Summary Background Infections with certain viruses, bacteria, and parasites are strong risk factors for specific cancers. As new cancer statistics and epidemiological findings have accumulated in the ...past 5 years, we aimed to assess the causal involvement of the main carcinogenic agents in different cancer types for the year 2012. Methods We considered ten infectious agents classified as carcinogenic to human beings by the International Agency for Research on Cancer. We calculated the number of new cancer cases in 2012 attributable to infections by country, by combining cancer incidence estimates (from GLOBOCAN 2012) with estimates of attributable fraction (AF) for the infectious agents. AF estimates were calculated from the prevalence of infection in cancer cases and the relative risk for the infection (for some sites). Estimates of infection prevalence, relative risk, and corresponding 95% CIs for AF were obtained from systematic reviews and pooled analyses. Findings Of 14 million new cancer cases in 2012, 2·2 million (15·4%) were attributable to carcinogenic infections. The most important infectious agents worldwide were Helicobacter pylori (770 000 cases), human papillomavirus (640 000), hepatitis B virus (420 000), hepatitis C virus (170 000), and Epstein-Barr virus (120 000). Kaposi's sarcoma was the second largest contributor to the cancer burden in sub-Saharan Africa. The AFs for infection varied by country and development status—from less than 5% in the USA, Canada, Australia, New Zealand, and some countries in western and northern Europe to more than 50% in some countries in sub-Saharan Africa. Interpretation A large potential exists for reducing the burden of cancer caused by infections. Socioeconomic development is associated with a decrease in infection-associated cancers; however, to reduce the incidence of these cancers without delay, population-based vaccination and screen-and-treat programmes should be made accessible and available. Funding Fondation de France.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract It has been suggested that NR2B-containing N -methyl- d -aspartate (NMDA) receptors have a selective tendency to promote pro-death signaling and synaptic depression, compared with the ...survival promoting, synapse potentiating properties of NR2A-containing NMDA receptors. A preferential localization of NR2A-containing NMDA receptors at the synapse in maturing neurons could thus explain differences in synaptic vs. extrasynaptic NMDA receptor signaling. We have investigated whether NMDA receptors can mediate signaling to survival, death, and synaptic potentiation, in dissociated rat neuronal cultures at a developmental stage prior to significant NR2A expression and subunit-specific differences between synaptic and extrasynaptic NMDA receptors. We show that in developing hippocampal neurons, the progressive reduction in sensitivity of NMDA receptor currents to the NR2B antagonist ifenprodil applies to both synaptic and extrasynaptic locations. However, the reduction is less acute in extrasynaptic currents, indicating that NR2A does partition preferentially, but not exclusively, into synaptic locations at DIV>12. We then studied NMDA receptor signaling at DIV10, when both synaptic and extrasynaptic NMDA receptors are both overwhelmingly and equally NR2B-dominated. To analyze pro-survival signaling we studied the influence of synaptic NMDA receptor activity on staurosporine-induced apoptosis. Blockade of spontaneous NMDAR activity with MK-801, or ifenprodil exacerbated the apoptotic insult. Furthermore, MK-801 and ifenprodil both antagonized neuroprotection promoted by enhancing synaptic activity. Pro-death signaling induced by a toxic dose of NMDA is also blocked by NR2B-specific antagonists. Using a cell culture model of synaptic NMDA receptor-dependent synaptic potentiation, we find that this is mediated exclusively by NR2B-containing N -methyl- d -aspartate receptors, as implicated by NR2B-specific antagonists and the use of selective vs. non-selective doses of the NR2A-preferring antagonist NVP-AAM077. Therefore, within a single neuron, NR2B-NMDA receptors are able to mediate both survival and death signaling, as well as model of NMDA receptor-dependent synaptic potentiation. In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signaling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aqueous and methanolic extracts of several microalgae (Ankistrodesmus sp., Spirogyra sp., Euglena cantabrica, and Caespitella pascheri) and cyanobacteria (Nostoc sp., Nostoc commune, Nodularia ...spumigena, Leptolyngbya protospira, Phormidiochaete sp., and Arthrospira platensis) were screened for their radical scavenging activity against the stable radical 1,1-diphenyl-2-picrylhydrazyl. Despite the fact that water was a more efficient solvent to extract greater amount of extractable substances, it seems that methanol was more efficient to extract a selected group of compounds with a higher antioxidant activity. In addition, the identification of 4 simple phenolics (gallic, syringic, protocatechuic, and chlorogenic acids) and the flavonoids (+) catechin and (-) epicatechin was carried out by using reverse phase high performance liquid chromatography. The strain Euglena cantabrica showed the highest concentration of phenolic compounds, particularly gallic and protocatechuic acids (5.87 and 2.97 mg per gram of dried biomass, resp.). Aqueous and methanolic extracts of microalgae Euglena cantabrica also exhibited the highest antioxidant activity, probably due to the presence of the high contents of phenolics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Context.
Protoplanetary discs are cold, dense, and weakly ionised environments that witness planetary formation. Among these discs, transition discs (TDs) are characterised by a wide cavity (up to ...tens of au) in the dust and gas distribution. Despite this lack of material, a considerable fraction of TDs are still strongly accreting onto their central star, possibly indicating that a mechanism is driving fast accretion in TD cavities.
Aims.
The presence of radially extended ‘dead zones’ in protoplanetary discs has recently revived interest in magnetised disc winds (MDWs), where accretion is driven by a large magnetic field extracting angular momentum from the disc. We propose that TDs could be subject to similar disc winds, and that these could naturally explain the fast-accreting and long-lived cavities inferred in TDs.
Methods.
We present the results of the first 2.5D global numerical simulations of TDs harbouring MDWs using the PLUTO code. We imposed a cavity in the gas distribution with various density contrasts, and considered a power-law distribution for the large-scale magnetic field strength. We assume the disc is weakly ionised and is therefore subject to ambipolar diffusion, as expected in this range of densities and temperatures.
Results.
We find that our simulated TDs always reach a steady state with an inner cavity and an outer ‘standard’ disc. These models also maintain an approximately constant accretion rate through the entire structure, reaching 10
−7
M
⊚
yr
−1
for typical surface density values. The MDW launched from the cavity is more magnetised and has a significantly larger lever arm (up to 10) than the MDW launched from the outer disc. The material in the cavity is accreted at sonic velocities, and the cavity itself is rotating at 70% of the Keplerian velocity due to the efficient magnetic braking imposed by the MDW. Overall, our cavity matches the dynamical properties of an inner jet emitting disc (JED) and of magnetically arrested discs (MADs) in black-hole physics. Finally, we observe that the cavity is subject to recurring accretion bursts that may be driven by a magnetic Rayleigh-Taylor instability of the cavity edge.
Conclusions.
Some strongly accreting TDs could be the result of magnetised wind sculpting protoplanetary discs. Kinematic diagnostics of the disc or the wind (orbital velocity, wind speeds, accretion velocities) could disentangle classic photo-evaporation from MDW models.
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FMFMET, NUK, UL, UM, UPUK
HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV‐attributable cancer burden ...can boost programs of HPV vaccination and HPV‐based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age‐standardized incidence rates of HPV‐attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from <3% in Australia/New Zealand and the USA to >20% in India and sub‐Saharan Africa. Cervix accounts for 83% of HPV‐attributable cancer, two‐thirds of which occur in less developed countries. Other HPV‐attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV‐attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV‐attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross‐protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.
What's new?
Most cervical cancers result from human papillomavirus (HPV) infection and therefore are preventable through screening and vaccination. Nonetheless, efforts toward HPV‐attributable cancer prevention frequently are undermined by limited access to necessary resources. The present study estimates that worldwide as many as 4.5% of new cancer cases, including cancers of the cervix, anogenital tract and head and neck, are associated with HPV infection. Cervical cancer alone accounts for 83% of those cases, most of which affect women in less‐developed countries. The findings emphasize the importance of HPV screening and vaccination and the need for less‐costly vaccines.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of ...glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation. Herein we review the compounds, both of natural and synthetic origin, found to interfere with uptake of glucose by breast cancer cells, and the consequences of interference with that mechanism on breast cancer cell biology. We will also present data where the interaction with GLUT is exploited in order to increase the efficiency or selectivity of anticancer agents, in breast cancer cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Microorganisms and specifically motile bacteria have been recently added to the list of micro-actuators typically considered for the implementation of microsystems and microrobots. Such trend has ...been motivated by the fact these microorganisms are self-powered actuators with overall sizes at the lower end of the micrometer range and which have proven to be extremely effective in low Reynolds number hydrodynamic regime of usually less than 10
−2
. Furthermore, the various sensors or taxes in bacteria influencing their movements can also be exploited to perform tasks that were previously considered only for futuristic artificial microrobots. Bacterial implementations and related issues are not only reviewed, but this paper also proposes many techniques and approaches that can be considered as building blocks for the implementations of more sophisticated microsystems and microrobots.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Contagious statistical distributions are a valuable resource for managing contagion by means of k-connected chains of distributions. Binomial, hypergeometric, Pólya, uniform distributions with the ...same values for all parameters except sample size n are known to be strongly associated. This paper describes how the relationship can be obtained via factorial moments, simplifying the process by including novel elements. We describe the properties of these distributions and provide examples of their real-world application, and then define a chain of k-connected distributions, which generalises the relationship among samples of any size for a given population and the Pólya urn model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The decoupled effects of Reynolds and Dean numbers are examined in inertial focusing flows. In doing so, a complex set of inertial focusing behavioral regimes is discovered within curved microfluidic ...channels over a range of channel Reynolds numbers, curvature ratios and particle confinement ratios. These regimes are characterized by particle migration either towards or away from the center of curvature as the channel Reynolds number is increased. The transition between these two regimes is shown to be a set of conditions where single-point equilibrium position focusing of particles of different sizes is achieved. A mechanism describing the observed motion of particles in such flows is hypothesized incorporating the redistribution of the main flow velocities caused by Dean flow and its effect on the balance forces on suspended particles.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Highlights•We present the first comprehensive review and comparison of the existing plug-and-play segmentation loss functions in an organized manner.•We conduct the largest experiments for 20 loss ...functions on four segmentation tasks with six public datasets from 10+ medical centers, and highlight the most robust loss functions.•The code is publicly available at https://github.com/JunMa11/SegLoss.
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The loss function is an important component in deep learning-based segmentation methods. Over the past five years, many loss functions have been proposed for various segmentation tasks. However, a systematic study of the utility of these loss functions is missing. In this paper, we present a comprehensive review of segmentation loss functions in an organized manner. We also conduct the first large-scale analysis of 20 general loss functions on four typical 3D segmentation tasks involving six public datasets from 10+ medical centers. The results show that none of the losses can consistently achieve the best performance on the four segmentation tasks, but compound loss functions (e.g. Dice with TopK loss, focal loss, Hausdorff distance loss, and boundary loss) are the most robust losses. Our code and segmentation results are publicly available and can serve as a loss function benchmark. We hope this work will also provide insights on new loss function development for the community.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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