BackgroundWe attempted to train and validate a model of deep learning for the preoperative prediction of the response of patients with intermediate-stage hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE).MethodAll computed tomography (CT) images were acquired for 562 patients from the Nan Fang Hospital (NFH), 89 patients from Zhu Hai Hospital Affiliated with Jinan University (ZHHAJU), and 138 patients from the Sun Yat-sen University Cancer Center (SYUCC). We built a predictive model from the outputs using the transfer learning techniques of a residual convolutional neural network (ResNet50). The prediction accuracy for each patch was revaluated in two independent validation cohorts.ResultsIn the training set (NFH), the deep learning model had an accuracy of 84.3% and areas under curves (AUCs) of 0.97, 0.96, 0.95, and 0.96 for complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively. In the other two validation sets (ZHHAJU and SYUCC), the deep learning model had accuracies of 85.1% and 82.8% for CR, PR, SD, and PD. The ResNet50 model also had high AUCs for predicting the objective response of TACE therapy in patches and patients of three cohorts. Decision curve analysis (DCA) showed that the ResNet50 model had a high net benefit in the two validation cohorts.ConclusionThe deep learning model presented a good performance for predicting the response of TACE therapy and could help clinicians in better screening patients with HCC who can benefit from the interventional treatment.Key Points• Therapy response of TACE can be predicted by a deep learning model based on CT images. • The probability value from a trained or validation deep learning model showed significant correlation with different therapy responses. • Further improvement is necessary before clinical utilization. Electronic supplementary materialThe online version of this article (10.1007/s00330-019-06318-1) contains supplementary material, which is available to authorized users.

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We demonstrate a high-performance pulsed optically pumped (POP) Rb vapor-cell clock based on a magnetron-type microwave cavity of only 44 cm 3 external volume. Using optical detection, an unprecedented 35% contrast of the Ramsey signal has been obtained. Both the signal-to-noise ratio (of 30 000) and the estimated shot-noise limit of 1.7 Â 10 À14 s À1/2 are at the same level as those found with a bigger cylindrical TE 011 cavity (100 cm 3 inner volume) and are sufficient for achieving excellent clock stability. Rabi oscillations are measured and indicate a sufficiently uniform microwave magnetic field distribution inside the cavity. The instability sources for the POP clock's performance are analyzed. A short-term stability of 2.1 Â 10 À13 s À1/2 is demonstrated which is consistent with the noise budget.

Lasers with high spectral purity can enable a diverse application space, including precision spectroscopy, coherent high‐speed communications, physical sensing, and manipulation of quantum systems. Already, meticulous design and construction of bench Fabry–Perot cavities has made possible dramatic achievements in active laser‐linewidth reduction, predominantly for optical‐atomic clocks. Yet, there is increasing demand for miniaturized laser systems operating with high performance in ambient environments. Here, a compact and robust photonic‐atomic laser comprising a 2.5 centimeter long, 20 000 finesse, monolithic Fabry–Perot cavity integrated with a micromachined rubidium vapor cell is presented. By leveraging the short‐time frequency stability of the cavity and the long‐time frequency stability of atoms, an ultranarrow‐linewidth laser that enables integration for extended measurements is realized. Specifically, the laser supports a fractional‐frequency stability of 1×10−13 at an averaging time of 20 millisecond, 7×10−13 at 300 second, an integrated linewidth of 25 Hz that results from thermal noise, frequency noise floor as low as 0.06 Hz2 Hz−1, and a passive vibration immunity as low as 10−10 g−1. The present work explores hybrid laser systems with monolithic photonic and atomic packages based on physical design.

BackgroundGenetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy.MethodsIn this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study. Tumor samples from the patients were molecularly profiled by MSK-IMPACT or whole exome sequencing. We developed a risk model named GMS based on the MSK training cohort (n=123). The predictive model was first validated in the separate internal MSK cohort (n=82) and then validated in an external cohort containing 111 patients from previously published clinical trials.ResultsA GMS risk model consisting of eight genes (TP53, KRAS, STK11, EGFR, PTPRD, KMT2C, SMAD4, and HGF) was generated to classify patients into high and low GMS groups in the training cohort. Patients with high GMS in the training cohort had longer progression-free survival (hazard ratio (HR) 0.41, 0.28–0.61, p<0.0001) and overall survival (HR 0.53, 0.32–0.89, p=0.0275) compared with low GMS. We noted equivalent findings in the internal validation cohort and in the external validation cohort. The GMS was demonstrated as an independent predictive factor for anti-PD-(L)1 therapy comparing with tumor mutational burden. Meanwhile, GMS showed undifferentiated predictive value in patients with different clinicopathological features. Notably, both GMS and PD-L1 were independent predictors and demonstrated poorly correlated; inclusion of PD-L1 with GMS further improved the predictive capacity for PD-1 blockade immunotherapy.ConclusionsOur study highlights the potential predictive value of GMS for immunotherapeutic benefit in non-squamous NSCLC. Besides, the combination of GMS and PD-L1 may serve as an optimal partner in guiding treatment decisions for anti-PD-(L)1 based therapy.

BackgroundFather–child interactions are associated with improved developmental outcomes among infants. However, to the best of our knowledge, no study has addressed the effects of paternal involvement on the neurodevelopment of infants who are less than 6 months of age, and no study has reported how maternal parenting stress mediates the relationship between paternal involvement and infant neurodevelopment during early infancy. This study investigates the direct and indirect relationship between paternal involvement and infant neurodevelopment at 3–4 months of age. The indirect relationship was assessed through the mediating factor of maternal parenting stress.MethodsThe participants were recruited through the Sesalmaul Research Center’s website from April to June 2014. The final data included 255 mothers and their healthy infants, who were aged 3–4 months. The mothers reported paternal involvement and maternal parenting stress by using Korean Parenting Alliance Inventory (K-PAI) and Parenting Stress Index (PSI), respectively. Experts visited the participants’ homes to observe infant neurodevelopment, and completed a developmental examination using Korean version of the Ages and Stages Questionnaire II (K-ASQ II). A hierarchical multiple regression analysis was used for data analysis.ResultsInfants’ mean ages were 106 days and girls accounted for 46.3%. The mean total scores (reference range) of the K-PAI, PSI, and the K-ASQ II were 55.5 (17–68), 45.8 (25–100), and 243.2 (0–300), respectively. Paternal involvement had a positive relationship with K-ASQ II scores (β = 0.29, p < 0.001) at 3–4 months of age, whereas maternal parenting stress was negatively related with K-ASQ II scores (β = −0.32, p < 0.001). Maternal parenting stress mediated the relationship between paternal involvement and early infant neurodevelopment (Z = 3.24, p < 0.001). A hierarchical multiple regression analysis showed that paternal involvement reduced maternal parenting stress (β = −0.25, p < 0.001), which led to positive infant outcomes (β = 0.23, p < 0.001).ConclusionsPaternal involvement is significantly associated with infant neurodevelopment during early infancy, and maternal parenting stress partially mediates that association. This result emphasizes the importance of fathers’ involvement and mothers’ parenting stress on early infant neurodevelopment.

Corresponding authors: liron.stern@nist.gov and scott.papp@nist.govMicroresonator-based soliton frequency combsmicrocombs -have recently emerged to offer low-noise, photonic-chip sources for optical measurements. Owing to nonlinear-optical physics, microcombs can be built with various materials 1 and tuned or stabilized with a consistent framework 2 . Some applications require phase stabilization 3 , including optical-frequency synthesis 4 and measurements 5 , optical-frequency division 6 , and optical clocks 7,8 . Partially stabilized microcombs can also benefit applications, such as oscillators 9 , ranging 10 , dual-comb spectroscopy 11,12 , wavelength calibration 13,14 , and optical communications 15 . Broad optical bandwidth, brightness, coherence, and frequency stability have made frequencycomb sources important for studying comb-matter interactions with atoms and molecules 16,17 . Here, we explore direct microcomb atomic spectroscopy, utilizing a cascaded, two-photon 1529-nm atomic transition of rubidium. Both the microcomb and the atomic vapor are implemented with planar fabrication techniques to support integration. By fine and simultaneous control of the repetition rate and carrier-envelope-offset frequency of the soliton microcomb, we obtain direct sub-Doppler and hyperfine spectroscopy of the 4 2 D5/2 manifold. Moreover, the entire set of microcomb modes are stabilized to this atomic transition, yielding absolute optical-frequency fluctuations of the microcomb at the kilohertz-level over a few seconds and <1 MHz day-to-day accuracy. Our work demonstrates atomic spectroscopy with microcombs and provides a rubidium-stabilized microcomb laser source, operating across the 1550 nm band for sensing, dimensional metrology, and communication.

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