Novel trace elements detected in multiple stages of pregnancy impact neonatal birth weight by affecting gestational age.

Prenatal exposure to elements may be associated with birth weight via shortening of gestation. This study aimed to determine if prenatal exposure is associated with birth weight, and to explore the potential mediating role of gestational age in the association. Within an established Bangladesh prospective birth cohort (2008-2011), we analyzed the concentrations of 15 elements in maternal serum samples collected during the first (n = 780) and second (n = 610) trimesters using inductively coupled plasma mass spectrometry. Mediation analyses explored the relationships between these elements, gestational age, and birth weight. Serum concentrations of cobalt (Co) (first trimester: b = 56.5; 95% confidence interval [CI]: 13.5-99.0; false discovery rate [FDR]-q = 0.035; second trimester: b = 73.3; 95% CI: 20.4-130.2; FDR-q = 0.037) and antimony (Sb) in both trimesters (first trimester:b = 92.1; 95% CI: 66.0-118.9; FDR-q < 0.001; second trimester: b = 93.3; 95% CI: 67.3-118.4; FDR-q < 0.001), and strontium (Sr) in the first trimester (b = 142.4; 95% CI: 41.6-247.9; FDR-q = 0.035) were positively associated with birth weight, while negative associations were observed for barium (Ba) (first trimester: b = -154.8; 95% CI: -217.9 to 91.8; FDR-q <0.001; second trimester: b = -26.7; 95% CI: -44.9 to 10.2; FDR-q < 0.001). These elements act partially by affecting gestation age and appear to have heightened impact among smaller infants. Further research is needed to determine the biological underpinnings of these effects, which may inform strategies to avert low birth weight.

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment: Evidence from a prospective birth cohort in rural Bangladesh.

BACKGROUND: Prenatal exposures to neurotoxic metals and trace elements are associated with early childhood neurodevelopmental outcomes. However, consequences of simultaneous exposure to mixtures of elements remain unclear. OBJECTIVE: To examine individual and joint effects of prenatal trace element exposure on early childhood neurodevelopment. METHODS: Using a well-established Bangladesh prospective birth cohort (2008-2011), we measured concentrations of 52 trace elements in umbilical cord serum of 569 mother-infant pairs using inductively coupled plasma mass spectrometry. Neurodevelopment was evaluated at 20-40 months of age using Bayley Scales of Infant and Toddler Development, Third Edition. Stability elastic net (ENET) was used to screen elements individually associated with the outcome; candidate exposures were combined by weighted linear combination to form a risk score representing their mixture effect on early childhood neurodevelopment. RESULTS: Stability ENET identified 15 trace elements associated with cognitive composite score and 14 associated with motor composite score, which were linearly combined to form the element risk score (ERS). Children with higher ERScognitive had lower probability of cognitive developmental delay (ORhighest vs lowest: 0.21; 95 %CI: 0.10, 0.40; P < 0.001; Ptrend < 0.001). Children with ERSmotor in the top quintile had a significantly lower risk of motor developmental delay (OR: 0.16; 95 %CI: 0.09, 0.31; P < 0.001; Ptrend < 0.001) versus the lowest quintile. In Bayesian kernel machine regression analyses, lithium [conditional posterior inclusion probability (cPIP) = 0.68], aluminum (cPIP = 0.83) and iron (cPIP = 1.00) contributed most to the lower cognitive composite score; zinc (cPIP = 1.00), silver (cPIP = 0.81), and antimony (cPIP = 0.65) mainly contributed to the change of motor composite score. CONCLUSION: Co-exposure to lithium/aluminum/iron or zinc/silver/antimony appears to impact children's neurodevelopment. ERS score reflecting maternal exposure could indicate children's risk of neurodevelopmental delay, warranting further studies to explore the underlying mechanism.

Diagnostic performance of DCE-MRI, multiparametric MRI and multimodality imaging for discrimination of breast non-mass-like enhancement lesions.

OBJECTIVE: The aim of this study was to investigate and compare the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI, multiparametric MRI (mpMRI), and multimodality imaging (MMI) combining mpMRI and mammography (MG) for discriminating breast non-mass-like enhancement (NME) lesions. METHODS: This retrospective study enrolled 193 patients with 199 lesions who underwent 3.0 T MRI and MG from January 2017 to December 2019. The features of DCE-MRI, turbo inversion recovery magnitude (TIRM), and diffusion-weighted imaging (DWI) were assessed by two breast radiologists. Then, all lesions were divided into microcalcification and non-microcalcification groups to assess the features of MG. Comparisons were performed between groups using univariate analyses. Then, multivariate analyses were performed to construct diagnostic models for distinguishing NME lesions. Diagnostic performance was evaluated by using the area under the curve (AUC) and the differences between AUCs were evaluated by using the DeLong test. RESULTS: Overall (n = 199), mpMRI outperformed DCE-MRI alone (AUCmpMRI = 0.924 vs. AUCDCE-MRI = 0.884; p = 0.007). Furthermore, MMI outperformed both mpMRI and MG (the microcalcification group [n = 140]: AUCMMI = 0.997 vs. AUCmpMRI = 0.978, p = 0.018 and AUCMMI = 0.997 vs. AUCMG = 0.912, p < 0.001; the non-microcalcification group [n = 59]: AUCMMI = 0.857 vs. AUCmpMRI = 0.768, p = 0.044 and AUCMMI = 0.857 vs. AUCMG = 0.759, p = 0.039). CONCLUSION & ADVANCES IN KNOWLEDGE: DCE-MRI combined with DWI and TIRM information could improve the diagnostic performance for discriminating NME lesions compared with DCE-MRI alone. Furthermore, MMI combining mpMRI and MG showed better discrimination than both mpMRI and MG.

Comprehensive estimation for the length and dispersion of COVID-19 incubation period: a systematic review and meta-analysis.

PURPOSE: To estimate the central tendency and dispersion for incubation period of COVID-19 and, in turn, assess the effect of a certain length of quarantine for close contacts in active monitoring. METHODS: Literature related to SARS-CoV-2 and COVID-19 was searched through April 26, 2020. Quality was assessed according to Agency for Healthcare Research and Quality guidelines. Log-normal distribution for the incubation period was assumed to estimate the parameters for each study. Incubation period median and dispersion were estimated, and distribution was simulated. RESULTS: Fifty-six studies encompassing 4095 cases were included in this meta-analysis. The estimated median incubation period for general transmissions was 5.8 days [95% confidence interval (95% CI): 5.3, 6.2]. Incubation period was significantly longer for asymptomatic transmissions (median: 7.7 days; 95% CI 6.3, 9.4) than for general transmissions (P = 0.0408). Median and dispersion were higher for SARS-CoV-2 incubation compared to other viral respiratory infections. Furthermore, about 12 in 10,000 contacts in active monitoring would develop symptoms after 14 days, or below 1 in 10,000 for asymptomatic transmissions. Meta-regression suggested that each 10-year increase in age resulted in an average 16% increment in length of median incubation (incubation period ratio, 1.16, 95% CI 1.01, 1.32; P = 0.0250). CONCLUSION: This study estimated the median and dispersion of the SARS-CoV-2 incubation period more precisely. A 14-day quarantine period is sufficient to trace and identify symptomatic infections.

Global COVID-19 Pandemic Waves: Limited Lessons Learned Worldwide over the Past Year.

The occurrence of coronavirus disease 2019 (COVID-19) was followed by a small burst of cases around the world; afterward, due to a series of emergency non-pharmaceutical interventions (NPIs), the increasing number of confirmed cases slowed down in many countries. However, the lifting of control measures by the government and the public's loosening of precautionary behaviors led to a sudden increase in cases, arousing deep concern across the globe. arousing deep concern across the globe. This study evaluates the situation of the COVID-19 pandemic in countries and territories worldwide from January 2020 to February 2021. According to the time-varying reproduction number (R(t)) of each country or territory, the results show that almost half of the countries and territories in the world have never controlled the epidemic. Among the countries and territories that had once contained the occurrence, nearly half failed to maintain their prevention and control, causing the COVID-19 pandemic to rebound across the world-resulting in even higher waves in half of the rebounding countries or territories. This work also proposes and uses a time-varying country-level transmission risk score (CTRS), which takes into account both R(t) and daily new cases, to demonstrate country-level or territory-level transmission potential and trends. Time-varying hierarchical clustering of time-varying CTRS values was used to successfully reveal the countries and territories that contributed to the recent aggravation of the global pandemic in the last quarter of 2020 and the beginning of 2021, and to identify countries and territories with an increasing risk of COVID-19 transmission in the near future. Furthermore, a regression analysis indicated that the introduction and relaxation of NPIs, including workplace closure policies and stay-at-home requirements, appear to be associated with recent global transmission changes. In conclusion, a systematic evaluation of the global COVID-19 pandemic over the past year indicates that the world is now in an unexpected situation, with limited lessons learned. Summarizing the lessons learned could help in designing effective public responses for constraining future waves of COVID-19 worldwide.

Determinants associated with doctors' prescribing behaviors in public hospitals in China.

Doctors' prescribing behaviors impact both medical expenses and health resources. This study aims to identify the significant determinants of prescribing behaviors of doctors, which could potentially provide theoretical evidence on how to improve prescribing decisions. A multistage, stratified, cluster, random sampling method was employed in this survey. Data were collected from Jiangsu and Shanxi provinces in China in 2018. A total of 444 doctors in public hospitals completed the self-administered questionnaires. A structural equation model based on the theory of planned behavior (TPB) was adopted for analysis. On the basis of the TPB, we constructed a model of doctors' prescribing behaviors, which explained the subjective and objective reasons for irrational prescribing behavior. Behavioral attitude, subjective norms, and perceived behavioral control could positively influence the actual behaviors, of which subjective norms impact prescribing behaviors the most. Employing the TPB helped in identifying determinants of prescribing behaviors from a new perspective. More significant policy changes and government support are required to help improve appropriate prescribing behaviors and ultimately make better prescribing decisions. This study provided a deeper understanding of this complex issue and will inform the development of a theory and evidence-based intervention for future research.

Cord serum elementomics profiling of 56 elements depicts risk of preterm birth: Evidence from a prospective birth cohort in rural Bangladesh.

Maternal exposure to some individual rare earth elements and trace elements is associated with preterm birth, but few elements have been studied and little is known about the potential effect of simultaneous exposure to multiple elements. We examined individual and mixture effects of elements on preterm birth among 745 pregnant women in a prospective birth cohort in Bangladesh (2008-2011). We measured 56 elements in umbilical cord blood collected during delivery using inductively coupled plasma-mass spectrometry. Using elastic net (ENET) regularization and multivariate logistic regression, we examined independent associations between element concentrations and preterm birth. Bayesian kernel machine regression identified mixture effects of elements most critical to preterm birth, accounting for correlated exposure and interaction. ENET identified titanium (Ti), arsenic (As), and barium (Ba) as the most important predictors of shortened gestational age and preterm birth. In adjusted models, cord blood Ti (OR = 2.52; 95% CI: 1.08-5.93; P = 0.033), As (odds ratio (OR) = 1.34; 95% CI: 1.04-1.73; P = 0.023), and Ba (OR = 1.18; 95% CI: 1.02-1.38; P = 0.029) were significantly associated with preterm birth. Bayesian kernel machine regression suggested an interaction effect between As and Ba. Further, we constructed an element risk score (ERS) using estimated weights from a multivariate regression model for Ti, As, and Ba and regressed preterm birth by this score (OR = 2.72, 95% CI: 1.57-4.69; P = 3.35 × 10-4). Additionally, we observed a significant modification effect of child marriage on ERS, which means marriage before the age of 18 (Pinteraction = 0.0438). This study identified element exposures profiles in cord blood and constructed metal risk score that are jointly associated with the risk of preterm birth. Ti, As, and Ba exposure may adversely affect birth outcomes as well as child marriage may be a modifiable factor potentially affecting environmental element exposure and preterm birth.

Mendelian Randomization With Refined Instrumental Variables From Genetic Score Improves Accuracy and Reduces Bias.

Mendelian randomization (MR) can estimate the causal effect for a risk factor on a complex disease using genetic variants as instrument variables (IVs). A variety of generalized MR methods have been proposed to integrate results arising from multiple IVs in order to increase power. One of the methods constructs the genetic score (GS) by a linear combination of the multiple IVs using the multiple regression model, which was applied in medical researches broadly. However, GS-based MR requires individual-level data, which greatly limit its application in clinical research. We propose an alternative method called Mendelian Randomization with Refined Instrumental Variable from Genetic Score (MR-RIVER) to construct a genetic IV by integrating multiple genetic variants based on summarized results, rather than individual data. Compared with inverse-variance weighted (IVW) and generalized summary-data-based Mendelian randomization (GSMR), MR-RIVER maintained the type I error, while possessing more statistical power than the competing methods. MR-RIVER also presented smaller biases and mean squared errors, compared to the IVW and GSMR. We further applied the proposed method to estimate the effects of blood metabolites on educational attainment, by integrating results from several publicly available resources. MR-RIVER provided robust results under different LD prune criteria and identified three metabolites associated with years of schooling and additional 15 metabolites with indirect mediation effects through butyrylcarnitine. MR-RIVER, which extends score-based MR to summarized results in lieu of individual data and incorporates multiple correlated IVs, provided a more accurate and powerful means for the discovery of novel risk factors.

Child marriage, maternal serum metal exposure, and risk of preterm birth in rural Bangladesh: evidence from mediation analysis.

BACKGROUND: The prevalence of preterm birth in Bangladesh is estimated to be 19.1%, the highest in the world. Although prenatal exposure to several metals has been linked with preterm birth, fewer prospective studies have investigated the socioeconomic factors that affect metal exposure, leading to preterm birth risk. OBJECTIVE: We aim to identify novel metal biomarkers and their critical exposure windows, as well as the upstream socioeconomic risk factors for preterm birth in rural Bangladeshi, to shed light for future interventional strategies. METHODS: This study included data from 780 mother-offspring pairs, who were recruited to participate in a prospective birth cohort in Bangladesh (2008-2011). Serum concentrations of 19 metals were measured in the first and second trimesters using inductively coupled plasma mass spectrometry. Mediation analysis was performed to explore the upstream socioeconomic factors that affect the risk of preterm birth mediated via metal exposure concentrations. RESULTS: Early pregnancy exposure to serum zinc, arsenic, and strontium and mid-pregnancy exposure to barium were significantly associated with risk of preterm birth. Furthermore, younger marriage age was associated with an exponential increase in the risk of preterm birth, and women who married after 18 years old had a considerably lower risk of preterm birth. Mediation analysis indicated that these four elements mediated 30.2% of the effect of marriage age on preterm birth. CONCLUSION: This study indicated that maternal serum metal exposure mediates the impact of child marriage on the increased risk of preterm birth via metal exposures. The findings shed light on the mechanisms underlying such association and provide insights into future interventional strategies.

The lab-confirmed interval of COVID-19 clusters and its application in the strength evaluation of prevention and control measures.

BACKGROUND: The lab-confirmed interval is the date from lab confirmation in a core case (infector) to lab confirmation in a second case (infectee); however, its distribution and application are seldom reported. This study aimed to investigate the lab-confirmed interval and its application in the preliminary evaluation of the strength of disease prevention and control measures. METHODS: Taking European countries and Chinese provinces outside Hubei as examples, we identified 63 infector-infectee pairs from European countries from Wikipedia, and 103 infector-infectee pairs from official public sources in Chinese provinces outside Hubei. The lab-confirmed intervals were obtained through analysis of the collected data and adopting the bootstrap method. RESULTS: The mean lab-confirmed interval was 2.6 (95% CI: 2.1-3.1) days for Europe and 2.6 (95% CI: 1.9-3.3) days for China outside Hubei, which were shorter than the reported serial intervals. For index patients aged ≥60 years old, the lab-confirmed interval in Europe was slightly longer (mean: 2.9; 95% CI: 2.0-3.6) and obviously longer in China outside Hubei (mean: 3.8; 95% CI: 1.9-5.5) than that for patients aged < 60 years. CONCLUSION: Investigation of the lab-confirmed interval can provide additional information on the characteristics of emergent outbreaks and can be a feasible indication to evaluate the strength of prevention and control measures. When the lab-confirmed interval was shorter than the serial interval, it could objectively reflect improvements in laboratory capacity and the surveillance of close contacts.

Association of Serum Mannose With Acute Respiratory Distress Syndrome Risk and Survival.

Importance: Acute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis. Objective: To systematically evaluate the association of blood metabolites with ARDS risk and survival. Design, Setting, and Participants: In this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019. Main Outcomes and Measures: Participants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival. Results: Of the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = 7.46 × 10-6) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97; P = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56; P = 6.95 × 10-4) and 60-day (OR, 0.36; 95% CI, 0.19-0.71; P = 3.12 × 10-3) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74; P = 6.41 × 10-4) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80; P = 2.11 × 10-3) survival. Conclusions and Relevance: In this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.

Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients.

DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.

Implementation of Clinical Diagnostic Criteria and Universal Symptom Survey Contributed to Lower Magnitude and Faster Resolution of the COVID-19 Epidemic in Wuhan.

The majority of cases infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China centered in the city of Wuhan. Despite a rapid increase in the number of cases and deaths due to the coronavirus disease 2019 (COVID-19), the epidemic was stemmed via a combination of epidemic mitigation and control measures. This study evaluates how the implementation of clinical diagnostics and universal symptom surveys contributed to epidemic control in Wuhan. We extended the susceptibles-exposed-infectious-removed (SEIR) transmission dynamics model by considering three quarantined compartments (SEIR+Q). The SEIR+Q dynamics model was fitted using the daily reported number of confirmed infections and unconfirmed cases by clinical diagnostic criteria up to February 14, 2020, in Wuhan. Applying the model to carry forward the pre-February 14 trend in Wuhan, the number of daily new diagnosed cases would be expected to drop below 100 by March 25, below 10 by April 29, and reach 0 by May 31, 2020. The observed case counts after February 14 demonstrated that the daily new cases fell below 100 by March 6, below 10 by March 11, and reached 0 by March 18, respectively, 19, 49, and 74 d earlier than model predictions. By March 30, the observed number of cumulative confirmed cases was 50 006, which was 19 951 cases fewer than the predicted count. Effective reproductive number R(t) analysis using observed frequencies showed a remarkable decline after the implementation of clinical diagnostic criteria and universal symptom surveys, which was significantly below the R(t) curve estimated by the model assuming that the pre-February 14 trend was carried forward. In conclusion, the proposed SEIR+Q dynamics model was a good fit for the epidemic data in Wuhan and explained the large increase in the number of infections during February 12-14, 2020. The implementation of clinical diagnostic criteria and universal symptom surveys contributed to a contraction in both the magnitude and the duration of the epidemic in Wuhan.

Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects.

BACKGROUND: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. RESEARCH QUESTION: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? STUDY DESIGN AND METHODS: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. RESULTS: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10-17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10-18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. INTERPRETATION: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.

Epigenetic-smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients.

Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30-2.09, P = 4.52 × 10-5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87-1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking (37.49LUAD vs 54.79LUSC, P = 1.03 × 10-19) and included a higher proportion of current smokers than LUAD patients (28.24%LUAD vs 34.09%LUSC, P = 0.037). cg05293407TRIM27 was significantly associated with overall survival only in NSCLC patients with medium-high pack-year of smoking (HR = 1.58, 95% CI: 1.26-1.96, P = 5.25 × 10-5). We conclude that cg05293407TRIM27 methylation is a potential predictor of LUSC prognosis, and smoking intensity may impact on its prognostic value across the various types of NSCLC.

SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic-smoking interaction analysis.

Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome-wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two-stage study design to identify DNA methylation-smoking cessation interactions that affect overall survival for early-stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology-stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation-smoking cessation interaction terms. Interactions with false discovery rate-q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology-specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510SIPA1L3 ) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR)interaction  = 1.12; 95% confidence interval (CI): 1.07-1.16; P = 4.30 × 10-7 ]. Further, the effect of smoking cessation on early-stage LUAD survival varied across patients with different methylation levels of cg02268510SIPA1L3 . Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34-0.82; P = 4.61 × 10-3 ) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86-1.70; P = 0.266) of cg02268510SIPA1L3 . Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA1L3 and smoking cessation (HRinteraction  = 2.1835; 95% CI: 1.27-3.74; P = 4.46 × 10-3 ). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510SIPA1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting.

Factors Associated With Smoking Intentions Among Chinese College Students.

Smoking intention is a strong predictor of future smoking behavior. The aim of this study is to identify the significant factors associated with smoking intention among Chinese college students. A total of 2,827 students in Eastern, Middle, and Western regions of China, randomly selected using a multistage sampling method, completed the self-administered questionnaires. The association of independent variables with smoking intention was evaluated using the logistic regression model. Overall, the proportion of college students with a strong smoking intention was 6.9%. Male students (odds ratio [OR] 2.205, 95% confidence interval [CI] [1.374, 3.538]), those students whose mothers smoked (OR 3.328, 95% CI [1.527, 7.252]), those whose mothers had a higher educational level (OR 0.583, 95% CI [0.346, 0.984]), current smokers (OR 14.081, 95% CI [9.306, 21.307]), former smokers (OR 3.824, 95% CI [1.728, 8.463]), and those for whom most (OR 2.663, 95% CI [1.348, 5.261]) or a few (OR 1.826, 95% CI [1.045, 3.191]) of their closest friends were smokers had statistically significant associations with the smoking intentions of Chinese college students. Further studies are needed to elucidate mechanisms and pathways across various factors, and these factors should be incorporated into future multilevel interventions designed to decrease smoking intention among college students.

Ultrafast and sensitive room temperature NH3 gas sensors based on chemically reduced graphene oxide.

Ultrafast and sensitive room temperature NH3 gas sensors based on chemically reduced graphene oxide (rGO) are demonstrated in this work. rGO, which was prepared via the reduction of graphene oxide by pyrrole, exhibited excellent responsive sensitivity and selectivity to ammonia (NH3) gas. The high sensing performance of these rGO sensors with resistance change as high as 2.4% and response time as fast as 1.4 s was realized when the concentration of NH3 gas was as low as 1 ppb. Furthermore, the rGO sensors could rapidly recover to their initial states with IR illumination. The devices also showed excellent repeatability and selectivity to NH3. These rGO sensors, with low cost, low power, and easy fabrication, as well as scalable properties, showed great potential for ultrasensitive detection of NH3 gas in a wide variety of fields.

Template-free Synthesis of One-dimensional Cobalt Nanostructures by Hydrazine Reduction Route.

One-dimensional cobalt nanostructures with large aspect ratio up to 450 have been prepared via a template-free hydrazine reduction route under external magnetic field assistance. The morphology and properties of cobalt nanostructures were characterized by scanning electron microscopy, X-ray diffractometer, and vibrating sample magnetometer. The roles of the reaction conditions such as temperature, concentration, and pH value on morphology and magnetic properties of fabricated Co nanostructures were investigated. This work presents a simple, low-cost, environment-friendly, and large-scale production approach to fabricate one-dimensional magnetic Co materials. The resulting materials may have potential applications in nanodevice, catalytic agent, and magnetic recording.