The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis.

The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis.

Comprehensive AI-assisted tool for ankylosing spondylitis based on multicenter research outperforms human experts.

Introduction: The diagnosis and treatment of ankylosing spondylitis (AS) is a difficult task, especially in less developed countries without access to experts. To address this issue, a comprehensive artificial intelligence (AI) tool was created to help diagnose and predict the course of AS. Methods: In this retrospective study, a dataset of 5389 pelvic radiographs (PXRs) from patients treated at a single medical center between March 2014 and April 2022 was used to create an ensemble deep learning (DL) model for diagnosing AS. The model was then tested on an additional 583 images from three other medical centers, and its performance was evaluated using the area under the receiver operating characteristic curve analysis, accuracy, precision, recall, and F1 scores. Furthermore, clinical prediction models for identifying high-risk patients and triaging patients were developed and validated using clinical data from 356 patients. Results: The ensemble DL model demonstrated impressive performance in a multicenter external test set, with precision, recall, and area under the receiver operating characteristic curve values of 0.90, 0.89, and 0.96, respectively. This performance surpassed that of human experts, and the model also significantly improved the experts' diagnostic accuracy. Furthermore, the model's diagnosis results based on smartphone-captured images were comparable to those of human experts. Additionally, a clinical prediction model was established that accurately categorizes patients with AS into high-and low-risk groups with distinct clinical trajectories. This provides a strong foundation for individualized care. Discussion: In this study, an exceptionally comprehensive AI tool was developed for the diagnosis and management of AS in complex clinical scenarios, especially in underdeveloped or rural areas that lack access to experts. This tool is highly beneficial in providing an efficient and effective system of diagnosis and management.

Biomarkers for primary open-angle glaucoma progression.

Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.

Anterior Segment OCT in Primary Angle Closure Disease Compared With Normal Subjects With Similar Shallow Anterior Chamber.

PRCIS: Compared with normal subjects with similar shallow anterior chamber depth (ACD), patients with primary angle closure disease (PACD) had narrower angle structures measured by swept-source optical coherence tomography (SS-OCT) at 250 µm from scleral spur (very root of iris), especially along oblique and vertical axis. PURPOSE: To examine anterior segment structures in normal subjects whose ACD was shallow on slit-lamp examination but did not meet the diagnostic criteria of PACD, and to compare them with PACD patients with similar ACD. MATERIALS AND METHODS: Patients were recruited from glaucoma clinic at Zhongshan Ophthalmic Center. A total of 40 eyes from 29 PACD patients and 40 eyes from 34 normal subjects received full ophthalmic examination and CASIA SS-1000 OCT tests. PACD eyes and control eyes were 1:1 matched for ACD at 0 degree of scan. Generalized linear model that accounted for inter-eye correlation was used to compare differences between the 2 groups for intraocular pressure and SS-OCT parameters. P-values were adjusted for multiple comparisons using the Bonferroni method. RESULTS: The PACD and control groups had similar age, but the PACD group had a significantly higher intraocular pressure (18.4 vs. 14.0 mm Hg, P=0.005). Angle parameters, representative of angle area, such as angle recess area and trabecular iris space area measured at 250 µm along axes of 90, 135, 225, and 315 degrees were significantly smaller in PACD group than those of control group (adjusted P<0.05), while most of angle parameters at 500 and 750 µm, volume parameters, and anterior chamber parameters, were similar (adjusted P>0.05). CONCLUSIONS: In PACD patients compared with normal subjects with similar anterior chamber shallowing, OCT findings measured at the iris root 250 µm from the scleral spur, especially in the oblique and vertical axes, including angle recess area and trabecular iris space area, may match gonioscopic findings more closely and provide further insight into mechanisms of PACD.

Repeatability and Reproducibility of Anterior Chamber Angle Measurement with Swept-Source Optical Coherence Tomography in Patients with Primary Angle Closure Suspect.

Purpose: To evaluate the inter- and intra-observer reliability of anterior chamber (AC) angle measurements obtained by swept-source optical coherence tomography (SS-OCT).Methods: Forty-eight consecutive patients diagnosed with primary angle closure suspect (PACS) were included. Three masked observers at different training levels (one glaucoma specialist, one ophthalmology resident, and one pre-medical college student) measured 192 SS-OCT images of the PACS patients. One observer (the glaucoma specialist) repeated measurements 1 week later. SS-OCT parameters included: Anterior segment volume, including corneal, AC, and iris volume; anterior segment dimensions, including AC depth and width (ACD, ACW), and lens vault (LV); and angle parameters, including angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and the trabecular iris angle (TIA). Intraclass correlation coefficients (ICCs) were used to measure reliability.Results: For inter-observer reproducibility, ICCs of corneal, AC, and iris volumes were 0.952 to 0.998. ICCs of ACD at all axes were above 0.989. ICCs of ACW and LV were smallest in the 90°-270° axis (0.751 and 0.768) but not significantly different from other axes. ARA, TISA, and TIA at all angles had significantly smallest ICCs 250 µm from the scleral spur compared with 500 µm and 750 µm. The ICCs comparing observers with different training levels had similar ranges and followed similar trends. For intra-observer repeatability, the smallest ICC was 0.843. Decreasing AC depth correlated with increased inter-observer reproducibility.Conclusions: We found excellent intra-observer repeatability for all SS-OCT parameters. Angle measurements have more variation among the observers when taken 250 µm from the scleral spur. Shallow AC might lead to more variability for angle parameters. Non-expert observers may be recruited for high-quality image grading with standard training.

Amino Acid Degrading Enzymes and Autophagy in Cancer Therapy.

Recently, there has been renewed interest in metabolic therapy for cancer, particularly in amino acid deprivation by enzymes. L-asparaginase was approved for the treatment of acute lymphoblastic leukemia by the U.S. Food and Drug Administration. Arginine deiminase and recombinant human arginase have been developed into clinical trials as potential cancer therapeutic agents for the treatment of arginine-auxotrophic tumors. Moreover, other novel amino acid degrading enzymes, such as glutaminase, methionase, lysine oxidase, phenylalanine ammonia lyase, have been developed for the treatment of malignant cancers. One of the greatest obstacles faced by anticancer drugs is the development of drug resistance, which is reported to be associated with autophagy. Autophagy is an evolutionarily conserved catabolic process that is responsible for the degradation of dysfunctional proteins and organelles. There is a growing body of literature revealing that, in response to metabolism stress, autophagy could be induced by amino acid deprivation. The manipulation of autophagy in combination with amino acid degrading enzymes is actively being investigated as a potential therapeutic approach in preclinical studies. Importantly, shedding light on how autophagy fuels tumor metabolism during amino acid deprivation will enable more potential combinational therapeutic strategies. This study summarizes recent advances, discussing several potential anticancer enzymes, and highlighting the promising combined therapeutic strategy of amino acid degrading enzymes and autophagy modulators in tumors.

The prevalence and risk factors of visual impairment among rural residents aged 50 years and above in Yugan county, China.

PURPOSE: The purpose of the study is to assess the prevalence of visual impairment (PVI) among rural residents aged 50 years and above in Yugan county, China. Researchers analyzed risk factors and obtained scientific baseline information for blindness prevention and control. METHODS: Stratified cluster random sampling was used in randomly selecting 5540 rural residents aged ≥50 in Yugan county. Eligible residents were invited to receive visual acuity measurement via ophthalmic examinations. Multivariable logistic regression was performed to analyze any risk factors. RESULTS: A total of 5119 rural residents participated the ophthalmic examination and investigation. The PVI was 19.2%. The prevalence of moderate and severe visual impairment (≥20/400 and <20/60) was 16.9%, and blindness (<20/400) was 2.27%. Multivariable logistic regression showed that age, gender, education, occupation, marital status, drinking attitude, dietary habits, amount of sleep, and daily fruit intake were the main factors that were most predictive of the PVI. CONCLUSION: The PVI among rural residents aged 50 years and above in Yugan county was higher than many other districts. Preventive work in Yuan and other local regions should be focused on older, separated/divorced, or widowed individuals, and those with a lower level of education. Strengthening public awareness consists of educating the public about visual health promotion and blindness intervention, including healthy diet and healthy habits, which will help to reduce visual impairment of the population.