A Magnetic Bead-Based Sensor for the Quantification of Multiple Prostate Cancer Biomarkers.

Novel biomarker assays and upgraded analytical tools are urgently needed to accurately discriminate benign prostatic hypertrophy (BPH) from prostate cancer (CaP). To address this unmet clinical need, we report a piezeoelectric/magnetic bead-based assay to quantitate prostate specific antigen (PSA; free and total), prostatic acid phosphatase, carbonic anhydrase 1 (CA1), osteonectin, IL-6 soluble receptor (IL-6sr), and spondin-2. We used the sensor to measure these seven proteins in serum samples from 120 benign prostate hypertrophy patients and 100 Gleason score 6 and 7 CaP using serum samples previously collected and banked. The results were analyzed with receiver operator characteristic curve analysis. There were significant differences between BPH and CaP patients in the PSA, CA1, and spondin-2 assays. The highest AUC discrimination was achieved with a spondin-2 OR free/total PSA operation--the area under the curve was 0.84 with a p value below 10(-6). Some of these data seem to contradict previous reports and highlight the importance of sample selection and proper assay building in the development of biomarker measurement schemes. This bead-based system offers important advantages in assay building including low cost, high throughput, and rapid identification of an optimal matched antibody pair

Highly Pathogenic Avian Influenza (H5N1) in Humans after the emergence of clade 2.3.4.4b in 2020.

The highly pathogenic avian influenza virus A (HPAI) H5N1 was first identified in a farmed goose in 1996 from China. High pathogenic avian influenza viruses cause severe disease in poultry and represent a smaller proportion of avian influenzas. In 2008, the H5Nx acquired the function to reassort its neuraminidase (N) and created the 2.3.4.4 H5Nx clade. Initial outbreaks of 2.3.4.4b began in H5N8 and H5N6 in 2016. However, in 2020, whole genome sequencing (WGS) conducted in the Netherlands detected a new H5N1 clade, 2.3.4.4b in wild birds along the Adriatic flyway, which reassorted from H5N8 2.3.4.4b clade. Currently, the 2.3.4.4b HPAI H5N1 outbreak is the dominant circulating strain in the panzootic outbreak. This clade has been responsible for large outbreaks within avian species and spillover into human cases has occurred. The earliest reported human case was in 2021. The reported human cases of this clade have been within the United Kingdom (UK), the United States (US), China, Spain, Vietnam, Ecuador, and Chile

Relation Extraction from News Articles (RENA): A Tool for Epidemic Surveillance

Relation Extraction from News Articles (RENA) is a browser-based tool designed to extract key entities and their semantic relationships in English language news articles related to infectious diseases. Constructed using the React framework, this system presents users with an elegant and user-friendly interface. It enables users to input a news article and select from a choice of two models to generate a comprehensive list of relations within the provided text. As a result, RENA allows real-time parsing of news articles to extract key information for epidemic surveillance, contributing to EPIWATCH, an open-source intelligence-based epidemic warning system.Comment: Under review in AAAI 202

Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria

The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling

Aligning the Measurement of Microbial Diversity with Macroecological Theory

The number of microbial operational taxonomic units (OTUs) within a community is akin to species richness within plant/animal (“macrobial”) systems. A large literature documents OTU richness patterns, drawing comparisons to macrobial theory. There is, however, an unrecognized fundamental disconnect between OTU richness and macrobial theory: OTU richness is commonly estimated on a per-individual basis, while macrobial richness is estimated per-area. Furthermore, the range or extent of sampled environmental conditions can strongly influence a study's outcomes and conclusions, but this is not commonly addressed when studying OTU richness. Here we (i) propose a new sampling approach that estimates OTU richness per-mass of soil, which results in strong support for species energy theory, (ii) use data reduction to show how support for niche conservatism emerges when sampling across a restricted range of environmental conditions, and (iii) show how additional insights into drivers of OTU richness can be generated by combining different sampling methods while simultaneously considering patterns that emerge by restricting the range of environmental conditions. We propose that a more rigorous connection between microbial ecology and macrobial theory can be facilitated by exploring how changes in OTU richness units and environmental extent influence outcomes of data analysis. While fundamental differences between microbial and macrobial systems persist (e.g., species concepts), we suggest that closer attention to units and scale provide tangible and immediate improvements to our understanding of the processes governing OTU richness and how those processes relate to drivers of macrobial species richness

3D printed biomimetic cochleae and machine learning co-modelling provides clinical informatics for cochlear implant patients.

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants

Educating Young Consumers about Food Hygiene and Safety with SafeConsume: A Multi-Centre Mixed Methods Evaluation

The SafeConsume educational suite was designed to improve knowledge about undertaking safer food practices and avoiding food-borne illnesses among young people. The resources were designed to support educators and members of the community who teach young people (aged 11–18 years) and include lesson plans and supporting teacher training resources. To assess the efficacy and suitability of the resources, an evaluation of the central lesson, the ‘user journey’, was conducted within four European countries. The mixed-methods evaluation included the following elements: a pre- and post-scenario-based questionnaire, a satisfaction questionnaire, focus groups with students; and interviews with teachers. Data from the scenario-based questionnaires were analysed using a mixed effects normal linear regression model. Qualitative data were thematically analysed, and the main themes were discussed. A total of 171 students and 9 educators took part from schools based in Portugal, Hungary, France and England. The results indicated a significant improvement in students’ knowledge and understanding of appropriate food hygiene practices overall, although this varied among countries. The resources were found to be well-suited to help teachers deliver the lesson, being considered by teachers to be both informative and flexible. Minor alternations were suggested, including alterations to lesson delivery or breaking the lesson into smaller sections, and increasing the lesson’s interactivity.info:eu-repo/semantics/publishedVersio

Systematic review of the relative social value of child and adult health

Objectives: We aimed to synthesise knowledge on the relative social value of child and adult health. Methods: Quantitative and qualitative studies that evaluated the willingness of the public to prioritise treatments for children over adults were included. A search to September 2023 was undertaken. Completeness of reporting was assessed using a checklist derived from Johnston et al. Findings were tabulated by study type (matching/person trade-off, discrete choice experiment, willingness to pay, opinion survey or qualitative). Evidence in favour of children was considered in total, by length or quality of life, methodology and respondent characteristics. Results: Eighty-eight studies were included; willingness to pay (n = 9), matching/person trade-off (n = 12), discrete choice experiments (n = 29), opinion surveys (n = 22) and qualitative (n = 16), with one study simultaneously included as an opinion survey. From 88 studies, 81 results could be ascertained. Across all studies irrespective of method or other characteristics, 42 findings supported prioritising children, while 12 provided evidence favouring adults in preference to children. The remainder supported equal prioritisation or found diverse or unclear views. Of those studies considering prioritisation within the under 18 years of age group, nine findings favoured older children over younger children (including for life saving interventions), six favoured younger children and five found diverse views. Conclusions: The balance of evidence suggests the general public favours prioritising children over adults, but this view was not found across all studies. There are research gaps in understanding the public’s views on the value of health gains to very young children and the motivation behind the public’s views on the value of child relative to adult health gains. Clinical Trial Registration: The review is registered at PROSPERO number: CRD42021244593. There were two amendments to the protocol: (1) some additional search terms were added to the search strategy prior to screening to ensure coverage and (2) a more formal quality assessment was added to the process at the data extraction stage. This assessment had not been identified at the protocol writing stage.</p