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We sought to describe the resolution time of chronic subdural hematoma (CSDH) after middle meningeal artery embolization (MMAE) and potential variables that may affect hematoma resolution. A retrospective analysis was performed on CSDH patients between December 2018 and December 2021. Patient characteristics, radiologic manifestations, and data of hematoma resolution were recorded. Univariate and multivariate analyses were conducted to identify predictors of CSDH resolution time. A total of 53 patients were enrolled including 53 hematomas. Only 1 participant relapsed and did not require surgical evacuation. Hematoma resolution was observed in 27 (50.9%) at 4 months and 48 (90.6%) cases at the last radiologic follow-up. The median MMAE-to-resolution time was 19 weeks (interquartile range: 8–24). The burr-hole irrigation + MMAE group showed faster hematoma resolution than MMAE alone during early follow-up periods, but no significant difference was found at 6 months. Increased thickness of residual hematoma, excessive postoperative midline shift, high-density hematoma, mixed-density hematoma, separated hematoma, and anticoagulant or antiplatelet agents used were predictive of nonresolution at 4 months as determined by univariate analysis, whereas anticoagulant or antiplatelet agents used and high-density hematoma were not significant on multivariate analysis. No significant association was noted between hematoma resolution and comorbidities or other hematoma radiologic features. MMAE is an effective and minimally invasive treatment for CSDH with a lower recurrence rate. The median resolution time of CSDH following MMAE was 19 weeks (interquartile range: 8–24). Burr-hole irrigation contributed to early hematoma resolution but had no significant effect at 6 months. In addition, residual hematoma thickness, postoperative midline shift, and specific type of hematoma were associated with delayed hematoma resolution at 4 months. [ABSTRACT FROM AUTHOR]

The gonadotropin-releasing hormone (GnRH) signaling pathway controls reproductive functions and cancer growth and progression. However, few studies investigated roles of genetic variants of GnRH pathway genes in survival of patients with non-small cell lung cancer (NSCLC). Therefore, we first evaluated associations between 22,528 single-nucleotide polymorphisms (SNPs) in 101 GnRH pathway genes and survival of 1185 NSCLC patients using a dataset from Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We found 572 SNPs to be significantly associated with overall survival (OS) of NSCLC (P ≤ 0.05, Bayesian false discovery probability ≤0.80). We then validated these SNPs in another dataset with 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. Finally, two independent SNPs (HBEGF rs4150236G>A and ITPR3 rs116454384C>T) remained significantly associated with NSCLC OS in the combined analysis with hazards ratios of 0.84 (95% confidence interval = 0.76-0.92, P = 0.0003) and 0.85 (0.78-0.94, 0.0012), respectively; their genetic score (the number of protective genotypes) was associated with a better OS and disease-specific survival (Ptrend = 0.0002 and 0.0001, respectively). Further expression quantitative trail loci analysis showed a significant correlation between ITPR3 rs116454384 T allele and an increased mRNA expression level in both whole blood and normal lung tissue, and high ITPR3 mRNA expression levels in tumors were associated with a better survival of NSCLC patients. Because ITPR3 mutations were rare in tumors, ITPR3 rs116454384C>T likely had an effect on cancer progression by regulating the gene expression. Therefore, genetic variants of HBEGF rs4150236G>A and ITPR3 rs116454384C>T may be predictors for NSCLC survival, but HBEGF rs4150236G>A functional relevance remains to be determined. [ABSTRACT FROM AUTHOR]

Background Tobacco smoke and alcohol drinking are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN). Smoking and drinking cause DNA damage leading to apoptosis, and insufficient apoptotic capacity may favour development of cancer because of the dysfunction of removing damaged cells. In the present study, we investigated the association between camptothecin (CPT)-induced apoptotic capacity and risk of SCCHN in a North American population. Methods In a case–control study of 708 SCCHN patients and 685 matched cancer-free controls, we measured apoptotic capacity in cultured peripheral blood lymphocytes in response to in vitro exposure to CPT by using the flow cytometry–based method. Results We found that the mean level of apoptotic capacity in the cases (45.9 ± 23.3%) was significantly lower than that in the controls (49.0 ± 23.1%) ( P = 0.002). When we used the median level of apoptotic capacity in the controls as the cutoff value for calculating adjusted odds ratios, subjects with a reduced apoptotic capacity had an increased risk (adjusted odds ratio = 1.42, 95% confidence interval = 1.13–1.78, P = 0.002), especially for those who were age ≥57 (1.73, 1.25–2.38, 0.0009), men (1.76, 1.36–2.27, <0.0001) and ever drinkers (1.67, 1.27–2.21, 0.0003), and these variables significantly interacted with apoptotic capacity ( P interaction = 0.015, 0.005 and 0.009, respectively). A further fitted prediction model suggested that the inclusion of apoptotic capacity significantly improved in the prediction of SCCHN risk. Conclusion Individuals with a reduced CPT-induced apoptotic capacity may be at an increased risk of developing SCCHN, and apoptotic capacity may be a biomarker for susceptibility to SCCHN. [ABSTRACT FROM AUTHOR]

Tobacco smoke and alcohol use play important roles in the etiology of squamous cell carcinoma of the head and neck (SCCHN). Smoking causes DNA damage, including double-strand DNA breaks (DSBs), that leads to carcinogenesis. To test the hypothesis that suboptimal DSB repair capacity is associated with risk of SCCHN, we applied a flow cytometry-based method to detect the DSB repair phenotype first in four EBV-immortalized human lymphoblastoid cell lines and then in human peripheral blood T-lymphocytes (PBTLs). With this blood-based laboratory assay, we conducted a pilot case-control study of 100 patients with newly diagnosed, previously untreated SCCHN and 124 cancer-free controls of non-Hispanic whites. We found that the mean DSB repair capacity level was significantly lower in cases (42.1%) than that in controls (54.4%) ( P < 0.001). When we used the median DSB repair capacity level in the controls as the cutoff value for calculating the odds ratios (ORs) with adjustment for age, sex, smoking and drinking status, the cases were more likely than the controls to have a reduced DSB repair capacity (adjusted OR = 1.93; 95% confidence interval, CI = 1.04–3.56, P = 0.037), especially for those subjects who were ever drinkers (adjusted OR = 2.73; 95% CI = 1.17–6.35, P = 0.020) and had oropharyngeal tumors (adjusted OR = 2.17; 95% CI = 1.06–4.45, P = 0.035). In conclusion, these findings suggest that individuals with a reduced DSB repair capacity may be at an increased risk of developing SCCHN. Larger studies are warranted to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Abstract: DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been reportedly to be associated with risk of several cancers, but few studies have investigated their roles in squamous cell carcinoma of the head and neck cancer (SCCHN). Here we report a hospital-based case–control study with 832 SCCHN patients and 843 cancer-free controls of non-Hispanic whites that evaluated the association between two DNMT3B single nucleotide polymorphisms (SNPs) DNMT3B −149C>T (rs2424913) and DNMT3B −579G>T (rs2424909) in the promoter region and risk of SCCHN. We found that compared with C-allele carriers, the DNMT3B −149 TT genotype was statistically significantly associated with increased risk of SCCHN (adjusted OR, 1.35, 95% CI, 1.01–1.80, P =0.043), whereas the DNMT3B −579 TT genotype showed only a non-statistically significant risk compared with G-allele carriers. Further analysis of the effects of combined genotypes suggested that subjects with either DNMT3B −149 TT or DNMT3B −579 TT homozygous genotypes had statistically significantly increased risk of SCCHN (adjusted OR=1.36, 95% CI=1.07–1.73, P =0.013). Stratification analysis showed a more profound risk in the subgroups of the young (⩽57 years, the median age of the controls), males, current smokers, current drinkers, and patients with primary tumor sites of pharynx and larynx. This large study provides reliable risk estimates for associations between DNMT3B variants and SCCHN risk in non-Hispanic whites, and our findings are consistent with that of previously reported cancer case–control studies of other cancers. Further mechanistic studies are needed to unravel the underlying molecular mechanisms. [Copyright &y& Elsevier]

Sunlight causes DNA damage but also induces production of vitamin D whose metabolite 1,25-(OH)2D3 has antiproliferative and pro-differentiative effects in both melanocytes and cutaneous melanoma (CM) cells mediated through the vitamin D receptor (VDR). We hypothesized that genetic polymorphisms of VDR are associated with risk of CM. In a hospital-based case–control study of 602 non-Hispanic white CM patients and 603 cancer-free control subjects frequency matched by age and sex, we genotyped two VDR polymorphisms (TaqI and FokI) and assessed their association with CM risk. We found that a significantly decreased risk was associated with VDR-TaqI Tt (adjusted odds ratio (OR), 0.70; 95% confidence interval (CI), 0.54–0.90) and Tt+tt (OR=0.70; 95% CI, 0.55–0.89) genotypes, compared with the VDR-TaqI TT genotype, whereas an increased risk was associated with VDR-FokI Ff genotype (OR=1.32; 95% CI, 1.03–1.68), and a borderline significantly increased risk was associated with Ff+ff (OR=1.26; 95% CI, 1.00–1.59) genotypes, compared with the VDR-FokI FF genotype. In conclusion, genetic variants (i.e., TaqI t protective allele and FokI f risk allele) in VDR may alter risk of CM.Journal of Investigative Dermatology (2007) 127, 276–280. doi:10.1038/sj.jid.5700544; published online 21 September 2006 [ABSTRACT FROM AUTHOR]

Meiofauna particularly marine nematodes around the Caiwei Guyot in the northwest Pacific Ocean and a Polymetallic Nodule Field in the northeast Pacific Ocean were studied. Due to the geographic structure, the Caiwei Guyot and the Polymetallic Nodule Field had different environmental characteristics. Meiofaunal abundances around the Guyot area ranged from 9.18 to 25.59 ind./10 cm2, which were much lower than those in the Polymetallic Nodule Field. Marine nematode was the most dominant group. A total of 123 species, belonging to 74 genera and 29 families were found. Xyalidae (21.43%), Cyatholaimidae (9.82%), Linhomoeidae (8.03%) were the dominant families. The values of species number, Margalef's species richness and Shannon-Wiener diversity index ranged from 15 to 62, 4.75 to 12.84 and 2.58 to 3.93, respectively. The combination of water depth, silt-clay content and chlorophyll- a concentration can best explain the differences of nematode community. This study provides a baseline for deep-sea meiofauna distribution. • Meiofauna and nematodes in different deep-sea habitats were studied. • Meiofaunal abundances in the guyot area were much lower. • A total of 123 nematode species were found in the study areas. • This study provides a baseline data for meiofauna and nematodes in deep sea. [ABSTRACT FROM AUTHOR]

It has been a great challenge to directly deposit uniform metal particles onto pristine graphene due to its low surface energy and chemical inertness. Without any surfactant or functionalization, we have developed a unique synthesis of high-quality PtRuNi trimetallic nanoparticles supported on pristine graphene via a simple but effective supercritical route. Due to excellent wettability between supercritical carbon dioxide and the carbon surface, ultrafine metal particles are uniformly and firmly anchored on the graphene sheets. While well retaining its intrinsic structure and outstanding electronic conductivity, the pristine graphene with well-dispersed PtRuNi trimetallic nanoparticles shows significantly improved catalytic activity towards methanol oxidation, which is at least ten times higher than those of the commercial Pt/C and homemade Pt/XC-72 catalysts. The resulting trimetallic hybrid also exhibits high stability as compared to Pt and PtRu/pristine graphene composites and the reduced graphene oxide counterparts. In principle, the supercritical method can be applied to other metal nanoparticles in fabrication of high-performance graphene-based nano-catalysts. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings. [Copyright &y& Elsevier]

• Developed a nonlinear model of droop-controlled sources, established a system-level model of direct current microgrids. • Proposed a low-conservation constrained region of attraction-based stability analysis method. • Those new achievements are verified by case studies and have been proved to be effective in expanding the existing knowledge base. Large-signal stability of direct current (DC) microgrids (MGs) are required to be seriously considered when more power converters are penetrated. For DC MGs suffering from large disturbances, the power electronics at both source and load sides are operated within the voltage and current limits to ensure the stability and safety. However, no existing methods have been developed to address the non-conservative stability analysis of a DC MGs with physical variable constraints. To this end, a comprehensive is developed in this paper to analyze the large-signal stability of typical DC MGs with voltage/current and pulse-width modulation duty cycle constraints, with a low level of conservatism. First, the system-level model of a DC MG is established as the basis of stability analysis. Then, a workflow based on the Lyapunov theory and numerical integration is developed to evaluate the large signal stability with physical variable constraints. The developed stability analysis method has less conservatism than the existing methods with only one moderate computational cost. The effectiveness of the proposed strategy is validated by case studies based on a single-bus direct current microgrid. [ABSTRACT FROM AUTHOR]

The Southwest Indian Ridge (SWIR) is an important section of the global mid-ocean ridge system providing a corridor for dispersion of vent fauna between the Pacific and Atlantic Oceans. However, very few studies focusing on the biodiversity and biogeography of this region have been performed. To better understand the biological baseline and biogeography of vent fields on SWIR, we have described the faunal assemblages at three hydrothermal fields on SWIR, the biogeographical relationships among the three fields and fields on neighboring ridges as well as community dynamics at Longqi on a short time-scale (3 years). Communities at two fields, Duanqiao and Tiancheng, were reported for the first time, and the Longqi community was characterized more comprehensively. Collected specimens, videos and images were examined and taxa identification was conducted by both morphological and molecular approaches (cytochrome oxidase I (COI) or 16 S ribosomal RNA gene). In total, 39 species were recorded, 18 of which were reported from SWIR for the first time. According to the multivariate analysis of occurrence of fauna from 16 vent fields on four ridge systems, the SWIR vent sites were generally more similar to Central Indian Ridge. Within Indian Ocean, Longqi and Duanqiao formed a subcluster, which appeared to be intermediate between the Central Indian Ridge, Mid-Atlantic Ridge and East Scotia Ridge. Distinct faunal zonation was described at Tiancheng and Longqi. Comparison of vent fauna discovered in 2011 and 2014/2015 revealed an interannual constancy in faunal zonation on most vents at Longqi, except DFF1 chimney, which displayed a successional change from an early stage featuring high-temperature venting and low species diversity, to a more mature stage characterized by diffuse fluid and more colonized taxa. Thus, the present study is the first interannual variation study on the ultra-slow spreading ridges, and will expand our understanding of biodiversity and biogeography of vent fields on SWIR. [ABSTRACT FROM AUTHOR]

Phasianus colchicus alaschanicus, Phasianidae, Galliformes is known only from the Helan Mountains of Ningxia and Inner Mongolia Autonomous Regions, China. Due to few studies on this subspecies, the taxonomic status of Phasianus colchicus alaschanicus in Galliformes is unclear. We sequenced the mitochondrial genome of one P. c. alaschanicus and downloaded 36 species of 22 genera from GeneBank to construct a phylogenetic tree based on the Maximum Likelihood (ML) method. The mitochondrial genome sequence length of P. c. alaschanicus was 16,688 bp with a base composition of 30.6% A, 25.3% T, 30.8% C, and 13.3% G, including two rRNA genes (12S rRNA, 16S rRNA), 22 tRNA genes, 13 protein-coding genes, and a control region. We confirmed the genetic classification status of P. c. alaschanicus in Galliformes. The Phasianidae formed a complex clade, which could be separated into eighteen lineages. P. c. alaschanicus was a sister group of the remaining taxa (posterior probabilities 100% in ML). [ABSTRACT FROM AUTHOR]

A scheme of the DME-diesel dual-fuel PCCI (premixed charge compression ignition) combustion is an attractive option of relatively high thermal efficiency, low emission and operating costs as well as availability of wide DME (dimethyl ether) resource. However, one of the main problems in the DME-diesel dual-fuel PCCI operation is that an early start of combustion easily leads to detonation due to high cetane number and better auto-ignition property of DME, and above-mentioned phenomenon is especially pronounced with a large DME energy ratio or at higher loads. Thus, LPG (liquefied petroleum gas), as a kind of ignition inhibitor, is added into DME for changing the property of port premixed fuel, and the effects of LPG quantity on the combustion and exhaust performance of a DME-diesel dual-fuel PCCI engine is investigated in this paper. Experimental results show that the appearing positions of the maximum cylinder pressure and mass-averaged temperature shift towards later crank angles and their peak values decline slightly when LPG mass fraction in DME/LPG mixture (f L ) increases. The start of combustion postpones, and the combustion duration shortens with a rise of f L. Simultaneously, brake thermal efficiency and NO x emission reduce slightly; whereas the number concentration of particles firstly increases but then decreases with a rise of f L . [ABSTRACT FROM AUTHOR]

Abstract: Background: LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods: We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results: Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32–6.72 and 1.01–4.94, P =0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24–4.28 and 1.11–3.62, and P =0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy. Conclusion: Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. [Copyright &y& Elsevier]

Abstract: Background: RASSF3 suppresses tumour formation through uncertain mechanisms, but it is an important gene of p53-dependent apoptosis. RASSF3 depletion impairs DNA repair after DNA damage, leading to polyploidy. The authors hypothesised that potential functional single-nucleotide polymorphisms (SNPs) of RASSF3 are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). Methods: The authors used a functional SNP approach to evaluate the associations between common (minor allele frequency⩾0.05), putative functional variants in RASSF3 and risk of SCCHN. Four selected such functional SNPs (rs6581580 T>G, rs7313765 G>A, rs12311754 G>C and rs1147098 T>C) in RASSF3 were identified and genotyped in 1087 patients and 1090 cancer-free controls in a non-Hispanic white population. Results: The authors found that two SNPs were significantly associated with SCCHN risk. Carriers of the variant rs6581580G and rs7313765A alleles were at a reduced SCCHN risk, compared with the corresponding common homozygotes [adjusted odds ratio (OR)=0.75 and 0.73 and 95% confidence interval (CI)=0.62–0.91 and 0.60–0.88, respectively, for dominant models; and P trend =0.012 and 0.041, respectively, for additive models], particularly for non-oropharyngeal tumours (adjusted OR=0.68 and 0.60 and 95% CI=0.53–0.86 and 0.47–0.77, respectively, for dominant models). In the genotype–phenotype correlation analysis of peripheral blood mononuclear cells from 102 cancer-free controls, the rs6581580 GG genotype was associated with significantly increased expression levels of RASSF3 mRNA (P =0.038), compared with the TT genotype. Additional functional experiments further showed that variant G allele of rs6581580 had a significantly stronger binding affinity to the nuclear protein extracts than the T allele. Conclusion: Taken together, these findings indicate that the RASSF3 promoter rs6581580 T>G SNP is potentially functional, modulating susceptibility to SCCHN among non-Hispanic whites. Larger replication studies are needed to confirm our findings. [Copyright &y& Elsevier]

Abstract: Background: LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods: We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results: Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32–6.72 and 1.01–4.94, P =0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24–4.28 and 1.11–3.62, and P =0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy. Conclusion: Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Abstract: To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G>C, hsa-mir-149 rs2292832 G>T, hsa-mir-196a2 rs11614913 C>T, and hsa-mir-499 rs3746444 A>G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan–Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4–4.1 and adjusted OR, 2.1, 95% CI, 1.2–3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP. [Copyright &y& Elsevier]

Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell''s C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC. [Copyright &y& Elsevier]

Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-β, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGFβ, TNFα, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade ≥3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data. Results: Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGFβ, VEGF, TNFα, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGFβ, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often. Conclusions: This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development. Methods and Materials: We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non–small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes. Results: We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade ≥2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24–0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64–7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001). Conclusions: SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC). Materials and methods: The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay. Results: Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10–0.91; P =0.033; multivariate HR 0.29; 95% CI, 0.09–0.97; P =0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period. Conclusions: The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials. [Copyright &y& Elsevier]

Abstract: Methylating agents are involved in carcinogenesis, and the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O6-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case–control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C>T and 16286C>T and two in the promoter region, 45996G>T and 46346C>A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT+TT, and 46346CA+AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR)=1.27; 95% confidence interval (CI)=1.05–1.53). This increased risk was also more pronounced among young subjects (OR=1.81; 95% CI=1.11–2.96), men (OR=1.24; 95% CI=1.00–1.55), ever smokers (OR=1.25; 95%=1.01–1.56), ever drinkers (OR=1.29; 95% CI=1.04–1.60), patients with oropharyngeal cancer (OR=1.45; 95% CI=1.12–1.87), and oropharyngeal cancer with regional lymph node metastasis (OR=1.52; 95% CI=1.16–1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites. [Copyright &y& Elsevier]

• Mismatch between phytoplankton and zooplankton was often observed in East China Sea. • Four hypotheses were tested to explain that mismatch in the present study. • Size diversity (SD) of zooplankton was the most important determinant of Z/P. • Seasonal change of determinants was also found. • It highlighted the SD approach in evaluation of carrying capacity for fish. The East China Sea (ECS) is the most important fishing ground in China. Field observations have always found no positive correlation between phytoplankton stocks and zooplankton biomass in the ESC. It has been suggested that under eutrophic conditions, the phytoplankton biomass is too high to limit mesozooplankton growth and lower the energy transfer efficiency from phytoplankton to mesozooplankton. However, this hypothesis does not explain the higher zooplankton biomass supported by lower chlorophyll a in offshore waters. This situation can be referred to as a "mismatch between phytoplankton and mesozooplankton" or "variation of Z/P". In this study, we used field data covering four seasons to test four hypotheses that (a) flatter slope of normalized biomass size spectrum (NBSS) of mesozooplankton enhances the Z/P; (b) higher mesozooplankton size diversity enhances the Z/P; (c) stronger predatory pressure from zooplanktivorous fish decreases the Z/P; and (d) larger-sized primary producers enhance the Z/P. The results of our study confirm that the size diversity of zooplankton was the most important determinant of spatial variation of Z/P in the ECS in each season except winter. The NBSS slope of zooplankton was also an important factor, but only significant in summer. Other potential mechanisms, including predation pressure from zooplanktivorous fish and larger-sized primary producers, were not determinants. This seasonal change was possibly due to seasonal variations of zooplankton community structure and functional structure in ECS, especially the large-sized and omnivorous Calanus sinicus transported by the stronger ECS Coastal Current during the winter. Our findings highlight the importance of a size diversity approach in the evaluation of the carrying capacity for fish in coastal ecosystems with conspicuous temporal and spatial variations. [ABSTRACT FROM AUTHOR]

Although many deep-sea species are considered to have transoceanic distribution, this assumption has rarely been critically tested. Using Hesiolyra (Hesionidae) as a case study, we show that careful molecular and morphological analyses are required for refuting/accepting claims about such wide distribution. Hesiolyra is a genus of polychaetes commonly found in hydrothermal vents of the Eastern Pacific, Atlantic and Indian Ocean. Nevertheless, H. bergi Blake, 1985, a species originally described from the Eastern Pacific Rise (EPR), is the only recognized species in this genus. Phylogenetic analyses based on the COI and 16 S rRNA genes revealed two monophyletic clades that were distinct from a clade consisting of H. bergi sequences. We erected two new species of Hesiolyra , herein named as H. longqiensis n. sp. from the Southwest Indian Ridge (SWIR) and H. heteropoda n. sp. from the Central Indian Ridge (CIR) and the Carlsberg Ridge (CR). Among them, H. longqiensis n. sp. is more closely related to H. bergi than to H. heteropoda n. sp.. Morphologically, the two newly described species can be easily distinguished from H. bergi. The notopodia and neuropodia of H. bergi and H. longqiensis n. sp. , are of similar sizes, but the morphology of their lyrate chaetae and their dorsal cirri alternation patterns are different. In H. heteropoda n. sp. , the notopodia are remarkably slimmer than the neuropodia, and it lacks lyrate chaetae. Overall, in this report two new species of Hesiolyra from the Indian Ocean ridges and show that the distribution of H. bergi is restricted to the Eastern Pacific Rise. Future exploration of other mid-ocean ridges is required to discover the true diversity of this genus of polychaetes inhabiting hydrothermal vent fields. • Hesiolyra are common polychaetes living on chimney walls of hydrothermal vents. • The genus was considered to be monospecific. • Hesiolyra bergi from East Pacific Rise was the only recognized species. • We described two new species of Hesiolyra from Indian Ocean ridges. [ABSTRACT FROM AUTHOR]

Reptiles are especially vulnerable to climate warming because their behavior, physiology, and life history are highly dependent on environmental temperature. In this study, we envisaged new probable mechanisms underlying the high vulnerability of lizards, wherein heat exposure induces oxidative stress and leads to immunosuppression. To test this hypothesis, we conducted a warming experiment on a lizard (Eremias multiocellata) from a desert steppe in Inner Mongolia from May to September using open-top chambers set up in their natural habitat and compared the components of oxidative stress (antioxidant ability [Superoxide dismutase (SOD) activity], extent of oxidative damage [malondialdehyde (MDA) content]), and immunocompetence (white blood cells [WBC] counts and immunoglobulin M [IgM] expression) between the warming and control groups. At the end of the experiment, the warming treatment did not affect the survival rate of the lizards. However, MDA content, but not SOD activity, was significantly higher in the warming group than in the control group. The WBC counts and IgM expression were significantly lower in the warming group than in the control group. Our results verified our hypothesis and provided novel cues and methods for the investigation of the mechanisms behind the high probability of extinction of other ectotherms under warming conditions. • Heat exposure induced oxidative stress. • Heat exposure led to immusuppression. • Providing new mechanisms that may contribute to the risk of extinction of lizard populations. [ABSTRACT FROM AUTHOR]

Purpose: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC). Methods and Materials: Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival. Results: Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045). Conclusions: Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations. [Copyright &y& Elsevier]