Health Navigator intervention to address the unmet social needs of populations living with cancer attending outpatient treatment at a major metropolitan hospital in Australia: protocol for a mixed-methods feasibility trial.

Introduction: Integrating health and social care to address unmet social needs is an emerging priority for health systems worldwide. Screening and referral interventions for unmet social needs, also known as Health Navigator (HN) interventions, in healthcare settings have shown mixed but promising results, mostly due to a large variability in intervention design and outcomes assessed. Most HN interventions are implemented in primary care, despite evidence that disadvantaged populations face substantial barriers to accessing such care, and these interventions are limited in Australia.

Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.

Protein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here, we describe a therapeutic strategy called "RING-Bait," which employs an aggregating protein sequence combined with an E3 ubiquitin ligase.

Aggregate-selective removal of pathological tau by clustering-activated degraders.

Selective degradation of pathological protein aggregates while sparing monomeric forms is of major therapeutic interest. The E3 ligase tripartite motif-containing protein 21 (TRIM21) degrades antibody-bound proteins in an assembly state-specific manner due to the requirement of TRIM21 RING domain clustering for activation, yet effective targeting of intracellular assemblies remains challenging. Here, we fused the RING domain of TRIM21 to a target-specific nanobody to create intracellularly expressed constructs capable of selectively degrading assembled proteins.

Medical oncologist perceptions and willingness to participate in voluntary assisted dying in South Australia.

This study surveyed South Australian medical oncologists to capture their perceptions, willingness to participate and perceived barriers and motivations to participation in voluntary assisted dying (VAD) activities. Approximately 70% of surveyed medical oncologists reported familiarity with VAD legislation. Less than half of physicians (39.

Patient Perception and Self-Reported Outcomes with Presbyopia-Correcting Intraocular Lenses (PCIOLs): A Social Media Listening Study.

Introduction: Presbyopia-correcting intraocular lens (PCIOL) implantation is a popular treatment option for cataract surgery patients who desire spectacle independence. This study aimed to understand patient perception and outcomes with PCIOLs by analyzing patient social media posts.

Methods: This was a non-interventional retrospective study that used predefined search strings to identify publicly available social media data discussing patient perceptions and outcomes with seven PCIOLs (three trifocal, one multifocal with continuous range of vision, and three extended depth-of-focus [EDOF] PCIOLs).

Super-resolution imaging unveils the self-replication of tau aggregates upon seeding.

Tau is a soluble protein interacting with tubulin to stabilize microtubules. However, under pathological conditions, it becomes hyperphosphorylated and aggregates, a process that can be induced by treating cells with exogenously added tau fibrils. Here, we employ single-molecule localization microscopy to resolve the aggregate species formed in early stages of seeded tau aggregation.

Reducing herbicide input and optimizing spray method can minimize nontarget impacts on native grassland plant species.

Invasive plants threaten biodiversity worldwide and effective management must control the target invader while conserving biodiversity. Herbicide is often used to control invasive plants, but potential negative impacts on biodiversity have led to spot spraying being recommended over boom spraying to minimize the exposure of nontarget species to chemicals. We examined the influence of herbicide application methods on off-target plant communities in threatened temperate grasslands of southeastern Australia, where spraying with the broadleaf herbicide fluroxypr is commonly used to control St.

Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.

Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology.

Curcumin, a dietary natural supplement, prolongs the action potential duration of KCNE1-D85N-induced pluripotent stem cell-derived cardiomyocytes.

Background: Curcumin, a polyphenolic dietary natural compound and active ingredient in turmeric, exerts antioxidant, anti-inflammatory, antidiabetic, anticancer, and antiarrhythmic properties. KCNE1-D85N, present in ∼1% of white, is a common, potentially proarrhythmic variant that predisposes individuals to drug-induced QT prolongation under certain conditions.

Objective: The purpose of this article was to test the hypothesis that curcumin might cause action potential duration (APD) prolongation in KCNE1-D85N-derived human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

Impact of roadside burning on genetic diversity in a high-biomass invasive grass.

The invasive grass-fire cycle is a widely documented feedback phenomenon in which invasive grasses increase vegetation flammability and fire frequency, resulting in further invasion and compounded effects on fire regimes. Few studies have examined the role of short-term adaptation in driving the invasive grass-fire cycle, despite invasive species often thriving after introduction to new environments. We used a replicated (nine locations), paired sampling design (burn vs unburnt sites) to test the hypothesis that roadside burning increases genetic diversity and thus adaptive potential in the invasive, high-biomass grass .

Cholesterol determines the cytosolic entry and seeded aggregation of tau.

Assemblies of tau can transit between neurons, seeding aggregation in a prion-like manner. To accomplish this, tau must cross cell-limiting membranes, a process that is poorly understood. Here, we establish assays for the study of tau entry into the cytosol as a phenomenon distinct from uptake, in real time, and at physiological concentrations.

Immunotherapy use in oesophagogastric cancers-a review of the literature.

Cancers of the upper gastrointestinal tract are a leading cause of cancer-related death world-wide and historically have a poor prognosis. The incidence and histology of these cancers have varied temporally and geographically over the last three decades, with an emerging understanding of the differences in the molecular and genetic profiles across different subgroups. Management of oesophagogastric cancers is by a multidisciplinary team with utilisation of surgery, radiotherapy and systemic treatments in combinations where appropriate.

Duration of immunotherapy - should we continue ad infinitum?

The optimal duration of immunotherapy treatment for cancer patients is unknown. As the survival data from early immunotherapy trials mature we are beginning to appreciate how durable responses can be post-discontinuation. The purpose of this brief communication is to comment on treatment duration of immunotherapy in patients with melanoma and non-small cell lung cancer and to provide practice guidance in support of discontinuation.

Global gene flow releases invasive plants from environmental constraints on genetic diversity.

When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales.

Managing uncertainty in movement knowledge for environmental decisions.

Species' movements affect their response to environmental change but movement knowledge is often highly uncertain. We now have well-established methods to integrate movement knowledge into conservation practice but still lack a framework to deal with uncertainty in movement knowledge for environmental decisions. We provide a framework that distinguishes two dimensions of species' movement that are heavily influenced by uncertainty: about movement and of movement to environmental decisions.

Successional changes in trophic interactions support a mechanistic model of post-fire population dynamics.

Models based on functional traits have limited power in predicting how animal populations respond to disturbance because they do not capture the range of demographic and biological factors that drive population dynamics, including variation in trophic interactions. I tested the hypothesis that successional changes in vegetation structure, which affected invertebrate abundance, would influence growth rates and body condition in the early-successional, insectivorous gecko Nephrurus stellatus. I captured geckos at 17 woodland sites spanning a succession gradient from 2 to 48 years post-fire.

Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer.

Background: Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity.

Dispersal responses override density effects on genetic diversity during post-disturbance succession.

Dispersal fundamentally influences spatial population dynamics but little is known about dispersal variation in landscapes where spatial heterogeneity is generated predominantly by disturbance and succession. We tested the hypothesis that habitat succession following fire inhibits dispersal, leading to declines over time in genetic diversity in the early successional gecko Nephrurus stellatus We combined a landscape genetics field study with a spatially explicit simulation experiment to determine whether successional patterns in genetic diversity were driven by habitat-mediated dispersal or demographic effects (declines in population density leading to genetic drift). Initial increases in genetic structure following fire were likely driven by direct mortality and rapid population expansion.

Guidelines for Using Movement Science to Inform Biodiversity Policy.

Substantial advances have been made in our understanding of the movement of species, including processes such as dispersal and migration. This knowledge has the potential to improve decisions about biodiversity policy and management, but it can be difficult for decision makers to readily access and integrate the growing body of movement science. This is, in part, due to a lack of synthesis of information that is sufficiently contextualized for a policy audience.

Fine-scale refuges can buffer demographic and genetic processes against short-term climatic variation and disturbance: a 22-year case study of an arboreal marsupial.

Ecological disturbance and climate are key drivers of temporal dynamics in the demography and genetic diversity of natural populations. Microscale refuges are known to buffer species' persistence against environmental change, but the effects of such refuges on demographic and genetic patterns in response to short-term environmental variation are poorly understood. We quantified demographic and genetic responses of mountain brushtail possums (Trichosurus cunninghami) to rainfall variability (1992-2013) and to a major wildfire.