Showing papers by "Bing Zhang published in 2020"

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19.

Abstract: With the dramatic increase of confirmed cases of coronavirus disease (COVID-19) and the increasing death toll in China, timely and effective management of severely and critically ill patients appears to be particularly important. Previous studies on COVID-19 mainly described the general features of patients (1). However, little attention has been paid to clinical characteristics and outcomes of intensive care patients, data on whom are scarce but are of paramount importance to reduce mortality. Some of the results of these studies have been previously reported in the form of an abstract (2).

Watering Down Environmental Regulation in China

Abstract: This article estimates the effect of environmental regulation on firm productivity using a spatial regression discontinuity design implicit in China's water quality monitoring system Because water quality readings are important for political evaluations and the monitoring stations only capture emissions from their upstream regions, local government officials are incentivized to enforce tighter environmental standards on firms immediately upstream of a monitoring station, rather than those immediately downstream Exploiting this discontinuity in regulation stringency with novel firm-level geocoded emission and production data sets, we find that immediate upstream polluters face a more than 24% reduction in total factor productivity (TFP), and a more than 57% reduction in chemical oxygen demand emissions, as compared with their immediate downstream counterparts We find that the discontinuity in TFP does not exist in nonpolluting industries, only emerged after the government explicitly linked political promotion to water quality readings, and was predominantly driven by prefectural cities with career-driven leaders Linking the TFP estimate with the emission estimate, a back-of-the-envelope calculation indicates that China's water regulation efforts between 2000 and 2007 were associated with an economic cost of more than 800 billion Chinese yuan

Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis

Abstract: Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.

Adjuvant corticosteroid therapy for critically ill patients with COVID-19

Abstract: Addition of adjuvant corticosteroid therapy to standard antiviral treatment of patients with coronavirus disease (COVID-19) is common in clinical practice. However, evidence is scarce regarding the efficacy of adjuvant corticosteroids in patients who are critically ill. We retrospectively evaluated the effects of adjuvant corticosteroid treatment on the outcome of 244 critically ill patients with COVID-19, using a risk stratification model that adjusts for potential differences between the steroid group (n=151) and the non-steroid group (n=93). We observed that adjuvant corticosteroid therapy was independent from 28-day mortality, either in multivariate logistic regression of the entire cohort after adjustment for major mortality-associated variables (age, SpO2/FiO2, and lymphocyte count) and individual propensity score (adjusted OR: 1.05; 95% CI: −1.92-2.01), or in propensity score-matched (1:1 without replacement) case-control analysis (62 patients in 31 pairs; log-rank test P=0.17). Additionally, subgroup analyses of 147 (60%) patients who had dyspnea and 87 (36%) patients who had ARDS revealed corticosteroid treatment was not associated with clinical outcome (both, P>0.3). However, increased corticosteroids dosage was significantly associated with elevated mortality risk after adjustment for administration duration (P=0.003); every ten-milligram increase in hydrocortisone-equivalent dosage was associated with additional 4% mortality risk (adjusted HR: 1.04, 95% CI: 1.01-1.07). Our findings indicated that limited effect of corticosteroid therapy could pose to overall survival and prudent dose within effective limits may be recommended for critically ill patients under certain circumstances.

Microstructural disruption of the right inferior fronto-occipital and inferior longitudinal fasciculus contributes to WMH-related cognitive impairment.

Abstract: Aims White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH-related cognitive impairment. Methods We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH-NC), and 23 cases of WMH with mild cognitive impairment (WMH-MCI). All individuals underwent diffusion tensor imaging (DTI) and a standardized neuropsychological assessment. Automated Fiber Quantification was used to extract altered DTI metrics between groups, and partial correlation was performed to assess the associations between WM integrity and cognitive performance. Furthermore, machine learning analyses were performed to determine underlying imaging markers of WMH-related cognitive impairment. Results Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto-occipital fasciculus (IFOF), the right inferior longitudinal fasciculus (ILF), and the right superior longitudinal fasciculus (SLF) were negatively correlated with memory function, while that of the anterior component of the right IFOF and the posterior and intermediate component of the right ILF showed significant negative correlation with MMSE and episodic memory, respectively. Furthermore, machine learning analyses showed that the accuracy of recognizing WMH-MCI patients from the WMH populations was up to 80.5% and the intermediate and posterior components of the right ILF and the anterior component of the right IFOF contribute the most. Conclusions Changes in the properties of DTI may be the potential mechanism of WMH-related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH-related cognitive dysfunction.

Tracing the accumulation of in vivo human oral microbiota elucidates microbial community dynamics at the gateway to the GI tract

Abstract: With great interest we read the article by Gaiser et al 1 that enrichment of oral bacterial taxa in pancreatic cancer highlights the role of oral microbiota. Not coincidentally, the presence of Fusobacterium nucleatum in paired saliva and colon samples of the patients with colorectal cancer has been reported,2 3 raising interest in whether disease starts in the mouth or in the intestine.4–6 Another reason people are interested in oral microbes is their potentials serving as biomarkers for systemic diseases.3 7–9 In this study, we examined how long the collapsed bacterial community can recover to its initial state when suffering from disturbance and whether oral microbes have sufficient robustness to serve as biomarkers. We longitudinally tracked the re-assembling process of human oral biofilms after clinical scaling. Paired saliva and dental plaque samples were collected from nine subjects at 11 time points (figure 1A and online supplementary figure S1). The 16S rRNA V3–V4 regions of 169 samples were amplified and sequenced, and the generated reads were analysed using QIIME.10 ### Supplementary data [gutjnl-2019-318977supp001.pdf] Figure 1 Longitudinal dynamics of in vivo human oral microbiota. (A) Overview of the study design and sample collection. (B) The alpha diversity of the dental plaque and salivary microbiota over time. The shadow around the line shows a 95% CI. (C) The Bray-Curtis distance calculated at the operational taxonomic unit (OTU) level across individual microbiota of the same time point. (D–E) The Bray-Curtis distance between microbiota of each time point and pre . Significance was measured using …

CHIMGEN: a Chinese imaging genetics cohort to enhance cross-ethnic and cross-geographic brain research

Abstract: The Chinese Imaging Genetics (CHIMGEN) study establishes the largest Chinese neuroimaging genetics cohort and aims to identify genetic and environmental factors and their interactions that are associated with neuroimaging and behavioral phenotypes. This study prospectively collected genomic, neuroimaging, environmental, and behavioral data from more than 7000 healthy Chinese Han participants aged 18–30 years. As a pioneer of large-sample neuroimaging genetics cohorts of non-Caucasian populations, this cohort can provide new insights into ethnic differences in genetic-neuroimaging associations by being compared with Caucasian cohorts. In addition to micro-environmental measurements, this study also collects hundreds of quantitative macro-environmental measurements from remote sensing and national survey databases based on the locations of each participant from birth to present, which will facilitate discoveries of new environmental factors associated with neuroimaging phenotypes. With lifespan environmental measurements, this study can also provide insights on the macro-environmental exposures that affect the human brain as well as their timing and mechanisms of action.

Biogeography and Assembly of Microbial Communities in Wastewater Treatment Plants in China.

Abstract: Scientific understanding of microbial biogeography and assembly is lacking for activated sludge microbial communities, even though the diversity of microbial communities in wastewater treatment plants (WWTPs) is thought to have a direct influence on system performance. Here, utilizing large-scale 16S rRNA gene data generated from 211 activated sludge samples collected from 15 cities across China, we show activated sludge microbes, whose growth and metabolism can be regulated followed with the metabolic theory of ecology with an apparent Ea value (apparent activation energy) of 0.08 eV. WWTPs at a lower latitude tend to harbor a more diverse array of microorganisms. In agreement with the general understanding, the activated sludge microbial assembly was mainly driven by deterministic processes and the mean annual temperature was identified as the most important factor affecting the microbial community structure. The treatment process types with similar microbial growth types and functions had a distinct impact on the activated sludge microbial community structure only when WWTPs were located near each other and received similar influent. Overall, these findings provide us with a deeper understanding of activated sludge microbial communities from an ecological perspective. Moreover, these findings suggest that, for a given set of performance characteristics (e.g., combined nitrification, denitrification, and phosphorus removal), it may be difficult to employ common engineering levers to control additional aspects of community structure due to the influence of natural environmental factors.

Structural insights into substrate recognition by the type VII secretion system.

Abstract: Type VII secretion systems (T7SSs) are found in many disease related bacteria including Mycobacterium tuberculosis (Mtb). ESX-1 [early secreted antigen 6 kilodaltons (ESAT-6) system 1] is one of the five subtypes (ESX-1~5) of T7SSs in Mtb, where it delivers virulence factors into host macrophages during infection. However, little is known about the molecular details as to how this occurs. Here, we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes. These structures adopt a classic RecA-like ɑ/β fold with a conserved Mg-ATP binding site. The structure of EccCb1 in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module "LxxxMxF" for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop. A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family, suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs. A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel. The diameter of the channel is ~25-A, with a size that would allow helix-bundle shaped substrate proteins to bind and pass through. Thus, our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.

Epigenetic age acceleration of cervical squamous cell carcinoma converged to human papillomavirus 16/18 expression, immunoactivation, and favourable prognosis.

Abstract: Ageing-associated molecular changes have been assumed to trigger malignant transformations and the epigenetic clock, and the DNA methylation age has been shown to be highly correlated with chronological age. However, the associations between the epigenetic clock and cervical squamous cell carcinoma (CSCC) prognosis, other molecular characteristics, and clinicopathological features have not been systematically investigated. To this end, we computed the DNA methylation (DNAm) age of 252 CSCC patients and 200 normal samples from TCGA and three external cohorts by using the Horvath clock model. We characterized the differences in human papillomavirus (HPV) 16/18 expression, pathway activity, genomic alteration, and chemosensitivity between two DNAm age subgroups. We then used Cox proportional hazards regression and restricted cubic spline (RCS) analysis to assess the prognostic value of epigenetic acceleration. DNAm age was significantly associated with chronological age, but it was differentiated between tumour and normal tissue (P < 0.001). Two DNAm age groups, i.e. DNAmAge-ACC and DNAmAge-DEC, were identified; the former had high expression of the E6/E7 oncoproteins of HPV16/18 (P < 0.05), an immunoactive phenotype (all FDRs < 0.05 in enrichment analysis), CpG island hypermethylation (P < 0.001), and lower mutation load (P = 0.011), including for TP53 (P = 0.002). When adjusted for chronological age and tumour stage, every 10-year increase in DNAm age was associated with a 12% decrease in fatality (HR 0.88, 95% CI 0.78–0.99, P = 0.03); DNAmAge-ACC had a 41% lower mortality risk and 47% lower progression rate than DNAmAge-DEC and was more likely to benefit from chemotherapy. RCS revealed a positive non-linear association between DNAm age and both mortality and progression risk (both, P < 0.05). DNAm age is an independent predictor of CSCC prognosis. Better prognosis, overexpression of HPV E6/E7 oncoproteins, and higher enrichment of immune signatures were observed in DNAmAge-ACC tumours.

Rapid Birth or Death of Centromeres on Fragmented Chromosomes in Maize.

Abstract: Comparative genomics has revealed common occurrences in karyotype evolution such as chromosomal end-to-end fusions and insertions of one chromosome into another near the centromere, as well as many cases of de novo centromeres that generate positional polymorphisms However, how rearrangements such as dicentrics and acentrics persist without being destroyed or lost remains unclear Here, we sought experimental evidence for the frequency and timeframe for inactivation and de novo formation of centromeres in maize (Zea mays) The pollen from plants with supernumerary B chromosomes was gamma-irradiated and then applied to normal maize silks of a line without B chromosomes In ∼8,000 first-generation seedlings, we found many B-A translocations, centromere expansions, and ring chromosomes We also found many dicentric chromosomes, but a fraction of these show only a single primary constriction, which suggests inactivation of one centromere Chromosomal fragments were found without canonical centromere sequences, revealing de novo centromere formation over unique sequences; these were validated by immunolocalization with Thr133-phosphorylated histone H2A, a marker of active centromeres, and chromatin immunoprecipitation-sequencing with the CENH3 antibody These results illustrate the regular occurrence of centromere birth and death after chromosomal rearrangement during a narrow window of one to potentially only a few cell cycles for the rearranged chromosomes to be recognized in this experimental regime

Combined clinical characteristics and multiparametric MRI parameters for prediction of cribriform morphology in intermediate-risk prostate cancer patients.

Abstract: Purpose To develop a risk model with combined clinical characteristics and multiparametric MRI parameters for prediction of cribriform morphology in intermediate-risk prostate cancer (CaP) patients. Methods We retrospectively included 215 CaP patients received multiparametric MRIexamination, targeted biopsy (TB) combined with systematic biopsy (SB), radical prostatectomy and final Gleason group 2 or 3. Cribriform status was confirmed on both biopsy slices and whole-mount sections. Characteristics were stratified by cribriform status. Mann Whitney U test was performed for continuous variables and the χ2 test for categorical variables. Univariate and multivariate logistic regression analyses were performed for significant predictors, followed by cribriform-risk nomogram construction. Receiver operating characteristic analysis was used for internal discrimination validation with corresponding area under the curve. Calibration curves were plotted and decision curve analysis was performed for clinical benefit exploration. Results Cribriform morphology was identified in 51.2% (110/215) patients. Cribriform-positive CaP demonstrated significantly higher prostate-specific antigen level, higher prostate-specific antigen density , larger lesion dimension on MRI, higher Prostate Imaging Reporting and Data System score, larger tumor dimension, higher Gleason score, higher pT stage, higher pN stage and more positive surgical margin (all P Conclusion A cribriform-risk nomogram was developed and well predicted aggressive cribriform morphology in intermediate-risk CaP patients.

The Asymmetry of White Matter Hyperintensity Burden Between Hemispheres Is Associated With Intracranial Atherosclerotic Plaque Enhancement Grade

Abstract: Purpose: The contribution of intracranial atherosclerotic stenosis (ICAS) to the development of white matter hyperintensities (WMHs) has not been fully elucidated. We aimed to retrospectively assess the relationship between WMH burden and unilateral ICAS by combined examination of lumen stenosis, plaque enhancement, and cerebral perfusion. Materials and Methods: A cross-sectional study of 41 patients with symptomatic unilateral ICAS (mean age 57 ± 10 years; 26 males) was conducted. Detailed clinical data, including vascular risk factors, were obtained. WMH volume was derived from 3D-fluid-attenuated inversion recovery (3D-FLAIR) and was assessed by using a validated semiautomated protocol. Lumen stenosis, plaque enhancement, and cerebral perfusion (assessed on time-to-peak parameter using the Alberta Stroke Program Early CT score (TTP-ASPECTS) scale) were evaluated. The WMH volumes of periventricular (PWMH) and deep (DWMH) white matter were calculated separately and compared between hemispheres. Associations between WMH volume (interhemispheric volume difference, ipsilateral and contralateral to the ICAS site separately), unilateral ICAS imaging metrics, and vascular risk factors were assessed by using linear regression. Results: The DWMH volume ipsilateral to the ICAS site (ipsilateral DWMH volume) was significantly greater than that of the contralateral site (P < 0.001), while the PWMH volume difference between hemispheres did not reach statistical significance. The interhemispheric DWMH volume difference was significantly associated with a higher plaque enhancement grade (β = 0.436, P = 0.005) and inversely associated with cerebral hypoperfusion (lower TTP-ASPECTS) (β = -0.613, P < 0.001). In the between-subjects multivariable regression analysis, while older age (β = 0.323, P = 0.025), hypoperfusion (β = -0.394, P = 0.007), and hypertension (β = 0.378, P = 0.011) were independently associated with ipsilateral DWMH volume, plaque enhancement did not show an association with ipsilateral DWMH volume. The association between ipsilateral DWMH volume and lumen stenosis approached statistical significance (β = 0.274, P = 0.084). Conclusion: The DWMH was attributed to chronic hypoperfusion secondary to atherosclerotic stenosis. The association between the asymmetry of deep white matter lesions and plaque enhancement might suggest that increased deep white matter lesions are those ischemic lesions, which are more prone to the development of stroke.

Investigation on the Effect of Dynamic Frequency on Fracture Evolution in Preflawed Rock under Multistage Cyclic Loads: Insight from Acoustic Emission Monitoring

Abstract: This study is aimed at revealing the effect of dynamic loading frequency on the fracture evolution behavior in preflawed rock samples under multistage cyclic loading conditions. The fracture evolution characteristics were investigated using stress-strain descriptions and in situ acoustic emission techniques. It is shown that rock strength, deformation, AE pattern, and fatigue life are strongly affected by the applied dynamic loading frequency. Rock fatigue strength and lifetime increase with the increase of dynamic loading frequency. The AE count and energy output both increase with the increase of the applied loading frequency. Six kinds of cracking modes were revealed by AE spectral frequency analysis. It is shown that large-scaled cracks are easy to be formed for rock subjected to high-frequency loads, reflected as the deceasing of AE signals with high-frequency–high-amplitude signal feature. It is suggested that applied dynamic loading frequency has obvious impact on the crack coalescence at the rock bridge segment. The testing results are helpful to enhance the cognitive of the influence of dynamic frequency on the crack communication behavior and can be expected to predict the stability of rock mass structures where rock mass is subjected to fatigue loading.

Altered sulcogyral patterns of orbitofrontal cortex in patients with mild cognitive impairment.

Abstract: Mild cognitive impairment (MCI) is increasingly recognized as a risk factor for Alzheimer's disease (AD). Neuroimaging studies have revealed structural abnormalities in the orbitofrontal cortex (OFC) in MCI patients, while other findings fail to report anatomical alterations. Accordingly, structural changes in this brain region amongst MCI patients has not been well characterized. Given that OFC sulcogyral organization has increasingly been demonstrated as a reliable pre-morbid marker of pathological conditions in several neuropsychiatric disorders, we examined the distribution of OFC sulcogyral patterns (classified into Type I, II and III) based on structural brain data from 68 MCI patients and 55 healthy controls. Our results, supported by both Frequentist and Bayesian statistics, showed that MCI patients exhibited an increased prevalence of Type II pattern compared with healthy controls, particularly in the right hemisphere. Meanwhile, MCI patients showed a decreased prevalence of Type I pattern compared with healthy controls. Taken together, our results reveal a skewed distribution of OFC sulcogyral in MCI patients, possibly reflecting a potential neurodevelopmental risk marker of MCI.

RNA processing genes characterize RNA splicing and further stratify colorectal cancer.

Abstract: Objectives Due to the limited evaluation of the prognostic value of RNA processing genes (RPGs), which are regulators of alternative splicing events (ASEs) that have been shown to be associated with tumour progression, this study sought to determine whether colorectal cancer (CRC) could be further stratified based on the expression pattern of RPGs Materials and methods The gene expression profiles of CRCs were collected from TCGA (training set) and three external validation cohorts, representing 1060 cases totally Cox regression with least absolute shrinkage and selection operator (LASSO) penalty was used to develop an RNA processing gene index (RPGI) risk score Kaplan-Meier curves, multivariate Cox regression and restricted mean survival (RMS) analyses were harnessed to evaluate the prognostic value of the RPGI Results A 22-gene RPGI signature was developed, and its risk score served as a strong independent prognostic factor across all data sets when adjusted for major clinical variables Moreover, ASEs for certain genes, such as FGFR1 and the RAS oncogene family, were significantly correlated with RPGI Expression levels of genes involved in splicing- and tumour-associated pathways were significantly correlated with RPGI score Furthermore, a combination of RPGI with age and tumour stage resulted in significantly improved prognostic accuracy Conclusions Our findings highlighted the prognostic value of RPGs for risk stratification of CRC patients and provide insights into specific ASEs associated with the development of CRC

One-Stop MR Neurovascular Vessel Wall Imaging With a 48-Channel Coil System at 3 T

Abstract: Objective: The purpose of this article was to build a radio frequency (RF) coil system to achieve high vessel wall image quality with coverage extending from the aortic arch to the intracranial vessels. Methods: A 48-channel coil system was built and characterized at a 3 tesla (T) Magnetic Resonance Imaging (MRI) scanner (uMR 790, Shanghai United Imaging Healthcare, Shanghai, China). The coil's performance was compared with a commercially available 36-channel coil system. By human studies, signal-to-noise ratio (SNR) units were evaluated and g-factors were calculated in the transverse planes of the brain and neck regions. Results: The SNR was increased by at least 28% in the brain region and up to fourfold in the neck region. The average g-factor with the acceleration factor, R = 3, was lowered by 21% in the transverse plane of the neck region. Intracranial and carotid arterial wall images with an isotropic spatial resolution of 0.63 mm were acquired within 7.7 minutes and thoracic aorta wall images with an isotropic spatial resolution of 1.1 mm were acquired within 2.7 minutes with the 48-channel coil system. The vessel wall can be more clearly visualized with the 48-channel coil system compared with the 36-channel coil system. Conclusion: A 48-channel coil system was developed and demonstrated superior performance for vessel wall imaging at the intracranial and cervical carotid arteries compared with a commercial 36-channel coil. Significance: The 48-channel coil system is potentially useful for clinical diagnostics, especially when attempting to diagnose ischemic stroke.

Clinically Applicable Deep Learning Strategy for Pulmonary Nodule Risk Prediction: Insights into HONORS

Abstract: Background and Purpose Limited optimization was clinically applicable for reducing missed diagnosis, misdiagnosis and inter-reader variability in pulmonary nodule diagnosis. We aimed to propose a deep learning-based algorithm and a practical strategy to better stratify the risk of pulmonary nodules, thus reducing medical errors and optimizing the clinical workflow. Materials and Methods A total of 2,348 pulmonary nodules (1,215 with lung cancer) containing screened nodules from National Lung Cancer Screening Trial (NLST) and incidentally detected nodules from Jinling Hospital (JLH) were used to train and evaluate a deep learning algorithm, Filter-guided pyramid network (FGP-NET). Internal and external test of FGP-NET were performed on two independent datasets (n=542). The performance of FGP-NET at Youden point which maximizing the Youden index was compared with 126 board-certificated radiologists. We further proposed Hierarchical Ordered Network ORiented Strategy (HONORS), which manipulates the emphasis either on sensitivity or specificity to target risk-stratified clinical scenarios, directly making decisions for some patients. Results FGP-NET achieved a high area under the curve (AUC) of 0.969 and 0.855 for internal and external testing, and was comparable or even outperformed the radiologists when considering sensitivity. HONORS-guided FGP-NET identified benign nodules with a high sensitivity (95.5%) in the screening scenario, and demonstrated satisfactory performance for the rest ambiguous nodules with 0.945 of AUC by the Youden point. FGP-NET also detected lung cancer with a high specificity of 94.5% in routine diagnostic scenario; an AUC of 0.809 was achieved for the rest nodules. Conclusion The combination of HONORS and FGP-NET provides well-organized stratification for pulmonary nodules and also offers the potential for reducing medical errors. Highlights Pulmonary nodules were managed for both screening and diagnostic scenarios Proposal of a hierarchical strategy for targeting risk-stratified clinical scenarios A large scale Human-deep learning contest for reliable performance evaluation