Integrating Cardio-Oncology Across the Research Pipeline, Policy, and Practice in Australia-An Australian Cardiovascular Alliance Perspective.

Over 18 million people worldwide were diagnosed with cancer in 2020, including over 150,000 people in Australia. Although improved early detection and treatment have increased the survival rates, cardiotoxic treatment and inadequate management of cardiovascular risk factors have resulted in cardiovascular disease (CVD) being one of the leading causes of non-cancer-related death and disability among cancer survivors. International guidelines outline the standards of care for CVD risk surveillance and management.

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study.

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia.

Challenges and solutions to cancer-related financial toxicity according to Australian health professionals: qualitative results from a national survey.

Purpose: To qualitatively explore Australian healthcare professionals' perspectives on how to improve the care and management of cancer-related financial toxicity, including relevant practices, services, and unmet needs.

Methods: We invited healthcare professionals (HCP) who currently provide care to people with cancer within their role to complete an online survey, which was distributed via the networks of Australian clinical oncology professional associations/organisations. The survey was developed by the Clinical Oncology Society of Australia's Financial Toxicity Working Group and contained 12 open-ended items which we analysed using descriptive content analysis and NVivo software.

When Cancer and Cardiovascular Disease Intersect: The Challenge and the Opportunity of Cardio-Oncology.

Cancer and cardiovascular disease (CVD) commonly coexist, with increasing evidence that long-term cancer survivors are more likely to die from CVD than the general population. Effective management of CVD and its risk factors requires identification of patients at increased risk who may benefit from early intervention and their appropriate monitoring across the disease trajectory. Improving outcomes requires new models of multidisciplinary cancer care supported by care pathways.

Opinions and strategies of Australian health professionals on tackling cancer-related financial toxicity: A nationwide survey.

Aim: To understand the opinions and current practices of health professionals on the topic of addressing cancer-related financial toxicity among patients.

Methods: A cross-sectional online survey was distributed through Australian clinical oncology professional organizations/networks. The multidisciplinary Clinical Oncology Society of Australia Financial Toxicity Working Group developed 25 questions relating to the frequency and comfort levels of patient-clinician discussions, opinions about their role, strategies used, and barriers to providing solutions for patients.

Inclusion of Hydroxycinnamic Acids in Methylated Cyclodextrins: Host-Guest Interactions and Effects on Guest Thermal Stability.

There is ongoing interest in exploiting the antioxidant activity and other medicinal properties of natural monophenolic/polyphenolic compounds, but their generally low aqueous solubility limits their applications. Numerous studies have been undertaken to solubilize such compounds via supramolecular derivatization with co-crystal formation with biocompatible coformer molecules and cyclodextrin (CD) complexation being two successful approaches. In this study, eight new crystalline products obtained by complexation between methylated cyclodextrins and the bioactive phenolic acids (ferulic, hydroferulic, caffeic, and -coumaric acids) were investigated using thermal analysis (hot stage microscopy, thermogravimetry, differential scanning calorimetry) and X-ray diffraction.

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews.

Background: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents.

Inclusion of the Phytoalexin -Resveratrol in Native Cyclodextrins: A Thermal, Spectroscopic, and X-Ray Structural Study.

The aim of the study was to determine the feasibility of complexation between the antioxidant -resveratrol (RSV) and underivatized cyclodextrins (CDs) using a variety of preparative methods, including physical mixing, kneading, microwave irradiation, co-evaporation, and co-precipitation techniques. Products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and powder X-ray diffraction (PXRD). With α-CD and RSV, sample amorphization was revealed by PXRD and FT-IR, but no definitive inclusion complexation was evident.

Mesophyll porosity is modulated by the presence of functional stomata.

The formation of stomata and leaf mesophyll airspace must be coordinated to establish an efficient and robust network that facilitates gas exchange for photosynthesis, however the mechanism by which this coordinated development occurs remains unclear. Here, we combine microCT and gas exchange analyses with measures of stomatal size and patterning in a range of wild, domesticated and transgenic lines of wheat and Arabidopsis to show that mesophyll airspace formation is linked to stomatal function in both monocots and eudicots. Our results support the hypothesis that gas flux via stomatal pores influences the degree and spatial patterning of mesophyll airspace formation, and indicate that this relationship has been selected for during the evolution of modern wheat.

Reduced stomatal density in bread wheat leads to increased water-use efficiency.

Wheat is a staple crop, frequently cultivated in water-restricted environments. Improving crop water-use efficiency would be desirable if grain yield can be maintained. We investigated whether a decrease in wheat stomatal density via the manipulation of epidermal patterning factor (EPF) gene expression could improve water-use efficiency.

Bacterial infection systemically suppresses stomatal density.

Many plant pathogens gain entry to their host via stomata. On sensing attack, plants close these pores to restrict pathogen entry. Here, we show that plants exhibit a second longer term stomatal response to pathogens.

Cardiovascular toxicity of targeted therapies for cancer: a protocol for an overview of systematic reviews.

Introduction: The introduction of targeted therapies for cancer has contributed to dramatic improvements in patient survival. Nevertheless, several targeted therapies have been associated with 'off-target' adverse effects, based on varying levels of evidence. To date, this evidence has not been systematically synthesised.

Reducing Stomatal Density in Barley Improves Drought Tolerance without Impacting on Yield.

The epidermal patterning factor (EPF) family of secreted signaling peptides regulate the frequency of stomatal development in model dicot and basal land plant species. Here, we identify and manipulate the expression of a barley () ortholog and demonstrate that when overexpressed HvEPF1 limits entry to, and progression through, the stomatal development pathway. Despite substantial reductions in leaf gas exchange, barley plants with significantly reduced stomatal density show no reductions in grain yield.

Formation of the Stomatal Outer Cuticular Ledge Requires a Guard Cell Wall Proline-Rich Protein.

Stomata are formed by a pair of guard cells which have thickened, elastic cell walls to withstand the large increases in turgor pressure that have to be generated to open the pore that they surround. We have characterized FOCL1, a guard cell-expressed, secreted protein with homology to Hyp-rich cell wall proteins. FOCL1-GFP localizes to the guard cell outer cuticular ledge and plants lacking FOCL1 produce stomata without a cuticular ledge.

Stomatal Function Requires Pectin De-methyl-esterification of the Guard Cell Wall.

Stomatal opening and closure depends on changes in turgor pressure acting within guard cells to alter cell shape [1]. The extent of these shape changes is limited by the mechanical properties of the cells, which will be largely dependent on the structure of the cell walls. Although it has long been observed that guard cells are anisotropic due to differential thickening and the orientation of cellulose microfibrils [2], our understanding of the composition of the cell wall that allows them to undergo repeated swelling and deflation remains surprisingly poor.

Manipulating stomatal density enhances drought tolerance without deleterious effect on nutrient uptake.

Manipulation of stomatal density was investigated as a potential tool for enhancing drought tolerance or nutrient uptake. Drought tolerance and soil water retention were assessed using Arabidopsis epidermal patterning factor mutants manipulated to have increased or decreased stomatal density. Root nutrient uptake via mass flow was monitored under differing plant watering regimes using nitrogen-15 ((15) N) isotope and mass spectrometry.

Light-induced stomatal opening is affected by the guard cell protein kinase APK1b.

Guard cells allow land plants to survive under restricted or fluctuating water availability. They control the exchange of gases between the external environment and the interior of the plant by regulating the aperture of stomatal pores in response to environmental stimuli such as light intensity, and are important regulators of plant productivity. Their turgor driven movements are under the control of a signalling network that is not yet fully characterised.

Genetic manipulation of stomatal density influences stomatal size, plant growth and tolerance to restricted water supply across a growth carbon dioxide gradient.

To investigate the impact of manipulating stomatal density, a collection of Arabidopsis epidermal patterning factor (EPF) mutants with an approximately 16-fold range of stomatal densities (approx. 20-325% of that of control plants) were grown at three atmospheric carbon dioxide (CO(2)) concentrations (200, 450 and 1000 ppm), and 30 per cent or 70 per cent soil water content. A strong negative correlation between stomatal size (S) and stomatal density (D) was observed, suggesting that factors that control D also affect S.

A shift toward smaller cell size via manipulation of cell cycle gene expression acts to smoothen Arabidopsis leaf shape.

Understanding the relationship of the size and shape of an organism to the size, shape, and number of its constituent cells is a basic problem in biology; however, numerous studies indicate that the relationship is complex and often nonintuitive. To investigate this problem, we used a system for the inducible expression of genes involved in the G1/S transition of the plant cell cycle and analyzed the outcome on leaf shape. By combining a careful developmental staging with a quantitative analysis of the temporal and spatial response of cell division pattern and leaf shape to these manipulations, we found that changes in cell division frequency occurred much later than the observed changes in leaf shape.

BASL and EPF2 act independently to regulate asymmetric divisions during stomatal development.

The initiation of stomatal development in the developing Arabidopsis epidermis is characterized by an asymmetric 'entry' division in which a small cell, known as a meristemoid, and a larger daughter cell is formed. The meristemoid may undergo further asymmetric divisions, regenerating a meristemoid each time, before differentiating into a guard mother cell which divides symmetrically to form a pair of guard cells surrounding a stomatal pore. Recently EPF2 and BASL have emerged as regulators of these asymmetric divisions and here we present results indicating that these two factors operate independently to control stomatal development.

The signalling peptide EPFL9 is a positive regulator of stomatal development.

The putative secretory peptides epidermal patterning factor 1 (EPF1) and EPF2 act as negative regulators of stomatal clustering and density early in Arabidopsis leaf development. Here, we investigated whether the related peptide gene epidermal patterning factor-like 9 (EPFL9), which is coexpressed with EPF1 and stomatal density and distribution 1 (SDD1), also plays a role in controlling stomatal development. Plants manipulated to constitutively overexpress EPFL9 showed increased stomatal density and clustering, and those manipulated to have reduced EPFL9 expression showed reduced stomatal density with no clustering, confirming that EPFL9 is a regulator of stomatal development.

The signaling peptide EPF2 controls asymmetric cell divisions during stomatal development.

Stomata are pores in the plant epidermis that control carbon dioxide uptake and water loss. They are major regulators of global carbon and water cycles [1]. Several signaling components that regulate stomatal development have been characterized.

Intercellular peptide signals regulate plant meristematic cell fate decisions.

Plant stem cells secrete peptides that, after processing to release the active form, prevent neighboring cells from adopting a stem cell fate by activating a leucine-rich repeat (LRR) receptor-mediated pathway. Other plant meristematic cell fate decisions, such as those made during the patterning of veins and stomata, also appear to be controlled by similar LRR receptor pathways that are activated by secreted peptide signals. It is therefore probable that peptide ligands regulate meristematic activity in many plant developmental processes.

The relationship between pyridine nucleotides and seed dormancy.

To investigate the proposed role for NAD metabolism in regulating seed dormancy, NAD metabolites and associated enzyme activities were analysed in seed of Arabidopsis thaliana ecotypes ranging from Col-0, which has low seed dormancy, to Cvi, which is highly dormant. Seed poly(ADP-ribosyl)ation levels did not correlate well with the depth of seed dormancy but did correlate with the sensitivity of germination to the DNA damaging agent MMS. Cvi seed had relatively high NAD and low NADP levels compared with the less dormant ecotypes and the NAD : NADP ratios correlated well with dormancy.