A Survey of the Metabolic Landscape of the Developing Cerebellum at Single-Cell Resolution.

The use of cell-culture models to investigate development and disease of the cerebellum is a recent advance, facilitated by the discovery that patterning of precursors is capable of giving rise to cells with specific neuronal identity. Pluripotent stem cell-derived organoids, which exhibit self-organisational characteristics reminiscent of early cerebellar tissue, present a number of challenges including recapitulation of conditions resembling the mature brain. An understanding of the processes driving fetal and postnatal maturation is required to reproduce these conditions in vitro and advance the capability of the system to model adult-onset disease.

Seroprevalence of chikungunya virus among military personnel in Papua New Guinea, 2019.

Objectives: The first outbreak of chikungunya virus (CHIKV) was reported in West Sepik, Papua New Guinea (PNG) in June 2012, and spread rapidly throughout PNG. CHIKV imported from PNG to Queensland has been reported occasionally, but transmission of CHIKV in PNG remains unclear due to the lack of testing capability. This study investigated the degree of CHIKV exposure among PNG military personnel (PNGMP) in 2019, 7 years after its first emergence.

A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED).

Objective: Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC).

Methods: Eligible patients with mBC were treated with nab-paclitaxel (100mg/m) weekly for 3 weeks with one week break in a 28-day cycle.

An "Uncharacterized" Australian Virus Is the Earliest Known Example of Ross River Virus with Changes in the nsP3 Protein Associated with the Explosive Outbreak of Ross River Virus Infection in the Pacific Region from 1979 to 1980.

Ross River virus recovered from a South Australian patient during an outbreak of epidemic polyarthritis in 1971 is the earliest known genome sequence with the duplicated 12-amino-acid motif in the nsP3 protein that was found in strains responsible for the outbreak of epidemic polyarthritis in the Pacific region from 1979 to 1980.

Risk and Protective Factors of Lifetime Cocaine-Associated Chest Pain.

Cocaine users often present with repetitive events of cocaine-associated chest pain (CACP), clinically resembling acute coronary syndromes. The aim of the study is to describe the specific risk factors for CACP. Cocaine users ( = 316) were recruited for a multicenter cross-sectional study.

Genetic Relationship Between Endometriosis and Melanoma.

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report.

Positive results from recent clinical trials have significantly expanded current therapeutic options for patients with chronic graft-versus-host disease (GVHD). However, new insights into the associations between clinical characteristics of chronic GVHD, pathophysiologic mechanisms of disease, and the clinical and biological effects of novel therapeutic agents are required to allow for a more individualized approach to treatment. The current report is focused on setting research priorities and direction in the treatment of chronic GVHD.

Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.

Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively).

Evaluation of Crizotinib Treatment in a Patient With Unresectable GOPC-ROS1 Fusion Agminated Spitz Nevi.

Importance: Spitz nevi are benign melanocytic neoplasms that classically present in childhood. Isolated Spitz nevi have been associated with oncogenic gene fusions in approximately 50% of cases. The rare agminated variant of Spitz nevi, thought to arise from cutaneous genetic mosaicism, is characterized by development of clusters of multiple lesions in a segmental distribution, which can complicate surgical removal.

In Search of the Holy Grail: A Specific Diagnostic Test for Rheumatic Fever.

Current diagnosis of Acute Rheumatic Fever and Rheumatic Heart Disease (ARF/RHD) relies on a battery of clinical observations aided by technologically advanced diagnostic tools and non-specific laboratory tests. The laboratory-based assays fall into two categories: those that (1) detect "evidence of preceding streptococcal infections" (ASOT, anti-DNAse B, isolation of the Group A from a throat swab) and (2) those that detect an ongoing inflammatory process (ESR and CRP). These laboratory tests are positive during any streptococcal infection and are non-specific for the diagnosis of ARF/RHD.

Requirements for a Robust Animal Model to Investigate the Disease Mechanism of Autoimmune Complications Associated With ARF/RHD.

The pathogenesis of Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral complications including Sydenham's chorea (SC) is complex. Disease complications triggered by Group A streptococcal (GAS) infection are confined to human and determining the early events leading to pathology requires a robust animal model that reflects the hallmark features of the disease. However, modeling these conditions in a laboratory animal, of a uniquely human disease is challenging.

ClearSight™ finger cuff versus invasive arterial pressure measurement in patients with body mass index above 45 kg/m.

Background: Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.

Are prescription misuse and illicit drug use etiologically distinct? A genetically-informed analysis of opioids and stimulants.

Background: Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue.

Trends in epidemiology, treatment and molecular testing of metastatic colorectal cancer in a real-world multi-institution cohort study.

Aim: Colorectal cancer (CRC) is the third most common cancer in Australia, and survival after diagnosis of metastatic disease is improving. Our aim was to assess trends in epidemiology, treatment, molecular testing and survival in patients with metastatic CRC (mCRC).

Methods: Clinical data from February 2013 to December 2018 was recorded in a prospective, observational, multicenter cohort study conducted in Queensland, Australia, examining clinical and molecular biomarkers in cases of mCRC.

Sex differences in the relative influence of marital status and parenthood on alcohol use disorder symptoms: A multilevel discordant twin design.

Marriage and parenthood are associated with alcohol use and use disorder (AUD), although they are confounded such that many studies struggle to identify their unique and/or causal effects. The present study utilized a genetically informed discordant twin design that strengthens the putative causal role of marital and parental status in the presentation of AUD symptoms by using each individual's cotwin as their own control while simultaneously modeling both predictors among men and women. Participants were 980 complete same-sex twin pairs from the Australian Twin Registry ( = 31.

Childhood maltreatment and disordered gambling in adulthood: disentangling causal and familial influences.

Background: Despite abundant research on the potential causal influence of childhood maltreatment (CM) on psychological maladaptation in adulthood, almost none has implemented the discordant twin design as a means of examining the role of such experiences in later disordered gambling (DG) while accounting for genetic and family environmental confounds. The present study implemented such an approach to disentangle the potential causal and familial factors that may account for the association between CM and DG.

Methods: Participants were 3750 twins from the Australian Twin Registry [Mage = 37.

Australian Aedes aegypti mosquitoes are susceptible to infection with a highly divergent and sylvatic strain of dengue virus type 2 but are unlikely to transmit it.

Background: Humans are the primary hosts of dengue viruses (DENV). However, sylvatic cycles of transmission can occur among non-human primates and human encroachment into forested regions can be a source of emergence of new strains such as the highly divergent and sylvatic strain of DENV2, QML22, recovered from a dengue fever patient returning to Australia from Borneo. The objective of the present study was to evaluate the vector competence of Australian Aedes aegypti mosquitoes for this virus.

If Human Brain Organoids Are the Answer to Understanding Dementia, What Are the Questions?

Because our beliefs regarding our individuality, autonomy, and personhood are intimately bound up with our brains, there is a public fascination with cerebral organoids, the "mini-brain," the "brain in a dish". At the same time, the ethical issues around organoids are only now being explored. What are the prospects of using human cerebral organoids to better understand, treat, or prevent dementia? Will human organoids represent an improvement on the current, less-than-satisfactory, animal models? When considering these questions, two major issues arise.

Genomic Investigation Reveals Contaminated Detergent as the Source of an Extended-Spectrum-β-Lactamase-Producing Klebsiella michiganensis Outbreak in a Neonatal Unit.

species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing colonizing neonates. Ceftriaxone-resistant spp.