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Abstract Background Human papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across studies. This study aimed to investigate the presence of HPV in eyelid SGC and SCC among Koreans and its correlation with clinicopathological characteristics. Methods Surgically resected eyelid samples diagnosed as SGC or SCC from January 1999 to June 2011 were identified from the pathology database of three referral centres in Korea. Clinicopathological information including origin (skin vs. tarsal conjunctiva) and treatment outcomes were retrospectively reviewed. Immunohistochemistry (IHC) for p16, HPV DNA in situ hybridisation (ISH), and polymerase chain reaction-based DNA microarray were performed in paraffin-embedded tissue sections. Results Our cohort included 34 SGC and 12 SCC cases with Asian ethnicity. HPV was detected in 4 SGC and 6 SCC by DNA microarray, while 2 SCC (16.7%) showed positivity in ISH. SCC of tarsal conjunctival origin was significantly more common in HPV-positive SCC than in HPV-negative SCC (5 of 6 vs. 0 of 6, P = 0.015, Fisher’s exact test). Among samples showing positive staining in p16 IHC, HPV positivity rates were 0.0% (0/19) in SGC and 100% (3/3) in SCC. There was no significant difference in overall and local recurrence rate in eyelid SGC and SCC according to the HPV status (P > 0.99). Conclusions HPV was found in a subset of eyelid SGC and SCC among Koreans and might be aetiologically related to SCC of tarsal conjunctival origin. Overexpression of p16 is considered to be inappropriate as an indicator of HPV infection in eyelid SGC. Further investigation is required to elucidate the transmission route and pathogenic roles of HPV.

Abstract Artificial intelligence as a screening tool for eyelid lesions will be helpful for early diagnosis of eyelid malignancies and proper decision-making. This study aimed to evaluate the performance of a deep learning model in differentiating eyelid lesions using clinical eyelid photographs in comparison with human ophthalmologists. We included 4954 photographs from 928 patients in this retrospective cross-sectional study. Images were classified into three categories: malignant lesion, benign lesion, and no lesion. Two pre-trained convolutional neural network (CNN) models, DenseNet-161 and EfficientNetV2-M architectures, were fine-tuned to classify images into three or two (malignant versus benign) categories. For a ternary classification, the mean diagnostic accuracies of the CNNs were 82.1% and 83.0% using DenseNet-161 and EfficientNetV2-M, respectively, which were inferior to those of the nine clinicians (87.0–89.5%). For the binary classification, the mean accuracies were 87.5% and 92.5% using DenseNet-161 and EfficientNetV2-M models, which was similar to that of the clinicians (85.8–90.0%). The mean AUC of the two CNN models was 0.908 and 0.950, respectively. Gradient-weighted class activation map successfully highlighted the eyelid tumors on clinical photographs. Deep learning models showed a promising performance in discriminating malignant versus benign eyelid lesions on clinical photographs, reaching the level of human observers.

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides’ termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.

Abstract The aim of this study is to characterize the microRNA (miRNA) expression signatures in patients with thyroid eye disease (TED) and identify miRNA biomarkers of disease activity. Total RNA was isolated from the sera of patients with TED (n = 10) and healthy controls (HCs, n = 5) using the miRNeasy Serum/Plasma Kit. The NanoString assay was used for the comprehensive analysis of 798 miRNA expression profiles. Analysis of specific miRNA signatures, mRNA target pathway analysis, and network analysis were performed. Patients with TED were divided into two groups according to disease activity: active and inactive TED groups. Differentially expressed circulating miRNAs were identified and tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests in the validation cohort. Among the 798 miRNAs analyzed, 173 differentially downregulated miRNAs were identified in TED patients compared to those in the HCs. Ten circulating miRNAs were differentially expressed between the active and inactive TED groups and regarded as candidate biomarkers for TED activity (one upregulated miRNA: miR-29c-3p; nine downregulated miRNAs: miR-4286, miR-941, miR-571, miR-129-2-3p, miR-484, miR-192-5p, miR-502-3p, miR-597-5p, and miR-296-3p). In the validation cohort, miR-484 and miR-192-5p showed significantly lower expression in the active TED group than in the inactive TED group. In conclusion, the expression levels of miR-484 and miR-192-5p differed significantly between the active and inactive TED groups, suggesting that these miRNAs could serve as circulating biomarkers of TED activity, however, these findings need to be validated in further studies.

Abstract Although the clinical activity score (CAS) is a validated scoring system for identifying disease activity of thyroid-associated orbitopathy (TAO), it may produce differing results depending on the evaluator, and an experienced ophthalmologist is required for accurate evaluation. In this study, we developed a machine learning (ML)-assisted system to mimic an expert’s CAS assessment using digital facial images and evaluated its accuracy for predicting the CAS and diagnosing active TAO (CAS ≥ 3). An ML-assisted system was designed to assess five CAS components related to inflammatory signs (redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and/or plica, and conjunctival edema) in patients’ facial images and to predict the CAS by considering two components of subjective symptoms (spontaneous retrobulbar pain and pain on gaze). To train and test the system, 3,060 cropped images from 1020 digital facial images of TAO patients were used. The reference CAS for each image was scored by three ophthalmologists, each with > 15 years of clinical experience. We repeated the experiments for 30 randomly split training and test sets at a ratio of 8:2. The sensitivity and specificity of the ML-assisted system for diagnosing active TAO were 72.7% and 83.2% in the test set constructed from the entire dataset. For the test set constructed from the dataset with consistent results for the three ophthalmologists, the sensitivity and specificity for diagnosing active TAO were 88.1% and 86.9%. In the test sets from the entire dataset and from the dataset with consistent results, 40.0% and 49.9% of the predicted CAS values were the same as the reference CAS, respectively. The system predicted the CAS within 1 point of the reference CAS in 84.6% and 89.0% of cases when tested using the entire dataset and in the dataset with consistent results, respectively. An ML-assisted system estimated the clinical activity of TAO and detect inflammatory active TAO with reasonable accuracy. The accuracy could be improved further by obtaining more data. This ML-assisted system can help evaluate the disease activity consistently as well as accurately and enable the early diagnosis and timely treatment of active TAO.

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-μm-high 3D electrodes on a 200-μm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-μm-thick sloped PDMS substrate without electrodes (group 2); and a 140-μm-thick sloped PDMS substrate with 20-μm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain–optical coherence tomography (SD–OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-μm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD–OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-μm-high electrodes showed better structural compatibility than the 75-μm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-μm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

Purpose To quantitatively analyze morphological and functional alterations of the meibomian glands in eyes with marginal entropion and their changes after surgery. Methods Sixty eyes of 52 patients with marginal entropion and underwent meibography and interferometer were included. One-hundred and seventeen age- and sex-matched eyes with minimal to mild meibomian gland dysfunction (MGD) were recruited as control eyes. Meibomian gland loss (MGL) and lipid layer thickness (LLT) were compared between eyes with marginal entropion and control eyes. Subgroup analysis was performed according to the extent of entropion. MGL and average LLT at 1 and 5 months after surgery were compared with those of 20 eyes with marginal entropion followed without surgery. Results In eyes with marginal entropion, MGL was higher (27.7% vs. 12.8%, P = 0.014), and average LLT was thinner (64 nm vs. 86 nm, P = 0.005) than those in control eyes. MGL was higher in eyes with more extensive entropion (> 2/3 eyelid width) than in eyes with less extensive entropion (≤ 1/3 eyelid width) (40.5% vs. 13.2%, P = 0.001). Average LLT increased after surgery (97 nm at 1 month, P = 0.003; 75 nm at 5 months, P = 0.319), and thicker than that of eyes followed without surgery (97 nm vs. 66 nm, P = 0.046). MGLs after surgery remained unchanged from the preoperative MGL (all P > 0.7). Conclusion Marginal entropion is associated with morphological and functional alterations of the meibomian glands. Functional improvement after entropion repair suggests that marginal entropion could cause or exacerbate MGD. Further studies are required to establish the role of entropion repair in managing MGD.

PurposeTo investigate the association between the bony nasolacrimal duct (NLD) size and outcomes of nasolacrimal silicone intubation for incomplete primary acquired nasolacrimal duct obstruction (PANDO).MethodsPatients who underwent silicone intubation for incomplete PANDO and had undergone facial computed tomography (CT) were included. Surgical success was judged by both epiphora improvement and normalized tear meniscus height (TMH; < 300 μm) on anterior segment optical coherence tomography at 3 months after tube removal. The area, major axis diameter, and minor axis diameter of the elliptic bony NLD sections were measured in 1.0 mm-thick axial CT images. These bony NLD sizes were analyzed for associations with surgical success and TMH normalization.ResultsEighty-one eyes of 48 patients were investigated. The smallest area and the smallest minor axis diameter were significantly larger in the success group (49 eyes), compared with those in the failure group (median smallest minor axis diameter: 4.7 mm vs. 3.8 mm, P = 0.008, Mann-Whitney U test). There was also a tendency for the TMH normalization rate to significantly increase as the smallest area and the smallest minor axis diameter increased (P = 0.028 and 0.037, respectively, Fisher's 2 × 4 tests). Under multivariable logistic regression analysis using generalized estimating equation, a larger smallest minor axis diameter was associated with success of the nasolacrimal silicone intubation (odds ratio: 2.481, 95% confidence interval: 1.143-5.384).ConclusionSurgical success of the nasolacrimal silicone intubation in incomplete PANDO is associated with a larger smallest minor axis diameter of the bony NLD. This finding will help understand the pathophysiology of surgical failure after nasolacrimal silicone intubation.

With the advancement of the Internet of Things (IoT), numerous electronic devices are connected to each other and exchange a vast amount of data via the Internet. As the number of connected devices increases, security concerns have become more significant. As one of the potential solutions for security issues, hardware intrinsic physical unclonable functions (PUFs) are emerging semiconductor devices that exploit inherent randomness generated during the manufacturing process. The unclonable security key generated from PUF can address the inherent limitations of conventional electronic systems which depend solely on software. Although numerous PUFs based on the emerging memory devices requiring switching operations have been proposed, achieving hardware intrinsic PUF with low power consumption remains a key challenge. Here, we demonstrate that the process-induced nonlinear conductance variations of oxide semiconductor-based Schottky diodes provide a suitable source of entropy for the implementation of PUF without switching operation. Using a mild oxygen plasma treatment, the surface electron accumulation layer that forms naturally in oxide semiconductor film can be partially eliminated, resulting in a large variation of nonlinearity as an exotic entropy source. The mild plasma-treated Schottky diodes showed near ideal 50% average uniformity and uniqueness, as well as an ideal entropy value without the need for additional hardware area and power costs. These findings will pave the way for the development of hardware intrinsic PUFs to realize energy-efficient cryptographic hardware.

Background Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study. Methods Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ’SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed. Results LOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing. Conclusions LOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Background/Aims To report the long-term outcomes of enucleation and insertion of porous polyethylene (PP) orbital implant according to the evolving surgical techniques and implant in patients with paediatric retinoblastoma. Methods Patients with paediatric retinoblastoma who underwent enucleation and PP implant insertion from December 1998 to December 2014 were retrospectively reviewed and divided into four groups: group A, classic enucleation +PP implant; group B, enucleation +PP implant +anterior closure of the posterior Tenon's (ACPT) capsule; group C, enucleation +PP implant +free orbital fat graft +ACPT and group D, enucleation +smooth surface tunnel PP implant +ACPT. Survival analysis of implant exposure and eyelid malpositions was performed. Results One hundred and ninety-eight eyes of 196 patients were included. The median follow-up period was 13.0 years (range, 5.0-21.1). A 20 mm implant was inserted for 149 eyes (75.3%). The 10-year exposure-free survival probabilities were 44.6% in group A, 96.4% in group B, 97.4% in group C and 97.7% in group D. ACPT was associated with significant reduction in implant exposure (p<0.001). The most common eyelid malposition was upper eyelid ptosis (24.2%). The eyelid malposition-free survival probability did not differ among the four groups. However, the insertion of a 20 mm implant was associated with significant reduction in upper eyelid ptosis and lower eyelid entropion (p=0.004 and 0.038, respectively). Conclusions The long-term postenucleation implant exposure was rare after PP implant insertion and ACPT, even with a 20 mm-diameter implant. A larger implant can be beneficial in long-term prevention of eyelid malposition. [ABSTRACT FROM AUTHOR]

This study reports intrinsic multimodal memristivity of a nonconjugated radical polymer with ambient stability. Organic memristive devices represent powerful candidates for biorealistic data storage and processing. However, there exists a substantial knowledge gap in realizing the synthetic biorealistic systems capable of effectively emulating the cooperative and multimodal activation processes in biological systems. In addition, conventional organic memristive materials are centered on conjugated small and macromolecules, making them synthetically challenging or difficult to process. In this work, we first describe the intrinsic resistive switching of the radical polymer that resulted in an exceptional state retention of >105 s and on/off ratio of >106. Next, we demonstrate its bimodal cooperative switching, in response to the proton accumulation as a biological input. Last, we expand our system toward an advanced in-sensor computing system. Our research demonstrates a nonconjugated radical polymer with intrinsic memristivity, which is directly applicable to future electronics including data storage, neuromorphics, and in-sensor computing. [ABSTRACT FROM AUTHOR]