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Glioblastoma (GB) is the most common and aggressive primary malignant astrocytoma correlated with poor patient survival. There are no curative treatments for GB, and it becomes resistant to chemotherapy, radiation therapy, and immunotherapy. Resistance in GB cells is closely related to their states of redox imbalance, and the role of reactive oxygen species and its impact on cancer cell survival is still far from elucidation. Boron-containing compounds, especially boric acid (BA) and borax (BX) exhibited interesting biological effects involving antibacterial, antiviral, anti-cancerogenic, anti-mutagenic, anti-inflammatory as well as anti-oxidative features. Recent studies indicated that certain boron compounds could be cytotoxic on human GB. Nevertheless, there is gap of knowledge in the literature on exploring the underlying mechanisms of anti-GB action by boron compounds. Here, we identified and compared the potential anti-GB effect of both BA and BX, and revealed their underlying anti-GB mechanism. We perf BX were associated with the BRAF/MAPK, PTEN and PI3K/AKT signaling pathways in respect of downregulatory manner. Especially, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes. In conclusion, our analysis indicated that boron compounds may be safe and promising for effective treatment of GB.

Traditional face-to-face training (FFT) for basic surgical skills is inaccessible and resource-intensive. Noninteractive computer-based learning is more economical but less educationally beneficial. click here Virtual classroom training (VCT) is a novel method that permits distanced interactive expert instruction. VCT may optimize resources and increase accessibility.

We aim to investigate whether VCT is superior to computer-based learning and noninferior to FFT in improving proficiency in basic surgical skills.

This is a protocol for a parallel-group, noninferiority, randomized controlled trial. A sample of 72 undergraduates will be recruited from 5 medical schools in London. Participants will be stratified by subjective and objective suturing experience level and allocated to 3 intervention groups at a 111 ratio. VCT will be delivered using the BARCO weConnect software, and FFT will be provided by expert instructors. Optimal student-to-teacher ratios of 121 for VCT and 41 for FFT will be maintained. The assessed task will be interrupted suturing with hand-tied knots.

The primary outcome will be the postintervention Objective Structured Assessment of Technical Skills score, adjudicated by 2 experts blinded to the study and adjusted for baseline proficiency. The noninferiority margin (δ) will be defined using historical data.

This study will serve as a comprehensive appraisal of the suitability of virtual basic surgical skills classroom training as an alternative to FFT. Our findings will assist the development and implementation of further resource-efficient, accessible, virtual basic surgical skills training programs during the COVID-19 pandemic and in the future.

International Standard Randomized Controlled Trial Number ISRCTN12448098; https//www.isrctn.com/ISRCTN12448098.

PRR1-10.2196/28671.

PRR1-10.2196/28671.

Supporting Our Valued Adolescents (SOVA) is a moderated and anonymous social media website intervention. SOVA ambassadors are adolescents and young adults (AYA) asked to write monthly blog posts and comments on others' posts on topics surrounding mental health.

This study aims to understand the feasibility and acceptability of peer blogging for a moderated mental health intervention website and explore whether bloggers-AYA who self-report symptoms of depression and anxiety-experience potential benefits.

AYA aged 14 to 26 years with a self-reported history of depression or anxiety were recruited to the SOVA Peer Ambassador Program. Participants were asked to write one blog post a month and comment at least four times a month on other blog posts, for which they were compensated for up to US $15 monthly. Outcome variables measured at baseline and 3 months after intervention included website usability and feasibility, depressive symptoms, anxiety symptoms, mental health treatment history, cybercoping, persoength-based assets-self-esteem, competence, and confidence-which map onto resilience.

A blogging intervention for AYA with a history of depression or anxiety was feasible with regular and active engagement and shows evidence in a one-sample design for positive changes in strength-based assets-self-esteem, competence, and confidence-which map onto resilience.

Digital health has the potential to revolutionize health care by improving accessibility, patient experience, outcomes, productivity, safety, and cost efficiency. In England, the NHS (National Health Service) Long Term Plan promised the right to access digital-first primary care by March 31, 2024. However, there are few global, fully digital-first providers and limited research into their effects on cost from a health system perspective.

The aim of this study was to evaluate the impact of highly accessible, digital-first primary care on acute hospital spending.

A retrospective, observational analysis compared acute hospital spending on patients registered to a 24/7, digital-first model of NHS primary care with that on patients registered to all other practices in North West London Collaboration of Clinical Commissioning Groups. Acute hospital spending data per practice were obtained under a freedom of information request. Three versions of NHS techniques designed to fairly allocate funding according to Y18/19 for the 3 weighting methodologies used. In FY19/20, it was 15%, 35%, and 51% (£114, P=.006; £246, P<.001; and £362, P<.001) lower. This amounted to lower costs for the Babylon GP at Hand population of £1.37, £4.40 million, and £11.6 million, respectively, in FY18/19; and £3.26 million, £9.54 million, and £18.8 million, respectively, in FY19/20.

Patients with access to 24/7, digital-first primary care incurred significantly lower acute hospital costs.

Patients with access to 24/7, digital-first primary care incurred significantly lower acute hospital costs.

Web-based screening may be suitable for identifying individuals with presymptomatic latent diseases for recruitment to clinical studies, as such people do not often visit hospitals in the presymptomatic stage. The promotion of such online screening studies is critical to their success, although it remains uncertain how the effectiveness of such promotion can differ, depending on the different promotion methods, domains of interest, or countries of implementation.

The Japanese Trial-Ready Cohort (J-TRC) web study is our ongoing online screening registry to identify individuals with presymptomatic Alzheimer disease (AD), aimed at facilitating the clinical trials for AD prevention. Within the first 9 months of its 2019 launch, the J-TRC web study recruited thousands of online participants via multiple methods of promotion, including press releases, newspaper advertisements, web advertisements, or direct email invitations. Here, we aimed to quantitatively evaluate efficacy and cost-effectiveness of each of thc participants to AD clinical trials in Japan.

Our multivariate time-series analysis showed that each promotion method had different features in their effect of recruiting participants to the J-TRC web study. Under the advertisement condition settings thus far, newspaper advertisements and initial press releases were the most effective promotion methods, with fair cost-effectiveness that was equivalent to earlier online studies. These results can provide important suggestions for future promotions for the recruitment of presymptomatic participants to AD clinical trials in Japan.The ophthalmic artery is an easily accessible vessel for Doppler assessment that provides information on the less accessible intracranial circulation. In women with preeclampsia, compared with normotensive pregnant women, there is a decrease in impedance to flow and an increase in velocities in the flow velocity waveforms from the ophthalmic arteries. This study aimed to report the methodology for ophthalmic artery Doppler and summarize findings from the clinical implementation of such assessment in the prediction of preeclampsia. The Embase and MEDLINE were searched from inception to November 2020 to identify studies reporting on the use of ophthalmic artery Doppler in the prediction of preeclampsia. Of note, 2 small studies in high-risk pregnancies, one at 11 to 14 weeks' gestation and another at 20 to 28 weeks' gestation, reported differences between women who developed preeclampsia, compared with unaffected pregnancies, in ophthalmic artery Doppler and suggested that this is a useful biomarker for screeni prediction of preeclampsia provided by all the other biomarkers; and fourth, in the study at 35 to 37 weeks' gestation, the peak systolic velocity ratio improved the prediction of subsequent development of preeclampsia provided by maternal factors alone and combinations of maternal factors with mean arterial pressure, uterine artery pulsatility index, placental growth factor, and serum placental growth factor. The ophthalmic artery Doppler provides a useful biomarker for the prediction of preeclampsia.The ratio of microbial population size relative to the amount of host tissue, or 'microbial load', is a fundamental metric of colonization and infection, but it cannot be directly deduced from microbial amplicon data such as 16S rRNA gene counts. Because existing methods to determine load, such as serial dilution plating, quantitative PCR, and whole metagenome sequencing add substantial cost and/or experimental burden, they are only rarely paired with amplicon sequencing. We introduce host-associated microbe PCR (hamPCR), a robust strategy to both quantify microbial load and describe interkingdom microbial community composition in a single amplicon library. We demonstrate its accuracy across multiple study systems, including nematodes and major crops, and further present a cost-saving technique to reduce host overrepresentation in the library prior to sequencing. Because hamPCR provides an accessible experimental solution to the well-known limitations and statistical challenges of compositional data, it has far-reaching potential in culture-independent microbiology.Morphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wnt homolog Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc. We discovered that delivery of Hh, Wg, and Dpp to their respective targets is regulated. We found that less then 5% of Hh and less then 25% of Wg are taken up by disc cells and activate signaling. The amount of morphogen that is taken up and initiates signaling did not change when the level of morphogen expression was varied between 50 and 200% (Hh) or 50 and 350% (Wg). Similar properties were observed for Dpp. We analyzed an area of 150 μm×150 μm that includes Hh-responding cells of the disc as well as overlying tracheal cells and myoblasts that are also activated by disc-produced Hh. We found that the extent of signaling in the disc was unaffected by the presence or absence of the tracheal and myoblast cells, suggesting that the mechanism that disperses Hh specifies its destinations to particular cells, and that target cells do not take up Hh from a common pool.