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Aiming at the problem that small and irregular detection targets such as cyclists have low detection accuracy and inaccurate recognition by existing 3D target detection algorithms, MAT-PointPillars (Multi-scale Attention and Transformer PointPillars), a 3D object detection algorithm, extends PointPillars with multi-scale vision Transformers and attention mechanisms. First, the algorithm employs pillar coding for semantic point cloud encoding and introduces an attention mechanism to refine the backbone’s upsampling process. Furthermore, the Transformer Encoder is introduced to improve the upsampling structure of the third stage of the backbone. On the KITTI dataset, our algorithm achieved 3D average detection accuracy (AP3D) of 81.15%, 62.02%, and 58.68% across three difficulty levels. Compared with the baseline model, the proposed algorithm improves AP3D by 2.44%, 1.19%, and 1.23% respectively. The real-time 3D object detection system is built based on ROS, and average running frames per second of the system is 22.63, which is higher than the sampling frequency of conventional LiDAR. By ensuring sufficient detection speed, the MAT-PointPillars algorithm can increase detection accuracy of cyclists in real-world scenarios.

Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs. SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing. Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1–16·7) in the surufatinib group and 16·6 months (9·2–not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4–11·1) in the surufatinib group versus 3·8 months (3·7–5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22–0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure). Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population. Hutchison MediPharma.

Ischemic stroke is a neurological disorder caused by vascular stenosis or occlusion, accounting for approximately 87% of strokes. Clinically, the most effective therapy for ischemic stroke is vascular recanalization, which aims to rescue neurons undergoing ischemic insults. Although reperfusion therapy is the most effective treatment for ischemic stroke, it still has limited benefits for many patients, and ischemia-reperfusion (I/R) injury is a widely recognized cause of poor prognosis. Here, we aim to investigate the mechanism of protein phosphatase Mg 2+ /Mn 2+ dependent 1 K (PPM1K) mediates metabolic disorder of branched-chain amino acids (BCAA) by promoting fatty acid oxidation led to ferroptosis after cerebral I/R injury. We established the I/R model in mice and used BT2, a highly specific BCAA dehydrogenase (BCKD) kinase inhibitor to promote BCAA metabolism. It was further verified by lentivirus knocking down PPM1K in neurons. We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKD E1α subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. We next demonstrated that BCAA could induce oxidative stress, lipid peroxidation, and ferroptosis in primary cultured cortical neurons in vitro. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown. Furthermore, BT2 was found to alleviate neurological behavior disorders after I/R injury in mice, and the effect was similar to ferroptosis inhibitor ferrostatin-1. Our findings reveal a novel role of BCAA in neuronal ferroptosis after cerebral ischemia and provide a new potential target for the treatment of ischemic stroke.

Connected and automated vehicles (CAVs) represent a significant development in the transport industry owing to their intelligent and interconnected features. Potential field theory has been extensively used to model CAV driving behaviour owing to its objectivity, universality, and measurability. However, existing car-following models do not consider the impact of time delays and the influence of information from multiple vehicles ahead and behind. This paper focuses on the driving-safety risks associated with CAVs, aiming to enhance vehicle safety and reliability during travelling. We developed a multi-vehicle car-following model based on safety potential fields (MIDM-SPF), taking into account the characteristics of multi-vehicle connected information and time delays. To enhance the model’s precision, real-world data from urban roads were employed, alongside an improved optimisation algorithm to fine-tune the car-following model. The simulation experiment revealed that MIDM-SPF significantly reduces stop-and-go traffic, thereby improving traffic flow stability in urban areas. Additionally, we validated the stability of our model under varying market penetration rates in large-scale mixed traffic. Our findings indicate that increasing the CAV proportion improves the stability of mixed traffic flows, which has important implications for alleviating traffic congestion and guiding the large-scale implementation of autonomous driving in the future.

Background Combining the programmed death-1 inhibitor toripalimab and the angio-immuno kinase inhibitor surufatinib showed preliminary antitumor activity in patients with advanced solid tumors in a phase I study. Here, we report the efficacy and safety of this combination regimen in treatment-naive advanced or metastatic non-small-cell lung cancer (NSCLC) patients with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or greater (PD-L1-positive) and patients with previously treated small-cell lung cancer (SCLC). Methods This open-label, single-arm phase II study included patients with treatment-naive advanced or metastatic PD-L1-positive NSCLC or previously treated SCLC in China. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Results Forty-three patients were treated (NSCLC cohort, n  = 23; SCLC cohort, n  = 20). ORRs (95% CIs) were 57.1% (34.0–78.2) in the NSCLC cohort and 15.8% (3.4–39.6) in the SCLC cohort. Median duration of response was not reached (NR) in both cohorts. Median PFS was 9.6 (5.5–NR) and 3.0 months (2.8–4.1), respectively, and median OS was 24.3 (10.8–NR) and 11.0 months (5.0–15.7), respectively. Grade ≥ 3 treatment-related adverse events were reported in 24 patients (55.8%) overall. Conclusion Surufatinib plus toripalimab showed encouraging antitumor activity and a tolerable safety profile in patients with treatment-naive advanced or metastatic PD-L1-positive NSCLC and previously treated SCLC.

As one of the early manifestations of road pavement structure degradation, road cracks will accelerate the deterioration of the road if not detected and repaired in time. Aiming at the problems of low recall and incomplete crack detection in current road detection, based on the U-Net network, this paper proposed an Attention-Dynamic Snake Convolution U-Net (ADSC-U-Net) network. Firstly, the dynamic snake-shaped convolution was added to the normal downsampling process to make the network adaptively focus on the slender and curved local features, which can solve the problem of low accuracy of small crack detection. Secondly, the attention mechanism was used to pay better attention to the significant features of positive samples under the condition of a large proportion gap between positive and negative samples, which solved the problem of the poor crack integrity detection effect. Finally, the dataset was expanded by random vertical and horizontal flip operations, which solved the problem of network training overfitting caused by the small-scale datasets. The experimental results showed that, when the input image had a resolution of 480 × 320, evaluation indices P, R, and F1 of ADSC-U-Net on the self-built dataset were 74.44%, 68.77%, and 69.42%, respectively. Compared to SegNet, DeepLab, and DeepCrack, the P was improved by 1.90%, 2.49%, and 11.64%, respectively; the R was improved by 8.01%, 4.70%, and 59.58%, respectively; and the comprehensive evaluation index F1 was improved by 5.73%, 4.02%, and 55.87%, respectively, which proves the effectiveness of the proposed method.

This report presents the primary analysis of the endometrial cancer (EMC) cohort of FRUSICA-1 (ClinicalTrials.gov identifier, NCT03903705), a multicenter, single-arm, phase Ib/II study evaluating fruquintinib plus sintilimab. The cohort included Chinese patients with inoperable or advanced mismatch-repair proficient (pMMR) EMC who had progressed on or could not tolerate up to two prior platinum-based therapies, and comprised exploratory and pivotal phases. Patients received fruquintinib (5 mg orally once daily on a 2 weeks on/1 week off schedule) plus sintilimab (200 mg intravenously once every 3 weeks). The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Secondary endpoints included ORR as assessed by the investigator, disease control rate, time to response, duration of response, progression-free survival (PFS) and tumor shrinkage as assessed by both the IRC and investigator, overall survival, and safety. By May 15, 2024, 98 patients with pMMR EMC were enrolled and treated. IRC-assessed ORR was 32.7% (95% confidence interval [CI] 23.5–42.9) for the total pMMR population ( n  = 98) and 31.6% (95% CI 21.4–43.3) for the pivotal population ( n  = 76). Median PFS was 8.6 months (95% CI 5.5–16.6) for the total population and 7.1 months (95% CI 5.4–16.6) for the pivotal population. The most common grade ≥3 treatment-related adverse event was hypertension (17.3%). In conclusion, fruquintinib plus sintilimab showed promising efficacy and tolerable safety in previously treated, advanced pMMR EMC. There is an unmet medical need for endometrial cancer patients with mismatch-repair proficient disease. Here, the authors report the primary analysis of the FRUSICA-1 phase Ib/II trial evaluating fruquintinib plus sintilimab in this population, showing an ORR of 32.7%, a median PFS of 8.6 months, and manageable toxicity.

Electric freight vehicles have become an important means of transportation in connected and automated environments owing to their numerous advantages. However, the generally short driving range of connected and automated electric freight vehicles (CAEFVs) does not satisfy the growing transport demand. In this study, wireless charging technology is employed to construct a complex driving scenario including urban roads and dynamic wireless charging facilities. A combination of variable-scale elements consisting of vehicles, roads, and the environment is analysed hierarchically to develop a wireless charging scheme for urban transport systems. Using passage efficiency, energy consumption, and passenger comfort as the joint optimisation objectives, an optimal driving model for CAEFVs in wireless charging scenarios at signalised intersections combining scenario boundaries and vehicle dynamic constraints is proposed. Considering the differentiated charging needs of vehicles, this model is divided into a time priority strategy (TPS), balance priority strategy (BPS), and charging priority strategy (CPS). The obtained results reveal that the CPS is superior to the TPS in terms of the charging benefits but requires a longer travel time. Meanwhile, the BPS increases the charging benefits and passing efficiency. This study provides guidance for the deployment of wireless charging lanes with a high application value.

Depression is a debilitating psychiatric disorder and a growing global public health issue. However, the relationships between microbial infections and depression remains uncertain. A computerized literature search of Medline, ISI Web of Knowledge, PsycINFO and the Cochrane Library was conducted up to May 2013 and 6362 studies were initially identified for screening. Case-control studies detected biomarker of microorganism were included. Based on inclusion and exclusion criteria, 28 studies were finally included to compare the detection of 16 infectious agents in unipolar depressed patients and healthy controls with a positive incident being defined as a positive biochemical marker of microbial infection. A customized form was used for data extraction. Pooled analysis revealed that the majority of the 16 infectious agents were not significantly associated with depression. However, there were statistically significant associations between depression and infection with Borna disease virus, herpes simplex virus-1, varicella zoster virus, Epstein-Barr virus and Chlamydophila trachomatis .

The enormous depth complexity of the human plasma proteome poses a significant challenge for current mass spectrometry-based proteomic technologies in terms of detecting low-level proteins in plasma, which is essential for successful biomarker discovery efforts. Typically, a single-step analytical approach cannot reduce this intrinsic complexity. Current simplex immunodepletion techniques offer limited capacity for detecting low-abundance proteins, and integrated strategies are thus desirable. In this respect, we developed an improved strategy for analyzing the human plasma proteome by integrating polyethylene glycol (PEG) fractionation with immunoaffinity depletion. PEG fractionation of plasma proteins is simple, rapid, efficient, and compatible with a downstream immunodepletion step. Compared with immunodepletion alone, our integrated strategy substantially improved the proteome coverage afforded by PEG fractionation. Coupling this new protocol with liquid chromatography-tandem mass spectrometry, 135 proteins with reported normal concentrations below 100 ng/mL were confidently identified as common low-abundance proteins. A side-by-side comparison indicated that our integrated strategy was increased by average 43.0% in the identification rate of low-abundance proteins, relying on an average 65.8% increase of the corresponding unique peptides. Further investigation demonstrated that this combined strategy could effectively alleviate the signal-suppressive effects of the major high-abundance proteins by affinity depletion, especially with moderate-abundance proteins after incorporating PEG fractionation, thereby greatly enhancing the detection of low-abundance proteins. In sum, the newly developed strategy of incorporating PEG fractionation to immunodepletion methods can potentially aid in the discovery of plasma biomarkers of therapeutic and clinical interest.