Cost-Effectiveness Analysis of Adalimumab Versus Cyclosporine for Vogt-Koyanagi-Harada Disease: A Randomized Controlled Study.

PURPOSE: To compare the 26-week cost-effectiveness of adalimumab-corticosteroids (ADA-CS) and cyclosporine-corticosteroids (CSA-CS) for Vogt-Koyanagi-Harada (VKH). METHODS: A preplanned cost-effectiveness analysis based on the per-protocol population of a randomized-controlled trial. VKH subjects were randomized to receive either cyclosporine (100-200 mg daily) combined with corticosteroids or adalimumab (40 mg twice monthly) combined with corticosteroids. The primary outcome of this cost-effectiveness study was the incremental cost-effectiveness ratio (ICER). Costs and quality-adjusted life-years (QALYs) data were calculated by the medical records and health utility, respectively. Subgroup (early and late-phase VKH) analysis and sensitivity analyses were performed. RESULTS: The ICER at 26 weeks was $62,425/QALY for the total participants. Compared to the CSA-CS group, costs in the ADA-CS group were more expensive (mean difference [ΔA-C]: $2,497) with more gains in QALYs (mean difference [ΔA-C]: 0.04). The probability of ADA-CS being cost-effective was 0.17 and 0.41 at willingness to pay (WTP) thresholds of $12,000/QALY and $36,000/QALY, respectively. Subgroup analysis and sensitivity analyses showed consistent findings with the primary analysis. CONCLUSIONS: Regardless of early or late-phase VKH, the CSA-CS strategy may be recommended as the preferred initial choice for the majority of VKH.

Improved REBA: deep learning based rapid entire body risk assessment for prevention of musculoskeletal disorders.

Preventing work-related musculoskeletal disorders (WMSDs) is crucial in reducing their impact on individuals and society. However, the existing mainstream 2D image-based approach is insufficient in capturing the complex 3D movements and postures involved in many occupational tasks. To address this, an improved deep learning-based rapid entire body assessment (REBA) method has been proposed. The method takes working videos as input and automatically outputs the corresponding REBA score through 3D pose reconstruction. The proposed method achieves an average precision of 94.7% on real-world data, which is comparable to that of ergonomic experts. Furthermore, the method has the potential to be applied across a wide range of industries as it has demonstrated good generalisation in multiple scenarios. The proposed method offers a promising solution for automated and accurate risk assessment of WMSDs, with implications for various industries to ensure the safety and well-being of workers.

This paper proposes a deep learning-based improved rapid entire body assessment (REBA) method for assessing work-related musculoskeletal disorders (WMSDs) risks using 3D pose reconstruction from videos, achieving 94.7% precision, comparable to ergonomic experts, with potential applications across various industries.

First screening for tick-borne pathogens in Chinese Milu deer (Elaphurus davidianus).

Ticks are primary vectors for many tick-borne pathogens (TBPs) and pose a serious threat to veterinary and public health. Information on the presence of TBPs in Chinese Milu deer (Elaphurus davidianus) is limited. In this study, a total of 102 Chinese Milu deer blood samples were examined for Anaplasma spp., Theileria spp., Babesia spp., Rickettsia spp., and Borrelia spp., and three TBPs were identified: Anaplasma phagocytophilum (48; 47.1 %), Candidatus Anaplasma boleense (47; 46.1%), and Theileria capreoli (8; 7.8 %). Genetic and phylogenetic analysis of the 16S rRNA and 18S rRNA confirmed their identity with corresponding TBPs. To our knowledge, this is the first report on Candidatus A. boleense and T. capreoli detection in Chinese Milu deer. A high prevalence of A. phagocytophilum with veterinary and medical significance was identified in endangered Chinese Milu deer, which could act as potential zoonotic reservoirs. The identification of the TBPs in Chinese Milu deer provides useful information for the prevention and control of tick-borne diseases.

Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions.

OBJECTIVE: Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to which extent next-generation sequencing techniques can aid in diagnosis. METHODS: We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications on patient care. RESULTS: Between May 1, 2008, and June 1, 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI, 14.9%-29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified to be associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome. CONCLUSION: Among some patients with pediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessing their diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one fifth of these cases and provided clinically relevant information for patient-care decisions.

Sorptive removal of cadmium using the attapulgite modified by the combination of calcination and iron.

Sorptive removal of cadmium (Cd) from the aqueous solutions using the easily available natural materials is an attractive method. However, the adsorption efficiencies of these materials, such as clays, are typically low. Besides, they are generally in relatively low stability and renewability, which restrict their application. Thus, modification of these materials to enhance their performance on Cd removal has gained growing attentions. Herein, the integration of calcination and ferric chloride (FeCl3) was used to modify a typical clay, i.e., attapulgite, to increase the adsorption sites, and thus to develop a robust adsorbent for Cd. Under the optimum conditions for attapulgite modification (i.e., the mass ratio of FeCl3 to attapulgite was 1:2, calcination temperature was 350 °C, and calcination time was 1.5 h) and Cd adsorption (i.e., initial pH of 6.0, adsorption temperature of 25 °C, and adsorbent dosage of 1.0 g/L), the maximum adsorption capacity of the modified attapulgite toward Cd was 149.9 mg/g. Mechanisms of surface complexation and electrostatic attraction were involved in the efficient removal of Cd. The adsorption of Cd increased with pH due to the increased electrostatic attraction. Metal cations inhibited the Cd adsorption through competing with the adsorption sites. The changes of Gibbs-free energy during the adsorption of Cd were lower than zero and decreased with temperature, suggesting the process was spontaneous and endothermic. The removal efficiency of Cd after 5 times of recycle maintained at 82% of that of the raw modified attapulgite demonstrated the stability of the adsorbent. These results suggested that the modified attapulgite is robust for Cd removal and is promising for land application.

Pedestrian re-identification based on attention mechanism and Multi-scale feature fusion.

Existing pedestrian re-identification models generally have low pedestrian retrieval accuracy when encountering factors such as changes in pedestrian posture and occlusion because the network cannot fully express pedestrian feature information. Therefore, this paper proposes a method to address this problem by combining the attention mechanism with multi-scale feature fusion, and combining the proposed cross-attention module with the ResNet50 backbone network. In this way, the ability of the network to extract strong salient features is significantly improved; at the same time, using the multi-scale feature fusion module to extract multi-scale features from different depths of the network, achieving the complementary advantages between features through feature addition, feature concatenation and feature weight selection. In addition, a feature enhancement method and an efficient pedestrian retrieval strategy are proposed to jointly promote the accuracy of pedestrian retrieval from both the training and testing levels. When tested on the occluded pedestrian recognition datasets Partial-REID and Partial-iLIDS, the accuracy of this method reached 70.1% and 65.6% on the Rank-1 indicator respectively, and 82.2% and 80.5% on the Rank-3 indicator respectively. At the same time, it also achieved high recognition accuracy when tested on the Market1501 dataset and DukeMTMC-reid dataset, reaching 95.9% and 89.9% on the Rank-1 indicator respectively, 89.1% and 80.3% on the mAP indicator respectively, and 67% and 46.2% on the mINP indicator respectively. It can be seen that this method has achieved good results in solving the above problems.

Identification of FCER1G as a cyclosporin A plus corticosteroid sensitization gene in female patients with Vogt-Koyanagi-Harada disease.

The resistance development of the combination regimen of corticosteroids (CS) with cyclosporin A (CsA) leads to therapeutic failure of some patients with autoimmune diseases. In the male patients with Vogt-Koyanagi-Harada (VKH) disease, we have identified RPS4Y1 as an important resistance gene of the regimen and a functional mediator of chlorambucil (CLB). However, it remains unclear what is responsible for the resistance in female patients. In the present study, we performed RNA sequencing, tandem mass tag (TMT) proteomics, gain- and loss-of-function assays and rescue assays to screen and validate potential resistant mediators. The results showed that only Fc epsilon receptor Ig (FCER1G) exhibited significantly differential expression in CD4+ T cells among female CsA & CS resistant, sensitive and CLB & CsA & CS treated patients at transcription and protein levels. Inhibition of FCER1G was demonstrated to modulate CD4+ T cell resistance to CsA & CS in female patients. Importantly, the inhibition was mediated by elevated DNA methylation in the promoter region of the FCER1G gene. Moreover, we found that the salvage effect of CLB on CsA & CS resistance was mediated by an increased FCER1G expression via DNA demethylation in female patients. Taken together, the downregulation of FCER1G due to DNA hypermethylation is responsible for the resistance to CsA & CS and CLB reverses this resistance by inducing FCER1G expression via DNA demethylation in female patients. Modulation of FCER1G would be a promising sensitization strategy in female patients with resistance to CsA & CS.

Risk factors, clinical features and treatment of Behçet's disease uveitis.

Behçet's disease is a systemic vasculitis frequently associated with intraocular inflammation. Recent findings identified independent clinical clusters in Behçet's disease, each involving distinct combinations of affected organs. Ocular Behçet's disease, mainly manifested as uveitis, is characterized as an independent cluster with a low likelihood of association with other system involvements, such as intestinal, cardiovascular, or central nervous system. A prevailing theory suggests that the pathogenesis of the disease is multifactorial, where a variety of genetic and infectious agents may interact with each other to cause the disease. Among sporadic cases, the human leukocyte antigen (HLA) genes, including HLA-B51, HLA-A26, HLA-B15, and HLA-B5701, have been found to be a key component conferring genetic susceptibility. Outside the HLA region, a set of susceptibility variants are identified, closely related to interleukin (IL)-23/IL-17 pathway, tumor necrosis factor (TNF) signaling, and pattern recognition receptor systems. Microbial infections, such as Streptococcus sanguinis, Mycobacterium tuberculosis, and Herpes simplex virus (HSV), are linked to play the triggering of disease in immunogenetically predisposed individuals. Clinically, due to the notable relapsing-remitting course of ocular Behçet's disease, the prevention of recurrent attack would be the primary treatment goal. Combination of corticosteroids and immunomodulatory drugs, such as anti-TNF agents, interferon, and conventional immunosuppressants (e.g. cyclosporine, azathioprine), have been the mainstream regimen for the disease. Future research may focus on comparing the effectiveness of immunomodulatory drugs and identifying the most suitable subgroups for a specific drug on the basis of the knowledge of the molecular heterogeneity of the disease.

3D micropattern force triggers YAP nuclear entry by transport across nuclear pores and modulates stem cells paracrine.

Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction. However, it is still unclear how cells sense and transduce the mechanical signals from 3D geometry to regulate cell function. Here, the mechanotransduction of human mesenchymal stem cells (MSCs) triggered by 3D micropatterns and its effect on the paracrine of MSCs are systematically investigated. Our findings show that 3D micropattern force could influence the spatial reorganization of the cytoskeleton, leading to different local forces which mediate nucleus alteration such as orientation, morphology, expression of Lamin A/C and chromatin condensation. Specifically, in the triangular prism and cuboid micropatterns, the ordered F-actin fibers are distributed over and fully transmit compressive forces to the nucleus, which results in nuclear flattening and stretching of nuclear pores, thus enhancing the nuclear import of YES-associated protein (YAP). Furthermore, the activation of YAP significantly enhances the paracrine of MSCs and upregulates the secretion of angiogenic growth factors. In contrast, the fewer compressive forces on the nucleus in cylinder and cube micropatterns cause less YAP entering the nucleus. The skin repair experiment provides the first in vivo evidence that enhanced MSCs paracrine by 3D geometry significantly promotes tissue regeneration. The current study contributes to understanding the in-depth mechanisms of mechanical signals affecting cell function and provides inspiration for innovative design of biomaterials.

A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.

Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is -7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is -0.8 letters (95% CI, -6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.

Association of ZC3HAV1 single nucleotide polymorphisms with the susceptibility of Vogt-Koyanagi-Harada Disease.

BACKGROUND: Polymorphisms of genes related to the immune response have been reported to confer susceptibility to Vogt-Koyanagi-Harada (VKH) disease. This study was carried out to determine whether zinc finger CCCH-type containing antiviral 1 (ZC3HAV1) and tripartite motif-containing protein 25 (TRIM25) genetic polymorphisms are associated with this disease. METHODS: A total of 766 VKH patients and 909 healthy individuals were enrolled in this two-stage case-control study. Thirty-one tag single nucleotide polymorphisms (SNPs) of ZC3HAV1 and TRIM25 were genotyped by MassARRAY System and iPLEX Gold Genotyping Assay. Allele and genotype frequencies were analyzed by the χ2 test or Fisher's exact test. Cochran-Mantel-Haenszel test was used to assess the pooled odds ratio (OR) in the combined study. A stratified analysis was performed in terms of the major clinical features of VKH disease. RESULTS: We found a statistically significant increased frequency of the minor A allele of ZC3HAV1 rs7779972 (P = 1.50 × 10- 4, pooled OR = 1.332, 95%CI = 1.149-1.545) in VKH disease as compared with controls by using the Cochran-Mantel-Haenszel test. The GG genotype of rs7779972 showed a protective association with VKH disease (P = 1.88 × 10- 3, OR = 0.733, 95%CI = 0.602-0.892). There was no difference regarding the frequency of the remaining SNPs between VKH cases and controls (all P > 2.08 × 10- 3). The stratified analysis showed no significant association of rs7779972 with the major clinical characteristics of VKH disease. CONCLUSION: Our study indicated that the ZC3HAV1 variant rs7779972 might confer susceptibility to VKH disease in Han Chinese.

Prognostic significance of increased preoperative red cell distribution width (RDW) and changes in RDW for colorectal cancer.

BACKGROUND: Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. METHODS: In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut-off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan-Meier method, and significant differences were evaluated by the log-rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early-stage disease (stage 0-II) for sensitivity analysis. RESULTS: Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19-9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11-2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19-2.28; p < 0.01) in all-stage patients, and was only linked to higher RDW in early-stage patients. In competing risk model, H-RDW and H-ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. CONCLUSIONS: High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC.

COVID-19 contact tracking based on person reidentification and geospatial data.

Efficient contact tracing is a crucial step in preventing the spread of COVID-19. However, the current methods rely heavily on manual investigation and truthful reporting by high-risk individuals. Mobile applications and Bluetooth-based contact tracing methods have also been adopted, but privacy concerns and reliance on personal data have limited their effectiveness. To address these challenges, in this paper, a geospatial big data method that combines person reidentification and geospatial information for contact tracing is proposed. The proposed real-time person reidentification model can identify individuals across multiple surveillance cameras, and the surveillance data is fused with geographic information and mapped onto a 3D geospatial model to track movement trajectories. After real-world verification, the proposed method achieves a first accuracy rate of 91.56%, a first-five accuracy rate of 97.70%, and a mean average precision of 78.03% with an inference speed of 13 ms per image. Importantly, the proposed method does not rely on personal information, mobile phones, or wearable devices, avoiding the limitations of existing contact tracing schemes and providing significant implications for public health in the post-COVID-19 era.

Case report: Gene mutation analysis and skin imaging of isolated café-au-lait macules.

Background: Café-au-lait macules (CALMs) are common birthmarks associated with several genetic syndromes, such as neurofibromatosis type 1 (NF1). Isolated CALMs are defined as multiple café-au-lait macules in patients without any other sign of NF1. Typical CALMs can have predictive significance for NF1, and non-invasive techniques can provide more accurate results for judging whether café-au-lait spots are typical. Objectives: The study aimed to investigate gene mutations in six Chinese Han pedigrees of isolated CALMs and summarize the characteristics of CALMs under dermoscopy and reflectance confocal microscopy (RCM). Methods: In this study, we used Sanger sequencing to test for genetic mutations in six families and whole exome sequencing (WES) in two families. We used dermoscopy and RCM to describe the imaging characteristics of CALMs. Results: In this study, we tested six families for genetic mutations, and two mutations were identified as novel mutations. The first family identified [NC_000017.11(NM_001042492.2):c.7355G>A]. The second family identified [NC_000017.11(NM_001042492.2):c.2739_2740del]. According to genotype-phenotype correlation analyses, proband with frameshift mutation tended to have a larger number of CALMs and a higher rate of having atypical CALMs. Dermoscopy showed uniform and consistent tan-pigmented network patches with poorly defined margins with a lighter color around the hair follicles. Under RCM, the appearance of NF1 comprised the increased pigment granules in the basal layer and significantly increased refraction. Conclusion: A new heterozygous mutation and a new frameshift mutation of NF1 were reported. This article can assist in summarizing the properties of dermoscopy and RCM with CALMs.

Vogt-Koyanagi-Harada disease in pediatric, adult and elderly: clinical characteristics and visual outcomes.

PURPOSE: To depict a whole spectrum of clinical feartures and visual prognosis among pediatric, adult, and elderly Vogt-Koyanagi-Harada disease (VKH) patients. METHODS: Retrospective chart review was conducted in 2571 VKH patients diagnosed from April 2008 to January 2022. Based on age of disease onset, patients were divided into pediatric (age ≤ 16 years), adult (16 < age < 65 years), and elderly (age ≥ 65 years) VKH group. Ocular and extraocular manifestations were compared among these patients. Visual outcomes and complications were evaluated using logistic regression models and restricted cubic splines analysis. RESULTS: The median follow-up time was 48 (IQR, 12-60) months. Pediatric, adult and elderly VKH were found in 106 (4.1%), 2355 (91.6%), and 110 (4.3%) patients, respectively. All of the patients showed similar ocular manifestations in the context of disease phasing. The proportion of neurological and auditory manifestations in pediatric (42.3% and 7.5%) VKH patients was significantly lower than that in adults (66.5% and 47.9%) and elderly (68.2% and 50%) (both p < 0.0001). An increased risk of macular abnormalities was seen in adults (OR, 3.43; 95% CI, 1.62-7.29) compared with elderly VKH. An inverted-U-shaped pattern was observed between disease onset age and a poor visual outcome (visual acuity 6/18 or worse) according to OR value in VKH patients. The highest risk of BCVA ≤ 6/18 was observed in 32 years at disease onset (OR, 1.51; 95% CI, 1.18-1.94). A higher risk of visual loss was observed in adult VKH patients (OR, 9.06; 95% CI, 2.18-37.6) compared with elderly VKH patients. And stratified by macular abnormalities, the interaction test was not significant (P = 0.634). CONCLUSION: Our study identified, for the first time, a whole spectrum of clinical features of VKH based on a large cohort of Chinese patients. Adult VKH patients have an increased risk of poor visual outcomes, possibly due to increased frequency of macular abnormalities.

Early vs Deferred Non-Messenger RNA COVID-19 Vaccination Among Chinese Patients With a History of Inactive Uveitis: A Randomized Clinical Trial.

Importance: Improper host response to COVID-19 vaccines could trigger immune-mediated adverse events. The question remains whether COVID-19 vaccination should be postponed until complete remission in patients with uveitis, a preexisting immune-related condition. Objective: To compare recommendations for early and deferred COVID-19 vaccination with respect to uveitis outcomes. Design, Setting, and Participants: This open-label, randomized clinical trial at a large, specialized teaching center for uveitis care in China enrolled unvaccinated patients with inactive uveitis between August 10, 2021, and February 22, 2022, with follow-up to June 6, 2022. Interventions: Participants were randomly assigned to receive recommendation for early or deferred COVID-19 vaccination after complete remission of uveitis. Non-messenger RNA (non-mRNA) COVID-19 vaccines were available in China during the trial. Main Outcomes and Measures: The primary outcome was the time to symptomatic uveitis worsening during 3 months of follow-up. Secondary outcomes included uveitis activity and best-corrected visual acuity at 3 months. Results: Of the 543 participants (304 women [56.0%]; median age, 35 [IQR, 26-49] years), 262 were recommended for early vaccination and 281 for deferred vaccination. By month 3, 109 patients (41.6%) in the early group had been vaccinated compared with 14 (5.0%) in the deferred recommendation group. In the intention-to-treat population, the time to symptomatic uveitis worsening was shorter in the early group than in the deferred group (hazard ratio, 1.68 [95% CI, 1.09-2.59]; P = .01 by log-rank test). Changes in anterior chamber cells, vitreous haze, and best-corrected visual acuity from baseline to month 3 appeared similar in the 2 groups in the evaluable population after the month 3 in-person visit. Conclusions and Relevance: In this randomized clinical trial of patients with inactive uveitis, recommendation for early non-mRNA COVID-19 vaccination resulted in a higher incidence of self-reported symptomatic uveitis worsening with possible reporting bias compared with recommendation for deferred vaccination, but no adverse effects were observed in disease and visual prognosis at 3 months. These findings would be useful to guide the individual timing choices of non-mRNA COVID-19 vaccination in this clinically vulnerable population. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100049467.

Advances in Sorptive Removal of Hexavalent Chromium (Cr(VI)) in Aqueous Solutions Using Polymeric Materials.

Sorptive removal of hexavalent chromium (Cr(VI)) bears the advantages of simple operation and easy construction. Customized polymeric materials are the attracting adsorbents due to their selectivity, chemical and mechanical stabilities. The mostly investigated polymeric materials for removing Cr(VI) were reviewed in this work. Assembling of robust functional groups, reduction of self-aggregation, and enhancement of stability and mechanical strength, were the general strategies to improve the performance of polymeric adsorbents. The maximum adsorption capacities of these polymers toward Cr(VI) fitted by Langmuir isotherm model ranged from 3.2 to 1185 mg/g. Mechanisms of complexation, chelation, reduction, electrostatic attraction, anion exchange, and hydrogen bonding were involved in the Cr(VI) removal. Influence factors on Cr(VI) removal were itemized. Polymeric adsorbents performed much better in the strong acidic pH range (e.g., pH 2.0) and at higher initial Cr(VI) concentrations. The adsorption of Cr(VI) was an endothermic reaction, and higher reaction temperature favored more robust adsorption. Anions inhibited the removal of Cr(VI) through competitive adsorption, while that was barely affected by cations. Factors that affected the regeneration of these adsorbents were summarized. To realize the goal of industrial application and environmental protection, removal of the Cr(VI) accompanied by its detoxication through reduction is highly encouraged. Moreover, development of adsorbents with strong regeneration ability and low cost, which are robust for removing Cr(VI) at trace levels and a wider pH range, should also be an eternally immutable subject in the future. Work done will be helpful for developing more robust polymeric adsorbents and for promoting the treatment of Cr(VI)-containing wastewater.

Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.

Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis. However, prolonged hypernutrition led to the production of proinflammatory cytokines TNF and IL-1ß in the liver to induce TREM2 shedding through ADAM17-dependent proteolytic cleavage. Loss of TREM2 resulted in aberrant accumulation of dying hepatocytes, thereby further augmenting proinflammatory cytokine production. This ultimately precipitated a vicious cycle that licensed chronic inflammation to drive simple steatosis transition to NASH. Therefore, impaired macrophage efferocytosis is a previously unrecognized key pathogenic event that enables chronic liver inflammation in obesity. Blocking TREM2 cleavage to restore efferocytosis may represent an effective strategy to treat NASH.

Data augmentation based on multiple oversampling fusion for medical image segmentation.

A high-performance medical image segmentation model based on deep learning depends on the availability of large amounts of annotated training data. However, it is not trivial to obtain sufficient annotated medical images. Generally, the small size of most tissue lesions, e.g., pulmonary nodules and liver tumours, could worsen the class imbalance problem in medical image segmentation. In this study, we propose a multidimensional data augmentation method combining affine transform and random oversampling. The training data is first expanded by affine transformation combined with random oversampling to improve the prior data distribution of small objects and the diversity of samples. Secondly, class weight balancing is used to avoid having biased networks since the number of background pixels is much higher than the lesion pixels. The class imbalance problem is solved by utilizing weighted cross-entropy loss function during the training of the CNN model. The LUNA16 and LiTS17 datasets were introduced to evaluate the performance of our works, where four deep neural network models, Mask-RCNN, U-Net, SegNet and DeepLabv3+, were adopted for small tissue lesion segmentation in CT images. In addition, the small tissue segmentation performance of the four different deep learning architectures on both datasets could be greatly improved by incorporating the data augmentation strategy. The best pixelwise segmentation performance for both pulmonary nodules and liver tumours was obtained by the Mask-RCNN model, with DSC values of 0.829 and 0.879, respectively, which were similar to those of state-of-the-art methods.

Risk for uveitis relapse after COVID-19 vaccination.

OBJECTIVES: Several studies suggested that coronavirus disease 2019 (COVID-19) vaccination may lead to uveitis, a vision-threatening condition often associated with a variety of autoimmune or autoinflammatory diseases. This study aims to explore factors that influence the risk of uveitis relapse after COVID-19 vaccination to guide the prevention of disease. METHODS: Uveitis relapse was evidenced by worsening activity of intraocular inflammation (e.g. anterior chamber cells, vitreous haze) as defined by the Standardization of Uveitis Nomenclature Working Group. Time to uveitis relapse since the administration of each dose of COVID-19 vaccine was compared across participants with modifiable variables. RESULTS: The primary analysis included 438 non-COVID-19 participants with 857 doses of COVID-19 vaccine administered in total. The median age was 41 years (interquartile range, 30 to 51), and 57.3% were female. A total of 39 episodes of uveitis relapse events occurred in 34 patients after the receipt of a dose of COVID-19 vaccine within 30 days. The median time to relapse after vaccination was 5 days (interquartile range, 1 to 14). Concomitant use of systemic glucocorticoids at the time of vaccination was independently associated with a decrease in risk of relapse after vaccination (HR, 0.23 [95% CI, 0.07-0.74]; P value = 0.014). There was a trend in attenuating the risk of relapse with increasing prednisone dose from none to less than 20 mg per day and then to 20 mg per day or greater (P value for trend = 0.029). CONCLUSIONS: Concomitant treatment with systemic glucocorticoids for uveitis at the time of COVID-19 vaccination was associated with a dose-dependent lower risk of uveitis relapse after vaccination.