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Tao Lu,1,* Longfeng Zhang,2,* Mingqiu Chen,3 Xiaobin Zheng,2 Kan Jiang,2 Xinlong Zheng,2 Chao Li,4 Weijin Xiao,4 Qian Miao,2 Shanshan Yang,2 Gen Lin2 1Department of Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 3Department of Thoracic Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gen LinDepartment of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of ChinaEmail fjzllg133@fjzlhospital.comBackground: Predictive markers for guidance and monitoring of immunotherapy in lung squamous cell carcinoma (LSCC) are an interesting topic but have yet to be fully explored. A primary characteristic of LSCC is tumor necrosis that results in extensive immune suppression in patients. We sought to assess whether tumor necrosis or cavity on baseline CT could effectively predict the efficacy of immune checkpoint inhibitors (ICIs) in advanced LSCC.Methods: Advanced LSCC cases undergoing pre-treatment chest CT imaging and receiving ICIs were retrospectively collected. All CT images were reviewed by an independent chest radiologist blinded to any previous diagnosis to confirm morphological alterations in necrosis or cavity. We performed Logistic regression and developed Cox proportional hazards models to assess the predictive performance of baseline necrosis or cavity characteristics in advanced LSCC. Survival estimates were observed using Kaplan–Meier curves.Results: Ninety-three patients were eligible for analysis, predominantly consisting of patients with ECOG performance status of 0 or 1 (97.8%), male patients (95.7%), and heavy smokers (92.5%). Intrapulmonic necrosis or cavity on CT scan was present in 52.7% of all patients. Generally, the objective response rate (ORR) in patients with necrosis or cavity to ICI treatment was significantly worse versus those without (30.6% vs 54.5%, p = 0.020), with the subgroup ORRs as follows: ICI monotherapy (necrosis vs non-necrosis: 10.0% vs 36.8%, p =0.047) and ICI combination therapy (44.8% vs 68.0%, p =0.088). Multivariable analysis identified intrapulmonic necrosis or cavity at baseline as a major risk factor for advanced LSCC (HR 4.042, 95% CI1.149– 10.908, p = 0.006). Multivariate Cox analysis showed that baseline necrosis or cavity and ICI monotherapy were unfavorable factors for progression-free survival (HR 1.729; 95% CI1.203– 2.484, p =0.003).Conclusion: LSCC patients with intrapulmonic cavity or necrosis on baseline CT scan may respond poorly to anti-PD-(L)1-treatment, monotherapy and combination therapy alike.Keywords: lung squamous cell carcinoma, immune-checkpoint inhibitor, predictive marker, necrosis, cavity

Immune checkpoint inhibitors (ICIs) have become an important milestone in the treatment of non-small cell lung cancer (NSCLC). High expression of protein ligand 1 (PD-L1) and tumor mutation burden (TMB) can help to select the dominant population for immunotherapy, but the expression of PD-L1 does not seem to be unchanged. A 61-year-old man with adenocarcinoma of the lung experienced postoperative recurrence. PD-L1 expression was negative before recurrence, and TMB was stable by next-generation sequencing (NGS) test. However, after radiotherapy and chemotherapy, PD-L1 positive expression was found in a re-biopsy specimen, and NGS detection indicated the loss of immune negative predictive genes. The patient achieved a durable response to a posterior-line immunotherapy combined chemotherapy. The tumor microenvironment maybe changed after chemoradiotherapy, which provides an opportunity for patients to benefit from immunotherapy. The use of NGS in dynamic detection and PD-L1 expression may help monitor this change in the tumor microenvironment, the transition from cold to hot tumor. This case maybe provides new clinical evidence that a non-immuno-dominant population in the initial state can be converted to a population with the benefit of immunotherapy after chemoradiotherapy. However, patients who are initially unsuitable for immunotherapy may still need to undergo combined immunotherapy to achieve a clinical benefit.

Acute spinal cord injury (SCI) is a devastating condition that results in tremendous physical and psychological harm and a series of socioeconomic problems. Although neurons in the spinal cord need neurotrophic factors for their survival and development to reestablish their connections with their original targets, endogenous neurotrophic factors are scarce and the sustainable delivery of exogeneous neurotrophic factors is challenging. The widely studied neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, and glial cell-derived neurotrophic factor have a relatively short cycle that is not sufficient enough for functionally significant neural regeneration after SCI. In the past decades, scholars have tried a variety of cellular and viral vehicles as well as tissue engineering scaffolds to safely and sustainably deliver those necessary neurotrophic factors to the injury site, and achieved satisfactory neural repair and functional recovery on many occasions. Here, we review the neurotrophic factors that have been used in trials to treat SCI, and vehicles that were commonly used for their sustained delivery., Graphical abstract

Anterior cruciate ligament (ACL) injury is one of the common injuries in sports and vehicle accidents. ACL decreases joint stability, leading to increased incidence of osteoarthritis. Although there are various approaches for the reconstruction of ACL, no consensus has been reached on the safest and most effective method to achieve joint stability. Here we have compared the biomechanical and histopathological outcomes of three different approaches: intra-articular ACL reconstruction, remnant-preserving and re-tensioning and non-remnant-preservation technique, using finite element analysis, histopathologic observation as well as qPCR and western blot analysis. Results of the current study showed no significant differences among the three methods concerning biomechanical, histopathological analysis and mRNA and protein levels of chondrocyte apoptotic markers such as JNK, MMP-1 and SIRT1 (P > 0 05). Those results indicated that remnant preservation techniques such as intra-articular ACL reconstruction and remnant-preserving and re-tensioning are similar in their ability to achieve joint stabilization and prevent chondrocyte regeneration to non-remnantpreservation technique.

Objectives: An association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC).Methods: Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA.Results: VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS.Conclusions: The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.

We are in the era that sport is increasingly defined by data. Rich data is a powerful enabling foundation for novel insights on the game and on player actions, and consequently used for fan engagement and better decision making. Detailed data that has specifications of each shot is currently missing in tennis, as the game dynamics is fast and it is beyond human ability to manually record all specifications of each and every shot, even using scoring software. In this paper, we present an intelligent system to automatically recognize player actions, ball and player movements, and important game events. The system annotates the video with a suitable set of keywords for fast retrieval in broadcast production. Various techniques of computer vision, alignment, filtering, and pre-trained deep learning models are utilized by our system. The evaluation of our results on multiple broadcast videos show great accuracy and timeliness. The implications of the work presented in this paper are profound in the current workflow in broadcast coverage of a tennis match where normally multiple video operators and judges are needed to identify events and retrieve the related clips from multiple cameras.

Background Leptomeningeal metastasis (LM) is a fatal complication, and its incidence is increasing in non-small cell lung cancer (NSCLC). Refractory LM (rLM) has become problematic due to the lack of uniform definition and standardized treatment guidelines. In this study, we assessed the efficacy and safety of multiple therapy based on intrathecal pemetrexed (IP) in patients with rLM in NSCLC. Methods From March 2019 to June 2020, patients with cytologically confirmed rLM who received IP and systemic salvage therapy were retrospectively analyzed. Our objectives were to assess progression-free survival (PFS), overall survival (OS), clinical response, and safety. Clinical response was assessed by an investigator according to the Response Assessment in Neuro-Oncology (RANO) proposal criteria. We performed next generation sequencing (NGS) of cerebrospinal fluid (CSF) to explore the gene profile of rLM. Results A total of 23 patients were enrolled, and the genetic status of the primary tissue was 16 epidermal growth factor receptor (EGFR) mutations (69.6%), two anaplastic lymphoma kinase (ALK) fusions (8.7%), one ROS proto-oncogene 1 (ROS1) fusion (4.3%), one Erb-B2 receptor tyrosine kinase 2 (ERBB2) mutation (4.3%), and three wild-type (13.0%). On the basis of IP therapy, 19 patients were rechallenged with tyrosine-kinase inhibitors (TKIs), 10 patients were treated with systemic chemotherapy, 10 patients were treated with antivascular therapy, one patient was treated with immunotherapy, and one patient was treated with whole-brain radiotherapy (WBRT). Thirteen patients received two or more of the aforementioned combination treatment modes. The median PFS (mPFS) was 9.6 months [95% confidence interval (CI): 3.4-15.8 months]. OS was not mature at the final follow-up. The clinical assessment was: response in eight patients (34.8%), stable in 11 patients (47.8%), worse in two patients (8.7%), and non-evaluable in two patients (8.7%). Adverse events (AEs) related to any component occurred in 14 patients (60.9%). The driver mutation status was highly consistent between the CSF and primary tumor samples (14/14), but we detected EGFR mutations in the CSF of two patients whose primary tumor samples tested wild-type. Conclusions IP-based multimodal therapy has significant efficacy and a controlled safety profile in patients with rLM in NCSLC.

Biogenic amines (BAs) are a class of bioactive organics produced during the fermentation of soy sauce. A high concentration of BAs may bring about serious physiological and toxicological effects on the human body. In this study, we reported an optimized process to produce soy sauce with lower BA concentration and found the contents of putrescine, cadaverine and histamine increased with the increase of fermentation temperature but decreased with the increase of NaCl concentration. The final content of total BAs with improved fermentation was 105.56 ± 0.13 mg/L, which was reduced by 89.11% compared to traditional brewing. Besides, the pilot production test was performed to verify the optimized conditions and physicochemical indexes were measured to better understand the change principle of the chemical compounds. Taken together, we present an effective process to inhibit the formation of BAs while ensuring that characteristic nutrients are not lost.

Purpose The relationship between examined lymph nodes (ELN) and survival has been confirmed in several single early-stage malignancies. We studied the association between the ELN count and the long-term survival of T1-2N0M0 double primary non-small cell lung cancer (DP-NSCLC) patients after surgery, based on the Surveillance, Epidemiology and End Results (SEER) database. Methods A total of 948 patients were identified and their independent prognostic factors were analyzed. These factors included the ELN count, which related to overall survival (OS) and the cancer-specific survival (CSS) of synchronous (n = 426) and metachronous (n = 522) T1-2N0M0 DP-NSCLC patients after surgery. Results X-tile analysis indicated that the cutoff value for the sum of ELNs was 22 for both OS and CSS in the synchronous DP-NSCLC group. Patients with a sum of ELNs >22 were statistically more likely to survive than those with ≤22 ELNs. X-tile analysis revealed that the ELN count of the second lesion was related to both OS and CSS in the metachronous DP-NSCLC group. The optimal cutoff value was nine. These results were confirmed using univariate and multivariate Cox regression analyses. Conclusion Our findings indicate that ELN count was highly correlated with the long-term survival of T1-2N0M0 double primary NSCLC patients after surgery.

The extent to which intratumoral heterogeneity of programmed death ligand 1 (PD-L1) expression causes discordance of PD-L1 expression between paired samples remains unclear. Here, PD-L1 status was compared between whole sections from NSCLCs and the corresponding tissue microarrays (TMAs) serving as surrogate biopsy specimens.PD-L1 expression was evaluated by 22C3 immunohistochemistry assay on 190 archival surgical specimens and matched to the TMA results. PD-L1 expression was determined by the tumor proportion score (TPS) and classified as TPS lower than 1%, TPS of 1% to 49%, and TPS of 50% or higher. Agreement statistics were used.The percentage of PD-L1 expression on tumor cells differed greatly between individual TMAs and matched surgical specimens. When PD-L1 TPS was adopted, a total of 36 of 190 discordance cases (18.9%) were observed, with a κ-value of 0.630 between paired samples. The TMAs underestimated or overestimated PD-L1 status in 19 of 36 (52.8%) and 17 of 36 (47.2%) of the matched surgical specimens, respectively (p = 0.118). The discordance rate was much lower in cases with a PD-L1 TPS lower than 1% compared with in cases with a TPS of 1% to 49% and TPS of 50% or higher (18.4% versus 56.7% and 43.3%, p0.001). When a TPS of 50% or higher was used as the cutoff, the discordance rate of PD-L1 TPS less than 50% was further reduced to 7.5%. Such discrepancies were due mainly to intratumoral heterogeneity of PD-L1 expression and nonsignificant association with clinicopathological features.PD-L1 expression in TMAs correlates moderately well with that in the corresponding surgical specimens, indicating that evaluating PD-L1 expression in diagnostic biopsy specimens could be misleading in defining sensitivity to pembrolizumab treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less than 50% from first-line pembrolizumab treatment.

Background Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. Patients and methods Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. Results The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0–11.2). Conclusions The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

Background Peripheral blood cell count ratios, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non‐surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. Methods 193 non‐surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response. Results In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis. Conclusions The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non‐surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response., In this retrospective study, we demonstrated that the cNLR at weeks 4 and 5 during RT had a significant negative correlation with the OS and clinical responses of non‐surgical ESCC patients treated with radiotherapy, while an elevated cPLR at weeks 4 and 5 was only related to poor clinical response. During radiotherapy, the median cNLR and cPLR increased gradually every week, reaching the highest values at week 5 and then declining. Conversely, cLMR decreased to the minimum value at week 5 but had no predictive ability for either OS or clinical response.

e20523 Background: Lung adenosquamous carcinoma (ASC) is a relatively uncommon malignancy that comprised of both adenocarcinoma component (ACC) and squamous cell carcinoma component (SCCC). We have reported its genomic profile, evolutionary origin, and clinical management. Information of tumor immune microenvironment (TIME) of ASC, including tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), T cell receptors (TCR) repertoire, and PD-L1 status remains scarce. Methods: 28 Surgical ASCs were collected and identified by immunohistochemistry (IHC). ACC and SCCC were obtained separately by microdissection. Targeted sequencing was performed for the two components using a 1021-gene-panel independently. TMB of ACC and SCCC were independently calculated. TMB of ASC calculation was based on aggregation (removing duplicates) of non-synonymous mutations from both ACC and SCCC. TILs and PD-L1were examined by multiplex immunohistochemistry (mIHC). The infiltration level of immune cells in tumor, stroma, and total region (named by both tumor and stroma regions) was investigated. T cell receptor (TCR) repertoires were sequenced and clonality and Shannon index were calculated. Results: SCCC (7.2 mutations/Mb) had a higher TMB level than ACC (6.5 muts/Mb), indicating the immunogenic heterogeneity between the different pathological components. The TMB value of ACC and SCCC were modestly proportional (Spearman r = 0.56, p = 0.001), which was related to the clonal origin. SCCC TMB was lower than the archival LUSC (10.1 muts/Mb), and ACC TMB was similar to LUAD (4.3 muts/Mb). The TMB of ASC was higher than LUAD and close to LUSC. The nonidentical TIL level in ACC and SCCC showed infiltration heterogeneity. For tumor region, CD3+ total T cells, CD4+ T cells, CD8+ T cells, and PD1+ cells accounted for the most proportion of immune cells, with no differences between ACC and SCCC; FOXP3+ CD4+ Treg cells were more abundant in SCCC than ACC ( p = 0.047), as well as CD3+ LAG3+ T cell ( p = 0.029). For stroma region, ACC and SCCC had similar level of CD4+, CD8+, and PD-1 immune cell infiltration; the amount of FOXP3+ CD4 + Treg cells was also higher in SCCC than ACC, as well as CD3+ LAG3+ T cells. For the total region, FOXP3+ CD4 + Treg cells, CD3+ LAG3+ T cells, and PD-1+ T cells were enriched in SCCC compared with ACC, while CD57+ natural killer T (NKT) cells were accumulated with a marginally higher level in ACC ( p = 0.049). TCR repertoires sequencing revealed a lower Shannon’s diversity ( p = 0.029) but higher clonality ( p = 0.047) of SCCC compared with ACC. PD-L1 expression identified by mIHC in SCCC was significantly higher than ACC, in the tumor ( p < 0.001), stroma ( p < 0.001), and total regions ( p < 0.001). Conclusions: SCCC of ASC had higher levels of TMB, Treg cells, TCR clonality, and PD-L1, and similar level of CD3+, CD4+, and CD8+ TILs, comprehensively reflecting the intratumor heterogeneity of TIME.

Background The aim of this study was to determine if anterior cruciate ligament (ACL) reconstruction by remnant preservation promotes cell proliferation, vascularization, proprioception recovery, and improved biomechanical properties of the tendon grafts. Material/Methods 75 New Zealand rabbits were randomly assigned into the control group (group A), conventional ACL reconstruction group (group B), ACL reconstruction using remnant preservation and graft through remnant sleeve technique group (group C), and ACL reconstruction using remnant preservation and remnant tensioning technique group (group D). The remnant and healing of tendon grafts in groups C and D were observed at 3, 6, and 12 weeks after surgery, and the mRNA expression levels of VEGF, NT-3 and GAP-43 in ACL (group A) or tendon graft samples (groups B, C, and D) were determined by real-time PCR. Tendon graft cell count, microvessel density (MVD), and proprioceptors were determined by H&E staining, CD34, and S-100 immunohistochemical staining. The biomechanical properties of the tendon graft at week 12 in groups B, C, and D were examined by using a tensile strength test. Results Remnant and tendon grafts were not healed at 3, 6, and 12 weeks after the operation in groups C and D. VEGF, NT-3, and GAP-43 mRNA expressions in groups B, C, and D were higher than those in group A (P0.05). Furthermore, tendon graft cell count, MVD, proprioception, and biomechanical properties showed no significant differences (P>0.05) among groups B, C, and D at various time points. Conclusions There was no significant difference in cell proliferation, vascularization, proprioception recovery, or biomechanical properties of the tendon grafts between remnant-preserving and conventional ACL reconstruction methods.

9536 Background: Cancer-related fibroblasts (CAFs) are important components of the tumor microenvironment (TME) and play a key role in tumor progression. There is growing evidence that CAF levels in tumors are highly correlated with treatment response and prognosis. However, the effect of CAFs on immunotherapy response remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The SVA package ComBat function was used to remove batch effects. The ssGSEA algorithm was used to assess the level of cell infiltration in each sample. OS (overall survival) and DFS (disease free survival) were analyzed using the Kaplan–Meier method. GO enrichment analysis was used to assess the biological processes of subgroup differential genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. The prognosis according to CD8+ T cells was not strong, but CD8+ T cells / fibroblasts (CFR) were significant protective prognostic factors [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.56–0.78; P < 0.001]. Multivariate analysis revealed that the CFR was an independent prognostic biomarker. The TCGA pan-cancer cohort confirmed the widespread presence of CMIRP in cancer. We further defined the CFR high and CFR low subgroups. CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β, epithelial-mesenchymal transition, and angiogenesis pathways. Finally, we combined TIDE and submap to speculate that CFR is a potential prognostic marker of immunotherapy for NSCLC. Conclusions: We proposed the term “CMIRP” to shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC.

Objective To investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjogren's syndrome (pSS) patients. Methods This study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation. Results We found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3. Conclusion Our findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS.

Deep Learning (DL) is good at finding the patterns hidden in big data, while Markov Decision Process (MDP) is good at modeling the dynamics in a complex system for formal analysis, e.g. Probabilistic Model Checking (PMC). The two models complement each other. Unlike the black box DL-Only model, the combined model is interpretable. Unlike the MDP-Only model, the combined model is able to draw deep insights from the data. Both interpretability and capability of finding deep insights are desirable in many applications, including sports analytics. In this paper, we propose to combine DL and PMC, and apply it in sports analytics to find an accurate and interpretable winning strategy.

The chassis is a key component of forestry vehicular equipment that directly determines its ability to drive and climb in rough mountainous or forested terrain. A six-wheeled luffing articulated chassis was designed to scale obstacles on forested land. This paper discusses the use of the Devanit-Hartenberg method to establish a kinematic model for this vehicle chassis; positive solutions of the kinematic model were then applied to an analysis of the luffing capabilities of the six-wheeled luffing articulated chassis. Theoretical calculations, simulations, and experimental results showed that the established kinematic model can be applied to the development and production of forestry equipment.

The paper introduces a novel auto-leveling system applied to the obstacle-surmounting robot with six wheellegs. The leveling model of the robot with six wheel legs and one articulated steering is analyzed. Besides, the kinematic model of the robot is presented. In order to optimize the leveling algorithm, a special PID control strategy with the leveling matrix is applied to the leveling system. The experiment shows that the new leveling system can improve the efficiency and the stability of the leveling performance: the leveling time is reduced by 3.5 seconds and the obvious tilt fluctuations are decreased by 5 times.

Different anti-PD-1 and anti-PD-L1 antibodies bind different epitopes. However, whether the results from the SP142 and 22C3 immunochemistry (IHC) assays can be interchanged to determine patient eligibility for immunotherapy remains largely unknown. Histologic sections from 135 tumor samples were probed with both 22C3 and SP142 antibodies. The concordance of PD-L1 expression determined by the two assays was assessed. Additionally, we evaluated the association of PD-L1 expression detected by different assays with clinicopathological features and prognosis. In total, 105 (77.78%) of 135 samples evaluated by the 22C3-IHC platform produced the same results with the SP142-IHC platform (Kappa value: 0.481, p

// Gen Lin 1 , Xirong Fan 1 , Weifeng Zhu 2 , Cheng Huang 1 , Wu Zhuang 1 , Haipeng Xu 1 , Xiandong Lin 3 , Dan Hu 2 , Yunjian Huang 1 , Kan Jiang 1 , Qian Miao 1 and Chao Li 2, 4 1 Department of Thoracic Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China 2 Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China 3 Department of Molecular Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China 4 Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China Correspondence to: Chao Li, email: lichao3501@163.com Keywords: non-small cell lung cancer, prognosis, programmed death ligand 1, tumor infiltrating lymphocytes Received: June 20, 2017 Accepted: July 26, 2017 Published: August 12, 2017 ABSTRACT Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit. The PD-L1 expression was determined by the Tumor Proportion Score (TPS) and classified into TPS

The advance of analytics technology has attracted more attention and adoption from sports, although modeling and analyzing the dynamic (and uncertain) behaviors of sports are challenging. Formal methods have been strongly recommended to deal with complex systems by their rigorous semantics and powerful reasoning capabilities. In this paper, we present our initiative as the first to apply probabilistic model checking techniques to strategy analytics for tennis based on Markov Decision Processes (MDP). Our approach can derive insights such as prediction of winning chances and identification of best improvement. We evaluate the effectiveness of our approach through real-life case study.

This study explores how to create a reciprocal relationship between online and offline channel by improving channel integration. Data for this study were collected from 552 Chinese customers who completed a questionnaire. Participants were asked to have purchased products or services with the use of at least two channels operated by a same retailer. The partial least square (PLS) structural equation modeling was conducted to test hypotheses. The results illustrate that channel integration has a direct influence on channel reciprocity and it also influences channel reciprocity indirectly through online or offline trust. Three constructs of channel integration are identified: integrated information, integrated channel access and integrated customer service. Trust transference, bidirectional channel referrals and image transference are found to construct channel reciprocity. Implications for multi-channel retailers are discussed based on these findings.

This paper presents a novel white blood cell (WBC) segmentation scheme based on two feature space clustering techniques: scale-space filtering and watershed clustering. In this scheme, nucleus and cytoplasm, the two components of WBC, are extracted, respectively, using different methods. First, a sub image containing WBC is separated from the original cell image. Then, scale-space filtering is used to extract nucleus region from sub image. Later, a watershed clustering in 3-D HSV histogram is processed to extract cytoplasm region. Finally, morphological operations are performed to obtain the entire connective WBC region. Through feature space clustering techniques, this scheme successfully avoids the variety and complexity in image space, and can effectively extract WBC regions from various cell images of peripheral blood smear. Experiments demonstrate that the proposed scheme performs much better than former methods.

e14515 Background: Pembrolizumab proves to be effective for clinical treatment of non-small cell lung cancer (NSCLC). The clinical application of pembrolizumab should be hinged on the magnitude of PDL1 expression justified by 22C3 assay on Dako platform. However, whether another diagnostic assay, SP142, can replace 22C3 in pembrolizumab-based immunotherapy thus far remains largely unknown. Methods: Forty-nine cases were randomly collected from 207 NSCLC patients with known PD-L1 expression detected by 22C3. Each case was stained with SP142 on ventana platform. The scores obtained with SP142 were compared with 22C3 , according to the interpretation of 22C3 standard. The concordance of PD-L1 expression between 22C3 and SP142 were assessed by weighted Kappa Coefficient and McNemar-Bowker test, respectively. Results: Based on Dako 22C3-IHC platform, 5 (10.2%), 9 (18.4%) and 35 (71.4%) of 49 cases were classified into groups of strongly positive, weakly positive, and negative for PD-L1, respectively. Yet, 37 (75.5%) of 49 cases had the same results with SP142 protocol (Kappa value: 0.472, p < 0.001). Six cases with weakly positive PD-L1, 3 cases with strongly positive PD-L1 and 1 case with negative PD-L1 according to the 22C3 were misdiagnosed as negative, weak positive and weak positive PD-L1 by SP142, respectively (McNemar-Bowker analysis: p = 0.037). When using the 50% tumor cell PD-L1 expression as the cut-off point, overall sensitivity and specificity of SP142 were 40% (95% [CI], 5.3%-85.3%) and 100% (95% CI, 87.1%-100%), respectively (Kappa value: 0.545, p = 0.009; McNemar-Bowker analysis: p = 0.125). When using the 1% tumor cell PD-L1 expression as the cut-off point, adoption of SP142 yielded the sensitivity of 57.1% (95% CI, 28.9%-82.3%) and the specificity of 97.1% (95% CI, 83.3%-99.9%), respectively (Kappa value: 0.608, p < 0.001; McNemar-Bowker analysis: p = 0.063). Conclusions: Compared with 22C3 assay, PD-L1 expression scores were usually underestimated by the SP142, and it has a higher specificity but lower sensitivity. Our findings collectively suggest that it is not applicable to adopt the SP142-PD-L1 IHC Ventana platform to stratify NSCLC patients for pembrolizumab-based immunotherapy.

Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

Water stress is the most common environmental threat that affects plants growing, so the diagnosis of water deficit is important and reasonable for plants’ irrigation and feature recognition. For plants, there are ecological and physiological regulatory mechanisms to adapt to water stress of soil, and to survive in adverse growing environment, which provides a signal and basis for diagnosis of water deficit. It has an important significance for plants’ reasonable irrigation to study plants’ water stress acoustic emission (referred to as AE) signal. The main purpose of the study is to establish plants’ water stress AE signal processing and analysis methods based on wavelet analysis, so as to lay a foundation for accurately grasping the plants’ water deficit information, achieving automatic detection of plants’ water stress and reasonable irrigation.

The principle and testing method of waste wood based panel connectors detecting system based on X-ray are introduced in this paper. In order to fix the shortcomings of small rightness, low contrast, slow gray change and serious noise pollution which X-ray image suffers from, the detecting image of waste wood-based panel connectors was processed by using the method of mathematical morphology. In this paper, the basic operation process and algorithm flowchart of mathematical morphology are proposed; the connectors were identified and features of their detecting image were extracted using cluster analysis. The analysis results of the experimental data show that the background information of X-ray image can be eliminated, and the information of the waste wood based panel connectors can be kept, and the characteristic parameters of the connectors can be identified simultaneously. The results provide a foundation for the future study of reprocessing of waste wood based panel.

Considering the path planning issue of an intelligent motion robot which will be used to acquire environment information and tree growing information in a planted forest, a kind of improved genetic algorithm based path optimization method is proposed. According to tree's distribution style in a planted forest the robot's working environment is modeled as many grids which are labeled either ordered couples or sequence numbers. Then how to initialize the population is introduced and the fitness function to optimize the motion path of an information acquiring robot in a planted forest is defined. Some genetic operators, such as selection operator, crossover operator and mutation operator, are designed and a kind of operator to detect redundant grids is put forward. The simulation under the VC++ Platform is carried out. The result indicates that the proposed algorithm is efficient way to plan a optimal path for the information acquiring motion robot in a planted forest.

This paper introduces the principle and testing method of the waste wood material connectors detecting system which is based on X-ray. For the shortcomings of small brightness, low contrast, slow gray change and serious noise pollution which X-ray image suffers from, the threshold segmentation method is chosen, which is based on genetic algorithm, as the segmentation method in detecting image of waste wood material connectors. The basic operation process and algorithm flowchart of Genetic algorithm are presented in the paper and the threshold is calculated maximum between cluster variance and maximum entropy associated with genetic algorithm. The experimental results show that this method can eliminate background information of X-ray image and keep information of the waste wood material connectors getting better segmentation effect. That laid the foundation for identifying the waste wood material connectors for the future.

Temperature and humidity control of the intelligent greenhouse is an important link of monitoring. This paper uses Surplus 16-bit single chip microcomputer as the core control of the system. Combined with wireless transceiver chip NRF401, USB interface device PDIUSBD12 and temperature and humidity module YXHT300U, we designed a wireless temperature and humidity monitoring system which used in intelligent greenhouse. This system is composed of one central station and several base stations. The datum of temperature and humidity are collected, and then are transmitted to the central station from the base stations which are monitored by the central station via the wireless transceiver/receiver-nRF401. The datum is received from the base stations to central station, then are transmitted to the computer where they are analyzed via the USB interface. The status of the wireless transceiver is monitored by the system software which made its reliability improved.

New service development (NSD) has emerged as an important research topic in service innovation and service marketing. NSD for experience enables customers get positive, unique and memorable experience and internal satisfaction. The concept of interactive experience leads to the identification of service design. Focusing on the service interaction between the customers and service providers, this paper presents a framework of service design which includes nine elements, and a process model of service design which realizes the integration of customer experience and service innovation strategy by experience needs identify, experience design, service system design, experience testing, and new service launch.

A fast algorithm is presented in this paper to track athletes in diving videos based on pose learning. In this algorithm, each diving motion is considered as a particular sequence of poses and each pose is represented by a set of landmarks. Firstly, the transformations between poses of successive frames are learned from sample videos. Then, in the video to be tracked, an initial pose is designated to the first frame and fits itself to the body contour by a curve-fitting algorithm. Later, in every following frame, the current pose transforms according to the parameters learned before, adjusts itself from the temporal information and fits itself to the body contour. In this way, the athlete in a diving video is effectively tracked. Experiments are carried out and the tracking results show that the proposed algorithm guarantees both efficiency and robustness.

Automated medical image processing and analysis offer a powerful tool for medical diagnosis. In this work, a decision-tree based white blood cell (WBC) classification scheme for peripheral blood images is developed. Based on the sufficient analysis on the characteristics of white blood cells, 10 efficient features are extracted, including size, shape, intensity and color, and a classification scheme based on decision-tree is designed to classify 6 different types of normal white blood cells. Especially, an efficient approach to separate two types of neutrophil is presented. The presented scheme is tested on 59 WBCs coming from 3 sets of blood images, which are obtained under different dying and imaging conditions. Results show classification accuracy above 96%.

In this paper, a novel white blood cell (WBC) segmentation scheme using scale-Space filtering and watershed clustering is proposed. In this scheme, nucleus and cytoplasm, the two components of WBC, are extracted respectively using different methods. First, a sub image containing WBC is separated from cell image. Then, scale-space filtering is used to extract nucleus region from sub image. Later, a watershed clustering in 3-D HSV histogram is processed to extract cytoplasm region. Finally, morphological operations are performed to obtain the entire connective WBC region. By using feature space clustering technique, this scheme successfully avoids the variety and complexity in image space, and can effectively extract various WBC regions from cell images of peripheral blood smear. Experiments demonstrate that the proposed scheme performs really well and HSV space is more appropriate than RGB space in WBC segmentation due to its low correlation.