Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Bistable response and quasi-periodicity excitation of the internal dynamics of soliton molecules.

Soliton molecules, a frequently observed phenomenon in most mode-locked lasers, have intriguing characteristics comparable to their matter molecule counterparts. However, there are rare explorations of the deterministic control of the underlying physics within soliton molecules. Here, we demonstrate the bistable response of intramolecular motion to external stimuli and identify a general approach to excite their quasi-periodic oscillations. By introducing frequency-swept gain modulation, the intrinsic resonance frequency of the soliton molecule is observed in the simulation model. Applying stronger modulation, the soliton molecule exhibits divergent response susceptibility to up- and down-sweeping, accompanied by a jump phenomenon. Quasi-periodic intramolecular oscillations appear at the redshifted resonance frequency. Given the leading role of bistability and quasi-periodic dynamics in nonlinear physics, our research provides insights into the complex nonlinear dynamics within dissipative soliton molecules. It may pave the way to related experimental studies on synchronization and chaos at an ultrafast time scale.

Combined Mutual Learning Net for Raman Spectral Microbial Strain Identification.

Infectious diseases pose a significant threat to global health, yet traditional microbiological identification methods suffer from drawbacks, such as high costs and long processing times. Raman spectroscopy, a label-free and noninvasive technique, provides rich chemical information and has tremendous potential in fast microbial diagnoses. Here, we propose a novel Combined Mutual Learning Net that precisely identifies microbial subspecies. It demonstrated an average identification accuracy of 87.96% in an open-access data set with thirty microbial strains, representing a 5.76% improvement. 50% of the microbial subspecies accuracies were elevated by 1% to 46%, especially for E. coli 2 improved from 31% to 77%. Furthermore, it achieved a remarkable subspecies accuracy of 92.4% in the custom-built fiber-optical tweezers Raman spectroscopy system, which collects Raman spectra at a single-cell level. This advancement demonstrates the effectiveness of this method in microbial subspecies identification, offering a promising solution for microbiology diagnosis.

On-Chip Fabrication-Tolerant Exceptional Points Based on Dual-Scatterer Engineering.

The intriguing and anomalous optical characteristics of exceptional points (EPs) in optical resonators have attracted significant attention. While EP-related phenomena have been observed by perturbing resonators with off-chip components, implementing EPs fully on-chip remains challenging due to their extreme susceptibility to fabrication errors. In this Letter, we propose a succinct and compact approach to reach EP in an on-chip integrated silicon microring resonator by manipulating the evolution of backscatterings with two nanocylinders of disparate diameters. The theoretical analysis unveils that the fabrication constraints could be significantly relieved by increasing the difference in diameters of the nanocylinders. The evolution from non-EP to EP is traced experimentally through the step-by-step tuning of the angular and radial positions of nanocylinders. The proposed method opens a pathway toward the on-chip high-density integration of non-Hermitian devices.

RSPSSL: A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization.

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology. It is also an emerging omics technique for metabolic profiling to shape precision medicine. However, precisely attributing vibration peaks coupled with specific environmental, instrumental, and specimen noise is problematic. Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction. Here, we propose a novel Raman spectral preprocessing scheme based on self-supervised learning (RSPSSL) with high capacity and spectral fidelity. It can preprocess arbitrary Raman spectra without further training at a speed of ~1 900 spectra per second without human interference. The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88% reduction in root mean square error and a 60% reduction in infinite norm ([Formula: see text]) compared to established techniques. With this advantage, it remarkably enhanced various biomedical applications with a 400% accuracy elevation (ΔAUC) in cancer diagnosis, an average 38% (few-shot) and 242% accuracy improvement in paraquat concentration prediction, and unsealed the chemical resolution of biomedical hyperspectral images, especially in the spectral fingerprint region. It precisely preprocessed various Raman spectra from different spectroscopy devices, laboratories, and diverse applications. This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput, cross-device, various analyte complexity, and diverse applications.