First Detection of Influenza D Virus Infection in Cattle and Pigs in the Republic of Korea.

Influenza D virus (IDV) belongs to the Orthomyxoviridae family, which also include the influenza A, B and C virus genera. IDV was first detected and isolated in 2011 in the United States from pigs with respiratory illness. IDV circulates in mammals, including pigs, cattle, camelids, horses and small ruminants. Despite the broad host range, cattle are thought to be the natural reservoir of IDV. This virus plays a role as a causative agent of the bovine respiratory disease complex (BRDC). IDV has been identified in North America, Europe, Asia and Africa. However, there has been no information on the presence of IDV in the Republic of Korea (ROK). In this study, we investigated the presence of viral RNA and seroprevalence to IDV among cattle and pigs in the ROK in 2022. Viral RNA was surveyed by the collection and testing of 999 cattle and 2391 pig nasal swabs and lung tissues using a real-time RT-PCR assay. IDV seroprevalence was investigated by testing 742 cattle and 1627 pig sera using a hemagglutination inhibition (HI) assay. The viral RNA positive rate was 1.4% in cattle, but no viral RNA was detected in pigs. Phylogenetic analysis of the hemagglutinin-esterase-fusion (HEF) gene was further conducted for a selection of samples. All sequences belonged to the D/Yamagata/2019 lineage. The seropositivity rates were 54.7% in cattle and 1.4% in pigs. The geometric mean of the antibody titer (GMT) was 68.3 in cattle and 48.5 in pigs. This is the first report on the detection of viral RNA and antibodies to IDV in the ROK.

Reproducibility of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness Measurements by Optical Coherence Tomography in Myopic Eyes.

PRECIS: In myopic eyes, reproducibility of circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer thickness measurement by optical coherence tomography (OCT) showed excellent reproducibility except for the temporal quadrant RNFL thickness measurement. PURPOSE: The aim of this study was to evaluate the long-term reproducibility of circumpapillary RNFL and macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements using OCT in myopic eyes. METHODS: Sixty-five eyes with moderate-to-high myopia (spherical equivalent <-3.0 D, myopia group) and 53 eyes with low-to-no myopia (spherical equivalent ≥-3.0 D, control group) without ocular disorders, such as glaucoma or retinal diseases, were included. Three serial OCT scans recorded at 1-year intervals were analyzed. Reproducibility was evaluated using within-subject SD (Sw), coefficient of variation (CVw), and intraclass correlation coefficient (ICC). RESULTS: Mean±SD refractive error was -0.30±0.80 and -6.26±2.45 D for control and myopia groups, respectively. The myopia group had thinner superior, inferior, and nasal quadrant RNFL, thicker temporal quadrant RNFL, and thinner GCIPL than the control group (P<0.05), except for the minimum and superotemporal GCIPL thicknesses (P>0.05). The myopia group had lower reproducibility in temporal quadrant RNFL thickness (Sw, 2.57 µm; CVw 3.27%; ICC, 0.979) than the control group (Sw, 1.80 µm; CVw 2.59%; ICC, 0.989), whereas in other sectors of RNFL and all GCIPL parameters, comparable reproducibility was observed between the 2 groups. CONCLUSIONS: Long-term reproducibility of RNFL and GCIPL thickness measurements in moderate-to-high myopia was comparable to that of low-to-no myopia, except RNFL thickness in the temporal quadrant. These findings should be considered when detecting RNFL and GCIPL changes.

Deep Learning Ensemble Method for Classifying Glaucoma Stages Using Fundus Photographs and Convolutional Neural Networks.

Purpose: This study developed and evaluated a deep learning ensemble method to automatically grade the stages of glaucoma depending on its severity.Materials and Methods: After cross-validation of three glaucoma specialists, the final dataset comprised of 3,460 fundus photographs taken from 2,204 patients were divided into three classes: unaffected controls, early-stage glaucoma, and late-stage glaucoma. The mean deviation value of standard automated perimetry was used to classify the glaucoma cases. We modeled 56 convolutional neural networks (CNN) with different characteristics and developed an ensemble system to derive the best performance by combining several modeling results.Results: The proposed method with an accuracy of 88.1% and an average area under the receiver operating characteristic of 0.975 demonstrates significantly better performance to classify glaucoma stages compared to the best single CNN model that has an accuracy of 85.2% and an average area under the receiver operating characteristic of 0.950. The false negative is the least adjacent misprediction, and it is less in the proposed method than in the best single CNN model.Conclusions: The method of averaging multiple CNN models can better classify glaucoma stages by using fundus photographs than a single CNN model. The ensemble method would be useful as a clinical decision support system in glaucoma screening for primary care because it provides high and stable performance with a relatively small amount of data.

Correction: A deep learning model for the detection of both advanced and early glaucoma using fundus photography.

[This corrects the article DOI: 10.1371/journal.pone.0207982.].

A deep learning model for the detection of both advanced and early glaucoma using fundus photography.

PURPOSE: To build a deep learning model to diagnose glaucoma using fundus photography. DESIGN: Cross sectional case study Subjects, Participants and Controls: A total of 1,542 photos (786 normal controls, 467 advanced glaucoma and 289 early glaucoma patients) were obtained by fundus photography. METHOD: The whole dataset of 1,542 images were split into 754 training, 324 validation and 464 test datasets. These datasets were used to construct simple logistic classification and convolutional neural network using Tensorflow. The same datasets were used to fine tune pre-trained GoogleNet Inception v3 model. RESULTS: The simple logistic classification model showed a training accuracy of 82.9%, validation accuracy of 79.9% and test accuracy of 77.2%. Convolutional neural network achieved accuracy and area under the receiver operating characteristic curve (AUROC) of 92.2% and 0.98 on the training data, 88.6% and 0.95 on the validation data, and 87.9% and 0.94 on the test data. Transfer-learned GoogleNet Inception v3 model achieved accuracy and AUROC of 99.7% and 0.99 on training data, 87.7% and 0.95 on validation data, and 84.5% and 0.93 on test data. CONCLUSION: Both advanced and early glaucoma could be correctly detected via machine learning, using only fundus photographs. Our new model that is trained using convolutional neural network is more efficient for the diagnosis of early glaucoma than previously published models.

Long-term comparison of postoperative refractive outcomes between phacotrabeculectomy and phacoemulsification.

PURPOSE: To compare long-term postoperative refractive outcomes between phacotrabeculectomy and phacoemulsification, both with posterior chamber intraocular lens implantation. SETTING: Department of Ophthalmology, Konyang University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, South Korea. DESIGN: Retrospective comparative study. METHODS: Postoperative refractive outcomes were compared between patients with cataract and coexisting primary or secondary open-angle glaucoma (OAG) who had phacotrabeculectomy (combined group) and patients with cataract with or without coexisting OAG who had phacoemulsification alone (phaco-only group). The refractive prediction error, mean absolute error, and median absolute error were compared between groups. Subgroup analysis based on preoperative axial length (AL) was performed (medium >22.0 to <24.5 mm; medium-long ≥24.5 to <26.0 mm; long ≥26.0 mm). RESULTS: The combined group comprised 51 eyes and the phaco-only group, 74 eyes. The mean interval between surgery and refraction measurement was 14.70 months ± 10.80 (SD) (median 13.0 months) and 4.81 ± 4.97 months (median 2.0 months), respectively. Postoperatively, there was no statistically significant between-group difference in the following mean values: refractive prediction error, -0.05 ± 0.64 versus -0.04 ± 0.52 (P = .905); mean absolute error, 0.46 ± 0.44 versus 0.38 ± 0.36 (P = .258); median absolute error, 0.32 (interquartile range [IQR], 0.17, 0.67) versus 0.28 (IQR, 0.13, 0.54) (P = .297). Subgroup analysis also did not show significant differences between the 2 groups (all P > .05). CONCLUSION: The long-term postoperative refractive outcomes of phacotrabeculectomy and phacoemulsification alone were not significantly different in eyes with OAG, regardless of preoperative AL.

Glaucomatous progression in the retinal nerve fibre and retinal ganglion cell-inner plexiform layers determined using optical coherence tomography-guided progression analysis.

BACKGROUND: To investigate the characteristics of glaucomatous progression in circumpapillary retinal nerve fibre layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) determined using optical coherence tomography-guided progression analysis (OCT-GPA). METHODS: Serial OCT images of 527 glaucomatous eyes with greater than four OCT tests were screened. Among them, 106 (20.1 per cent) eyes with progression in either RNFL or GCIPL determined using OCT-GPA were included. Based on the agreement of progression detection between RNFL and GCIPL, the eyes were classified into the 'RNFL progression earlier group', 'GCIPL progression earlier group', or 'simultaneous progression group'. The type of progression was classified as diffuse, localised or mixed. RESULTS: Among the 106 eyes with progression, 100 (94.3 per cent) showed RNFL progression and 83 (78.3 per cent) showed GCIPL progression. Fifty-four (50.9 per cent), 13 (12.3 per cent), and 39 (36.8 per cent) eyes were classified into the RNFL progression earlier group, GCIPL progression earlier group, and simultaneous progression group, respectively. Diffuse-type progression was found in three (three per cent) eyes with RNFL progression and 32 (38.6 per cent) eyes with GCIPL progression. The most common location of progression was the 7 o'clock sector (42.0 per cent) in the RNFL and the inferotemporal sector (39.8 per cent) in the GCIPL. CONCLUSIONS: The most common characteristic of RNFL and GCIPL progression determined using OCT-GPA was localised thinning in the inferotemporal area. Progression was more frequently found in the RNFL than in the GCIPL, and diffuse-type progression was more frequent in the GCIPL than in the RNFL.

Detection of progression of glaucomatous retinal nerve fibre layer defects using optical coherence tomography-guided progression analysis.

PURPOSE: The aim was to investigate the agreement for detection of progression of glaucomatous retinal nerve fibre layer defects (RNFLD) between optical coherence tomography-guided progression analysis (OCT GPA) and conventional red-free fundus photography. METHODS: Four hundred and fifteen glaucomatous eyes that underwent at least four serial red-free photographic and OCT examinations were included in the study. Based on the inspection of the red-free fundus photographs and GPA maps, RNFLD progression was defined as the development of a new defect, widening or deepening of a pre-existing RNFLD in red-free fundus photography (photographic progression) or 'Likely Loss' on a GPA map (GPA progression). The agreement of photographic and OCT GPA progression and the factors influencing it, including refractive error, severity of glaucoma (mean deviation of the visual field), type of RNFLD (localised versus diffuse), width of the baseline RNFLD, type of RNFLD progression (new defect, widening, deepening) and location of RNFLD progression (clock-hour sector) were assessed. RESULTS: Among the 415 eyes, 82 (19.8 per cent) showed photographic or GPA progression. Among the 82 eyes with progression, progression was detected only in red-free fundus photography in nine (11.0 per cent) eyes and only in GPA in 32 (39.0 per cent) eyes. In 41 eyes (50.0 per cent), progression was detected with both methods. Detection of RNFLD progression only in GPA was associated with a higher myopia, diffuse RNFLD, deepening of the RNFLD and RNFLD progression at the 6, 9 and 12 o'clock positions (p < 0.05). CONCLUSIONS: OCT GPA may be a useful supplement to conventional red-free fundus photography for detecting RNFLD progression.

Changes in Tear Volume after 3% Diquafosol Treatment in Patients with Dry Eye Syndrome: An Anterior Segment Spectral-domain Optical Coherence Tomography Study.

PURPOSE: To evaluate changes in the tear meniscus area and tear meniscus height over time in patients with dry eye syndrome, using anterior segment spectral-domain optical coherence tomography after the instillation of 3% diquafosol ophthalmic solution. METHODS: Sixty eyes from 30 patients with mild to moderate dry eye syndrome were included. Tear meniscus images acquired by anterior segment spectral-domain optical coherence tomography were analyzed using National Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30 minutes after instillation of a drop of diquafosol in one eye and normal saline in the other eye. Changes in ocular surface disease index score, tear film break-up time, corneal staining score by Oxford schema, and meibomian expressibility were also evaluated at baseline, and after 1 week and 1 month of a diquafosol daily regimen. RESULTS: Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men and 22 women) were included. In eyes receiving diquafosol, tear volume was increased at 5 and 10 minutes compared with baseline. It was also higher than saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with respect to baseline were not statistically different after the use of diquafosol for 1 month. Ocular surface disease index score, tear film break-up time, and Oxford cornea stain score were significantly improved after 1 week and 1 month of daily diquafosol instillation, but meibomian expressibility did not change. CONCLUSIONS: Topical diquafosol ophthalmic solution effectively increased tear volume for up to 30 minutes, compared to normal saline in patients with dry eye syndrome.

Clusterin, a novel modulator of TGF-beta signaling, is involved in Smad2/3 stability.

Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. It is known that CLU interacts with TGF-beta type ll receptor (TbetaRll). However, the relationship of CLU and TGF-beta signaling is unclear. Here we present that CLU is a novel modulator of TGF-beta signaling by regulating Smad2/3 proteins. Overexpression of CLU enhanced TGF-beta-induced transcriptional activity and increased the amount of Smad2/3 proteins, while CLU siRNA repressed TGF-beta-induced transcriptional activity and decreased the amount of Smad2/3 proteins in Hep3B cells. We also found that CLU was involved in Smad2/3 stability at the protein level. These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins.

Clusterin mRNA expression in apoptotic and activated rat thymocytes.

Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exact biological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavily disputed, since data supporting both views have been reported in several independent studies. To clarify this issue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the present study, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis in thymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and after induction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering of apoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptotic processes. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expression was restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolytic cleavage site and is therefore predicted to encode a monomeric protein. The biological function under normal circumstances, however, will need further investigations for clarification. While apoptosis could not modulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted in up-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control of cell activation-mediated rather than apoptosis-induced signals.