Ribosome decision graphs for the representation of eukaryotic RNA translation complexity.

The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, within both annotated protein-coding and noncoding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term ribosome decision graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the latter "translons." Nondeterministic events, such as initiation, reinitiation, selenocysteine insertion, or ribosomal frameshifting, are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions and for analyzing genetic variation and quantitative genome-wide data on translation for characterization of regulatory modulators of translation.

Coblation versus BiZact extra-capsular tonsillectomy in adults: a randomized control trial.

INTRODUCTION: Tonsillectomy is a frequently performed otolaryngological procedure and is associated with significant postoperative pain and bleeding. A number of studies have investigated methods to reduce pain and bleeding. Coblation and BiZact devices have both been claimed to have favourable pain outcomes following tonsillectomy. This study was designed to investigate these two techniques in a direct comparison of postoperative pain and bleeding. METHODS: In this single blinded, randomized control trial, 61 patients were randomly assigned to undergo tonsillectomy with either the BiZact or Coblation device. Pain scores were collected for 14 days postoperatively using a Visual Analogue Score scale. Secondary outcome data was collected for duration of surgery, intra-operative bleeding, return to normal, and secondary bleeding rates. RESULTS: Coblation was found to have lower postoperative pain on day 1 (P < 0.05). BiZact was found to have lower postoperative pain on day 7 (P < 0.05) and day 11 (P < 0.05). Pain scores for other days were not significant. There was no significant difference in set-up time, procedural time and return to normal activities. The BiZact group had a longer time to achieve haemostasis (P < 0.001) and greater intraoperative blood loss (P < 0.01). There was a trend towards more significant secondary bleeding in the BiZact arm, however, this study was not adequately powered to assess this finding. CONCLUSION: Both Coblation and BiZact devices appear to provide a safe and effective method for tonsillectomy in adults. Reduced pain on day 1 may make Coblation more suitable for day-case surgery.

Increased Rates of Late Periprosthetic Fractures in Larger Hydroxyapatite-Coated Cementless Stems: Are Collared Stems a Better Alternative for Total Hip Arthroplasty?

BACKGROUND: Cementless hip stems are widely used for total hip arthroplasty (THA) and have demonstrated excellent survivorship. This study aimed to investigate the effects of stem size and calcar collars on rates of revision due to periprosthetic fracture. METHODS: All primary THA procedures recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from September 1999 to December 2021 for a diagnosis of osteoarthritis using a single cementless hip stem with modern bearings were included. The primary outcome measure was revision due to periprosthetic fracture. Stems were divided into 2 groups for comparison, large (size 14 to 20) and small-medium (6 to 13). A subanalysis was performed for collared stems. A total of 59,518 primary THA procedures were included. RESULTS: The cumulative percent revision for periprosthetic fracture was significantly higher for large stems compared to small-medium stems (hazard ratio [HR] = 1.57 [95% confidence interval {CI} 1.18, 2.09] P = .002). Furthermore, collared stems had significantly lower revision rates due to late periprosthetic fracture compared to collarless variants (2 week + HR = 4.55 [95% CI 3.23, 6.42], P < .001). Large collarless stems were found to have greater revision rates due to fracture compared to small-medium collarless stems (HR = 1.55 [95% CI 1.13, 2.12] P = .006), but no difference was found between collared groups (HR = 1.37 [95% CI 0.68, 2.78] P = .382). CONCLUSION: Large cementless hip stems have a higher rate of revision due to periprosthetic fracture compared to small-medium stems. Using a collared stem reduces the rate of periprosthetic fracture.

Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity.

The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, both within annotated protein-coding and non-coding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term Ribosome Decision Graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the later 'translons'. Non-deterministic events, such as initiation, re-initiation, selenocysteine insertion or ribosomal frameshifting are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions, analysis of genetic variation and quantitative genome-wide data on translation for characterisation of regulatory modulators of translation.

RiboGalaxy: A Galaxy-based Web Platform for Ribosome Profiling Data Processing - 2023 Update.

Ribosome profiling (Ribo-Seq) captures a "snapshot" of ribosomes' locations at the entire transcriptome of a cell at sub-codon resolution providing insights into gene expression and enabling the discovery of novel translated regions. RiboGalaxy (https://ribogalaxy.genomicsdatascience.ie/), a Galaxy-based platform for processing Ribo-Seq data is a RiboSeq.Org (https://riboseq.org/) resource. RiboSeq.Org is an online gateway to a set of integrated tools for the processing and analysis of Ribo-Seq data. In this RiboGalaxy update we introduce changes to both the tools available on RiboGalaxy and to how the resource is managed on the backend. For example, in order to improve interoperability between Riboseq.Org resources, we added tools that link RiboGalaxy outputs with Trips-Viz and GWIPS-viz browsers for downstream analysis and visualisation. RiboGalaxy's backend now utilises Ansible configuration management which enhances its stability and jobs are executed within Singularity containers and are managed by Slurm, strengthening reproducibility and performance respectively.