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Clinical Oral Investigations - To determine the usefulness of Serum C-terminal telopeptide cross-link of type 1 collagen (sCTX) as a preoperative marker for predicting the risk of developing...  相似文献   
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Clinical Oral Investigations - By means of a systematic review and network meta-analysis, this study aims to answer the following questions: (a) does the placement of a biomaterial over an...  相似文献   
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Cosmological simulations of galaxy formation are limited by finite computational resources. We draw from the ongoing rapid advances in artificial intelligence (AI; specifically deep learning) to address this problem. Neural networks have been developed to learn from high-resolution (HR) image data and then make accurate superresolution (SR) versions of different low-resolution (LR) images. We apply such techniques to LR cosmological N-body simulations, generating SR versions. Specifically, we are able to enhance the simulation resolution by generating 512 times more particles and predicting their displacements from the initial positions. Therefore, our results can be viewed as simulation realizations themselves, rather than projections, e.g., to their density fields. Furthermore, the generation process is stochastic, enabling us to sample the small-scale modes conditioning on the large-scale environment. Our model learns from only 16 pairs of small-volume LR-HR simulations and is then able to generate SR simulations that successfully reproduce the HR matter power spectrum to percent level up to 16h1Mpc and the HR halo mass function to within 10% down to 1011M. We successfully deploy the model in a box 1,000 times larger than the training simulation box, showing that high-resolution mock surveys can be generated rapidly. We conclude that AI assistance has the potential to revolutionize modeling of small-scale galaxy-formation physics in large cosmological volumes.

As telescopes and satellites become more powerful, observational data on galaxies, quasars, and the matter in intergalactic space becomes more detailed and covers a greater range of epochs and environments in the Universe. Our cosmological simulations (see, e.g., ref. 1) must also become more detailed and more wide-ranging in order to make predictions and test the effects of different physical processes and different dark-matter candidates. Even with supercomputers, we are forced to decide whether to maximize either resolution or volume, or else compromise on both. These limitations can be overcome through the development of methods that leverage techniques from the artificial intelligence (AI) revolution (see, e.g., ref. 2) and make superresolution (SR) simulations possible. In the present work, we begin to explore this possibility, combining knowledge and existing superscalable codes for petascale-plus cosmological simulations (3) with machine learning (ML) techniques to effectively create representative volumes of the Universe that incorporate information from higher-resolution models of galaxy formation. Our first attempts, presented here, involve simulations with dark matter and gravity only, and extensions to full hydrodynamics will follow. This hybrid approach, which will imply offloading simulations to neural networks (NNs) and other ML algorithms, has the promise to enable the prediction of quasar, supermassive black hole, and galaxy properties in a way that is statistically identical to full hydrodynamic models, but with a significant speed-up.Adding details to images below the resolution scale (SR image enhancement) has become possible with the latest advances in deep learning (DL; ML with NN; ref. 4), including generative adversarial networks (GANs; ref. 5). The technique has applications in many fields, from microscopy to law enforcement (6). It has been used for observational astronomical images by (7), to recover galaxy features from below the resolution scale in degraded Hubble Space Telescope images. Besides SR image enhancement, DL has started to find applications in cosmological simulations. For example, refs. 8 and 9 showed how NNs can predict the nonlinear formation of structures given simple linear theory predictions. NN models have also been trained to predict galaxies (10, 11) and 21-cm emission from neutral hydrogen (12) from simulations that only contain dark matter. GANs have been used in ref. 13 to generate image slices of cosmological models and to generate dark-matter halos from density fields (14). ML techniques other than DL find many applications, too. For example, Kamdar et al. (15) have applied extremely randomized trees to dark-matter simulations to predict hydrodynamic galaxy properties.Generating mocks for future sky surveys requires large volumes and high accuracy, a task that quickly becomes computationally prohibitive. To alleviate the cost, recently, Dai and Seljak (16) developed a Lagrangian-based parametric ML model to predict various hydrodynamical outputs from the dark-matter density field. In other work, Dai et al. (17, 18) sharpened the particle distribution using a potential gradient descent method starting from low-resolution (LR) simulations. Note, however, that these approaches did not aim to enhance the spatial or mass resolution of a simulation.On the DL side, recently, Ramanah et al. (19) explored using the SR technique to map density fields of LR cosmological simulations to that of the high-resolution (HR) ones. While the goal is similar, our work has the following three key differences. First, instead of focusing on the dark-matter density field, we aim to enhance the number of particles and predict their displacements, from which the density fields can be inferred. This approach allows us to preserve the particle nature of the N-body simulations and therefore to interpret the SR outputs as simulations themselves. Second, we test our technique at a higher SR ratio. Compared to ref. 19, which increased the number of Eulerian voxels by 8 times, we increase the number of particles and thus the mass resolution by a factor of 512. Finally, to facilitate future applications of SR on hydrodynamic simulations in representative volumes, we test our method at much smaller scales and in large simulations whose volume is much bigger than that of the training data.  相似文献   
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Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.  相似文献   
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Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.

Patients and Methods

This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.

Results

From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.

Conclusion

The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response.  相似文献   
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