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PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None. SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24 to 2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean ± SD age at first test 12.0 ± 3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (P < .04). Mean ± SD patient-level reliability score was 51.7 ± 38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all P < .02), and number of prior VF tests was not (P = .56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

Recent research in multi-principal element alloys (MPEAs) has increasingly focused on the role of short-range order (SRO) on material performance. However, the mechanisms of SRO formation and its precise control remain elusive, limiting the progress of SRO engineering. Here, leveraging advanced additive manufacturing techniques that produce samples with a wide range of cooling rates (up to 107 K s-1) and an enhanced semi-quantitative electron microscopy method, we characterize SRO in three CoCrNi-based face-centered-cubic (FCC) MPEAs. Surprisingly, irrespective of the processing and thermal treatment history, all samples exhibit similar levels of SRO. Atomistic simulations reveal that during solidification, prevalent local chemical order arises in the liquid-solid interface (solidification front) even under the extreme cooling rate of 1011 K s-1. This phenomenon stems from the swift atomic diffusion in the supercooled liquid, which matches or even surpasses the rate of solidification. Therefore, SRO is an inherent characteristic of most FCC MPEAs, insensitive to variations in cooling rates and even annealing treatments typically available in experiments.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

【Objective】The baseline drift of the Fiber Bragg Grating (FBG) spectral signal is usually one of the main problems, caused by the complex external environment. A spectral baseline correction method based on the improved Long Short Term Memory (LSTM) model is proposed in this paper.【Methods】Compared with LSTM model, the improved LSTM model extracts feature information of FBG spectral signal by the Convolutional Neural Network (CNN). The improved LSTM model is composed of CNN, full connection, and LSTM network. In this paper, the improved LSTM model is trained by artificial datasets and measured datasets. The artificial datasets are made up of feature noise, baseline, and FBG spectroscopy. Five methods including wavelet soft threshold method, penalty least square method, Recurrent Neural Network (RNN), LSTM, and the improved LSTM model are used as baseline correction. Identification signal probability and Root Mean Square Error (RMSE) are used to evaluate correction results by the five methods.【Results】The artificial datasets of FBG signal are corrected by the improved LSTM model, and the identification signal probability is increased by 60.8%. The improved LSTM model with training by artificial datasets and measured datasets shows better correction results, compared with training by measured datasets. The mean of the RMSE for FBG spectrum decreases by 10.95%. The standard deviation of RMSE decreases by 4%. The measured datasets of FBG signal are corrected by the improved LSTM model, and the identification signal probability is increased by 50.5%. Compared with wavelet soft threshold method, penalty least square method, RNN and LSTM, the improved LSTM model shows best correction results. The mean values of RMSE and the standard deviation of RMSE are 0.012 2 and 0.002 4, respectively. The RMSE value of the demodulated central wavelength is 0.036 pm. And the baseline correction process takes only 9.68 ms.【Conclusion】The improved LSTM model is an effective method to achieve baseline correction, and has wide range of application prospects in complex external environment.

Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1's role in mediating neuronal resiliency in glaucoma.

Glaucoma drainage devices (GDD) are increasingly utilized in the management of childhood glaucoma. This systematic review and meta-analysis assesses the efficacy of first-time Ahmed or Baerveldt implantation in children. PubMed, Embase, and Cochrane Library were searched for relevant English-language, peer-reviewed literature. Postoperative outcomes were pooled using random effects regression models with restricted maximum likelihood estimation. Thirty-two studies (1,221 eyes, 885 children) were included. Mean ± standard deviation preoperative IOP was 31.8 ± 3.4 mm Hg. Pooled mean IOP at 12 and 24 months postoperatively were 16.5 mm Hg (95% CI, 15.5-17.6) and 17.6 mm Hg (95% CI, 16.4-18.7), respectively. Pooled proportions of success were 0.87 (95% CI, 0.83-0.91) at 12 months, 0.77 (95% CI, 0.71-0.83) at 24 months, 0.54 (95% CI, 0.44-0.65) at 48 months, 0.60 (95% CI, 0.48-0.71) at 60 months, and 0.37 (95% CI, 0.32-0.42) at 120 months. There were no differences in proportion of success at 12 and 24 months among eyes that received Ahmed and Baerveldt tube shunts, nor between eyes with primary glaucoma, glaucoma following cataract surgery, or other secondary glaucoma. Our findings show that Ahmed and Baerveldt shunts substantially reduced IOP for at least 24 months in childhood glaucoma, with similar findings among device types and glaucoma etiologies.

To explore the effect of slightly acidic electrolyzed water (SAEW) on the storage quality of postharvest chives, the changes in the microbial load and storage quality of postharvest chives subjected to SAEW immersion treatment at different concentrations (0, 100, 200 and 300 mg/L) for 5 minutes were analyzed during low temperature ((4 ± 1) ℃) storage. The results showed that immersion treatment with 200 mg/L SAEW was more effective in maintaining the organoleptic quality of chives and inhibiting the increase of the total number of colonies when compared with the other groups. Furthermore, 200 mg/L SAEW treatment was able to inhibit the increase of mass loss and rot rate, slow down the decrease of chlorophyll, vitamin C, soluble sugar, and soluble protein contents, and reduce the accumulation of total free amino acids, malondialdehyde (MDA) and nitrite in chives. It is evident that immersion treatment with 200 mg/L SAEW can not only effectively inhibit microbial growth on chives during low-temperature storage, but also effectively delay the loss of nutrients in chives, thus improving the quality preservation of chives. Therefore, SAEW can be used as an effective sterilization and preservation method to maintain the storage quality and delay the aging process of postharvest chives.

People’s perception of and preference for cities have a close relationship with the shaping and transmission of the city’s image. This article explores the factors that influence the audience’s city preference by applying empathy theory to the mobile urban music “Xi'an People’s Song.” The branding of urban music and its mobile socialization appear to affect urban music empathy positively, although awareness has no significant effect. Urban music empathy fully mediates between branding and goodwill and between the social function of urban music and goodwill. However, the moderating effect of people’s familiarity with urban culture is not significant for urban music empathy and urban preference. The hypothesized relationships are further illustrated on this basis, and the optimization of urban music as a creative medium for promoting city image is discussed.

PurposeWe evaluated the noninferiority of 10.4 μl of eye drops eluted with a commercially available eye drop adapter, the Nanodropper (Nanodropper, Inc), on pupillary dilation and cycloplegia in children compared with the standard of care (SOC), 50 μl of eye drops.DesignProspective randomized trial.ParticipantsPediatric patients scheduled for routine pupillary dilation at the University of California, San Francisco, at the Pediatric Ophthalmology Clinic were enrolled. Each participant provided 1 eye for the intervention group (Nanodropper) and 1 eye for the control group (SOC).MethodsParticipants were randomized to receive small-volume dilating drops in 1 eye (Nanodropper) and SOC dilating drops in the other eye. Dilation was performed using 1 drop each of 1% cyclopentolate, 1% tropicamide, and 2.5% phenylephrine. Refraction and pupillometry were obtained before and 30 minutes after dilation. A noninferiority analysis was performed to assess change from before to after dilation in spherical equivalent and in pupil constriction percentage and maximum pupil diameter after dilation.Main outcome measuresSpherical equivalent, maximum pupil diameter, and pupil constriction percentage.ResultsOne hundred eyes of 50 patients were included, with a mean ± standard deviation age of 9 ± 3 years. After controlling for baseline measurements, the spherical equivalent after dilation was 0.05 diopter (D) more (95% confidence interval [CI], -0.28 to 0.37 D) in the Nanodropper arm, which did not achieve noninferiority. Maximum pupil diameter after dilation was lower in the Nanodropper group (mean, -0.01 mm; 95% CI, -0.20 to -0.03), which did achieve noninferiority. Constriction percentage after dilation was 0.57 percentage points more (95% CI, -1.38 to 2.51 percentage points) in the Nanodropper group, which did not achieve noninferiority.ConclusionsAdministration of eye drops using a small-volume adapter demonstrated similar efficacy to SOC in a pediatric population. Strict noninferiority was met only for pupillary dilation and not for cycloplegia or constriction percentage; however, the small differences in the effect of the Nanodropper versus SOC on all primary outcomes were not clinically significant. We conclude that small-volume eye drops have the potential to decrease unnecessary medical waste and medication toxicity while maintaining therapeutic effect.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Abstract Background and Aims To assess patient comfort, wound healing, and scarring at the 6‐month follow‐up of split‐skin graft donor sites treated with Ba‐Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self‐control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6‐month follow‐up were assessed. Results The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6‐month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion BHBO resulted in faster donor‐site healing, reduced postoperative pain, and improved scar quality at the 6‐month follow‐up than petrolatum gauze alone.

ObjectivesTo evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants.DesignProspective observational study.SettingSingle-center, tertiary-level neonatal intensive care unit.PatientsInfant born

Summary: Transient anoxia causes amnesia and neuronal death. This is attributed to enhanced glutamate release and modeled as anoxia-induced long-term potentiation (aLTP). aLTP is mediated by glutamate receptors and nitric oxide (·NO) and occludes stimulation-induced LTP. We identified a signaling cascade downstream of ·NO leading to glutamate release and a glutamate-·NO loop regeneratively boosting aLTP. aLTP in entothelial ·NO synthase (eNOS)-knockout mice and blocking neuronal NOS (nNOS) activity suggested that both nNOS and eNOS contribute to aLTP. Immunostaining result showed that eNOS is predominantly expressed in vascular endothelia. Transient anoxia induced a long-lasting Ca2+ elevation in astrocytes that mirrored aLTP. Blocking astrocyte metabolism or depletion of the NMDA receptor ligand D-serine abolished eNOS-dependent aLTP, suggesting that astrocytic Ca2+ elevation stimulates D-serine release from endfeet to endothelia, thereby releasing ·NO synthesized by eNOS. Thus, the neuro-glial-endothelial axis is involved in long-term enhancement of glutamate release after transient anoxia.

BackgroundThe antiepileptic medication vigabatrin has been associated with ocular toxicity, and close ophthalmic monitoring has been recommended; however, there is no clear consensus regarding the value and feasibility of such monitoring in children. We describe ophthalmic assessments in children in a real-world clinical setting, the incidence of vigabatrin-related ocular toxicity, and the utility of regular screening or ancillary testing in children taking vigabatrin.MethodsThe medical records of children taking vigabatrin with one or more ophthalmic assessments at Children's Hospital of Philadelphia or University of California, San Francisco, between May 2010 and May 2021, were reviewed retrospectively. Abnormalities on ophthalmic examination, visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT) were reviewed and categorized as attributable to vigabatrin, possibly attributable to vigabatrin, or not attributable to vigabatrin.ResultsA total of 1,281 assessments of 284 children (mean age, 2.09 years) were included. Of these, 283 (99.6%) had funduscopic examination(s), 37 (13.0%) had ERG, 19 (6.7%) had OCT, and 6 (2.1%) had formal VF. Rate of examinations and ERGs per child decreased over the 10-year study period. Two children (0.7%) had definite vigabatrin-related ocular toxicity, both identified on ERG. An additional 4 children (1.4%) had optic atrophy of unclear relation to vigabatrin, categorized as possible toxicity. The remaining 278 children did not have abnormal examination or testing findings attributable to vigabatrin.ConclusionsThe incidence of vigabatrin-related ocular toxicity in children was low in our cohort. Ocular and neurologic comorbidities and limited examinations in children make identification of such toxicity challenging and the value of screening is unclear.

Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected 18F-fluorodeoxyglucose (18F-FDG) PET brain images from two independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 127) and the Xuanwu Hospital of Capital Medical University, Beijing, China (N = 84). During follow-up (mean 80.60 months), 23 participants in the ADNI cohort converted to cognitive impairment. ARGMPs were identified using the scaled subprofile model/principal component analysis method, and cross-validations were conducted in both independent cohorts. A survival analysis was further conducted to calculate the predictive effect of conversion risk by using ARGMPs. The results showed that ARGMPs were characterized by hypometabolism with increasing age primarily in the bilateral medial superior frontal gyrus, anterior cingulate and paracingulate gyri, caudate nucleus, and left supplementary motor area and hypermetabolism in part of the left inferior cerebellum. The expression network scores of ARGMPs were significantly associated with chronological age (R = 0.808, p