To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer.
Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was ...identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets.
In UKBB, the presence of CH was associated with increased risk of lung cancer (cases: 12.5%
controls: 8.7%; multivariable-adjusted odds ratio OR, 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases: 15.6%
controls: 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung
breast cancer: 1.61; 95% CI, 1.03 to 2.53).
Independent of known risk factors, CH is associated with increased risk of lung cancer.
Risk factors contributing to more than 10-fold increase in esophageal cancer in the last 50 years remain underexplored. We aim to examine the associations of sleep behaviors with esophageal ...adenocarcinoma (EAC) and squamous cell carcinoma (ESCC).
We prospectively assessed the associations between sleep behaviors (chronotype, duration, daytime napping, daytime sleepiness, snoring, and insomnia) and EAC and ESCC risk in 393,114 participants in the UK Biobank (2006-2016). Participants with 0, 1, and ≥2 unhealthy behaviors, including sleep <6 or >9 h/d, daytime napping, and usual daytime sleepiness were classified as having a good, intermediate, and poor sleep. For EAC, we also examined interactions with polygenic risk score (PRS). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).
We documented 294 incident EAC and 95 ESCC. Sleep >9 h/d (HR, 2.05; 95% CI, 1.18-3.57) and sometimes daytime napping (HR, 1.36; 95% CI, 1.06-1.75) were individually associated with increased EAC risk. Compared with individuals with good sleep, those with intermediate sleep had a 47% (HR, 1.47; 95% CI, 1.13-1.91) increased EAC risk, and those with poor sleep showed an 87% (HR, 1.87; 95% CI, 1.24-2.82) higher risk (Ptrend < 0.001). The elevated risks for EAC were similar within strata of PRS (Pinteraction = 0.884). Evening chronotype was associated with elevated risk of ESCC diagnosed after 2 years of enrollment (HR, 2.79; 95% CI, 1.32-5.88).
Unhealthy sleep behaviors were associated with an increased risk of EAC, independent of genetic risk.
Sleep behaviors may serve as modifiable factors for the prevention of EAC.
The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly ...understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.
•A new fault diagnosis method based on Bi-LSTM and capsule network is proposed.•This paper focuses on the impact of the number of training samples on accuracy.•The characteristics of small sample of ...capsule network are investigated.•The performance of this method is validated in the data of bearings and gears.•The adaption to different working loads and signal-to-noise ratios is good.
For the application of deep learning in the field of fault diagnosis, its recognition accuracy is limited by the size and quality of the training samples, such as small size samples, low signal-to-noise ratio and different working conditions. In order to solve above problems, one novel method for fault classification is proposed based on a Bidirectional Long Short-Term Memory (Bi-LSTM) and a Capsule Network with convolutional neural network (BLC-CNN). The Bi-LSTM is utilized to achieve the feature denoising and fusion, which is extracted by CNN. The fault diagnosis with insufficient training samples is carried out by the capsule network. The influence of sample size on the method is discussed emphatically. The effectiveness and superiority of the proposed method are validated through analyzing the data of bearings and gears under different working conditions with different noise. The results indicate that the proposed method has good performance and immunity to noise.
For the established fault classification system, new faults cannot be identified due to lack of training data in the process of equipment operation. Aiming at the problems of multi-classification, ...small samples, and cross-domain brought by the new faults, one meta learning intelligent fault diagnosis method is proposed based on multi-scale dilated convolution and relation module. Firstly, multi-scale convolution is utilized to improve the feature extraction effectiveness in the extraction module. Subsequently, the fusion module is designed by dilated convolution and stochastic pooling. Finally, the relation module is employed to evaluate the distance between samples for fault diagnosis. Crucially, the meta learning strategy is executed to transform the training set into multiple tasks to train the proposed method. The superiority and effectiveness of the proposed method is validated by bearing and gearbox experiments with a few labeled fault samples. For the bearing fault diagnosis test, the verification results show that the accuracy rate of this method is 95.11% in 8way 1-shot, which is increased by 6.15% on average.
Adhesion and scarring after neural surgery are detrimental to nerve regeneration and functional recovery. Amniotic membranes have been used in tissue repair due to their immunogenicity and richness ...in cytokines. In this study, an electrospun polycaprolactone (PCL)-amnion nanofibrous membrane was prepared for the treatment of sciatic nerve compression in a rat model. The effects of the PCL-amnion nanofibrous membrane on the prevention of adhesion formation and nerve regeneration were evaluated using electrophysiology and histological analyses. Compared with the medical chitosan hydrogel dressing, the PCL-amnion nanofibrous membrane significantly reduced peripheral nerve adhesion and promoted the rapid recovery of nerve conduction. Moreover, the immunohistochemical analysis identified more Schwann cells and less pro-inflammatory M1 macrophages in the PCL-amnion group. Western blot and RT-PCR results showed that the expression levels of type-Ⅰ and Ⅲ collagen in the PCL-treated rats were half of those in the control group after 12 weeks, while the expression level of nerve growth factor was approximately 3.5 times that found in the rats treated with medical chitosan hydrogel. In summary, electrospun PCL-amnion nanofibrous membranes can effectively reduce adhesion after neural surgery and promote nerve repair and regeneration. The long-term retention in vivo and sustained release of cytokines make PCL-amnion a promising biomaterial for clinical application.
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