Deep learning for multi-type infectious keratitis diagnosis: A nationwide, cross-sectional, multicenter study.

The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.

Co-delivery Nano System of MS-275 and V-9302 Induces Pyroptosis and Enhances Anti-Tumor Immunity Against Uveal Melanoma.

In the treatment of uveal melanoma (UVM), histone deacetylase inhibitors (HDACi) have emerged as a promising epigenetic therapy. However, their clinical efficacy is hindered by the suboptimal pharmacokinetics and the strong self-rescue of tumor cells. To overcome these limitations, reactive oxygen species (ROS)-responsive nanoparticles (NPs) are designed that encapsulate HDACi MS-275 and the glutamine metabolism inhibitor V-9302. Upon reaching the tumor microenvironment, these NPs can disintegrate, thereby releasing MS-275 to increase the level of ROS and V-9302 to reduce the production of glutathione (GSH) related to self-rescue. These synergistic effects lead to a lethal ROS storm and induce cell pyroptosis. When combined with programmed cell death protein 1 monoclonal antibodies (α-PD-1), these NPs facilitate immune cell infiltration, improving anti-tumor immunity, converting "immune-cold" tumors into "immune-hot" tumors, and enhancing immune memory in mice. The findings present a nano-delivery strategy for the co-delivery of epigenetic therapeutics and metabolic inhibitors, which induces pyroptosis in tumors cells and improves the effectiveness of chemotherapy and immunotherapy.

Undersampling and cumulative class re-decision methods to improve detection of agitation in people with dementia.

Agitation is one of the most prevalent symptoms in people with dementia (PwD) that can place themselves and the caregiver's safety at risk. Developing objective agitation detection approaches is important to support health and safety of PwD living in a residential setting. In a previous study, we collected multimodal wearable sensor data from 17 participants for 600 days and developed machine learning models for detecting agitation in 1-min windows. However, there are significant limitations in the dataset, such as imbalance problem and potential imprecise labels as the occurrence of agitation is much rarer in comparison to the normal behaviours. In this paper, we first implemented different undersampling methods to eliminate the imbalance problem, and came to the conclusion that only 20% of normal behaviour data were adequate to train a competitive agitation detection model. Then, we designed a weighted undersampling method to evaluate the manual labeling mechanism given the ambiguous time interval assumption. After that, the postprocessing method of cumulative class re-decision (CCR) was proposed based on the historical sequential information and continuity characteristic of agitation, improving the decision-making performance for the potential application of agitation detection system. The results showed that a combination of undersampling and CCR improved F1-score and other metrics to varying degrees with less training time and data. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00313-8.

Controlling the spin current around the rectangular cavities in two-dimensional topological insulators.

Controlling spin current in topological insulators (TIs) is a crucial requirement for applications in quantum computing and spintronics. Using the non-equilibrium Keldysh Green's function formalism, we demonstrate that such control can be established around rectangular cavities of two-dimensional TIs by breaking their time reversal symmetry via exchange magnetic fields and magnetic defects. In the presence of magnetic defects with xy symmetry or Ising symmetry, the density of states is localized, and the spin current forms a current loop around the rectangular cavity in TIs interfacing with two ferromagnetic stripes. We also observe that the spin direction of the traveling electrons is inverted under the reversal of bias and gate voltages. The change in the spin-polarized current around the cavities is predicted by varying the strength of Rashba spin-orbit coupling. This result allows for the creation and control of nearly fully spin-polarized currents with various spatial patterns around the cavities in TIs, and the design of tunable spin diodes for highly integrated spintronics.

Impact of tidal dynamics and typhoon-induced inundation on saltwater intrusion in coastal farms.

The increase in storm surge events caused by climate change exacerbates adverse effects on seawater inundation in coastal areas. An accurate description of the water level curve is crucial for understanding the process of saltwater intrusion (SWI) resulting from storm surge. Most studies involving empirical surges as inputs to groundwater models, often simplify spatial and temporal seawater inundation processes, which may increase the uncertainty in vertical seawater intrusion. To address this gap, we employed a comprehensive modeling approach using storm surge model ADCIRC and numerical simulator HydroGeoSphere to reveal SWI dynamics during a historical storm surge event in a coastal farm, considering varying tidal-surge phases and typhoon intensities. Our findings indicate pronounced SWI variations even with consistently highest water level during a storm surge, contingent on prior tidal processes. The timing of typhoon landfall on an hourly scale yielded diverse water level curves, altering the function of SWI. Intriguingly, SWI exacerbates following a high tide with 31.2 % average salinity higher, highlighting the profound modulation effect of tidal levels on SWI. Local topography significantly influenced SWI dynamics. Ponds, for instance, retained elevated salinity levels for over 15 h, indicating a more prolonged exposure to salinity than roads. These findings underscore the importance of considering both tidal influences and topographical factors in understanding and mitigating SWI in coastal agricultural management.

False Correlation Reduction for Offline Reinforcement Learning.

Offline reinforcement learning (RL) harnesses the power of massive datasets for resolving sequential decision problems. Most existing papers only discuss defending against out-of-distribution (OOD) actions while we investigate a broader issue, the false correlations between epistemic uncertainty and decision-making, an essential factor that causes suboptimality. In this paper, we propose falSe COrrelation REduction (SCORE) for offline RL, a practically effective and theoretically provable algorithm. We empirically show that SCORE achieves the SoTA performance with 3.1x acceleration on various tasks in a standard benchmark (D4RL). The proposed algorithm introduces an annealing behavior cloning regularizer to help produce a high-quality estimation of uncertainty which is critical for eliminating false correlations from suboptimality. Theoretically, we justify the rationality of the proposed method and prove its convergence to the optimal policy with a sublinear rate under mild assumptions.

cGAS-STING Pathway Activation and Systemic Anti-Tumor Immunity Induction via Photodynamic Nanoparticles with Potent Toxic Platinum DNA Intercalator Against Uveal Melanoma.

The cGAS-STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS-a cationic platinum (II) agent-to form NPPDT -56MESS. The accumulation of NPPDT -56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT -56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT -56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double-stranded DNA (dsDNA). This way, the cGAS-STING pathway is activated to induce anti-tumor immune responses and ultimately enhance anti-cancer activity. Additionally, the administration of NPPDT -56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT -56MESS functions as a chemotherapeutic agent and cGAS-STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.

Folium crataegi boosts skin regeneration for burn injury in rats through multiple ways.

Appropriate topical dressings for burn treatments are important to accelerate skin wound recovery and prevent external infections. This study aimed to evaluate the effect and investigate the mechanism of folium crataegi (Crataegus pinnatifida Bge.) for the treatment of burn wounds, as well as to compare the therapeutic effects of aqueous extracts (HLW) and alcoholic extracts (HLE) from folium crataegi. The results demonstrated that both HLW and HLE groups exhibited a higher wound contraction rate than the silver sulfadiazine (SSD) ointment group. Moreover, HLW showed more significant wound repair effects than HLE. HLW significantly increased levels of EGF and FGF-2 in wound tissue, as well as TGF-ß1, VEGF, CAT and IL-10 in serum. Folium crataegi extract, especially aqueous extracts, exerted good anti-inflammatory, anti-oxidant and anti-bacterial effects by upregulating the expression of lag3, txn1 and slpi, respectively. Folium crataegi extract significantly inhibits the expression of npas2, a key gene in the circadian rhythm pathway. In conclusion, this research illustrated that the folium crataegi extract, especially aqueous extracts, had better therapeutic effects on skin burns through multiple ways, possibly including a novel mechanism related to circadian rhythm pathway. These findings suggest that folium crataegi could be a valuable source of compounds for enhancing skin regeneration through multiple ways.

G3SR: Global Graph Guided Session-Based Recommendation.

Session-based recommendation tries to make use of anonymous session data to deliver high-quality recommendations under the condition that user profiles and the complete historical behavioral data of a target user are unavailable. Previous works consider each session individually and try to capture user interests within a session. Despite their encouraging results, these models can only perceive intra-session items and cannot draw upon the massive historical relational information. To solve this problem, we propose a novel method named global graph guided session-based recommendation (G3SR). G3SR decomposes the session-based recommendation workflow into two steps. First, a global graph is built upon all session data, from which the global item representations are learned in an unsupervised manner. Then, these representations are refined on session graphs under the graph networks, and a readout function is used to generate session representations for each session. Extensive experiments on two real-world benchmark datasets show remarkable and consistent improvements of the G3SR method over the state-of-the-art methods, especially for cold items.

Erratum: Human Umbilical Cord MSCs as New Cell Sources for Promoting Periodontal Regeneration in Inflammatory Periodontal Defect: Errautm.

[This corrects the article DOI: 10.7150/thno.19888.].

Identification of Hub Genes Associated with Nonspecific Orbital Inflammation by Weighted Gene Coexpression Network Analysis.

Background: Nonspecific orbital inflammation is a common ophthalmopathy with a high prevalence among adult females. Yet, its molecular mechanisms behind are poorly understood. Regulation of gene expression probably plays an important role in this disease. Thus, we utilized gene coexpression networks to identify key modules and hub genes involved in nonspecific orbital inflammation. Methods: Data of gene expression in nonspecific orbital inflammation samples (n = 61) and healthy samples (n = 28) were obtained from the public Gene Expression Omnibus database. Afterward, differentially expressed genes were performed. Then, weighted correlation network analysis was done to define the key modules. Next, functional enrichment analysis was conducted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway in key modules. Finally, a protein-protein interaction network and Cytohubba plugin were used to screen hub genes. Results: Differential expression of 716 genes was identified, among which 169 genes were upregulated and 547 genes were downregulated in the nonspecific orbital inflammation group. In weighted correlation network analysis, we clarified 2 key modules (MEturquoise and MEblue) that are likely to play key roles in nonspecific orbital inflammation. Functional enrichment analysis indicated that these genes are predominately involved in immune response and matrix homeostasis. In addition, among 2 key modules, there are 20 hub genes identified. Conclusion: With this new approach, we identified several genes that could be critical to pathologies of nonspecific orbital inflammation. These findings may contribute to further therapeutic target development.

An osmium-peroxo complex for photoactive therapy of hypoxic tumors.

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O2•- upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

Comparison of oblique and transforaminal approaches to lumbar interbody fusion for lumbar degenerative disease: An updated meta-analysis.

Objective: Oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) are widely used in the treatment of lumbar degenerative diseases. A meta-analysis was performed to examine the clinical and radiological effects of these two techniques. Methods: A search of relevant literature from several databases was conducted until November 2021. Perioperative outcomes, clinical and radiological results, and complications were analyzed. Results: Fifteen qualified studies were included. OLIF showed a shorter operative time and length of hospital stay and less blood loss than TLIF. Early postoperative Visual Analogue Scale for back pain were significantly lower in OLIF than in TLIF (P = 0.004). Noteworthy, although the preoperative Oswestry Disability Index (ODI) of the OLIF group was higher than that of the TLIF group (P = 0.04), the postoperative ODI was significantly lower (P < 0.05). Radiologically, the results showed that the disc and foraminal heights of OLIF were significantly higher than those of TLIF postoperatively. Moreover, OLIF can restore more segmental lordosis than TLIF in the early postoperative period. Furthermore, OLIF showed better fusion rates than TLIF (P = 0.02), with no difference in cage subsidence (13.4% vs. 16.6%). No significant differences in overall and approach-related complications between the two groups. Conclusion: The OLIF group showed an advantage in terms of operative time, hospitalization, intraoperative blood loss, early back pain relief, postoperative function recovery, disc and foraminal heights, early segmental lordosis, and fusion rate compared to TLIF. For both procedures, the incidence rates of overall and approach-related complications were comparable.

Keratomycosis Caused by a Rare Pathogen, Myrothecium verrucaria.

PURPOSE: To report a case of keratomycosis caused by a very rare pathogen, Myrothecium verrucaria. METHODS: This is a case report. A 53-year-old man complaint of left eye redness, irritation, intermittent pain after ashes entered his left eye. The patient was examined by slit lamp, anterior segment OCT and in vivo confocal microscopy. The HRT III-RCM image showed massive interlocking white thin lines in the cornea stroma. Corneal scrapings were collected for pathogen culture and PCR test. M. verrucaria was isolated and identified. RESULTS: Hourly topical natamycin (5%) and voriconazole (10 mg/ml) was given as well as intravenous fluconazole (200 mg per day). Treatment was continued with oral itraconazole, 200 mg/day, topical natamycin (5%), 4 times/day, and pranoprofen, 4 times/day. The therapy was tapered off over one and half a month. The cornea lesion healed with scar formation two months later. CONCLUSIONS: This is the first case report of M. verrucaria keratomycosis in China. We are the first to show the characteristic of M. verrucaria on cornea with In vivo confocal microscopy. A combination treatment of tropical natamycin, voriconazole and systemic fluconazole was effective in the treatment of M. verrucaria.

Apoptotic vesicles restore liver macrophage homeostasis to counteract type 2 diabetes.

Apoptosis is a naturally occurring process generating plenty of apoptotic vesicles (apoVs), but the feature, fate and function of apoVs remain largely unknown. Notably, as an appealing source for cell therapy, mesenchymal stem cells (MSCs) undergo necessary apoptosis and release apoVs during therapeutic application. In this study, we characterized and used MSC-derived apoVs to treat type 2 diabetes (T2D) mice, and we found that apoVs were efferocytosed by macrophages and functionally modulated liver macrophage homeostasis to counteract T2D. We showed that apoVs can induce macrophage reprogramming at the transcription level in an efferocytosis-dependent manner, leading to inhibition of macrophage accumulation and transformation of macrophages towards an anti-inflammation phenotype in T2D liver. At the molecular level, we discovered that calreticulin (CRT) was exposed on the surface of apoVs to act as a critical 'eat-me' signal mediating apoV efferocytosis and macrophage regulatory effects. Importantly, we demonstrated that CRT-mediated efferocytosis of MSC-derived apoVs contributes to T2D therapy with alleviation of T2D phenotypes including glucose intolerance and insulin resistance. These findings uncover that functional efferocytosis of apoVs restores liver macrophage homeostasis and ameliorates T2D.

Combination Model of Thyrotrophin Receptor Antibody and Volumetric Orbital Apex Crowding Index as an Indicator of Dysthyroid Optic Neuropathy.

BACKGROUND: Dysthyroid optic neuropathy (DON) is one of the most serious vision-threatening complications of thyroid eye disease (TED); however, accurate and established diagnostic tools for DON are yet lacking. The present study was aimed at identifying new diagnostic factors for the accurate diagnosis of DON. METHODS: This retrospective cross-sectional study included 25 TED patients (50 eyes) with enlarged extraocular muscles, no previous anti-inflammatory therapy, and the absence of other vision-affecting diseases between May 2017 and August 2019. Baseline data, such as gender, age, ophthalmological history, thyroid disease and management, TED history including clinical features, management, and long-term results, ophthalmological examinations, serology examinations, and single-photon emission computed tomography/computed tomography (SPECT/CT) results, were extracted. The diagnostic criteria were as follows: (1) best-corrected visual acuity (BCVA) loss coexisting with either of the following-increased latency or reduction of amplitude on visual evoked potential (VEP), impaired color vision, visual field defects, contrast sensitivity impairment, and optic disk swelling-and (2) Barrett's index ≥ 60% in CT. Univariate and multivariate logistic regression analyses assessed the differences in age, gender, eyes, medical history, clinical activity, thyroid hormone and antibodies, uptake ratio (UR) of extraocular muscles in SPECT/CT, and volumetric orbital apex crowding index (VACI) using the generalized estimation equation. Consequently, the receiver operating characteristic curve (ROC) of the significant factors was constructed. RESULTS: Univariate analysis revealed significant differences in the clinical activity, free triiodothyronine (FT3), free thyroxine (FT4), thyrotrophin receptor antibody (TRAb) levels, the UR of superior and medial rectus, and VACI between DON and TED (without DON) groups. Multivariate regression analysis revealed that TRAb and VACI were significantly different. ROC analysis showed that the univariate models of TRAb or VACI and the multivariate model were effective indicators of DON, while the multivariate model had the highest area under the ROC curve. CONCLUSION: A combination of TRAb and VACI is an effective indicator for DON.

The effect of Wnt/ß-catenin pathway on the scleral remolding in the mouse during form deprivation.

BACKGROUND: Many reports have shown that Wnt/ß-Catenin pathway is associated with a variety of diseases, but its role in the pathogenesis of myopia is still unknown. In order to clarify the role of Wnt/ß-catenin pathway in the development of form deprivation myopia (FDM), this study investigated the expression of scleral Wls, ß-catenin and TCF4 in mice model of form deprivation (FD) myopia. METHODS: Three parallel experimental groups, including FD, monocular exposure (SC) and binocular exposure (NC) group, were designed to investigate the effects of Wnt/ß-Catenin pathway on scleral remodeling mouse during form deprivation in three-week-old C57BL/6 mice. Diopters and axial lengths (AL) in each sample were measured with an infrared eccentric refractometer or spectral-domain optical coherence tomography. The expression of scleral Wls, ß-catenin and TCF4 were detected with Western blot. Morphological changes of posterior sclera were observed with a transmission electron microscope (TEM). The above characterization and analysis were performed on the 0th, 7th, 14th, 21st and 28th days, respectively. RESULTS: The difference of diopter and AL between the three groups (SC, NC and FD group) gradually increased with the prolongation of FD time (except AL between SC and NC groups). The changes of diopter and AL gradually increased with the prolongation of FD time. Especially, the diopter and AL will increase sharply after FD lasts for a long time, such as the measurement on the 21st for diopter and 28th days for AL. Most notably, the AL of FD eyes significantly increased after 28 days of deprivation. Thinning and disordered arrangement of collagen fibers and a decrease of extracellular matrix were observed with TEM. The expression of scleral Wls, ß-catenin and TCF4 increased with age in the NC and SC group. In FD group, they increased significantly on the 7th, 14th and 21st days but decreased on the 28th day. CONCLUSIONS: The expression of Wls, ß-Catenin and TCF4 to FD were more sensitive indicators than that of diopter and AL. Within the first 7 days of FD, the expression of Wls, ß-Catenin and TCF4 in sclera increased sharply. With the extension of FD duration, it gradually decreased. It is suggested that the Wnt/ß-catenin pathway might be involved in the scleral remodeling induced in FDM mice.