The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors.

The FDA-approved anti-DNA virus agent cidofovir (CDV) is being evaluated in phase II/III clinical trials for the treatment of human papillomavirus (HPV)-associated tumors. However, previous observations had shown that CDV also inhibits the growth of vascular tumors induced by fibroblast growth factor-2 (FGF2)-transformed FGF2-T-MAE cells. Here, we demonstrate that CDV inhibits metastasis induced by FGF2-driven, virus-independent tumor cells. Pre-treatment of luciferase-expressing FGF2-T-MAE cells with CDV reduced single cell survival and anchorage-independent growth in vitro and lung metastasis formation upon intravenous inoculation into SCID mice. This occurred in the absence of any effect on homing of FGF2-T-MAE cells to the lungs and on the growth of subconfluent cell cultures or subcutaneous tumors in mice. Accordingly, CDV protected against lung metastasis when given systemically after tumor cell injection. Lung metastases in CDV-treated mice showed reduced Ki67 expression and increased nuclear accumulation of p53, indicating that CDV inhibits metastasis by affecting single cell survival properties. The anti-metastatic potential of CDV was confirmed on B16-F10 melanoma cells, both in zebrafish embryos and mice. These findings suggest that CDV may have therapeutic potential as an anti-metastatic agent and warrants further study to select those tumor types that are most likely to benefit from CDV therapy

Understanding the nature of psychiatric comorbidity in migraine: A systematic review focused on interactions and treatment implications

Background: Migraine is a highly prevalent and disabling neurological disorder which is commonly linked with a broad range of psychiatric comorbidities, especially among subjects with migraine with aura or chronic migraine. Defining the exact nature of the association between migraine and psychiatric disorders and bringing out the pathophysiological mechanisms underlying the comorbidity with psychiatric conditions are relevant issues in the clinical practice. Methods: A systematic review of the most relevant studies about migraine and psychiatric comorbidity was performed using "PubMed", "Scopus", and "ScienceDirect" electronic databases from 1 January 1998 to 15 July 2018. Overall, 178 studies met our inclusion criteria and were included in the current review. Results: According to the most relevant findings of our overview, the associations with psychiatric comorbidities are complex, with a bidirectional association of major depression and panic disorder with migraine. Importantly, optimizing the pharmacological and non-pharmacological treatment of either migraine or its psychiatric comorbidities might help clinicians to attenuate the burden of both these conditions. Conclusions: The available data highlight the need for a comprehensive evaluation of psychiatric disorders in migraine in order to promote an integrated model of care and carefully address the burden and psychosocial impairment related to psychiatric comorbidities in migraine

Awe and Wonder in Scientific Practice: Implications for the Relationship Between Science and Religion

This paper examines the role of awe and wonder in scientific practice. Drawing on evidence from psychological research and the writings of scientists and science communicators, I argue that awe and wonder play a crucial role in scientific discovery. They focus our attention on the natural world, encourage open-mindedness, diminish the self (particularly feelings of self-importance), help to accord value to the objects that are being studied, and provide a mode of understanding in the absence of full knowledge. I will flesh out implications of the role of awe and wonder in scientific discovery for debates on the relationship between science and religion. Abraham Heschel argued that awe and wonder are religious emotions because they reduce our feelings of self-importance, and thereby help to cultivate the proper reverent attitude towards God. Yet metaphysical naturalists such as Richard Dawkins insist that awe and wonder need not lead to any theistic commitments for scientists. The awe some scientists experience can be regarded as a form of non-theistic spirituality, which is neither a reductive naturalism nor theism. I will attempt to resolve the tension between these views by identifying some common ground

Biocompatible cellulose nanocrystal-based Trojan horse enables targeted delivery of nano-Au radiosensitizers to triple negative breast cancer cells

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e. gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This “Trojan horse” approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays

Duration of adenosine-induced myocardial hyperemia - Insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging

AIMS To assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared to a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects. METHODS AND RESULTS Quantitative MBF at rest (rMBF), during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET-MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 minutes between adenosine infusion offset and rest-imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group (0.80 [IQR 0.66-1.00] vs. 0.70 [0.58-0.83] ml·min-1·g-1, p < 0.001) and, as sMBF was identical between groups (2.52 [2.20-2.96] vs. 2.50 [1.96-3.11], p = 0.347), MFR was significantly lower in the stress-rest group (3.07 [2.43-3.88] vs. 3.50 [2.63-4.10], p < 0.001). There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, p = 0.002) and between Δtstress-rest and MFR (r = 0.163, p = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest. CONCLUSIONS Intravenously applied adenosine induces a long-lasting hyperemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR

The LOFAR Tied-Array All-Sky Survey: Timing of 35 radio pulsars and an overview of the properties of the LOFAR pulsar discoveries

The LOFAR Tied-Array All-Sky Survey (LOTAAS) is the most sensitive untargeted radio pulsar survey performed at low radio frequencies (119-151 MHz) to date and has discovered 76 new radio pulsars, including the 23.5-s pulsar J0250+5854, which up until recently was the slowest spinning radio pulsar known. In this paper, we report on the timing solutions of 35 pulsars discovered by LOTAAS, which include a nulling pulsar and a mildly recycled pulsar, and thereby complete the full timing analysis of the LOTAAS pulsar discoveries. We give an overview of the findings from the full LOTAAS sample of 76 pulsars, discussing their pulse profiles, radio spectra, and timing parameters. We found that the pulse profiles of some of the pulsars show profile variations in time or frequency, and while some pulsars show signs of scattering, a large majority display no pulse broadening. The LOTAAS discoveries have on average steeper radio spectra and longer spin periods (1.4 7), as well as lower spin-down rates (3.1 7) compared to the known pulsar population. We discuss the cause of these differences and attribute them to a combination of selection effects of the LOTAAS survey as well as previous pulsar surveys, though we cannot rule out that older pulsars tend to have steeper radio spectra

Magnetic Modulation in Mechanical Alloyed Cr1.4fe0.6o3 Oxide

We have synthesized Cr1.4Fe0.6O3 compound through mechanical alloying of Cr2O3 and Fe2O3 powders and subsequent thermal annealing. The XRD spectrum, SEM picture and microanalysis of EDAX spectrum have been used to understand the structural evolution in the alloyed compound. The alloyed samples are matching to rhombohedral structure with R3C space group. The observation of a modulated magnetic order confirmed a systematic diffusion of Fe atoms into the Cr sites of lattice structure. A field induced magnetic behaviour is seen in the field dependence of magnetization data of the annealed samples. The behaviour is significantly different from the mechanical alloyed samples. The experimental results provided the indications of considering the present material as a potential candidate for opto-electronic applications.Comment: 8 figure

Design, construction, and test of the Gas Pixel Detectors for the IXPE mission

Due to be launched in late 2021, the Imaging X-Ray Polarimetry Explorer (IXPE) is a NASA Small Explorer mission designed to perform polarization measurements in the 2-8 keV band, complemented with imaging, spectroscopy and timing capabilities. At the heart of the focal plane is a set of three polarization-sensitive Gas Pixel Detectors (GPD), each based on a custom ASIC acting as a charge-collecting anode. In this paper we shall review the design, manufacturing, and test of the IXPE focal-plane detectors, with particular emphasis on the connection between the science drivers, the performance metrics and the operational aspects. We shall present a thorough characterization of the GPDs in terms of effective noise, trigger efficiency, dead time, uniformity of response, and spectral and polarimetric performance. In addition, we shall discuss in detail a number of instrumental effects that are relevant for high-level science analysis -- particularly as far as the response to unpolarized radiation and the stability in time are concerned.Comment: To be published in Astroparticle Physic