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The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC.Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort.A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model.CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.

Purpose This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). Methods Information on patients with SBA, MSBA, and SRCSB (2004–2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan–Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. Results In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. Conclusion Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.

Background: EGFR and ERBB2 exon 20 insertion (Ex20ins) comprised a small subset of patients with EGFR mutations. The efficacy of immune checkpoint inhibitors (ICIs), especially in combination with chemotherapy, for these patients was still controversial. Methods: This retrospective study enrolled lung cancer patients harboring either EGFR or ERBB2 Ex20ins mutations. For comparison, lung cancer patients without EGFR mutations or with EGFR classic mutation were also enrolled as controls. All the patients were treated with platinum-based chemotherapy plus ICI (immunochemotherapy) or platinum-based chemotherapy. The demographic feature and clinical outcome of each patient were reviewed and analyzed.Results: When treated with immunochemotherapy, patients with EGFR/ERBB2 Ex20ins mutations (n=31) had poor PFS compared with those without EGFR mutations (n= 141, 5.0 mon and 11.2 mon, pp=0.625), ORR (37.5% vs 48.4%) and DCR (70.8% vs 77.4%). In the patients with EGFR/ERBB2 Ex20ins mutations, those treated with chemotherapy (n=54) had a longer PFS over those treated with immunochemotherapy (n=31, 6.5mon vs 5.0mon, p=0.066). Accordingly, chemoimmunotherapy was found to be significantly associated with poor PFS in multivariate analysis for the patients with EGFR/ERBB2 Ex20ins mutations. In the EGFR Ex20ins subgroup, the addition of bevacizumab to chemotherapy (n=20) led to longer PFS over chemotherapy alone (n=16, 8.8mon and 5.2mon, p=0.082) or immunochemotherapy (n=15, 8.8mon and 5.0mon, p=0.097). Similarly, in the ERBB2 subgroup, the combination of bevacizumab and chemotherapy achieved a numerically long PFS over chemotherapy alone (9.1 mon and 4.5 mon, p=0.253).Conclusion: This study showed that platinum-based chemotherapy plus ICI had limited efficiency compared to platinum-based chemotherapy for patients with EGFR/ERBB2 Ex20ins. Chemotherapy plus bevacizumab maybe a potential scheme for these patients.

Only a minority of patients benefit from immune checkpoint inhibitors (ICIs) therapy, although they have become the standard of care for patients of non-small cell lung cancer (NSCLC) without driver mutations. Zoledronic acid (ZA) enhances the anti-tumor efficacy of endocrine therapy, chemotherapy and targeted therapy. However, little is known about the effect of ZA on the clinical outcomes of ICIs, or its possible mechanisms.Patients with advanced NSCLC treated with ICIs alone or in combination with ZA were recruited. The clinical efficacy was compared between the two cohorts. We used an LL2 mouse model to confirm the combined effects of ZA with ICIs. Immune cell populations and cytokines in the tumor microenvironment and circulation were assayed and analyzed.The median PFS for the patients treated with and without ZA was 5.4 months and 2.8 months, respectively. The combination group showed a higher rate of disease control. In the mouse LL2 lung cancer model, tumor growth was significantly inhibited in mice treated with the combination treatment. More CD8 + IFN-γ + T cells and γδ T cells, and fewer CD11b cells were found in the circulation and TILs in the combination group. Anti-tumor cytokines INF-γ and IL-18 were elevated in the sera after combination therapy.Our study provides preclinical and clinical evidence to show that ZA could improve the therapeutic effects of ICIs. This effect was likely related to the activation of immune cells and elevated cytokines, which provided a new way to improve the effect of ICIs therapy, and is worth exploring further.

Currently, the predictive role of POLE mutations for immunotherapy is under intense investigation. The POLE gene encodes one of the four subunits of DNA polymerase important for DNA replication and repair. POLE mutations are related to other favorable predicative factors such as high expression of PD-L1, high TMB, and infiltration of CD8+ cells in the tumor microenvironment. No formal clinical trials studied the efficacy of immunotherapy in lung patients harboring POLE mutation, and only few cases were mentioned in the literature. Moreover, lung cancer patients are prone to brain metastasis, which is notorious for the unresponsiveness to chemotherapy. The efficacy of immunotherapy for brain metastasis is still controversial. Here, we described a case of a POLEmt non-small-cell lung cancer (NSCLC) patient with brain metastasis who was treated with immunotherapy. His brain lesions disappeared after treatment. Our report strongly supported the benefit of immune-combined therapy for advanced NSCLC patients with POLE mutation, even with brain metastasis.

The fifth-generation technology is emerging with various real-time applications that demand high data rate. The number of connected devices is expected to increase. However, spectral and energy resources are limited. Therefore, it is challenging to meet users satisfaction. Thus, the necessity for a structure that can sustain real-time performance of wireless communication systems is pressing. This paper presents an efficient radio resource allocation scheme using regularized particle filter with optimized kernel size and kernel bandwidth, and Monte Carlo Markov chain move step based on metropolis algorithm is used to estimate next state of channel. Channel state is calculated from the temporal channel correlation using maximum likelihood estimation. Throughput for the next user state is predicted using posterior probability with normalized weights. The main aim of this paper is to observe the user throughput. The problem is modeled as throughput maximization subject to channel state. The optimization problem is formulated as a non convex optimization and solved using branch and bound method. It has been shown in the simulation results that the average throughput is increased by ${\text{5.94}\%}{\text{--52.98}\%}$ compared to sequential importance sampling with resampling (SISR) method. Therefore, the RPF scheme has proved to be efficient by its remarkable increase in user throughput compared to the SISR particle filter algorithm.

BackgroundIt’s widely accepted that Obesity is closely associated with the elevated risk of various cancers. However, there’s no consensus regarding the impact of body mass index (BMI) on the outcome of targeted therapy targeted-therapy efficacy in lung cancer. MethodsTreatment-naive advanced NSCLC patients harboring EGFR mutation prescribed TKI were screened and enrolled from 3 referral centers. Patients enrolled from West China Hospital were set as the training group, and the others as validation group. Both the demographic features including mutation status and BMI, and therapeutic effects including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were collected.ResultsIn the training group, patients were dichotomized according to their BMI. Those with higher BMI (>22.5) achieved a prolonged PFS compared with those with lower BMI (13.8 and 10.9 mon, HR: 0.68; 95% CI: 0.54-0.86; P = 0.001), and the priority persisted irrespective of different cut-off values. Besides, the favorable association of high BMI with long PFS was confirmed in the validation cohort (14.0 and 11.6 mon, P=0.089) and whole cohort (13.7 and 11.3 mon, P=0.004). In the multivariate analysis, BMI was an independent favorable factor of PFS, together with gender, albumin, and performance. By integration of these factors, a nomogram to predict to 1-,3-year PFS was established. Finally, higher BMI was associated with better objective response rate (ORR, 74% and 69%) and longer overall survival (OS, 41.4 and 33.5 mon, P=0.011). ConclusionHigh BMI was independently associated with efficacy of EGFR-TKI treatment in advanced NSCLC patients.

Nowadays, it has been reported by researchers that the biggest spectrum assignment problem is not scarcity of radio resources, but rather spectrum utilization. Cognitive radio (CR) emerges as a potential candidate to increase spectral efficiency. However, for a single CR to accurately detect the activity state of PUs, many factors have made it hard. Therefore, Cooperate Spectrum Sensing (CSS) has been introduced to improve detection performance; but this introduces security problem due to the presence of malicious attackers; which can be for instance incumbent emulation by Primary User Emulation Attacker (PUEA). In this paper, A Modified Advanced Orthogonal Matching Pursuit (MAOMP) is proposed to detect the presence of PEUA in a CR network based on locations of the users. Restricted Issometry Property (RIP) is used to evaluate the performace. This paper presents a fast, accurate and efficient approach to detect PUEAs present in the network.

Background: Epithelial growth factor receptor tyrosine kinase inhibitor (EGFR TKI) revolutionize the standard of care for advanced non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutation. Liver toxicity is the dose-limiting factor for TKI but its importance is largely overlooked. Here the relationship between the elevation of transaminase and progression-free survival (PFS) was explored. Methods: This was a retrospective study where patients with advanced NSCLC were screened. And those treatment-naïve and with sensitive EGFR mutation who were prescribed with EGFR TKI were enrolled. The highest level of transaminase (alanine aminotransferase, ALT, and aspartate transaminase, AST) during the treatment course was recorded. Results: Totally 208 patients were recruited, and most of them (48.6%) took gefitinib. The whole cohort achieved a median PFS of 11.2 months (95% CI: 10.0-12.3 m). 73 (35.1%) patients had elevated transaminase and most was attributed to gefitinib (n=43, 42.5%). Specifically, ALT was elevated in 65 patients (31.3%) while AST in 24 patients (11.5%). Again, gefitinib was associated with more cases of ALT (40.6%) and AST (17.8%) elevation. The elevation of AST was not related to PFS (P=0.259, HR=0.751, 95% CI: 0.464-1.214). Interestingly, those with normal ALT level had a longer PFS (12.6m, 95% CI: 10.6-14.5 m) than those with elevated ALT (9.5m 95% CI: 7.9-11.0 m, P=0.025, HR=0.682, 95% CI: 0.488-0.953). The inverse relationship was confirmed in the COX regression analysis (P=0.047). Conclusion: This study revealed the side effects of elevated ALT was inversely related to the PFS of EGFR TKI treatment. The liver impairment by TKI should not be overlooked.

e20531 Background: Both EGFR-TKI and pemetrexed doublet chemotherapy (P) are two effective therapies in advanced NSCLC patients with EGFR mutant tumors. But which one should be used in first-line remains controversial. Methods: This was a retrospective study where patients prescribed with EGFR-TKI (gefitinib or icotinib) from Jan 2013 to Jan 2016 were screened. Patients must have metastastic diseases harboring TKI-sensitizing EGFR mutation. They must be older than 18 years, and have evaluable target lesions. Whether TKI or P was used in the first line, it must be switched to the other in the second line. PFS in both first line (PFS1) and second line (PFS2) was collected. Results: We screened totally 550 patients (gefitinib n = 455, icotinib n = 95) to enroll a cohort of 36 patients. They were all adenocarcinoma except 1 adenosquamous carcinoma. Gender (M or F), PS (0 or 1), mutation type (Exon19Ddel or other) were equally distributed. The median age was 50.5 years. For the whole cohort, the total PFS (PFS1+PFS2) was 18.1 m (95%CI: 15.2-21.1 m). For those (n = 24) receiving first-line TKI, PFS1, PFS2, and total PFS were 10.3 m, 6.6 m, and 19.2 m. And for those receiving first-line P (n = 12), they were were 3.4 m, 11.5 m, and 16.5m. The total PFS in both groups did not differ significantly (p = 0.548). Conclusions: Our results argued the sequential usage of TKI and P achieve a comparable PFS irrespective of the sequence.

In this paper, we re-annotated the genome of Pyrobaculum aerophilum str. IM2, particularly for hypothetical ORFs. The annotation process includes three parts. Firstly and most importantly, 23 new genes, which were missed in the original annotation, are found by combining similarity search and the ab initio gene finding approaches. Among these new genes, five have significant similarities with function-known genes and the rest have significant similarities with hypothetical ORFs contained in other genomes. Secondly, the coding potentials of the 1645 hypothetical ORFs are re-predicted by using 33 Z curve variables combined with Fisher linear discrimination method. With the accuracy being 99.68%, 25 originally annotated hypothetical ORFs are recognized as non-coding by our method. Thirdly, 80 hypothetical ORFs are assigned with potential functions by using similarity search with BLAST program. Re-annotation of the genome will benefit related researches on this hyperthermophilic crenarchaeon. Also, the re-annotation procedure could be taken as a reference for other archaeal genomes. Details of the revised annotation are freely available at http://cobi.uestc.edu.cn/resource/paero/