Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples.

A scoping review to map public-facing websites for non-traumatic wrist disorders with quality evaluation.

Introduction: Public-facing resources for non-traumatic wrist disorders (NTWD) exist, but care recipients and healthcare professionals alike are uncertain where to access the most useful resources and have raised concerns over the quality of information provided. Previous studies involving stakeholders highlight a need for quality evaluation of these resources. The aim of this study was to identify website resources accessible to UK-based online health seekers and explore their content through quality assessment.

Multiarm, non-randomised, single-centre feasibility study-investigation of the differential biology between benign and malignant renal masses using advanced magnetic resonance imaging techniques (IBM-Renal): protocol.

Introduction: Localised renal masses are an increasing burden on healthcare due to the rising number of cases. However, conventional imaging cannot reliably distinguish between benign and malignant renal masses, and renal mass biopsies are unable to characterise the entirety of the tumour due to sampling error, which may lead to delayed treatment or overtreatment. There is an unmet clinical need to develop novel imaging techniques to characterise renal masses more accurately.

VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau () tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of , and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in -null ccRCC cell lines and impairs tumour establishment and growth . This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in -null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β.

Multifocal, multiphenotypic tumours arising from an MTOR mutation acquired in early embryogenesis.

Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing.

High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades.

Background: Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades.

Methods: Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC).

mRNA psi profiling using nanopore DRS reveals cell type-specific pseudouridylation.

Pseudouridine (psi) is one of the most abundant human mRNA modifications generated via psi synthases, including and . Nanopore direct RNA sequencing combined with our recently developed tool, Mod- ID, enables psi mapping, transcriptome-wide, without chemical derivatization of the input RNA and/or conversion to cDNA. This method is sensitive for detecting differences in the positional occupancy of psi across cell types, which can inform our understanding of the impact of psi on gene expression.

A scoping review to map evidence regarding key domains and questions in the management of non-traumatic wrist disorders.

Introduction: Non-traumatic wrist disorders (NTWD) are commonly encountered yet sparse resources exist to aid management. This study aimed to produce a literature map regarding diagnosis, management, pathways of care and outcome measures for NTWDs in the United Kingdom.

Methods: An interdisciplinary team of clinicians and academic researchers used Joanna Briggs Institute guidelines and the PRISMA ScR checklist in this scoping review.

Management of gunshot wounds near the elbow: experiences at a high-volume level I trauma center.

Background: Gunshot-related fractures near the elbow are challenging, and available data to guide the practitioner are lacking. This report analyzes injury patterns and treatment strategies in a case series from a high-volume urban trauma center.

Methods: All periarticular gunshot fractures near the elbow treated at a level 1 trauma center from 2014 to 2018 were retrospectively reviewed.

Technical Factors Contributing to Nonunion in Supracondylar Distal Femur Fractures Treated With Lateral Locked Plating: A Risk-Stratified Analysis.

Objective: To identify technical factors associated with nonunion after operative treatment with lateral locked plating.

Design: Retrospective cohort study.

Setting: Ten Level I trauma centers.

De novo detection of somatic mutations in high-throughput single-cell profiling data sets.

Characterization of somatic mutations at single-cell resolution is essential to study cancer evolution, clonal mosaicism and cell plasticity. Here, we describe SComatic, an algorithm designed for the detection of somatic mutations in single-cell transcriptomic and ATAC-seq (assay for transposase-accessible chromatin sequence) data sets directly without requiring matched bulk or single-cell DNA sequencing data. SComatic distinguishes somatic mutations from polymorphisms, RNA-editing events and artefacts using filters and statistical tests parameterized on non-neoplastic samples.

Pediatric Hand and Wrist Fractures in Osteogenesis Imperfecta: An Analysis of Incidence, Patient-specific Risk Factors, and Fracture-specific Characteristics.

Background: Children with osteogenesis imperfecta (OI) frequently present with fractures; however, hand and wrist fractures (HWFs), those distal to the radial and ulnar diaphysis, are seldom observed. Yet, HWFs remain among the most common fractures in children with non-OI. The objective of this study was to identify the incidence of OI HWFs.

Fumarate induces vesicular release of mtDNA to drive innate immunity.

Mutations in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell carcinoma. Loss of FH in the kidney elicits several oncogenic signalling cascades through the accumulation of the oncometabolite fumarate. However, although the long-term consequences of FH loss have been described, the acute response has not so far been investigated.

Examining European Talent Development Environments: Athlete, Parent and Coach Perceptions.

Talent Development Environments (TDEs) aim to provide the appropriate conditions for youth athletes to realise their full sporting potential. How TDEs are designed and operated is therefore of great importance for the development of elite athletes. Stakeholders are vital in this process, yet their perspectives are poorly understood.

Complication Rates in Patients With Classic and Radiographic Variants of Seymour Fractures.

Background: At a tertiary-care, level 1 pediatric trauma center, we have observed fractures of the distal phalanx involving the physis, with associated nail bed injuries, that are distinct from the classic description of the Seymour fracture. We investigated the time to definitive management and the associated morbidity of these Seymour fracture variants compared with classically described Seymour fractures. We hypothesize that these Seymour variants are similarly problematic in terms of complications and delays to the definitive treatment and thus warrant increased awareness.