Notes

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Additionally, we found a significant positive correlation between ccfmtDNA levels and GDF-15 concentrations (r = 0.59, P = 0.016).

CSF ccfmtDNA levels are significantly higher in patients with MD in comparison to controls and, thus, they can be used as a novel biomarker for MD research. Our results could also be valuable to support the clinical outcome assessment of MD patients.
CSF ccfmtDNA levels are significantly higher in patients with MD in comparison to controls and, thus, they can be used as a novel biomarker for MD research. Our results could also be valuable to support the clinical outcome assessment of MD patients.Possvm (Phylogenetic Ortholog Sorting with Species oVerlap and MCL) is a tool that automates the process of identifying clusters of orthologous genes from precomputed phylogenetic trees and classifying gene families. It identifies orthology relationships between genes using the species overlap algorithm to infer taxonomic information from the gene tree topology, and then uses the Markov Clustering Algorithm (MCL) to identify orthology clusters and provide annotated gene families. Our benchmarking shows that this approach, when provided with accurate phylogenies, is able to identify manually curated orthogroups with very high precision and recall. Overall, Possvm automates the routine process of gene tree inspection and annotation in a highly interpretable manner, and provides reusable outputs that can be used to obtain phylogeny-informed gene annotations and inform comparative genomics and gene family evolution analyses.
The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with systemic lupus erythematosus (SLE) remains unclear and data on clinical manifestations after infection are lacking. The aim of this multicentre study is to describe the effect of SARS-CoV-2 in SLE patients.

SLE patients referring to 4 Italian centres were monitored between February 2020 and March 2021. All patients with SARS-CoV-2 infection were included. Disease characteristics, treatment, disease activity, and SARS-CoV-2 related symptoms were recorded before and after the infection.

Fifty-one (6.14%) SLE patients were included among 830 regularly followed-up. Nine (17.6%) had an asymptomatic infection. Five (9.8%), out of 42 (82.6%) symptomatic, developed interstitial pneumonia (no identified risk factor). The presence of SLE major organ involvement (particularly renal involvement) was associated with asymptomatic SARS-CoV-2 infection (p-value = 0.02). Chronic corticosteroid therapy was found to be associated with asymptomatic infection (p-value = 0.018). Three SLE flares (5.9%) were developed after SARS-CoV-2 infection one of them was characterized by MPO-ANCA positive pauci-immune crescentic necrotizing glomerulonephritis and granulomatous pneumonia.

SARS-CoV-2 infection determined autoimmune flares in a small number of our patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.
SARS-CoV-2 infection determined autoimmune flares in a small number of our patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends in DNA at sequences relevant to several functions including transcription and recombination, and is also responsible for general DNA compaction when bound non-specifically. learn more We show that IHF-DNA structural multimodality is more elaborate than previously thought, and provide insights into how this drives mechanical switching towards strongly bent DNA. Using single-molecule atomic force microscopy and atomic molecular dynamics simulations we find three binding modes in roughly equal proportions 'associated' (73° of DNA bend), 'half-wrapped' (107°) and 'fully-wrapped' (147°), only the latter occurring with sequence specificity. We show IHF bridges two DNA double helices through non-specific recognition that gives IHF a stoichiometry greater than one and enables DNA mesh assembly. We observe that IHF-DNA structural multiplicity is driven through non-specific electrostatic interactions that we anticipate to be a general NAP feature for physical organization of chromosomes.
A major goal of personalized medicine in oncology is the optimization of treatment strategies given measurements of the genetic and molecular profiles of cancer cells. To further our knowledge on drug sensitivity, machine learning techniques are commonly applied to cancer cell line panels.

We present a novel integer linear programming (ILP) formulation, called MEthod for Rule Identification with multi-omics DAta (MERIDA), for predicting the drug sensitivity of cancer cells. The method represents a modified version of the LOBICO method by Knijnenburg et al. and yields easily interpretable models amenable to a Boolean logic based interpretation. Since the proposed altered logical rules lead to an enormous acceleration of the running times of MERIDA compared to LOBICO, we can not only consider larger input feature sets integrated from genetic and molecular omics data but also build more comprehensive models that mirror the complexity of cancer initiation and progression. Moreover, we enable the inclusion of a priori knowledge that can either stem from biomarker databases or can also be newly acquired knowledge gathered iteratively by previous runs of MERIDA. Our results show that this approach does not only lead to an improved predictive performance but also identifies a variety of putative sensitivity and resistance biomarkers. We also compare our approach to state-of-the-art machine learning methods and demonstrate the superior performance of our method. Hence, MERIDA has great potential to deepen our understanding of the molecular mechanisms causing drug sensitivity or resistance.

The corresponding code is available on github (https//github.com/unisb-bioinf/MERIDA.git).

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Desmoplakin (DSP) cardiomyopathy is an increasingly recognized form of arrhythmogenic cardiomyopathy. With a genotype-specific approach, we characterized the diagnosis, natural history, and risk for ventricular arrhythmia and heart failure in DSP cardiomyopathy.

We followed 91 individuals [45 probands, 34% male, median age 27.5 years (interquartile interval 20.0-43.9)] with pathogenic or likely pathogenic DSP variants for a median of 4.3 years. Regarding the ventricular involvement, left predominance was most common (n = 22, 28%) followed by bi-ventricular in 12 (15%) and right predominance in 5 (6%). Myocardial injury (chest pain, elevated troponin, normal coronary angiogram) occurred in 20 (22%) individuals. Incidence rates of sustained ventricular arrhythmia and heart failure (ventricular dysfunction ± symptoms) were 5.9 [95% confidence interval (CI) 3.9-9.1] and 6.7 (95% CI 4.5-9.8) per 100 person-years, respectively. In univariate regression, myocardial injury was associated with sustained ventriculastratification of DSP cardiomyopathy need refinement.
Hand-eye coordination and ergonomics are important for the success of delicate ultrasound-guided medical procedures. These can be improved using smart glasses (head-mounted display) by decreasing the head movement on the ultrasound screen. The hypothesis was that the smart glasses could improve the success rate of ultrasound-guided pediatric radial arterial catheterization.

This prospective, single-blinded, randomized controlled, single-center study enrolled pediatric patients (n = 116, age less than 2 yr) requiring radial artery cannulation during general anesthesia. The participants were randomized into the ultrasound screen group (control) or the smart glasses group. After inducing general anesthesia, ultrasound-guided radial artery catheterization was performed. The primary outcome was the first-attempt success rate. The secondary outcomes included the first-attempt procedure time, the overall complication rate, and operators' ergonomic satisfaction (5-point scale).

In total, 116 children were inclusisted ultrasound-guided radial artery catheterization improved the first-attempt success rate and ergonomic satisfaction while reducing the first-attempt procedure time and overall complication rates in small pediatric patients.

There is an increasing amount of data coming from genome-wide studies identifying disease-specific survivability-essential proteins and host factors critical to a cell becoming infected. Targeting such proteins has a strong potential for targeted, precision therapies. Typically however, too few of them are drug targetable. An alternative approach is to influence them through drug targetable proteins upstream of them. Structural target network controllability is a suitable solution to this problem. It aims to discover suitable source nodes (e.g., drug targetable proteins) in a directed interaction network that can control (through a suitable set of input functions) a desired set of targets.

We introduce NetControl4BioMed, a free open-source web-based application that allows users to generate or upload directed protein-protein interaction networks and to perform target structural network controllability analyses on them. The analyses can be customized to focus the search on drug targetable source nodes, thus providing drug therapeutic suggestions. The application integrates protein data from HGNC, Ensemble, UniProt, NCBI, and InnateDB, directed interaction data from InnateDB, Omnipath, and SIGNOR, cell-line data from COLT and DepMap, and drug-target data from DrugBank.

The application and data are available online at https//netcontrol.combio.org/. link2 The source code is available at https//github.com/Vilksar/NetControl4BioMed under an MIT license.
The application and data are available online at https//netcontrol.combio.org/. The source code is available at https//github.com/Vilksar/NetControl4BioMed under an MIT license.
To assess the effect of filgotinib, which preferentially inhibits Janus kinase 1 (JAK1), on magnetic resonance imaging (MRI) measures of structural change in the sacroiliac (SI) joint in patients with active ankylosing spondylitis (AS) in the TORTUGA trial.

Adults with active AS and inadequate response/intolerance to ≥ 2 non-steroidal anti-inflammatory drugs were randomized (11) to filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12weeks. In this post-hoc analysis, T1-weighted MRI scans of the SI joint were evaluated by two independent readers using Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Structural Score (SSS) definitions for erosion, backfill, fat metaplasia and ankylosis. link3 Correlations between SPARCC SSS and improvement in clinical outcomes were also assessed.

. MRI scans from 87 patients (48 filgotinib, 39 placebo) were evaluated. At baseline, there were no notable differences between filgotinib and placebo for any MRI structural lesion types. From baseline to week 12, filgotinib was associated with a significant reduction in SI joint erosion score (p = 0.
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