Single cell transcriptomics of the cerebral cortex of mice lacking the PRC2 gene eed.

Objective: The Polycomb Repressive Complex 2 (PRC2) regulates neural stem cell behaviour during development of the cerebral cortex, yet how the loss of PRC2 developmentally influences cell identity in the mature brain is poorly defined. Using a mouse model in which the PRC2 gene Embryonic ectoderm development (Eed) was conditionally deleted from the developing mouse dorsal telencephalon, we performed single nuclei RNA sequencing (snRNA-seq) on the cortical plate of an adult heterozygote Eed knockout mouse and an adult homozygote Eed knockout mouse compared to a littermate control. This work was part of a larger effort to understand consequences of mutations to PRC2 within the mature brain.

Diagnostic yield of upper gastrointestinal tract endoscopy and colonoscopy in patients with iron deficiency anaemia while on direct oral anticoagulants.

Background: Iron deficiency anaemia (IDA) related to occult gastrointestinal tract (GIT) blood loss is associated with high rates of GIT malignancies. Major society guidelines recommend bidirectional endoscopic evaluation for all men and post-menopausal women with newly diagnosed, unexplained IDA. However, in patients prescribed direct oral anticoagulants (DOACs), the endoscopic yield, specifically the rate of high-risk findings, including colorectal cancers (CRCs) and advanced adenomas (AAs), is unknown.

Gross anatomical features of the insular cortex in affective disorders.

Introduction: The number of insular gyri is elevated in patients with schizophrenia. Thus, it has potential as a marker of early neurodevelopmental abnormalities. However, currently it remains unclear whether patients with other neuropsychiatric disorders, such as affective disorders, also have this gross brain anatomical feature.

ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP-IV, α-amylase, and α-glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential.

The study investigates the inhibitory properties of Mangiferin and Friedelin against glucokinase, DPP-IV, α-amylase, and α-glucosidase using computational methods, in vitro enzyme assays, and in-depth ADMET analysis. The study utilized a computer-aided drug design approach to assess the potential therapeutic properties of Mangiferin and Friedelin as T2DM therapeutic agents. Molecular docking studies' outcomes encouraged the evaluation of both compounds in in vitro enzymatic assays.

CBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.

The MYC proto-oncogene is upregulated in >60% of triple-negative breast cancers (TNBCs), it can directly promote tumor cell proliferation, and its overexpression negatively regulates anti-tumor immune responses. For all these reasons, MYC has long been considered as a compelling therapeutic target. However, pharmacological inhibition of MYC function has proven difficult due to a lack of a drug-binding pocket.

Intuitive eating predictors and outcomes in people with severe mental illness participating in a lifestyle intervention.

Issue Addressed: People with severe mental illness (SMI) are at higher risk of preventable diseases than the general population; poor diet contributes to heightened risk. Adaptive approaches designed to improve intuitive eating may improve dietary behaviours in people with SMI. Aims of this study were to investigate predictors of, and assess the impact of a nutrition program on, intuitive eating in people with SMI.

Risk treatment thresholds for initiating cardiovascular disease pharmacotherapy: Synthesis of international evidence to support guideline recommendations.

Background: A new Australian guideline for cardiovascular disease (CVD) risk assessment and management was published in 2023, including new risk treatment thresholds.

Objective: This article summarises the published peer-reviewed global evidence that informed guideline recommendations on risk treatment thresholds for initiating blood pressure- and lipid-lowering therapy for CVD primary prevention.

Discussion: Evidence from 13 meta-analyses, randomised controlled trials and modelling studies involving more than 515,700 patients showed that preventive pharmacotherapy reduced the number of CVD events at all risk levels.

Differences in mean age at diagnosis of invasive melanoma for men and women, by anatomic site, thickness, and subtype.

Background: Understanding the factors influencing age at melanoma diagnosis by sex and anatomic site is crucial for developing effective prevention and early detection strategies. While previous research has highlighted sex-based differences in melanoma incidence by age and anatomic distribution, the underlying mechanisms remain unclear. We aimed to investigate sex-specific patterns in melanoma age at diagnosis across different anatomic sites and thickness categories, considering the potential influence of disease progression and detection rates.

An unusual case of primary pituitary abscess due to Corynebacterium pseudodiphtheriticum.

Pituitary abscesses are an uncommon cause of pituitary lesions. A 77-year-old woman presented for elective resection of a presumed non-functioning pituitary macroadenoma in the context of a progressive left-sided visual field deficit. She proceeded to trans-sphenoidal resection of the pituitary lesion, with purulent fluid found upon opening the pituitary capsule.

Rates of colorectal cancer diagnosis and mortality in people with severe mental illness: results from Australia's National Bowel Cancer Screening Programme.

Aims: Studies show that people with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC). These studies mostly predate the introduction of national bowel cancer screening programmes (NBCSPs) and it is unknown if these have reduced disparity in CRC-related mortality for people with SMI.

Methods: We compared mortality rates following CRC diagnosis at colonoscopy between a nationally representative sample of people with and without SMI who participated in Australia's NBCSP.

Development of a latex microsphere-based lateral flow immunoassay for the diagnosis of schistosomiasis japonica.

Background: Zoonotic schistosomiasis, caused by Schistosoma japonicum, is prevalent in China, the Philippines and Indonesia. Rapid point-of-care (POC) diagnostics are attractive and promising tools for evaluating the efficacy of intervention strategies for schistosomiasis control.

Methodology: The diagnostic potential of five recombinant antigens was tested by enzyme-linked immunosorbent assay (ELISA) using sera from individuals with positive Kato-Katz (KK) results for S.

Long-term co-circulation of multiple arboviruses in southeast Australia revealed by xeno-monitoring and viral whole-genome sequencing.

Arbovirus surveillance of wild-caught mosquitoes is an affordable and sensitive means of monitoring virus transmission dynamics at various spatial-temporal scales, and emergence and re-emergence during epidemic and interepidemic periods. A variety of molecular diagnostics for arbovirus screening of mosquitoes (known as xeno-monitoring) are available, but most provide limited information about virus diversity. Polymerase chain reaction (PCR)-based screening coupled with RNA sequencing is an increasingly affordable and sensitive pipeline for integrating complete viral genome sequencing into surveillance programs.

Genomic network analysis characterizes genetic architecture and identifies trait-specific biology.

Pervasive genetic overlap across human complex traits necessitates developing multivariate methods that can parse pleiotropic and trait-specific genetic signals. Here, we introduce Genomic Network Analysis (GNA), an analytic framework that applies the principles of network modelling to estimates of genetic overlap derived from genome-wide association study (GWAS) summary statistics. The result is a genomic network that describes the conditionally independent genetic associations between traits that remain when controlling for shared signal with the broader network of traits.

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.

Divers treated in Townsville, Australia: worse symptoms lead to poorer outcomes.

Introduction: Hyperbaric oxygen treatment (HBOT) is considered definitive treatment for decompression illness. Delay to HBOT may be due to dive site remoteness and limited facility availability. Review of cases may help identify factors contributing to clinical outcomes.

Validation and Performance of Quantitative BRCA1 and RAD51C Promoter Hypermethylation Testing in Breast and Ovarian Cancers.

Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors represent a significant advancement in the treatment of epithelial ovarian cancer, triple-negative breast cancer, pancreatic cancer, and castrate-resistant prostate cancer, and they are poised to improve treatment in an increasing number of other cancer types. PARP inhibitor efficacy as monotherapy has been primarily observed in tumors with deleterious genetic variants in genes involved in the homologous recombination repair pathway. Tumors without these variants have also been shown to respond; notably, those with hypermethylation at all alleles of the BRCA1 or RAD51C promoter can respond to PARP inhibitors.

totally implantable venous access device infection in a person with cystic fibrosis: Complex management considerations.

Totally implantable venous access devices (TIVADs) are frequently used in people with cystic fibrosis as a means of securing consistent vascular access, particularly in the context of severe disease and microbial colonization. Infection of TIVADs is not uncommon and typically associated with coagulase negative staphylococci, though infection with other organisms does occur too. We report on the first case of a TIVAD infection caused by in person with cystic fibrosis.

The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study.

Background: Eritrea was the first African country to discontinue the use of histidine rich protein 2 (HRP2)-detecting rapid diagnostic tests (RDTs) for malaria diagnosis following reports of a high prevalence of pfhrp2/3-deleted Plasmodium falciparum parasites causing false-negative results in the country. Eritrea was also the first African country to report partial artemisinin resistance due to the P falciparum kelch13 (pfk13) Arg622Ile mutation. We aimed to characterise the spatial distribution of pfk13 mutants and their interactions with pfhrp2/3 deletions in Eritrea and to assess the role of the use of HRP2-detecting RDTs and antimalarial (artesunate-amodiaquine) therapy in the spread of the two variants.

Agreement between clinical criteria and quantitative polymerase chain reaction for diagnosing scabies in Auckland children.

Aim: We sought to determine the degree of agreement between clinical and laboratory methods for diagnosing scabies in school-aged children.

Methods: Clinical information and samples were collected from children aged 7 months to 14 years attending educational institutions in Auckland, New Zealand. Two methods determined scabies status: the International Alliance for the Control of Scabies clinical criteria (IACS) and quantitative polymerase chain reaction (qPCR).

Comprehensive humoral and cellular immune responses to COVID-19 vaccination in adults with cancer.

Background: The COVID-19 pandemic has significantly impacted people with cancer. Initial vaccine studies excluded patients with malignancy. Immunocompromised individuals remain vulnerable to SARS-CoV-2, necessitating detailed understanding of vaccine response.

Prevalence and characteristics of online child sexual victimization: Findings from the Australian Child Maltreatment Study.

Background: Online child sexual victimization is increasingly facilitated by technology, but evidence of its prevalence and characteristics remains scarce. Reliable population-based data is critical to understand the magnitude and nature of the problem, and inform evidence-based prevention.

Objective: To determine the prevalence of nonconsensual sharing of sexual images of the child by any perpetrator, and of online sexual solicitation by any adult perpetrator; and to determine the characteristics of these experiences.