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BACKGROUND The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P 2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. CONCLUSIONS The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

Organic solid wastes (OSWs) should be regarded as valuable resources rather than dead-end landfill waste that causes public health and odor concerns. Anaerobic digestion (AD) is an ideal approach for managing organic solid waste issues and involves using a group of anaerobic microorganisms to transform OSWs into useful products. In this review, over 100 publications related to AD of OSWs have been compiled, discussed, and analyzed. A comprehensive analysis of the environmental and safety impacts of AD, its key environmental factors, co-digestion, and pretreatment, as well as the AD of OSWs by various anaerobic microbes uncovered by high throughput sequencing-based approaches, is presented. The purpose of this review is to provide an outline of the current knowledge of AD processes from a multi-angle perspective. A comprehensive understanding of AD of OSWs and genome-enabled biology development could be helpful for providing up-to-date knowledge of AD, developing it, overcoming its drawbacks and, ultimately, improving global waste control for more efficient environmental management. © 2018 Society of Chemical Industry.

Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1-induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1-induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p l 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel-cisplatin-5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin-5-fluorouracil (PF) (PF and docetaxel-cisplatin [TP]; all p l 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1-induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p l 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p0·0001), disease-free survival (HR 3·51, 2·43-5·07; p0·0001), and overall survival (HR 3·22, 2·18-4·76; p0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status.The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.The National Natural Science Foundation of China, the National ScienceTechnology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the HealthMedical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.

Objectives To investigate the role of sequential chemoradiotherapy (SCRT; induction chemotherapy [IC] followed by intensity-modulated radiotherapy [IMRT]) in stage II and low-risk stage III–IV nasopharyngeal carcinoma (NPC). Materials and methods Four well-matched groups were individually generated using propensity score matching in patients (n = 689) with stage II (SCRT vs. concurrent chemoradiotherapy [CCRT], SCRT vs. IMRT alone) and low-risk stage III–IV NPC (SCRT vs. CCRT, SCRT vs. IC + CCRT). Five-year overall/disease-free/locoregional relapse-free/distant metastasis-free survival (OS/DFS/LRRFS/DMFS) and acute hematological toxicities were compared between groups. The value of SCRT was further investigated in multivariate analysis and subgroup analysis by adjusting for covariates and limiting IC-to-IMRT time interval, respectively. Results SCRT led to equivalent survival outcomes compared to CCRT/IMRT alone and CCRT/IC + CCRT in stage II and low-risk stage III–IV NPC, respectively (all P > .050). In multivariate analysis, patients with stage II NPC treated by SCRT obtained higher DMFS (AHR = 0.22, 95% CI = 0.05–1.00, P = .050), but not OS, DFS or LRRFS, compared to patients receiving CCRT; non-significant differences were observed between SCRT and other treatments. SCRT with short IC-to-IMRT time interval (≤70 days) achieved higher 5-year survival rates than IMRT alone (DMFS: P = .046), CCRT (stage II NPC; OS: P = .047; DMFS: P = .020) and IC + CCRT (DFS: P = .041). Moreover, SCRT was associated with higher, equivalent and lower frequencies of acute hematological toxicities than IMRT alone, CCRT and IC + CCRT, respectively. Conclusion SCRT is mainly beneficial in stage II NPC, leading to better DMFS and/or equivalent acute hematological toxicities compared to CCRT/IMRT alone. CCRT is still the best choice for low-risk stage III–IV NPC.

To comprehensively understand the profile of free-living bacteria and potential bacterial pathogens in sewage treatment plants (STPs), this study applied high-throughput sequencing-based metagenomics approaches to investigate the effects of activated sludge (AS) treatment process and ultraviolet (UV) disinfection on the community of bacterial pathogens in two full-scale STPs. A total of 23 bacterial genera were identified as free-living bacteria, and 243 species/OTU97% were identified as potential bacterial pathogens, 6 of which were confidently detected in the STPs (with the total abundances ranging from 0.02 to 14.19%). Both diversity and relative abundance of the detected bacterial pathogens decreased obviously after AS treatment process (p

To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally‐advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Using the NPC‐specific database from the established big‐data intelligence platform at Sun Yat‐Sen University Cancer Center, 583 non‐disseminated, locoregionally‐advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m2 after IC (range, 40‐300 mg/m2); only 74 patients (12.7%) achieved CCD >200 mg/m2. Patients receiving >200 mg/m2 CCD did not show significantly improved 5‐year overall survival (OS) (HR = 1.19; 95% confidence intervals [CI] 0.69‐2.06, P = .53) and progression‐free survival (PFS) (HR = 1.03; 95% CI: 0.63‐1.68, P = .92) compared with patients receiving 160 mg/m2 and CCD < 160 mg/m2 in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein–Barr virus deoxyribonucleic acid (EBV DNA)

In this study, metagenomic analyses were combined with cultivation-based techniques as a nested approach to identify functionally significant bacteria for sulfadiazine biodegradation within enrichment communities. The metagenomic investigations indicated that our previously isolated sulfadiazine degrader, Arthrobacter sp. D2, and another Pimelobacter bacterium concomitantly occurred as most abundant members in the community of an enrichment culture that performed complete sulfadiazine mineralization for over two years. Responses of the enriched populations to sole carbon source alternation further suggested the ability of this Pimelobacter member to grow on 2-aminopyrimidine, the most prominent intermediate metabolite of sulfadiazine. Taking advantage of this propensity, additional cultivation procedures have enabled the successful isolation of Pimelobacter sp. LG209, whose genomic sequences exactly matched that of the dominant Pimelobacter bacterium in the sulfadiazine enrichment culture. Integration of metagenomic investigations with the physiological characteristics of the isolates conclusively demonstrated that the sulfadiazine mineralization in a long-running enrichment culture was prominently mediated by primary sulfadiazine-degrading specialist strain Arthrobacter sp. D2 in association with the 2-aminopyrimidine-degrading partner strain Pimelobacter sp. LG209. Here, we provided the first mechanistic insight into microbial interactions in steady sulfadiazine mineralization processes, which will help develop appropriate bioremediation strategies for sulfadiazine-contaminated hotspot sites.

Long noncoding RNAs (lncRNAs) play an important role in the development and progression of cancers. However, the clinical significances of lncRNAs and their functions and mechanisms in nasopharyngeal carcinoma (NPC) remain largely unclear. Methods: Quantitative RT-PCR was used to determine DANCR expression and Kaplan-Meier curves were used to evaluate its prognostic value. RNA sequencing followed by bioinformatic analysis was performed to determine the potential function of DANCR. In vitro and in vivo experiments were conducted to investigate its biological effects. DANCR-interacting proteins were identified by RNA pull-down assay followed by mass spectrometry and western blotting, and then confirmed by RNA immunoprecipitation (RIP) assays. Results: Our previous microarray analysis identified a metastasis-associated lncRNA DANCR. Here, we found that DANCR was upregulated in NPC, especially in those with lymph lode metastasis, and its upregulation could predict poor survival. We then constructed a prognostic predictive model. RNA sequencing followed by bioinformatic analysis revealed that DANCR was responsible for NPC metastasis and hypoxia phenotype. Functional studies showed that DANCR promoted NPC cell invasion and metastasis in vitro and in vivo. Further investigation suggested that DANCR could increase HIF-1α mRNA stability through interacting with the NF90/NF45 complex. Additionally, overexpression of HIF-1α in DANCR knockdown cells restored its suppressive effects on NPC cell migration and invasion. Conclusions: Taken together, our results suggest that DANCR acts as a prognostic biomarker and increases HIF-1α mRNA stability by interacting with NF90/NF45, leading to metastasis and disease progression of NPC.

Background and purpose While parotid-sparing intensity modulated radiotherapy (IMRT) has demonstrated superiority to conventional RT in terms of observer-rated xerostomia, patient-reported outcome measures (PROMs) have only marginally improved. We investigated how sparing all salivary glands affects PROMs. Materials and methods Patients treated to the bilateral neck with all-gland-sparing IMRT answered xerostomia (XQ) and head-and-neck quality of life (HNQOL) questionnaires. Longitudinal regression was used to assess the relationship between questionnaire scores and mean bilateral parotid gland (bPG), contralateral submandibular gland (cSMG), and oral cavity (OC) doses. Marginal R 2 and Akaike information criterion (AIC) were used for model evaluation. Results 252 patients completed approximately 600 questionnaires. On univariate analysis, bPG, cSMG, and OC doses significantly correlated with XQ-summary, XQ-eating, and HNQOL-eating scores. On multivariate analysis, bPG and OC doses significantly correlated with XQ-summary, XQ-eating, and HNQOL-eating scores; and cSMG dose with HNQOL-summary. Combining doses to all three structures yielded the highest R 2 for XQ-summary, XQ-rest, XQ-eating, and HNQOL-eating. In the 147 patients who received a mean cSMG dose ≤39 Gy, there were no failures in contralateral level IB. Conclusions Reducing doses to all salivary glands maximizes PROMs. A cSMG dose constraint of ≤39 Gy does not increase failure risk.

Background Little is known about the nature of metastasis to small cervical lymph nodes (SCLNs) in the patients with nasopharyngeal carcinoma (NPC) examined by using 18-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients. Methods Magnetic resonance images (MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage. Results In total, 2082 SCLNs were identified, with 808 (38.8%) ≥ 5 and

Recycling of spent lithium-ion batteries (LIBs) has become a global issue because of the potential environment risks raised by spent LIBs as well as high valuable metal content remaining in them. Although bioleaching is an environmentally friendly method to recover metals from spent LIBs, the commonly utilized bioleaching bacterial consortia or strains enriched/isolated from acidic environments cannot be applied at large scales owing to their long leaching cycle and poor tolerance to organic compounds. Here, two bioleaching consortia were enriched in 60 days from neutral activated sludge and were identified phylogenetically divergent from the documented bioleaching bacteria. The results showed that the novel consortia shortened the leaching cycle almost by half when compared to the previous reported consortia or strains, of which one consortium dominated by Acidithiobacillus ferrooxidans displayed high bioleaching efficiency on LiMn2O4, as 69.46% lithium (Li) and 67.60% manganese (Mn) were leached out in seven days. This consortium was further domesticated using cathodic materials for 100 days and proved consisted of three mixotrophs and two chemoautotrophs, three of which were novel species from the genera Sulfobacillus and Leptospirillum. More genes coding for proteins that utilize organic compounds were annotated in the metagenomic assembled genomes (MAGs) than previously reported. A mutualistic relationship between mixotrophs and chemoautotrophs was suggested to help the consortium surviving under either organic- rich or shortage environments. The results discovered that novel bioleaching bacteria with shorter leaching cycle and higher tolerance to organics could be enriched from non-acidic environments, which showed high potential for the metal recovering from spent LIBs or other organic-rich environments.

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications.

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity‐modulated radiotherapy (IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log‐rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end‐point was overall survival (OS); secondary end‐points were disease‐free survival (DFS), locoregional relapse‐free survival (LRRFS), and distant metastasis‐free survival (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end‐points. Five‐year survival for non‐anemia and non‐CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P

We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number. The mutational and neoepitope features of the tumor were compared according to the four TMITs. We found that PD-L1/CD8A/CYT subgroups could not distinguish different mutation and neoantigen numbers in certain tumor types such as glioblastoma multiforme, prostate adenocarcinoma, and head and neck and lung squamous cell carcinoma. For the remaining tumor types, compared with TIMT II (low PD-L1 and CD8A/CYT), TIMT I (high PD-L1 and CD8A/CYT) had a significantly higher number of mutations or neoantigens in bladder urothelial carcinoma, breast and cervical cancer, colorectal, stomach and lung adenocarcinoma, and melanoma. In contrast, TMIT I of kidney clear cell, liver hepatocellular, and thyroid carcinoma were negatively correlated with mutation burden or neoantigen numbers. Our findings show that the TMIT stratification proposed could serve as a favorable approach for tailoring optimal immunotherapeutic strategies in certain tumor types. Going forward, it will be important to test the clinical practicability of TMIT based on quantification of immune infiltrates using mRNA-seq to predict clinical response to these and other immunotherapeutic strategies in more different tumors.

The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into “biopsy of the primary site or neck.” Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC. A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy. Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89–1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81–1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes. The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

The discovery of complete ammonia oxidizer (comammox) has fundamentally upended our perception of the global nitrogen cycle. Here, we reported four metagenome assembled genomes (MAGs) of comammox Nitrospira that were retrieved from metagenome datasets of tap water in Singapore (SG-bin1 and SG-bin2), Hainan province, China (HN-bin3) and Stanford, CA, USA (ST-bin4). Genes of phylogenetically distinct ammonia monooxygenase subunit A (amoA) and hydroxylamine dehydrogenase (hao) were identified in these four MAGs. Phylogenetic analysis based on ribosomal proteins, AmoA, hao and nitrite oxidoreductase (subunits nxrA and nxrB) sequences indicated their close relationships with published comammox Nitrospira. Canonical ammonia-oxidizing microbes (AOM) were also identified in the three tap water samples, ammonia-oxidizing bacteria (AOB) in Singapore's and Stanford's samples and ammonia-oxidizing archaea (AOA) in Hainan's sample. The comammox amoA-like sequences were also detected from some other drinking water systems, and even outnumbered the AOA and AOB amoA-like sequences. The findings of MAGs and the occurrences of AOM in different drinking water systems provided a significant clue that comammox are widely distributed in drinking water systems.

The subgroups of patients with nasopharyngeal carcinoma (NPC) who benefit from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) remain unclear.We established prognostic nomograms for overall survival (OS) and disease-free survival (DFS), and validated the nomograms in 1230 patients with NPC and subgroup of 923 patients with locoregionally advanced NPC (LANPC). Three well-matched risk groups (i.e., low, intermediate and high risk) were created via recursive partitioning and 1-to-1 propensity score matching; IC+CCRT was compared with CCRT in each risk group.Histological type, T category, N category, plasma Epstein-Barr virus deoxyribonucleic acid (and the same factors plus age and neutrophil-lymphocyte ratio) were included in the nomograms for DFS (and OS). Both nomograms had higher c-indexes than the 7th edition staging system in both NPC/LANPC (all P-values≤0.010). The nomogram for OS also had a higher c-index in LANPC than the 8th edition staging system (P-value=0.052). OS was significantly different between all three risk groups in the individualized risk stratification (all P-values0.001), while the 7th and 8th edition staging systems failed to clearly separate OS for stage II and III disease (P-value=0.415 and 0.347, respectively). IC+CCRT improved OS in intermediate and high risk patients with LANPC compared to CCRT alone (P-value0.001 and P-value=0.002, respectively).These prognostic nomograms could accurately guide treatment of individual patients with NPC. IC+CCRT could improve OS for patients with LANPC at intermediate to high risk.

The effect of socioeconomic factors on receipt of definitive treatment and survival outcomes in non‐metastatic head and neck squamous cell carcinoma (HNSCC) remains unclear. Eligible patients (n = 37 995) were identified from the United States Surveillance, Epidemiology and End Results (SEER) database between 2007 and 2012. Socioeconomic factors (i.e., median household income, education level, unemployment rate, insurance status, marital status and residence) were included in univariate/multivariate Cox regression analysis; validated factors were used to generate nomograms for cause‐specific survival (CSS) and overall survival (OS), and a prognostic score model for risk stratification. Low‐ and high‐risk groups were compared for all cancer subsites. Impact of race/ethnicity on survival was investigated in each risk group. Marital status, median household income and insurance status were included in the nomograms for CSS and OS, which had higher c‐indexes than the 6th edition TNM staging system (all P < 0.001). Based on three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income

BACKGROUND Chemotherapy, target therapy, and immunotherapy are increasingly being used in the systematic treatment of nasopharyngeal carcinoma (NPC), during which the occurrence of hepatitis B virus (HBV) reactivation might increase. However, data regarding HBV screening and reactivation and the clinical management of NPC patients with HBV infections are lacking. This study was aimed at clarifying the risk of reactivation for NPC patients on different regimens while providing evidence concerning HBV screening and management in an endemic area. METHODS With the NPC database from an established big-data intelligence platform at Sun Yat-Sen University Cancer Center in China, NPC patients who were diagnosed between 2008 and 2016 and underwent HBV screening and regular monitoring of liver enzymes and HBV deoxyribonucleic acid (DNA) were analyzed. RESULTS Among the 46,919 patients identified, the HBV screening rate was 24.8% (11,616 of 46,919). Among the screened patients with an HBV infection, regular monitoring of liver enzymes and HBV DNA occurred for 563 patients. The incidence of HBV reactivation and HBV-related hepatitis was 9.1% (51 of 563) and 2.5% (14 of 563), respectively. The reactivation risk varied for different treatments and regimens and ranged from 0.0% to 21.4%. Detectable baseline HBV DNA (odds ratio [OR], 2.93; P < .01), the presence of liver metastasis at diagnosis (OR, 7.19; P < .01), and antiviral prophylaxis (OR, 0.29; P < .01) were significantly associated with reactivation. CONCLUSIONS In NPC patients with chronic HBV infections on high-risk regimens, the reactivation risk is similar to or exceeds the risk associated with other immunosuppressive therapies for which screening and prophylaxis are recommended. Our findings, therefore, support HBV screening and prophylaxis for these patients, whereas regular monitoring might be appropriate for patients with resolved HBV infections or those receiving low-risk regimens. Cancer 2017;123:3540-9. © 2017 American Cancer Society.

An alternative process for anaerobic wastewater treatment with methane recovery is to elongate the carbon chain of volatile fatty acids (VFAs) with a formation of medium chain carboxylic acids (MCCAs), e.g. n-caproic acid with higher monetary value. A potential electron donor is glycerol as a surplus byproduct from the rapid growth of waste-derived biodiesel industry. In the current approach, an industrial chemical, 1,3-propanediol (1,3-PDO) is produced from crude glycerol along with a formation of other soluble byproducts including ethanol and volatile fatty acids (VFAs), which necessitates a significant amount of energy input for separation and purification. To circumvent the energy sink requirement and upcycle both the wastewater treatment process and the biodiesel industry, it is highly beneficial to produce a valuable secondary product from the byproducts. This pioneer study reports on thermodynamic and physiological insights gained into the co-production of 1,3-PDO and caproate from glycerol. Thermodynamics analysis demonstrated that a higher pH range is more favorable when either glycerol or ethanol acting as an electron donor, whereas a high partial pressure (27% at 1 atm) and a low pH (≤5.5) are advantageous for caproate formation with hydrogen. With the glycerol-to-acetate molar ratio of 4 and pH of 7, the physiological experiments achieved a co-production of 1,3-PDO and caproate. However, the caproate yield was low and found to be kinetic-limited. Caproate formation was significantly increased by the intermediate ethanol addition with the optimal mono-caproate formation obtained at the ethanol-to-acetate molar ratio of 3. A synergistic relationship was evinced through microbial characterization, resulting in Clostridium kluyveri and some bacteria with function of converting glycerol to VFAs. This study demonstrates that sufficient ethanol produced as an intermediate is capable of enhancing caproate formation in a synergistic pathway along with 1,3-PDO. The knowledge gleaned paves new avenues for the biodiesel industry by upcycling the byproduct crude glycerol into 1,3-PDO and caproate.

Aim of the study Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). Methods Patients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. Results Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14). Conclusion Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. Registration number NCT00677118 .

Background: Given the distinct biological characteristics and regional distribution of nasopharyngeal carcinoma (NPC) compared with other head and neck cancers, and uncertainties regarding therapeutic strategies, physicians require high-quality clinical practice guidelines (CPGs) to provide transparent recommendations for NPC treatment. This study aimed to critically appraise the quality of NPC CPGs and assess the consistency of their recommendations. Methods: We identified CPGs that provided recommendations on the diagnosis and management of NPC published up to December 2015. Four investigators independently appraised CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Key recommendations by CPGs were also evaluated. Results: A total of 7 CPGs were eligible for this study: 5 produced by professional organizations or governmental agencies and 2 were developed based on expert consensus. Of the 6 AGREE II domains, the applicability domain scored consistently low across CPGs (range, 13.5%-30.2%); no CPG achieved a score of >50% in all 6 domains. The scope and purpose domain (≥73.6% for 4 CPGs) and editorial independence domain (≥75.0% for 6 CPGs) scored highest. Of the 23 AGREE II items, 9 scored less than half of the points available in all 7 CPGs. The recommendations by CPGs were consistent in general; heterogeneity mainly existed among recommended therapeutic strategies. Conclusions: Variation exists in NPC CPG development processes and recommendations. Increased efforts are required to make comprehensive resources available to guide healthcare providers and enhance delivery of high-quality, evidence-based care for NPC. International collaboration is necessary to enable the development of high-quality and regionally relevant CPGs for NPC.

Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain.

Background: Literature pertaining to prophylactic inguinal nodal treatment for anal adenocarcinoma in China is scarce. Methods: In this retrospective study, we analyzed 126 patients from 1965 to 2015. Among these, 67 patients received surgery only, 18 patients received chemoradiotherapy only, 27 patients received a combination of both, and the remaining 14 patients received palliative treatment. Results: The median follow up period was 30 months. The 1-year, 3-year, and 5-year overall survival rates were 85.8%, 62.5%, and 43.4%, respectively. The 5-year overall survival was 46.9% for patients with negative inguinal lymph nodes and 19.1% for patients with positive inguinal lymph nodes (p=0.007). The overall 5-year inguinal node relapse-free survival was 83.0%. The 5-year inguinal node relapse-free survival was 87.5% for stage I, 86.9% for stage II, and 76.5% for stage III cancers. Among those with negative inguinal nodes, the 5-year inguinal node relapse-free survival was 85.7% for negative regional lymph nodes and 75.4% for positive regional lymph nodes (p=0.089). Conclusion: Inguinal lymph node is a high-risk subclinical area. Prophylactic inguinal nodal treatment is necessary for patients with anal adenocarcinoma irrespective of positive or negative inguinal lymph nodes.

Background: Value of neoadjuvant chemotherapy (NACT) is still controversial in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Based on competing risk analysis model, we aim at evaluating the efficacy of NACT in decreasing cancer-specific mortality for LA-NPC (except T3-4N0) treated by intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with LA-NPC were retrospectively reviewed. The cumulative incidence of cancer-specific and non-cancer-specific (competing) mortality was determined by univariate and multivariate competing risk analysis. Results: 542 (56.6%) patients received NACT using docetaxel with cisplatin (TP) or fluorouracil with cisplatin (PF) regimens. The median follow-up duration was 57.23 months (range, 1.27-78.53 months). In total, 161/957 (16.8%) patients died, with 140 cancer-specific and 21 non-cancer-specific deaths were observed, respectively. In univariate analysis, the 3- and 5-year cumulative cancer-specific mortality rates for NACT vs. non-NACT group were 8.58% vs. 7.32% and 14.74% vs. 14.52% (P = 0.95), respectively. With regard to competing mortality, the 3- and 5-year cumulative rates (0.93% vs. 1.22% and 1.31% vs. 3.06%; P = 0.196) were comparable between the two groups. Multivariate competing risk analysis established NACT as an independent prognostic factor in decreasing cancer-specific mortality (HR, 0.681; 95% CI, 0.488-0.951; P = 0.016) and overall mortality (HR, 0.654; 95% CI, 0.471-0.909; P = 0.011). Conclusions: NACT may be a powerful approach in decreasing cancer-specific mortality and overall mortality in LA-NPC treated by IMRT, and our findings would strengthen the role of NACT.

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P

BACKGROUND Tumor response to neoadjuvant chemotherapy using the regimen of cisplatin and 5-fluorouracil could define high-risk patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, the regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) appears to be more effective than the regimen of cisplatin and 5-fluorouracil. Therefore, one needs to redefine the high-risk subpopulation of patients receiving neoadjuvant chemotherapy with TPF. METHODS A total of 231 patients from a randomized phase 3 trial with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC (except T3-T4N0 disease) who were receiving treatment with the TPF regimen were enrolled. Patient survival rates between different groups were compared. RESULTS Of the 231 patients, the overall response to neoadjuvant chemotherapy was a complete response (CR) for 26 (11.3%), a partial response (PR) for 184 patients (79.6%), and stable disease (SD) for 21 patients (9.1%). Univariate analysis revealed the 3-year failure-free survival (FFS) rates in the CR (88.5% vs 61.9%; P =.017) and PR (81.2% vs 61.9%; P = .01) groups, and the 3-year overall survival rates for the CR (96.2% vs 76.2%; P =.048) and PR (93.4% vs 76.2%; P =.025) groups were obviously higher compared with that of the SD group. In multivariate analysis, CR was established as a favorable prognostic factor for FFS (hazard ratio [HR], 0.210; 95% confidence interval [95% CI], 0.057-0.779 [P =.02]), and PR for FFS (HR, 0.447; 95% CI, 0.213-0.936 [P =.033]) and OS (HR, 0.361; 95% CI, 0.132-0.986 [P =.047]) when compared with SD. No survival difference was observed between the CR and PR groups. CONCLUSIONS Tumor response to TPF may be a properly powerful prognosis predictor and help to develop individualized treatment strategies for patients with locoregionally advanced NPC. Cancer 2017;123:1643–1652. © 2017 American Cancer Society.

Background The purpose of this study was to determine the predictive value of pretreatment serum uric acid (SUA) for metastasis in locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy. Methods This retrospective study examined 1063 patients with locally advanced NPC. Multivariate survival analysis was used. Results High pretreatment SUA level (>353.4 μmol/L) independently predicted distant metastasis-free survival (p = .013) and was associated with high white blood cell (p = .005), lymphocyte counts (p < .001), and male sex (p < 0.001). In addition, SUA levels were significantly elevated in patients with T1 to T3 classification (p = .042). For patients with subsequent lung metastases after treatment, markedly higher pretreatment SUA levels were detected compared with patients who had other distant metastases (p =.012) and patients without distant metastasis (p = .024). Conclusion Pretreatment SUA may be a useful biomarker for evaluating treatment options for patients with locally advanced NPC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 492–497, 2017

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor., Methane metabolism by some lineages of Archaea contributes to the cycling of carbon on Earth. Here, the authors show high diversity of methyl-coenzyme M reductase (Mcr), a key enzyme associated with archaeal methane/alkane metabolism, in hot spring Archaea, and investigate their ecological roles and evolution.

Background and Purpose: Evidence for induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) in nasopharyngeal carcinoma (NPC) was derived from landmark clinical trials excluding the T3N0, T3N1, T4N0 subgroups. This study used Epstein-Barr virus (EBV) DNA to select IC beneficiaries from the three subgroups. Materials and Methods: Significant predictors of overall survival (OS) were identified using multivariate Cox analyses. Risk stratification was generated using recursive partitioning analysis (RPA). IC+CCRT was compared with CCRT in each risk stratification and in different subgroups. Individual-level data from a clinical trial (NCT01245959) was used for validation. Results: Gender and EBV DNA were included in RPA-generated risk stratification, categorizing patients into low-risk (EBV DNA

Background The lack of pure cultures limits our understanding into 99% of bacteria. Proper interpretation of the genetic and the transcriptional datasets can reveal clues for the enrichment and even isolation of the not-yet-cultured populations. Unraveling such information requires a proper mining method. Results Here, we present a method to infer the hidden traits for the enrichment of not-yet-cultured populations. We demonstrate this method using Candidatus Accumulibacter. Our method constructs a whole picture of the carbon, electron, and energy flows in the not-yet-cultured populations from the genomic datasets. Then, it decodes the coordination across three flows from the transcriptional datasets. Based on it, our method diagnoses the status of the not-yet-cultured populations and provides strategy to optimize the enrichment systems. Conclusion Our method could shed light to the exploration into the bacterial dark matter in the environments. Electronic supplementary material The online version of this article (10.1186/s40168-019-0708-4) contains supplementary material, which is available to authorized users.

This study investigated the polyphosphates accumulation rate in a novel sulfur transformation-centric enhanced biological phosphorus removal (SEBPR) process. The SEBPR system was continuously operated over 120 days in a sequencing batch reactor (SBR) that alternated between the anaerobic mode and the anoxic mode of operation (temperature: 30 °C and salinity: 6000 mg/L Cl−). In addition to the SBR, batch experiments were carried out to test the effect of two different sulfate concentrations on the system performance and sulfur-phosphorus transformations. The key intercellular polymers of polyphosphates and polysulfur (poly-S) were identified by employing advanced microscopes. Metagenomic analysis was performed to characterize the diversity of microbes and their functions enriched in the SEBPR system. Finally, several molecular techniques including flow cytometry cell sorting and 16S DNA high-throughput sequencing were applied to identify the phosphorus-accumulating organisms (PAOs). The amounts of P release and P uptake in the SEBPR increased gradually to nearly 18 ± 6.4 mg P/L and 26.5 ± 6.7 mg P/L respectively, yielding a net P removal efficiency of 84 ± 25%. Batch tests indicated no polyhydroxyalkanate (PHA) synthesis, but P uptake was observed and it was correlated with the intracellular poly-S consumption, suggesting that the poly-S could act as an intracellular energy source for P uptake and polyphosphates formation. Moreover, CLSM and TEM micrographs clearly showed the presence of intercellular polyphosphates and poly-S respectively. Metagenomic analysis revealed that Proteobacteria (36.5%), Bacteroidetes (23.3%), Thermotogae (7.1%), Chloroflexi (4.5%) and Firmicutes (2.3%) were the dominant phyla in Bacteria. The conventional PAO of Candidatus Accumulibacter was found at a low abundance of 0.32% only; and an uncultured genus close to Rhodobacteraceae at the family level is speculated to be the putative sulfur PAO (SPAO). Finally, this research suggests that poly-S considerably impacts on polyphosphates accumulation in the SEBPR system when no PHAs are formed.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC) merged T4N0–2 and T1–4N3 to create stage IVa. In the present study, we aimed to assess the difference in clinical outcomes and patterns of failure between 8th AJCC T4N0–2 and T1–4N3 NPC patients treated with intensity-modulated radiotherapy (IMRT). We included 3107 patients with stage IVa NPC disease (1871 with T4N0–2 and 1236 with T1–4N3) according to the 8th AJCC staging system. Overall survival (OS) was the primary endpoint. The clinical outcomes between T4N0–2 and T1–4N3 patients were compared. T1–4N3 patients had significantly worse 3-year OS (84.1% vs. 89.2%; p < 0.001) and distant metastasis–free survival (DMFS; 78.3% vs. 85.9%; p < 0.001), but better local relapse–free survival (LRFS; 94.9% vs. 92.2%; p = 0.003), as compared with T4N0–2 patients. Multivariate analysis showed that T1–4N3 was still an independent adverse prognostic factor for both DMFS (hazard ratio [HR] = 1.517, 95% confidence interval [CI] = 1.274–1.806, p < 0.001) and OS (HR = 1.315, 95% CI = 1.100–1.572, p = 0.003), whereas T4N0–2 was an independent adverse prognostic factor for LRFS (HR = 1.581, 95% CI = 1.158–2.158, p = 0.004). In terms of the OS, T4N0–2 patients had better prognosis compared with T1–4N3 patients, and the patterns of failure differed between T4N0–2 and T1–4N3 patients. We believe that future modifications of the AJCC/UICC staging system should separate T4N0–2 from T1–4N3. • In nasopharyngeal carcinoma, T4N0–2 patients tended to develop local relapse, whereas T1–4N3 patients were more likely to develop distant metastasis. • In terms of overall survival, T4N0–2 patients had better prognosis than T1–4N3 patients. • T4N0–2 should be separated from T1–4N3 in the UICC/AJCC staging system.

Heavy metal pollution is one of the most widespread and complex environmental issues globally, posing a great threat to the ecosystem as well as human health. Bioremediation through heavy metal-resistant bacteria (HMRB) is currently the most promising technology to address this issue. To obtain HMRB to remediate heavy metal pollution potentially, 15 culturable HMRB strains were isolated from the sludge samples of an electroplating wastewater treatment plant (EWWTP), which belonged to the Bacillus, Shewanella, Lysinibacillus, and Acinetobacter genera. Their maximum tolerance concentrations to Cu2+, Ni2+, Mn2+, Co2+, and Cr2O72− were 40 mM, 10 mM, 200 mM, 40 mM, and 10 mM, respectively, and strain Mn1-4 showed much higher Mn2+ tolerance and removal effectiveness (3.355 g/L) than previously published reports. Moreover, multiple heavy metal-resistant genotypes and phenotypes were identified among these strains, of which strain Co1-1 carried the most of resistant gene sequences (10) and exhibited resistance to 7 categories of heavy metals, and the co-occurrence of heavy metal and antibiotic resistance were clearly observed in strain Ni1-3. In addition, flanked insert sequence (IS) elements on the heavy metal resistant genes (HMRGs) suggested that horizontal gene transfer (HGT) events may have resulted in multiple heavy metal resistance phenotypes and genotypes in these strains, and IS982 family transposase was presumed to result in the high Ni2+ tolerance in strain Ni1-3. This study expands our understanding of bacterial heavy metal resistance and provides promising candidates for heavy metal bioremediation.

Alzheimer’s disease (AD) is one of the most frequent diseases in elderly people and causes high mortality. Its incidence is increasing annually and no effective therapeutic treatment currently exists. In the present study, salidroside, a major active ingredient of Rhodiola rosea, was able to protect PC-12 cells from the toxicity and apoptosis induced by AD inducer amyloid (A)β1--42. Salidroside significantly protected PC-12 cells by inhibiting Aβ1-42-induced cytotoxicity and mitochondria-mediated endogenous caspase apoptotic pathways. Mechanistic studies demonstrated that salidroside significantly activated the extracellular signal regulated kinase (ERK)1/2 and protein kinase B (AKT) signaling pathways. This observation was further confirmed using the ERK1/2 inhibitor PD98059 and the AKT inhibitor LY294002, which demonstrated that salidroside promoted PC-12 cell survival and proliferation by activating the ERK1/2 and AKT signaling pathways. Salidroside is a therapeutic candidate for the treatment of AD and provides a basis for further drug development.

Objective To observe the effect of Qingshen Granule (QG) on the immune function of chronic renal failure (CRF) patients with damp-heat syndrome (DHS). Methods A total of 162 CRF patients were assigned to the treated group and the control group by random digit table, 81 in each group. All patients were treated with conventional Western medical therapy. Those in the treated group addition- ally took QG, one package each time (10 g) , thrice per day. The therapeutic course for all was 12 weeks. The clinical efficacy was observed in the two groups. The contents of peripheral blood CD4 ⁺ T cells, CD8 ⁺ T cells, Thl7 cells, and nuclear factor-κB p65 (NF-κBp65) activity were detected using flow cy- tometry. Expressions of serum IL-17, tumor necrosis factor receptor-associated factor 6 (TRAF6), ma- trix metalloproteinase-9 (MMP-9) , matrix metalloproteinase inhibitor-I (TIMP-1 ) , collagen N (Col-V) were detected using ELISA. Results Finally 156 patients completed the trial (77 cases in the treated group and 79 cases in the control group). The total clinical curative effective rate was significantly higher in the treated group (80. 52%, 62/77) than in the control group (68. 35%, 54/79) with statistical differ- ences between the two groups (x² = 54. 849, P0. 05). Compared with before treatment in the same group, the levels of peripheral blood CD4 ⁺ /CD8 ⁺ , Thl7 cell content, NF-κB p65 activity, serum levels of IL-17, TRAF6, and TIMP-1 , TIMP-1/MMP-9 ratio, Col-IV level all decreased in the treated group after treat- ment (P0. 05) ; serum MMP-9 level decreased .(P0. 05) and TIMP-1 /MMP-9 ratio increased (P0. 05) in the control group. Compared with the control group, CD4⁺/CD8 ⁺ T cell ratio, Th17 cell content, NF-κB p65 activity decreased more obviously in the treated group after treatment (P0. 05). Serum levels of IL- 17, TRAF6, TIMP-1, TIMP-1/MMP-9 ratio, and Col-IV all decreased (P0.05) and MMP-9 level increased (P0. 05) in the treated group (P0. 05). Conclusion QG could adjust immune dysfunction and disar- ranged immunity mediated inflammatory response, and attenuate renal fibrosis in CKD patients with DHS.

The development of low-cost cocatalysts is desirable for photocatalytic H2 generation. Here, we are the first to demonstrate the in situ hydrothermal growth of NiCo2S4 nanosheets on g-C3N4 surfaces to construct a “sheet-on-sheet” heterostructure. The as-prepared NiCo2S4/CN heterostructured nanohybrid exhibits remarkably enhanced rates of visible-light-driven photocatalytic H2 evolution without using a noble metal cocatalyst, such as Pt. Notably, the optimum loading of NiCo2S4 nanosheets is 10 wt%, providing the best H2 performance rate of 293.4 μmolh−1g−1, which is approximately 7 times higher than that of the single-component bulk CN. This result suggested that the improved photocatalytic activity can be primarily ascribed to the efficient interfacial transfer of the photogenerated charge pairs from CN to the NiCo2S4 nanosheets. These nanosheets serve as temporary electron reservoirs, resulting in a reduced charge recombination rate on the CN surfaces and increasing the amount of photogenerated charge pairs in the NiCo2S4 nanosheets. Furthermore, the increased potential of reactive surface sites, together with the extended light absorption range after the introduction of NiCo2S4 nanosheets on the CN substrate, may also play a certain role in improving the photocatalytic performance. This study reveals a promising and efficient route for using CN-based photocatalysts incorporated with a ternary transition metal sulfide cocatalyst, which have been prepared by the nanoarchitecture engineering of noble metal-free heterostructured interfaces for use in renewable energy production.

Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m 2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m 2 on day 1), intravenous cisplatin (60 mg/m 2 on day 1), and continuous intravenous fluorouracil (600 mg/m 2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).

Background Little is known about the extent of selective publication in contemporary oncology randomised controlled trials (RCTs) worldwide. This study aimed to evaluate the rates of publication and timely publication (within 24 months) for contemporary oncology RCTs from all over the world. We also investigated the trial characteristics associated with publication and timely publication. Patients and methods We identified all phase III oncology RCTs registered on ClinicalTrials.gov with a primary completion date between January 2008 and December 2012. We searched PubMed and EMBASE to identify publications. The final search date was 31 December 2015. Our primary outcome measure was the time to publication from the primary completion date to the date of primary publication in a peer-reviewed journal. Results We identified 598 completed oncology RCTs; overall, 398 (66.6%) had been published. For published trials, the median time to publication was 25 months (interquartile range, 16–37 months). Only 192 trials (32.1%) were published within 24 months. Timely publication was independently associated with trials completed late in 2012. Trials conducted in Asia and other regions were less likely to have timely publication, but trials conducted in different locations were all equally likely to be published. Industry- and NIH-funded trials were equally likely to be published timely or at any time after trial completion. Among 391 published trials with clear primary outcomes, there was a trend for timely publication of positive trials compared with negative trials. Conclusions Despite the ethical obligations and societal expectations of disclosing findings promptly, oncology RCTs performed poorly.

Two aerobic sulfadiazine (SDZ) degrading bacterial strains, D2 and D4, affiliated with the genus Arthrobacter, were isolated from SDZ-enriched activated sludge. The degradation of SDZ by the two isolates followed first-order decay kinetics. The half-life time of complete SDZ degradation was 11.3 h for strain D2 and 46.4 h for strain D4. Degradation kinetic changed from nongrowth to growth-linked when glucose was introduced as the cosubstrate, and accelerated biodegradation rate was observed after the adaption period. Both isolates could degrade SDZ into 12 biodegradation products via 3 parallel pathways, of which 2-amino-4-hydroxypyrimidine was detected as the principal intermediate product toward the pyrimidine ring cleavage. Compared with five Arthrobacter strains reported previously, D2 and D4 were the only Arthrobacter strains which could degrade SDZ as the sole carbon source. The draft genomes of D2 and D4, with the same completeness of 99.7%, were compared to other genomes of related species. Overall, these two isolates shared high genomic similarities with the s-triazine-degrading Arthrobacter sp. AK-YN10 and the sulfonamide-degrading bacteria Microbacterium sp. C448. In addition, the two genomes contained a few significant regions of difference which may carry the functional genes involved in sulfonamide degradation.

Biofilms are widely used in wastewater treatment for their particular enhancement of nitrogen removal and other significant advantages. In this study, the diversity and potential functions of nitrogen removal bacteria in suspended activated sludge (AS) and biofilm of a full-scale hybrid reactor were uncovered by metagenomes (∼34 Gb), coupled with PCR-based 454 reads (>33 K reads). The results indicated that the diversity and abundance of nitrifiers and denitrifiers in biofilm did not surpass that in AS, while more nitrification and denitrification genes were indeed found in biofilm than AS, suggesting that the increased nitrogen removal ability by applying biofilm might be attributed to the enhancement of removal efficiency, rather than the biomass accumulation of nitrogen removal bacteria. The gene annotation and phylogenetic analysis results revealed that AS and biofilm samples consisted of 6.0 % and 9.4 % of novel functional genes for nitrogen removal and 18 % and 30 % of new Nitrospira species for nitrite-oxidizing bacteria, respectively. Moreover, the identification of Nitrospira-like amoA genes provided metagenomic evidence for the presence of complete ammonia oxidizer (comammox) with the functional potential to perform the complete oxidation of ammonia to nitrate. These findings have significant implications in expanding our knowledge of the biological nitrogen transformations in wastewater treatment.

// Rui Guo 1,* , Yan-Ping Mao 1,* , Lei chen 1 , Ling-Long Tang 1 , Guan-Qun Zhou 1 , Li-Zhi Liu 2 , Li Tian 2 , Mu-Sheng Zeng 3 , Wei-Hua Jia 3 , Jian-Yong Shao 4 , Ai-Hua Lin 5 , and Jun Ma 1 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 2 Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 3 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 4 Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 5 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Ma, email: // Keywords : comorbidity, Initiation of chemotherapy, nasopharyngeal carcinoma, treatment outcome Received : September 11, 2015 Accepted : March 14, 2016 Published : April 06, 2016 Abstract Background: To assess the impact of comorbidity on the initiation of chemotherapy and its ultimate treatment outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: Data on 1316 patients with NPC treated between February 2003 and January 2007 was retrospectively reviewed. Comorbidity was assessed using the Adult Comorbidity Evaluation-27 (ACE-27) system. The association of various factors with chemotherapy was evaluated. And treatment outcomes of chemoradiotherapy regimes in patients with comorbidity were compared. Results: Comorbidity was present in 42.2% of patients; mild, moderate and severe comorbidity were observed in 33.6%, 8.1% and 0.5% of patients, respectively. Comorbidity (as indicated by ACE-27 score) was a negative prognostic factor for overall survival (OS) (hazard ratio HR=1.577; P 0), 5-year OS for the concomitant chemoradiotherapy group (CCRT) was 74.5% vs. 56.9% in the radiotherapy (RT) only group ( P = 0.008), the 5-year DFS rate was 64.0% in the CCRT group vs . 49.4% for RT only ( P = 0.015). Conclusions: Comorbidity should be assessed during treatment strategy decision-making to improve survival in NPC. Concomitant chemoradiotherapy is feasible and effective in patients with comorbidity in locoregionally advanced stages.

// Jia-Wei Lv 1, * , Yu-Pei Chen 1, * , Guan-Qun Zhou 1, * , Ling-Long Tang 1 , Yan-Ping Mao 1 , Wen-Fei Li 1 , Rui Guo 1 , Ai-Hua Lin 2 , Jun Ma 1 , Ying Sun 1 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China 2 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Ying Sun, e-mail: sunying@sysucc.org.cn Key words: baseline plasma EBV DNA, cigarette smoking, intensity-modulated radiation therapy, nasopharyngeal carcinoma, prognostication Received: December 12, 2015 Accepted: February 11, 2016 Published: February 23, 2016 ABSTRACT We evaluated the combined prognostic value of cigarette smoking and baseline plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Of consecutive patients, 1501 with complete data were eligible for retrospective analysis. Smoking index (SI; cigarette packs per day times smoking duration [years]), was used to evaluate the cumulative effect of smoking. Primary end-point was overall survival (OS); progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were secondary end-points. Both cigarette smoking and baseline plasma EBV DNA load were associated with poorer survival ( P

The aim of this study was to determine the prognostic value of wait time from histological diagnosis to primary treatmen for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Between October 2009 and February 2012, a total of 1672 NPC patients were retrospectively analyzed. A cutoff value of > 4 weeks was used to define prolonged wait time. Matched patients according to the wait time were identified using propensity score matching (PSM), which was also used to identify matched patients for subsequent stratified analyses. Differences in progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were estimated using the Kaplan-Meier method and Cox proportional hazards models. In total, 407 pairs of NPC patients were selected by PSM. The 3-year PFS rate was significantly lower for patients with a prolonged wait time (> 4 weeks) than for those with an acceptable wait time (P = 0.035). Stratified analyses revealed that the negative effects of a prolonged wait time occurred primarily in patients with advanced NPC without neoadjuvant chemotherapy (NACT; PFS:P = 0.040; DMFS:P = 0.028). In multivariate analysis, a prolonged wait time was found to be an independent unfavorable prognostic factor for PFS and DMFS in advanced-staged patients without NACT. These results suggest that a prolonged time (> 4 weeks) between diagnosis and primary radical radiotherapy is a disadvantage for NPC patients, particularly those with advanced disease receiving no NACT. Thus, it is necessary to optimize resources for decreasing this wait time, although additional studies are warranted to further clarify our findings.

// Yuan Zhang 1, * , Wen-Fei Li 1, * , Yan-Ping Mao 1 , Rui Guo 1 , Ling-Long Tang 1 , Hao Peng 1 , Ying Sun 1 , Qing Liu 2 , Lei Chen 1 , Jun Ma 1 1 Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 2 Department of Cancer Prevention Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Ma, e-mail: majun2@mail.sysu.edu.cn Lei Chen, e-mail: chenlei@sysucc.org.cn Keywords: nasopharyngeal neoplasms, tumor markers, biological, Epstein-Barr virus, DNA Received: August 21, 2015 Accepted: January 13, 2016 Published: January 30, 2016 ABSTRACT Background: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV). The current study investigated change in the plasma EBV DNA load in the first 3 months after treatment and its clinical significance in NPC. Methods: A total of 273 patients with non-metastatic, histologically-proven NPC treated with radiotherapy or chemoradiotherapy were retrospectively reviewed. Results: EBV DNA was detectable in 19/273 (7.0%) patients at the end of therapy (end-DNA). Three months later, 16/273 (5.9%) patients had detectable EBV DNA (3-month-DNA). To investigate risk stratified by the pattern of change in post-treatment EBV-DNA, we divided patients into four subgroups: Group 1, undetectable end-DNA and 3-month-DNA ( n = 244); Group 2, detectable end-DNA and undetectable 3-month-DNA ( n = 13); Group 3, undetectable end-DNA and detectable 3-month-DNA ( n = 7); and Group 4, detectable end-DNA and 3-month-DNA ( n = 2). Patients with delayed remission of EBV DNA after treatment (Group 2) had significantly poorer 3-year DFS (48.6% vs. 89.7%, P < 0.001), DMFS (48.6% vs. 94.6%, P < 0.001) and OS (91.7% vs. 97.5%, P < 0.001) than those with persistently undetectable EBV DNA post-treatment (Group 1). Five of the seven patients with re-emergent EBV DNA (Group 3) and both patients with persistent EBV DNA post-treatment (Group 4) developed disease failure. Conclusion: Plasma EBV DNA load continues to change during the first 3 months after treatment. The pattern of change in EBV DNA load post-treatment could help identify patients with different prognoses.

Background: The optimal treatment for early-stage nasopharyngeal carcinoma (NPC) remains controversial. Identification of prognostic factors for metastasis and tumor progression is urgently required to improve clinical decision-making for patients with American Joint Committee on Cancer (AJCC) 2009 stage II NPC from the endemic area. Methods: Consecutive newly-diagnosed patients (n=296) with non-disseminated, biopsy-proven stage II NPC were retrospectively reviewed; all patients received intensity-modulated radiotherapy and MRI follow-up. Plasma EBV DNA level, serum lactate dehydrogenase, serum albumin, serum globulin and leukocyte counts were measured before therapy. Survival rates were analyzed using the Kaplan-Meier method and log-rank test and multivariate Cox proportional hazards model. Results: Median follow-up was 50.2 months (range, 8-69.5 months). Multivariate analysis demonstrated a plasma Epstein-Barr virus (EBV) DNA level ≥ 4000 copies/mL, maximal axial diameter (MAD) of the cervical lymph nodes ≥ 30 mm and serum globulin level < 29.5 g/L were independent predictors of poor DMFS (P = 0.018; P = 0.019; P = 0.006, respectively). On the basis of these parameters, a prognostic model was developed as follows: 1) patients with no risk factors; 2) one risk factor; and 3) two or three risk factors. The 3-year distant metastasis-free survival rates for groups 1, 2 and 3 were 100%, 94.6% and 84.3%, respectively (P = 0.001). Conclusion: The prognostic model based on EBV DNA, serum globulin and nodal size may facilitate individualized treatment of patients with stage II NPC at high risk of distant metastasis.

Objectives To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and CCRT plus adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and methods The propensity score-matched (PSM) method was adopted to balance variables. We identified independent prognostic factors using Cox regression analysis and compared outcomes between two chemotherapy treatment combinations for patients in different subgroups. Results A total of 550 patients were selected by one-to-two PSM. Survival outcomes for the matched data set indicated that the IC + CCRT group achieved higher 5-year overall survival (OS; 89.3% vs 85.3%, P = 0.119), failure-free survival (FFS; 80.2% vs 79.0%, P = 0.722) and distant metastasis-free survival (DMFS; 87.4% vs 84.4%, P = 0.322) compared with CCRT + AC, although this was statistically non-significant. Subgroup analysis revealed that IC + CCRT was associated with significantly improved OS (Hazard ratio [HR] = 2.68, 95% Confidence interval [CI] = 1.16–6.22, P = 0.017), FFS (HR = 1.94, 95% CI = 1.06–3.57, P = 0.029) and locoregional relapse-free survival (LRRFS; HR = 2.63, 95% CI = 1.04–6.68, P = 0.034) in T3 disease. Moreover, this combination of treatment could significantly prolong OS (HR = 3.72, 95% CI = 1.41–9.80, P = 0.004) in N2 disease. However, the superiority of CCRT + AC was only observed in LRRFS (HR = 0.18, 95% CI 0.04–0.79, P = 0.010) for the T4 subgroup. Conclusion IC + CCRT should be strongly considered by patients with LANPC, especially those with T3 or N2 disease.

6522 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene expression signature that can identify patients who will benefit from IC. Methods: We screened chemoresistance-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemoresistance-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Results: We identified 43 chemoresistance-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] 0.87, sensitivity = 87.5%, specificity = 75.6%). We then apply the 6-gene signature to classify patients into the benefit group and the no-benefit group. In the benefit group, patients could benefit from IC in terms of failure-free survival (hazard ratio [HR] 0.54 [95% confidence interval 0.34-0.87]; p = 0.01), while patients in the no-benefit group could not (HR 1.25 [95%CI 0.62-2.51]; p = 0.53). In the clinical trial cohort, the developed 6-gene signature was also highly accurate at predicting the response to IC (AUC = 0.82; sensitivity = 87.5%; specificity = 71.8%). Additionally, IC conferred failure-free survival benefits only on patients in the benefit group (HR 0.37 [95%CI 0.18-0.75], p = 0.004) and not on those in the no-benefit group (HR 0.70 [95%CI 0.27-1.82]; p = 0.46). In the external independent cohort, similar results were observed. Conclusions: The 6-gene signature can help select patients who will benefit from IC and thus lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.