from nine areas covering a 700-km coastline, we examined whether formation of macroalgal blooms could be linked to the composition of the fish community.

Effects of temperature on the production of hydrogen peroxide and volatile halocarbons by brackish-water algae.

Marine algae produce volatile halocarbons, which have an ozone-depleting potential. The formation of these compounds is thought to be related to oxidative stress, involving H2O2 and algal peroxidases. In our study we found strong correlations between the releases of H2O2 and brominated and some iodinated compounds to the seawater medium, but no such correlation was found for CHCl3, suggesting the involvement of other formation mechanisms as well.