Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.

Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

Preparing Australian diabetes educators for practice: workforce perceptions of the credentialling pathway.

The Australian Credentialled Diabetes Educator (CDE) registered trademark signifies quality care and education to those with diabetes. A review of the Australian Diabetes Educators Association (ADEA) CDE pathway was undertaken to ensure the quality of the CDE credential. The purpose of this study was to examine perceptions of the diabetes education workforce on the current pathway for educating and qualifying CDEs for practice.

High-intensity focused ultrasound: an innovative approach for micro-manipulation of demineralized dentine.

Background: Treatment of deep carious lesions poses significant challenges in dentistry, as complete lesion removal risks compromising pulp vitality, while selective removal often reduces the longevity of restorations. Herein, we propose a minimally invasive approach using High-Intensity Focused Ultrasound (HIFU) for microscale removal of carious dentine. Concurrently, HIFU's antimicrobial effects against associated cariogenic biofilms and the corresponding thermal and biological impacts on surrounding tissues were investigated.

Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.

Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development.

Developing clinical reasoning along the cognitive continuum: a mixed methods evaluation of a novel Clinical Diagnosis Assessment.

Background: Clinical reasoning is a professional capability required for clinical practice. In preclinical training, clinical reasoning is often taught implicitly, and feedback is focused on discrete outcomes of decision-making. This makes it challenging to provide meaningful feedback on the often-hidden metacognitive process of reasoning to address specific clinical reasoning difficulties.

Community knowledge of Australia's national preventive health strategy focus areas: a nationally representative survey of 1509 adults.

Background: While some general patterns and trends of health information seeking and literacy in the Australian population are known, there is a need to understand these behaviours and skills specific to the focus areas outlined in the National Preventive Health Strategy (NPHS).

Methods: In response, this study employed a cross-sectional online survey of adults in the Australian general population (n = 1509) to investigate their knowledge and health information seeking behaviour regarding the NPHS' seven focus areas. It also explored primary care practitioners as a preventive health information source.

Public health economic modelling in evaluations of salt and/or alcohol policies: a systematic scoping review.

Background: Public health economic modelling is an approach capable of managing the intricacies involved in evaluating interventions without direct observational evidence. It is used to estimate potential long-term health benefits and cost outcomes. The aim of this review was to determine the scope of health economic models in the evaluation of salt and/or alcohol interventions globally, to provide an overview of the literature and the modelling methods and structures used.

Awareness of cardiovascular disease risk and care received among Australian women with a history of hypertensive disorders of pregnancy: a cross-sectional survey.

Background: Women with a history of hypertensive disorders of pregnancy (HDP), including chronic hypertension, gestational hypertension, and preeclampsia have an increased risk of cardiovascular disease (CVD). Current research suggests that general practitioners are unaware of women's HDP history, and although ideally placed to follow-up with these women, there is limited understanding of current CVD prevention practices in women after HDP. Additionally, preeclampsia confers a higher CVD risk compared to other types of HDP, and Australian research suggests that lower socioeconomic status (SES) is associated with a higher incidence of both HDP and CVD.

Exploring artificial intelligence for differentiating early syphilis from other skin lesions: a pilot study.

Background: Early diagnosis of syphilis is vital for its effective control. This study aimed to develop an Artificial Intelligence (AI) diagnostic model based on radiomics technology to distinguish early syphilis from other clinical skin lesions.

Methods: The study collected 260 images of skin lesions caused by various skin infections, including 115 syphilis and 145 other infection types.

Exploring the experiences of women and people with diabetes in pregnancy in metropolitan and rural Australia: a national survey.

Background: Women and people diagnosed with diabetes in pregnancy, are recommended to have frequent monitoring and careful management for optimal pregnancy outcomes. This health care management should be supported by a multidisciplinary healthcare team. For individuals living in rural areas, there are increased barriers to healthcare access, with subsequent worse health outcomes compared to those in metropolitan regions.

Does the School Environment and School Engagement in Early High School Predict Trajectories of Anti-Social Behaviour? A National Longitudinal Study of Australian Youth From 12 to 19 years.

Background: Schools are widely considered important agents of social control for young people. Consequently, school engagement, disengagement and the school environment are key to understanding behavioural outcomes during adolescence. This study addresses an empirical gap in longitudinal research by examining new types of school engagement, as well as school-level environmental factors.

Course of Mental Disorders in Early Cancer Survivorship in Relation to Socioeconomic Status: A Multi-Center Prospective Longitudinal Study (LUPE).

Objective: Individuals with low socioeconomic status (SES) exhibit higher rates of mental disorders; however, data in oncological populations are insufficient. This study investigated the course of DSM-5 mental disorders in cancer patients, stratified by SES, over a period of 1.5 years following initial cancer diagnosis.

Longitudinal strain enhancement and bending deformations in piezoceramics.

Piezoelectric materials directly convert between electrical and mechanical energies. They are used as transducers in applications such as nano-positioning and ultrasound imaging. Improving the properties of these devices requires piezoelectric materials capable of delivering a large longitudinal strain on the application of an electric field.

Dynamic supramolecular snub cubes.

Mimicking the superstructures and properties of spherical biological encapsulants such as viral capsids and ferritin offers viable pathways to understand their chiral assemblies and functional roles in living systems. However, stereospecific assembly of artificial polyhedra with mechanical properties and guest-binding attributes akin to biological encapsulants remains a formidable challenge. Here we report the stereospecific assembly of dynamic supramolecular snub cubes from 12 helical macrocycles, which are held together by 144 weak C-H hydrogen bonds.

Evaluation of clinical risk stratification to determine benefit from long-term versus short-term androgen deprivation in high-risk localized prostate cancer.

Background: Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT).

Methods: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials.

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.

Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

A decade of advances in human gut microbiome-derived biotherapeutics.

Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

Sulfide-rich continental roots at cratonic margins formed by carbonated melts.

The cratonic crust contains abundant mineral deposits of metals such as gold, copper and rare earths and is underlain by a thick mantle lithosphere rich in the volatiles carbon, sulfur and water. Although volatiles are known to be key components in metallogenesis, how and where they are distributed in the cratonic lithosphere mantle and their role in the initial enrichment of metals have not been sufficiently explored. Here we compile sulfur and copper contents of global cratonic peridotites, identifying sulfide-rich and copper-rich continental roots at depths of 160-190 km at cratonic margins.

Heritable polygenic editing: the next frontier in genomic medicine?

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.

Biomass carbon emissions from nickel mining have significant implications for climate action.

Global nickel demand is projected to double by 2050 to support low-carbon technologies and renewable energy production. However, biomass carbon emissions from clearing vegetation for nickel mining are rarely included in corporate sustainability reports or considered in mineral sourcing decisions. Here, we compiled data for 481 nickel mines and undeveloped deposits to show that the footprint of nickel mining could be 4 to 500 times greater than previously reported (depending on the mine site), and thus the environmental impacts of nickel products, including batteries, have been underestimated to date.