Achieving excellence in paediatric cardiac care in resource limited and resource plentiful settings and building successful care networks across different countries.

Background: The delivery of paediatric cardiac care across the world occurs in settings with significant variability in available resources. Irrespective of the resources locally available, we must always strive to improve the quality of care we provide to our patients and simultaneously deliver such care in the most efficient and cost-effective manner. The development of cardiac networks is used widely to achieve these aims.

Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.

Dorsal root ganglion (DRG) toxicity has been consistently reported as a potential safety concern after delivery of adeno-associated viruses (AAVs) containing gene-replacement vectors but has yet to be reported for RNAi-based vectors. Here, we report DRG toxicity after AAV intra-CSF delivery of an RNAi expression construct-artificial microRNA targeting superoxide dismutase 1 (SOD1)-in non-human primates (NHPs) and provide evidence that this can be recapitulated within mice. Histopathology evaluation showed that NHPs and mice develop DRG toxicity after AAV delivery, including DRG neuron degeneration and necrosis and nerve-fiber degeneration that were associated with increases in cerebrospinal fluid (CSF) and serum phosphorylated neurofilament heavy chain (pNF-H).

Nutritional Composition of Forage Available to the Northern Hairy-Nosed Wombat.

Access to adequate nutrition supports an animal's chance of survival and reproduction; thus, it is particularly important for threatened species. The nutritional quality of forage available to the critically endangered northern hairy-nosed wombat (; NHW) has not been assessed for two decades. The NHW Recovery Action Plan 2022 highlighted a need to investigate the effects of invasive buffel grass () on the species' diet - reassessing the relative nutritional quality of highly abundant buffel grass will assist this investigation.

Touching Technology-Parents' Experiences of Remote Consultations for Children With Severe Congenital Cardiac Conditions: Quasi-Experimental Cohort Study.

Background: Remote consultations (RCs) using videoconferencing was recommended by the General Medical Council as the method for clinicians to provide patient consultations during the COVID-19 pandemic. Facilitating this while providing high-quality care depends on the usability and acceptability of the technology.

Objective: This project aimed to investigate parents' experiences of using videoconferencing technology for real-time RCs with children who had congenital heart defects during the COVID-19 pandemic lockdown.

Epicardial Pacemaker Causing Cardiac Strangulation.

Cardiac strangulation is a rare but potentially lethal complication of epicardial pacemaker insertion. We present the case of a 9-year-old girl who was identified as having cardiac strangulation on routine follow-up for an epicardial pacemaker inserted on day 1 of life for congenital complete heart block (CCHB). The potential clinical presentations and risk factors for pacemaker strangulation are then discussed.

Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion.

DNA metabarcoding analysis of the bare-nosed wombat () diet.

Wombats are native herbivorous grazers that have adapted to Australia's low-quality forage. Studies on diet selection by bare-nosed wombats () are limited and are either observational or based on microhistological studies. The current study determined the diet of wombats through DNA metabarcoding across five study sites in New South Wales over a one-year period.

The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.

Objectives: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.

Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative.

Automated pupillometry and optic nerve sheath diameter ultrasound to define tuberculous meningitis disease severity and prognosis.

Background: Tuberculous meningitis (TBM) causes high mortality and morbidity, in part due to raised intracranial pressure (ICP). Automated pupillometry (NPi) and optic nerve sheath diameter (ONSD) are both low-cost, easy-to-use and non-invasive techniques that correlate with ICP and neurological status. However, it is uncertain how to apply these techniques in the management of TBM.

Assessment of the diet of the critically endangered northern hairy-nosed wombat () using DNA metabarcoding.

Invasive buffel grass () is considered a threat to the critically endangered northern hairy-nosed wombat (; NHW). Buffel grass outcompetes native grasses, reducing availability of native food items for NHW, and causes more intense fires due to the large volumes of dead matter it produces. Previous studies suggested buffel grass was increasing in the diet; however, the diet of the NHW has not been reassessed for over two decades and was limited to Epping Forest National Park, with the population at Richard Underwood Nature Refuge having never been assessed.

scRNASequest: an ecosystem of scRNA-seq analysis, visualization, and publishing.

Background: Single-cell RNA sequencing is a state-of-the-art technology to understand gene expression in complex tissues. With the growing amount of data being generated, the standardization and automation of data analysis are critical to generating hypotheses and discovering biological insights.

Results: Here, we present scRNASequest, a semi-automated single-cell RNA-seq (scRNA-seq) data analysis workflow which allows (1) preprocessing from raw UMI count data, (2) harmonization by one or multiple methods, (3) reference-dataset-based cell type label transfer and embedding projection, (4) multi-sample, multi-condition single-cell level differential gene expression analysis, and (5) seamless integration with cellxgene VIP for visualization and with CellDepot for data hosting and sharing by generating compatible h5ad files.

Paediatric heart failure - understanding the pathophysiology and the current role of cardiac biomarkers in clinical practice.

Introduction: Paediatric heart failure is a common clinical syndrome that may be experienced by children with congenital heart disease (CHD) and/or cardiomyopathy. It is characterised by clinical signs/symptoms which reflect the underlying pathophysiology based on one of three main clinical states: Pulmonary over-circulation, pressure overload, and ventricular failure. Current diagnosis relies on clinical assessment and echocardiogram imaging as cardiac biomarkers has been predominantly scientific to date.

RNASequest: An End-to-End Reproducible RNAseq Data Analysis and Publishing Framework.

We present RNASequest, a customizable RNA sequencing (RNAseq) analysis, app management, and result publishing framework. Its three-in-one RNAseq data analysis ecosystem consists of (1) a reproducible, configurable expression analysis (EA) module, (2) multi-faceted result presentation in R Shiny, a Bookdown document and an online slide deck, and (3) a centralized data management system. In principle, following up our well-received omics data visualization tool Quickomics, RNASequest automates the differential gene expression analysis step, eases statistical model design by built-in covariates testing module, and further provides a web-based tool, ShinyOne, to manage apps powered by Quickomics and reports generated by running the pipeline on multiple projects in one place.

Interobserver variation of clinical oncologists compared to therapeutic radiographers (RTT) prostate contours on T2 weighted MRI.

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours.

Evaluation of therapeutic radiographer contouring for magnetic resonance image guided online adaptive prostate radiotherapy.

Background And Purpose: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed.

Materials And Methods: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession.

How to interpret cardiac biomarkers in children?

Cardiac biomarkers are used as first-line diagnostic tools in suspected myocardial injury and heart failure in adult patients. Their use in paediatric patients has been limited by variability caused by age, gender and the presence of an underlying congenital cardiac condition. There are established reference ranges for both NT-proBNP and troponin in healthy children, but these cannot be applied to all paediatric patients because of limited large studies focusing on children with congenital heart disease and/or cardiomyopathy.

Editorial Board Composition Among Pediatric Cardiology Journals: Time to Cast the Net Wider.

Background: No data currently exist on the diversity of editorial board members (EBMs) of pediatric cardiology journals.

Objectives: The objective was to investigate the editorial boards of 5 pediatric cardiology journals to assess the composition of these boards in terms of the geographical, gender, and economic representation of their members.

Methods: Information on EBMs was collected directly from 5 journal websites accessed in February 2022.

Characterizing the composition of iPSC derived cells from bulk transcriptomics data with CellMap.

Induced pluripotent stem cell (iPSC) derived cell types are increasingly employed as in vitro model systems for drug discovery. For these studies to be meaningful, it is important to understand the reproducibility of the iPSC-derived cultures and their similarity to equivalent endogenous cell types. Single-cell and single-nucleus RNA sequencing (RNA-seq) are useful to gain such understanding, but they are expensive and time consuming, while bulk RNA-seq data can be generated quicker and at lower cost.

Prevalence and trends of congenital heart defects among live births from 2005 to 2014 in Northern Ireland.

Rationale: Congenital heart defects (CHD) are the most frequent group of congenital anomalies representing a significant burden of mortality and morbidity and health service load.

Objective: In the Northern Ireland population, served by a single paediatric cardiology centre, we determine the prevalence and trends of CHD among live births.

Methods: This is a descriptive cross-sectional population-based study, using the paediatric cardiology database.

Plasma-Based Measurements of Tumor Heterogeneity Correlate with Clinical Outcomes in Metastatic Colorectal Cancer.

Sequencing circulating tumor DNA (ctDNA) from liquid biopsies may better assess tumor heterogeneity than limited sampling of tumor tissue. Here, we explore ctDNA-based heterogeneity and its correlation with treatment outcome in STEAM, which assessed efficacy and safety of concurrent and sequential FOLFOXIRI-bevacizumab (BEV) vs. FOLFOX-BEV for first-line treatment of metastatic colorectal cancer.

OmicsView: Omics data analysis through interactive visual analytics.

With advances in NGS technologies, transcriptional profiling of human tissue across many diseases is becoming more routine, leading to the generation of petabytes of data deposited in public repositories. There is a need for bench scientists with little computational expertise to be able to access and mine this data to understand disease pathology, identify robust biomarkers of disease and the effect of interventions ( or ). To this end we release an open source analytics and visualization platform for expression data called OmicsView, http://omicsview.

MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients' Cells.

Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease.

Investigating spatial fractionation and radiation induced bystander effects: a mathematical modelling approach.

Radiation induced bystander effects (RIBEs) have been shown to cause death in cells receiving little or no physical dose. In standard radiotherapy, where uniform fields are delivered and all cells are directly exposed to radiation, this phenomenon can be neglected. However, the role of RIBEs may become more influential when heterogeneous fields are considered.

Perfluorooctanoic Acid Transport in Soil and Absorption and Distribution in Alfalfa (Medicago sativa).

Abstract: Perfluorooctanoic acid (PFOA) is used as a surfactant in consumer and industrial products and is frequently found in biosolids from wastewater treatment plants. When present in biosolids applied to croplands, PFOA can contaminate feed and fodder used by livestock, but the extent of PFOA transfer from soil to plants is not well characterized. A single dose of radiocarbon (14C)-tagged PFOA was applied to unplanted soil or soil containing growing alfalfa.