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Superconducting circuits can operate at higher energy efficiencies than their room-temperature counterparts and have the potential to enable large-scale control and readout of quantum computers. However, the required interface with room-temperature electronics creates difficulties in scaling up such cryogenic systems. One option is to use optical fibres as a medium in conjunction with fast optical modulators that can be efficiently driven by electrical signals at low temperatures. However, as superconducting circuits are current operated with low impedances, they interface poorly with conventional electro-optical modulators. Here we report an integrated current-driven modulator that is based on the magneto-optic effect and can operate at temperatures as low as 4 K. The device combines a magneto-optic garnet crystal with a silicon waveguide resonator and integrates an electromagnet to modulate the refractive index of the garnet. The modulator offers data rates of up to 2 Gbps with an energy consumption below 4 pJ per bit of transferred information, which could be reduced to less than 50 fJ per bit by replacing dissipative electrodes with superconductors and optimizing the geometric parameters.

Circular RNAs (circRNAs) are regulatory elements that are involved in orchestrating gene expression and protein functions and are implicated in various biological processes including cancer. Notably, breast cancer has a significant mortality rate and is one of the most common malignancies in women. CircRNAs have been demonstrated to contribute to the pathogenesis of breast cancer including its initiation, progression, metastasis, and resistance to drugs. By acting as miRNA sponges, circRNAs can indirectly influence gene expression by disrupting miRNA regulation of their target genes, ultimately altering the course of cancer development and progression. Additionally, circRNAs can interact with proteins and modulate their functions including signaling pathways involved in the initiation and development of cancer. Recently, circRNAs can encode peptides that play a role in the pathophysiology of breast cancer and other diseases and their potential as diagnostic biomarkers and therapeutic targets for various cancers including breast cancer. CircRNAs possess biomarkers that differentiate, such as stability, specificity, and sensitivity, and can be detected in several biological specimens such as blood, saliva, and urine. Moreover, circRNAs play an important role in various cellular processes including cell proliferation, differentiation, and apoptosis, all of which are integral factors in the development and progression of cancer. This review synthesizes the functions of circRNAs in breast cancer, scrutinizing their contributions to the onset and evolution of the disease through their interactions with exosomes and cancer-related intracellular pathways. It also delves into the potential use of circRNA as a biomarker and therapeutic target against breast cancer. It discusses various databases and online tools that offer crucial circRNA information and regulatory networks. Lastly, the challenges and prospects of utilizing circRNAs in clinical settings associated with breast cancer are explored.

Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims.

We present a novel practical and efficient mathematical formulation for light intensity calibration of multi-light image collections (MLICs). Inspired by existing and orthogonal calibration methods, we design a hybrid solution that leverages their strengths while overcoming most of their weaknesses. We combine the rationale of approaches based on fixed analytical models with the interpolation scheme of image domain methods. This allows us to minimize the final residual error in light intensity estimation, without imposing an overly constraining illuminant type. Unlike previous approaches, the proposed calibration strategy proved to be simpler, more efficient and versatile, and extremely adaptable in different setup scenarios. We conduct an extensive analysis and validation of our new light model compared to several state-of-the-art techniques, and we show how the proposed solution provides a more reliable outcomes in terms of accuracy and precision, and a more stable calibration across different light positions/orientations, and with a more general light form factor.

BackgroundSafe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians.MethodsRetrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator).Results441 patients received SACT in 2020 (292 prostate, 101 renal, 38 urothelial, 10 testicular) compared to 518 patients in 2019 (340 prostate, 121 renal, 42 urothelial, 15 testicular). In 2020, there were 75.00% fewer patients with stage 3 cancers receiving SACT (p p = 0.00194). The number of patients started on a new line of SACT was similar between both years (118 in 2019 vs 102 in 2020;p = 0.898) but with 53.45% fewer patients started on chemotherapy in 2020 (p p = 0.649) whereas 6-month mortality was lower (9.32% in 2019 vs 1.96% in 2020;p = 0.0209) in 2020.ConclusionThis study suggests that delivery of SACT to uro-oncology patients during COVID-19 pandemic may be safe in high-incidence areas with appropriate risk-reduction strategies.

Background\ud \ud Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy.\ud \ud \ud \ud Methods\ud \ud We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020.\ud \ud \ud \ud Results\ud \ud In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: “Ward, CC, Ward”, “Ward, CC”, “CC” and “CC, Ward”. Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days.\ud \ud \ud \ud For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities.\ud \ud \ud \ud Conclusions\ud \ud We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19.\ud \ud \ud \ud Trial registration\ud \ud The ISARIC WHO CCP-UK study ISRCTN66726260 was retrospectively registered on 21/04/2020 and designated an Urgent Public Health Research Study by NIHR.

We present a novel approach to automatically recover, from a small set of partially overlapping spherical images, an indoor structure representation in terms of a 3D floor plan registered with a set of 3D environment maps. % We introduce several improvements over previous approaches based on color/spatial reasoning exploiting \emph{Manhattan World} priors. In particular, we introduce a new method for geometric context extraction based on a 3D facets representation, which combines color distribution analysis of individual images with sparse multi-view clues. Moreover, we introduce an efficient method to combine the facets from different points of view in a single consistent model, considering the reliability of the facets contribution. The resulting capture and reconstruction pipeline automatically generates 3D multi-room environments where most of the other previous approaches fail, such as in presence of hidden corners and large clutter, even without involving additional dense 3D data or tools. % We demonstrate the effectiveness and performance of our approach on different real-world indoor scenes. Our test data will be released to allow for further studies and comparisons.

Background Fatty alcohol polyoxyethylene ether-7 (AEO-7), a non-ionic surfactant, has recently been receiving extensive attention from the ocean pipeline industry for its ability to inhibit corrosion. However, the present lack of information concerning the potential environmental toxicity of AEO-7, especially towards aquatic organisms, is a major impediment to its wider application. Here, we assess potential adverse effects of AEO-7 on zebrafish embryos employing a variety of assays, including (i) a mortality/survival assay which allowed the median lethal concentration (LC50) to be calculated; (ii) a teratogenicity assay on the basis of which the no observed effect concentration (NOEC) was determined; and (iii) specific assays of cardiotoxicity, neurotoxicity (based on locomotion), hematopoietic toxicity (the level of hemoglobin as revealed by o-dianisidine staining) and hepatotoxicity (liver steatosis and yolk retention examined by staining with Oil Red O). Results AEO-7 caused mortality with a calculated LC50 of 15.35 μg/L, which, according to the U.S. Fish and Wildlife Service (USFWS) Acute Toxicity Rating scale, should be considered “super toxic”. Although at its NOEC (0.8 μg/L), there were no signs of significant teratogenicity, cardiotoxicity, or hemopoiesis toxicity, 3.2 µg/L AEO-7 exerted dramatic detrimental effects on organ development. Conclusion On the basis of these findings, we recommend that the industrial usage and environmental impact of AEO-7 be re-evaluated and strictly monitored by environmental and public health organizations.

Background Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for the treatment of breast cancer susceptibility genes 1 and 2 (BRCA1/2) mutant ovarian and breast cancers, and are now being evaluated in metastatic castration-resistant prostate cancer (mCRPC). Reversion mutations that restore BRCA1/2 function have been shown to be responsible for resistance to platinum-based chemotherapy and PARP inhibitors, however there is no information on the sequential use of these agents in prostate cancer. Case presentation A patient with mCRPC associated with a germline BRCA2 mutation was sequentially treated with carboplatin and the PARP inhibitor rucaparib. Genomic profiling of the available baseline tumor and progression blood samples using next-generation sequencing panel tests identified polyclonal BRCA2 reversion mutations post carboplatin treatment but prior to rucaparib treatment. A total of 12 somatic reversion mutations were detected and ranged from small indels to larger deletions of up to 387 amino acids. These alterations are all predicted to restore the BRCA2 open reading frame and potentially protein function. The patient received limited benefit while on rucaparib, likely due to these reversion mutations observed prior to treatment. Conclusions Here we report a case of a patient with prostate cancer who received a platinum agent and PARP inhibitor sequentially and in whom polyclonal BRCA2 reversion mutations were identified as the likely mechanism of acquired resistance to carboplatin and primary resistance to PARP inhibition. These findings suggest caution is warranted in sequencing these agents.

Sardinian honeys obtained from different floral sources (Arbutus, Asphodelus, Eucalyptus, Thistle, and Sulla) were evaluated for their ability to inhibit tyrosinase and xanthine oxidase enzymes and for their antioxidant activity. Physicochemical parameters, total phenolic, and flavonoids content were also determined. Honey from Arbutus flowers had the highest antioxidant activity followed by Eucalyptus and Thistle ones. These three honeys showed good tyrosinase and xanthine oxidase inhibition properties. Thus, these Sardinian honeys could have a great potential as antioxidant sources for pharmaceutical and cosmetic applications.

The 2-methylene-furan-3-one reductase or Fragaria x ananassa Enone Oxidoreductase (FaEO) catalyses the last reductive step in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a major component in the characteristic flavour of strawberries. In the present work, we describe the association between FaEO and the vacuolar membrane of strawberry fruits. Even if FaEO lacks epitopes for stable or transient membrane-interactions, it contains a calmodulin-binding region, suggesting that in vivo FaEO may be associated with the membrane via a peripheral protein complex with calmodulin. Moreover, we also found that FaEO occurs in dimeric form in vivo and, as frequently observed for calmodulin-regulated proteins, it may be expressed in different isoforms by alternative gene splicing. Further mass spectrometry analysis confirmed that the isolated FaEO consists in the already known isoform and that it is the most characteristic during ripening. Finally, a characterization by absorption spectroscopy showed that FaEO has specific flavoprotein features. The relevance of these findings and their possible physiological implications are discussed.

The study and characterization of old artifacts such as pigments requires the use of techniques that need a small amount of sample to perform the analysis because of the high value of these samples. In recent years, organic molecules such as anthraquinone dyes have been identified by surface-enhanced Raman spectroscopy (SERS). However, different sample treatments must be applied to isolate the organic dye from the mordant, which produces great fluorescence in the Raman measurements. In this work, optimization of sample treatment for the SERS analysis of anthraquinone dyes was performed. Sample mass, the organic solvent, and its volume were optimized and different slide materials and excitation lasers were compared to choose the best conditions for the identification of the dyes. The optimization of sample treatment resulted in 5 mg of sample as the optimum amount. Further, two consecutive extractions with 0.5 mL of ethyl acetate was the best option for the extraction of the dye. A quartz slide was used instead of a glass slide to reduce background signal, and an excitation laser of 532 nm offers better results than one of 785 nm. The optimized method was applied to the characterization of the dyes used in Pompeian pink and purple lake pigments. Alizarin and purpurin anthraquinone dyes, obtained from madder lake, were identified as the organic colorants. The SERS results were confirmed by those obtained by means of UV-visible spectroscopy. Graphical Abstract ᅟ.

The dietary flavonoids epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) have been shown to interact with circulating albumin for transport in blood to different body tissues. This interaction may modulate their bioavailability and effectiveness. Using affinity capillary electrophoresis to assess binding constants (K b), we investigated whether posttranslational modification of human serum albumin (HSA) through N- and S-homocysteinylation, commonly observed in hyperhomocysteinemia, may modify its interaction with catechins. S-Hcy HSA had lower Kb values toward EC (14 %), EGC (18 %), ECG (24 %) and EGCG (30 %). Similarly, N-Hcy HSA had lower Kb values toward EC (17 %), EGC (22 %), ECG (23 %) and EGCG (32 %). No differences were observed in the affinity between catechins, albumin and mercaptalbumin. Therefore, HSA posttranslational modifications typical of hyperhomocysteinemia reduce its affinity to catechins, potentially affecting their pharmacokinetics and availability at the active sites.

Background Small molecule Nutlin-3 reactivates p53 in cancer cells by interacting with the complex between p53 and its repressor Mdm-2 and causing an increase in cancer cell apoptosis. Therefore, Nutlin-3 has potent anticancer properties. Clinical and experimental studies of Nutlin-3 showed that some cancer cells may lose sensitivity to this compound. Here we analyze possible mechanisms for insensitivity of cancer cells to Nutlin-3. Methods We applied upstream analysis approach implemented in geneXplain platform (genexplain.com) using TRANSFAC® database of transcription factors and their binding sites in genome and using TRANSPATH® database of signal transduction network with associated software such as Match™ and Composite Module Analyst (CMA). Results Using genome-wide gene expression profiling we compared several lung cancer cell lines and showed that expression programs executed in Nutlin-3 insensitive cell lines significantly differ from that of Nutlin-3 sensitive cell lines. Using artificial intelligence approach embed in CMA software, we identified a set of transcription factors cooperatively binding to the promoters of genes up-regulated in the Nutlin-3 insensitive cell lines. Graph analysis of signal transduction network upstream of these transcription factors allowed us to identify potential master-regulators responsible for maintaining such low sensitivity to Nutlin-3 with the most promising candidate mTOR, which acts in the context of activated PI3K pathway. These finding were validated experimentally using an array of chemical inhibitors. Conclusions We showed that the Nutlin-3 insensitive cell lines are actually highly sensitive to the dual PI3K/mTOR inhibitor NVP-BEZ235, while no responding to either PI3K –specific LY294002 nor Bcl-XL specific 2,3-DCPE compounds. Electronic supplementary material The online version of this article (10.1186/s12920-018-0330-5) contains supplementary material, which is available to authorized users.

The aim of this study was to evaluate the concentration of l-ergothioneine in follicular fluid of some domestic farm animals, such as mare, sheep, goat, sow, and unweaned lamb. The group of unweaned lambs was the cluster with the lowest mean concentration (0.12 ± 0.06 μmol/L), while the mares showed the highest mean values (3.16 ± 1.27 μmol/L). The mean levels in the sheep and goats were similar (0.72 ± 0.21 vs. 0.73 ± 0.50 μmol/L), while the mean values in the sows were slightly higher (1.04 ± 0.37 μmol/L) than the other two groups. Except for sheep vs. goats, the differences in the concentrations of l-ergothioneine between animal groups were statically significant. After grouping data according to the follicular diameter, a not statistically significant trend of increase of l-ergothioneine levels with the rise of follicular diameter was observed in sheep, goats, and unweaned lambs while an opposite tendency was observed in mares.

This international research project examined the value of utilizing an early childhood program assessment instrument as a tool for in-service professional development and self-reflection for kindergarten teachers in Parma, Italy. Teacher educators from universities in Italy and the USA conducted the study collaboratively. Goals of the study were to engage the kindergarten teachers in testing the ACEI-GGA tool in Italy for validity and reliability; utilize the tool as a means of self-reflection and study of the classroom context; and enhance the teachers’ feelings and attitudes about the program assessment process. Data sources were the kindergarten teachers who utilized ACEI-GGA tool in their classrooms as a means of evaluating their practices and determining the clarity and ease of use of the assessment tool in Italian kindergarten classrooms. Teacher responses provided the researchers with helpful information on the clarity of the items across the five content areas or domains, especially the content area related to “serving children with special needs and their families.” Results indicate that the kindergarten teachers benefited from the use of the program assessment tool for professional development purposes. In addition, the kindergarten teachers provided helpful feedback on the clarity and usefulness of the tool.