Effects of X-ray dose on rhizosphere studies using X-ray computed tomography

X-ray Computed Tomography (CT) is a non-destructive imaging technique originally designed for diagnostic medicine, which was adopted for rhizosphere and soil science applications in the early 1980s. X-ray CT enables researchers to simultaneously visualise and quantify the heterogeneous soil matrix of mineral grains, organic matter, air-filled pores and water-filled pores. Additionally, X-ray CT allows visualisation of plant roots in situ without the need for traditional invasive methods such as root washing. However, one routinely unreported aspect of X-ray CT is the potential effect of X-ray dose on the soil-borne microorganisms and plants in rhizosphere investigations. Here we aimed to i) highlight the need for more consistent reporting of X-ray CT parameters for dose to sample, ii) to provide an overview of previously reported impacts of X-rays on soil microorganisms and plant roots and iii) present new data investigating the response of plant roots and microbial communities to X-ray exposure. Fewer than 5% of the 126 publications included in the literature review contained sufficient information to calculate dose and only 2.4% of the publications explicitly state an estimate of dose received by each sample. We conducted a study involving rice roots growing in soil, observing no significant difference between the numbers of root tips, root volume and total root length in scanned versus unscanned samples. In parallel, a soil microbe experiment scanning samples over a total of 24 weeks observed no significant difference between the scanned and unscanned microbial biomass values. We conclude from the literature review and our own experiments that X-ray CT does not impact plant growth or soil microbial populations when employing a low level of dose (<30 Gy). However, the call for higher throughput X-ray CT means that doses that biological samples receive are likely to increase and thus should be closely monitored

IS ONLINE VIDEO-BASED EDUCATION AN EFFECTIVE METHOD TO TEACH BASIC SURGICAL SKILLS TO STUDENTS AND SURGICAL TRAINEES? A SYSTEMATIC REVIEW AND META-ANALYSIS

BACKGROUND: Online education has been increasingly utilized over the past decades. The COVID-19 pandemic accelerated the transition of conventional face-to-face curricula to online platforms, with limited evidence for its teaching efficacy. This systematic review aims to assess the effectiveness of online video-based education compared with standard conventional education in teaching basic surgical skills to surgical trainees and students undergoing medical training. METHODS: We performed a literature search in Embase, Medline, Cochrane CENTRAL and Scopus from inception until February 2022. Studies included were randomised controlled trials (RCTs) and observational studies. We included randomised controlled trials only for meta-analysis. The primary outcome was surgical skill proficiency. The secondary outcomes were participant perception, confidence and satisfaction. Two authors independently assessed the search results for eligibility, extracted the data and assessed the risk of bias using the Cochrane Risk of Bias tool 2. Where appropriate, we performed random effects meta-analyses of the pooled study data to calculate a standardized mean difference. RESULTS: A total of 11 studies met the inclusion criteria totaling 715 participants; 603 were included in qualitative analysis and 380 in meta-analysis. All included studies were assessed as having a low risk of bias. The majority of studies found no significant difference between conventional and video-based education in teaching basic surgical skills, three studies found video-based education was superior and one study found conventional education was superior. There was no statistically significant difference in skill proficiency between the two groups (standardized mean difference of -0.02 (95% CI: -0.34, 0.30); p=0.90). Video-based education results in an equivalent improvement in confidence and satisfaction rates. Additional benefits of video-based education include convenience, accessibility and efficiency. CONCLUSIONS: Basic surgical skills can be taught as effectively through online video-based education as conventional teaching methods. Online education should be utilized as an adjunct to medical curricula beyond the COVID-19 era

HGF/c-MET pathway inhibition combined with chemotherapy increases cytotoxic T-cell infiltration and inhibits pancreatic tumour growth and metastasis

Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to target cancer cells effectively decreases tumour volume, EMT, and stemness, and importantly, eliminates metastasis. Notably, HGF/c-MET inhibition decreases TGF-β secretion by cancer cells, resulting in an increase in cytotoxic T-cell infiltration, thus contributing to cancer cell death in tumours. HGF/c-MET inhibition + chemotherapy was also found to normalise the gut microbiome and improve gut microbial diversity. These findings provide a strong platform for assessment of this triple therapy (HGF/c-MET inhibition + chemotherapy) approach in the clinical setting

Early national trends in non-abortion reproductive care access after Roe

BackgroundRoe was overturned in 2022. No peer-reviewed evidence exists for the indirect spillover effects of overturning Roe on non-abortion reproductive care access for diverse patient populations.MethodsNational data were from 2013–2023 HHS Title X Directory, 2013–2020 CDC Artificial Reproductive Technologies (ART) Surveillance and 2021–2023 manual collection, and Guttmacher Institute. Outcome measures included numbers of ART clinics and Title X entities. Title X entities are those that receive federal funds to establish and operate voluntary family planning projects, especially for low-income patients. We reported pre-and post-Roe changes, associations between changes in measures and abortions, and characteristics of changed measures by region and political geography.ResultsPost-Roe America witnessed national declines of 1.03% in ART clinics and 18.34% in Title X entities, and average state decreases of 0.08 ART clinics (p &lt; 0.05) and 18 Title X entities (p &lt; 0.001). State-level ART clinic closures and abortion reductions had little association except for Texas, Oklahoma, Arizona, New York, and California. Plummets in Title X entities and abortions were positively associated: Reducing 100 abortions was associated with defunding two Title X entities (p &lt; 0.05). The South experienced the largest losses of both, while 83.39% of lost Title X entities were in states that voted Republican in the 2020 presidential election, disproportionate to the 49.02% of states that voted Republican and the 42.52% of US population residing in these states.ConclusionWe provide one of the first few evidence of spillover impacts of overturning Roe on non-abortion care access for diverse populations: low-income men and women, single parents by choice, and biologically and socially infertile patients. Early evidence warns of worsening challenges of inequities and calls for immediate policy actions

Review of Current Human Genome-Scale Metabolic Models for Brain Cancer and Neurodegenerative Diseases.

Brain disorders represent 32% of the global disease burden, with 169 million Europeans affected. Constraint-based metabolic modelling and other approaches have been applied to predict new treatments for these and other diseases. Many recent studies focused on enhancing, among others, drug predictions by generating generic metabolic models of brain cells and on the contextualisation of the genome-scale metabolic models with expression data. Experimental flux rates were primarily used to constrain or validate the model inputs. Bi-cellular models were reconstructed to study the interaction between different cell types. This review highlights the evolution of genome-scale models for neurodegenerative diseases and glioma. We discuss the advantages and drawbacks of each approach and propose improvements, such as building bi-cellular models, tailoring the biomass formulations for glioma and refinement of the cerebrospinal fluid composition

Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU)

BackgroundPrevious studies have revealed the role of dysregulated urokinase plasminogen activator (encoded by PLAU) expression and activity in several pathways associated with cancer progression. However, systematic investigation into the association of PLAU expression with factors that modulate PDAC (pancreatic ductal adenocarcinoma) progression is lacking, such as those affecting stromal (pancreatic stellate cell, PSC)-cancer cell interactions, tumour immunity, PDAC subtypes and clinical outcomes from potential PLAU inhibition.MethodsThis study used an integrated bioinformatics approach to identify prognostic markers correlated with PLAU expression using different transcriptomics, proteomics, and clinical data sets. We then determined the association of dysregulated PLAU and correlated signatures with oncogenic pathways, metastatic phenotypes, stroma, immunosuppressive tumour microenvironment (TME) and clinical outcome. Finally, using an in vivo orthotopic model of pancreatic cancer, we confirmed the predicted effect of inhibiting PLAU on tumour growth and metastasis.ResultsOur analyses revealed that PLAU upregulation is not only associated with numerous other prognostic markers but also associated with the activation of various oncogenic signalling pathways, aggressive phenotypes relevant to PDAC growth and metastasis, such as proliferation, epithelial-mesenchymal transition (EMT), stemness, hypoxia, extracellular cell matrix (ECM) degradation, upregulation of stromal signatures, and immune suppression in the tumour microenvironment (TME). Moreover, the upregulation of PLAU was directly connected with signalling pathways known to mediate PSC-cancer cell interactions. Furthermore, PLAU upregulation was associated with the aggressive basal/squamous phenotype of PDAC and significantly reduced overall survival, indicating that this subset of patients may benefit from therapeutic interventions to inhibit PLAU activity. Our studies with a clinically relevant orthotopic pancreatic model showed that even short-term PLAU inhibition is sufficient to significantly halt tumour growth and, importantly, eliminate visible metastasis.ConclusionElevated PLAU correlates with increased aggressive phenotypes, stromal score, and immune suppression in PDAC. PLAU upregulation is also closely associated with the basal subtype type of PDAC; patients with this subtype are at high risk of mortality from the disease and may benefit from therapeutic targeting of PLAU

Root hydrotropism is controlled via a cortex-specific growth mechanism

Plants can acclimate by using tropisms to link the direction 41 of growth to environmental conditions. Hydrotropism allows roots to forage for water, a process known to depend on abscisic acid (ABA) but whose molecular and cellular basis remains unclear. Here, we show that hydrotropism still occurs in roots after laser ablation removed the meristem and root cap. Additionally, targeted expression studies reveal that hydrotropism depends on the ABA signalling kinase, SnRK2.2, and the hydrotropism-specific MIZ1, both acting specifically in elongation zone cortical cells. Conversely, hydrotropism, but not gravitropism, is inhibited by preventing differential cell-length increases in the cortex, but not in other cell types. We conclude that root tropic responses to gravity and water are driven by distinct tissue-based mechanisms. In addition, unlike its role in root gravitropism, the elongation zone performs a dual function during a hydrotropic response, both sensing a water potential gradient and subsequently undergoing differential growth