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This study aims to investigate the impact of vagus nerve stimulation (VNS) on the connectivity and small-world metrics of brain functional networks during seizure periods.

This study aimed to determine the safety and effectiveness of DTI-assisted neuroendoscopy for treating intracranial hemorrhage (ICH).

ObjectivesThis two-part study evaluated trametinib, a MEK1/2 inhibitor, in combination with anticancer agents. Inhibition of MEK, a downstream effector of KRAS, demonstrated preclinical synergy with chemotherapy in KRAS-mutant NSCLC cell lines. Part 1 of this study identified recommended phase 2 doses of trametinib combinations. Part 2, reported herein, evaluated the safety, tolerability, pharmacokinetics, and efficacy of trametinib combinations in patients with NSCLC with and without KRAS mutations.MethodsPhase 1b evaluated trametinib plus docetaxel with growth factor support (trametinib, 2.0 mg once daily, and docetaxel, 75 mg/m2 every 3 weeks) or pemetrexed (trametinib, 1.5 mg once daily, and pemetrexed, 500 mg/m2 every 3 weeks). Eligibility criteria for the expansion cohorts included metastatic NSCLC with measurable disease, known KRAS mutation status, Eastern Cooperative Oncology Group performance status of 1 or lower, and no more than two prior regimens.ResultsThe primary end point of overall response rate (ORR) was met for both combinations. A confirmed partial response (PR) was observed in 10 of the 47 patients with NSCLC who received trametinib plus docetaxel (21%). The ORR was 18% (four PRs in 22 patients) in those with KRAS wild-type NSCLC versus 24% (six PRs in 25 patients) in those with KRAS-mutant NSCLC. Of the 42 patients with NSCLC treated with trametinib plus pemetrexed, six (14%) had a PR; the ORR was 17% (four of 23) in patients with KRAS-mutated NSCLC versus 11% (two of 19) in KRAS wild-type NSCLC. Adverse events-most commonly diarrhea, nausea, and fatigue-were manageable.ConclusionsTrametinib-plus-chemotherapy combinations were tolerable. Clinical activity exceeding the ORRs previously reported with docetaxel or pemetrexed alone in KRAS-mutated NSCLC and meeting prespecified criteria was observed.

The paper focuses on a variant of hub location routeing problem arising in the design of intra-city express service networks, named as capacitated single allocation hub location routeing problem, in which each non-hub node should be served by exactly one hub, and both hub capacity and vehicle capacity are considered. A new mixed-integer programming formulation for the problem is provided, and a solution algorithm is developed on the basis of the column generation scheme to exactly solve the problem for the first time. The pricing subproblem is solved by a bidirectional labelling algorithm, and the master problem is strengthened by valid inequalities. Numerical experiments are conducted on the instances generated from the Australian Post dataset to test the performance of the model and the developed algorithm. Computational results prove that the algorithm outperforms the CPLEX and is able to provide optimal solutions for instances with up to 35 non-hub nodes and high-quality solutions for instances with 40 non-hub nodes within reasonable computational time, which indicates the feasibility and efficiency of the model and algorithm proposed. [ABSTRACT FROM AUTHOR]

Objective: Sodium phenylbutyrate and taurursodiol (PB and TURSO) was evaluated in amyotrophic lateral sclerosis (ALS) in the CENTAUR trial encompassing randomized placebo‐controlled and open‐label extension phases. On intent‐to‐treat (ITT) survival analysis, median overall survival (OS) was 4.8 months longer and risk of death 36% lower in those originally randomized to an initial 6‐month double‐blind period of PB and TURSO versus placebo. To estimate PB and TURSO treatment effect without placebo‐to‐active crossover, we performed a post hoc survival analysis comparing PB and TURSO‐randomized participants from CENTAUR and a propensity score–matched, PB and TURSO‐naïve external control cohort from the Pooled Resource Open‐Access ALS Clinical Trials (PRO‐ACT) database. Methods: Clinical trial control participants from the PRO‐ACT database who met prespecified eligibility criteria were propensity score matched 1:1 with PB and TURSO‐randomized CENTAUR participants using prognostically significant covariates in ALS. Results: Baseline characteristics including propensity score–matched covariates were generally well balanced between CENTAUR PB and TURSO (n = 89) and PRO‐ACT external control (n = 85) groups. Estimated median (IQR) OS was 23.54 (14.56–39.32) months in the CENTAUR PB and TURSO group and 13.15 (9.83–19.20) months in the PRO‐ACT external control group; hazard of death was 52% lower in the former group (hazard ratio, 0.48; 95% CI, 0.31–0.72; p = 0.00048). Interpretation: This analysis suggests potentially greater survival benefit with PB and TURSO in ALS without placebo‐to‐active crossover than seen on ITT analysis in CENTAUR. Analyses using well‐matched external controls may provide additional context for evaluating survival effects in future ALS trials. [ABSTRACT FROM AUTHOR]

Recently, advanced in-vehicle technologies have led to the emergence of connected and automated vehicles (CAVs). CAVs are supposed to improve traffic efficiency and safety by coordinating the vehicles based on the communication among vehicles. This study addresses the trajectory optimization of CAVs in the drop-off area of the departure curbside, which consists of many conflict points. We first propose a centralized control method to optimize the trajectories of CAVs and then propose an implementation procedure to deal with the dynamic features and reduce the problem scales for practical instances. Contrast experiments are conducted to test the performance of the proposed control method. Results under various scenarios (different volumes, safety gaps, and desired speeds) demonstrate that CAVs controlled by the proposed method significantly outperform human-driven vehicles without control concerning mean travel time in the drop-off area. [ABSTRACT FROM AUTHOR]