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Vortex-induced vibration (VIV) is a kind of abnormal vibration which needs to be automatically identified and warned in real time to guarantee the operational safety of a bridge. However, the existing VIV identification methods only focus on identification and have limitations in visualizing identification results, which causes difficulty for bridge governors in other fields to quickly confirm the identification results. This paper proposes an automatic VIV identification, warning, and visualization method. First, a recurrence plot is introduced to analyze the signal to extract the characteristics of the vibration signal in a time domain. Then, a feature index defined as recurrence cycle smoothness is proposed to quantify the stability of the vibration signal, based on which the VIV can be automatically identified. An automatic VIV identification and multi-level warning process is finally established based on the severity of the vibration amplitude. The proposed method is validated through a suspension bridge with serious VIVs. The result indicates that the proposed method can automatically identify the VIV correctly without any manual intervention and can visualize the identification results using a graph, providing a good tool to quickly confirm the VIV identification results. The multi-level warning can successfully warn the serious VIV and provide possible early warning for large amplitude VIV.

Object detection in unmanned aerial vehicle (UAV) images is an extremely challenging task and involves problems such as multi-scale objects, a high proportion of small objects, and high overlap between objects. To address these issues, first, we design a Vectorized Intersection Over Union (VIOU) loss based on YOLOv5s. This loss uses the width and height of the bounding box as a vector to construct a cosine function that corresponds to the size of the box and the aspect ratio and directly compares the center point value of the box to improve the accuracy of the bounding box regression. Second, we propose a Progressive Feature Fusion Network (PFFN) that addresses the issue of insufficient semantic extraction of shallow features by Panet. This allows each node of the network to fuse semantic information from deep layers with features from the current layer, thus significantly improving the detection ability of small objects in multi-scale scenes. Finally, we propose an Asymmetric Decoupled (AD) head, which separates the classification network from the regression network and improves the classification and regression capabilities of the network. Our proposed method results in significant improvements on two benchmark datasets compared to YOLOv5s. On the VisDrone 2019 dataset, the performance increased by 9.7% from 34.9% to 44.6%, and on the DOTA dataset, the performance increased by 2.1%.

First-line nivolumab plus ipilimumab has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to investigate whether the addition of a limited course (two cycles) of chemotherapy to this combination would further enhance the clinical benefit. This randomised, open-label, phase 3 trial was done at 103 hospitals in 19 countries. Eligible patients were aged 18 years or older with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, and an Eastern Cooperative Oncology Group performance status of 0–1. Patients were randomly assigned (1:1) by an interactive web response system via permuted blocks (block size of four) to nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) combined with histology-based, platinum doublet chemotherapy (intravenously every 3 weeks for two cycles; experimental group), or chemotherapy alone (every 3 weeks for four cycles; control group). Randomisation was stratified by tumour histology, sex, and PD-L1 expression. The primary endpoint was overall survival in all randomly assigned patients. Safety was analysed in all treated patients. Results reported here are from a pre-planned interim analysis (when the study met its primary endpoint) and an exploratory longer-term follow-up analysis. This study is active but no longer recruiting patients, and is registered with ClinicalTrials.gov, number NCT03215706. Between Aug 24, 2017, and Jan 30, 2019, 1150 patients were enrolled and 719 (62·5%) randomly assigned to nivolumab plus ipilimumab with two cycles of chemotherapy (n=361 [50%]) or four cycles of chemotherapy alone (n=358 [50%]). At the pre-planned interim analysis (median follow-up 9·7 months [IQR 6·4–12·8]), overall survival in all randomly assigned patients was significantly longer in the experimental group than in the control group (median 14·1 months [95% CI 13·2–16·2] vs 10·7 months [9·5–12·4]; hazard ratio [HR] 0·69 [96·71% CI 0·55–0·87]; p=0·00065). With 3·5 months longer median follow-up (median 13·2 months [IQR 6·4–17·0]), median overall survival was 15·6 months (95% CI 13·9–20·0) in the experimental group versus 10·9 months (9·5–12·6) in the control group (HR 0·66 [95% CI 0·55–0·80]). The most common grade 3–4 treatment-related adverse events were neutropenia (in 24 [7%] patients in the experimental group vs 32 [9%] in the control group), anaemia (21 [6%] vs 50 [14%]), diarrhoea (14 [4%] vs two [1%]), increased lipase (22 [6%] vs three [1%]), and febrile neutropenia (14 [4%] vs ten [3%]). Serious treatment-related adverse events of any grade occurred in 106 (30%) patients in the experimental group and 62 (18%) in the control group. Seven (2%) deaths in the experimental group (acute kidney failure, diarrhoea, hepatotoxicity, hepatitis, pneumonitis, sepsis with acute renal insufficiency, and thrombocytopenia; one patient each) and six (2%) deaths in the control group (anaemia, febrile neutropenia, pancytopenia, pulmonary sepsis, respiratory failure, and sepsis; one patient each) were treatment related. Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk–benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC. Bristol Myers Squibb. For the Polish and Russian translations of the Article see Supplementary Materials section.

Since the demonstration of p-type gallium nitride (GaN) through doping with substitutional magnesium (Mg) atoms 1 , 2 , rapid and comprehensive developments, such as blue light-emitting diodes, have considerably shaped our modern lives and contributed to a more carbon-neutral society 3 – 5 . However, the details of the interplay between GaN and Mg have remained largely unknown 6 – 11 . Here we observe that Mg-intercalated GaN superlattices can form spontaneously by annealing a metallic Mg film on GaN at atmospheric pressure. To our knowledge, this marks the first instance of a two-dimensional metal intercalated into a bulk semiconductor, with each Mg monolayer being intricately inserted between several monolayers of hexagonal GaN. Characterized as an interstitial intercalation, this process induces substantial uniaxial compressive strain perpendicular to the interstitial layers. Consequently, the GaN layers in the Mg-intercalated GaN superlattices exhibit an exceptional elastic strain exceeding −10% (equivalent to a stress of more than 20 GPa), among the highest recorded for thin-film materials 12 . The strain alters the electronic band structure and greatly enhances hole transport along the compression direction. Furthermore, the Mg sheets induce a unique periodic transition in GaN polarity, generating polarization-field-induced net charges. These characteristics offer fresh insights into semiconductor doping and conductivity enhancement, as well as into elastic strain engineering of nanomaterials and metal–semiconductor superlattices 13 . The spontaneous formation of magnesium-intercalated gallium nitride superlattices by the interstitial intercalation of two-dimensional magnesium results in considerable compressive strain perpendicular to the layers, leading to enhanced hole transport.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments. In this study, a novel mechanical matching DMF/RSF/P:P conduit based on RSF and bioencapsulated PEDOT:PSS is designed and developed, which can inhibit Schwann cell pyroptosis and induce macrophage polarization toward the M2 subtype to improve peripheral nerve regeneration. The current study shows a promising strategy to promote peripheral nerve regeneration by remodeling the intraconduit IME at the nerve injury site.

Lung cancer is the leading cause of cancer death in China, and approximately one third of these cancers are squamous cell carcinoma (SqCC) of the lung. Ethnic diversity and country-specific environmental factors can account for interindividual variations in response to and tolerability of anticancer therapies. Although several targeted therapies have recently been approved for patients with relapsed/refractory SqCC of the lung, only afatinib, an irreversible ErbB family blocker, has data of Chinese patients. In the Phase III LUX-Lung 8 trial, afatinib demonstrated a significant clinical benefit vs the reversible first-generation EGFR tyrosine kinase inhibitor erlotinib in both the overall population and the Chinese subset, with a manageable safety profile. Emerging biomarker data from LUX-Lung 8 suggest that patients with ErbB mutations, especially ErbB2, and those classified as \"good\" in the VeriStrat proteomic test, may benefit from afatinib treatment in particular, regardless of ethnicity, and may get a long-term response. In conclusion, afatinib is a valid second-line option for Chinese patients with SqCC of the lung, and specific biomarkers may help guide in treatment decision-making. Ongoing studies will provide further guidance on afatinib's place in the treatment algorithm, alongside the other novel targeted therapies.

Epithelial–mesenchymal transition (EMT) is an important process for cancer metastasis, drug resistance, and cancer stem cells. Activation of fibroblast growth factor receptor 1 (FGFR1) was found to promote EMT and metastasis in prostate and breast cancers, but the effects and mechanisms in lung cancer was unclear. In this study, we aimed to explore whether and how activation of FGFR1 promotes EMT and metastasis in FGFR1-amplified lung cancer. We show that activation of FGFR1 by its ligand fibroblast growth factor 2 (FGF2) promoted proliferation, EMT, migration, and invasion in FGFR1-amplified lung cancer cell lines H1581 and DMS114, whereas inhibition of FGFR1 suppressed these processes. FGFR1 activation upregulated expression of Sry-related HMG box 2 (SOX2) by downstream phosphorylated ERK1/2; moreover, the upregulation of SOX2 by autophosphorylation variant ERK2_R67S plasmid transfection was not suppressed by FGFR1 inhibitor AZD4547 or MEK/ERK inhibitor AZD6244 in vitro. And SOX2 expression was also significantly upregulated in ERK2_R67S lentivirus-transfected stable cell lines in vivo. Overexpression of SOX2 promoted cell proliferation, EMT, migration, and invasion. Importantly, activation of FGFR1 could not promote these processes in SOX2-silenced stable cell lines. In orthotopic and subcutaneous lung cancer xenograft models, inhibition of FGFR1 suppressed tumor growth, SOX2 expression, EMT, and metastasis in vivo; however, these processes caused by SOX2-overexpressing stable cell lines were not suppressed by FGFR1 inhibition. Higher expression of FGFR1 and SOX2 were positively correlated, and both were associated with shorter survival in lung cancer patients. In conclusion, our findings reveal that activation of FGFR1 promotes cell proliferation, EMT, and metastasis by the newly defined FGFR1-ERK1/2-SOX2 axis in FGFR1-amplified lung cancer.

Genetic deletion of two fatty acid receptors in beta cells improves insulin secretion and diabetes. Type 2 diabetes is a major health problem worldwide, and one of its key features is the inability of elevated glucose to stimulate the release of sufficient amounts of insulin from pancreatic beta cells to maintain normal blood glucose levels 1 , 2 . New therapeutic strategies to improve beta cell function are therefore believed to be beneficial 3 , 4 . Here we demonstrate that the short-chain fatty acid receptors FFA2 (encoded by FFAR2 ) and FFA3 (encoded by FFAR3 ) are expressed in mouse and human pancreatic beta cells and mediate an inhibition of insulin secretion by coupling to G i -type G proteins. We also provide evidence that mice with dietary-induced obesity and type 2 diabetes, as compared to non-obese control mice, have increased local formation by pancreatic islets of acetate, an endogenous agonist of FFA2 and FFA3, as well as increased systemic levels. This elevation may contribute to the insufficient capacity of beta cells to respond to hyperglycemia in obese states. Indeed, we found that genetic deletion of both receptors, either on the whole-body level or specifically in pancreatic beta cells, leads to greater insulin secretion and a profound improvement of glucose tolerance when mice are on a high-fat diet compared to controls. On the other hand, deletion of Ffar2 and Ffar3 in intestinal cells did not alter glucose tolerance in diabetic animals, suggesting these receptors act in a cell-autonomous manner in beta cells to regulate insulin secretion. In summary, under diabetic conditions elevated acetate acts on FFA2 and FFA3 to inhibit proper glucose-stimulated insulin secretion, and we expect antagonists of FFA2 and FFA3 to improve insulin secretion in type 2 diabetes.

VEGF inhibitors can enhance the efficacy of immunotherapy. However, despite high initial response rates, almost all patients eventually develop treatment resistance to EGFR tyrosine-kinase inhibitors. We aimed to evaluate the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin, compared with pemetrexed and cisplatin alone, for the treatment of patients with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy. This randomised, double-blind, multicentre, phase 3 trial was conducted at 52 hospitals in China. Eligible participants were adults aged 18–75 years with locally advanced or metastatic NSCLC and EGFRmut who progressed after receiving a EGFR tyrosine-kinase inhibitor, had an Eastern Cooperative Oncology Group performance status of 0 or 1 with at least one measurable lesion, and an estimated life expectancy of at least 3 months. Participants were randomly assigned (1:1:1) to receive sintilimab (200 mg) plus IBI305 (15 mg/kg) plus pemetrexed (500 mg/m2) and cisplatin (75 mg/m2), sintilimab plus pemetrexed and cisplatin, or pemetrexed and cisplatin (chemotherapy alone) using block randomisation with stratification according to sex and presence or absence of brain metastases. All study drugs were administered intravenously on day 1 of each cycle, once every 3 weeks. Except for cisplatin, which was only given in the first four cycles, treatment was given for 24 months or until disease progression, intolerable toxic effects, withdrawal of consent, death, or other protocol-specified conditions, whichever occurred first. The primary endpoint was progression-free survival in the intention-to-treat population. We herein report the first planned interim analysis, with progression-free survival results for the comparison between sintilimab plus IBI305 plus chemotherapy versus chemotherapy alone. The progression-free survival results for the sintilimab plus pemetrexed and cisplatin group are immature and not reported here. This study is registered with ClinicalTrials.gov, NCT03802240 (recruiting). Between July 11, 2019, and July 31, 2021, 936 patients were screened and 444 were randomly assigned (148 to the sintilimab plus IBI305 plus chemotherapy group, 145 to the sintilimab plus chemotherapy group, and 151 to the chemotherapy alone group). Data cutoff for this interim analysis was July 31, 2021. After a median follow-up of 9·8 months (IQR 4·4–13·3), progression-free survival was significantly longer in the sintilimab plus IBI305 plus chemotherapy group versus the chemotherapy alone group (median 6·9 months [95% CI 6·0–9.3] vs 4·3 months [4·1–5·4]; hazard ratio 0·46 [0·34–0·64]; p<0·0001). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophil count (30 [20%] in the sintilimab plus IBI305 plus chemotherapy group vs 26 [18%] in the sintilimab plus chemotherapy group vs 27 [18%] in the chemotherapy alone group), decreased white blood cell count (17 [11%] vs 12 [8%] vs 13 [9%]), and anaemia (18 [12%] vs ten [7%] vs 15 [10%]). Potentially treatment-related deaths occurred in six patients (intestinal obstruction, gastrointestinal haemorrhage, and myelosuppression in one patient each, and three deaths of unknown cause) in the sintilimab plus IBI305 plus chemotherapy group, and in one patient in the chemotherapy alone group (unknown cause). In this interim analysis, sintilimab plus IBI305 plus cisplatin and pemetrexed was generally efficacious and well tolerated in patients with EGFR-mutated NSCLC who progressed after receiving EGFR tyrosine-kinase inhibitor therapy. Innovent Biologics and the National Natural Science Foundation of China. For the Chinese translation of the abstract see Supplementary Materials section.

Background The main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs. Methods A real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation. Results Two subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification. Conclusion This study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy.