Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents.

Background: Glioblastoma multiforme (GBM) is an aggressive cancer with poor prognosis, partly due to resistance to the standard chemotherapy treatment, temozolomide (TMZ). Phytocannabinoid cannabidiol (CBD) has exhibited anti-cancer effects against GBM, however, CBD's ability to overcome common resistance mechanisms to TMZ have not yet been investigated. 4'-Fluoro-cannabidiol (4'-F-CBD, or HUF-101/PECS-101) is a derivative of CBD, that exhibits increased activity compared to CBD during in vivo behavioural studies.

An interconnected data infrastructure to support large-scale rare disease research.

The Solve-RD project brings together clinicians, scientists, and patient representatives from 51 institutes spanning 15 countries to collaborate on genetically diagnosing ("solving") rare diseases (RDs). The project aims to significantly increase the diagnostic success rate by co-analyzing data from thousands of RD cases, including phenotypes, pedigrees, exome/genome sequencing, and multiomics data. Here we report on the data infrastructure devised and created to support this co-analysis.

Watershed analysis of urban stormwater contaminant 6PPD-Quinone hotspots and stream concentrations using a process-based ecohydrological model.

Coho salmon () are highly sensitive to 6PPD-Quinone (6PPD-Q). Details of the hydrological and biogeochemical processes controlling spatial and temporal dynamics of 6PPD-Q fate and transport from points of deposition to receiving waters (e.g.

Heteroallene Insertions into Tin(II) Alkoxide Bonds.

A series of iso-carbamate complexes have been synthesized by the reaction of [Sn(OPr)] or [Sn(OBu)] with either aryl or alkyl isocyanates, ONC-R (R = 2,4,6-trimethylphenyl (Mes), 2,6-diisopropylphenyl (Dipp), isopropyl (Pr), cyclohexyl (Cy) and -butyl (Bu)). In the case of aryl isocyanates, mono-insertion occurs to form structurally characterized complexes [Sn{κ--R-NC(OPr)O}(μ-OPr)] (: R = Mes, : R = Dipp) and [Sn{κ--R-NC(OBu)O}(μ-OBu)] (: R = Mes, : R = Dipp). The complicated solution-state chemistry of these species has been explored using H DOSY experiments.

Improved urban runoff prediction using high-resolution land-use, imperviousness, and stormwater infrastructure data applied to a process-based ecohydrological model.

Modeling large-scale hydrological impacts brought about by site-level green and gray stormwater remediation actions is difficult because urbanized areas are extremely complex dynamic landscapes that include engineered features that, by design, expedite urban runoff to streams, creeks, and other water bodies to reduce urban flooding during storm events. Many urban communities use heavily engineered gray infrastructure to achieve that goal, along with more recent additions of green infrastructure such as rain gardens, bioswales, and riparian corridors. Therefore, successfully characterizing those design details and associated management practices, interactions, and impacts requires a detailed understanding of how fine and course-scale hydrologic processes and routing are altered and managed in urban watersheds.

Getting your DUCs in a row - standardising the representation of Digital Use Conditions.

Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level.

Common conditions of use elements. Atomic concepts for consistent and effective information governance.

Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse 'use conditions'. We report a core lexicon of terms that are atomic, non-directional 'concepts of use', called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility.

Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer's Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project.

The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer's disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention.

Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018.

Transitioning through the vapour-liquid equilibrium for low energy thermal stripping of ammonia from wastewater: Enabling transformation of NH into a zero-carbon fuel.

Vacuum thermal stripping permits the recovery of ammonia from wastewater in a concentrated form, which is key to its exploitation in the circular economy, but the latent heat demand for thermal separation remains a critical barrier to exploitation. In this study, we investigate the vapor-liquid equilibrium (VLE) for ammonia-water as a mechanism to enhance recovered ammonia quality and minimise the thermal energy required for ammonia separation. Below the dew point (65 °C at 0.

Impact of changing from autopsy to post-mortem CT in an entire HM Coroner region due to a shortage of available pathologists.

A significant problem facing routine medicolegal coroner-referred autopsies is a shortfall of pathologists prepared to perform them. This was particularly acute in Lancashire, where the coroner decided to initiate a service that relied on post-mortem computed tomography (PMCT). This involved training anatomical pathology technologists (APTs) to perform external examinations, radiographers to perform scans, and radiologists to interpret them.

Data sharing in neurodegenerative disease research: challenges and learnings from the innovative medicines initiative public-private partnership model.

Efficient data sharing is hampered by an array of organizational, ethical, behavioral, and technical challenges, slowing research progress and reducing the utility of data generated by clinical research studies on neurodegenerative diseases. There is a particular need to address differences between public and private sector environments for research and data sharing, which have varying standards, expectations, motivations, and interests. The Neuronet data sharing Working Group was set up to understand the existing barriers to data sharing in public-private partnership projects, and to provide guidance to overcome these barriers, by convening data sharing experts from diverse projects in the IMI neurodegeneration portfolio.

On the Risk of Nitrosamine Contamination During Drug Product Blister Packaging.

Most N-Nitrosamine compounds are found to be genotoxic in several animal species. Some are classified as probable or possible human carcinogens and very low acceptable daily intake has been established such as 96 ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/N-nitrosodiethylamine (NDEA).

Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain.

Delivery to the brain is a challenging task due to its protection by the blood-brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabidiol (CBD) has high therapeutic potential in the brain, therefore, this work investigated CBD delivery to anatomical brain regions following oral administration in lipid-based and lipid-free vehicles.

Data and sample sharing as an enabler for large-scale biomarker research and development: The EPND perspective.

Biomarker discovery, development, and validation are reliant on large-scale analyses of high-quality samples and data. Currently, significant quantities of data and samples have been generated by European studies on Alzheimer's disease (AD) and other neurodegenerative diseases (NDD), representing a valuable resource for developing biomarkers to support early detection of disease, treatment monitoring, and patient stratification. However, discovery of, access to, and sharing of data and samples from AD and NDD research are hindered both by silos that limit collaboration, and by the array of complex requirements for secure, legal, and ethical sharing.

Tough places and safe spaces: Can refuges save salmon from a warming climate?

The importance of thermal refuges in a rapidly warming world is particularly evident for migratory species, where individuals encounter a wide range of conditions throughout their lives. In this study, we used a spatially explicit, individual-based simulation model to evaluate the buffering potential of cold-water thermal refuges for anadromous salmon and trout ( spp.) migrating upstream through a warm river corridor that can expose individuals to physiologically stressful temperatures.

Developing Social-ABI-lity: An Online Course to Support Safe Use of Social Media for Connection After Acquired Brain Injury.

Purpose: People who have an acquired brain injury (ABI) experience challenges using social media. Inversely, rehabilitation clinicians report feeling inadequately prepared to support them in its use. We aimed to develop a collaboratively designed, evidence-based online training resource to support people with an ABI to learn about using social media.

'It gives you encouragement because you're not alone': A pilot study of a multi-component social media skills intervention for people with acquired brain injury.

Background: People with an acquired brain injury (ABI) find it challenging to use social media due to changes in their cognition and communication skills. Using social media can provide opportunities for positive connection, but there is a lack of interventions specifically designed to support safe and successful social media use after ABI.

Aims: To investigate the outcomes of completing a social media skills intervention and identify barriers and facilitators for future implementation.

GWAS Central: an expanding resource for finding and visualising genotype and phenotype data from genome-wide association studies.

The GWAS Central resource gathers and curates extensive summary-level genome-wide association study (GWAS) data and puts a range of user-friendly but powerful website tools for the comparison and visualisation of GWAS data at the fingertips of researchers. Through our continued efforts to harmonise and import data received from GWAS authors and consortia, and data sets actively collected from public sources, the database now contains over 72.5 million P-values for over 5000 studies testing over 7.

Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle.

Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the efficiency of drug delivery to the retroperitoneal lymph nodes (RPLN) has not been assessed.

Beacon v2 and Beacon networks: A "lingua franca" for federated data discovery in biomedical genomics, and beyond.

Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple "yes" or "no" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations.