Notes

Chromosome Business in Early Meiotic Prophase.
Intravenous immunoglobulins are an efficacious treatment for chronic inflammatory demyelinating polyradiculoneuropathy. Biomarkers for disease activity are lacking, making the need for ongoing treatment difficult to assess, leading to potential overtreatment and high health-care costs. Our objective was to determine whether intravenous immunoglobulin withdrawal is non-inferior to continuing intravenous immunoglobulin treatment and to determine how often patients are overtreated. We performed a randomized, double-blind, intravenous immunoglobulin-controlled non-inferiority trial in seven centres in the Netherlands (Trial registration ISRCTN 13637698; www.isrctn.com/ISRCTN13637698). Adults with clinically stable chronic inflammatory demyelinating polyradiculoneuropathy using intravenous immunoglobulin maintenance treatment for at least 6 months were included. Patients received either intravenous immunoglobulin withdrawal (placebo) as investigational treatment or continuation of intravenous immunoglobulin treatmiably. NSC663284 Overall, this study suggests that withdrawal attempts are safe and should be performed regularly in clinically stable patients.
Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricemia or chronic gout.

We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥ 19 years; had CKD G3-G4; and used drugs including colchicine, allopurinol, and febuxostat for hyperuricemia or chronic gout during April 2000-October 2020. Patients with CKD progression, which was defined as ≥ 40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age, and sex.

Overall, 3085 patients with CKD progression were matched to 11715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥ 90 cumulative daily colchicine doses were associated with a lower risk of CKD progression (adjusted odds ratio [AOR], 0.77; 95% confidence interval [CI], 0.61-0.96) than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI, 0.62-0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3.

Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricemia, or chronic gout.
Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricemia, or chronic gout.
A substantial proportion of patients with heart failure (HF) with preserved ejection fraction (HFpEF) present with normal natriuretic peptide (NP) levels. The pathophysiology and natural history for this phenotype remain unclear.

Consecutive subjects undergoing invasive cardiopulmonary exercise testing for unexplained dyspnoea at Mayo Clinic in 2006-18 were studied. Heart failure with preserved ejection fraction was defined as a pulmonary arterial wedge pressure (PAWP) ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF and normal NP [N-terminal of the pro-hormone B-type natriuretic peptide (NT-proBNP) < 125 ng/L] were compared with HFpEF with high NP (NT-proBNP ≥ 125 ng/L) and controls with normal haemodynamics. Patients with HFpEF and normal (n = 157) vs. high NP (n = 263) were younger, yet older than controls (n = 161), with an intermediate comorbidity profile. Normal NP HFpEF was associated with more left ventricular hypertrophy and worse diastolic function compared with controls, but bettevation in filling pressures. While clinical outcomes are not as poor compared with patients with high NP, patients with normal NP HFpEF exhibit increased risk of death or HF readmissions compared with patients without HF, emphasizing the importance of this phenotype.
Patients with HFpEF and normal NP display mild diastolic dysfunction and preserved CO reserve during exercise, despite marked elevation in filling pressures. While clinical outcomes are not as poor compared with patients with high NP, patients with normal NP HFpEF exhibit increased risk of death or HF readmissions compared with patients without HF, emphasizing the importance of this phenotype.
Machine learning algorithms for link prediction can be valuable tools for hypothesis generation. However, many current algorithms are black boxes or lack good user interfaces that could facilitate insight into why predictions are made. We present LinkExplorer, a software suite for predicting, explaining and exploring links in large biomedical knowledge graphs. LinkExplorer integrates our novel, rule-based link prediction engine SAFRAN, which was recently shown to outcompete other explainable algorithms and established black box algorithms. Here, we demonstrate highly competitive evaluation results of our algorithm on multiple large biomedical knowledge graphs, and release a web interface that allows for interactive and intuitive exploration of predicted links and their explanations.

A publicly hosted instance, source code and further documentation can be found at https//github.com/OpenBioLink/Explorer.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.Macrophages are a heterogeneous population of cells involved in tissue homeostasis, inflammation, and cancer. Although macrophages are densely distributed throughout the human intestine, our understanding of how gut macrophages maintain tissue homeostasis is limited. Here we show that colonic lamina propria macrophages (LpMs) and muscularis macrophages (MMs) consist of monocyte-like cells that differentiate into multiple transcriptionally distinct subsets. LpMs comprise subsets with proinflammatory properties and subsets with high antigen-presenting and phagocytic capacity. The latter are strategically positioned close to the surface epithelium. Most MMs differentiate along two trajectories one that upregulates genes associated with immune activation and angiogenesis, and one that upregulates genes associated with neuronal homeostasis. Importantly, MMs are located adjacent to neurons and vessels. Cell-cell interaction and gene network analysis indicated that survival, migration, transcriptional reprogramming, and niche-specific localization of LpMs and MMs are controlled by an extensive interaction with tissue-resident cells and a few key transcription factors.
Reconciliation between a host and its symbiont phylogenies or between a species and a gene phylogenies is a prevalent approach in evolution, however no simple generic tool (i.e. virtually usable by all reconciliation software, from host/symbiont to species/gene comparisons) is available to visualise reconciliation results. Moreover there is no tool to visualise 3-levels reconciliations, i.e. to visualise 2 nested reconciliations as for example in a host/symbiont/gene complex.

Thirdkind is a light and easy to install command line software producing svg files displaying reconciliations, including 3-levels reconciliations. It takes a standard format recPhyloXML as input, and is thus usable with most reconciliation software.

https//github.com/simonpenel/thirdkind/wiki.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Ubiquitination is widely involved in protein homeostasis and cell signaling. Ubiquitin E3 ligases are critical regulators of ubiquitination that recognize and recruit specific ubiquitination targets for the final rate-limiting step of ubiquitin transfer reactions. Understanding the ubiquitin E3 ligase activities will provide knowledge in the upstream regulator of the ubiquitination pathway and reveal potential mechanisms in biological processes and disease progression. Recent advances in mass spectrometry-based proteomics have enabled deep profiling of ubiquitylome in a quantitative manner. Yet, functional analysis of ubiquitylome dynamics and pathway activity remains challenging.

Here, we developed a UbE3-APA, a computational algorithm and stand-alone python-based software for Ub E3 ligase Activity Profiling Analysis. Combining an integrated annotation database with statistical analysis, UbE3-APA identifies significantly activated or suppressed E3 ligases based on quantitative ubiquitylome proteomics datasets. Benchmarking the software with published quantitative ubiquitylome analysis confirms the genetic manipulation of SPOP enzyme activity through overexpression and mutation. Application of the algorithm in the re-analysis of a large cohort of ubiquitination proteomics study revealed the activation of PARKIN and the co-activation of other E3 ligases in mitochondria depolarization-induced mitophagy process. We further demonstrated the application of the algorithm in the DIA-based quantitative ubiquitylome analysis.

Source code and binaries are freely available for download at URL https//github.com/Chenlab-UMN/Ub-E3-ligase-Activity-Profiling-Analysis, implemented in python and supported on Linux and MS Windows.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.Over the past decade, short-read sequence alignment has become a mature technology. Optimized algorithms, careful software engineering, and high-speed hardware have contributed to greatly increased throughput and accuracy. With these improvements, many opportunities for performance optimization have emerged.In this review, we examine three general-purpose short-read alignment tools - BWA-MEM, Bowtie 2, and Arioc - with a focus on performance optimization. We analyze the performance-related behavior of the algorithms and heuristics each tool implements, with the goal of arriving at practical methods of improving processing speed and accuracy. We indicate where an aligner's default behavior may result in suboptimal performance, explore the effects of computational constraints such as end-to-end mapping and alignment scoring threshold, and discuss sources of imprecision in the computation of alignment scores and mapping quality.With this perspective, we describe an approach to tuning short-read aligner performance to meet specific data-analysis and throughput requirements while avoiding potential inaccuracies in subsequent analysis of alignment results. Finally, we illustrate how this approach avoids easily overlooked pitfalls and leads to verifiable improvements in alignment speed and accuracy.
Supplementary data and appendices are available at Bioinformatics online.
Supplementary data and appendices are available at Bioinformatics online.
Limited data access has hindered the field of precision medicine from exploring its full potential, e.g., concerning machine learning and privacy and data protection rules.

Our study evaluates the efficacy of federated Random Forests (FRF) models, focusing particularly on the heterogeneity within and between datasets. We addressed three common challenges (i) number of parties, (ii) sizes of datasets, and (iii) imbalanced phenotypes, evaluated on five biomedical datasets.

The FRF outperformed the average local models and performed comparably to the data-centralized models trained on the entire data. With an increasing number of models and decreasing dataset size, the performance of local models decreases drastically. The FRF, however, do not decrease significantly. When combining datasets of different sizes, the FRF vastly improve compared to the average local models. We demonstrate that the FRF remain more robust and outperform the local models by analyzing different class-imbalances.

Our results support that FRF overcome boundaries of clinical research and enables collaborations across institutes without violating privacy or legal regulations.
Homepage: https://www.selleckchem.com/products/nsc-663284.html