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Mismatch Repair Deficiency (dMMR)/Microsatellite Instability (MSI) is a key biomarker in colorectal cancer (CRC). Universal screening of CRC patients for MSI status is now recommended, but contributes to increased workload for pathologists and delayed therapeutic decisions. Deep learning has the potential to ease dMMR/MSI testing and accelerate oncologist decision making in clinical practice, yet no comprehensive validation of a clinically approved tool has been conducted. We developed MSIntuit, a clinically approved artificial intelligence (AI) based pre-screening tool for MSI detection from haematoxylin-eosin (H&E) stained slides. After training on samples from The Cancer Genome Atlas (TCGA), a blind validation is performed on an independent dataset of 600 consecutive CRC patients. Inter-scanner reliability is studied by digitising each slide using two different scanners. MSIntuit yields a sensitivity of 0.96–0.98, a specificity of 0.47-0.46, and an excellent inter-scanner agreement (Cohen’s κ: 0.82). By reaching high sensitivity comparable to gold standard methods while ruling out almost half of the non-MSI population, we show that MSIntuit can effectively serve as a pre-screening tool to alleviate MSI testing burden in clinical practice. Microsatellite instability is a known risk factor for colorectal cancer development and treatment response. Here, the authors utilise deep learning to develop MSIntuit, a pre-screening tool to detect MSI from H&E stained slides.

Background. Viability and left ventricular ejection fraction (LVEF) are essential measures for the assessment of myocardial infarction (MI). These 2 variables may be evaluated simultaneously by means of thallium-201 gated single photon emission computed tomography (SPECT); however, the precision and accuracy of LVEF measurements with this isotope remain controversial, particularly in cases of extended perfusion defects and poor count densities. Methods and Results. Fifty patients with a history of MI underwent a 20-minute rest and a 4-hour redistribution Tl-201 gated SPECT viability protocol, immediately followed by a technetium-99m planar equilibrium radionuclide angiography (ERNA). On gated SPECT images, various count statistics were calculated, and perfusion was automatically quantified by means of CardioMatch, which provided both the size and severity of MI defects. Rest and redistribution LVEFs were determined from gated SPECT with Germano's algorithm, whereas LVEFs were calculated from ERNA using the manufacturer's software. Mean LVEF values calculated with rest gated SPECT, redistribution gated SPECT, and planar ERNA were 30% ± 13%, 30% ± 13% and 33% ± 13%, respectively. Significant differences between repeated gated SPECT LVEFs were not shown by means of the paired t test. Correlation coefficients were high between 20-minute and 4-hour scans (r = 0.89) and between gated SPECT and ERNA (r = 0.88 and r = 0.92 at 20 minutes and 4 hours, respectively). Additionally, close agreement between gated SPECT and ERNA was shown by means of the Bland-Altman plot, despite an underestimation of 3 units. Finally, neither the technical conditions (count density, heart rate, lung uptake, etc) nor the perfusion alteration (size, severity, redistribution) appeared to interfere with the precision and accuracy of gated SPECT LVEF measurement. Conclusion. Tl-201 gated SPECT is a precise method for assessing LVEF within the same patient at 4-hour intervals, even with a substantial count decay, and it gives accurate results compared with planar ERNA, even in the case of large perfusion defects. (J Nucl Cardiol 2001;8:31-9.)

Background: Correctly classifying early estrogen receptor-positive and HER2-negative (ER+/HER2) breast cancer (EBC) cases allows to propose an adapted adjuvant systemic treatment strategy. We developed a new AI-based tool to assess the risk of distant relapse at 5 years for ER+/HER2- EBC patients from pathological slides.Patients and Methods: The discovery dataset (GrandTMA) included 1429 ER+/HER2- EBC patients, with long-term follow-up and an available hematoxylin-eosin and saffron (HES) whole slide image (WSI). A Deep Learning (DL) network was trained to predict metastasis free survival (MFS) at five years, based on the HES WSI only (termed RlapsRisk). A combined score was then built using RlapsRisk and well established prognostic factors. A threshold corresponding to a probability of MFS event of 5% at 5 years was applied to dichotomize patients into low or high-risk groups. The external validation, as well as assessment of the additional prognosis value of the DL model beyond standard clinico-pathologic factors were carried out on an independent, prospective cohort (CANTO, NCT01993498) including 889 HES WSI of ER+/HER2- EBC patients.Results:RlapsRisk was an independent prognostic factor of MFS in multivariable analysis adjusted for established clinico-pathological factors (p<0.005 in GrandTMA and CANTO). Combining RlapsRisk score and the clinico-pathological factors improved the prognostic discrimination as compared to the clinico-pathological factors alone (increment of c-index in the validation set 0.80 versus 0.76, +0.04, p-value < 0.005). After dichotomization, the Combined Model showed a higher cumulative sensitivity on the entire population (0.76 vs 0.61) for an equal dynamic specificity (0.76) in comparison with the clinical score alone.Conclusions:Our deep learning model developed on digitized HES slides provided additional prognostic information as compared to current clinico-pathological factors and has the potential of valuably informing the decision making process in the adjuvant setting when combined with current clinico-pathological factors.Competing Interest StatementSuzette Delaloge reports grants and non-financial support from Pfizer, grants from Novartis, grants and non-financial support from AstraZeneca, grants from Roche Genentech, grants from Lilly, grants from Orion, grants from Amgen, grants from Sanofi, grants from Genomic Health, grants from Servier, grants from MSD, grants from BMS, grants from Pierre Fabre, grants from Exact Sciences, grants from Besins, grants from European Commission grants, grants from French government grants, grants from Fondation ARC grants, grants from Taiho, grants from Elsan, outside the submitted work. Fabrice Andre declares institutional financial interests, research grants with Novartis, Pfizer, Astra Zeneca, Eli Lilly, Daiichi, Roche.

Magnetic skyrmions are chiral spin structures with a whirling configuration. Their topological properties, nanometre size and the fact that they can be moved by small current densities have opened a new paradigm for the manipulation of magnetization at the nanoscale. Chiral skyrmion structures have so far been experimentally demonstrated only in bulk materials and in epitaxial ultrathin films, and under an external magnetic field or at low temperature. Here, we report on the observation of stable skyrmions in sputtered ultrathin Pt/Co/MgO nanostructures at room temperature and zero external magnetic field. We use high lateral resolution X-ray magnetic circular dichroism microscopy to image their chiral Néel internal structure, which we explain as due to the large strength of the Dzyaloshinskii–Moriya interaction as revealed by spin wave spectroscopy measurements. Our results are substantiated by micromagnetic simulations and numerical models, which allow the identification of the physical mechanisms governing the size and stability of the skyrmions. Stable, single magnetic skyrmions are demonstrated at room temperature in ultrathin cobalt nanostructures.

Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study. A single 24-hour urine sample was analysed for each subject from 4 European countries. The highest median levels were observed for phenolic acids such as 4-hydroxyphenylacetic acid (157 μmol/24 h), followed by 3-hydroxyphenylacetic, ferulic, vanillic and homovanillic acids (20–50 μmol/24 h). The lowest concentrations were observed for equol, apigenin and resveratrol (<0.1 μmol/24 h). Urinary polyphenols significantly varied by centre, followed by alcohol intake, sex, educational level and energy intake. This variability is largely explained by geographical variations in the diet, as suggested by the high correlations (r > 0.5) observed between urinary polyphenols and the intake of their main food sources (e.g., resveratrol and gallic acid ethyl ester with red wine intake; caffeic, protocatechuic and ferulic acids with coffee consumption; and hesperetin and naringenin with citrus fruit intake). The large variations in urinary polyphenols observed are largely determined by food preferences. These polyphenol biomarkers should allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies.

This corrects the article DOI: 10.1038/nnano.2015.315.

Nature Nanotechnology 11, 449–454 (2016); published online 25 January 2016; corrected after print 18 July 2017 In the version of this Article originally published, the Dzyaloshinskii–Moriya interaction parameter, D, should have been multiplied by √3. The vertical scale of Fig. 2 has been updated accordingly as has the following sentence concerning D values: “For 5 monolayers (ML) of Co, equivalent to a total Co thickness of 1 nm, the ab initio calculations predict = 4.

Magnetic skyrmions are topological spin textures holding great potential as nanoscale information carriers. Recently, skyrmions have been predicted in antiferromagnets, with key advantages in terms of stability, size, and dynamical properties over their ferromagnetic analogs. However, their experimental demonstration is still lacking. Here, we show the imprint from ferromagnetic skyrmions into a thin film of an IrMn antiferromagnet, at room temperature and zero external magnetic field, using exchange-bias. Using high-spatial-resolution x-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM), we observed the imprinted spin textures within the IrMn from the XMCD signal of the uncompensated Mn spins at the interface with the ferromagnet. This result opens up a path for logic and memory devices based on skyrmion manipulation in antiferromagnets.

We present the benefits of using diffuse illumination in laser holography for ophthalmic applications. Integrating a diffusing element introduces angular diversity in the optical radiation and reduces spatial coherence, effectively distributing the illumination beam's energy across the focal plane of the eyepiece. This configuration allows for an expanded field of view in digitally computed retinal images, as the eyepiece can be positioned closer to the cornea to achieve a Maxwellian view of the retina without compromising ocular safety. By avoiding the formation of a laser hot spot near the cornea, diffuse illumination facilitates easier compliance with American and European safety standards for ophthalmic devices. Importantly, this approach does not introduce any adverse effects on digitally computed Doppler images.