Optical properties of silicon-implanted polycrystalline diamond membranes

We investigate the optical properties of polycrystalline diamond membranes containing silicon-vacancy (SiV) color centers in combination with other nano-analytical techniques. We analyze the correlation between the Raman signal, the SiV emission, and the background luminescence in the crystalline grains and in the grain boundaries, identifying conditions for the addressability of single SiV centers. Moreover, we perform a scanning transmission electron microscopy (STEM) analysis, which associates the microscopic structure of the membranes and the evolution of the diamond crystal along the growth direction with the photoluminescence properties, as well as a time-of-flight secondary ion mass spectrometry (ToF-SIMS) to address the distribution of silicon in implanted and un-implanted membranes. The results of the STEM and ToF-SIMS studies are consistent with the outcome of the optical measurements and provide useful insight into the preparation of polycrystalline samples for quantum nano-optics.Comment: 21 pages, 8 figure

Validation of standard and new criteria for the differential diagnosis of narrow QRS tachycardia in children and adolescents

To establish an appropriate treatment strategy and determine if ablation is indicated for patients with narrow QRS complex supraventricular tachycardia (SVT), analysis of a standard 12-lead electrocardiogram (ECG) is required, which can differentiate between the 2 most common mechanisms underlying SVT: atrioventricular nodal reentry tachycardia (AVNRT) and orthodromic atrioventricular reentry tachycardia (OAVRT). Recently, new, highly accurate electrocardiographic criteria for the differential diagnosis of SVT in adults were proposed; however, those criteria have not yet been validated in a pediatric population. All ECGs were recorded during invasive electrophysiology study of pediatric patients (n = 212; age: 13.2 ± 3.5, range: 1–18; girls: 48%). We assessed the diagnostic value of the 2 new and 7 standard criteria for differentiating AVNRT from OAVRT in a pediatric population. Two of the standard criteria were found significantly more often in ECGs from the OAVRT group than from the AVNRT group (retrograde P waves [63% vs 11%, P < 0.001] and ST-segment depression in the II, III, aVF, V1–V6 leads [42% vs 27%; P < 0.05]), whereas 1 standard criterion was found significantly more often in ECGs from the AVNRT group than from the OAVRT group (pseudo r′ wave in V1 lead [39% vs 10%, P < 0.001]). The remaining 6 criteria did not reach statistical significance for differentiating SVT, and the accuracy of prediction did not exceed 70%. Based on these results, a multivariable decision rule to evaluate differential diagnosis of SVT was performed. These results indicate that both the standard and new electrocardiographic criteria for discriminating between AVNRT and OAVRT have lower diagnostic values in children and adolescents than in adults. A decision model based on 5 simple clinical and ECG parameters may predict a final diagnosis with better accuracy

Phototoxic aptamers selectively enter and kill epithelial cancer cells

The majority of cancers arise from malignant epithelial cells. We report the design of synthetic oligonucleotides (aptamers) that are only internalized by epithelial cancer cells and can be precisely activated by light to kill such cells. Specifically, phototoxic DNA aptamers were selected to bind to unique short O-glycan-peptide signatures on the surface of breast, colon, lung, ovarian and pancreatic cancer cells. These surface antigens are not present on normal epithelial cells but are internalized and routed through endosomal and Golgi compartments by cancer cells, thus providing a focused mechanism for their intracellular delivery. When modified at their 5′ end with the photodynamic therapy agent chlorin e6 and delivered to epithelial cancer cells, these aptamers exhibited a remarkable enhancement (>500-fold increase) in toxicity upon light activation, compared to the drug alone and were not cytotoxic towards cell types lacking such O-glycan-peptide markers. Our findings suggest that these synthetic oligonucleotide aptamers can serve as delivery vehicles in precisely routing cytotoxic cargoes to and into epithelial cancer cells

Randomised phase 2 study comparing the efficacy and safety of the oral tyrosine kinase inhibitor nintedanib with single agent ifosfamide in patients with advanced, inoperable, metastatic soft tissue sarcoma after failure of first-line chemotherapy: EORTC-1506-STBSG "ANITA"

Purpose: EORTC-1506-STBSG was a prospective, multicentric, randomised, open-label phase 2 trial to assess the efficacy and safety of second-line nintedanib versus ifosfamide in patients with advanced, inoperable metastatic soft tissue sarcoma (STS). The primary end-point was progression-free survival.Patients/methods: Patients with a variety of STS subtypes were randomised 1:1 to nintedanib (200 mg b.i.d. p.o. until disease progression) or ifosfamide (3 g/m(2) i.v. days 1-3, every 21 days for <= 6 cycles). A Korn design was applied aiming to detect an improvement in median progression-free survival (mPFS) from 3 to 4.5 months (HR = 0.667). An interim look was incorporated to stop the trial for futility if <19 of the first 36 patients treated with nintedanib were progression-free at week 12.Results: At the interim analysis, among the first 36 eligible and evaluable patients randomised for nintedanib, only 13 (36%) were progression-free at week 12. The trial was closed for further accrual as per protocol. In total, 80 patients were randomised (40 per treatment group). The mPFS was 2.5 months (95% CI: 1.5-3.4) for nintedanib and 4.4 months (95% CI: 2.9-6.7) on ifosfamide (adjusted HR = 1.56 [80% CI: 1.14-2.13], p = 0.070). The median overall survival was 13.7 months (95% CI: 9.4-23.4) on nintedanib and 24.1 months (95% CI: 10.9-NE) on ifosfamide (adjusted HR = 1.65 [95%CI:0.89-3.06], p = 0.111). The clinical benefit rate for nintedanib and ifosfamide was 50% versus 62.5% (p = 0.368), respectively. Common treatment-related adverse events (all grades) were diarrhoea (35.9% of patients), fatigue (25.6%) and nausea (20.5%) for nintedanib; and fatigue (52.6%), nausea (44.7%) and vomiting, anorexia and alopecia (28.9% each) for ifosfamide.Conclusion: The trial was stopped for futility. The activity of nintedanib did not warrant further exploration in non-selected, advanced STSs. (C) 2021 The Authors. Published by Elsevier Ltd.Experimentele farmacotherapi