Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification.

Purpose: Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment. Methods: SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein-Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment. Results: Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1ß, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1ß, and FAS were significantly higher than the sham group. Conclusion: CD14, FAS, and IL1ß may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.

Enhancing the quality of fermented plant leaves: the role of metabolite signatures and associated fungi.

Fungi play a pivotal role in fermentation processes, influencing the breakdown and transformation of metabolites. However, studies focusing on the effects of fungal-metabolite correlations on leaf fermentation quality enhancement are limited. This study investigated specific metabolites and fungi associated with high- and low-quality fermented plant leaves. Their changes were monitored over fermentation periods of 0, 8, 16, and 24 days. The results indicated that organoheterocyclic compounds, lipids, lipid-like molecules, organic nitrogen compounds, phenylpropanoids, and polyketides were predominant in high-quality samples. The fungi Saccharomyces (14.8%) and Thermoascus (4.6%) were predominantly found in these samples. These markers exhibited significant changes during the 24-day fermentation period. The critical influence of fungal community equilibrium was demonstrated by interspecies interactions (e.g., between Saccharomyces and Eurotium). A co-occurrence network analysis identified Saccharomyces as the primary contributor to high-quality samples. These markers collectively enhance the quality and sensory characteristics of the final product.

A DNA origami device spatially controls CD95 signalling to induce immune tolerance in rheumatoid arthritis.

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey.

Objective: Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. Methods: A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. Results: The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion: The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.

Flexible calorimetric flow sensor with unprecedented sensitivity and directional resolution for multiple flight parameter detection.

The accurate perception of multiple flight parameters, such as the angle of attack, angle of sideslip, and airflow velocity, is essential for the flight control of micro air vehicles, which conventionally rely on arrays of pressure or airflow velocity sensors. Here, we present the estimation of multiple flight parameters using a single flexible calorimetric flow sensor featuring a sophisticated structural design with a suspended array of highly sensitive vanadium oxide thermistors. The proposed sensor achieves an unprecedented velocity resolution of 0.11 mm·s-1 and angular resolution of 0.1°. By attaching the sensor to a wing model, the angles of attack and slip were estimated simultaneously. The triaxial flight velocities and wing vibrations can also be estimated by sensing the relative airflow velocity due to its high sensitivity and fast response. Overall, the proposed sensor has many promising applications in weak airflow sensing and flight control of micro air vehicles.

Development of a Strategy for the Total Synthesis of Aspidosperma Alkaloids via the Cyclobutenone-Based PET-Initiated Cationic Radical-Driven [2+2]/Retro-Mannich Reaction.

A novel strategy for the synthesis of Aspidosperma alkaloids has been achieved via a photoredox-initiated [2+2]/retro-Mannich reaction of tryptamine-substituted enaminones as a key step. The developed chemistry has been applied to the construction of the core tetracycle of Aspidosperma alkaloids (±)-aspidospermidine and (±)-limaspermidine.

A Practical Tool for Measuring Home-Based Cardiac Rehabilitation Self-Management Behavior: A Multiphase Cross-Sectional Study.

BACKGROUND: Optimal self-management is the key to home-based cardiac rehabilitation for patients with heart disease. At present, there is a lack of a specific assessment tool to evaluate the home-based cardiac rehabilitation self-management behavior in patients with heart disease. Therefore, the aim of this study was to develop the Home-Based Cardiac Rehabilitation Self-Management Scale and validate its psychometric properties among patients with coronary heart disease. METHODS AND RESULTS: A multiphase cross-sectional study was conducted that study covered 3 phases: (1) item generation and revision, (2) item evaluation and preliminary exploration, and (3) assessment of the psychometric properties of the scale. A scale with 21 items was developed to measure the home-based cardiac rehabilitation self-management behavior. The content validity index of the scale was 0.980. In exploratory factor analysis, the 5-factor structure supported by eigenvalues and screen plot explained 74.326% of the total variation. In confirmatory factor analysis, all fitting indicators were acceptable, further supporting the construct validity of the scale. The criterion validity of the scale was 0.783. In the reliability analysis, the Cronbach's α coefficient of the scale was 0.882, with a dimensionality range of 0.780 to 0.936. The split-half reliability coefficient and test-retest reliability coefficient were 0.774 and 0.770, respectively. CONCLUSIONS: This study is the first to develop and validate a practical tool. This scale can comprehensively and accurately assess the self-management behavior of patients with heart disease in a home-based cardiac rehabilitation environment.

Lagging pollution of polycyclic aromatic hydrocarbons in the rebuilt e-waste site: From the perspective of characteristics, sources, and risk assessment.

Little information is known regarding how the lagged pollution of polycyclic aromatic hydrocarbon (PAH) influenced the environment and human health after an e-waste dismantling site was rebuilt. This study investigated the characteristics, sources, and risk assessment of PAHs in a rebuilt e-waste site and its surrounding farmland by analyzing the samples of soil, dust, water, and vegetable. Concentrations of PAHs in soil, vegetable and water in the rebuilt site were relatively higher than in its surrounding farmland. The concentrations in surface soils, soil columns, dust, vegetables, and water varied from 55.4 to 3990 ng g-1, 1.65 to 5060 ng g-1, 2190 to 2420 ng g-1, 2670 to 10,300 ng g-1, and 46.8 to 110 µg L-1 in the e-waste site, respectively. On the farmland, PAH concentrations in surface soils, vegetables, and water ranged from 41.5 to 2760 ng g-1, 506 to 7640 ng g-1, and 56.6 to 89.2 µg L-1, respectively. A higher proportion of high-molecular-weight PAHs (HMW-PAHs) appeared in all multimedia compared with low-molecular-weight PAHs (LMW-PAHs). Diagnostic ratio together with positive matrix factorization (PMF) revealed that vehicle emission was the primary source in this area, and the activity of e-waste disposal was another important source in the rebuilt e-waste site. Based on the deterministic health risks, people working in the reconstructed e-waste site were exposed to low risks, whereas the residents living near the surrounding farmland were exposed to low risk. Sensitivity analyses indicated that exposure frequency and PAH concentrations were the main factors that influenced exposure risk. This study provides valuable insight into the comprehension of the lagging pollution effects of PAH on the environment and human health after the e-waste site was rebuilt.

Forging the Tetracyclic Core Framework of Rhodomolleins XIV and XLII: A Ring-Distortion Approach.

A ring distortion approach for the synthesis of an advanced intermediate en route to rhodomolleins XIV and XLII was described, which led to successful construction of the 5/8/5/5 tetracyclic core framework of the kalmane diterpenoids. Key steps of the strategy include an oxidative dearomatization-induced (ODI)-Diels-Alder cycloaddition, a Dowd-Beckwith rearrangement, and a bioinspired Wagner-Meerwein rearrangement.

Align While Fusion: A Generalized Nonaligned Multiview Multilabel Classification Method.

In the task of multiview multilabel (MVML) classification, each object is described by several heterogeneous view features and annotated with multiple relevant labels. Existing MVML methods usually assume that these heterogeneous features are strictly view-aligned, and they directly conduct cross-view information fusion to train a multilabel prediction model. However, in real-world scenarios, such strict view-aligned requirement can be hardly satisfied due to the recurrent spatiotemporal asynchronism when collecting MVML data, which would cause inaccurate multiview fusion results and degrade the classification performance. To address this issue, we propose a generalized nonaligned MVML (GNAM) classification method, which achieves multiview information fusion while aligning cross-view features and accordingly learns a desired multilabel classifier. Specifically, we first introduce a multiorder matching alignment strategy to achieve cross-view feature alignments, where both first-order feature correspondence and second-order structure correspondence are jointly integrated to guarantee the compactness of the view-alignment results. Afterward, a commonality-and individuality-based multiview fusion structure is formulated on the aligned-view features to excavate the consistencies and complementarities across different views, which leads all relevant multiview semantic labels, especially rare labels, to be characterized more comprehensively. Finally, we embed adaptive global label correlations to multilabel classification model to further enhance its semantic expression integrity and develop an alternative algorithm to optimize the whole model. Extensive experimental results have verified that GNAM is significantly superior to other state-of-the-art methods.

Real-world evidence on treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with B-cell acute lymphoblastic leukemia.

Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context. This retrospective study provided real-world data on the treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with newly diagnosed (ND) and relapsed/refractory (R/R) B-ALL. Patients with B-ALL who received at least one dose of blinatumomab in frontline or R/R settings between August 2021 and June 2023 were included. The primary outcome was the treatment pattern of blinatumomab. Key secondary outcomes included complete remission (CR)/CR with incomplete blood cell recovery (CRi) rate, minimal residual disease (MRD) negativity, median event-free survival (EFS), and safety. The study included 96 patients with B-ALL; 53 (55.2%) patients were in the ND group and 43 (44.8%) patients were in the R/R group. The median treatment duration was one cycle (range: 1-5). Most patients underwent chemotherapies, allo-HSCT, or experimental CAR-T following blinatumomab. The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re-induction patients, the CR/CRi rate was 50%; MRD negativity rate was 64.2%. In R/R patients using blinatumomab for consolidation, MRD negativity rate was 90.9%. The median EFS was not reached in both ND and R/R patients; 1-year EFS rate was 90.8% (95% CI: 67%, 97%) and 55.1% (95% CI: 30%, 74%), respectively. Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting.

HOXA-AS2 Epigenetically Inhibits HBV Transcription by Recruiting the MTA1-HDAC1/2 Deacetylase Complex to cccDNA Minichromosome.

Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non-coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation. In this study, lncRNA sequencing (lncRNA seq) is conducted on five pairs of HBV-positive and HBV-negative liver tissue. Through analysis, HOXA-AS2 (HOXA cluster antisense RNA 2) is identified as a significantly upregulated lncRNA in HBV-infected livers. Further experiments demonstrate that HBV DNA polymerase (DNA pol) induces HOXA-AS2 after establishing persistent high-level HBV replication. Functional studies reveal that HOXA-AS2 physically binds to cccDNA and significantly inhibits its transcription. Mechanistically, HOXA-AS2 recruits the MTA1-HDAC1/2 deacetylase complex to cccDNA minichromosome by physically interacting with metastasis associated 1 (MTA1) subunit, resulting in reduced acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) associated with cccDNA and subsequently suppressing cccDNA transcription. Altogether, the study reveals a mechanism to self-limit HBV replication, wherein the upregulation of lncRNA HOXA-AS2, induced by HBV DNA pol, can epigenetically suppress cccDNA transcription.

Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Regioselective Syntheses of 1,4- and 1,6-Dicarbonyl Compounds via Photoredox-Based Oxidative Heterocoupling of Enolsilanes with Oxygen as an Oxidant.

A photoredox-based oxidative heterocoupling of enolsilanes to the corresponding 1,4- and 1,6-dicarbonyl compounds was developed by using Mes-Acr+BF4- as the photocatalyst, and oxygen was used as the oxidant. This newly developed chemistry adheres to the principles of atom economy, step economy, and redox economy, making it a concise and efficient method.

Carbon ion irradiation combined with PD-1 inhibitor trigger abscopal effect in Lewis lung cancer via a threshold dose.

Background and goal: Carbon ion beam is radio-biologically more efficient than photons and is beneficial for treating radio-resistant tumors. Several animal experiments with tumor-bearing suggest that carbon ion beam irradiation in combination with immunotherapy yields better results, especially in controlling distant metastases. This implies that carbon ion induces a different anti-tumor immune response than photon beam. More complex molecular mechanisms need to be uncovered. This in vivo and in vitro experiment was carried out in order to examine the radio-immune effects and the mechanism of action of carbon ion beam versus X-ray in combination with PD-1 inhibitors. Methods and Materials: Lewis lung adenocarcinoma cells and C57BL/6 mice were used to create a tumor-bearing mouse model, with the non-irradiated tumor growing on the right hind leg and the irradiated tumor on the left rear. 10Gy carbon ion beam or X-ray radiation, either alone or in combination with PD-1 inhibitor, were used to treat the left back tumor. The expression of molecules linked to immunogenicity and the infiltration of CD8+ T lymphocytes into tumor tissues were both identified using immunohistochemistry. IFN-ß in mouse serum was measured using an ELISA, while CD8+ T cells in mouse peripheral blood were measured using flow cytometry. Lewis cells were exposed to different dose of X-ray and carbon ion. TREX1, PD-L1, and IFN-ß alterations in mRNA and protein levels were identified using Western blot or RT-PCR, respectively. TREX1 knockdown was created by siRNA transfection and exposed to various radiations. Using the CCK8 test, EdU assay, and flow cytometry, changes in cell viability, proliferation, and apoptosis rate were discovered. Results: Bilateral tumors were significantly inhibited by the use of carbon ion or X-ray in combination with PD-1, particularly to non-irradiated tumor(p<0.05). The percentage of infiltrating CD8+ T cells and the level of IFN-ß expression were both raised by 10Gy carbon ion irradiation in the irradiated side tumor, although PD-L1 and TREX1 expression levels were also elevated. Lewis cell in vitro experiment further demonstrated that both X-ray and carbon ion irradiation can up-regulate the expression levels of PD-L1 and TREX1 with dose-dependent in tumors, particularly the trend of up-regulation TREX1 is more apparent at a higher dose in carbon ion, i.e. 8 or 10Gy, while the level of IFN-ß is decreased. IFN-ß levels were considerably raised under hypofractionated doses of carbon ion radiation by gene silencing TREX1. Conclusions: By enhancing tumor immunogenicity and increasing CD8+T infiltration in TME through a threshold dosage, X-ray or carbon ion radiation and PD-1 inhibitors improve anti-tumor activity and cause abscopal effect in Lewis lung adenocarcinoma-bearing mice. TREX1 is a possible therapeutic target and prognostic marker.

A novel prognostic signature of coagulation-related genes leveraged by machine learning algorithms for lung squamous cell carcinoma.

Coagulation-related genes (CRGs) have been demonstrated to be essential for the development of certain tumors; however, little is known about CRGs in lung squamous cell carcinoma (LUSC). In this study, we adopted CRGs to construct a coagulation-related gene prognostic signature (CRGPS) using machine learning algorithms. Using a set of 92 machine learning integrated algorithms, the CRGPS was determined to be the optimal prognostic signature (median C-index = 0.600) for predicting the prognosis of an LUSC patient. The CRGPS was not only superior to traditional clinical parameters (e.g., T stage, age, and gender) and its commutative genes but also outperformed 19 preexisting prognostic signatures for LUSC on predictive accuracy. The CRGPS score was positively correlated with poor prognoses in patients with LUSC (hazard ratio > 1, p < 0.05), indicating its suitability as a prognostic marker for this disease. The CRGPS was observed to be inversely correlated with the degree of infiltration of natural killer cells. For some tumors, patients with lower CRGPS scores are more likely to experience enhanced immunotherapy effects (area under the curve = 0.70), which implies that the CRGPS can potentially predict immunotherapy efficacy. A high CRGPS score is predictive of an LUSC patient being sensitive to several drugs. Collectively, these findings indicate that the CRGPS may be a reliable indicator of the prognoses of patients with LUSC and may be useful for the clinical management of such patients.

Effect of scapular stabilization exercises on subacromial pain (impingement) syndrome: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the effectiveness of scapular stabilization exercises (SSE) in the treatment of subacromial pain syndrome (SAPS). Methods: Clinical randomized controlled trials (RCTs) on SSE in the treatment of SAPS were searched electronically in PubMed, Science Direct, Cochrane Central Register of Controlled Trials (CENTRAL), EBSCOhost, Physiotherapy Evidence Database (PEDro), Web of Science, and other databases from 2000 to 2022, supplemented by manual search. Final RCTs were selected based on inclusion and exclusion criteria, and the Physiotherapy Evidence Database scale was used to evaluate the methodological quality of the study. A meta-analysis was conducted on data using the RevMan5.4 software. Results: Eight RCTs involving 387 participants were included. The meta-analysis showed that the experimental group (SSE) had greater improvements in the Visual Analog Scale score [Weighted Mean Difference (WMD) = -0.94, 95% CI (-1.23, -0.65), p < 0.001] and the Shoulder Pain and Disability Index score [WMD = -10.10, 95% CI (-18.87, -1.33), p = 0.02] than the control group (conventional physical therapy). However, range of motion (ROM) was not found to be greater in the experimental group than in the control group. Conclusion: Existing evidence moderately supports the efficacy of SSE for reducing pain and improving function in SAPS, without significant improvement in ROM. Future research should focus on larger, high-quality, standardized protocols to better understand SSE's effects across diverse SAPS populations, treatment, and outcome measures. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307437, CRD42022307437.

Multi-omics pan-cancer analyses identify MCM4 as a promising prognostic and diagnostic biomarker.

Minichromosome Maintenance Complex Component 4 (MCM4) is a vital component of the mini-chromosome maintenance complex family, crucial for initiating the replication of eukaryotic genomes. Recently, there has been a growing interest in investigating the significance of MCM4 in different types of cancer. Despite the existing research on this topic, a comprehensive analysis of MCM4 across various cancer types has been lacking. This study aims to bridge this knowledge gap by presenting a thorough pan-cancer analysis of MCM4, shedding light on its functional implications and potential clinical applications. The study utilized multi-omics samples from various databases. Bioinformatic tools were employed to explore the expression profiles, genetic alterations, phosphorylation states, immune cell infiltration patterns, immune subtypes, functional enrichment, disease prognosis, as well as the diagnostic potential of MCM4 and its responsiveness to drugs in a range of cancers. Our research demonstrates that MCM4 is closely associated with the oncogenesis, prognosis and diagnosis of various tumors and proposes that MCM4 may function as a potential biomarker in pan-cancer, providing a deeper understanding of its potential role in cancer development and treatment.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.