Electronic medical records provide large-scale real-world clinical data for use in developing clinical decision systems. However, sophisticated methodology and analytical skills are required to ...handle the large-scale datasets necessary for the optimisation of prediction accuracy. Myopia is a common cause of vision loss. Current approaches to control myopia progression are effective but have significant side effects. Therefore, identifying those at greatest risk who should undergo targeted therapy is of great clinical importance. The objective of this study was to apply big data and machine learning technology to develop an algorithm that can predict the onset of high myopia, at specific future time points, among Chinese school-aged children.
Real-world clinical refraction data were derived from electronic medical record systems in 8 ophthalmic centres from January 1, 2005, to December 30, 2015. The variables of age, spherical equivalent (SE), and annual progression rate were used to develop an algorithm to predict SE and onset of high myopia (SE ≤ -6.0 dioptres) up to 10 years in the future. Random forest machine learning was used for algorithm training and validation. Electronic medical records from the Zhongshan Ophthalmic Centre (a major tertiary ophthalmic centre in China) were used as the training set. Ten-fold cross-validation and out-of-bag (OOB) methods were applied for internal validation. The remaining 7 independent datasets were used for external validation. Two population-based datasets, which had no participant overlap with the ophthalmic-centre-based datasets, were used for multi-resource validation testing. The main outcomes and measures were the area under the curve (AUC) values for predicting the onset of high myopia over 10 years and the presence of high myopia at 18 years of age. In total, 687,063 multiple visit records (≥3 records) of 129,242 individuals in the ophthalmic-centre-based electronic medical record databases and 17,113 follow-up records of 3,215 participants in population-based cohorts were included in the analysis. Our algorithm accurately predicted the presence of high myopia in internal validation (the AUC ranged from 0.903 to 0.986 for 3 years, 0.875 to 0.901 for 5 years, and 0.852 to 0.888 for 8 years), external validation (the AUC ranged from 0.874 to 0.976 for 3 years, 0.847 to 0.921 for 5 years, and 0.802 to 0.886 for 8 years), and multi-resource testing (the AUC ranged from 0.752 to 0.869 for 4 years). With respect to the prediction of high myopia development by 18 years of age, as a surrogate of high myopia in adulthood, the algorithm provided clinically acceptable accuracy over 3 years (the AUC ranged from 0.940 to 0.985), 5 years (the AUC ranged from 0.856 to 0.901), and even 8 years (the AUC ranged from 0.801 to 0.837). Meanwhile, our algorithm achieved clinically acceptable prediction of the actual refraction values at future time points, which is supported by the regressive performance and calibration curves. Although the algorithm achieved balanced and robust performance, concerns about the compromised quality of real-world clinical data and over-fitting issues should be cautiously considered.
To our knowledge, this study, for the first time, used large-scale data collected from electronic health records to demonstrate the contribution of big data and machine learning approaches to improved prediction of myopia prognosis in Chinese school-aged children. This work provides evidence for transforming clinical practice, health policy-making, and precise individualised interventions regarding the practical control of school-aged myopia.
The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the ...paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network.
Introduction Currently, few methods are available to measure orthodontic treatment need and treatment outcome from the lay perspective. The objective of this study was to explore the function of an ...eye-tracking method to evaluate orthodontic treatment need and treatment outcome from the lay perspective as a novel and objective way when compared with traditional assessments. Methods The scanpaths of 88 laypersons observing the repose and smiling photographs of normal subjects and pretreatment and posttreatment malocclusion patients were recorded by an eye-tracking device. The total fixation time and the first fixation time on the areas of interest (eyes, nose, and mouth) for each group of faces were compared and analyzed using mixed-effects linear regression and a support vector machine. The aesthetic component of the Index of Orthodontic Treatment Need was used to categorize treatment need and outcome levels to determine the accuracy of the support vector machine in identifying these variables. Results Significant deviations in the scanpaths of laypersons viewing pretreatment smiling faces were noted, with less fixation time ( P <0.05) and later attention capture ( P <0.05) on the eyes, and more fixation time ( P <0.05) and earlier attention capture ( P <0.05) on the mouth than for the scanpaths of laypersons viewing normal smiling subjects. The same results were obtained when comparing posttreatment smiling patients, with less fixation time ( P <0.05) and later attention capture on the eyes ( P <0.05), and more fixation time ( P <0.05) and earlier attention capture on the mouth ( P <0.05). The pretreatment repose faces exhibited an earlier attention capture on the mouth than did the normal subjects ( P <0.05) and posttreatment patients ( P <0.05). Linear support vector machine classification showed accuracies of 97.2% and 93.4% in distinguishing pretreatment patients from normal subjects (treatment need), and pretreatment patients from posttreatment patients (treatment outcome), respectively. Conclusions The eye-tracking device was able to objectively quantify the effect of malocclusion on facial perception and the impact of orthodontic treatment on malocclusion from the lay perspective. The support vector machine for classification of selected features achieved high accuracy of judging treatment need and treatment outcome. This approach may represent a new method for objectively evaluating orthodontic treatment need and treatment outcome from the perspective of laypersons.
Perovskite solar cells (PSCs) have attracted enormous attention owing to their high power conversion efficiency and low cost. In this work, solvent engineering techniques for PSCs are reviewed using ...co-solvents, anti-solvents, and solvent additives. In the part of co-solvents, binary solvent systems and ternary solvent systems illustrate their respective properties and their application in PSCs. In the part of the anti-solvents, the use of a common anti-solvent such as chlorobenzene or toluene in the solution treatment provides a method for preparing a pinhole-free and dense structure perovskite film. Meanwhile, the continuous exploration of green anti-solvent projects has made it possible to mass-produce mixed-stabilised perovskite films, which is pinhole-free and uniform. In the solvent additives section, the application of different additives can slow down crystal growth and increases the stability of the PSC. Each section outlines the application and potential of solvent engineering technology to improve the performance of PSCs, illustrating potential applications in the future. This work aims to provide some ideas for the improvement of PSC performance and accelerate another leap of solvent engineering technology in the field of PSCs.
Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor ...to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms including hyperphagia and hyperghrelinemia. In this study, male Snord116del mice were characterized and tested for their acute and chronic responses to anorexic substances related to the ghrelin pathway. In comparison with their wild-type littermates, the food intake rate of Snord116del mice was 14% higher when fed ad libitum, and 32% to 49% higher within 12 hours after fasting. Fasted Snord116del mice were less sensitive to the acute anorexic effect of competitive antagonist d-Lys3-GHRP6, YIL-781, and reverse agonist d-Arg1,d-Phe5,d-Trp7,9,Leu11-substance P (SPA) of ghrelin receptor GHS-R. All 3 GHS-R inhibitors failed to inhibit chronic food intake of either Snord116del or wild-type mice due to rapid adaptation. Although fasted Snord116del mice had normal sensitivity to the acute anorexic effect of glucagon-like peptide 1 receptor agonist exenatide, those fed ad libitum required a higher dose and more frequent delivery to achieve ∼15% suppression of long-term food intake in comparison with wild-type mice. Ghrelin, however, is unlikely to be essential for the anorexic effect of exenatide in fed mice, as shown by the fact that exenatide did not reduce ghrelin levels in fed mice and food intake of ghrelin−/− mice fed ad libitum could be suppressed by exenatide. In conclusion, this study suggests that GHS-R may not be an effective therapeutic target, and in contrast, exenatide may produce anorexic effect in PWS individuals.
Abstract Background Refractive status is crucial to visual function and can change throughout life. For patients with congenital cataract, the developmental profile of refraction is complicated owing ...to the potential influence of diverse clinical manifestations and various treatments, and has not yet been fully characterised. Methods In this prospective cohort study, we enrolled patients with congenital cataract from the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH). Two experienced cataract surgeons (YL and WC) did cataract removal or intraocular lens (IOL) implantation at Zhongshan Ophthalmic Center. Patients were followed up at 1 week, 1 month, and 3 months postoperatively, then every 3 months thereafter. Follow-up refraction assessments were conducted with objective retinoscopy and cycloplegia, and were performed by experienced independent optometrists. We compared refraction status (presented as spherical equivalent), and the rate of myopic shift between bilateral and unilateral congenital cataract with linear mixed model (LMM) analysis, then compared the range of myopic shift between bilateral and unilateral congenital cataract with multivariate linear regression Ethical approval was provided by the institutional review board of the Zhongshan Ophthalmic Center (Guangzhou, China). Parents of participating children provided written informed consent. Findings Between Jan 1, 2010, and Oct 31, 2013, we enrolled 1258 participants, all of whom underwent cataract removal and/or intraocular lens (IOL) implantation. By study completion on Oct 31, 2015, 1164 (93%) participants had attended at least one follow-up visit and had refraction status recorded (6585 follow-ups total). Median follow-up was 3 years (IQR 2·5–4·5 years). Spherical equivalent measurements decreased by 1·36 D (SD 0·06) per year between 0·5 years and 4 years of age in bilateral and unilateral congenital cataract aphakic patients. The spherical equivalent of unilateral aphakia was 0·67 D (SD 0·31) smaller than that of bilateral aphakia after correcting for age and sex (p=0·0325). Spherical equivalents in congenital cataract pseudophakia decreased by 0·28 D (SD 0·02) between 1·5 years and 18 years of age (p<0·0001). Spherical equivalents in unilateral pseudophakia did not differ from bilateral pseudophakia (p=0·2996). With the current strategy for IOL calculation, the spherical equivalent in congenital cataract pseudophakia reached emmetropia around 6 years of age, while the healthy eyes of unilateral congenital cataract reached emmetropia at 9–10 years. The rate of myopic shift peaked in both young childhood and early adolescence in all participants. The range of myopic shift in the unilaterally congenital cataract affected eyes was correlated with age at refraction measurement, cataract removal, and IOL implantation, as well as with sex. Interpretation Factors that dictate the range of myopic shift in unilateral congenital cataract seem to be different from those in bilateral congenital cataract, indicating differences in the aetiopathogenesis and refractive prognosis between bilateral and unilateral congenital cataract. Refraction data from patients with congenital cataract are of clinical significance to the guidelines for congenital cataract treatment, especially for IOL calculation concerning the laterality of congenital cataract. Funding National Natural Science Foundation of China (number 81300750), the Ministry of Science and Technology of China Grants (973 program, 2015CB964600), the Key Research Plan for the National Natural Science Foundation of China (number 91546101) and the Guangdong Provincial Natural Science Foundation for Distinguished Young Scholars of China (number 2014A030306030).
Metal perovskite halides have led to the development of light-emitting diodes due to their excellent optical and electrical properties. However, compared to near-infrared, red, and green perovskite ...light-emitting diodes, blue-emitting light-emitting diodes lag far behind in development due to poor stability and low quantum efficiency. In this review, the latest advances in blue perovskite light-emitting diodes are described, including three-dimensional perovskites, two-dimensional/quasi-two-dimensional perovskites, and perovskite nanocrystals. In the three-dimensional perovskite section, the choices of halide perovskite composition, electron transport layer and hole transport layer enable tunable light emission from sky blue to dark blue. In the two-dimensional/quasi-two-dimensional perovskite discussion, the co-surfactant colloid chemistry, and component engineering precisely control the stacking number, which produces a significant blue shift by quantum confinement effects. In the perovskite nanocrystal section, the selection of organic ligands and inorganic passivation are the key strategies to keep the nanocrystal structure stable and fully passivate surface defects. In each section, the present situation and major challenges are overviewed. Next, the evolutions of the methods to overcome these challenges and the most important breakthroughs are highlighted. In conclusion, future directions that may improve the performance of blue perovskite light-emitting diodes are discussed.
Abstract
The medium and long-term operation of the unit is an important part of the operation of the power energy system. With the development of IES, the coupling of various energy forms such as ...electricity, heat and natural gas has been continuously strengthened. When a CHP unit or a gas unit is shut down, its impact will involve a variety of energy systems. Therefore, It is of great significance to formulate a reasonable annual unit combination plan and a coordinated optimization plan for the maintenance plan. First of all, starting from the coupling mechanism of the power supply, heating and gas supply of the unit, consider the relationship between each system and equipment. On this basis, taking into account the system operation constraints, unit maintenance constraints and unit operation constraints, a combined dispatch model of IES unit combination and maintenance plan including power-to-gas (P2G) and electric boiler equipment are proposed. The accuracy and effectiveness of the proposed model are verified through simulation analysis of a numerical example. The calculation example results show that the overall arrangement of the unit maintenance plan and the unit combination plan in the integrated energy system can improve the operating economy of the system; the introduction of coupling equipment such as P2G and electric boilers can effectively improve the new energy consumption rate and reduce the system operating cost.
Abstract
This paper proposes a bilevel optimal scheduling model considering the flexibility and peak shaving benefits of gas-steam combined cycle units, which realizes “thermoelectric decoupling” and ...the flexibility of the unit by configuring electric boilers, and adds the benefit of peak shaving to the upper model to maximize the profit of the unit. Among them, the upper model is the unit optimal bidding model considering flexibility and peak shaving benefits, and the lower model is the power market-clearing model considering the maximization of social welfare. The bilayer model is transformed into a mixed-integer linear programming problem through KKT conditions and other solution methods. The effectiveness and rationality of the model are verified by the analysis of examples. The results of examples show that “thermoelectric decoupling” and start-stop peak shaving can effectively improve the profit of the gas-steam combined cycle unit and the wind power consumption capacity of the system. Finally, the strategic bidding behavior of gas-steam combined cycle units in different periods of the power market is explored.
The majority of rare diseases are complex diseases caused by a combination of multiple morbigenous factors. However, uncovering the complex etiology and pathogenesis of rare diseases is difficult due ...to limited clinical resources and conventional statistical methods. This study aims to investigate the interrelationship and the effectiveness of potential factors of pediatric cataract, for the exploration of data mining strategy in the scenarios of rare diseases.
We established a pilot rare disease specialized care center to systematically record all information and the entire treatment process of pediatric cataract patients. These clinical records contain the medical history, multiple structural indices, and comprehensive functional metrics. A two-layer structural equation model network was applied, and eight potential factors were filtered and included in the final modeling.
Four risk factors (area, density, location, and abnormal pregnancy experience) and four beneficial factors (axis length, uncorrected visual acuity, intraocular pressure, and age at diagnosis) were identified. Quantifiable results suggested that abnormal pregnancy history may be the principle risk factor among medical history for pediatric cataracts. Moreover, axis length, density, uncorrected visual acuity and age at diagnosis served as the dominant factors and should be emphasized in regular clinical practice.
This study proposes a generalized evidence-based pattern for rare and complex disease data mining, provides new insights and clinical implications on pediatric cataract, and promotes rare-disease research and prevention to benefit patients.
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