Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer.

Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.

Up-front autologous stem cell transplant in peripheral T-cell lymphoma patients achieving complete response after first-line treatment: A multicentre real-world analysis.

We conducted a retrospective, multicentre study to compare consolidation therapy with or without first-line autologous stem cell transplant (ASCT) for peripheral T-cell lymphoma (PTCL) patients in a real-world setting. We enrolled 347 PTCL patients who achieved complete response after first-line treatment. Of these, 257 received consolidation chemotherapy (non-ASCT group) and 90 received ASCT (ASCT group). Clinical outcomes were comparable between ASCT and non-ASCT groups. After propensity score matching, the 2-year cumulative incidence of treatment-related mortality and relapse remained similar between groups (1.9% vs. 2.0%, p = 0.985; 24.7% vs. 47.1%, p = 0.021). However, significant differences emerged in progression-free survival and overall survival probabilities. Within the T-cell lymphoma subgroup, ASCT patients exhibited favourable outcomes compared to non-ASCT patients: 2-year progression-free survival (73.4% vs. 50.8%, p = 0.024) and overall survival (92.1% vs. 73.5%, p = 0.021). Notably, no significant differences were observed for patients with NK/T-cell lymphoma. These real-world data suggest that up-front ASCT is a safe and effective consolidation option for PTCL patients in remission, particularly those with T-cell lymphoma.

Computed tomography-based radiomics model to predict adverse clinical outcomes in acute pulmonary embolism.

This preliminary study investigated the feasibility of a combined model constructed using radiomic features based on computed tomography (CT) and clinical features to predict adverse clinical outcomes in acute pulmonary embolism (APE). Currently, there is no widely recognized predictive model. Patients with confirmed APE who underwent CT pulmonary angiography were retrospectively categorized into good and poor prognosis groups. Seventy-four patients were randomized into a training (n = 51) or validation (n = 23) cohort. Feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator regression was used to identify the optimal radiomics features and calculate the radiomics scores; subsequently, the radiomics model was developed. A combined predictive model was constructed based on radiomics scores and selected clinical features. The predictive efficacy of the three models (radiomics, clinical and combined) was assessed by plotting receiver operating characteristic curves. Furthermore, the calibration curves were graphed and the decision curve analysis was performed. Four radiomic features were screened to calculate the radiomic score. Right ventricular to left ventricular ratio (RV/LV) ≥ 1.0 and radiomics score were independent risk factors for adverse clinical outcomes. In the training and validation cohorts, the areas under the curve (AUCs) for the RV/LV ≥ 1.0 (clinical) and radiomics score prediction models were 0.778 and 0.833 and 0.907 and 0.817, respectively. The AUCs for the combined model of RV/LV ≥ 1.0 and radiomics score were 0.925 and 0.917, respectively. The combined and radiomics models had high clinical assessment efficacy for predicting adverse clinical outcomes in APE, demonstrating the clinical utility of both models. Calibration curves exhibited a strong level of consistency between the predictive and observed probabilities of poor and good prognoses in the combined model. The combined model of RV/LV ≥ 1.0 and radiomics score based on CT could accurately and non-invasively predict adverse clinical outcomes in patients with APE.

Tracheostomy care of non-ventilated patients and COVID considerations: A scoping review of clinical practice guidelines and consensus statements.

BACKGROUND: The purpose of this study is to examine and evaluate the existing clinical practice guidelines and consensus statements regarding tracheostomy care for non-mechanically ventilated patients. METHODS: A systematic search of databases, and professional organisations was conducted from inception to 19 March 2023. Two appraisers evaluated each guideline using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Text and Opinion Papers. RESULTS: No specific clinical guidelines exist on airway management in non-mechanically ventilated patients. Of 6318 articles identified, we included 12 clinical practice guidelines, and 9 consensus statements, which were from China, the US, the UK, South Korea, Australia, France and Belgium. The AGREE II scores in six domains are (1) the scope and purpose, 70.30%; (2) stakeholder involvement, 37.61%; (3) rigor of development, 33.97%; (4) clarity of presentation, 68.16%; (5) applicability, 44.23% and (6) editorial independence, 40.06%. The overall quality of evidence was level B. The summarised recommendations for clinical practice encompass the following six areas: airway humidification, management of the trach cuff, management of inner cannula, tracheostoma care, tracheostomy suctioning and management and prevention of common post-operative complications. CONCLUSIONS: The overall quality of the clinical guidelines on non-ventilated tracheostomy care was moderate, and further improvements are needed in domains of stakeholder involvement, applicability, clarity of presentation and editorial independence. Recommendations on non-ventilated tracheostomy care are often embedded in the guidelines on ventilated tracheostomy. Specific clinical guidelines are needed to provide a standardised approach to tracheostomy care for non-ventilated patients. RELEVANCE TO CLINICAL PRACTICE: Patients with non-ventilated tracheostomy need specialised airway management. Improving patient outcomes requires standardised protocols, patient involvement, quality evaluation, and interdisciplinary approaches. NO PATIENT OR PUBLIC CONTRIBUTION: The study reviewed clinical practice guidelines and consensus statements, therefore patient or public input was not needed.

A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for lung cancer in Chinese populations.

Although dozens of susceptibility loci have been identified for lung cancer in genome-wide association studies (GWASs), the susceptibility genes and underlying mechanisms remain unclear. In this study, we conducted a cross-tissue transcriptome-wide association study (TWAS) with UTMOST based on summary statistics from 13 327 lung cancer cases and 13 328 controls and the genetic-expression matrix over 44 human tissues in the Genotype-Tissue Expression (GTEx) project. After further evaluating the associations in each tissue, we revealed 6 susceptibility genes in known loci and identified 12 novel ones. Among those, five novel genes, including DCAF16 (Pcross-tissue = 2.57 × 10-5, PLung = 2.89 × 10-5), CBL (Pcross-tissue = 5.08 × 10-7, PLung = 1.82 × 10-4), ATR (Pcross-tissue = 1.45 × 10-5, PLung = 9.68 × 10-5), GYPE (Pcross-tissue = 1.45 × 10-5, PLung = 2.17 × 10-3) and PARD3 (Pcross-tissue = 5.79 × 10-6, PLung = 4.05 × 10-3), were significantly associated with the risk of lung cancer in both cross-tissue and lung tissue models. Further colocalization analysis indicated that rs7667864 (C > A) and rs2298650 (G > T) drove the GWAS association signals at 4p15.31-32 (OR = 1.09, 95%CI: 1.04-1.12, PGWAS = 5.54 × 10-5) and 11q23.3 (OR = 1.08, 95%CI: 1.04-1.13, PGWAS = 5.55 × 10-5), as well as the expression of DCAF16 (ßGTEx = 0.24, PGTEx = 9.81 × 10-15; ßNJLCC = 0.29, PNJLCC = 3.84 × 10-8) and CBL (ßGTEx = -0.17, PGTEx = 2.82 × 10-8; ßNJLCC = -0.32, PNJLCC = 2.61 × 10-7) in lung tissue. Functional annotations and phenotype assays supported the carcinogenic effect of these novel susceptibility genes in lung carcinogenesis.

The association of donor hepatitis C virus infection with 3-year kidney transplant outcomes in the era of direct-acting antiviral medications.

To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT- [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT- (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

Distinct Denitrifying Phenotypes of Predominant Bacteria Modulate Nitrous Oxide Metabolism in Two Typical Cropland Soils.

Denitrifying nitrous oxide (N2O) emissions in agroecosystems result from variations in microbial composition and soil properties. However, the microbial mechanisms of differential N2O emissions in agricultural soils are less understood. In this study, microcosm experiments using two main types of Chinese cropland soil were conducted with different supplements of nitrate and glucose to simulate the varying nitrogen and carbon conditions. The results show that N2O accumulation in black soil (BF) was significantly higher than that in fluvo-aquic soil (FF) independent of nitrogen and carbon. The abundance of most denitrifying genes was significantly higher in FF, but the ratios of genes responsible for N2O production (nirS and nirK) to the gene responsible for N2O reduction (nosZ) did not significantly differ between the two soils. However, the soils showed obvious discrepancies in denitrifying bacterial communities, with a higher abundance of N2O-generating bacteria in BF and a higher abundance of N2O-reducing bacteria in FF. High accumulation of N2O was verified by the bacterial isolates of Rhodanobacter predominated in BF due to a lack of N2O reduction capacity. The dominance of Castellaniella and others in FF led to a rapid reduction in N2O and thus less N2O accumulation, as demonstrated when the corresponding isolate was inoculated into the studied soils. Therefore, the different phenotypes of N2O metabolism of the distinct denitrifiers predominantly colonized the two soils, causing differing N2O accumulation. This knowledge would help to develop a strategy for mitigating N2O emissions in agricultural soils by regulating the phenotypes of N2O metabolism.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Development and Evaluation of Health Recommender Systems: Systematic Scoping Review and Evidence Mapping.

BACKGROUND: Health recommender systems (HRSs) are information retrieval systems that provide users with relevant items according to the users' needs, which can motivate and engage users to change their behavior. OBJECTIVE: This study aimed to identify the development and evaluation of HRSs and create an evidence map. METHODS: A total of 6 databases were searched to identify HRSs reported in studies from inception up to June 30, 2022, followed by forward citation and grey literature searches. Titles, abstracts, and full texts were screened independently by 2 reviewers, with discrepancies resolved by a third reviewer, when necessary. Data extraction was performed by one reviewer and checked by a second reviewer. This review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) statement. RESULTS: A total of 51 studies were included for data extraction. Recommender systems were used across different health domains, such as general health promotion, lifestyle, and generic health service. A total of 23 studies had reported the use of a combination of recommender techniques, classified as hybrid recommender systems, which are the most commonly used recommender techniques in HRSs. In the HRS design stage, only 10 of 51 (19.6%) recommender systems considered personal preferences of end users in the design or development of the system; a total of 29 studies reported the user interface of HRSs, and most HRSs worked on users' mobile interfaces, usually a mobile app. Two categories of HRS evaluations were used, and evaluations of HRSs varied greatly; 62.7% (32/51) of the studies used the offline evaluations using computational methods (no user), and 33.3% (17/51) of the studies included end users in their HRS evaluation. CONCLUSIONS: Through this scoping review, nonmedical professionals and policy makers can visualize and better understand HRSs for future studies. The health care professionals and the end users should be encouraged to participate in the future design and development of HRSs to optimize their utility and successful implementation. Detailed evaluations of HRSs in a user-centered approach are needed in future studies.

Determination of acetic acid in enzymes based on the cataluminescence activity of graphene oxide-supported carbon nanotubes coated with NiMn layered double hydroxides.

A cataluminescence (CTL) method has been developed for the rapid determination of acetic acid in enzyme products. The NiMn LDH/CNT/GO was synthesized based on the nanohybridization of NiMn layered double hydroxide (NiMn LDH), carbon nanotubes (CNTs), and graphene oxide (GO). The composite has excellent CTL activity against acetic acid. It could be ascribed to the larger specific surface area and more exposure to active sites. NiMn LDH/CNT/GO is used as a catalyst in the CTL method based on its special structure and advantages. There is a linear relationship between CTL response and the acetic acid concentration in the range 0.31-12.00 mg·L-1 with the detection limit of 0.10 mg·L-1. The developed method is rapid and takes only about 13 s. The method is applied to the determination of acetic acid in enzyme samples with little sample preparation. The result of the CTL method shows good agreement with that of the gas chromatography method. The proposed CTL method possesses promising potential in the quality monitoring of enzymes.

Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes.

Excessive hepatic lipid accumulation is a common phenomenon in cultured fish; however, its underlying mechanisms are poorly understood. Lipid droplet (LD)-related proteins play vital roles in LD accumulation. Herein, using a zebrafish liver cell line (ZFL), we show that LD accumulation is accompanied by differential expression of seven LD-annotated genes, among which the expression of dehydrogenase/reductase (SDR family) member 3 a/b (dhrs3a/b) increased synchronously. RNAi-mediated knockdown of dhrs3a delayed LD accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma (pparg) in cells incubated with fatty acids. Notably, Dhrs3 catalyzed retinene to retinol, the content of which increased in LD-enriched cells. The addition of exogenous retinyl acetate maintained LD accumulation only in cells incubated in a lipid-rich medium. Correspondingly, exogenous retinyl acetate significantly increased pparg mRNA expression levels and altered the lipidome of the cells by increasing the phosphatidylcholine and triacylglycerol contents and decreasing the cardiolipin, phosphatidylinositol, and phosphatidylserine contents. Administration of LW6, an hypoxia-inducible factor 1α (HIF1α) inhibitor, reduced the size and number of LDs in ZFL cells and attenuated hif1αa, hif1αb, dhrs3a, and pparg mRNA expression levels. We propose that the Hif-1α/Dhrs3a pathway participates in LD accumulation in hepatocytes, which induces retinol formation and the Ppar-γ pathway.

Building Machine Learning Models to Correct Self-Reported Anthropometric Measures.

Monitoring population obesity risk primarily depends on self-reported anthropometric data prone to recall error and bias. This study developed machine learning (ML) models to correct self-reported height and weight and estimate obesity prevalence in US adults. Individual-level data from 50 274 adults were retrieved from the National Health and Nutrition Examination Survey (NHANES) 1999-2020 waves. Large, statistically significant differences between self-reported and objectively measured anthropometric data were present. Using their self-reported counterparts, we applied 9 ML models to predict objectively measured height, weight, and body mass index. Model performances were assessed using root-mean-square error. Adopting the best performing models reduced the discrepancy between self-reported and objectively measured sample average height by 22.08%, weight by 2.02%, body mass index by 11.14%, and obesity prevalence by 99.52%. The difference between predicted (36.05%) and objectively measured obesity prevalence (36.03%) was statistically nonsignificant. The models may be used to reliably estimate obesity prevalence in US adults using data from population health surveys.

Circulating C-reactive protein increases lung cancer risk: Results from a prospective cohort of UK Biobank.

Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted  = .003, Padjusted  = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.

DNA Aptamer Selected against Esophageal Squamous Cell Carcinoma for Tissue Imaging and Targeted Therapy with Integrin ß1 as a Molecular Target.

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin ß1 as the binding target of A2 through pull-down and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin ß1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine-glycine-aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.

Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70-0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68-0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68-0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62-0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56-0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55-0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.

Corrigendum: Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

[This corrects the article DOI: 10.3389/ti.2022.10618.].

Air Pollution, Genetic Factors, and the Risk of Lung Cancer: A Prospective Study in the UK Biobank.

Rationale: Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. Objectives: To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. Methods: We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM) (PM ⩽2.5 µm in aerodynamic diameter [PM2.5], coarse PM between 2.5 µm and 10 µm in aerodynamic diameter [PMcoarse], and PM ⩽10 µm in aerodynamic diameter [PM10]), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated by using land-use regression models, and the association between air pollutants and incident lung cancer was investigated by using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. Measurements and Main Results: The results showed significant associations between the risk of lung cancer and PM2.5 (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.33-2.01; per 5 µg/m3), PM10 (HR, 1.53; 95% CI, 1.20-1.96; per 10 µg/m3), NO2 (HR, 1.10; 95% CI, 1.05-1.15; per 10 µg/m3), and NOx (HR, 1.13; 95% CI, 1.07-1.18; per 20 µg/m3). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution exposure, those with high air pollution exposure and high genetic risk had the highest risk of lung cancer (PM2.5: HR, 1.71; 95% CI, 1.45-2.02; PM10: HR, 1.77; 95% CI, 1.50-2.10; NO2: HR, 1.77; 95% CI, 1.42-2.22; NOx: HR, 1.67; 95% CI, 1.43-1.95). Conclusions: Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.

Parenting styles in relation to childhood obesity, smoking and drinking: A gene-environment interaction study.

BACKGROUND: The present study assessed gene-environment interactions linking maternal parenting styles to childhood obesity and alcohol and tobacco use. METHODS: Data were retrieved from the first wave of the German Twin Family Panel. Participants comprised three birth cohorts, aged 5, 11 and 17 years, with approximately 500 pairs of same-sex monozygotic twins and 500 pairs of same-sex dizygotic twins per cohort. Self-reported parenting styles were measured in five dimensions: emotional warmth, psychological control, negative communication, monitoring and inconsistent parenting. Outcome variables included children's body mass index z-score (BMIz) and smoking and alcohol drinking frequency. Gene-environment interaction models were used to assess how parenting styles might moderate genetic and environmental influences on BMIz and smoking and drinking behaviours. RESULTS: A positive interaction of genetic effects with psychological control was found for BMIz at age 5 years, indicating that genetic influences on BMIz increased with psychological control. No interaction effect was found for BMIz at ages 11 and 17 years. Regarding adolescent smoking, positive interaction between genetic effects and negative communication was found, indicating that genetic influences on smoking increased with negative communication. There was no significant moderating effect of parenting styles on adolescent drinking. CONCLUSIONS: The present study found preliminary evidence indicating that parenting styles moderated genetic and environmental impacts on body weight status and smoking. Moderation effects of parenting on BMIz were observed only at a very young age. The moderating effects of parenting influenced adolescent smoking but not drinking.

Evidence map of recommendations on diabetic foot ulcers care：A systematic review of 22 guidelines.

BACKGROUND: Diabetic foot ulcers (DFUs) are one of the major complications of diabetes, representing a leading cause of hospitalization and non-traumatic lower limb amputations. Clinical practice guidelines (CPGs) are statements that include recommendations intended to improve patients' outcomes by providing recommendations for key clinical issues with alternative care options. The aim of this study is to systematically review CPGs on DFUs care and generate an evidence-map for visualizing research trends and gaps in the CPGs. METHODS: A search of the PubMed, Embase, and Web of Science, guideline databases and website of diabetes society was performed to include the diabetic CPGs. We exacted the basic information, methodological quality and reporting quality of CPGs, recommendations for DFUs care by the Excel 2016. Four researchers evaluated the methodological and reporting quality of diabetic foot CPGs by AGREE Ⅱ instrument and RIGHT checklist. The bubble plot format of evidence map was reduced by R (3.5.1) software. RESULTS: 22 CPGs proved eligible, which included 10 diabetic foot guidelines and 12 comprehensive diabetes guidelines. According to the recommendations of diabetic CPGs, current standard of care for DFUs care mainly involves offloading of pressure, wound care, choice of shoes and adjunctive treatment. Recommendations on offloading of pressure and wound care were consistent in 22 CPGs. However, there were some conflicts on adjunctive treatment recommendations and recommendations for choice of shoes were not accurate. CONCLUSION: There is mixed quality evidence of CPGs for DFUs care, and some recommendations are inconsistent. This evidence map could provide new perspectives in presentation of evidence and help us know the need for future research to address the current gaps, as well as areas of opportunity for CPG development.

Genome-wide gene-smoking interaction study identified novel susceptibility loci for non-small cell lung cancer in Chinese populations.

Gene-smoking interactions play important roles in the development of non-small cell lung cancer (NSCLC). To identify single-nucleotide polymorphisms (SNPs) that modify the association of smoking behavior with NSCLC risk, we conducted a genome-wide gene-smoking interaction study in Chinese populations. The genome-wide interaction analysis between SNPs and smoking status (ever- versus never-smokers) was carried out using genome-wide association studies of NSCLC, which included 13 327 cases and 13 328 controls. Stratified analysis by histological subtypes was also conducted. We used a genome-wide significance threshold of 5 × 10-8 for identifying significant gene-smoking interactions and 1 × 10-6 for identifying suggestive results. Functional annotation was performed to identify potential functional SNPs and target genes. We identified three novel loci with significant or suggestive gene-smoking interaction. For NSCLC, the interaction between rs2746087 (20q11.23) and smoking status reached genome-wide significance threshold [odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.54-0.74, P = 3.31 × 10-8], and the interaction between rs11912498 (22q12.1) and smoking status reached suggestive significance threshold (OR = 0.72, 95% CI: 0.63-0.82, P = 8.10 × 10-7). Stratified analysis by histological subtypes identified suggestive interactions between rs459724 (5q11.2) and smoking status (OR = 0.61, 95% CI: 0.51-0.73, P = 7.55 × 10-8) in the risk of lung squamous cell carcinoma. Functional annotation indicated that both classic and novel biological processes, including nicotine addiction and airway clearance, may modulate the susceptibility to NSCLC. These novel loci provide new insights into the biological mechanisms underlying NSCLC risk. Independent replication in large-scale studies is needed and experimental studies are warranted to functionally validate these associations.