Endometrial cancer (EC) patients with metastatic/recurrent disease have limited treatment options and poor survival outcomes. Recently, we discovered the FGFR2c splice isoform is associated with poor prognosis in EC patients. Here we report the establishment of 16 EC patient-derived xenografts (PDX)-derived organoids (PDXOs) with or without FGFR2c expression. In vitro treatment of 5 EC PDXOs with BGJ398 showed significant cell death in 3 models with FGFR2c expression. PDXs with high/moderate FGFR2c expression showed significant tumour growth inhibition (TGI) following 21-day treatment with FGFR inhibitors (BGJ398 or pemigatinib) and significantly prolonged survival in 4/5 models. Pemigatinib + cisplatin combination therapy (n = 5) resulted in significant TGI and prolonged survival in one of two p53abn PDXs. All five models treated with cisplatin alone showed de novo resistance and no survival benefit. Seven-day treatment with BGJ398 revealed a significant reduction in angiogenesis and CD206 + M2 macrophages. These data collectively support the evaluation of FGFR inhibitors in a clinical trial.

Background and aimsTriple Negative Breast Cancer (TNBC) is associated with increased angiogenesis, which is known to aid tumour growth and metastasis. Anti-angiogenic therapies that have been developed to target this feature have mostly generated disappointing clinical results. Further research into targeted approaches is limited by a lack of understanding of the in situ molecular profile of tumour-associated vasculature. In this study, we aimed to understand the differences in the molecular profiles of tumour endothelial cells vs normal-adjacent endothelial cells in TNBC tissues. MethodWe have applied unbiased whole transcriptome spatial profiling of in situ gene expressions of endothelial cells localized in full-face patient TNBC tissues (n = 4) and normal-adjacent regions of the same patient breast tissues. ResultsOur comparative analysis revealed that 2412 genes were differentially expressed (padj < 0.05) between the tumour endothelial cells and normal-adjacent endothelial cells. Pathway enrichment showed the enrichment of gene sets related to cell-cell, cell-ECM adhesion, chromatin organization and remodeling, and protein-DNA complex subunit organization. ConclusionOverall, the results revealed unique molecular profiles and signalling pathways of tumour-associated vasculature, which is a critical step towards larger cohort studies investigating potential targets for TNBC prognosis and anti-angiogenic treatments.

The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N-glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N-glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody COVA2-17 binding. Glycan site-occupancy analyses revealed that the mutation resulted in N-glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles.

Background: In community and school settings, gardens and garden interventions have been shown to confer several psychosocial, physiological, and nutritional benefits. However, little is known about the implementation and impact of health care gardens on patients, visitors, and staff health and well-being. The primary aim of this review is to identify and describe the types of gardens and common design elements implemented in health care settings and the impact these gardens have on the health and well-being of patients, visitors, and staff. A secondary aim is to assess the quality of available evidence. Methods: PubMed, CINAHL, EMBASE, and PsycINFO were systematically searched on October 28, 2022. Primary qualitative and quantitative studies (excluding case reports and studies) were eligible for inclusion if they described the types of gardens and common design elements implemented in health care settings (hospitals, aged care, rehabilitation facilities, and medical centers) and/or assessed the impact of garden interventions on the health and well-being of patients, visitors, and staff. Review, selection, and data extraction were conducted by two independent researchers, with findings synthesized and presented in narrative form. Articles were critically appraised using the mixed methods appraisal tool (MMAT). Results: Eighteen articles were included. Eight studies provided detailed descriptions of the types of gardens implemented in health care settings (healing [n = 3], therapeutic [n = 2], sensory [n = 2], children's fairy gardens [n = 1], and enriched [n = 1] gardens). Studies examining the psychosocial impacts of gardens were most frequently reported (n = 16), followed by physical (n = 4) and nutritional (n = 2). A wide range of positive outcomes, predominantly relating to patients (n = 12), were reported, including improvements in stress, quality of life (QOL), cognitive function, physical activity, and fruit and vegetable intake. The evidence was heterogeneous and low-medium quality. Conclusions: The findings suggest that implementing gardens and garden interventions in health care settings may positively impact the health and well-being of patients, visitors, and staff. Most studies related to the impact of gardens on patients' mental health and QOL, indicating the need for further research to explore physical and nutritional outcomes, as well as health outcomes of staff and visitors. Findings also suggest the need for high-quality study designs (e.g., cluster control trials) and standardized measurement tools.

Non-small-cell lung cancer (NSCLC) is a prevalent and often fatal malignancy. Advancements in targeted therapies have improved outcomes for NSCLC patients in the last decade. Kirsten rat sarcoma virus (KRAS) is a commonly mutated oncogene in NSCLC, contributing to tumorigenesis and proliferation. Though classically difficult to target, recently developed KRAS G12C inhibitors (sotorasib and adagrasib) have now overcome this therapeutic hurdle. We discuss the evidence for these medications, their pitfalls and adverse effects, as well as future directions in this space. Though these medications demonstrate substantial response rates in a heavily pre-treated advanced NSCLC cohort, as phase-3 evidence does not yet demonstrate an overall survival benefit versus standard-of-care chemotherapy, docetaxel. Additionally, these medications appear to have a negative interaction in combination with immunotherapies, with substantially greater hepatotoxicity rates observed. Despite this, it is undeniable that these medications represent an important advancement in targeted and personalised oncological treatment. Current and future trials assessing these medications in combination and through sequencing strategies will likely yield further clinically meaningful outcomes to guide treatment in this patient cohort.

BackgroundPerinatal women are highly vulnerable to developing mental health issues and particularly susceptible to a recurrence of psychiatric illness. Poor mental health during the perinatal period can have long-term impacts on the physical and psychiatric health of both mother and child. A potentially useful strategy to improve women’s mental health is through a mobile application teaching mindfulness, an evidence-based technique helping individuals focus on the present moment.MethodsA mixed method, prospective randomised controlled trial. The study group comprise women aged 18 years and over, who are attending the public and private maternity clinics at Mater Mothers’ Hospital. A sample of 360 prenatal women will be randomised into the intervention group (with the use of the mindfulness app) or usual care. Participants will remain in the study for 11 months and will be assessed at four timepoints for changes in postnatal depression, mother-infant bonding, and quality of life. A cost-effectiveness evaluation will also be conducted using quality-adjusted life year (QALY) calculations. A random selection of intervention participants will be invited to attend focus groups to give feedback on the mindfulness app.DiscussionPrevious studies have found mindfulness interventions can reduce stress, anxiety, depression, and sleep disturbances in a prenatal population. The risks of the intervention are low, but could be of significant benefit for women who are unable to attend face-to-face appointments due to geographical, financial, or time barriers; during endemic or pandemic scenarios; or due to health or mobility issues.Trial registrationThis study was approved by the Mater Misericordiae Human Research Ethics Committee (83,589). Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622001581752 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385107&isReview=true). Registered on 22 Dec. 2022.

Lp(a) is one of the most atherogenic lipoproteins, and significant progress has been made to understand its pathophysiology over the last 20 years. There are now selective therapies in late-stage clinical trials to lower Lp(a). Yet there are many outstanding questions about Lp(a). This review outlines 10 of the most burning questions and tries to answer some of them. Antisense oligonucleotide (ASO) treatment is currently the most advanced therapy to lower plasma Lp(a) by 60-80%. There are, however, also two small molecule medications in early stage of development with similar efficacy. This review aims to answer important preclinical and clinical questions about the metabolism and physiological role of Lp(a) and also outlines possible therapeutic approaches with nutraceuticals, currently available lipid-lowering therapies and new medications. In addition, ways are illustrated to use Lp(a) as a marker to better predict cardiovascular risk.

Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH. This association could, however, be mediated by visuoperceptual impairment. To understand the drivers of performance on the NPT, we contrasted performances in patient groups that varied both in terms of visuoperceptual ability and rates of VH. N = 43 patients were studied of whom n = 13 had DLB or PD with Dementia (PDD); n = 13 had PD; n = 12 had typical, memory-onset Alzheimer's Disease (tAD); and n = 5 had Posterior Cortical Atrophy (PCA) due to Alzheimer's disease. All patient groups reported pareidolias. Within the Lewy body disorders (PD, DLB, PDD), there was no significant difference in pareidolic response rates between hallucinating and non-hallucinating patients. Visuoperceptual deficits and pareidolic responses were most frequent in the PCA group-none of whom reported VH. Regression analyses in the entire patient cohort indicated that pareidolias were strongly predicted by visuoperceptual impairment but not by the presence of VH. These findings suggest that pareidolias reflect the underlying visuoperceptual impairment of Lewy body disorders, rather than being a direct marker for VH.

This review will identify, synthesize, and make recommendations regarding the effectiveness of interventions to reduce sexually transmitted infections (STIs) and blood-borne viruses (BBVs) in incarcerated adult settings. High-risk sexual behaviors, intravenous drug use, piercing, and tattooing are well documented within incarceration environments. Despite the World Health Organization's Global Health Sector Strategy on Sexually Transmitted Infections 2016-2021 and the Global Health Sector Strategies on, Respectively, HIV, Viral Hepatitis, and Sexually Transmitted Infections for the Period 2022-2030, STI rates within adult incarceration environments continue to rise. Identifying and implementing best-practice interventions to prevent and manage STIs and BBVs will aid infection reduction in correctional settings. The review results will inform the development of educational programs, health promotion, and policies and procedures to improve health outcomes for incarcerated populations. This review will consider studies in any language from any adult incarceration facility. Studies set in juvenile facilities or detention centers will be excluded. Any intervention for preventing or reducing STI and/or BBV transmission will be included. This review will follow the JBI methodology for systematic reviews of effectiveness. Databases to be searched will include PubMed, CINAHL (EBSCO), Ovid Library, PsycINFO (EBSCO), Cochrane CENTRAL, and Scopus. Two independent reviewers will screen titles and abstracts and assess full-text citations against inclusion criteria. Methodological quality will be appraised using JBI's standardized critical appraisal instruments. Where possible, studies will be pooled using meta-analysis. Where statistical pooling is not possible, findings will be presented in narrative format. Certainty of evidence will be ascertained using the GRADE approach. PROSPERO CRD42022325077.

ObjectiveEvaluate the acceptability and feasibility and explore the potential health impacts of a hospital-based herb and vegetable garden. MethodsMixed-method program evaluation assessed dietetic and food service staff health, well-being, and garden engagement. Surveys were administered at baseline and follow-up (6 months). Key informant interviews (n = 6) were conducted at 6 months to evaluate program feasibility. ResultsThere was good acceptance and engagement with the garden, with 18 participants volunteering to maintain the garden. Key informant interviews identified workforce, leadership, and garden design engagement factors. Participants also noted several psychosocial benefits. Conclusion and ImplicationsA hospital-based garden for staff is feasible if programmatic improvements are addressed. More robust evaluations considering challenges with measuring key outcomes with survey methodology and extended periods are warranted.