Clinical outcomes and severity of laboratory-confirmed RSV compared with influenza, parainfluenza and human metapneumovirus in Australian children attending secondary care.

Introduction: Acute lower respiratory infections (ALRIs) are a major contributor to the global infectious disease burden and a common cause of hospitalisation for children under 2 years. We compared clinical severity in children hospitalised with respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV) and influenza virus (IFV).

Methods: We used a probabilistically linked population cohort born in Western Australia between 2010 and 2020 and hospitalised before the age of 2 years.

Comprehensive Assessment of Cannabidiol and HU308 in Acute and Chronic Colitis Models: Efficacy, Safety, and Mechanistic Innovations.

Cannabinoids are emerging as promising treatments for inflammatory diseases such as ulcerative colitis. Specifically, cannabinoid 2 (CB2) receptors, which are upregulated during inflammation, have been distinctively linked to anti-inflammatory and analgesic effects. HU308, a synthetic cannabinoid developed to activate CB2 receptors selectively, aims to minimize unwanted off-target side effects.

Imaging of prostate micro-architecture using three-dimensional wide-field optical coherence tomography.

Prostate cancer is a global health issue that requires new diagnostic methods to provide accurate and precise visualization of prostate tissue on the micro-scale. Such methods have the potential to improve nerve-sparing surgery and to provide image guidance during prostate biopsy. In this feasibility study, we assess the potential of three-dimensional wide-field optical coherence tomography (OCT), covering a volumetric imaging field-of-view up to 46 × 46 × 1 mm, to visualize micro-architecture in 18 freshly excised human prostate specimens.

Consultation informs strategies to improve functional evidence use in variant classification.

To determine if a variant identified by diagnostic genetic testing is causal for disease, applied genetics professionals evaluate all available evidence to assign a clinical classification. Experimental assay data can provide strong functional evidence for or against pathogenicity in variant classification, but appears to be underutilised. We surveyed genetic diagnostic professionals in Australasia to assess their application of functional evidence in clinical practice.

Diagnostic performance of assays for urgent MPO, PR3 and GBM autoantibodies in suspected vasculitis.

Rapid testing for antineutrophil cytoplasmic antibodies (ANCAs) and glomerular basement membrane (GBM) antibodies may assist in the early diagnosis of small vessel vasculitis. Clinical utility of urgent testing of these antibodies in an Australian context is not known. Our retrospective study examined the urgent test requests for ANCA and/or GBM antibodies performed over a 2-year period.

The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of licensed COVID-19 vaccinations administered as a second booster in BNT162b2 primed individuals aged 18-<50 and 50-<70 years old.

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we present data for second boosters among individuals aged 18-<50 and 50-<70 years old primed with BNT162b2 until Day (D) 84.

Methods: Immunocompetent adults who had received two doses of BNT162b2 and any licensed COVID-19 booster at least three months prior were eligible.

Non-invasive brain stimulation enhances the effect of physiotherapy for balance and mobility impairment in people with Multiple Sclerosis.

Background: Impairment of balance and gait is common in Multiple Sclerosis (MS). Non-invasive Brain Stimulation techniques are promising adjuncts to physical therapy to improve disability.

Objective: To determine if combining transcranial direct current stimulation (tDCS) with conventional exercise therapy enhances balance and mobility in people with multiple sclerosis (PwMS) compared to exercise alone.

Feto-placental vascular structure and in silico haemodynamics: Of mice, rats, and human.

Introduction: The complex arborization of the feto-placental vasculature is crucial for optimal fetal nutrition, waste exchange and ultimately, development. Ethical and experimental limitations constrain research into the human placenta, hence experimental animal models such as mice and rats, are crucial to understand placental function. It is unclear how well the mouse and rat feto-placental vascular structure emulates human.

Antimicrobial resistance in Staphylococcus aureus and Enterococci spp. isolates from bloodstream infections in Australian children, 2013 - 2021.

Background: Rising proportions of antimicrobial resistance (AMR) have been observed in both Staphylococcus aureus and Enterococcus spp. isolates.

Methods: The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia.

Antimicrobial resistance in Enterobacterales, Acinetobacter spp. and Pseudomonas aeruginosa isolates from bloodstream infections in Australian children, 2013-2021.

Background: Gram-negative bloodstream infections are associated with significant morbidity and mortality in children. Increasing antimicrobial resistance (AMR) is reported globally, yet efforts to track pediatric AMR at a national level over time are lacking.

Methods: The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia.

Understanding the Significance of Layer Bonding in Melt Electrowriting.

Melt electrowriting (MEW) is a high-resolution additive manufacturing technology capable of depositing micrometric fibers onto a moving collector to form 3D scaffolds of controlled mechanical properties. While the critical role of layer bonding to achieve mechanical integrity in fused deposition modeling has been widely reported, it remains largely unknown in MEW, in part due to a lack of methods to assess it. Here, a systematic framework is developed to unravel the significance of layer bonding in MEW scaffolds and its ultimate effect on their mechanical properties.

NucBalancer: streamlining barcode sequence selection for optimal sample pooling for sequencing.

Unlabelled: Recent advancements in next-generation sequencing (NGS) technologies have brought to the forefront the necessity for versatile, cost-effective tools capable of adapting to a rapidly evolving landscape. The emergence of numerous new sequencing platforms, each with unique sample preparation and sequencing requirements, underscores the importance of efficient barcode balancing for successful pooling and accurate demultiplexing of samples. Recently launched new sequencing systems claiming better affordability comparable to more established platforms further exemplifies these challenges, especially when libraries originally prepared for one platform need conversion to another.

Unrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres.

Breast cancer remains a significant global health challenge. In Australia, the adoption of publicly-funded multigene panel testing for eligible cancer patients has increased accessibility to personalised care, yet has also highlighted the increasing prevalence of variants of uncertain significance (VUS), complicating clinical decision-making. This project aimed to explore the spectrum and actionability of breast cancer VUS in Australian familial cancer centers (FCCs).

Corrigendum: Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

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The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old.

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84.

Methods: Immunocompetent adults who received any first booster ≥three months prior were eligible.

Multimodal three-dimensional characterization of murine skeletal muscle micro-scale elasticity, structure, and composition: Impact of dysferlinopathy, Duchenne muscular dystrophy, and age on three hind-limb muscles.

Skeletal muscle tissue function is governed by the mechanical properties and organization of its components, including myofibers, extracellular matrix, and adipose tissue, which can be modified by the onset and progression of many disorders. This study used a novel combination of quantitative micro-elastography and clearing-enhanced three-dimensional (3D) microscopy to assess 3D micro-scale elasticity and micro-architecture of muscles from two muscular dystrophies: dysferlinopathy and Duchenne muscular dystrophy, using male BLA/J and mdx mice, respectively, and their wild-type (WT) controls. We examined three muscles with varying proportions of slow- and fast-twitch myofibers: the soleus (predominantly slow), extensor digitorum longus (EDL; fast), and quadriceps (mixed), from BLA/J and WT mice aged 3, 10, and 24 months, and mdx and WT mice aged 10 months.

A novel stress sensor enables accurate estimation of micro-scale tissue mechanics in quantitative micro-elastography.

Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation.

Hyperactive Nickase Activity Improves Adenine Base Editing.

Base editing technologies enable programmable single-nucleotide changes in target DNA without double-stranded DNA breaks. Adenine base editors (ABEs) allow precise conversion of adenine (A) to guanine (G). However, limited availability of optimized deaminases as well as their variable efficiencies across different target sequences can limit the ability of ABEs to achieve effective adenine editing.

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.

T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice.

MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.

Hepatocellular carcinoma (HCC) presents a significant global health burden, with alarming statistics revealing its rising incidence and high mortality rates. Despite advances in medical care, HCC treatment remains challenging due to late-stage diagnosis, limited effective therapeutic options, tumor heterogeneity, and drug resistance. MicroRNAs (miRNAs) have attracted substantial attention as key regulators of HCC pathogenesis.