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Additional file 2. Table S2: Analytics for the assessment of rivaroxaban plasma concentrations in healthy volunteers in sub-centers

Additional file 7. Table S7: Comparison of plasma miR-320a and miR-483 levels between 3 and 0 h in healthy volunteers

Additional file 3. Table S3: Comparison of plasma miR-320a and miR-483 levels between the case and control groups in healthy volunteers

Additional file 6. Table S6: Risk estimates of 3 h miRNA levels for rivaroxaban response by univariate logistic analysis in patients

In this paper, a new approach to design terahertz (THz) E-plane crossover coupler is reported. By cascading two symmetrical septum polarizers, a simple structure with wide operating bandwidth and high isolation performance is achieved. The working principle is explained by operating waveguide modes. To simplify the optimization process, the scattering matrix (S-matrix) of the crossover is calculated. Two prototypes loaded and unloaded electromagnetic band gap (EBG) are fabricated and measured. The electrical contact problem at assembly plane is eliminated by the prototype loaded EBG. A measured bandwidth of 17.3% from 92.5 to 110 GHz for reflection and isolation coefficients −2 dB is achieved.

Xiao Fu,1,* Zhiyan Liu,2,* Luochengling Xiang,1 Mengjie Liu,1 Xiaoqiang Zheng,1 Jingjing Wang,1 Na Liu,1 Huan Gao,1 Aimin Jiang,1 Yujuan Yang,3 Xuan Liang,1 Zhiping Ruan,1 Tao Tian,1 Yu Yao1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Northwest University, Xi’an No. 3 Hospital, Xi’an, Shaanxi Province, 710018, People’s Republic of China; 3The Third Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi Province, 710068, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, People’s Republic of ChinaTel +86 13572206784Fax +86 29 85324086Email tiantao0607@163.comYu YaoDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, People’s Republic of ChinaTel +86 13572101611Fax +86 29 85324086Email yaoyu123@xjtufh.edu.cnPurpose: Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine tumor with limited treatment strategies. Programmed death 1 (PD-1) and its ligand (PD-L1), delta-like ligand-3 (DLL-3), and poly ADP-ribose polymerase (PARP) inhibitors have shed light on the treatment of extensive stage-SCLC. However, the expression and prognostic role of PD-L1, DLL-3, and PARP are barely explored in surgically resected limited stage-SCLC (LS-SCLC).Methods: We retrospectively reviewed 404 SCLC patients from 2011 to 2018 in the First Affiliated Hospital of Xi’an Jiaotong University and collected 43 surgically resected LS-SCLC samples with adequate materials and histological specimens containing abundant tumor cells. Immunohistochemistry staining of PD-L1, DLL-3, and PAPR1 was performed by anti-PD-L1 (22C3/Dako), anti-DLL-3, and anti-PAPR1 antibodies, respectively. Positive expression of PD-L1 was characterized as > 5% tumor cells and/or tumor-infiltrating immune cells expressing PD-L1. The correlation between PD-L1, DLL-3, PARP1, and clinicopathological characteristics of surgically resected LS-SCLC patients was performed by χ2 test. The survival curves were calculated by the Kaplan–Meier method and analyzed by the Log rank test and Cox proportional hazards model.Results and Conclusion: 63.04% patients were positive for PD-L1, 65.12% were positive for DLL-3, and 20.93% were positive for PARP1. DLL-3 was significantly overexpressed in SCLC tissues, compared with matched para-noncancerous tissues. Male, elder than 60 years old, advanced TNM stage, smoking, and positive PD-L1 expression predicted shorter DFS, while patients received adjuvant therapy performed better DFS. Further multivariate analysis revealed that TNM stage (HR=2.51, 95% CI=1.31– 4.78, P=0.005) was an individual prognostic factor for DFS in LS-SCLC. Moreover, advanced TNM stage and positive PD-L1 expression also indicated worse OS, but adjuvant therapy improved OS in LS-SCLC. Multivariate analysis demonstrated that PD-L1 and TNM stage were independent and significant negative predictive factors for OS (HR=2.89, 95% CI=1.21– 6.93, P=0.017; HR=2.49, 95% CI=1.25– 4.94, P=0.009 for PD-L1 and TNM stage, respectively), while adjuvant treatment was an independent positive prognostic factor for OS (HR=0.37, 95% CI=0.17– 0.81, P=0.012).Keywords: surgically resected LS-SCLC, PD-L1, DLL-3, PARP1

BackgroundNuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a NUT gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma.MethodUltrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence in situ hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC.ResultsWe describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the NUT gene on chromosome 15q14. The NGS results revealed a BRD4-NUT gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of NUTM1 occurred in the exon region, and the mutation site was 15q14. Moreover, BRD4 single-nucleotide variation (SNV) occurs in the 3′ UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery.ConclusionThyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of IGKV gene fusions in addition to the BRD4-NUT fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.

Additional file 1. Search strategy of this systematic review and meta-analysis.

Additional file 3. Trial sequential analysis of pooled results of outcomes.

Additional file 2. The quality of the included studies assessed using the Newcastle���Ottawa Scale.