Achieving ergodicity in three-dimensional conservative chaotic systems remains a formidable challenge, severely restricting their deployment in applications such as cryptography. This research presents a novel methodology for constructing such systems by bypassing the constraints inherent in Boltzmann-Gibbs statistical mechanics. The proposed framework leverages the unique structural properties of matrix differential equations inspired by the Nosé-Hoover thermostat. To demonstrate its efficacy, we designed and systematically analyzed a prototypical system. Through comprehensive numerical simulations and experimental validation, we uncovered a diverse range of complex dynamics, encompassing strong and weak chaos as well as invariant tori. Critically, we establish that the system exhibits robust ergodicity across specific parameter domains. Its chaotic output satisfies the rigorous National Institute of Standards and Technology (NIST) test suite. Consequently, this work introduces a new blueprint for the systematic design of ergodic conservative chaotic systems, thereby creating significant opportunities for the development of next-generation information security solutions based on conservative chaos.

Anaerobic digesters exhibit nonlinear dynamics, long input-output delays, irregular sampling, and operational constraints that complicate biogas prediction and control. This study develops a delay-aware digital-twin MPC benchmarking framework in which Anaerobic Digestion Model No. 1 (ADM1) serves as a mechanistic reference plant, while established machine-learning surrogates (Random Forest, KNN, SVR, XGBoost, LSTM, and TabPFN) provide fast one-step predictions under irregular measurements. A unified workflow integrates time-stamp alignment, sliding-window reconstruction, and Bayesian hyperparameter optimization. The surrogates are evaluated on an industrial dataset and an ADM1-based simulator incorporating a 7-day actuator delay, seasonal variability, noise, and missing data. The trained models are embedded in a constrained MPC layer, where multi-day inputs are optimized using Bayesian Optimization or Particle Swarm Optimization under hard bounds and daily ramp-rate limits. Both open-loop replay and closed-loop digital-twin MPC are investigated. Results show that PSO-MPC with inexpensive surrogates achieves the largest methane gains (up to approximately 25%), whereas BO-MPC is preferable for computationally expensive surrogates due to superior sample efficiency. Closed-loop simulations demonstrate that steady-state performance is preserved through feedback correction despite surrogate mismatch. The primary contribution is a reproducible digital-twin MPC scaffold enabling systematic integration and benchmarking of surrogate-optimizer combinations. The framework provides a reusable evaluation testbed for data-driven control of slow, delay-dominated biochemical processes, with potential extension to other chemical and energy systems subject to long delays and irregular monitoring.

This paper proposes a hybrid modulation strategy to address harmonic suppression and load current imbalance in dual three-phase machines under low switching frequencies. The method combines low-frequency 5th/7th harmonic rotating coordinate PI control for targeted harmonic mitigation, and mid/high-frequency synchronous symmetric PWM modulation to optimize harmonic distribution and balance load currents. Simulations confirm significant reductions in total harmonic distortion (THD), torque ripple, and current imbalance, demonstrating an effective solution for high-power, low-harmonic motor control while providing insights for future multiphase drive system optimization.

The use of immune checkpoint inhibitors including PD-1 and PD-L1 inhibitors is recommended for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC) patients. The immunohistochemical detection of PD-L1 expression on tumor cells has emerged as the most widely utilized biomarker in clinical practice. However, the predictive value of tumor mutation burden (TMB) remains controversial. Here, we reported the result of two cohorts of an umbrella trial, to evaluate the efficacy and safety of sintilimab monotherapy in untreated NSCLC with PD-L1 expression ≥50% (PD-L1high, 14th arm) or with TMB ≥10 mut/Mb & PD-L1 expression <50% (TMBhigh, 15th arm). Patients received sintilimab monotherapy 200mg every 21 days. The primary objective was objective response rate (ORR). To determine whether sintilimab monotherapy has sufficient activity, we used Simon's minimax two-stage to calculate sample size for these two treatments cohorts. Between May 29, 2019 and January 6, 2022,831 untreated advanced NSCLC patients were screened with tumor tissue by next-generation sequencing. 63 patients were enrolled and received sintilimab monotherapy in PD-L1high arm (n = 34) or TMBhigh arm (n = 29). As the cutoff data of October 31, 2023, the median follow-up is 21.6 months. The primary endpoint was reached with a confirmed ORR of 47.1% (16/34) and 37.9% (11/29) in PD-L1high and TMBhigh arms, respectively. The median progression-free survival (PFS) was 6.9 months and 14.1 months; the median overall survival (OS) was NR and 37.8 months in PD-L1high and TMBhigh arms, respectively. Treatment-related adverse events with grade ≥3 occurred in 19% (12/63) patients, which was 14.7% (5/34) and 24.1% (7/29) patients in these two arms. The most common adverse events are rash and increased glutamic pyruvic transaminase. In this prospective trial, PD-L1 high expression is a good biomarker for PD-1 inhibitor monotherapy for untreated advanced NSCLC; high TMB also seems to be a predictive marker for PD-1 inhibitor monotherapy, that could achieve long PFS and OS.

Osimertinib represents the current standard treatment for advanced EGFR-mutated NSCLC in the first-line (1L) setting. Acquired resistance inevitably occurs. The exploration of genomic profiles in resistant patients (pts) is vital. EGFR mutant locally advanced or metastatic NSCLC pts post osimertinib 1L treatment failure were prospectively enrolled. Genomic profiles of paired tissues and plasma samples at progression were analyzed using NGS. Considering tissues as references, the sensitivity and specificity of EGFR amplification (amp), MET amp, EGFR C797S mutation and other non-sensitive EGFR mutations in plasma samples were analyzed. From Feb 2022 to Oct 2023, 86 pts were analyzed with paired tissue and plasma samples. The median age was 63 years (range, 33-84 years), and 45.3% were males. The majority had ECOG PS 0-1 (97.7%). At progression, EGFR C797S mutation (3.5%), other non-sensitive EGFR mutation (15.1%), EGFR amp (30.2%), MET amp (27.9%), other amps (16.3%), cell cycle gene alterations (25.6%), fusion (11.6%) and other mutations (20.9%) in tissue samples were detected. Two pts (2.3%) had histological transformation, one experienced SCLC transformation, the other one experienced squamous carcinoma transformation. Same genomic profile with different proportions were detected in paired plasma samples, including EGFR C797S mutation (4.7%), other non-sensitive EGFR mutation (17.4%), EGFR amp (10.5%), MET amp (8.1%), other amps (7.0%), cell cycle gene alterations (4.7%), fusion (14.0%) and other mutations (11.6%). Using tissues as references, the sensitivity of EGFR amp, MET amp, EGFR C797S mutation and other non-sensitive EGFR mutation were 34.62%, 16.67%, 66.67% and 76.92%, respectively in paired plasma samples. The specificity were 100.00%, 95.16%, 97.59% and 93.15%, respectively in paired plasma samples. Genomic profiles were complicated in EGFR mutant locally advanced or metastatic NSCLC pts post osimertinib 1L treatment failure, with the most common being EGFR amp and MET amp. Plasma genotyping is an alternative method to identify resistance profiles when tissues are not available.

This paper introduces a novel group single-criteria decision-making algorithm that addresses the challenges from personal biases. The algorithm utilizes offset centroid-driven weight adaptation to enhance the fairness and reliability of decisions, providing robust decision-making. The core steps of the new algorithm include splitting the evaluation dataset, calculating the offset centroid, introducing dynamic adjustment coefficients, constructing a comparison matrix, and calculating the weighted mean. To empirically validate the effectiveness and applicability of the proposed algorithm, we conducted a case study involving five appearance design alternatives for automotive steering wheels, and the numerical results demonstrate the algorithm’s substantial improvements on group decision-making outcomes. Remarkably, the algorithm not only facilitates the flourishing of a fair decision-making environment but also can effectively handles biased decision-making scenarios and mitigate the impact of unfairness. By utilizing this algorithm, decision-makers can alleviate individual biases and enable fairer and more reliable decision-making processes. Consequently, this algorithm introduces a novel approach for tackling complex decision problems and exhibits promising prospects for practical applications. Its versatility renders it highly valuable in diverse decision-making processes, empowering decision-makers to achieve fairness and precision in their choices.

Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its long-acting pegylated form (PEG-rhG-CSF) are the important drugs for the management of chemotherapy induced neutropenia (CIN). This study was to evaluate the efficacy and safety of telpegfilgrastim, a Y-shape branched pegylated G-CSF for the prophylaxis of CIN. This randomized, open label, positive drug controlled phase III study enrolled patients with breast cancer (BC) or with non–small cell lung cancer (NSCLC) who received 1-4 chemotherapy cycles, 21 days per cycle. According to tumor type, patients were separately randomized (1:1:1) to receive a single subcutaneous injection of 2 mg telpegfilgrastim (group 1), 33 μg/kg telpegfilgrastim (group 2), or positive drugs (control group) per cycle. Patients in control group received daily rhG-CSF（Topneuter®） 5μg/kg at first cycle, then chose to take PEG-rhG-CSF（Xinruibai®） 6 mg or the same treatment with the 1st cycle in cycle 2-4. The primary endpoint was the duration of grade 4 neutropenia in cycle 1. The full analysis set involved 397 patients (BC, n=265; NSCLC. n=132). Single dose of 2 mg or 33 μg/kg telpegfilgrastim was non-inferiority to rhG-CSF on the duration of grade 4 neutropenia in cycle 1, the least square means of the difference with control group in group 1 and group 2 were 0.097 (95% CI: -0.189, 0.383) and 0.217 (95% CI: -0.091, 0.524) days for BC, -0.143 (95% CI: -0.349, 0.064) and -0.059 (95% CI: -0.264, 0.146) for NSCLC.There was no significant difference between telpegfilgrastim treated group with control group regarding to all secondary efficacy endpoints and safety endpoint. The average exposure per cycle of telpegfilgrastim was similar to the cumulative exposure per cycle of rhG-CSF, and was 1/3 exposure dose of PEG-rhG-CSF. Single dose of 2 mg or 33 μg/kg telpegfilgrastim per cycle was as tolerable and effective as multiple daily doses of the rhG-CSF and single dose of the PEG- rhG-CSF in prophylactic therapy of CIN. Telpegfilgrastim at a fixed single dose of 2 mg may be a more convenient mode of administration.

为了激发克东满绣非遗文化的传承活力,解决满绣发展局限性的问题,更好地实施乡村振兴战略,提出一种基于TRIZ理论分析克东满绣元素的创新发展思路.以克东满绣为研究对象,提取具有代表性的元素,通过TRIZ理论的 40 条创新原理将提取的元素进行转化.通过分析克东满绣市场的产业化发展路径,将萃取出的文化符号进行产品内容和形式上的创新,开发出相关文创系列产品,取得克东满绣文化传承和资源营销上的突破,最终形成非遗资源发展方案.将TRIZ理论应用于非遗文化的发展方案研究,有助于系统分析非遗资源发展的新思路,制定出有利于克东满绣传承与发展的新途径.

Osimertinib is the standard of care for the first-line treatment of advanced NSCLC (aNSCLC) patients (pts) with epidermal growth factor receptor (EGFR) activating mutations. Limited Chinese patients’ data in real-world setting are available regarding the effectiveness of osimertinib in EGFRm aNSCLC, especially in patients harboring uncommon EGFR mutations. Patients treated with first-line osimertinib were retrospectively collected from 11 hospitals in China between March 25, 2017 and December 31, 2022. Mutations were categorized as EGFR activating mutations (19del/21L858R; cohort 1) and uncommon mutations (G719X, L861Q, S768I, 20ins, de novo T790M; cohort 2). Patient characteristics, progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), and disease control rate (DCR) were analyzed. A total of 385 patients with stage IV NSCLC were included, 308 pts in cohort 1 and 77 pts in cohort 2. The median age was 59 years, 214 (55.6%) were female, 350 (90.9%) were adenocarcinoma, and 141 (36.6%) patients had documented brain metastases (35 patients received whole-brain radiotherapy). In cohort 1, the median follow-up was 32.8 months and mPFS was 20.8 months (19del subgroup: 22.7 months; 21L858R subgroup: 14.8 months). For patients with/without documented brain metastases, mPFS was 15.6 months and 23.4 months, respectively. mTTP was 21.5 months for all patients. ORR was 75.6%, including 3 patients with CR and 230 patients with PR. DCR was 94.2%. In cohort 2, ORR was 64.9% (50 patients with SD) and DCR was 93.5%. with a median follow-up of 8.3 months, both mPFS and mTTP were 7.3 months. No new safety signals were observed.Table: 570PCohort 1 (19del, 21L858R)Cohort 2 (G719X, L861Q, S768I, 20ins, de novo T790M)n (%)308 (80%)77 (20%)CRPRSDPD3 (0.9%)230 (74.7%)57 (18.5%)18 (5.9%)0 (0%)50 (64.9%)22 (28.6%)5 (6.5%)ORR (%)75.6%64.9%DCR (%)94.2%93.5%mPFS (month)20.8m7.3mmTTP(month)21.5m7.3m Open table in a new tab The result is consistent with FLAURA study for patients with EGFR-activating mutation. Osimeritinib showed clinical activity in patients with EGFR uncommon mutations as first-line treatment.

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated, highly invasive subtype of non-small cell lung cancer (NSCLC), with extremely poor prognosis. Immunotherapy and targeted therapy have become the mainstay of management of advanced NSCLC, however, have been scarcely reported in PSC. Herein, we conducted a multi-center, single-arm, phase II study to assess the efficacy and safety of camrelizumab plus famitinib as first-line treatment in pts with locally advanced or metastatic PSC. In this study, treatment-naïve pts with histologically confirmed stage IIIB-IV PSC received camrelizumab (200 mg, i.v., q3w) plus famitinib (20 mg, orally, qd) until disease progression or intolerable toxicity. Simon's two-stage design was adopted, and 15 pts were planned to be enrolled in the first stage, with 3 or more responses observed to progress to the second stage. The primary endpoint was objective response rate (ORR) as per RECIST 1.1. Here, we reported the first-stage results. From August 4, 2021 to April 24, 2023, 15 pts were enrolled, with a median age of 64 years (range 45-72) and all being male (100%). Of the 15 pts, seven (46.7%) achieved a partial response and six (40.0%) had stable disease, with the confirmed ORR of 46.7% (95% CI 21.3-73.4) and disease control rate of 86.7% (95% CI 59.5-98.3). As of August 16, 2023, the median follow-up was 10.0 months (IQR 3.9-14.5). The median duration of response was 7.1 months (95% CI 5.0-NR), median progression-free survival was 7.8 months (95% CI 1.6-NR), and median overall survival was 18.2 months (95% CI 18.0-NR). The median number of camrelizumab cycles was 7.0 (range 1-19). Treatment-related adverse events (TRAEs) of any grade occurred in 15 pts (100.0%), with seven (46.7%) developing grade ≥3 TRAEs. The most common TRAEs were proteinuria (53.3%), hypertension, neutrophil count decreased, and platelet count decreased (46.7% each). Two pts had grade 5 AEs (unknown cause). Camrelizumab plus famitinib as first-line therapy for PSC showed promising activity and acceptable safety during the first stage of this study. Enrollment for the second stage is ongoing.