Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study.

Background: Previous studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear. Methods: A two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality. Results: The phylum Firmicutes (OR = 0.62; 95% CI, 0.48-0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62-0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62-0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05). Conclusion: Our MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

Speed-enhanced scattering compensation method with sub-Nyquist sampling.

A rapid feedback-based scattering compensation method is particularly important for guiding light precisely within turbid tissues, especially the dynamic tissues. However, the huge number of measurements that come from the underutilization of the signal frequency channel greatly limits the modulation speed. This paper introduces a rapid compensation method with the sub-Nyquist sampling which improves the channel utilization and the speed of wavefront shaping. The number of measurements is reduced to ∼1500 with 32 × 32 freedom, and the PBR of the focus reaches ∼200. The system performances are demonstrated by focusing the light through brain slices of different thicknesses.

Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study.

Background: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy for exposure and can be used to inferentially determine the causal effect of exposure on outcomes. We thus used MR analysis to investigate whether there is a causal relationship between the biomarkers of Tregs and IHD. Methods: Selected genetic variants (P<5.00E-08) from the summary data of a genome-wide association study (GWAS) were used to conduct a two-sample bidirectional MR analysis. The analysis included 51 extensive Treg subtypes involving 3,757 individuals from the general population. Summary statistics of IHD were obtained from the IEU open GWAS project, which contains 30,952 cases and 187,845 controls. The populations in both GWAS studies were of European ancestry. Results: We identified a set of 197 single-nucleotide polymorphisms (SNPs) that served as instrumental variables (IVs) for evaluating 51 Treg subtypes. Thirteen significant variables were found to be potentially associated with IHD. After false-discovery rate (FDR) adjustment, we identified four Treg subtypes to be causally protective for IHD risk: CD28 on activated & secreting CD4 Tregs [odds ratio (OR) =0.89; 95% confidence interval (CI): 0.82-0.96; P=3.10E-03; adjusted P=0.04], CD28 on activated CD4 Tregs (OR =0.87; 95% CI: 0.80-0.95; P=3.10E-03; adjusted P=0.04), CD28 on CD4 Tregs (OR =0.87; 95% CI: 0.80-0.96; P=3.41E-03; adjusted P=0.04), and CD28 on resting CD4 Treg cell (OR =0.91; 95% CI: 0.85-0.97; P=3.48E-03; adjusted P=0.04). Reverse MR analysis found eight potential causal variables, but these associations were nonsignificant after FDR correction (all adjusted P values >0.05). Conclusions: This study identified the significance of elevated CD28 expression on CD4 Tregs as a novel molecular modifier that may influence IHD occurrence, suggesting that targeting CD28 expression on CD4 Tregs could offer a promising therapeutic approach for IHD.

Tophi and carotid atherosclerosis in gout patients: Role of insulin resistance.

BACKGROUND AND AIM: Gout and cardiovascular disease are closely related, but the mechanism linking them is still unknown. Gout may affect the insulin signaling pathway inducing insulin resistance (IR). The study aims to evaluate the association between tophi and carotid atherosclerosis, considering the potential role of IR. METHODS AND RESULTS: A total of 595 patients with gout aged 18 to 80 were enrolled in this study. Carotid intima-media thickness, plaques and tophi were evaluated by B-mode ultrasonography. IR was assessed by the HOMA index (hepatic IR) and Gutt index (peripheral IR). Multivariable logistic regression and interaction analysis were used to examine the association between tophi and IR and its impact on carotid atherosclerosis. Among these participants, the average age was 55.4 (±12.54) years, and 94.6 % were male. Tophi were associated with increased odds of carotid atherosclerosis and burden after adjustment for confounders (P < 0.05). Tophi and IR synergically interacted for inducing carotid atherosclerosis. The interaction between peripheral IR with tophi was more pronounced than hepatic IR with tophi. CONCLUSIONS: Tophi were independently associated with carotid atherosclerosis risk. IR mediated a significant amount of the effect of tophi on the development of carotid atherosclerosis. Peripheral IR probably plays a more important role than hepatic IR does.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

High-axial-resolution speckle-free holographic reconstruction via cylindrical quadratic phase method and temporal focusing.

Holographic techniques enable precise laser manipulation, but suffer from two considerable limitations: speckle and deterioration of axial distribution. Here, we propose a cylindrical quadratic phase (CQP) method with temporal focusing (TF) to generate speckle-free holographic illumination with high axial resolution. TF-CQP utilizes a superposed cylindrical phase as the initial guess to iteratively optimize phase hologram, realizing speckle-free holographic reconstruction on the target focal plane and eliminating secondary focus on the defocused planes. TF-CQP further disperses defocused beams symmetrically by a blazed grating, placed conjugate to the focal plane, which enhances axial confinement. Simulation and experimental results show that TF-CQP reconstructs speckle-free illumination with arbitrary shapes and <10 µm axial resolution. Compared to TF-GS (Gerchberg-Saxton algorithm), widely used in holographic optogenetics, TF-CQP shows increased uniformity of 200% and improved modulation efficiency of 32.33% for parallel holographic illumination, as well as a 10% increment in axial resolution.

Speckle suppression in arbitrary parallel holographic illumination by the spatial frequency regaining method.

This Letter proposes a spatial frequency regaining method for parallel holographic illumination (SFR-PHI) to suppress speckle noise in phase-only computer-generated holography (CGH). Based on the accurate calculation of the beam bandwidth, this method uses the bandwidth-limited quadratic initial phase and weighted constraint iteration to generate the optimized phase hologram, which can provide the accurate spatial frequency of multiple illumination patterns. The results show that SFR-PHI performs superiorly in speckle suppression for generating dozens of illumination patterns in parallel and with arbitrary shapes and numbers. Compared with other speckle-suppression methods, it exhibits significant advantages in terms of accuracy and modulation efficiency.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review.

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

External stenting for saphenous vein grafts in coronary artery bypass grafting: A meta-analysis.

OBJECTIVES: Autologous saphenous vein grafts (SVGs) are the most commonly used bypass conduits in coronary artery bypass grafting (CABG) with multivessel coronary artery disease. Although external support devices for SVGs have shown promising outcomes, the overall efficacy and safety remains controversial. We aimed to evaluate external stenting for SVGs in CABG versus non-stented SVGs. METHODS: MEDLINE, EMBASE, Cochrane Library and clinicaltrails.gov were searched for randomized controlled trials (RCTs) to evaluate external-stented SVGs versus non-stented SVGs in CABG up to 31 August 2022. The risk ratio and mean difference with 95% confidence interval were analysed. The primary efficacy outcomes included intimal hyperplasia area and thickness. The secondary efficacy outcomes were graft failure (≥50% stenosis) and lumen diameter uniformity. RESULTS: We pooled 438 patients from three RCTs. The external stented SVGs group showed significant reductions in intimal hyperplasia area (MD: -0.78, p < 0.001, I2 = 0%) and thickness (MD: -0.06, p < 0.001, I2 = 0%) compared to the non-stented SVGs group. Meanwhile, external support devices improved lumen uniformity with Fitzgibbon I classification (risk ratio (RR):1.1595, p = 0.05, I2 = 0%). SVG failure rates were not increased in the external stented SVGs group during the short follow-up period (RR: 1.14, p = 0.38, I2 = 0%). Furthermore, the incidences of mortality and major cardiac and cerebrovascular events were consistent with previous reports. CONCLUSIONS: External support devices for SVGs significantly reduced the intimal hyperplasia area and thickness, and improved the lumen uniformity, assessed with the Fitzgibbon I classification. Meanwhile, they did not increase the overall SVG failure rate.

Flexible waveguide integrated thermo-optic switch based on TiO2 platform.

Mechanically flexible photonic devices are critical components of novel bio-integrated optoelectronic and high-end wearable systems, in which thermo-optic switches (TOSs) as optical signal control devices are crucial. In this paper, flexible titanium oxide (TiO2) TOSs based on a Mach-Zehnder interferometer (MZI) structure were demonstrated around 1310 nm for, it is believed, the first time. The insertion loss of flexible passive TiO2 2 × 2 multi-mode interferometers (MMIs) is -3.1 dB per MMI. The demonstrated flexible TOS achieves power consumption (Pπ) of 0.83 mW, compared with its rigid counterpart, for which Pπ is decreased by a factor of 18. The proposed device could withstand 100 consecutive bending operations without noticeable degradation in TOS performance, indicating excellent mechanical stability. These results provide a new perspective for designing and fabricating flexible TOSs for flexible optoelectronic systems in future emerging applications.

Exploring the mechanisms of self-made Kuiyu Pingchang recipe for the treatment of ulcerative colitis and irritable bowel syndrome using a network pharmacology-based approach and molecular docking.

BACKGROUND: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are common intestinal diseases. According to the clinical experience and curative effect, the authors formulated Kuiyu Pingchang Decoction (KYPCD) comprised of Paeoniae radix alba, Aurantii Fructus, Herba euphorbiae humifusae, Lasiosphaera seu Calvatia, Angelicae sinensis radix, Panax ginseng C.A. Mey., Platycodon grandiforus and Allium azureum Ledeb. OBJECTIVE: The aim of the present study was to explore the mechanisms of KYPCD in the treatment of UC and IBS following the Traditional Chinese Medicine (TCM) theory of "Treating different diseases with the same treatment". METHODS: The chemical ingredients and targets of KYPCD were obtained using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP). The targets of UC and IBS were extracted using the DisGeNET, GeneCards, DrugBANK, OMIM and TTD databases. The "TCM-component-target" network and the "TCM-shared target-disease" network were imaged using Cytoscape software. The protein-protein interaction (PPI) network was built using the STRING database. The DAVID platform was used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using Autodock Tools software, the main active components of KYPCD were molecularly docked with their targets and visualized using PyMOL. RESULTS: A total of 46 active ingredients of KYPCD corresponding to 243 potential targets, 1,565 targets of UC and 1,062 targets of IBS, and 70 targets among active ingredients and two diseases were screened. Core targets in the PPI network included IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA. GO and KEGG enrichment analysis demonstrated 563 biological processes, 48 cellular components, 82 molecular functions and 144 signaling pathways. KEGG enrichment results revealed that the regulated pathways were mainly related to the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways. The results of molecular docking analysis indicated that the core active ingredients of KYPCD had optimal binding activity to their corresponding targets. CONCLUSION: KYPCD may use IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA as the key targets to achieve the treatment of UC and IBS through the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways.

End-to-End Deep-Learning-Based Diagnosis of Benign and Malignant Orbital Tumors on Computed Tomography Images.

Determining the nature of orbital tumors is challenging for current imaging interpretation methods, which hinders timely treatment. This study aimed to propose an end-to-end deep learning system to automatically diagnose orbital tumors. A multi-center dataset of 602 non-contrast-enhanced computed tomography (CT) images were prepared. After image annotation and preprocessing, the CT images were used to train and test the deep learning (DL) model for the following two stages: orbital tumor segmentation and classification. The performance on the testing set was compared with the assessment of three ophthalmologists. For tumor segmentation, the model achieved a satisfactory performance, with an average dice similarity coefficient of 0.89. The classification model had an accuracy of 86.96%, a sensitivity of 80.00%, and a specificity of 94.12%. The area under the receiver operating characteristics curve (AUC) of the 10-fold cross-validation ranged from 0.8439 to 0.9546. There was no significant difference on diagnostic performance of the DL-based system and three ophthalmologists (p > 0.05). The proposed end-to-end deep learning system could deliver accurate segmentation and diagnosis of orbital tumors based on noninvasive CT images. Its effectiveness and independence from human interaction allow the potential for tumor screening in the orbit and other parts of the body.

Engineered exosome-mediated messenger RNA and single-chain variable fragment delivery for human chimeric antigen receptor T-cell engineering.

BACKGROUND AIMS: Most current chimeric antigen receptor (CAR) T cells are generated by viral transduction, which induces persistent expression of CARs and may cause serious undesirable effects. Messenger RNA (mRNA)-based approaches in manufacturing CAR T cells are being developed to overcome these challenges. However, the most common method of delivering mRNA to T cells is electroporation, which can be toxic to cells. METHODS: The authors designed and engineered an exosome delivery platform using the bacteriophage MS2 system in combination with the highly expressed protein lysosome-associated membrane protein 2 isoform B on exosomes. RESULTS: The authors' delivery platform achieved specific loading and delivery of mRNA into target cells and achieved expression of specific proteins, and anti-CD3/CD28 single-chain variable fragments (scFvs) expressed outside the exosomal membrane effectively activated primary T cells in a similar way to commercial magnetic beads. CONCLUSIONS: The delivery of CAR mRNA and anti-CD3/CD28 scFvs via designed exosomes can be used for ex vivo production of CAR T cells with cancer cell killing capacity. The authors' results indicate the potential applications of the engineered exosome delivery platform for direct conversion of primary T cells to CAR T cells while providing a novel strategy for producing CAR T cells in vivo.

The risk of nonalcoholic fatty liver disease in gout patients with frequent flares: a retrospective cohort study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that is related to high serum uric acid; however, the association between the frequency of gout flares and NAFLD risk remains unclear. This study aimed to investigate whether frequent gout flares were associated with incident NAFLD and analyze the interaction of frequency of gout flares and Adipo-IR on NAFLD in the gout Chinese population. METHODS: A total of 350 cases of gout patients were enrolled in this retrospective cohort study. Cox proportional hazard regression analyses were performed to determine the association between frequent gout flares and NAFLD during follow-up and analyze the interaction of frequency of gout flares and Adipo-IR on NAFLD. Receiver operating curves (ROC) were plotted to explore the diagnostic value of frequent gout flares and Adipo-IR on the occurrence of NAFLD. RESULTS: NAFLD developed in 78 participants (22.3%) during follow-up. Logistic regression showed that Adipo-IR was an independent factor associated with frequent gout flares risk. The multivariate Cox regression analysis revealed that frequent gout flares and Adipo-IR were associated with NAFLD risk (HR: 7.88, 95% CI: 2.11-29.48, p < 0.01; HR: 1.058, 95% CI: 1.01-1.2, p < 0.05). And ROC showed that both of them had a great discriminant ability to diagnose NAFLD. CONCLUSIONS: Our data showed an independent association between the frequency of gout flares or Adipo-IR and incident NAFLD. Frequent gout flares and elevated Adipo-IR had a good predictive capability towards NAFLD development and played a synergistic role in the development of NAFLD. KEY POINTS: • Frequent gout flares and elevated Adipo-IR had a good diagnostic capability towards NAFLD development. • Frequent gout flares and Adipo-IR played a synergistic role in the development of NAFLD.

Robust and adjustable dynamic scattering compensation for high-precision deep tissue optogenetics.

The development of high-precision optogenetics in deep tissue is limited due to the strong optical scattering induced by biological tissue. Although various wavefront shaping techniques have been developed to compensate the scattering, it is still a challenge to non-invasively characterize the dynamic scattered optical wavefront inside the living tissue. Here, we present a non-invasive scattering compensation system with fast multidither coherent optical adaptive technique (fCOAT), which allows the rapid wavefront correction and stable focusing in dynamic scattering medium. We achieve subcellular-resolution focusing through 500-µm-thickness brain slices, or even three pieces overlapped mouse skulls after just one iteration with a 589 nm CW laser. Further, focusing through dynamic scattering medium such as live rat ear is also successfully achieved. The formed focus can maintain longer than 60 s, which satisfies the requirements of stable optogenetics manipulation. Moreover, the focus size is adjustable from subcellular level to tens of microns to freely match the various manipulation targets. With the specially designed fCOAT system, we successfully achieve single-cellular optogenetic manipulation through the brain tissue, with a stimulation efficiency enhancement up to 300% compared with that of the speckle.

Association between serum free fatty acid levels and tophus in patients with gout: a cross-sectional study.

OBJECTIVES: To explore the relationship between serum free fatty acid (FFA) and tophus in gout patients, and to investigate whether FFA increases the risk of tophus deposition by lowering urine pH. METHODS: A total of 595 patients with gout aged 18 to 80 were enrolled between June 2018 and August 2021. The subjects were divided into four groups according to FFA. Logistic regression was used to analyse the association between serum FFA and tophus. Receiver operating curves (ROC) were plotted to explore the predictive value of FFA on the occurrence of tophus. RESULTS: Accompanying the increase of FFA levels, the prevalence of tophus in groups Q3 and Q4 was significantly higher than in groups Q1 and Q2 (33.6%, 36.5% vs. 6.3%, 19.6%, p<0.001). According to the Spearman correlation, serum FFA levels were positively correlated with tophus while negatively with urine pH (p<0.001). FFA had a significant interaction with urine pH on tophus risk. Multivariate logistic regression showed that participants in Q2-Q4 had a higher OR of tophus than those in Q1 (OR were 2.770, 5.878 and 7.958 in Q2-Q4, respectively). ROC showed the best cut-off value of serum FFA level in predicting the onset of tophus was 0.46 mmol/L. Serum FFA had a great discriminant ability to predict tophus. CONCLUSIONS: High FFA levels are independently associated with tophus risk and FFA may promote tophi deposition by lowering urine pH. Serum FFA levels have a great screening value to identify tophus.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

A multi-feature deep learning system to enhance glaucoma severity diagnosis with high accuracy and fast speed.

Glaucoma is the leading cause of irreversible blindness, and the early detection and timely treatment are essential for glaucoma management. However, due to the interindividual variability in the characteristics of glaucoma onset, a single feature is not yet sufficient for monitoring glaucoma progression in isolation. There is an urgent need to develop more comprehensive diagnostic methods with higher accuracy. In this study, we proposed a multi- feature deep learning (MFDL) system based on intraocular pressure (IOP), color fundus photograph (CFP) and visual field (VF) to classify the glaucoma into four severity levels. We designed a three-phase framework for glaucoma severity diagnosis from coarse to fine, which contains screening, detection and classification. We trained it on 6,131 samples from 3,324 patients and tested it on independent 240 samples from 185 patients. Our results show that MFDL achieved a higher accuracy of 0.842 (95 % CI, 0.795-0.888) than the direct four classification deep learning (DFC-DL, accuracy of 0.513 [0.449-0.576]), CFP-based single-feature deep learning (CFP-DL, accuracy of 0.483 [0.420-0.547]) and VF-based single-feature deep learning (VF-DL, accuracy of 0.725 [0.668-0.782]). Its performance was statistically significantly superior to that of 8 juniors. It also outperformed 3 seniors and 1 expert, and was comparable with 2 glaucoma experts (0.842 vs 0.854, p = 0.663; 0.842 vs 0.858, p = 0.580). With the assistance of MFDL, junior ophthalmologists achieved statistically significantly higher accuracy performance, with the increased accuracy ranged from 7.50 % to 17.9 %, and that of seniors and experts were 6.30 % to 7.50 % and 5.40 % to 7.50 %. The mean diagnosis time per patient of MFDL was 5.96 s. The proposed model can potentially assist ophthalmologists in efficient and accurate glaucoma diagnosis that could aid the clinical management of glaucoma.