The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine.

Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develop a POW virus-like-particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001.

Effects of COVID-19 virus-like particles on the behavioral and cognitive performance of human apolipoprotein E targeted replacement mice.

Introduction: The effects of viral infections might be apolipoprotein E (apoE) isoform-dependent. In humans, there are three major apoE isoforms, E2, E3, and E4. E4 is associated with the enhanced entry of several viruses into the brain and their disease progression.

Systemic exposure to COVID-19 virus-like particles modulates firing patterns of cortical neurons in the living mouse brain.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. We used virus-like particles (VLPs) to explore how exposure to the SARS-CoV-2 proteins affects brain activity patterns in wild-type (WT) mice and in mice that express the wild-type human tau protein (htau mice). VLP exposure elicited dose-dependent changes in corticosterone and distinct chemokine levels.

A genomic approach to Porites (Anthozoa: Scleractinia) megadiversity from the Indo-Pacific.

Porites corals are vital components of tropical reef ecosystems worldwide, serving as ecosystem engineers and hubs of biodiversity in shallow water coral reefs. Despite their ecological significance and the widespread use of Porites spp. as models for research, the richness and evolutionary relationships of species within the genus remain elusive.

Strength of Sexual Selection and Sex Roles Vary between Social Groups in a Coral Reef Cardinalfish.

AbstractThe strength and direction of sexual selection can vary among populations. However, spatial variability is rarely explored at the level of the social group. Here we investigate sexual selection and sex roles in the paternally mouthbrooding, socially monogamous, and site-attached pajama cardinalfish, .

Master of nursing programs in Australia: A desktop analysis.

Background: Master of Nursing (MN) programs serve as an important structured pathway to prepare the nursing workforce to develop advanced capabilities. Little research has been done to examine the key characteristics of MN programs in Australia and their responsiveness to meeting the health needs of the community.

Aim: The aim of this desktop analysis is to provide a detailed overview of the key characteristics of MN programs in Australia.

State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?

Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening.

A novel preclinical model of the normal human breast.

Improved screening and treatment have decreased breast cancer mortality, although incidence continues to rise. Women at increased risk of breast cancer can be offered risk reducing treatments, such as tamoxifen, but this has not been shown to reduce breast cancer mortality. New, more efficacious, risk-reducing agents are needed.

Symbiodiniaceae diversity varies by host and environment across thermally distinct reefs.

Endosymbiotic dinoflagellates (Symbiodiniaceae) influence coral thermal tolerance at both local and regional scales. In isolation, the effects of host genetics, environment, and thermal disturbances on symbiont communities are well understood, yet their combined effects remain poorly resolved. Here, we investigate Symbiodiniaceae across 1300 km in Australia's Coral Sea Marine Park to disentangle these interactive effects.

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.

Background: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Nursing students' experience of bullying and/or harassment during clinical placement.

Problem Or Background: Bullying is a recognised problem in nursing. Nursing students are particularly vulnerable. Bullying and harassment of nursing students can be detrimental to both students and recipients of care.

A qualitative study exploring the challenges and enablers of pharmacists with a recent background in community pharmacy transitioning into primary care.

Background: Pharmacists are an increasing part of the primary care health care team in Scotland. Recruitment to this expanding sector has largely come from community pharmacy. However, it is unknown if these pharmacists have specific needs to perform their role within the primary care team.

Risk Prediction Models for Oral Cancer: A Systematic Review.

In the last 30 years, there has been an increasing incidence of oral cancer worldwide. Earlier detection of oral cancer has been shown to improve survival rates. However, given the relatively low prevalence of this disease, population-wide screening is likely to be inefficient.

Discovery and Characterization of a Bicyclic Peptide (Bicycle) Binder to Thymic Stromal Lymphopoietin.

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that is difficult to drug with conventional small molecules due to the extended protein-protein interactions it forms with both receptors. The hit series was shown to bind to TSLP in a hotspot, that is also used by IL-7Rα.

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold.

Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data.

Risk-stratified screening for the early detection of kidney cancer.

Earlier detection and screening for kidney cancer has been identified as a key research priority, however the low prevalence of the disease in unselected populations limits the cost-effectiveness of screening. Risk-stratified screening for kidney cancer may improve early detection by targeting high-risk individuals whilst limiting harms in low-risk individuals, potentially increasing the cost-effectiveness of screening. A number of models have been identified which estimate kidney cancer risk based on both phenotypic and genetic data, and while several of the former have been shown to identify individuals at high-risk of developing kidney cancer with reasonable accuracy, current evidence does not support including a genetic component.

Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.

Objective: To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.

Methods And Analysis: eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment.

Using science to respond to public exposures from chemical hazards during emergencies in England.

This paper describes how toxicological considerations are an essential component of acute chemical incident response, and how the UK Health Security Agency (UKHSA), as Category 1 responders under the Civil Contingencies Act (2004), provide that expert, authoritative, and timely advice to protect people from exposure to harmful substances. Background information about the general response to emergencies is provided, which gives context to how scientific advice has a positive impact. The importance of chemical identification and speciation, local, and systemic effects, and exposure characteristics are described.

Building the capacity of rural allied health generalists through online postgraduate education: a qualitative evaluation.

Introduction: Workforce development is a key strategy for building the capacity and capability of a workforce. Accordingly, rural and remote practising allied health professionals require relevant and accessible continuing professional development to enhance their knowledge and skills and improve consumer health outcomes. This study explored the impact of an online postgraduate allied health rural generalist education program, from the perspective of allied health professionals participating in the program and their supervisors and managers.

The challenge of screen mediated shared reading for children's learning and engagement.

Introduction: Screen mediated shared reading (SMSR), which involves an adult reading a child a book through video-chat, is a recent development in shared reading. In this study, we investigated whether, as in in-person shared reading, children could learn new words from SMSR, and whether having a physical copy of the book to follow along with impacted children's novel word retention and engagement in this setting.

Method: Three- to 5-year-old participants ( = 34) were read an 8-page rhyming, "Meet the Friendly Monsters" story by a researcher over Zoom, via screen sharing an e-version of the story used in previous studies.

Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.

Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models.

Introducing a group-based psychoeducation intervention for older people in an inpatient mental healthcare setting.

This article reports on a service evaluation of a group-based psychoeducation programme for older people in an inpatient mental healthcare setting. It sought to explore how the programme was experienced by patients and staff, as well as its acceptability and the feasibility for implementation in the longer term. Via questionnaires, views were gathered from patients and staff.

A case of retroperitoneal abscess secondary to duodenal perforation.

The development of a retroperitoneal abscess in the setting of duodenal perforation is a rare occurrence. There are various causes of duodenal perforation such as trauma, iatrogenic injury and, most commonly, peptic ulcer disease [1]. Urgent surgical intervention is required when a patient presents with a perforated duodenal ulcer and signs of peritonitis.

Ageing of juvenile coral grouper () reveals year-round spawning and recruitment: implications for seasonal closures.

Temporal patterns in spawning and juvenile recruitment can have major effects on population size and the demographic structure of coral reef fishes. For harvested species, these patterns are crucial in determining stock size and optimizing management strategies such as seasonal closures. For the commercially important coral grouper ( spp.