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(a)Overall survival, (b) progression-free survivalcurves of heavy smokers versus light smokers according to pack-years inthe intensity-modulated radiotherapy or three-dimensional conformal radiotherapy cohort.A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for one year.

The process and result of exploring the two continuous variables - AGE and PACK-YEARS - using restricted cubic splines nested within Cox models by RCS-macro of SAS (SAS Institute, Cary, NC).

Background: Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown.Methods: We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model.Results: The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58–4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03–3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89–3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses.Conclusions: Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years.Impact: It is clear that cigarette smoking not only promotes carcinogenesis in the normal nasopharyngeal epithelium, but also affects the survival of patients with nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev; 22(12); 2285–94. ©2013 AACR.

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The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18-65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0-N1 disease (according to International Union Against Cancer-American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66-70 Gy (for the involved cervical lymph nodes), 60-62 Gy (for the high-risk target volume), and 54-56 Gy (for the low-risk target volume) were administered in 30-33 fractions, five fractions per week. Patients with stage II-IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46-59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7-99·7] in the UNI group vs 96·3% [93·8-98·8] in the WNI group; difference -1·4% [95% CI -4·6 to 1·8]; pElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0-N1 nasopharyngeal carcinoma.Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.For the Chinese translation of the abstract see Supplementary Materials section.

Objectives We aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC). Methods A total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation. Results The sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p p n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort. Conclusions T3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC. Key Points • [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy.

Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the immune response in dynamic infections (e.g., respiratory viruses). Here we present an at-home self-collection methodology,homeRNA, to study the host transcriptional response during acute SARS-CoV-2 infections. This method uniquely enables high frequency measurement of the host immune kinetics in non-hospitalized adults during the acute and most dynamic stage of their infection. COVID-19+ and healthy participants self-collected blood every other day for two weeks with daily nasal swabs and symptom surveys to track viral load kinetics and symptom burden, respectively. While healthy uninfected participants showed remarkably stable immune kinetics with no significant dynamic genes, COVID-19+ participants, on the contrary, depicted a robust response with over 418 dynamic genes associated with interferon and innate viral defense pathways. When stratified by vaccination status, we detected distinct response signatures between unvaccinated and breakthrough (vaccinated) infection subgroups; unvaccinated individuals portrayed a response repertoire characterized by higher innate antiviral responses, interferon signaling, and cytotoxic lymphocyte responses while breakthrough infections portrayed lower levels of interferon signaling and enhanced early cell-mediated response. Leveraging cross-platform longitudinal sampling (nasal swabs and blood), we observed thatIFI27, a key viral response gene, tracked closely with SARS-CoV-2 viral clearance in individual participants. Taken together, these results demonstrate that at-home sampling can capture key host antiviral responses and facilitate frequent longitudinal sampling to detect transient host immune kinetics during dynamic immune states.One Sentence SummarySelf-blood collection usinghomeRNA captures temporal dynamics in host transcriptional immune response during acute SARS-CoV-2 infection.

Additional file 1: Figure S1. Location of sampling sites in the gas hydrate zone of Shenhu area (SH) and Qiongdongnan (QDN) Basin from the South China Sea.All the four drilling sites werelocated above deep subsurface gas chimneys. They wereretrieved from the Shenhu area (n =1; SH-W20A) and Qiongdongnan Basin (n =3; QDN-W01B, W03B and W04B). The drilling depths of sediments are between 100and 188 mbsf in water depths ranging from 1000 to 1500 meters. Figure S2. Comparison of Chao1 and Shannon indices of the microbial community between sedimentsabove and below the SMI in the gas hydrate zone. Chao1 and Shannon indices werecalculated based on the SingleM ((https://github.com/wwood/singlem) OTU tablesfor 14 universal single-copy genes. P-values of differences between redox zones were calculated using Wilcoxon rank sum test. Asterisks denote significance (*** for P < 0.001). Figure S3. Relative abundances of each class from the Halobacterota phylum inferredfrom 16S rRNA gene fragments in metagenomes. Figure S4. MAG recovery information across differenttaxonomic levels. A Sankey diagram based on assigned GTDB taxonomy showing archaeal (a) and bacterial (b) MAGs at different phylogenetic levels. Numbers indicate the number of MAGs recovered for this lineage. (c) Total MAGs unclassified by GTDB-Tk at each taxonomic level. MAGs were dereplicated at strain level (i.e., 95% ANI). Detailed statistics for 578 MAGs are provided in Table S3. Figure S5. Phylogenetic placement of 349 MAGs for microbial communities in the deep subsurface sediments from the gas hydrate zone. Branches in red indicate unclassified MAGs. The maximum-likelihood phylogenomic tree was built based on concatenated amino acid sequences of 43 conserved single-copy genes using RAxML with the PROTCATLG model. The scale bar represents the average number of substitutions per site. Relative abundances of those microorganisms can be found in Table S4. Figure S6. Carbohydrate-active enzyme composition of the deep subseafloor microbiome from the gas hydrate zone. GTs: glycosyltransferases; GHs: glycoside hydrolases; CEs: carbohydrate esterases; CMBs: carbohydrate-binding modules; AA: auxiliary activities; PLs: polysaccharide lyases. Figure S7. Percentage of extracellular carbohydrate-activeenzymes (CAZymes) encoded in each phylogenetic cluster. The number of MAGs per phylogenetic cluster is shown in brackets. CMBs: carbohydrate-binding modules; CEs: carbohydrate esterases; GHs: glycoside hydrolases; GTs: glycosyltransferases; PLs: polysaccharide lyases. Figure S8. Percentage of extracellular peptidases encoded in each phylogenetic cluster. The number of MAGs per phylogenetic cluster is shown in brackets. Figure S9. Presence and absence of genes in sulfate-reducing pathway for recovered sulfate reducers reported in this study. Figure S10. Phylogenomic placement of MCR-containing MAGs based on 43 conserved protein sequences. Black dots indicate bootstrap values of 70–100%. Scale bars indicate the average number of substitutions per site. Figure S11. Co-localization of mcr with genes nearby. Genes are colored according to their functions. Red: Mcr complex; Purple: Methane/Alkane metabolism-related; Brown: Methanol utilization; Pink: Methylamine utilization; Orange: ABC transporter; Green: Cas protein; Greenyellow: tRNA/rRNA; Grey: Others. Figure S12. Predicted pathways of hydrogen-dependent methylotrophic methanogenesis. Grey colors indicate the absence of the enzyme or pathway. mWL pathway, methyl-branch of the Wood–Ljungdahl pathway. The percentages between brackets indicate the estimated completeness of the corresponding MAGs. A complete list of metabolic information can be found in Table S11. Figure S13. Relative abundances of hydrocarbon-metabolizing archaea and sulfate reducers inferred from metabolic pathway reconstructions. The MAG with the highest genome quality from each species cluster is picked as the representative. Details on species clusters and their relative abundances are presented in Table S4. Figure S14. Predicted pathways of anaerobic oxidation of methane. Grey colors indicate the absence of the enzyme or pathway. The percentages between brackets indicate the estimated completeness of the corresponding MAGs. A complete list of metabolic information can be found in Table S11.

Gene expression analysis (e.g., targeted gene panels, transcriptomics) from whole blood can elucidate mechanisms of immune function and aid in the discovery of biomarkers. Conventional venipuncture offers only a small snapshot of our broad immune landscape as immune responses may occur outside of the time and location parameters available for conventional venipuncture. A self-operated method that enables flexible sampling of liquid whole blood coupled with immediate stabilization of cellular RNA is instrumental in facilitating capture and preservation of acute or transient immune fluxes. To this end, we developed homeRNA: a kit for self-collection of peripheral blood (∼0.5 mL) and immediate stabilization of cellular RNA, using the Tasso- SST™ blood collection device with a specially designed stabilizer tube containing RNAlater™. To assess the feasibility of homeRNA for self-collection and stabilization of whole blood RNA, we conducted a pilot study (n = 47 participants) where we sent homeRNA to participants aged 21-69, located across 10 US states (94% successful blood collections, n = 61/65). Among participants who successfully collected blood, 93% reported no or minimal pain/discomfort using the kit (n = 39/42), and 79% reported very easy/somewhat easy stabilization protocol (n = 33/42). Total RNA yield from the stabilized samples ranged between 0.20 µg and 5.99 µg (mean = 1.51 µg), and all but one RNA Integrity Number (RIN) values were above 7.0 (mean = 8.1), indicating limited RNA degradation. Results from this study demonstrate the self-collection and RNA stabilization of whole blood with homeRNA by participants themselves, in their own home.

Background To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. Methods The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. Results PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p p p p p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). Conclusion PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.