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Human-object interaction (HOI) detection aims to localize and recognize the relationship between humans and objects, which helps computers understand high-level semantics. In HOI detection, two-stage and one-stage methods have distinct advantages and disadvantages. The two-stage methods can obtain high-quality human-object pair features based on object detection but lack contextual information. The one-stage transformer-based methods can model good global features but cannot benefit from object detection. The ideal model should have the advantages of both methods. Therefore, we propose the Pairwise Convolutional neural network (CNN)-Transformer (PCT), a simple and effective two-stage method. The model both fully utilizes the object detector and has rich contextual information. Specifically, we obtain pairwise CNN features from the CNN backbone. These features are fused with pairwise transformer features to enhance the pairwise representations. The enhanced representations are superior to using CNN and transformer features individually. In addition, the global features of the transformer provide valuable contextual cues. We fairly compare the performance of pairwise CNN and pairwise transformer features in HOI detection. The experimental results show that the previously neglected CNN features still have a significant edge. Compared to state-of-the-art methods, our model achieves competitive results on the HICO-DET and V-COCO datasets.
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OBJECTIVE: To study the safety and feasibility of implementation of precise radiotherapy with inducement of an apnea-like condition. METHODS: Two patients with lung tumors underwent precise radiotherapy under an apnea-like condition. The apnea-like condition was induced 11 times between the two patients for tumor localization and treatment. The changes in the blood oxygen saturation, blood pressure, heart rate, and end-tidal carbon dioxide during the apnea-like periods were observed, and the incidence of adverse reactions was recorded. RESULTS: The average apnea-like time was 6.2 minutes (range, 3-9 minutes), and the average radiotherapy time was 4.6 minutes (range, 1-7 minutes). The lowest blood oxygen saturation level was 97%, with a change of <1%. The heart rate and average arterial blood pressure increased during the apnea-like periods. Contact sores appeared on the patients' posterior pharyngeal wall after the first apnea-like period; no other adverse events occurred. CONCLUSION: Precise radiotherapy under an apnea-like condition is safe and feasible for patients with lung tumors.
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Anestésicos , Apneia , Frequência Cardíaca , Humanos , Hipóxia , Oximetria , OxigênioRESUMO
BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.
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Medicamentos Biossimilares , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , China , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Resultado do TratamentoRESUMO
This Article contains an error in Figure 3. In panel g, images representing miR-222-TuD and miR-424-TuD were both taken from the miR-222-TuD image. The correct version of Figure 3 is shown in the accompanying Author Correction.
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Accumulating evidence demonstrates that miRNAs, a class of small non-coding RNAs, are involved in the regulation of tumor-initiating cells (TICs) which are considered to be the origin of cancer development according to the cancer stem cell hypothesis. We have previously identified that miR-31 may play suppressive roles in α2δ1+ hepatocellular carcinoma (HCC) TICs. Here, we confirm that the expression of miR-31 is significantly downregulated in α2δ1+ HCC TICs. Overexpression of miR-31 in α2δ1+ HCC TICs results in significant suppression of the self-renewal and tumorigenicity abilities of these cells. Conversely, knockdown the expression of miR-31 in PLC/PRF/5 cells is able to reprogram them into TICs with stem cell-like properties. Furthermore, the expression of ISL LIM Homeobox 1(ISL1), a transcription factor involved in recognition of undifferentiated cardiac progenitors, is negatively regulated by miR-31, and the luciferase reporters' activities with the 3'-UTRs of ISL1 are inhibited significantly by miR-31. Collectively, our results suggest that miR-31 can negatively regulate the self-renewal ability of α2δ1+ liver TICs via silencing ISL1.
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Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel α2δ1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that α2δ1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of α2δ1(+) HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.