Findings from a Project Which Established Hepatitis C Point-of-Care Testing and Linkage to Care at a Homelessness Service in Adelaide, Australia, 2021-2022.

Background: Point-of-care hepatitis C virus (HCV) testing streamlines testing and treatment pathways. In this study, we established an HCV model of care in a homelessness service by offering antibody and RNA point-of-care testing.

Methods: A nurse and peer-led HCV model of care with peer support were implemented between November 2021 and April 2022 at a homelessness service in Adelaide, Australia.

A Covalent Chemical Probe for nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity.

RA-0003022 () was identified as a high-quality covalent chemical probe for nsP2 cysteine protease (nsP2pro). Isoxazole covalently captured the active site C478 and inactivated the enzyme with a / ratio of 6000 Ms. A negative control analog RA-0025453 () retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition.

The 5-year outcomes of a health-empowerment program on low-income children's behaviors and quality of life.

Background: This study aims to evaluate the 5-year impact of a Health Empowerment Program (HEP) on mitigating problematic conducts and enhancing the health-related quality of life (HRQOL) among children living in poverty.

Methods: A prospective cohort study (N = 239, Intervention group: n = 124, Comparison group: n = 115) was established with participants recruited between July 2013 and March 2016 and followed until November 2021. During the 5-year study period, children and their parents from the intervention group were invited to join a multi-dimensional HEP.

Cryo-EM structure of a novel α-synuclein filament subtype from multiple system atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by accumulation of α-synuclein cross-β amyloid filaments in the brain. Previous structural studies of these filaments by cryo-electron microscopy (cryo-EM) revealed three discrete folds distinct from α-synuclein filaments associated with other neurodegenerative diseases. Here, we use cryo-EM to identify a novel, low-populated MSA filament subtype (designated Type I) in addition to a predominant class comprising MSA Type II filaments.

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

Updates in digital shared care: Launching into the 21st century.

Background: The recent Intergenerational Report (2023) highlighted that the Australian healthcare system will face increasing economic and logistical challenges, with projected growth in health spending due to an ageing population and an increasing number of chronic diseases. Shared care, a model emphasising collaboration between nursing and allied health, general practice and specialist care providers, has emerged as one solution.

Objective: This paper explores the contemporary shared care landscape in Australia, highlighting the digital transformation of healthcare, the adoption of eHealth technologies, and their impact on improving patient care coordination.

Amyloid accelerator polyphosphate fits as the mystery density in α-synuclein fibrils.

Aberrant aggregation of α-Synuclein is the pathological hallmark of a set of neurodegenerative diseases termed synucleinopathies. Recent advances in cryo-electron microscopy have led to the structural determination of the first synucleinopathy-derived α-Synuclein fibrils, which contain a non-proteinaceous, "mystery density" at the core of the protofilaments, hypothesized to be highly negatively charged. Guided by previous studies that demonstrated that polyphosphate (polyP), a universally conserved polyanion, significantly accelerates α-Synuclein fibril formation, we conducted blind docking and molecular dynamics simulation experiments to model the polyP binding site in α-Synuclein fibrils.

CuFe Cooperativity at the Membrane-Electrode Interface Elicits a Tandem 2e+2e Mechanism for Exclusive O-To-HO Electroreduction.

High O reduction reaction (ORR) kinetics and exclusive 4e pathway selectivity are keys to realizing a sustainable society. However, nonprecious electrocatalysts at present cannot enhance the ORR turnover frequency and HO Faradaic efficiency (FE) concurrently. To address these two challenges, hybrid bilayer membrane (HBM) electrodes with earth-abundant metal centers are developed to control proton-coupled electron transfer (PCET) in ORR.

Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies.

Inhibition of human carcinomas has previously been linked to vitamin D due to its effects on cancer cell proliferation, migration, angiogenesis, and apoptosis induction. The anticancer activity of vitamin D has been confirmed by several studies, which have shown that increased cancer incidence is associated with decreased vitamin D and that dietary supplementation of vitamin D slows down the growth of xenografted tumors in mice. Vitamin D inhibits the growth of cancer cells by the induction of apoptosis as well as by arresting the cells at the G0/G1 (or) G2/M phase of the cell cycle.

Open Source Code Contributions to Global Health: The Case of Antimalarial Drug Discovery.

The discovery of treatments for infectious diseases that affect the poorest countries has been stagnant for decades. As long as expected returns on investment remain low, pharmaceutical companies' lack of interest in this disease area must be compensated for with collaborative efforts from the public sector. New approaches to drug discovery, inspired by the "open source" philosophy prevalent in software development, offer a platform for experts from diverse backgrounds to contribute their skills, enhancing reproducibility, progress tracking, and public discussion.

eHealth Platforms Facilitate Prostate Cancer Shared Care: A Systematic Review.

Background: Prostate cancer survivorship care is essential for the early identification of cancer recurrence and progression and the monitoring of adverse effects. Prostate cancer survivorship programs have enabled care to be shared between specialists using digital healthcare platforms. We systematically reviewed the literature to examine if prostate cancer survivorship care had been successfully digitalised.

Increasing the tumour targeting of antitumour drugs through anlotinib-mediated modulation of the extracellular matrix and the RhoA/ROCK signalling pathway.

Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing (RNA-seq) and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness.

Chemical Auxiliary for Photocatalytic Active Colloids.

Active colloids with the ability to self-propel and collectively organize are emerging as indispensable elements in microrobotics and soft matter physics. For chemically powered colloids, their activity is often induced by gradients of chemical species in the particle's vicinity. The direct manipulation of these gradients, however, presents a considerable challenge, thereby limiting the extent to which active colloids can be controlled.

External validation of the Hong Kong Chinese non-laboratory risk models and scoring algorithm for case finding of prediabetes and diabetes mellitus in primary care.

Aims/introduction: Two Hong Kong Chinese non-laboratory-based prediabetes/diabetes mellitus (pre-DM/DM) risk models were developed using logistic regression (LR) and machine learning, respectively. We aimed to evaluate the models' validity in case finding of pre-DM/DM in a Chinese primary care (PC) population. We also evaluated the validity of a risk-scoring algorithm derived from the LR model.

Evening dosing versus morning dosing of antihypertensive medications for nocturnal hypertension: a systematic review and meta-analysis of 107 randomized controlled trials.

Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration.

Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

Introduction: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy.

Methods: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years.

Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?

Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity and dysbalanced metabolism were associated with the disruption of intracellular respiration and the development of various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which was also observed in malignant cells, representing an attractive anti-cancer instrument.

Metal-detection based techniques and their applications in metallobiology.

Metals are essential for human health and play a crucial role in numerous biological processes and pathways. Gaining a deeper insight into these biological events will facilitate novel strategies for disease prevention, early detection, and personalized treatment. In recent years, there has been significant progress in the development of metal-detection based techniques from single cell metallome and proteome profiling to multiplex imaging, which greatly enhance our comprehension of the intricate roles played by metals in complex biological systems.

Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly.

The mitochondrial chaperonin, mitochondrial heat shock protein 60 (mtHsp60), promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin progresses through its ATP-dependent client folding cycle are not clear. Here, we determined cryo-EM structures of a hyperstable disease-associated human mtHsp60 mutant, V72I.