BRCA Mutation Testing in Men with Metastatic Castration-Resistant Prostate Cancer: Practical Guidance for Australian Clinical Practice.

Some patients with metastatic castration-resistant prostate cancer (mCRPC) possess germline or acquired defects in the DNA damage repair (DDR) genes BRCA1 and BRCA2. Tumors with BRCA mutations exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) such as olaparib and rucaparib. As a result, molecular diagnostic testing to identify patients with BRCA mutations eligible for the PARPi therapy has become an integral component of managing patients with mCRPC.

Final Analysis of the Phase 1b Chemotherapy And Venetoclax in Elderly Acute Myeloid Leukaemia Trial (CAVEAT).

Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The chemotherapy and venetoclax in elderly AML trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients ≥65 years. In this final analysis, 85 patients (median age 71 years) were followed for a median of 41.

An observational study of socioeconomic disparities in psychiatry consultation uptake in Australia, using routinely collected national data from 2015 to 2022.

Background: The COVID-19 pandemic was associated with increased psychological distress and psychiatric service usage in Australia. Previous research into the first few months of the pandemic found severe inequality in telehealth psychiatry but no change in inequality for psychiatry service usage overall. However, it is unknown how inequality evolved over the remainder of the pandemic, as extended lockdowns continued in major Australian cities.

Study of Children Aged Under 2 Years Admitted With RSV at Four Australian Hospitals [2021-2022].

Aims: Primary aim was to review severe acute respiratory infections (SARI) hospitalisations caused by respiratory syncytial virus (RSV) in children aged < 2 years in paediatric hospitals in Australia. Secondary aims included RSV subtyping, assessing RSV seasonality and contributing to the World Health Organisation's RSV surveillance programme.

Methods: We prospectively reviewed the medical records of children (< 2 years of age) with a confirmed SARI who were admitted to one of four major Australian paediatric hospitals and had a respiratory sample analysed by Polymerase Chain Reaction (PCR).

Acalculous Cholecystitis as an Atypical Presentation of Viral Pericarditis: A Case Report.

BACKGROUND Acalculous cholecystitis is a rare form of gallbladder inflammation that occurs without the presence of gallstones. It primarily affects critically ill patients and warrants prompt treatment given its association with high mortality. Pericarditis, an inflammation of the pericardium, typically arises from viral infections but can also be secondary to rheumatological, malignant, or bacterial causes.

Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.

Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.

Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease ( = 18), non-Alzheimer's disease neurodegeneration ( = 23) or primary psychiatric disorders ( = 24).

Prevalence of and risk factors for osteoporosis and fragility fracture in adults with cerebral palsy: A systematic review.

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors.

Tumour DNA methylation markers associated with breast cancer survival: a replication study.

Background: Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies.

Methods: This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity).

Assessing mental health of people with complex communication needs: A systematic review.

Mental health is "a state of wellbeing" as per the World Health Organisation. People with disabilities generally experience poorer wellbeing than those without disabilities. Instruments which assess wellbeing or its three core components (emotional, psychological, social) may be less accessible or appropriate for people with complex communication needs (CCN).

Resolving spatially distinct phytohormone response zones in Arabidopsis thaliana roots colonized by Fusarium oxysporum.

Jasmonic acid (JA), ethylene (ET) and salicylic acid (SA) are the three major phytohormones coordinating plant defense responses, and all three are implicated in the defense against the fungal pathogen Fusarium oxysporum. However, their distinct modes of action and possible interactions remain unknown, in part because all spatial information on their activity is lacking. Here, we set out to probe this spatial aspect of plant immunity by using live-microscopy with newly developed fluorescence-based transcriptional reporter lines.

Electrostatically tuning radical addition and atom abstraction reactions with distonic radical ions.

Although electrostatic catalysis can enhance the kinetics and selectivity of reactions to produce greener synthetic processes, the highly directional nature of electrostatic interactions has limited widespread application. In this study, the influence of oriented electric fields (OEF) on radical addition and atom abstraction reactions are systematically explored with ion-trap mass spectrometry using structurally diverse distonic radical ions that maintain spatially separated charge and radical moieties. When installed on rigid molecular scaffolds, charged functional groups lock the magnitude and orientation of the internal electric field with respect to the radical site, creating an OEF which tunes the reactivity across the set of gas-phase carbon-centred radical reactions.

Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health.

Introduction: Melanopsin is a photopigment with roles in mediating sleep and circadian-related processes, which are often disrupted in Alzheimer's disease (AD). Melanopsin also impacts cognition and synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, and markers of brain health.

Large-scale and long-term wildlife research and monitoring using camera traps: a continental synthesis.

Camera traps are widely used in wildlife research and monitoring, so it is imperative to understand their strengths, limitations, and potential for increasing impact. We investigated a decade of use of wildlife cameras (2012-2022) with a case study on Australian terrestrial vertebrates using a multifaceted approach. We (i) synthesised information from a literature review; (ii) conducted an online questionnaire of 132 professionals; (iii) hosted an in-person workshop of 28 leading experts representing academia, non-governmental organisations (NGOs), and government; and (iv) mapped camera trap usage based on all sources.

Differential recruitment drives pathogen-mediated competition between species in an amphibian chytridiomycosis system.

Pathogens that infect multiple host species have an increased capacity to cause extinctions through parasite-mediated apparent competition. Given unprecedented and continuing losses of biodiversity due to Batrachochytrium dendrobatidis (Bd), the causative fungus of the amphibian skin disease chytridiomycosis, a robust understanding of the mechanisms driving cross-species infection dynamics is essential. Here, we used stage-structured, susceptible-infected compartmental models to explore drivers of Bd-mediated apparent competition between two sympatric amphibians, the critically endangered Litoria spenceri and the non-threatened Litoria lesueurii.

Speech, Language and Non-verbal Communication in CLN2 and CLN3 Batten Disease.

CLN2 and CLN3 diseases, the most common types of Batten disease (also known as neuronal ceroid lipofuscinosis), are childhood dementias associated with progressive loss of speech, language and feeding skills. Here we delineate speech, language, non-verbal communication and feeding phenotypes in 33 individuals (19 females) with a median age of 9.5 years (range 3-28 years); 16 had CLN2 and 17 CLN3 disease; 8/15 (53%) participants with CLN2 and 8/17 (47%) participants with CLN3 disease had speech and language impairments prior to genetic diagnosis.

Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity.

Both intrinsic and extrinsic mechanisms underpin the profound intertumoral heterogeneity in breast cancer. Increasing evidence suggests that the intrinsic characteristics of breast epithelial precursor cells may influence tumour phenotype. These "cells-of-origin" of cancer preside in normal breast tissue and are uniquely susceptible to mutagenesis upon exposure to distinct oncogenic stimuli.

Drug delivery strategies for the treatment of relapse behavior in substance use disorder- A systematic review.

Substance use disorders (SUDs) pose a significant global health challenge, with relapse being a major obstacle in achieving successful treatment outcomes. In recent years, drug delivery strategies have emerged as promising tools to improve treatment efficacy and patient compliance in the context of SUD. Here we explore a diverse range of drug delivery strategies that have been investigated for addressing relapse behavior in SUD.

A rare case of a zero-field single-ion magnet in a cerium(III) pseudo-icosahedral complex.

The synthesis and structural characterisation of [Ln(Tp)]I (1-Ln; Ln = La, Ce, Pr, Nd) (Tp = hydrotris(3-(2'-furyl)-pyrazol-1-yl)borate) have been reported as an isomorphous series adopting pseudo-icosahedral ligand field geometries. Continuous shape measurement (CShM) analyses on the crystal field environments of 1-Ln show the smallest values yet reported for complexes employing two hexadentate ligands (-scorpionate environments), with the smallest belonging to 1-La. Single-ion magnetism for 1-Ce, 1-Pr and 1-Nd was probed with ac magnetic susceptibility studies revealing slow magnetic relaxation for 1-Nd in applied magnetic fields and in zero-applied field for 1-Ce, which is a rare observation for Ce(III)-based single-ion magnets.

Therapeutic blockade of CCL17 in obesity-exacerbated osteoarthritic pain and disease.

Objectives: We previously reported that CCL17 gene-deficient mice are protected from developing pain-like behaviour and exhibit less disease in destabilization of medial meniscus (DMM)-induced OA, as well as in high-fat diet (HFD)-exacerbated DMM-induced OA. Here, we explored if therapeutic neutralization of CCL17, using increasing doses of a neutralizing monoclonal antibody (mAb), would lead to a dose-dependent benefit in these two models.

Design: DMM-induced OA was initiated in male mice either fed with a control diet (7% fat) or 8 weeks of a 60% HFD, followed by therapeutic intraperitoneal administration (i.

Mitochondrial segmentation and function prediction in live-cell images with deep learning.

Mitochondrial morphology and function are intrinsically linked, indicating the opportunity to predict functions by analyzing morphological features in live-cell imaging. Herein, we introduce MoDL, a deep learning algorithm for mitochondrial image segmentation and function prediction. Trained on a dataset of 20,000 manually labeled mitochondria from super-resolution (SR) images, MoDL achieves superior segmentation accuracy, enabling comprehensive morphological analysis.

Gene content of seawater microbes is a strong predictor of water chemistry across the Great Barrier Reef.

Background: Seawater microbes (bacteria and archaea) play essential roles in coral reefs by facilitating nutrient cycling, energy transfer, and overall reef ecosystem functioning. However, environmental disturbances such as degraded water quality and marine heatwaves, can impact these vital functions as seawater microbial communities experience notable shifts in composition and function when exposed to stressors. This sensitivity highlights the potential of seawater microbes to be used as indicators of reef health.

Climate change and the cost-of-living squeeze in desert lizards.

Climate warming can induce a cost-of-living "squeeze" in ectotherms by increasing energetic expenditures while reducing foraging gains. We used biophysical models (validated by 2685 field observations) to test this hypothesis for 10 ecologically diverse lizards in African and Australian deserts. Historical warming (1950-2020) has been more intense in Africa than in Australia, translating to an energetic squeeze for African diurnal species.

Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal-phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts.