Notes

Gene therapy in epilepsy.
Mirror symmetries are of particular importance because they are connected to fundamental properties and conservation laws. Spatial inversion and time reversal are typically associated to charge and spin phenomena, respectively. When both are broken, magnetoelectric cross-coupling can arise. In the optical regime, a difference between forward and backward propagation of light may result. Usually, this nonreciprocal response is small. We show that a giant nonreciprocal optical response can occur when transferring from linear to nonlinear optics, specifically second harmonic generation (SHG). CuB2O4 exhibits SHG transmission changes by almost 100% upon reversal of a magnetic field of just ±10 mT. The observed nonreciprocity results from an interference between magnetic-dipole and electric-dipole SHG. Although the former is inherently weaker than the latter, a resonantly enhanced magnetic-dipole transition has a comparable amplitude as a nonresonant electric-dipole transition, thus maximizing the nonreciprocity. Multiferroics and magnetoelectrics are an obvious materials platform to exhibit nonreciprocal nonlinear optical functionalities.The avascular nature of cornea tissue limits its regenerative potential, which may lead to incomplete healing and formation of scars when damaged. Here, we applied micro- and ultrafine porcine urinary bladder matrix (UBM) particulate to promote type 2 immune responses in cornea wounds. Results demonstrated that UBM particulate substantially reduced corneal haze formation as compared to the saline-treated group. Flow cytometry and gene expression analysis showed that UBM particulate suppressed the differentiation of corneal stromal cells into α-smooth muscle actin-positive (αSMA+) myofibroblasts. UBM treatments up-regulated interleukin-4 (IL-4) produced primarily by eosinophils in the wounded corneas and CD4+ T cells in draining lymph nodes, suggesting a cross-talk between local and peripheral immunity. Gata1-/- mice lacking eosinophils did not respond to UBM treatment and had impaired wound healing. In summary, stimulating type 2 immune responses in the wounded cornea can promote proregenerative environments that lead to improved wound healing for vision restoration.Angular momentum of spinning bodies leads to their remarkable interactions with fields, waves, fluids, and solids. Orbiting celestial bodies, balls in sports, liquid droplets above a hot plate, nanoparticles in optical fields, and spinning quantum particles exhibit nontrivial rotational dynamics. Pictilisib purchase Here, we report self-guided propulsion of magnetic fast-spinning particles on a liquid surface in the presence of a solid boundary. Above some critical spinning frequency, such particles generate localized 3D vortices and form composite "spinner-vortex" quasiparticles with nontrivial, yet robust dynamics. Such spinner-vortices are attracted and dynamically trapped near the boundaries, propagating along the wall of any shape similarly to "liquid wheels." The propulsion velocity and the distance to the wall are controlled by the angular velocity of the spinner via the balance between the Magnus and wall repulsion forces. Our results offer a new type of surface vehicles and provide a powerful tool to manipulate spinning objects in fluids.
Studies have shown beneficial effects of real-time continuous glucose monitoring (rtCGM) usage on clinical outcomes. The objective of this analysis was to identify which therapy adjustments were made by people with type 1 diabetes with impaired hypoglycemia awareness during rtCGM usage enabling reductions in the number of low glucose events observed in the HypoDE (Hypoglycemia in Deutschland) study.

In the multicenter randomized controlled trial in people with type 1 diabetes on multiple daily injections with impaired hypoglycemia awareness, participants recorded their diabetes therapy in 7-day logbooks at baseline and at 6-month follow-up. They used rtCGM or self-monitoring of blood glucose for therapy adjustments. This mechanistic analysis looked at changes in various aspects of therapy.

Logbooks were completed by 70 participants in the rtCGM group and 65 participants in the control group. Participants in the rtCGM group kept their total carbohydrate consumption, daily insulin doses and distribution constant during the study. However, they reported an increased intake of rescue carbohydrates (0.8±0.6 (mean±SD) vs 1.0±0.8 intake/day; baseline-adjusted between-group difference 0.3 intake (0.1-0.5), p=0.031). The glucose threshold at which rescue carbohydrate intake was initiated was elevated from 71±13 mg/dL (3.9±0.7 mmol/L) to 79±14 mg/dL (4.4±0.8 mmol/L) (adjusted between-group difference +7.6 mg/dL (2.4-12.8) (+0.4 mmol/L (0.1-0.7)); p=0.005) in the rtCGM group. Regression analysis showed that follow-up low glucose events were associated with group allocation (p<0.001), low glucose events at baseline (p=0.016) and rescue threshold (p=0.001).

No major adjustments in insulin therapy were made by study participants with impaired hypoglycemia awareness; however, they were more active in preventing hypoglycemia by taking rescue carbohydrates earlier and more often.

NCT02671968.
NCT02671968.
Approximately 40% of the 55 000 women diagnosed with breast cancer each year in the UK undergo mastectomy because they are considered unsuitable for standard breast-conserving surgery (BCS) due to tumour size or multiple tumour foci. Mastectomy can significantly impact women's quality of life, and only one in four women currently undergo immediate breast reconstruction (IBR).Level 2 oncoplastic breast-conserving surgery (OPBCS) combines removing the cancer with a range of plastic surgical volume replacement (eg, local perforator flaps) and volume displacement techniques (eg, therapeutic mammaplasty) that can extend the role of BCS and may allow some women not suitable for standard BCS to avoid mastectomy. High-quality research to determine whether OPBCS offers a safe and effective alternative to mastectomy±IBR is currently lacking. Preliminary work is needed to ensure a future large-scale study is feasible and well designed and addresses questions important to patients and the National Health Service.

Mixnal Research Ethics Service (REC Ref 20/WA/0225). Results will be presented at national and international meetings and published in peer-reviewed journals. We will work with patients to develop lay summaries and share these through patient groups and breast cancer charities.

ISRCTN18238549.
ISRCTN18238549.
Dental anxiety remains widespread among children, may continue into adulthood and affect their oral health-related quality of life and clinical management. The aim of the study was to explore the trend of children's dental anxiety over time and potential risk factors.

Longitudinal study.

Children aged between 5 and 12 years were investigated with the Chinese version of face version of Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) and Frankl Behavior Rating scale from 2008 to 2017, and influential factors were explored.

Clinical data were available from 1061 children, including 533 (50.2%) male participants and 528 (49.8%) female participants. The total CFSS-DS scores ranged from 16 to 66, with a mean of 24.8±10.3. The prevalence of dental anxiety is 11.59%. No significant differences in total CFSS-DS scores between girls and boys were found. According to the Frankl scale, 238 children were allocated to the uncooperative group and the remaining 823 children were allocated to the cooperative's dental anxiety in a new era of information, but the results may be extrapolated to other populations with caution.
There are increasing requirements to make research data, especially clinical trial data, more broadly available for secondary analyses. However, data availability remains a challenge due to complex privacy requirements. This challenge can potentially be addressed using synthetic data.

Replication of a published stage III colon cancer trial secondary analysis using synthetic data generated by a machine learning method.

There were 1543 patients in the control arm that were included in our analysis.

Analyses from a study published on the real dataset were replicated on synthetic data to investigate the relationship between bowel obstruction and event-free survival. Information theoretic metrics were used to compare the univariate distributions between real and synthetic data. Percentage CI overlap was used to assess the similarity in the size of the bivariate relationships, and similarly for the multivariate Cox models derived from the two datasets.

Analysis results were similar between the real and synthetic datasets. The univariate distributions were within 1% of difference on an information theoretic metric. All of the bivariate relationships had CI overlap on the tau statistic above 50%. The main conclusion from the published study, that lack of bowel obstruction has a strong impact on survival, was replicated directionally and the HR CI overlap between the real and synthetic data was 61% for overall survival (real data HR 1.56, 95% CI 1.11 to 2.2; synthetic data HR 2.03, 95% CI 1.44 to 2.87) and 86% for disease-free survival (real data HR 1.51, 95% CI 1.18 to 1.95; synthetic data HR 1.63, 95% CI 1.26 to 2.1).

The high concordance between the analytical results and conclusions from synthetic and real data suggests that synthetic data can be used as a reasonable proxy for real clinical trial datasets.

NCT00079274.
NCT00079274.Myeloid cells in the tumor microenvironment exhibited the highest uptake of intratumoral glucose.The FDA's Accelerated Approval program is under scrutiny after four drug companies announced plans in recent months to withdraw indications for checkpoint inhibitors that, despite showing early promise, failed to demonstrate a survival benefit in confirmatory trials. The agency's Oncologic Drugs Advisory Committee will meet in late April to discuss whether six more indications for some of these same immunotherapies should be nullified as well.Extrachromosomal DNA (ecDNA) molecules associated with transcriptionally active genes on linear chromosomes.Altering metabolic flux at a key branch point in metabolism has commonly been accomplished through gene knockouts or by modulating gene expression. An alternative approach to direct metabolic flux preferentially toward a product is decreasing the activity of a key enzyme through protein engineering. In Escherichia coli, pyruvate can accumulate from glucose when carbon flux through the pyruvate dehydrogenase complex is suppressed. Based on this principle, 16 chromosomally expressed AceE variants were constructed in E. coli C and compared for growth rate and pyruvate accumulation using glucose as the sole carbon source. To prevent conversion of pyruvate to other products, the strains also contained deletions in two nonessential pathways lactate dehydrogenase (ldhA) and pyruvate oxidase (poxB). The effect of deleting phosphoenolpyruvate synthase (ppsA) on pyruvate assimilation was also examined. The best pyruvate-accumulating strains were examined in controlled batch and continuous processes. In a nitrogen-limited chemostat process at steady-state growth rates of 0.
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