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Background: Recent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear. Methods: Here, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15 HCC-associated genetic loci from two PRSs and FinnGen GWAS data to calculate a PRS-combined score and to fit the related PRS model in the UK Biobank cohort (N = 436,162). The PRS-combined score was further assessed for risk stratification for HCC integrating with the recommended clinical risk scores. Results: The PRS-combined model achieved a better AUC (0.657) than that of PRS-HFC (0.637) and PRS-cirrhosis (0.645). The top 20% of the PRS-combined distribution had a 3.25 increased risk of HCC vs. the middle decile (45–55%). At the population level, the addition of PRS-combined to the CLivD score significantly increased the C-statistic (from 0.716 to 0.746) and provided a remarkable improvement in reclassification (NRI = 0.088) at the 10-year risk threshold of 0.2%. In clinic, additional assessment of PRS-combined would reclassify 34,647 intermediate-risk participants as high genetic risk, corresponding to an increase of 63.92% (62/97) of the HCC events classified at high risk using the Fibrosis-4 alone. Conclusions: The PRS may enhance HCC risk prediction effectiveness in the general population and refine risk stratification of the conventional clinical indicator. [ABSTRACT FROM AUTHOR]

The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never‐smoking women. We first performed a large GWAS meta‐analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never‐smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta‐analysis identified eight known loci and a novel locus (5q11.2) at the genome‐wide statistical significance level of P < 5 × 10−8. Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS‐21) for lung cancer in never‐smoking women. Furthermore, PRS‐21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18‐1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00‐1.72) and high (HR = 2.09, 95% CI: 1.56‐2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS‐21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS‐derived PRS‐21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never‐smoking Asian women, demonstrating the potential for identification of high‐risk individuals and early screening. [ABSTRACT FROM AUTHOR]

Background: Screening reduces colorectal cancer (CRC) burden by allowing early resection of precancerous and cancerous lesions. An adequate selection of high-risk individuals and a high uptake rate for colonoscopy screening are critical to identifying people more likely to benefit from screening and allocating healthcare resources properly. We evaluated whether combining a questionnaire-based interview for risk factors with fecal immunochemical test (FIT) outcomes for high-risk assessment is more efficient and economical than a questionnaire-based interview-only strategy. Methods and findings: In this multicenter, population-based, prospective cohort study, we enrolled community residents aged 40 to 74 years in 29 provinces across China. From 2016 to 2020, a total of 1,526,824 eligible participants were consecutively enrolled in the Cancer Screening Program in Urban China (CanSPUC) cohort, and 940,605 were enrolled in the Whole Life Cycle of Cancer Screening Program (WHOLE) cohort, with follow-up to December 31, 2022. The mean ages were 56.89 and 58.61 years in CanSPUC and WHOLE, respectively. In the WHOLE cohort, high-risk individuals were identified by combining questionnaire-based interviews to collect data on risk factors (demographics, diet history, family history of CRC, etc.) with FIT outcomes (RF–FIT strategy), whereas in the CanSPUC cohort, high-risk individuals were identified using only interview-based data on risk factors (RF strategy). The primary outcomes were participation rate and yield (detection rate of advanced neoplasm, early-stage detection rate of CRCs [stage I/II], screening yield per 10,000 invitees), which were reported for the entire population and for different gender and age groups. The secondary outcome was the cost per case detected. In total, 71,967 (7.65%) and 281,985 (18.47%) individuals were identified as high-risk and were invited to undergo colonoscopy in the RF–FIT group and RF group, respectively. The colonoscopy participation rate in the RF–FIT group was 26.50% (19,071 of 71,967) and in the RF group was 19.54% (55,106 of 281,985; chi-squared test, p < 0.001). A total of 102 (0.53%) CRCs and 2,074 (10.88%) advanced adenomas were detected by the RF–FIT, versus 90 (0.16%) and 3,593 (6.52%) by the RF strategy (chi-squared test, both p < 0.001). The early-stage detection rate using the RF–FIT strategy was significantly higher than that by the RF strategy (67.05% versus 47.95%, Fisher's exact test, p = 0.016). The cost per CRC detected was $24,849 by the RF–FIT strategy versus $55,846 by the RF strategy. A limitation of the study was lack of balance between groups with regard to family history of CRC (3.5% versus 0.7%). Conclusions: Colonoscopy participation and screening yield were better with the RF–FIT strategy. The association with CRC incidence and mortality reduction should be evaluated after long-term follow-up. Author summary: Why was this study done?: ➢ The burden of colorectal cancer (CRC) in China has been growing in recent years. ➢ More specific selection of individuals to undergo colonoscopy, based on both questionnaire-based risk assessment and fecal immunochemical test (FIT) results, could result in more efficiency allocation of colonoscopy resources. ➢ There is limited evidence on the colonoscopy screening yield when combining FITs and risk assessment through questionnaires. What did the researchers do and find?: ➢ We calculated the baseline screening yield, participation, and cost per case detected in a national CRC screening program with a combined questionnaire-based risk assessment–FIT strategy. ➢ The baseline screening yield and participation rate were improved in the combined risk assessment–FIT group compared with risk factor assessment only group. ➢ The cost per CRC detected was $24,849 by the combined risk factor–FITs strategy, which was much lower than by the risk factor strategy ($55,846). What do these findings mean?: ➢ A combined CRC screening strategy is feasible in China. ➢ The association between the combined RF-FIT strategy with CRC incidence and mortality reduction should be evaluated after long-term follow-up. [ABSTRACT FROM AUTHOR]

The Taihu Biobank of Tumour Biomarkers (TBTB) study is a large-scale research project conducted in Wuxi, China, with the aim of understanding the prevalence, incidence, and mortality rates of cancer in middle-aged and elderly urban populations. The study recruited over 500,000 participants aged 45 and older and collected baseline data through physical examinations, serum tumor biomarkers, and questionnaire surveys. The study has identified thousands of new cancer cases and encourages collaborations with researchers worldwide. The study provides valuable data on demographic and health-related variables, laboratory test results, and the most commonly diagnosed cancers. However, there are limitations to the study, such as the lack of information on early life exposures and limited data on lifestyle factors. Researchers interested in the study are welcome to collaborate. [Extracted from the article]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Jiangsu Birth Cohort (JBC) is a research study in China that examines the health outcomes of families who underwent assisted reproductive technology (ART) treatment compared to families with spontaneous pregnancies. The cohort consists of over 7,600 ART-treated families and nearly 15,000 families with spontaneous pregnancies. Data on health were collected through questionnaires, medical records, and biospecimens from both parents and children. The study aims to assess the health and well-being of children conceived through ART and determine any factors that may contribute to elevated risks. The data from the study are available for research purposes. [Extracted from the article]

Household air pollution (HAP) is associated with the development of lung cancer, yet few studies investigated the exposure patterns and joint associations with tobacco smoking. In our study, we included 224 189 urban participants from China Kadoorie Biobank (CKB), 3288 of which diagnosed with lung cancer during the follow‐up. Exposure to four HAP sources (solid fuels for cooking/heating/stove and environmental tobacco smoke exposure) was assessed at baseline. Distinct HAP patterns and their associations with lung cancer were examined through latent class analysis (LCA) and multivariable Cox regression. A total of 76.1% of the participants reported regular cooking and 52.2% reported winter heating, of which 9% and 24.7% used solid fuels, respectively. Solid fuel heating increased lung cancer risk (Hazards ratio [HR]: 1.25, 95% confidence interval [CI]: 1.08‐1.46). LCA identified three HAP patterns; the "clean fuel cooking and solid fuel heating" pattern significantly increased lung cancer risk (HR: 1.25, 95% CI: 1.10‐1.41), compared to low HAP pattern. An additive interaction was observed between heavy smoking and "clean fuel cooking and solid fuel heating" (relative excess risk [RERI]: 1.32, 95% CI: 0.29‐2.47, attributable proportion [AP]: 0.23, 95% CI: 0.06‐0.36). Cases resulting from solid fuel account for ~4% of total cases (population attribute fraction [PAF]overall: 4.31%, 95% CI: 2.16%‐6.47%, PAFever smokers: 4.38%, 95% CI: 1.54%‐7.23%). Our results suggest that in urban China, solid fuel heating increased the risk of lung cancer, particularly among heavy smokers. The whole population could benefit from cleaner indoor air quality by reducing using solid fuels, especially smokers. [ABSTRACT FROM AUTHOR]

The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Gray's models were used for hazard ratios (HRs), their 95% confidence intervals (CIs), and the lifetime risk according to PRS and clinical risk categories. A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were included. Comparing the top versus bottom 5% of the PRS, the HR was 3.01 (95%CI 2.03–4.45) in the total population, and similar findings were observed within clinical risk strata. Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories. Notably, among individuals with intermediate clinical risk, the 10-year risk for those in the top 5% of the PRS (7.3%, 95%CI 7.1%–7.5%) reached the threshold of high clinical risk (⩾7.0%) for initiating preventive treatment, and this effect of the PRS on refining risk stratification was evident for ischemic stroke. Even among those in the top 10% and 20% of the PRS, the 10-year risk would also exceed this level when aged ⩾50 and ⩾60 years, respectively. Overall, the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk. [ABSTRACT FROM AUTHOR]

Background Growing evidence indicates the adverse effect of ultra-processed food (UPF) consumption. However, it remains unknown whether UPF consumption influences the risk of colorectal cancer (CRC) precursors, namely conventional adenomas and serrated lesions. Methods We drew data from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study, comprising 142 052 participants who had undergone at least 1 lower gastrointestinal endoscopy during follow-up. To handle multiple records per participants, we used multivariable logistic regression for clustered data to calculate odds ratios (OR) and 95% confidence intervals (CIs) of colorectal polyps in relation to cumulative average consumption of UPFs. All statistical tests were 2-sided. Results We documented 11 644 patients with conventional adenomas and 10 478 with serrated lesions during 18-20 years of follow-up. Compared with participants in the lowest quintile of UPF consumption, those in the highest quintile had an increased risk of conventional adenomas (OR = 1.18, 95% CI = 1.11 to 1.26) and serrated lesions (OR = 1.20, 95% CI = 1.13 to 1.28). Similar results were found for high-risk polyps (ie, advanced adenomas and ≥10 mm serrated lesions; OR = 1.17, 95% CI = 1.07 to 1.28). These associations were slightly attenuated but remained statistically significant after further adjusting for body mass index, Western dietary pattern score, or individual dietary factors (fiber, folate, calcium, and vitamin D). The results remained essentially unchanged after excluding processed meat from total UPF intake. Conclusions Higher consumption of UPFs is associated with an increased risk of CRC precursors. UPFs might be a modifiable target for early prevention of CRC. [ABSTRACT FROM AUTHOR]

Obesity is a leading contributor to colorectal cancer (CRC) risk, but the metabolic mechanisms linking obesity to CRC are not fully understood. We leveraged untargeted metabolomics data from two 1:1 matched, nested case–control studies for CRC, including 223 pairs from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and 190 pairs from a prospective Chinese cohort. We explored serum metabolites related to body mass index (BMI), constructed a metabolomic signature of obesity, and examined the association between the signature and CRC risk. In total, 72 of 278 named metabolites were correlated with BMI after multiple testing corrections (p FDR < 0.05). The metabolomic signature was calculated by including 39 metabolites that were independently associated with BMI. There was a linear positive association between the signature and CRC risk in both cohorts (p for linear < 0.05). Per 1-SD increment of the signature was associated with 38% (95% CI: 9–75%) and 28% (95% CI: 2–62%) higher risks of CRC in the US and Chinese cohorts, respectively. In conclusion, we identified a metabolomic signature for obesity and demonstrated the association between the signature and CRC risk. The findings offer new insights into the underlying mechanisms of CRC, which is critical for improved CRC prevention. [ABSTRACT FROM AUTHOR]

Background: The genetic architectures of colorectal cancer are distinct across different populations. To date, the majority of polygenic risk scores (PRSs) are derived from European (EUR) populations, which limits their accurate extrapolation to other populations. Here, we aimed to generate a PRS by incorporating East Asian (EAS) and EUR ancestry groups and validate its utility for colorectal cancer risk assessment among different populations. Methods: A large-scale colorectal cancer genome-wide association study (GWAS), harboring 35,145 cases and 288,934 controls from EAS and EUR populations, was used for the EAS-EUR GWAS meta-analysis and the construction of candidate EAS-EUR PRSs via different approaches. The performance of each PRS was then validated in external GWAS datasets of EAS (727 cases and 1452 controls) and EUR (1289 cases and 1284 controls) ancestries, respectively. The optimal PRS was further tested using the UK Biobank longitudinal cohort of 355,543 individuals and ultimately applied to stratify individual risk attached by healthy lifestyle. Results: In the meta-analysis across EAS and EUR populations, we identified 48 independent variants beyond genome-wide significance (P < 5 × 10−8) at previously reported loci. Among 26 candidate EAS-EUR PRSs, the PRS-CSx approach-derived PRS (defined as PRSCSx) that harbored genome-wide variants achieved the optimal discriminatory ability in both validation datasets, as well as better performance in the EAS population compared to the PRS derived from known variants. Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (Ptrend = 8.15 × 10−53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk. Conclusions: In summary, we systemically constructed an EAS-EUR PRS to effectively stratify colorectal cancer risk, which highlighted its clinical implication among diverse ancestries. Importantly, these findings also supported that a healthy lifestyle could reduce the genetic impact on incident colorectal cancer. [ABSTRACT FROM AUTHOR]

Characterization of metabolic perturbation prior to hepatocellular carcinoma (HCC) may deepen the understanding of causal pathways and identify novel biomarkers for early prevention. We conducted two 1:1 matched nested case‐control studies (108 and 55 pairs) to examine the association of plasma metabolome (profiled using LC‐MS) with the risk of HCC based on two prospective cohorts in China. Differential metabolites were identified by paired t tests and orthogonal partial least‐squares discriminant analysis (OPLS‐DA). Weighted gene coexpression network analysis (WGCNA) was performed to classify metabolites into modules for identifying biological pathways involved in hepatocarcinogenesis. We assessed the risk predictivity of metabolites using multivariable logistic regression models. Among 612 named metabolites, 44 differential metabolites were identified between cases and controls, including 12 androgenic/progestin steroid hormones, 8 bile acids, 10 amino acids, 6 phospholipids, and 8 others. These metabolites were associated with HCC in the multivariable logistic regression analyses, with odds ratios ranging from 0.19 (95% confidence interval [CI]: 0.11‐0.35) to 5.09 (95% CI: 2.73‐9.50). WGCNA including 612 metabolites showed 8 significant modules related to HCC risk, including those representing metabolic pathways of androgen and progestin, primary and secondary bile acids, and amino acids. A combination of 18 metabolites of independent effects showed the potential to predict HCC risk, with an AUC of 0.87 (95% CI: 0.82‐0.92) and 0.86 (95% CI: 0.80‐0.93) in the training and validation sets, respectively. In conclusion, we identified a panel of plasma metabolites that could be implicated in hepatocellular carcinogenesis and have the potential to predict HCC risk. [ABSTRACT FROM AUTHOR]

Background: Besides featured glucose consumption, recent studies reveal that cancer cells might prefer "addicting" specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. Methods: Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of LINC01614 into exosomes were identified using flow cytometric sorting, fluorescence in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 in lung adenocarcinoma (LUAD) and CAFs were investigated using 4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were performed to investigate the underlying mechanisms involved. Results: We demonstrate that cancer-associated fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived exosomes, mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-κB, which leads to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. Conclusion: Our study highlights the therapeutic potential of targeting a CAF-specific lncRNA to inhibit glutamine utilization and cancer progression in LUAD. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations.Methods: We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them.Results: During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) Poverall < 0.001 and FDR-adjusted Pnon-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted Poverall < 0.050 and FDR-adjusted Pnon-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including "fast-to-low increase" (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), "increase-to-decrease" (breast cancer), and "decrease-to-platform" (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers.Conclusions: Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks. [ABSTRACT FROM AUTHOR]

There has been no validated tool to assess workplace infection control towards SARS-Cov-2 in non-healthcare industries. In this first year survey during 07/2020–04/2021, 6684 workers were recruited from varied non-healthcare settings of Hong Kong, Nanjing and Wuhan of China and responded standard questionnaires containing information of prevention measures and policies implemented by companies and personal preventive behaviour towards infection control. All participants were randomly stratified into two sub-samples as training and validation sample. Workplace safety index towards SARS-Cov-2 (WSI-SC2) was developed and validated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We identified 14 manifest variables in WSI-SC2, with three sub-indices named "Workplace infection control measures and prevention", "Company occupational safety and health management and commitment" and "Worker's personal preventive behavior and awareness towards infectious control". WSI-SC2 obtained a good internal consistency reliability (Cronbach's alpha coefficients ranged: 0.76–0.91), good composite reliability (composite reliability ranged: 0.70–0.95) and satisfactory fit of the model (GFI = 0.95; SRMR = 0.05; RMSEA = 0.07). We further performed stratified analysis according to cities, and the index remained stable. Workers with higher scores of WSI-SC2 were more likely to uptake COVID-19 test. This multi-city large study developed a novel and validated tool that could horizontally measure the workplace safety towards SARS-Cov-2 in non-healthcare workers. [ABSTRACT FROM AUTHOR]

Sichuan Province spawned abundant of indigenous buffalo varieties, which probably harbor valuable gene resources beneficial to the genetic improvement of buffalo. However, limited genetic information was publicly available. To better understand their selection signatures between different populations, we performed a restriction site-associated DNA sequencing (RADseq) to explore genome-wide SNPs among two indigenous breeds of Sichuan buffaloes. As a result, a total of 2,110,077 high-quality SNPs were finally obtained. Population genetic analysis indicated a obviously genetic differentiation between two breeds. The detection of selective genes showed that 995 and 910 protein-coding genes underwent positive selection in Yibin buffalo (GYBS) and Dechang buffalo (XCS). Further functional analysis revealed distinctly discrepant selection in two breeds. Candidate genes that positively selected from Yibin buffaloes have mainly occurred in functions closely related to meat quality, complex living environment adaption capability, and disease resistance. While they were significantly enriched in cell proliferation and cell components in Dechang buffalo, indicating the selection pressure primarily derived from the requirement of organism growth and development speed during breed formation. Our dataset constitutes a promising reservoir of genome-wide SNP markers of Sichuan buffaloes and provides potentially traits selected in different local populations. Such comprehensive genetic resources offer an unprecedented opportunity for genetic association analysis of economically important traits and precision breeding programs in buffaloes. [ABSTRACT FROM AUTHOR]

(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33–7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61–0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70–0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC. [ABSTRACT FROM AUTHOR]

Many workers experienced income reduction during the coronavirus disease 2019 (COVID-19) pandemic, which may link to adverse mental health. This study aimed to examine the association of current income and reduction in income during COVID-19 with anxiety and depression levels among non-healthcare workers. This is a multi-city cross-sectional study. We used standardized questionnaires to collect information. We regrouped the current income and income reduction during COVID-19 according to the tertile and median value of each specific city. Depression, Anxiety and Stress Scales-21 item short version (DASS-21) was used to assess anxiety and depression levels. We performed multinomial logistic regression to examine the association of current and reduced income with anxiety and depression. Path models were developed to outline the potential modification/indirect effect of subsidies from government. Large income reduction and low current income were significantly associated with more anxiety/depression symptoms. Path analysis showed that government subsidies could not significantly alleviate the impact of reduced income on anxiety/depression. Our findings showed that large income reduction and low current income were independently associated with anxiety/depression, while these symptoms may not be ameliorated by one-off government funds. This study suggests the need for long-term policies (e.g. developing sustained economic growth policies) to mitigate negative impacts of the COVID-19. [ABSTRACT FROM AUTHOR]

Coal workers' pneumoconiosis (CWP) is a type of typical occupational lung disease caused by prolonged inhalation of coal mine dust. The individuals' different genetic background may underlie their different susceptibility to develop pneumoconiosis, even under the same exposure level. This study aimed to identify susceptibility genes associated with CWP. Based on our previous genome‐wide association study (GWAS, 202 CWP cases vs. 198 controls) and gene expression data obtained by analyzing human lungs and whole blood from the Genotype‐Tissue Expression (GTEx) Portal, a transcriptome‐wide association study (TWAS) was applied to identify CWP risk‐related genes. Luciferase report gene assay, qRT‐PCR, Western blot, immunofluorescence assay, and TUNEL assay were conducted to explore the potential role of the candidate gene in CWP. Proteasome 20S subunit beta 9 (PSMB9) was identified as a strong risk‐related gene of CWP in both lungs and whole blood (Lungs: PTWAS = 4.22 × 10−4; Whole blood: PTWAS = 2.11 × 10−4). Single nucleotide polymorphisms (SNPs) rs2071480 and rs1351383, which locate in the promoter region and the first intron of the PSMB9 gene, were in high linkage disequilibrium (LD, r2 = 0.98) with the best GWAS SNP rs4713600 (G>T, OR = 0.55, 95% CI: 0.42–0.74, P = 6.86 × 10−5). Both rs2071480 and rs1351383 significantly enhanced the transcriptional activity of PSMB9. Functional experiments revealed that silica exposure remarkably reduced the PSMB9 expression and caused cell apoptosis, while overexpression of PSMB9 markedly abolished silica‐induced cell apoptosis. We here identified PSMB9 as a novel susceptibility gene for CWP and provided important insights into the further exploration of the CWP pathogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited. Methods: Participants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer. Results: The detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose‐effect relationship between NLR, PLR, or SII and PNs (pnon‐linear > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11–1.28), 1.11 (1.04–1.19) or 1.11 (1.03–1.18), respectively. Meanwhile, NLR showed the U‐shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08–1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99–1.68) and 1.35 (1.04–1.74) comparing to the lowest quintile. Conclusions: The high levels of systemic inflammation markers were associated with the risk of positive pulmonary nodules and lung cancer, which suggested systemic immune response may be an important pre‐clinical feature for the early identification of diseases. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) has been found to be associated with a decreased risk of non-small cell lung cancer (NSCLC); however, the effect of BMI trajectories and potential interactions with genetic variants on NSCLC risk remain unknown.Methods: Cox proportional hazards regression model was applied to assess the association between BMI trajectory and NSCLC risk in a cohort of 138,110 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. One-sample Mendelian randomization (MR) analysis was further used to access the causality between BMI trajectories and NSCLC risk. Additionally, polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between BMI trajectories and genetic variants in NSCLC risk.Results: Compared with individuals maintaining a stable normal BMI (n = 47,982, 34.74%), BMI trajectories from normal to overweight (n = 64,498, 46.70%), from normal to obese (n = 21,259, 15.39%), and from overweight to obese (n = 4,371, 3.16%) were associated with a decreased risk of NSCLC (hazard ratio [HR] for trend = 0.78, P < 2×10-16). An MR study using BMI trajectory associated with genetic variants revealed no significant association between BMI trajectories and NSCLC risk. Further analysis of PRS showed that a higher GWAS-identified PRS (PRSGWAS) was associated with an increased risk of NSCLC, while the interaction between BMI trajectories and PRSGWAS with the NSCLC risk was not significant (PsPRS= 0.863 and PwPRS= 0.704). In GWIA analysis, four independent susceptibility loci (P < 1×10-6) were found to be associated with BMI trajectories on NSCLC risk, including rs79297227 (12q14.1, located in SLC16A7, Pinteraction = 1.01×10-7), rs2336652 (3p22.3, near CLASP2, Pinteraction = 3.92×10-7), rs16018 (19p13.2, in CACNA1A, Pinteraction = 3.92×10-7), and rs4726760 (7q34, near BRAF, Pinteraction = 9.19×10-7). Functional annotation demonstrated that these loci may be involved in the development of NSCLC by regulating cell growth, differentiation, and inflammation.Conclusions: Our study has shown an association between BMI trajectories, genetic factors, and NSCLC risk. Interestingly, four novel genetic loci were identified to interact with BMI trajectories on NSCLC risk, providing more support for the aetiology research of NSCLC.Trial Registration: http://www.Clinicaltrials: gov , NCT01696968 . [ABSTRACT FROM AUTHOR]

Molecular variation between geographical populations and subtypes indicate potential genomic heterogeneity and novel genomic features within CCA. Here, we analyze exome-sequencing data of 87 perihilar cholangiocarcinoma (pCCA) and 261 intrahepatic cholangiocarcinoma (iCCA) cases from 3 Asian centers (including 43 pCCAs and 24 iCCAs from our center). iCCA tumours demonstrate a higher tumor mutation burden and copy number alteration burden (CNAB) than pCCA tumours, and high CNAB indicates a poorer pCCA prognosis. We identify 12 significantly mutated genes and 5 focal CNA regions, and demonstrate common mutations in post-transcriptional modification-related potential driver genes METTL14 and RBM10 in pCCA tumours. Finally we demonstrate the tumour-suppressive role of METTL14, a major RNA N6-adenosine methyltransferase (m6A), and illustrate that its loss-of-function mutation R298H may act through m6A modification on potential driver gene MACF1. Our results may be valuable for better understanding of how post-transcriptional modification can affect CCA development, and highlight both similarities and differences between pCCA and iCCA. Cholangiocarcinoma is a heterogenous group of cancers, with large genetic variation seen within subtypes. Here, the authors find 12 significantly mutated genes and 5 focal CNA regions were found in perihilar cholangiocarcinoma, and identified METTL14 to have a potential tumour suppressive role. [ABSTRACT FROM AUTHOR]

How metabolome changes influence the early process of colorectal cancer (CRC) development remains unknown. We conducted a 1:2 matched nested case–control study to examine the associations of pre-diagnostic plasma metabolome (profiled using LC–MS) with risk of CRC precursors, including conventional adenomas (n = 586 vs. 1141) and serrated polyps (n = 509 vs. 993), in the Nurses' Health Study (NHS) and NHSII. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We used the permutation-based Westfall and Young approach to account for multiple testing. Subgroup analyses were performed for advanced conventional adenomas (defined as at least one adenoma of ≥ 10 mm or with high-grade dysplasia, or tubulovillous or villous histology) and high-risk serrated polyps that were located in the proximal colon or with size of ≥ 10 mm. After multiple testing correction, among 207 metabolites, higher levels of C36:3 phosphatidylcholine (PC) plasmalogen were associated with lower risk of conventional adenomas, with the OR (95% CI) comparing the 90th to the 10th percentile of 0.62 (0.48–0.81); C54:8 triglyceride (TAG) was associated with higher risk of serrated polyps (OR = 1.79, 95% CI: 1.31–2.43), and phenylacetylglutamine (PAG) was associated with lower risk (OR = 0.57, 95% CI:0.43–0.77). PAG was also inversely associated with advanced adenomas (OR = 0.57, 95% CI: 0.36–0.89) and high-risk serrated polyps (OR = 0.54, 95% CI: 0.32–0.89), although the multiple testing-corrected p value was > 0.05. Our findings suggest potential roles of lipid metabolism and phenylacetylglutamine, a microbial metabolite, in the early stage of colorectal carcinogenesis, particularly for the serrated pathway. [ABSTRACT FROM AUTHOR]

Background: Little prospective evidence exists about whether a combination of healthy lifestyle factors is related to a considerable reduction of liver cancer risk.Methods: Based on the prospective China Kadoorie Biobank (CKB) cohort with a total of 492,640 Chinese adults, we examined the associations of five lifestyle factors with risk of liver cancer. Low-risk lifestyle factors were defined as non-smoking, non-drinking, median or higher level of physical activity, a healthy diet, and waist-to-hip ratio (WHR) < 0.90 for men and <0.85 for women.Results: During a median of 10.12 years of follow-up, 2529 liver cancer events were observed. There was a significant decrease in liver cancer risk with the increasing of the healthy lifestyle index scores (P < 0.001). Participants with a favourable lifestyle (4 or 5 healthy lifestyle factors) had a 43% reduced liver cancer risk compared with those with an unfavourable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.57 [95% CI, 0.47-0.68]). The cumulative protective effect of a healthy lifestyle on liver cancer appeared to be more dramatic for patients with hepatitis B surface antigen (HBsAg) positive, the individuals at high risk of liver cancer.Conclusions: Individuals adhering to a favourable lifestyle was associated with a considerable absolute risk reduction of liver cancer. [ABSTRACT FROM AUTHOR]

Background: Adolescents aged from 19 to 22 are the main high-risk population of pulmonary tuberculosis (PTB). This study aimed to understand the current status of knowledge, attitudes and practices (KAP) about TB among freshmen from Jiangsu colleges and universities. Analyze its influencing factors and explore the interrelationships of KAP. This provides a basis for building a reversing mechanism for health education on tuberculosis prevention and treatment in middle and high schools. Methods: A multistage randomly was used to select freshmen to conduct this online survey. The χ2 test was used to compare the rates. Construct linear regression model, logistic regression model, decision tree model and random forest model, use grid search to adjust the parameters of the model, and use multiple models to explore the influencing factors of the overall awareness rate of students' core knowledge of tuberculosis. Results: A total of 6980 freshmen in colleges and universities were investigated. The total awareness rate was 89.02%, and the awareness rate of all core knowledge about TB was 58.94%. It is characterized by general demographic data, and all core knowledge is known as a label to establish a model, based on the f1- of the four models The score believes that the random forest model has the best fitting effect, and the ranking of the influencing factors included in the model is school type (0.72) >father's education (0.15) >family monthly income (0.03) >mother's education, gender, region (0.02); a structural equation model is established, and the modified knowledge and attitude path coefficient is 0.29 (P< 0.05); the attitude and behavior path coefficient is 0.64 (P< 0.05). Conclusion: The total awareness rate of core knowledge of Jiangsu college freshmen reaches the national requirements, but the overall awareness rate is low. It is necessary to strengthen the health education of tuberculosis for those with identified risk factors. [ABSTRACT FROM AUTHOR]

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. What's new? Chronic inflammation has been associated with the development of lung cancer. Here, the authors examined the association between circulating C‐reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomisation to clarify the causality. Circulating CRP levels were significantly associated with the risk of lung cancer across different histological subtypes. Although the etiological role of CRP in lung cancer remains unproven, CRP improved lung cancer risk prediction by allowing pre‐diagnosis as long as 8 years in advance among current smokers. The study provides additional evidence for the utility of CRP measurements in lung cancer risk stratification. [ABSTRACT FROM AUTHOR]

Adenosine-to-inosine (A-to-I) RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis. Here, we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma (LUAD) patients from our Nanjing Lung Cancer Cohort (NJLCC) and 486 LUAD patients from the TCGA database. The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients. The high RNA editing level in tumors was attributed to both RNA (ADAR1 expression) and DNA alterations (mutation load). Consensus clustering on RNA editing sites revealed a new molecular subtype (EC3) that was associated with the poorest prognosis of LUAD patients. Importantly, the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation. We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients. The model was further validated in the TCGA dataset and had an area under the curve (AUC) of the receiver operating characteristic curve of 0.93 (95%CI: 0.91–0.95). In addition, we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs. These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer. [ABSTRACT FROM AUTHOR]

Background Epidemiological evidence remains conflicting regarding diet and risk of lung cancer. Objectives We sought to systematically investigate whether dietary factors are associated with the risk of incident lung cancer in the UK Biobank. Methods A total of 416,588 participants (54% women) from the UK Biobank were included in the present study. Based on baseline data from FFQs, 3 main dietary patterns were identified by using principal component analysis. Cox proportional hazards models were used to investigate the association of individual food groups and dietary patterns with lung cancer risk. Results During a median follow-up of 7.13 y, 1782 incident lung cancer cases were documented. The association analysis showed high intake of red meat and processed meat was associated with an increased risk of lung cancer (HRper 50 g/d: 1.36; 95% CI: 1.13, 1.65 for red meat; HRper 25 g/d: 1.30; 95% CI: 1.10, 1.53 for processed meat). However, the consumption of fruits (HRper 100 g/d: 0.90; 95% CI: 0.84, 0.95), vegetables (HRper 100 g/d: 0.89; 95% CI: 0.81, 0.99), breakfast cereals (HRper 50 g/d: 0.81; 95% CI: 0.74, 0.89), and dietary fiber (HRper 5 g/d: 0.76; 95% CI: 0.69, 0.84) was inversely associated with the risk of lung cancer. For the dietary pattern analysis [quartile (Q) comparison], high adherence to the Prudent pattern (HRQ4 compared with Q1: 0.84; 95% CI: 0.73, 0.96) was associated with a lower risk of lung cancer, whereas the Western pattern (HRQ4 compared with Q1: 1.27; 95% CI: 1.11, 1.46) was associated with a higher risk of lung cancer. Conclusions Our study indicated that a diet characterized by high intake of fruits, vegetables, breakfast cereals, and dietary fiber, as well as low intake of red meat and processed meat, was associated with a lower risk of lung cancer. [ABSTRACT FROM AUTHOR]

Inner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating. Previous studies indicated that defects of IDA protein complex result in multiple morphological abnormalities of the sperm flagellum (MMAF) and male infertility. However, the genetic causes and molecular mechanisms in the IDAs need further exploration. Here we identified two loss-of-function variants of WDR63 in both MMAF and non-obstructive azoospermia (NOA) affected cohorts. WDR63 encodes an IDA-associated protein that is dominantly expressed in testis. We next generated Wdr63-knockout (Wdr63-KO) mice through the CRISPR-Cas9 technology. Remarkably, Wdr63-KO induced decreased sperm number, abnormal flagellar morphology and male infertility. In addition, transmission electron microscopy assay showed severely disorganized "9 + 2" axoneme and absent inner dynein arms in the spermatozoa from Wdr63-KO male mice. Mechanistically, we found that WDR63 interacted with WDR78 mainly via WD40-repeat domain and is necessary for IDA assembly. Furthermore, WDR63-associated male infertility in human and mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. In conclusion, the present study demonstrates that bi-allelic variants of WDR63 cause male infertility via abnormal inner dynein arms assembly and flagella formation and can be used as a genetic diagnostic indicator for infertility males. [ABSTRACT FROM AUTHOR]

Inner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating. Previous studies indicated that defects of IDA protein complex result in multiple morphological abnormalities of the sperm flagellum (MMAF) and male infertility. However, the genetic causes and molecular mechanisms in the IDAs need further exploration. Here we identified two loss-of-function variants of WDR63 in both MMAF and non-obstructive azoospermia (NOA) affected cohorts. WDR63 encodes an IDA-associated protein that is dominantly expressed in testis. We next generated Wdr63-knockout (Wdr63-KO) mice through the CRISPR-Cas9 technology. Remarkably, Wdr63-KO induced decreased sperm number, abnormal flagellar morphology and male infertility. In addition, transmission electron microscopy assay showed severely disorganized "9 + 2" axoneme and absent inner dynein arms in the spermatozoa from Wdr63-KO male mice. Mechanistically, we found that WDR63 interacted with WDR78 mainly via WD40-repeat domain and is necessary for IDA assembly. Furthermore, WDR63-associated male infertility in human and mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. In conclusion, the present study demonstrates that bi-allelic variants of WDR63 cause male infertility via abnormal inner dynein arms assembly and flagella formation and can be used as a genetic diagnostic indicator for infertility males. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to investigate the associations between maternal diabetes before or during pregnancy and the risk of high refractive error (RE) in offspring until the age of 25 years. Methods: This nationwide register-based cohort study comprised 2,470,580 individuals born in 1977–2016. The exposure was maternal diabetes during or before pregnancy (type 1 diabetes, type 2 diabetes and gestational diabetes). Cox regression was used to examine the association between maternal diabetes and the risk of high RE in offspring from birth until the age of 25 years, adjusting for multiple potential confounders. Results: During up to 25 years of follow-up, 553 offspring of mothers with diabetes and 19,695 offspring of mothers without diabetes were diagnosed with high RE. Prenatal exposure to maternal diabetes was associated with a 39% increased risk of high RE: HR 1.39 (95% CI 1.28, 1.51), p < 0.001; standardised cumulative incidence in unexposed offspring at 25 years of age 1.18% (95% CI 1.16%, 1.19%); cumulative incidence difference 0.72% (95% CI 0.51%, 0.94%). The elevated risks were observed for hypermetropia (HR 1.37 [95% CI 1.24, 1.51], p < 0.001), myopia (HR 1.34 [95% CI 1.08, 1.66], p = 0.007) and astigmatism (HR 1.58 [95% CI 1.29, 1.92], p < 0.001). The increased risks were more pronounced among offspring of mothers with diabetic complications (HR 2.05 [95% CI 1.60, 2.64], p < 0.001), compared with those of mothers with diabetes but no diabetic complications (HR 1.18 [95% CI 1.02, 1.37], p = 0.030). Conclusions/interpretation: Our findings suggest that maternal diabetes during pregnancy is associated with an increased risk of high RE in offspring, in particular among those of mothers with diabetic complications. Early ophthalmological screening should be recommended in offspring of mothers with diabetes diagnosed before or during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives. Human adenoviruses (HAdV) are classified as 7 HAdV species, and some serotypes in species B like HAdV 3, HAdV 7, HAdV 21, and HAdV 55 caused severe symptoms, even fatalities. Patients may be misdiagnosed and inadequately treated without reliable and practical methods for HAdV serotyping. Developing rapid, sensitive, and specific diagnostic methods for HAdV is critical. Methods. Detection methods were established based on a recombinase polymerase amplification (RPA) assay and lateral flow (LF) test. Specific target sequence was screened, targeting which, primers and probes were designed, synthesized, and screened for establishing assay with high amplification efficiency. Primer or probe concentrations and amplification time were optimized. Detection limit, sensitivity, and specificity were evaluated. Results and Conclusions. Simple, sensitive, and specific RPA-LF methods for detection of four serotypes of HAdV together or separately were established, which had detection limits of 10 to 280 copies/reaction comparable to real-time PCR without recognizing other pathogens. The sensitivity and specificity were >92% and >98%, respectively, evaluated by limited clinical samples. The detection can be completed in 25 min without requirement of any instrument except a constant temperature equipment, showing superior detection performance and promising for a wide use in the field and resource-limited area. [ABSTRACT FROM AUTHOR]

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19. [ABSTRACT FROM AUTHOR]

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up‐to‐date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10‐year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person‐years of follow‐up. Excellent discrimination of the model was observed in both development and validation datasets, with c‐statistics (95% CI) of 0.80 (0.79‐0.81) and 0.80 (0.78‐0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10‐year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB‐PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high‐risk groups among the general population. What's new? A personalized risk prediction model for liver cancer based on hepatitis B virus infection status, medical history, and metabolic and lifestyle‐related risk factors could facilitate early diagnosis and thereby improve patient outcome. Here, a personalized risk prediction model based on these routinely available factors was developed and found to effectively discriminate between individuals at how and low risk of liver cancer. The model further exhibited improved screening benefit compared with current HBsAg carrier screening and demonstrated promise as a risk counseling tool. The findings suggest that the model could be readily implemented as a clinical aid to liver cancer screening. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1–5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively. Fragment size analysis using DNAs from these fractions showed dramatical differences from a peak of 7–10 kb in fraction 1 to 140–160 bp in fraction 6. To determine ctDNA content, we performed whole genome sequencing and applied copy number-based algorithm to calculate ctDNA percentage. This analysis showed the highest ctDNA content in EV-depleted plasma (average = 27.22%), followed by exosomes (average = 22.09%) and large vesicles (average = 19.70%). Comparatively, whole plasma, which has been used in most ctDNA studies, showed an average of 23.84% ctDNA content in the same group of patients. To further demonstrate higher ctDNA content in fraction 6, we performed mutational analysis in the plasma samples from 22 non-small cell lung cancer (NSCLC) patients with known EGFR mutations. This analysis confirmed higher mutation detection rates in fraction 6 (14/22) than whole plasma (10/22). This study provides a new insight into potential application of using fractionated plasma for an improved ctDNA detection. [ABSTRACT FROM AUTHOR]

The genetic architecture of non-small cell lung cancer (NSCLC) is relevant to smoking status. However, the genetic contribution of long-term smoking cessation to the prognosis of NSCLC patients remains largely unknown. We conducted a genome-wide association study primarily on the prognosis of 1299 NSCLC patients of long-term former smokers from independent discovery (n = 566) and validation (n = 733) sets, and used in-silico function prediction and multi-omics analysis to identify single nucleotide polymorphisms (SNPs) on prognostics with NSCLC. We further detected SNPs with at least moderate association strength on survival within each group of never, short-term former, long-term former, and current smokers, and compared their genetic similarity at the SNP, gene, expression quantitative trait loci (eQTL), enhancer, and pathway levels. We identified two SNPs, rs34211819TNS3 at 7p12.3 (P = 3.90 × 10−9) and rs1143149SEPT7 at 7p14.2 (P = 9.75 × 10−9), were significantly associated with survival of NSCLC patients who were long-term former smokers. Both SNPs had significant interaction effects with years of smoking cessation (rs34211819TNS3: Pinteraction = 8.0 × 10−4; rs1143149SEPT7: Pinteraction = 0.003). In addition, in silico function prediction and multi-omics analysis provided evidence that these QTLs were associated with survival. Moreover, comparison analysis found higher genetic similarity between long-term former smokers and never-smokers, compared to short-term former smokers or current smokers. Pathway enrichment analysis indicated a unique pattern among long-term former smokers that was related to immune pathways. This study provides important insights into the genetic architecture associated with long-term former smoking NSCLC. [ABSTRACT FROM AUTHOR]

Two thousand sixty‐four lung cancer cases and 5342 controls were evaluated in this International Lung Cancer Consortium (ILCCO) pooled analysis on estrogen‐related hormonal factors and lung cancer in Asian women. Random effect of study site and fixed effect of age, smoking status, comprehensive smoking index and family history of lung cancer were adjusted for in the multivariable logistic regression models. We found that late onset of menarche conferred elevated odds of lung cancer with adjusted odds ratio (OR) of 1.24 (95% confidence interval [CI] = 1.05, 1.45) for 17 years or older, compared to 14 years or younger. Late onset of menopause at 55 years old or older was associated with lung cancer with OR = 1.24 (95% CI = 1.02, 1.51). Nonnatural menopause was associated with an OR of 1.39 (95% CI = 1.13, 1.71). More live births showed reversed association with lung cancer (ORs of 5 or more live births: 0.71 (95% CI = 0.60, 0.84), compared to 0‐2 live births (Ptrend < 0.001). A later first child delivery seemed associated with an increased susceptibility: OR of 21 to 25 years old: 1.23 (95% CI = 1.06, 1.40), 26 or older: 1.27 (95% CI = 1.06, 1.52), Ptrend =.010). The use of oral contraceptives appeared to be protective with an OR of 0.69 (95% CI = 0.57, 0.83). Stronger for adenocarcinoma than squamous cell carcinoma, these relationships were not clearly modified by smoking status, probably because of lower prevalence of smoking. This is a first and largest pooling study of lung cancer among Asian women and the results suggested potential roles of hormone‐related pathways in the etiology of this disease. What's new? Evidence suggests a relationship between estrogen‐related hormones and lung cancer, but most of these studies have been done in European populations. Here, the authors built the largest ever female Asian lung cancer population, by pooling 6 epidemiological studies. They found a correlation between lung cancer risk and older age at menarche and menopause. On the other hand, having more children was associated with reduced risk of lung cancer, as was oral contraceptive use. Interestingly, these associations differ from those reported in Europeans, in particular the associations with childbirth and with age at menache. [ABSTRACT FROM AUTHOR]

The article presents the discussion on showing no signs of growth for benign nodules receiving a diagnosis of histoplasmosis infection by fungal serology and diagnosis being made on bronchoscopy in the patient.

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments. [ABSTRACT FROM AUTHOR]