The (Mis)understanding of Scientific Uncertainty? How Experts View Policy-Makers, the Media and Publics

Frequent claims that publics ‘misunderstand’ science ignore the contested definition of scientific uncertainty itself. Scientific uncertainty means different things in the natural sciences, social sciences and the humanities, while public controversies show that these interpretations of scientific uncertainty have different implications for policy and decision-making. This prompts analysis of the ways that experts view scientific uncertainty and how they characterise the (mis)understandings of this uncertainty by policy-makers, media and publics. Experts from diverse academic fields define scientific uncertainty differently depending on their disciplinary background. For example, mathematics provides experts from the natural sciences with a practice language that facilitates communication with those sharing this cultural competence, but it does not suffice for engaging with wider audiences. Further, experts’ views of diverse publics come across as folk theories, in Arie Rip’s terms, which, compiled from disparate pieces of information, can be used to fill a gap in the knowledge about publics

The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

Simple Summary: One of the reasons that pancreatic cancer is such a deadly disease is that it is able to evade the body’s usual defence system (the immune system). It has been shown that the population of microorganisms in the human gut (the gut microbiome) plays a role in regulating the human immune system. This article outlines the ways in which the gut microbiome influences the immune system in pancreatic cancer both within the bloodstream (systemic) and around the pancreatic tumour itself (local). These are important mechanisms because greater understanding of these will direct the development of future treatments for pancreatic cancer. It is possible that some of these treatment options will target the gut microbiome in order to boost the immune system’s response to pancreatic cancer. Abstract: The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients

Assessing drivers of plantation forest productivity on eroded and non-eroded soils in hilly land, eastern North Island, New Zealand

Methods: The impact of soil erosion by mass movement on forest productivity was investigated in a paired plot trial in a planted forest in a mainly hilly to steepland catchment (Pakuratahi) near Napier, eastern North Island, New Zealand. Tree growth and form were measured and soil properties analysed to compare productivity and productivity drivers in adjacent non-eroded and eroded plots. Background: The effect of soil erosion on New Zealand production forestry is not well known and there has been no research prior to our study into the relationship between soil nutrient status and planted forests growing in eroded soils in steeplands. Results: Regression analysis showed that the decreased soil total nitrogen, total carbon, total phosphorus, and soil organic matter content in eroded plots had a negative impact on tree volume, resulting in a 10% decrease in measured tree volume. Based on an assessment of log quality, trees in the eroded plots were forecast to produce 16% less volume from high-quality pruned logs (with associated reduction in revenue of around $4000 per hectare), than trees in non-eroded plots. The total recoverable volume (TRV), estimated (for a 25-year rotation) from the measured Pinus radiata D. Don trees growing on the eroded sites, was valued at$68,500, about 9% less than the estimated TRV from trees measured on non-eroded plots ($76,000). Tree form and mean tree height in eroded and non-eroded plots were not significantly different. Conclusions: Soil erosion impacts production in planted forests. Afforestation of erodible land provides a valuable ecosystem service through land and soil stabilisation but this service is currently not reflected in the market prices for timber in New Zealand. Maintaining the productive capacity of erodible soils through practices such as fertilisation or continuous-cover forestry can add further costs to production forestry. To ensure that sustainable forest practices are carried out to protect the productivity of soils, financial incentives may be justified

Interplay in galectin expression predicts patient outcomes in a spatially restricted manner in PDAC

BACKGROUND: Galectins (Gal's) are a family of carbohydrate-binding proteins that are known to support the tumour microenvironment through their immunosuppressive activity and ability to promote metastasis. As such they are attractive therapeutic targets, but little is known about the cellular expression pattern of galectins within the tumour and its neighbouring stromal microenvironment. Here we investigated the cellular expression pattern of Gals within pancreatic ductal adenocarcinoma (PDAC).METHODS: Galectin gene and protein expression were analysed by scRNAseq (n=4) and immunofluorescence imaging (n=19) in fibroblasts and epithelial cells of pancreatic biopsies from PDAC patients. Galectin surface expression was also assessed on tumour adjacent normal fibroblasts and cancer associated primary fibroblasts from PDAC biopsies using flow cytometry.RESULTS: scRNAseq revealed higher Gal-1 expression in fibroblasts and higher Gal-3 and -4 expression in epithelial cells. Both podoplanin (PDPN+, stromal/fibroblast) cells and EpCAM+ epithelial cells expressed Gal-1 protein, with highest expression seen in the stromal compartment. By contrast, significantly more Gal-3 and -4 protein was expressed in ductal cells expressing either EpCAM or PDPN, when compared to the stroma. Ductal Gal-4 cellular expression negatively correlated with ductal Gal-1, but not Gal-3 expression. Higher ductal cellular expression of Gal-1 correlated with smaller tumour size and better patient survival. CONCLUSIONS: In summary, the intricate interplay and cell-specific expression patterns of galectins within the PDAC tissue, particularly the inverse correlation between Gal-1 and Gal-4 in ducts and its significant association with patient survival, highlights the complex molecular landscape underlying PDAC and provides valuable insights for future therapeutic interventions.</p