Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures.

The functionality of supramolecular nanostructures can be expanded if systems containing multiple components are designed to either self-sort or mix into coassemblies. This is critical to gain the ability to craft self-assembling materials that integrate functions, and our understanding of this process is in its early stages. In this work, we have utilized three different peptide amphiphiles with the capacity to form ß-sheets within supramolecular nanostructures and found binary systems that self-sort and others that form coassemblies. This was measured using atomic force microscopy to reveal the nanoscale morphology of assemblies and confocal laser scanning microscopy to determine the distribution of fluorescently labeled monomers. We discovered that PA assemblies with opposite supramolecular chirality self-sorted into chemically distinct nanostructures. In contrast, the PA molecules that formed a mixture of right-handed, left-handed, and flat nanostructures on their own were able to coassemble with the other PA molecules. We attribute this phenomenon to the energy barrier associated with changing the handedness of a ß-sheet twist in a coassembly of two different PA molecules. This observation could be useful for designing biomolecular nanostructures with dual bioactivity or interpenetrating networks of PA supramolecular assemblies.

miR-200-mediated inactivation of cancer-associated fibroblasts via targeting of NRP2-VEGFR signaling attenuates lung cancer invasion and metastasis.

Cancer-associated fibroblasts (CAFs) play a substantial role in promoting cancer cell motility, drug resistance, angiogenesis, and metastasis; therefore, extensive research has been conducted to determine their mode of activation. We aimed to identify whether miRNA-200 (miR-200), a widely recognized suppressor of epithelial-mesenchymal transition, prevents CAFs from promoting cancer progression. Overexpression of miR-200 prevented CAFs from promoting lung cancer cell migration, invasion, tumorigenicity, and metastasis. Additionally, miR-200 suppressed the ability of CAFs to recruit and polarize macrophages toward the M2 phenotype, as well as the migration and tube formation of vascular endothelial cells. NRP2, a co-receptor of vascular endothelial growth factor receptor (VEGFR), was confirmed to be a target of miR-200, which mediates the functional activity of miR-200 in CAFs. NRP2-VEGFR signaling facilitates the secretion of VEGF-D and pleiotrophin from CAFs, leading to the activation of cancer cell migration and invasion. These findings suggest that miR-200 remodels CAFs to impede cancer progression and metastasis and that miR-200 and NRP2 are potential therapeutic targets in the treatment of lung cancer.

Enhanced Hydrogen Bonding by Urea Functionalization Tunes the Stability and Biological Properties of Peptide Amphiphiles.

Self-assembled nanostructures such as those formed by peptide amphiphiles (PAs) are of great interest in biological and pharmacological applications. Herein, a simple and widely applicable chemical modification, a urea motif, was included in the PA's molecular structure to stabilize the nanostructures by virtue of intermolecular hydrogen bonds. Since the amino acid residue nearest to the lipid tail is the most relevant for stability, we decided to include the urea modification at that position. We prepared four groups of molecules (13 PAs in all), with varying levels of intermolecular cohesion, using amino acids with distinct ß-sheet promoting potential and/or containing hydrophobic tails of distinct lengths. Each subset contained one urea-modified PA and nonmodified PAs, all with the same peptide sequence. The varied responses of these PAs to variations in pH, temperature, counterions, and biologically related proteins were examined using microscopic, X-ray, spectrometric techniques, and molecular simulations. We found that the urea group contributes to the stabilization of the morphology and internal arrangement of the assemblies against environmental stimuli for all peptide sequences. In addition, microbiological and biological studies were performed with the cationic PAs. These assays reveal that the addition of urea linkages affects the PA-cell membrane interaction, showing the potential to increase the selectivity toward bacteria. Our data indicate that the urea motif can be used to tune the stability of a wide range of PA nanostructures, allowing flexibility on the biomaterial's design and opening a myriad of options for clinical therapies.

The Posthyaluronidase Syndrome: Dosing Strategies for Hyaluronidase in the Dissolving of Facial Filler and Independent Predictors of Poor Outcomes.

Background: Hyaluronic acid dermal fillers are used extensively in periocular aesthetic medicine, and the incidence of filler-related complications is increasing. This study aimed to investigate the optimal dosing strategy for hyaluronidase and to identify predictors of poor outcomes. Methods: We performed a retrospective review of 157 orbits of 90 patients treated with hyaluronidase over a 4-year period. Demographic data, indication, and details of hyaluronidase treatment and outcomes were recorded. Results: The primary indication for dissolving filler was swelling in 52%, lumpiness in 20%, and before surgical blepharoplasty in 17%. The most frequently used hyaluronidase concentration was 150 U per mL in 66%, followed by 75 U per mL in 31%, 37.5 U per mL in 3%, and 100 U per mL in 1%. Outcomes were characterized as follows: 59% with a satisfactory result; 24% as insufficient treatment requiring further hyaluronidase; and 18% complaining of facial changes such as hollowing, indicating a post hyaluronidase syndrome. There was no statistical difference in outcomes between the 75 and 150 U per mL dosage groups (P = 0.625). A significant correlation was identified between posthyaluronidase syndrome and duration of filler in situ (P = 0.00019) and volume of filler (P = 0.000017). Conclusions: The posthyaluronidase syndrome may be related to previous filler volume and duration, rather than the concentration or dose of hyaluronidase used. All patients should be informed about the risks of adverse effects after hyaluronidase treatment; patients with longer histories of filler use and higher total volumes should be advised of the increased risk.

Early inner plexiform layer thinning and retinal nerve fiber layer thickening in excitotoxic retinal injury using deep learning-assisted optical coherence tomography.

Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation. Before and after unilateral intravitreal NMDA injection in nine adult Long Evans rats, spectral-domain optical coherence tomography (OCT) was used to acquire volumetric retinal images in both eyes over 4 weeks. Ten retinal layers were automatically segmented from the OCT data using our deep learning-based algorithm. Retinal degeneration was evaluated using layer-specific retinal thickness changes at each time point (before, and at 3, 7, and 28 days after NMDA injection). Within the inner retina, our OCT results showed that retinal thinning occurred first in the inner plexiform layer at 3 days after NMDA injection, followed by the inner nuclear layer at 7 days post-injury. In contrast, the retinal nerve fiber layer exhibited an initial thickening 3 days after NMDA injection, followed by normalization and thinning up to 4 weeks post-injury. Our results demonstrated the pathological cascades of NMDA-induced neurotoxicity across different layers of the retina. The early inner plexiform layer thinning suggests early dendritic shrinkage, whereas the initial retinal nerve fiber layer thickening before subsequent normalization and thinning indicates early inflammation before axonal loss and cell death. These findings implicate the inner plexiform layer as an early imaging biomarker of excitotoxic retinal degeneration, whereas caution is warranted when interpreting the ganglion cell complex combining retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses in conventional OCT measures. Deep learning-assisted retinal layer segmentation and longitudinal OCT monitoring can help evaluate the different phases of retinal layer damage upon excitotoxicity.

Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.

PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).

Dual-attention-based recurrent neural network for hand-foot-mouth disease prediction in Korea.

Hand-foot-mouth disease (HFMD) is a viral disease that occurs primarily in children. Meteorological factors have a significant impact on its popularity annually in Korea. This study proposes a new HFMD prediction model using a dual-attention-based recurrent neural network (DA-RNN) and important weather factors for HFMD in Korea. First, suspected cases of HFMD in each state were predicted using meteorological factors from the DA-RNN. Second, the weather factors were divided into six categories: temperature, wind, rainfall, day length, humidity, and air pollution to conduct sensitivity analysis. Because of this prediction, the proposed model showed the best performance in predicting the number of suspected HFMD cases in a week compared with other RNN methods. Sensitivity analysis showed that air pollution and rainfall play an important role in HFMD in Korea. This model provides information for HFMD prevention and control and can be extended to predict other infectious diseases.

miR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6.

Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3'-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.

Tear Trough Filler Using the Three-point Tangent Technique: Lessons from 1452 Tear Trough Applications.

This study describes a novel three-point tangent technique for tear trough filler and the results from the largest series to date. Methods: A retrospective case review was performed for all patients treated between 2016 and 2020. Patient demographics, filler details and complications were recorded. The injection technique involves using a blunt cannula to deliver filler along three linear tangents bespoke to each patient. Results: A total of 1452 applications of filler to the orbits of 583 patients were recorded. The median patient age was 41 years (range 19-77), and 84% were women. The mean volume of applied filler at the first appointment was 0.34 mL to each orbit (range 0.1--1.5); 82% reported no complication, 10% reported swelling with a median duration of 4 weeks (range 1-52), 4.3% experienced bruising, 4.6% reported contour irregularities, and 3.3% experienced a Tyndall effect. Retrobulbar hemorrhage occurred in one patient (0.17%), which was managed immediately with no lasting visual compromise. Volume of filler injected was significantly associated with a risk of edema (P < 0.00001) and contour irregularities (P = 0.012). In total, 50% of cases of edema resolved spontaneously after 4 weeks. Filler was dissolved in 1.9% of orbits. Patients with a history of dissolving were significantly more likely to require dissolving after subsequent reinjection (P = 0.043). Conclusions: The three-point tangent technique is a safe and effective method. Increasing volume of filler administered is associated with complications of edema and contour irregularities. Edema is the most common complication and resolves spontaneously in half of patients by 4 weeks.

DataCurator.jl: efficient, portable and reproducible validation, curation and transformation of large heterogeneous datasets using human-readable recipes compiled into machine-verifiable templates.

Large-scale processing of heterogeneous datasets in interdisciplinary research often requires time-consuming manual data curation. Ambiguity in the data layout and preprocessing conventions can easily compromise reproducibility and scientific discovery, and even when detected, it requires time and effort to be corrected by domain experts. Poor data curation can also interrupt processing jobs on large computing clusters, causing frustration and delays. We introduce DataCurator, a portable software package that verifies arbitrarily complex datasets of mixed formats, working equally well on clusters as on local systems. Human-readable TOML recipes are converted into executable, machine-verifiable templates, enabling users to easily verify datasets using custom rules without writing code. Recipes can be used to transform and validate data, for pre- or post-processing, selection of data subsets, sampling and aggregation, such as summary statistics. Processing pipelines no longer need to be burdened by laborious data validation, with data curation and validation replaced by human and machine-verifiable recipes specifying rules and actions. Multithreaded execution ensures scalability on clusters, and existing Julia, R and Python libraries can be reused. DataCurator enables efficient remote workflows, offering integration with Slack and the ability to transfer curated data to clusters using OwnCloud and SCP. Code available at: https://github.com/bencardoen/DataCurator.jl.

Aurozyme: A Revolutionary Nanozyme in Colitis, Switching Peroxidase-Like to Catalase-Like Activity.

A therapeutic strategy that could address colitis of multiple etiologies while restoring the dysbiosis of gut microbiota is attractive. Here, Aurozyme, a novel nanomedicine comprised of gold nanoparticles (AuNPs) and glycyrrhizin (GL) with a glycol chitosan coating layer, as a promising approach for colitis, is demonstrated. The unique feature of Aurozyme is the conversion of harmful peroxidase-like activity of AuNPs to beneficial catalase-like activity due to the amine-rich environment provided by the glycol chitosan. This conversion process enables Aurozyme to oxidize the hydroxyl radicals derived from AuNP, producing water and oxygen molecules. In fact, Aurozyme effectively scavenges reactive oxygen/reactive nitrogen species (ROS/RNS) and damage-associated molecular patterns (DAMPs), which can attenuate the M1 polarization of macrophage. It exhibits prolonged adhesion to the lesion site, promoting sustained anti-inflammatory effects and restoring intestinal function in colitis-challenged mice. Additionally, it increases the abundance and diversity of beneficial probiotics, which are essential for maintaining microbial homeostasis in the gut. The work highlights the transformative potential of nanozymes for the comprehensive treatment of inflammatory disease and represents an innovative switching technology of enzyme-like activity by Aurozyme.

Segmentation-guided domain adaptation and data harmonization of multi-device retinal optical coherence tomography using cycle-consistent generative adversarial networks.

BACKGROUND: Medical images such as Optical Coherence Tomography (OCT) images acquired from different devices may show significantly different intensity profiles. An automatic segmentation model trained on images from one device may perform poorly when applied to images acquired using another device, resulting in a lack of generalizability. This study addresses this issue using domain adaptation methods improved by Cycle-Consistent Generative Adversarial Networks (CycleGAN), especially when the ground-truth labels are only available in the source domain. METHODS: A two-stage pipeline is proposed to generate segmentation in the target domain. The first stage involves the training of a state-of-the-art segmentation model in the source domain. The second stage aims to adapt the images from the target domain to the source domain. The adapted target domain images are segmented using the model in the first stage. Ablation tests were performed with integration of different loss functions, and the statistical significance of these models is reported. Both the segmentation performance and the adapted image quality metrics were evaluated. RESULTS: Regarding the segmentation Dice score, the proposed model ssppg achieves a significant improvement of 46.24% compared to without adaptation and reaches 87.4% of the upper limit of the segmentation performance. Furthermore, image quality metrics, including FID and KID scores, indicate that adapted images with better segmentation also have better image qualities. CONCLUSION: The proposed method demonstrates the effectiveness of segmentation-driven domain adaptation in retinal imaging processing. It reduces the labor cost of manual labeling, incorporates prior anatomic information to regulate and guide domain adaptation, and provides insights into improving segmentation qualities in image domains without labels.

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.

Biomimetic Extracellular Scaffolds by Microfluidic Superstructuring of Nanofibers.

The extracellular matrix is a dynamic framework bearing chemical and morphological cues that support many cellular functions, and artificial analogs with well-defined chemistry are of great interest for biomedical applications. Herein, we describe hierarchical, extracellular-matrix-mimetic microgels, termed "superbundles" (SBs) composed of peptide amphiphile (PA) supramolecular nanofiber networks created using flow-focusing microfluidic devices. We explore the effects of altered flow rate ratio and PA concentration on the ability to create SBs and develop design rules for producing SBs with both cationic and anionic PA nanofibers and gelators. We demonstrate the morphological similarities of SBs to decellularized extracellular matrices and showcase their ability to encapsulate and retain proteinaceous cargos with a wide variety of isoelectric points. Finally, we demonstrate that the novel SB morphology does not affect the well-established biocompatibility of PA gels.

Effects of Myopia and Glaucoma on the Neural Canal and Lamina Cribrosa Using Optical Coherence Tomography.

PRCIS: Glaucoma was associated with axial bowing and rotation of Bruchs membrane opening (BMO) and anterior laminar insertion (ALI), skewed neural canal, and deeper anterior lamina cribrosa surface (ALCS). Longer axial length was associated with wider, longer, and more skewed neural canal and flatter ALCS. PURPOSE: Investigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomography. PATIENTS: 19 control (38 eyes) and 38 glaucomatous subjects (63 eyes). MATERIALS AND METHODS: Participants were imaged with swept-source optical coherence tomography, and the images were analyzed for the BMO and ALI dimensions, prelaminar neural canal dimensions, and ALCS depth. RESULTS: Glaucomatous eyes had more bowed and nasally rotated BMO and ALI, more horizontally skewed prelaminar neural canal, and deeper ALCS than the control eyes. Increased axial length was associated with a wider, longer, and more horizontally skewed neural canal and a decrease in the ALCS depth and curvature. CONCLUSION: Our findings suggest that glaucomatous posterior bowing or cupping of lamina cribrosa can be significantly confounded by the myopic expansion of the neural canal. This may be related to higher glaucoma risk associated with myopia from decreased compliance and increased susceptibility to IOP-related damage of LC being pulled taut.

Predicting time-to-conversion for dementia of Alzheimer's type using multi-modal deep survival analysis.

Dementia of Alzheimer's Type (DAT) is a complex disorder influenced by numerous factors, and it is difficult to predict individual progression trajectory from normal or mildly impaired cognition to DAT. An in-depth examination of multiple modalities of data may yield an accurate estimate of time-to-conversion to DAT for preclinical subjects at various stages of disease development. We used a deep-learning model designed for survival analyses to predict subjects' time-to-conversion to DAT using the baseline data of 401 subjects with 63 features from MRI, genetic, and CDC (Cognitive tests, Demographic, and CSF) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our study demonstrated that CDC data outperform genetic or MRI data in predicting DAT time-to-conversion for subjects with Mild Cognitive Impairment (MCI). On the other hand, genetic data provided the most predictive power for subjects with Normal Cognition (NC) at the time of the visit. Furthermore, combining MRI and genetic features improved the time-to-event prediction over using either modality alone. Finally, adding CDC to any combination of features only worked as well as using only the CDC features.

A long term study of the difference in efficacy and effect rate of various concentrations of retinol (1500-6600 IU) in middle aged women.

Retinol is widely used for topical application for antiaging. However, the efficacy and effect rate of different concentrations of retinol have been rarely analyzed. Therefore, in this study, the efficacy and rate of effect of retinol concentrations from 1500 to 6600 IU, on various skin parameters, have been compared. Seventy-two Korean women aged 40-59 years participated in this study. Retinol was used by them for 24 weeks; the effects were measured at 0, 2, 4, 8, 12, and 24 weeks. The measurement parameters for aging were crow's feet, forehead wrinkles, nasolabial fold, dermal density, and elasticity and that for skin color were skin brightness, yellowness, redness, and standard deviation of skin brightness. The texture of the skin was measured by measuring the skin roughness and pores, and the skin barrier function was evaluated through hydration, sebum, and desquamation. Low concentration retinol (1500-2500 IU) had a significantly higher effect in skin color, brightness, and elasticity and faster improvement rate in skin brightness and elasticity compared to that for high concentration (3300-6600 IU). High concentration of retinol had a significantly higher effect in wrinkles, dermal density and pores and faster improvement rate for wrinkles, skin texture, pores, and desquamation compared to that for low concentration. This study evaluated the changes caused by different concentration of retinol over a long period of time. The results of this study have great implications as the optimal concentration of retinol can be prescribed for an accurate period for the desired results without side effects.

SPECHT: Self-tuning Plausibility based object detection Enables quantification of Conflict in Heterogeneous multi-scale microscopy.

Identification of small objects in fluorescence microscopy is a non-trivial task burdened by parameter-sensitive algorithms, for which there is a clear need for an approach that adapts dynamically to changing imaging conditions. Here, we introduce an adaptive object detection method that, given a microscopy image and an image level label, uses kurtosis-based matching of the distribution of the image differential to express operator intent in terms of recall or precision. We show how a theoretical upper bound of the statistical distance in feature space enables application of belief theory to obtain statistical support for each detected object, capturing those aspects of the image that support the label, and to what extent. We validate our method on 2 datasets: distinguishing sub-diffraction limit caveolae and scaffold by stimulated emission depletion (STED) super-resolution microscopy; and detecting amyloid-ß deposits in confocal microscopy retinal cross-sections of neuropathologically confirmed Alzheimer's disease donor tissue. Our results are consistent with biological ground truth and with previous subcellular object classification results, and add insight into more nuanced class transition dynamics. We illustrate the novel application of belief theory to object detection in heterogeneous microscopy datasets and the quantification of conflict of evidence in a joint belief function. By applying our method successfully to diffraction-limited confocal imaging of tissue sections and super-resolution microscopy of subcellular structures, we demonstrate multi-scale applicability.

Early detection of norovirus outbreak using machine learning methods in South Korea.

BACKGROUND: The norovirus is a major cause of acute gastroenteritis at all ages but particularly has a high chance of affecting children under the age of five. Given that the outbreak of norovirus in Korea is seasonal, it is important to try and predict the start and end of norovirus outbreaks. METHODS: We predicted weekly norovirus warnings using six machine learning algorithms using test data from 2017 to 2018 and training data from 2009 to 2016. In addition, we proposed a novel method for the early detection of norovirus using a calculated norovirus risk index. Further, feature importance was calculated to evaluate the contribution of the estimated weekly norovirus warnings. RESULTS: The long short-term memory machine learning (LSTM) algorithm proved to be the best algorithm for predicting weekly norovirus warnings, with 97.2% and 92.5% accuracy in the training and test data, respectively. The LSTM algorithm predicted the observed start and end weeks of the early detection of norovirus within a 3-week range. CONCLUSIONS: The results of this study show that early detection can provide important insights for the preparation and control of norovirus outbreaks by the government. Our method provides indicators of high-risk weeks. In particular, last norovirus detection rate, minimum temperature, and day length, play critical roles in estimating weekly norovirus warnings.

Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.

Amyloid beta (Aß) deposits in the retina of the Alzheimer's disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aß with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aß in the AD retina. Significantly higher Aß load was found in AD compared to controls, and specifically in the mid-peripheral region. AD retina showed significantly less immunoreactivity against glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) compared to control eyes. Immunoreactivity against ionized calcium binding adapter molecule-1 (IBA-1), a microglial marker, demonstrated a higher level of microgliosis in AD compared to control retina. Within AD retina, more IBA-1 immunoreactivity was present in the mid-peripheral retina, which contained more Aß than the central AD retina. GFAP co-localized rarely with Aß, while IBA-1 co-localized with Aß in more layers of control than AD donor retina. These results suggest that dysfunction of the Müller and microglial cells may be key features of the AD retina.