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Background: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified., Objective: This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS)., Methods: A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs)., Results: Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline ( n = 967) and fluvoxamine ( n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders., Conclusions and Relevance: Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The dihedral angle of the protein backbone can describe the main structure of the protein, which is of great significance for determining the protein structure. Many computational methods have been proposed to predict this critically important protein structure, including deep learning. However, these heavyweight methods require more computational resources, and the training time becomes intolerable. In this article, we introduce a novel lightweight method, named dilated convolution and multi-head attention (DCMA), that predicts protein backbone torsion dihedral angles ( ϕ , ψ ) . DCMA is stacked by five layers of two hybrid inception blocks and one multi-head attention block (I2A1) module. The hybrid inception blocks consisting of multi-scale convolutional neural networks and dilated convolutional neural networks are designed for capturing local and long-range sequence-based features. The multi-head attention block supplementally strengthens this operation. The proposed DCMA is validated on public critical assessment of protein structure prediction (CASP) benchmark datasets. Experimental results show that DCMA obtains better or comparable generalization performance. Compared to best-so-far methods, which are mostly ensemble models and constructed of recurrent neural networks, DCMA is an individual model that is more lightweight and has a shorter training time. The proposed model could be applied as an alternative method for predicting other protein structural features., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zheng, Zhang and Quan.)

Aims: To investigate the associations of genetic variants previously linked to axial length (AL) and spherical equivalent refraction (SE) in adults with refractive error and related endophenotypes in children, at baseline and 3-year follow-up., Methods: 15 candidate single-nucleotide polymorphisms (SNPs), selected from previous Genome-Wide Association Studies and meta-analyses, were genotyped in 2819 Chinese children, who had undergone baseline and 3-year follow-up cycloplegic refraction, ocular biometry and ocular health examinations. Linear regression analyses were conducted to assess the associations of the SNPs with baseline measurements and longitudinal changes in SE, spherical power (SPH), AL, corneal radius of curvature (CR) and AL/CR ratio., Results: SNPs ZMAT4 rs7829127, ZMAT4 rs16890057, TOX rs7837791, GRIA4 rs11601239 and RDH5 rs3138142 were associated with SE (β=0.233, p=4.21×10 -4 ; β=0.221, p=7.87×10 -4 ; β=0.106, p=0.0076; β=0.084, p=0.041; β=0.14, p=0.013, respectively) and SPH (β=0.24, p=2.3×10 -4 ; β=0.232, p=3.8×10 -4 ; β=0.088, p=0.025; β=0.086, p=0.034; β=0.14, p=0.012, respectively). Among them, ZMAT4 rs7829127 and rs16890057, were also associated with AL (β=-0.128, p=5.6×10 -4 ; β=-0.128, p=5.21×10 -4 ) and AL/CR ratio (β=-0.014, p=0.0028; β=-0.014, p=0.0034), whereas TOX rs7837791 was associated with AL (β=-0.062, p=0.0058) and GRIA4 11 601 239 with AL/CR ratio (β=-0.0058, p=0.049). Additionally, CD55 rs1652333 and RDH5 rs3138142 were associated with 3-year longitudinal changes in AL (β=0.062, p=0.018; β=-0.079, p=0.029) and CR (β=0.014, p=0.027; β=-0.018, p=0.035)., Conclusion: Among SNPs previously associated with AL and SE in adults, variants in ZMAT4 , TOX and GRIA4 were associated with AL, SE, SPH, and/or AL/CR ratio, while variants in RDH5 and CD55 showed associations with AL and CR changes in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the long-term outcomes of mucosal-sparing mechanical endoscopic dacryocystorhinostomy (MMED) for primary acquired nasolacrimal duct obstruction (PANDO) with or without silicone intubation., Methods: An 11-year follow-up study of the Silicone intubation in Endoscopic Dacryocystorhinostomy (SEND) randomized controlled trial (RCT) was conducted at a university-affiliated dacryology clinic from December 2019 to March 2023. Questionnaires on symptoms, anterior segment examination, endoscopic examination with functional endoscopic dye test (FEDT) and FICI grading, and ostial size measurements using Image J software were performed by a masked ophthalmologist. The primary outcome was surgical success, defined by Munk's score ≤1 and a positive fluorescein endoscopic dye test. Secondary outcomes included risk factors for failure and outcomes of revision surgeries., Results: Fifty-three of the original 118 patients were evaluated at 155 ± 21 (136-218) months postoperatively. Seventy-seven percent (46/60) ostia remained successful, including 70% (19/27) of unstented and 82% (27/33) of stented ostia (p = .3). Stented ostia had larger size (p = .003), but this did not confer higher success (p = .14). Successful ostia had higher FICI scores and better ostial dynamicity (p < .05). Ostium movement was the only parameter associated with surgical success on multivariate analysis (OR 13.1, p = .01). Four (1 stented) underwent revision MMED, intraoperative mitomycin-C, and 12-week intubation. All revision ostia were functional after 141 ± 43 months., Conclusions: Surgical success of MMED after 11-years was 77%, a notable reduction compared to 96% success at 1-year. Statistical advantage of silicone intubation for primary MMED was not demonstrated, though clinically, stented ostia had a higher success (82% vs 70%). The presence of a dynamic internal common opening was highly associated with long-term surgical success.

Purpose: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5., Design: Randomized, double-masked extended trial., Participants: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study., Methods: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups., Main Outcomes Measures: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5., Results: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively., Conclusions: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The regulatory serine protease, complement factor I (FI), in conjunction with one of its cofactors (FH, C4BP, MCP, or CR1), plays an essential role in controlling complement activity through inactivation of C3b and C4b. The functional impact by missense variants in the CFI gene, particularly those with minor allele frequencies of 0.01% to 0.1%, is infrequently studied. As such, these variants are typically classified as variants of uncertain significance (VUS) when they are identified by clinical testing. Herein, we utilized a minigene splicing assay to assess the functional impact of 36 ultra-rare variants of CFI . These variants were selected based on their minor allele frequencies (MAF) and their association with low-normal FI levels. Four variants lead to aberrant splicing-one 5' consensus splice site (NM&#95;000204.5: c.1429G>C, p.Asp477His) and three exonic changes (c.355G>A, p.Gly119Arg; c.472G>A, p.Gly158Arg; and c.950G>A, p.Arg317Gln)-enabling their reclassification to likely pathogenic (LP) or pathogenic (P) based on ACMG guidelines. These findings underscore the value of functional assays, such as the minigene assay, in assessing the clinical relevance of rare variants in CFI ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Donelson, Ghiringhelli Borsa, Taylor, Smith and Zhang.)

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children., (© 2024. The Author(s).)

Aims: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA)., Methods: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA., Results: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively)., Conclusion: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective., Prospero Registration Number: Clinical studies: CRD42022368998; animal studies: CRD42022368671., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence from in vitro studies and observational human disease data suggest the complement system plays a significant role in SARS-CoV-2 pathogenesis, although how complement dysregulation develops in patients with severe COVID-19 is unknown. Here, using a mouse-adapted SARS-CoV-2 virus (SARS2-N501Y MA30 ) and a mouse model of severe COVID-19, we identify significant serologic and pulmonary complement activation following infection. We observed C3 activation in airway and alveolar epithelia, and in pulmonary vascular endothelia. Our evidence suggests that while the alternative pathway is the primary route of complement activation, components of both the alternative and classical pathways are produced locally by respiratory epithelial cells following infection, and increased in primary cultures of human airway epithelia in response to cytokine exposure. This locally generated complement response appears to precede and subsequently drive lung injury and inflammation. Results from this mouse model recapitulate findings in humans, which suggest sex-specific variance in complement activation, with predilection for increased C3 activity in males, a finding that may correlate with more severe disease. Our findings indicate that complement activation is a defining feature of severe COVID-19 in mice and lay the foundation for further investigation into the role of complement in COVID-19., Competing Interests: The authors have declared that no conflict of interest exists.

Purpose: To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers., Methods: We performed a search on EMBASE and PubMed for studies up to 15 th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale., Results: In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed., Conclusion: Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cultivating drought-tolerant tea varieties enhances both yield and quality of tea plants in northern China. However, the mechanisms underlying their drought tolerance remain largely unknown. Here we identified a key regulator called CsREV, which differentially regulates xylem patterns between leaves and stems, thereby conferring drought tolerance in tea plants. When drought occurs, upregulation of CsREV activates the CsVND7a-dependent xylem vessel differentiation. However, when drought persists, the vessel differentiation is hindered as CsVND7a is downregulated by CsTCP4a. This, combined with the CsREV-promoted secondary-cell-wall thickness of xylem vessel, leads to the enhanced curling of leaves, a characteristic closely associated with plant drought tolerance. Notably, this inhibitory effect of CsTCP4a on CsVND7a expression is absent in stems, allowing stem xylem vessels to continuously differentiate. Overall, the CsREV-CsTCP4-CsVND7 module is differentially utilized to shape the xylem patterns in leaves and stems, potentially balancing water transportation and utilization to improve tea plant drought tolerance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Urban agglomerations are emerging as new regional units for national participation in global competition and the international division of labor. However, they face increasingly severe resource and eco-environment pressures during urbanization. The coordination of the relationship between urbanization and the eco-environment has attracted global attention. In this study, we used Coupling Coordination Degree and Vector Autoregression models to examine the dynamic evolution, coupling relationships, coordinated development patterns, and interaction mechanisms between urbanization and the eco-environment. The results indicate that: (1) The level of urbanization in the Chengdu-Chongqing Urban agglomeration was relatively low, and the region showed a good eco-environment background. However, rapid urbanization is gradually straining the carrying capacity of the eco-environment. (2) A close and stable coupling relationship exists between urbanization and the eco-environment, which has reached an advanced coupling stage. The status of coordinated development among cities differs considerably, and multiple stable forms may exist simultaneously. (3) Urbanization has a substantial impact on environmental changes, whereas the restrictive effect of the eco-environment on urbanization development is not particularly notable. (4) Various interactive relationships exist between the urbanization and eco-environment subsystems, including positive promotion and negative constraint effects. The positive promotion effect mainly manifests between the economic, social, and ecological response subsystems, while the negative constraint effect is most evident in the mutual coercion and inhibition between the regional urbanization, economic urbanization, ecological status, and ecological pressure subsystems. These findings have important policy implications for decision makers exploring the path of coordinated and sustainable development in urbanization and the eco-environment in Urban agglomerations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: None declared.

Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin. Second, in vitro tests of C3 conversion to C3b do not detect differences when sera from patients with high renin levels are compared to sera from patients with normal/low renin levels. Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase. Fourth, aliskiren does not block dysregulated complement activity on cell surfaces. Fifth, recombinant renin from different sources does not cleave C3 even after 24 hours of incubation at 37 °C. Sixth, direct spiking of recombinant renin into sera samples of patients with C3G and aHUS does not enhance complement activity in either the fluid phase or on cell surfaces. And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The phytohormone auxin, and its directional transport through tissues, plays a fundamental role in the development of higher plants. This polar auxin transport predominantly relies on PIN-FORMED (PIN) auxin exporters. Hence, PIN polarization is crucial for development, but its evolution during the rise of morphological complexity in land plants remains unclear. Here, we performed a cross-species investigation by observing the trafficking and localization of endogenous and exogenous PINs in two bryophytes, Physcomitrium patens and Marchantia polymorpha, and in the flowering plant Arabidopsis thaliana. We confirmed that the GFP fusion did not compromise the auxin export function of all examined PINs by using a radioactive auxin export assay and by observing the phenotypic changes in transgenic bryophytes. Endogenous PINs polarize to filamentous apices, while exogenous Arabidopsis PINs distribute symmetrically on the membrane in both bryophytes. In the Arabidopsis root epidermis, bryophytic PINs have no defined polarity. Pharmacological interference revealed a strong cytoskeletal dependence of bryophytic but not Arabidopsis PIN polarization. The divergence of PIN polarization and trafficking is also observed within the bryophyte clade and between tissues of individual species. These results collectively reveal the divergence of PIN trafficking and polarity mechanisms throughout land plant evolution and the co-evolution of PIN sequence-based and cell-based polarity mechanisms., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of urbanization and the protection of the ecological environment are important aspects of sustainable development in urban agglomerations; thus, their coordination and synergy are crucial. Scholars in both China and other countries have conducted extensive research on the relationship between urbanization and the ecological environment from the perspective of coordinated development. However, there is a lack of research on the synergistic effects of urbanization and the ecological environment. Taking the Chengdu-Chongqing urban agglomeration as an example, this study uses the Haken model to analyze the synergistic evolution mechanism, development patterns, and future trends of urbanization and the ecological environment. This study draws the following conclusions: (1) while a synergistic development mechanism has been established between urbanization and the ecological environment, the current system is still in a stage of low-level synergy, and the control system's parameter for the direction and path of evolution is urbanization. (2) From 2001 to 2020, the level of synergistic development between urbanization and the ecological environment was relatively low, mainly moving from low-level synergy to medium-low-level synergy to medium-level synergy. (3) There is a significant spatial disparity in the levels of synergistic development, for which the leading region centers on Chengdu and Chongqing in the northwest and southeast, respectively, and the lagging region comprises the eastern part of the urban agglomeration, mainly represented by Dazhou, Kaizhou, and Yunyang. (4) The future trend of synergistic development between urbanization and the ecological environment in the Chengdu-Chongqing urban agglomeration is promising but requires increased infrastructure construction in mountainous urban areas, enhanced cooperation and circulation in transportation, logistics, information and other aspects, and balanced improvements in the level of synergistic development between urbanization and the ecological environment. The study of the synergistic development effect of urbanization and the ecological environment in urban agglomerations is of great significance for reducing the negative impact of urbanization on the ecological environment, increasing the positive interaction between the two, and promoting sustainable development in urban agglomerations., (© 2024. The Author(s).)

Introduction: C3 glomerulopathy (C3G) is an ultrarare renal disease characterized by deposition of complement component C3 in the glomerular basement membrane (GBM). Rare and novel genetic variation in complement genes and autoantibodies to complement proteins are commonly identified in the C3G population and thought to drive the underlying complement dysregulation that results in renal damage. However, disease heterogeneity and rarity make accurately defining characteristics of the C3G population difficult., Methods: Here, we present a retrospective analysis of the Molecular Otolaryngology and Renal Research Laboratories C3G cohort. This study integrated complement biomarker testing and in vitro tests of autoantibody function to achieve the following 3 primary goals: (i) define disease profiles of C3G based on disease drivers, complement biomarkers, and age; (ii) determine the relationship between in vitro autoantibody tests and in vivo complement dysregulation; and (iii) evaluate the association between autoantibody function and disease progression., Results: The largest disease profiles of C3G included patients with autoantibodies to complement proteins (48%) and patients for whom no genetic and/or acquired drivers of disease could be identified (43%). The correlation between the stabilization of convertases by complement autoantibodies as measured by in vitro modified hemolytic assays and systemic biomarkers that reflect in vivo complement dysregulation was remarkably strong. In patients positive for autoantibodies, the degree of stabilization capacity predicted worse renal function., Conclusion: This study implicates complement autoantibodies as robust drivers of systemic complement dysregulation in approximately 50% of C3G but also highlights the need for continued discovery-based research to identify novel drivers of disease., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Importance: Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared., Objective: To determine cost-effective options for controlling myopia progression in children., Design, Setting, and Participants: In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center., Main Outcome and Measures: The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years., Results: Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction., Conclusions and Relevance: These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.

Background: A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children., Methods: This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables., Results: Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001)., Conclusions: Exposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary., (© 2023. The Author(s).)

Background/aims: To identify normative values and determinants for Bruch's membrane opening (BMO) and the minimum rim width of BMO (BMO-MRW) among healthy children., Methods: A population-based cross-sectional study from the Hong Kong Children Eye Study, recruiting 1, 226 children aged 6-8 years. Spherical refractive error, axial length (AL), body mass index and intraocular pressure (IOP) were measured. The optic nerve head and the peripapillary retinal nerve fibre layer (p-RNFL) were imaged through spectral domain-optical coherence tomography, using 24 equally spaced radial B-scans. Global and sectoral BMO-MRW values, BMO area and fovea-to-BMO (FoBMO) angle were calculated. Multiple regression analysis was performed to define the determinants of BMO area and BMO-MRW in relation to demographic and ocular parameters., Results: The mean values for global BMO-MRW, BMO area and FoBMO angle among children were 345.76±54.08 µm, 2.34±0.49 mm 2 and -5.45±4.36°, respectively. Global and sectoral values for BMO-MRW correlated with p-RNFL thickness (r=0.11-0.35, p<0.001). After adjusting for demographic and ocular parameters, global BMO-MRW increased with age (β=6.4, p<0.001) and greater global p-RNFL thickness (β=1.41, p<0.001), but decreased with larger BMO area (β=-47.46, p<0.001) and higher IOP (β=-1.73, p<0.001). Global BMO-MRW did not associate with AL, whereas both BMO area and FoBMO angle associated with AL (β=0.04, p=0.02 and β=0.31, p=0.03, respectively), but not with age., Conclusion: We observed that BMO-MRW increases with age among children. Our results provide normative values and the determinants of BMO parameters among Chinese children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies have primarily focused on the relationships among the health locus of control (HLC), healthy lifestyle and life satisfaction of college students. However, little is known about the mediating mechanism of healthy lifestyle on the other two aspects. This study aims to address this issue., Methods: A total of 2394 students from six colleges in Hubei Province validly completed self-report questionnaires, including the Satisfaction with Life Scale (SWLS), Healthy Lifestyle Questionnaire for college students and Multidimensional Health Locus of Control Scale (MHLC), which covered three dimensions: internal HLC, powerful others HLC and chance HLC. Partial least squares structural equation modelling (PLS-SEM) was employed to analyses the hypothesized relationships in the path model, and a mediation analysis was used to verify the indirect relationships., Results: Healthy lifestyle and life satisfaction showed positive relations with both internal HLC and powerful others HLC, but a significant negative association with chance HLC. In addition, healthy lifestyle mediated the relationships of internal HLC, powerful others HLC and chance HLC with life satisfaction., Conclusions: Healthy lifestyle mediates the impact of HLC on life satisfaction. Students with high IHLC tend to develop a healthier lifestyle and have higher LS. Powerful others also exert positive effects in collectivist cultural backgrounds. Thus, colleges should give full play to the positive role of psychological health and physical education courses in improving students' IHLC. Meanwhile, the positive guiding effect of powerful others should be stressed. Further, particular emphasis should also be placed on the peer influence, new media publicity functions, community intervention, and college systematic appraisal, especially during and after public health emergencies., (© 2023. The Author(s).)

Purpose: To identify gene variants associated with anisometropia development in children., Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children. Anisometropia was defined by an interocular difference in SE of ≥1 diopter (D) (Aniso-SE) and an interocular difference in axial length (AL) of ≥0.3 mm (Aniso-AL), respectively. Genetic associations of individual SNPs and joint SNP effects were analyzed., Results: ZFHX1B rs13382811 was associated nominally with Aniso-AL (odds ratio [OR], 1.66; P = 0.003) at baseline. At 3 years, rs13382811 was significantly associated with Aniso-AL (OR, 1.49; P = 0.001) and became nominally associated with Aniso-SE (OR, 1.40; P = 0.01). In addition, PAX6 rs644242 was significantly associated with Aniso-AL at 3 years (OR, 1.45; P = 0.002). At the 3-year follow-up, PAX6 rs644242 was associated significantly with Aniso-AL development (OR, 1.61; P = 0.0003) and nominally with Aniso-SE development (P = 0.03) in children who were not anisometropic at baseline, whereas ZFHX1B rs13382811 was associated nominally with Aniso-AL development (P = 0.02). An additive SNP analysis indicated children carrying the risk allele T of ZFHX1B rs13382811 and allele A of PAX6 rs644242 might have a 4.33- and 6.90-fold of increased risk of Aniso-SE and Aniso-AL development by 3 years, respectively., Conclusions: This study identified two susceptible gene variants, ZFHX1B rs13382811 and PAX6 rs644242, for anisometropia development in Hong Kong Chinese children, implicating their role in imbalanced refractive change and axial elongation between both eyes.

Importance: Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown., Objective: To examine the association between SHS exposure and childhood myopia., Design, Setting, and Participants: Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations., Exposure: Secondhand smoke exposure., Main Outcomes and Measures: Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset., Results: A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (β = -0.09 [95% CI, -0.14 to -0.03]) and longer axial length (β = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child's exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (β = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (β = -0.05 [95% CI, -0.08 to -0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (β = -0.07 [95% CI, -0.11 to -0.02]), axial length (β = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (β = -1.30 [95% CI, -2.32 to -0.27])., Conclusions and Relevance: The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

Introduction: This study aimed to evaluate the habitual reading distance among non-myopic children and also myopic children with undercorrection and with full correction., Methods: This was a population-based cross-sectional study with a total of 2363 children aged 6-8 years who were recruited from the Hong Kong Children Eye Study. Cycloplegic autorefraction, subjective refraction, habitual visual acuity, and best corrected visual acuity were measured. The entire reading process (9 min) was recorded using a hidden video camera placed 5 m away from the reading desk. Reading distances were taken at 6, 7, 8, and 9 min after the child began reading and were measured using a customized computer program developed in MATLAB. The main outcome was the association of habitual reading distances with refraction status. Habitual reading distances of children were documented via video camera footage., Results: The habitual reading distances of undercorrected myopic children (23.37 ± 4.31 cm) were the shortest when compared to non-myopic children (24.20 ± 4.73 cm, P = 0.002) and fully corrected myopic children (24.81 ± 5.21 cm, P < 0.001), while there was no significant difference between the last two children groups (P = 0.17). A shorter reading distance was associated with myopia (OR 1.67; 95% CI 1.11-2.51; P = 0.013) after adjusting for age, sex, height, near work time, outdoor time, and parental myopia. The association of reading distance with myopia did not hold after undercorrected myopic children were excluded (OR 0.97, 95% CI 0.55-1.73; P = 0.92). A shorter reading distance correlated with poorer vision under habitual correction (β = - 0.003, P < 0.001)., Conclusion: A shorter reading distance was present among undercorrected myopic children. Myopia undercorrection is not recommended as a strategy for slowing myopic progression., (© 2022. The Author(s).)

Background: To compare the prevalence of refractive (RA), corneal (CA), and internal astigmatism (IA) in Hong Kong children and adults and evaluate the role of IA in compensating for total astigmatism and its relations to myopic traits., Methods: The Hong Kong Children Eye Study is a population-based cross-sectional study. Totally 3704 school children (mean age 7.5 ± 1.0 years) and 5577 adults (mean age 41.1 ± 7.5 years), who were their parents, were recruited. Cycloplegic and non-cycloplegic refractive cylinders were obtained from children and adults, respectively. Spearman correlation was applied to detect associations between astigmatism, ocular biometrics, refraction, and lens power. Astigmatism compensation factor (CF) was derived from the power vector analysis J0 and J45., Results: The prevalence of RA (≤-1.0 D), CA (≥+1.0 D) and IA (≥+1.0 D) was 21.9%, 63.9%, and 9.9% in children, and 30.9%, 39.5%, and 23.7% in adults respectively. The mean RA, CA and IA values in children and adults were -0.69 ± 0.66 D, +1.14 ± 0.61 D, +0.62 ± 0.32 D, and -0.80 ± 0.74 D, +0.97 ± 0.69 D, and +0.76 ± 0.43 D, respectively. In adults and children, IA was negatively correlated with axial length (p < 0.0001), but positively correlated with spherical values and equivalent (p < 0.0001), suggesting an association of astigmatism with myopic traits. A greater proportion of children exhibited compensation by IA than adults in J0 (86.6% vs. 66.0%, p < 0.0001) and J45 components (55.5% vs. 41.7%, p < 0.0001)., Conclusions: Chinese children in Hong Kong exhibit a higher prevalence of RA and CA than in other cities. Children displayed a greater compensation by IA than adults, suggesting an age-related attenuation of IA compensation. IA is associated with myopic traits., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Polystyrene nanoplastics (PSNPs, <100nm), an artificial pollutant that is widespread in the environment, can be assimilated by plants to alter plant gene expression and its metabolic pathway; thus, interfering with physiological homeostasis and growth of plants. Recently, the biosafety and potential environmental risks of PSNPs have attracted enormous attention. However, the knowledge regarding the uptake and phytotoxicity of atmosphere PSNPs subsiding to plant leaves is still limited. Here, we separately applied 50 mg/L and 100 mg/L PSNPs on cucumber leaves to simulate the plant response to the atmosphere PSNPs. We found that the PSNPs can be accumulated on the surface of cucumber leaves and are also able to be uptake by cucumber leaf stomata. The repertoires of metabolomics and transcriptomics from cucumber leaves upon PSNPs treatment demonstrated that the deposition of PSNPs on leaves alters the biosynthesis of various metabolites and the expression of a variety of genes. The leaves exposure to low concentration (50 mg/L) of PSNPs impact the genes involved in carbohydrate metabolism and the biosynthesis of metabolites related to membrane stability maintenance, thereby, probably enhancing plant tolerance to the stress caused by PSNPs. Whereas, exposure to high concentration (100 mg/L) of PSNPs, both nitrogen and carbohydrate metabolism in cucumber leaves are affected, as well as that the photosynthetic capacity was decreased, leading to the threat to plant health. Combined omics technologies, our findings advance our understanding about how the PSNPs released to ecological environment influence the terrestrial plant growth and provide phytotoxic mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Childhood myopia increased during the COVID-19 pandemic. Limited evidence exists about whether myopia development was reversed or worsened after the lockdown., Objective: To determine the prevalence of myopia and its associated factors before, during, and after COVID-19 restrictions., Design, Setting, and Participants: This population-based, repeated cross-sectional study evaluated children aged 6 to 8 years from the Hong Kong Children Eye Study between 2015 and 2021 in 3 cohorts: before COVID-19 (2015-2019), during COVID-19 restrictions (2020), and after COVID-19 restrictions were lifted (2021)., Exposures: All the children received ocular examinations, including cycloplegic autorefraction and axial length. Data about the children's lifestyle, including time spent outdoors, near-work time, and screen time, were collected from a standardized questionnaire., Main Outcomes and Measures: The main outcomes were the prevalence of myopia, mean spherical equivalent refraction, axial length, changes in lifestyle, and the associated factors over 7 years. Data were analyzed using descriptive statistics, logistic regression, and generalized estimating equations., Results: Of 20 527 children (mean [SD] age, 7.33 [0.89] years; 52.8% boys and 47.2% girls), myopia prevalence was stable from 2015 to 2019 (23.5%-24.9%; P = .90) but increased to 28.8% (P < .001) in 2020 and 36.2% (P < .001) in 2021. The mean (SD) time spent outdoors was much lower in 2020 (0.85 [0.53] h/d; P < .001) and 2021 (1.26 [0.48] h/d; P < .001) compared with pre-COVID-19 levels (1.40 [0.47]-1.46 [0.65] h/d). The trend was reversed for total near-work time and screen time. High myopia prevalence was associated with the COVID-19 pandemic (odds ratio [OR], 1.40; 95% CI, 1.28-1.54; P < .001), younger age (OR, 1.84; 95% CI, 1.76-1.93; P < .001), male sex (OR, 1.11; 95% CI, 1.03-1.21; P = .007), lower family income (OR, 1.05; 95% CI, 1.00-1.09; P = .04), and parental myopia (OR, 1.61; 95% CI, 1.52-1.70; P < .001). During the pandemic, mean (SD) near-work and screen times in children from lower-income families were 5.16 (2.05) h/d and 3.44 (1.97) h/d, more than from higher-income families (4.83 [1.85] and 2.90 [1.61] h/d, respectively)., Conclusions and Relevance: The findings of this cross-sectional study revealed that after COVID-19 restrictions were lifted in Hong Kong, myopia prevalence among children was higher than before the pandemic, and lifestyle did not return to pre-COVID-19 levels. Younger children and those from low-income families were at a higher risk of myopia development during the pandemic, suggesting that collective efforts for myopia control should be advocated for these groups.

The rising prevalence of myopia is a major global public health concern. Economic evaluation of myopia interventions is critical for maximizing the benefits of treatment and the healthcare system. This systematic review aimed to evaluate the cost-effectiveness of interventions for treating myopia. Five databases were searched - Embase, Emcare, PubMed, Web of Science, and ProQuest - from inception to July 2022 and a total of 2,099 articles were identified. After careful assessments, 6 studies met the eligibility criteria. The primary outcomes of this systematic review were costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The secondary outcomes included utility values and net monetary benefits (NMB). One study determined the cost-effectiveness of photorefractive screening plus treatment with 0.01% atropine, 2 studies examined cost-effectiveness of corneal refractive surgery, and 3 studies evaluated cost-effectiveness of commonly used therapies for pathologic myopia. Corneal refractive surgeries included laser in situ keratomileusis (LASIK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), photorefractive keratectomy (PRK), and small-incision lenticule extraction (SMILE). Interventions for pathologic myopia included ranibizumab, conbercept, and photodynamic therapy (PDT). At an incremental cost of NZ$ 18 (95% CI 15, 20) (US$ 11) per person, photorefractive screening plus 0.01% atropine resulted in an ICER of NZ$ 1,590/QALY (US$ 1,001/QALY) (95% CI NZ$ 1,390, 1,791) for an incremental QALY of 0.0129 (95% CI 0.0127, 0.0131). The cost of refractive surgery in Europe ranged from €3,075 to €3,123 ([US$4,046 to $4,109 - adjusted to 2021 inflation). QALYs associated with these procedures were 23 (FS-LASIK) and 24 (SMILE and PRK) with utility values of 0.8 and ICERs ranging from approximately €14 (US$17)/QALY to €19 (US$23)/QALY. The ICER of LASIK was US$683/diopter gained (inflation-adjusted). The ICER of ranibizumab and PDT were £8,778 (US$12,032)/QALY and US$322,460/QALY respectively, with conbercept yielding a saving of 541,974 RMB (US$80,163)/QALY, respectively. The use of 0.01% atropine and corneal refractive surgery were cost-effective for treating myopia. Treating pathologic myopia with ranibizumab and conbercept were more cost-effective than PDT. Prevention of myopia progression is more cost-effective than treating pathologic myopia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Agyekum, Chan, Zhang, Huo, Yip, Ip, Tham, Chen, Zhang, Pang and Yam.)

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed., Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia., Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022., Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years., Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D)., Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year., Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

Introduction: C3 glomerulopathies (C3G) are ultra-rare complement-mediated diseases that lead to end-stage renal disease (ESRD) within 10 years of diagnosis in ~50% of patients. Overactivation of the alternative pathway (AP) of complement in the fluid phase and on the surface of the glomerular endothelial glycomatrix is the underlying cause of C3G. Although there are animal models for C3G that focus on genetic drivers of disease, in vivo studies of the impact of acquired drivers are not yet possible., Methods: Here we present an in vitro model of AP activation and regulation on a glycomatrix surface. We use an extracellular matrix substitute (MaxGel) as a base upon which we reconstitute AP C3 convertase. We validated this method using properdin and Factor H (FH) and then assessed the effects of genetic and acquired drivers of C3G on C3 convertase., Results: We show that C3 convertase readily forms on MaxGel and that this formation was positively regulated by properdin and negatively regulated by FH. Additionally, Factor B (FB) and FH mutants impaired complement regulation when compared to wild type counterparts. We also show the effects of C3 nephritic factors (C3Nefs) on convertase stability over time and provide evidence for a novel mechanism of C3Nef-mediated C3G pathogenesis., Discussion: We conclude that this ECM-based model of C3G offers a replicable method by which to evaluate the variable activity of the complement system in C3G, thereby offering an improved understanding of the different factors driving this disease process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pisarenka, Meyer, Xiao, Goodfellow, Nester, Zhang and Smith.)

Complement factor I deficiency (CFID; OMIM #610984) is a rare immunodeficiency caused by deficiencies in the serine protease complement factor I (CFI). CFID is characterized by predisposition to severe pneumococcal infection, often in infancy. We report a previously healthy adolescent male who presented with respiratory failure secondary to pneumococcal pneumonia and severe systemic inflammatory response. Rapid genome sequencing (rGS) identified compound heterozygous variants in CFI in the proband, with a novel maternally inherited likely pathogenic variant, a single nucleotide deletion resulting in premature stop (c.1646del; p.Asn549ThrfsTer25) and a paternally inherited novel likely pathogenic deletion (Chr 4:110685580-110692197del)., (© 2022 Rodriguez et al.; Published by Cold Spring Harbor Laboratory Press.)

With the rapid development of the internet, the application of internet search data has been seen as a novel data source to offer timely infectious disease surveillance intelligence. Moreover, the advancements in internet search data, which include rich information at both space and time scales, enable investigators to sufficiently consider the spatiotemporal uncertainty, which can benefit researchers to better monitor infectious diseases and epidemics. In the present study, we present the necessary groundwork and critical appraisal of the use of internet search data and spatiotemporal analysis approaches in infectious disease surveillance by updating the current stage of knowledge on them. The study also provides future directions for researchers to investigate the combination of internet search data with the spatiotemporal analysis in infectious disease surveillance. Internet search data demonstrate a promising potential to offer timely epidemic intelligence, which can be seen as the prerequisite for improving infectious disease surveillance., Competing Interests: HS, YZ, GG, and DW were employed by Popsmart Technology (Zhejiang) Co., Ltd., (Copyright © 2022 Sun, Zhang, Gao and Wu.)

Background: The impacts of social restrictions for COVID-19 on children's vision and lifestyle remain unknown., Aims: To investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic., Methods: Two separate longitudinal cohorts of children aged 6-8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits., Results: A total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was -0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001)., Conclusions: We showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia-a potential public health crisis as a result of COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To determine the prevalence of amblyopia and the factors associated with delayed diagnosis among school-aged children in Hong Kong., Methods: Completed comprehensive ophthalmoscopic examinations were conducted among 4.273 children aged 6-8 years in the population-based Hong Kong Children Eye Study. New and previous diagnoses of amblyopia were identified. Socioeconomic status was surveyed through questionnaires., Results: According to criteria from the Multi-Ethnic Pediatric Eye Disease Study (MEPEDS), amblyopia was present in 43 out of 4,273 children (1.01%; 95% CI, 0.71-1.31). Among them, 33 (0.77%) were newly detected cases that were more likely from families living in Public Rental Housing or subdivided flats (OR, 4.22; P = .012), with lower paternal (OR 6.68, P = .008) and maternal education levels (OR, 4.38; P = .039). Multivariate analysis revealed associations of amblyopia with hyperopia (≥+2.00D; OR, 6.23; 95% CI, 2.86-13.56, P < .001), astigmatism (≥+2.00D; OR, 24.88; 95% CI, 10.69-57.91, P < .001) and anisometropia (≥2.00D; OR, 14.49; 95% CI, 5.93-37.63, P < .001)., Conclusion: These children with delayed diagnoses of amblyopia were more likely to come from lower socioeconomic backgrounds. Public education aimed at increasing awareness and utilization of child vision screening among such families is needed.

Importance: Parental astigmatism is a factor associated with risk for development of child astigmatism; however, the magnitude of the association has not been determined., Objective: To determine the association between parental and child astigmatism., Design, Setting, and Participants: This population-based, cross-sectional study included participants from familial trios, each comprising a child aged 6 to 8 years and both parents, recruited from the Hong Kong Children Eye Study. No restriction criteria were set on the children in terms of refractive status. Data were analyzed from February to June 2022., Exposures: Cycloplegic autorefraction and autokeratometry were conducted on the children, whereas noncycloplegic autorefraction and autokeratometry were conducted on their parents. The children were categorized into 6 groups on the basis of the severity of astigmatism of both parents. Information on parental education, family income, and children's outdoor and near work time were obtained by questionnaires., Main Outcomes and Measures: The primary outcome was the odds of child astigmatism among the 6 categories of children. Associations of factors with child astigmatism were evaluated by logistic regression analyses., Results: A total of 17 124 participants from 5708 trios (2964 boys and 2754 girls) at a mean (SD) age of 7.32 (0.87) years, and 11 416 parents were examined. Astigmatism of 1.0 D or greater in both parents was associated with greater odds of refractive astigmatism (RA) (odds ratio [OR], 1.62; 95% CI, 1.15-2.26) and corneal astigmatism (CA) (OR, 1.94; 95% CI, 1.50-2.50) in the child. The respective ORs increased to 3.10 (95% CI, 1.34-7.21) and 4.31 (95% CI, 1.76-10.55) when both parents had astigmatism 2.0 D or greater. Higher parental astigmatism conferred higher risks for both RA and CA in children (P for trend <.001). Parental astigmatism was significantly associated with greater odds of corresponding child astigmatism (maternal RA: OR, 0.76; 95% CI, 0.68-0.84; paternal RA: OR, 0.82; 95% CI, 0.74-0.91; maternal CA: OR, 1.70; 95% CI, 1.51-1.93; paternal CA: OR, 1.33; 95% CI, 1.19-1.49)., Conclusions and Relevance: The findings of this cross-sectional study suggest that parental astigmatism may confer an independent and dose-dependent association with child astigmatism. Children with parents with astigmatism should have early eye examinations for timely detection of astigmatism to facilitate age-appropriate vision correction and visual development.

Strigolactones (SLs) are a class of phytohormones that regulate plant shoot branching and adventitious root development. However, little is known regarding the role of SLs in controlling the behavior of the smallest unit of the organism, the single cell. Here, taking advantage of a classic single-cell model offered by the cotton (Gossypium hirsutum) fiber cell, we show that SLs, whose biosynthesis is fine-tuned by gibberellins (GAs), positively regulate cell elongation and cell wall thickness by promoting the biosynthesis of very long-chain fatty acids (VLCFAs) and cellulose, respectively. Furthermore, we identified two layers of transcription factors (TFs) involved in the hierarchical regulation of this GA-SL crosstalk. The top-layer TF GROWTH-REGULATING FACTOR 4 (GhGRF4) directly activates expression of the SL biosynthetic gene DWARF27 (D27) to increase SL accumulation in fiber cells and GAs induce GhGRF4 expression. SLs induce the expression of four second-layer TF genes (GhNAC100-2, GhBLH51, GhGT2, and GhB9SHZ1), which transmit SL signals downstream to two ketoacyl-CoA synthase genes (KCS) and three cellulose synthase (CesA) genes by directly activating their transcription. Finally, the KCS and CesA enzymes catalyze the biosynthesis of VLCFAs and cellulose, respectively, to regulate development of high-grade cotton fibers. In addition to providing a theoretical basis for cotton fiber improvement, our results shed light on SL signaling in plant development at the single-cell level., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Economic forecasting is a scientific decision-making tool, and it is one of the important basis for the government to formulate economic plans, predict the implementation of the plan, and guide the implementation of the plan. Current knowledge about the use of online news in the prediction of economic patterns in China is limited, especially considering the spatio-temporal dynamics over time. This study explored the spatio-temporal patterns of economic output values in Yinzhou, Ningbo, China between 2018 and 2021, and proposed generalized linear model (GLM) and Geographically weighted regression (GWR) model to predict the dynamics using online news data. The results indicated that there were spatio-temporal variations in the economic dynamics in the study area. The online news showed a great potential to predict economic dynamics, with better performance in the GWR model. The findings suggested online news combining with spatio-temporal approach can better forecast economic dynamics, which can be seen as a pre-requisite for developing an online news-based surveillance system The advanced spatio-temporal analysis enables governments to garner insights about the patterns of economic dynamics over time, which may enhance the ability of government to formulate economic plans and to predict the implementation of the plan. The proposed model may be extended to greater geographic area to validate such approach., (© 2022. The Author(s).)

The capacitated arc routing problem (CARP) has attracted much attention for its many practical applications. The large-scale multidepot CARP (LSMDCARP) is an important CARP variant, which is very challenging due to its vast search space. To solve LSMDCARP, we propose an iterative improvement heuristic, called route clustering and search heuristic (RoCaSH). In each iteration, it first (re)decomposes the original LSMDCARP into a set of smaller single-depot CARP subproblems using route cutting off and clustering techniques. Then, it solves each subproblem using the effective Ulusoy's split operator and local search. On one hand, the route clustering helps the search for each subproblem by focusing more on the promising areas. On the other hand, the subproblem solving provides better routes for the subsequent route cutting off and clustering, leading to better problem decomposition. The proposed RoCaSH was compared with the state-of-the-art MDCARP algorithms on a range of MDCARP instances, including different problem sizes. The experimental results showed that RoCaSH significantly outperformed the state-of-the-art algorithms, especially for the large-scale instances. It managed to achieve much better solutions within a much shorter computational time.

Extensive distribution of widespread species and the loss of native species driven by anthropogenic disturbances modify community similarity, resulting in a decrease or increase in community distinctiveness. Data from four basins in the Wannan Mountains, China, were used to evaluate the effects of low-head dams on patterns of fish faunal homogenization and differentiation based on abundance data. We aimed to examine the spatial changes in taxonomic and functional similarities of fish assemblages driven by low-head dams and to examine whether the changes in the similarity of fish assemblages differed between taxonomic and functional components. We found that low-head dams significantly decreased the mean taxonomic similarity but increased the mean functional similarity of fish assemblages in impoundments using abundance-based approaches, suggesting that taxonomic differentiation accompanied functional homogenization in stream fish assemblages. These results show the importance of population abundance in structuring fish faunal homogenization and differentiation at small scales, especially when the major differences among assemblages are in species abundance ranks rather than species identities. Additionally, we also found only a weak positive correlation between changes in mean taxonomic and functional similarities, and partial pairs exhibited considerable variation in patterns of fish faunal homogenization and differentiation for taxonomic and functional components. In conclusion, this study highlighted that the observed taxonomic differentiation of current fish assemblages (short-term phenomenon) is probably an early warning sign of further homogenization in regions where native species are completely predominated and that changes in taxonomic similarity cannot be used to predict changes in functional similarity., Competing Interests: We declare that we have no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Environmental filtering, spatial factors and species interactions are fundamental ecological mechanisms for community organisation, yet the role of such interactions across different environmental and spatial settings remains mostly unknown. In this study, we investigated fish community organisation scenarios and seasonal species-to-species associations potentially reflecting biotic associations along the Qiupu River (China). Based on a latent variable approach and a tree-based method, we compared the relative contribution of the abiotic environment, spatial covariates and potential species associations for variation in the community structure, and assessed whether different assembly scenarios were modulated by concomitant changes in the interaction network structure of fish communities across seasons. We found that potential species associations might have been underestimated in community-based assessments of stream fish. Omnivore species, since they have more associations with other species, were found to be key components sustaining fish interaction networks across different stream orders. Hence, we suggest that species interactions, such as predation and competition, likely played a key role in community structure. For instance, indices accounting for network structure, such as connectance and nestedness, were strongly correlated with the unexplained residuals from our latent variable approach, thereby re-emphasising that biotic signals, potentially reflecting species interactions, may be of primary importance in determining stream fish communities across seasons. Overall, our findings indicate that interaction network structures are a powerful tool to reflect the contribution of potential species associations to community assembly. From an applied perspective, this study should encourage freshwater ecologists to empirically capture and manage biotic constraints in stream ecosystems across different geographical and environmental settings, especially in the context of the ever-increasing impacts of human-induced local extinction debts and species invasions.

This paper proposes an efficient multi-level encryption scheme for stereoscopic medical images based on coupled chaotic systems and Otsu threshold segmentation. In our method, first, the stereoscopic medical image is divided into the image top, middle, and lower parts. Moreover, each part is divided into background areas and regions of interest utilizing Otsu threshold segmentation, increasing about 40% the encryption efficiency when the background area is discarded. Second, compared with existing chaotic systems, the proposed coupled chaotic system has better ergodicity and randomness, with all NIST SP800-22 test data exceeding 0.01. Third, we develop a robust watermarking algorithm based on forwarding Meyer wavelet transform and singular value decomposition. Furthermore, the watermark algorithm embedded the two-dimensional code doctor-patient information in the region of interest. Finally, the experimental results demonstrate that the proposed algorithm has appealing encryption and watermark performance, the histogram and scatter graphs are governed by approximately uniform distribution, the NPCR and UACI of plaintext sensitivity and the key sensitivity are close to 99.6094% and 33.4635%, affording robustness to noise and clipping attacks., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) are two rare diseases caused by dysregulated activity of the alternative pathway of complement secondary to the presence of genetic and/or acquired factors. Complement factor I (FI) is a serine protease that downregulates complement activity in the fluid phase and/or on cell surfaces in conjunction with one of its cofactors, factor H (FH), complement receptor 1 (CR1/CD35), C4 binding protein (C4BP) or membrane cofactor protein (MCP/CD46). Because altered FI activity is causally related to the pathogenesis of C3G and aHUS, we sought to test functional activity of select CFI missense variants in these two patient cohorts. We identified 65 patients (16, C3G; 48, aHUS; 1 with both) with at least one rare variant in CFI (defined as a MAF < 0.1%). Eight C3G and eleven aHUS patients also carried rare variants in either another complement gene, ADAMTS13 or THBD . We performed comprehensive complement analyses including biomarker profiling, pathway activity and autoantibody testing, and developed a novel FI functional assay, which we completed on 40 patients. Seventy-eight percent of rare CFI variants (31/40) were associated with FI protein levels below the 25 th percentile; in 22 cases, FI levels were below the lower limit of normal (type 1 variants). Of the remaining nine variants, which associated with normal FI levels, two variants reduced FI activity (type 2 variants). No patients carried currently known autoantibodies (including FH autoantibodies and nephritic factors). We noted that while rare variants in CFI predispose to complement-mediated diseases, phenotypes are strongly contingent on the associated genetic background. As a general rule, in isolation, a rare CFI variant most frequently leads to aHUS, with the co-inheritance of a CD46 loss-of-function variant driving the onset of aHUS to the younger age group. In comparison, co-inheritance of a gain-of-function variant in C3 alters the phenotype to C3G. Defects in CFH (variants or fusion genes) are seen with both C3G and aHUS. This variability underscores the complexity and multifactorial nature of these two complement-mediated renal diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Goodfellow, Ghiringhelli Borsa, Dunlop, Presti, Meyer, Shao, Roberts, Jones, Pitcher, Taylor, Nester and Smith.)

Purpose: To evaluate longitudinal changes in subfoveal choroidal thickness (SFChT) among children receiving atropine 0.05%, 0.025%, or 0.01% over 2 years and their associations with treatment outcomes in myopia control., Design: Double-blinded randomized controlled trial., Methods: SFChT was measured at 4-month intervals using spectral domain optical coherence tomography. Cycloplegic spherical equivalent (SE), axial length (AL), best-corrected visual acuity, parental SE, outdoor time, near work diopter hours, and treatment compliance were also measured., Results: 314 children were included with qualified choroidal data. The 2-year changes in SFChT from baseline were 21.15 ± 32.99 µm, 3.34 ± 25.30 µm, and -0.30 ± 27.15 µm for the atropine 0.05%, 0.025%, and 0.01% groups, respectively (P < .001). A concentration-dependent response was observed, with thicker choroids at higher atropine concentrations (β = 0.89, P < .001). Mean SFChT thickness significantly increased at 4 months in the atropine 0.025% (P = .001) and 0.05% groups (P < .001) and then remained stable until the end of the second year (P > .05 for all groups). Over 2 years, an increase in SFChT was associated with slower SE progression (β = 0.074, P < .001) and reduced AL elongation (β = -0.045, P < .001). In the mediation analysis, 18.45% of the effect on SE progression from atropine 0.05% was mediated via its choroidal thickening., Conclusions: Low concentration atropine induced a choroidal thickening effect along a concentration-dependent response throughout the treatment period. The choroidal thickening was associated with a slower SE progression and AL elongation among all the treatment groups. Choroidal response can be used for assessment of long-term treatment outcomes and as a guide for concentration titrations of atropine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Little research has been conducted on the spatio-temporal relationship between the severe cases and the enteroviruses infections of hand, foot and mouth disease (HFMD). This study aimed to investigate epidemic features and spatial clusters of HFMD incidence rates and assess the relationship between Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) and severe cases of HMFD in Gansu province, China., Methods: Weekly county-specific data on HFMD between 1st January and 31st December 2018 were collected from the China Infectious Disease Information System (CIDIS), including enterovirus type (EV71 and CoxA16), severe and non-severe cases in Gansu province, China. Temporal risk [frequency index (α), duration index (β) and intensity index (γ)] and spatial cluster analysis were used to assess epidemic features and identify high-risk areas for HFMD. Time-series cross-correlation function and regression model were used to explore the relationship between the ratios of two types of viruses (i.e. EV71/Cox16) (EC) and severe cases index (i.e. severe cases/non-severe cases) (SI) of HFMD., Results: Some counties in Dingxi City, Gansu were identified as a hot spot for the temporal risk indices. Time-series cross-correlation analysis showed that SI was significantly associated with EC (r = 0.417, P < 0.05) over a 4-week time lag. The regression analysis showed that SI was positively associated with EC (β = 0.04, 95% confidence interval (CI) 0.02-0.06)., Conclusion: The spatial patterns of HFMD incidence were associated with enteroviruses in Gansu. The research suggested that the EC could be considered a potential early warning sign for predicting severe cases of HFMD in Gansu province., (© 2022. The Author(s).)

The adaptation aftereffect plays a critical role in human development and survival. Existing studies have found that, compared with general individuals, individuals with learning disability, autism and dyslexia show a smaller amount of non-affective-based cognitive adaptation aftereffect. Nevertheless, it is unclear whether individuals with depression or depression tendency show similar phenomenon in the adaptation aftereffect, and whether such depression tendency occurs in the non-affective-based cognitive or emotional adaptation aftereffect. To address this question, the present study conducted two experiments. Experiments 1A and 1B used the emotional facial expression adaptation paradigm to examine whether Chinese participants showed the emotional adaptation aftereffect and whether the emotional adaptation aftereffect was influenced by physical features of faces, respectively. Experiment 2 recruited two groups of participants, with high and low depression, respectively, to examine whether they showed differences in the emotional or cognitive adaptation aftereffect. Results showed that Chinese participants showed the typical emotional adaptation aftereffect, which was not influenced by physical features of faces. More importantly, compared to the low-depression group, the high-depression group showed a smaller emotional adaptation aftereffect, but the two groups showed a similar cognitive adaptation aftereffect. These results suggest that level of depressive symptoms is associated with the emotional adaptation aftereffect.

Background: Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed to investigate trends in global retinoblastoma survival and globe preservation during the past 40 years. We also examined associated socioeconomic and health-care factors and global survival disparity., Methods: We did a systematic review and meta-analysis by screening articles in any language in nine databases (PubMed, Embase, ScienceDirect, Web of Science, OpenGrey, Global Burden of Disease, Global Health Data Exchange, Global Index Medicus, and International Agency for the Prevention of Blindness) published between Jan 1, 1981, and Oct 8, 2021. We screened for articles that described retinoblastoma overall survival or globe salvage, or both. All reported studies were subsequently stratified into four periods: 1980-89, 1990-99, 2000-09, and 2010-20. Indicators on socioeconomic and health-care factors were extracted from the World Bank and WHO. Ophthalmology-related indicators were further parsed from the International Agency for the Prevention of Blindness. Between-study heterogeneities by income level were assessed by mixed-effect meta-analysis. Associations of retinoblastoma outcome with socioeconomic and health-care factors and factors for survival prediction were investigated by multivariable linear regressions. This study is registered with PROSPERO, number CRD42020221556., Findings: Our search identified 14 621 articles, of which 314 studies were included for analysis after screening, including 38 130 patients from 80 regions globally presenting during 1980-2020. 255 articles were entered for time-trend meta-analysis, covering 29 106 patients from 73 countries. Both overall survival (from 79% [95% CI 74-84] to 88% [83-93]; p=0·017) and globe salvage rate (from 22% [14-32] to 44% [36-52]; p=0·0003) improved significantly over the four decades. Wide disparities were observed between higher-income and lower-income countries. Overall survival, globe salvage, and globe salvage for advanced intraocular disease correlated positively with income level. Higher overall survival was associated with lower Gini index (p=0·0001) and with populations that had smaller percentages living in rural areas (p=0·0005). Higher globe salvage was associated with better health-care financing and accessibility (p=0·030). Overall survival (p=0·0024) and globe salvage (p=0·022) were both associated positively with education level. Survival gaps were observed in sub-Saharan Africa and southeast and southwest Asia., Interpretation: Retinoblastoma treatment outcomes have improved globally over the past four decades but large disparities persist between higher-income and lower-income countries, with some areas having major survival gaps. Targeted health-care policy making with increased health-care financing and accessibility are needed in low-income and lower-middle-income countries to improve retinoblastoma outcomes worldwide., Funding: Health and Medical Research Fund (Hong Kong) and Children Cancer's Foundation (Hong Kong)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: (1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment., Design: A randomized, double-masked extended trial., Participants: A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study., Methods: At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals., Main Outcome Measures: Changes in SE and AL between groups., Results: A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: -0.68 ± 0.49 diopters (D) versus -0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; -0.57 ± 0.38 D versus -0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; -0.56 ± 0.40 D versus -0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were -0.73 ± 1.04 D, -1.31 ± 0.92 D, and -1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and -1.15 ± 1.13 D, -1.47 ± 0.77 D, and -1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001)., Conclusions: During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)