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  • BMJ  (2)
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  • BMJ  (2)
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  • 1
    Online Resource
    Online Resource
    BMJ ; 2020
    In:  British Journal of Ophthalmology Vol. 104, No. 7 ( 2020-07), p. 932-937
    In: British Journal of Ophthalmology, BMJ, Vol. 104, No. 7 ( 2020-07), p. 932-937
    Abstract: Leber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation profile and phenotypic characteristics in Chinese patients with LCA or EOSRD. Methods Retrospective consecutive case series (2010–2017) study was performed in 148 probands (91 with LCA and 57 with EOSRD). All patients underwent ophthalmic evaluation. Mutations were revealed using targeted next-generation sequencing, followed by Sanger DNA-sequencing and real-time quantitative PCR analysis. Results We identified two diseasing-causing mutations in 88 unrelated patients, heterozygous autosomal dominant mutations in 11 probands and X-linked hemizygous mutations in 11 patients, for an overall mutation detection rate of 74.3% (110/148). We detected 158 different disease-causing mutations involving 14 LCA genes, 16 retinitis pigmentosa or cone-rod dystrophy genes and 3 syndromic retinal dystrophy genes. Of these 158 mutations, 98 were novel. The most common mutation was p.Q141X of AIPL1 , with a gene-specific allele frequency of 60%. The first five most frequently mutated genes were AIPL1 (11.0%), RPGRIP1 (8.8%) and CEP290 , GUCY2D and RPE65 (each 7.7%) in the patients with LCA and RPGR (12.3%), CRB1 (10.5%), RPE65 (10.5%), RDH12 (7.0%) and RP2 (5.3%) in the patients with EOSRD. Conclusions Our results revealed that the mutation spectrum of patients with LCA differs from that of the patients with EOSRD and established the configuration of the mutation frequencies for each LCA gene in Chinese patients, thereby providing essential information for future genetic counselling and gene therapy.
    Type of Medium: Online Resource
    ISSN: 0007-1161 , 1468-2079
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1482974-5
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  • 2
    In: BMJ Open, BMJ, Vol. 9, No. 7 ( 2019-07), p. e024409-
    Abstract: Tuberculosis (TB) remains a major deadly threat in mainland China. Early warning and advanced response systems play a central role in addressing such a wide-ranging threat. The purpose of this study is to establish a new hybrid model combining a seasonal autoregressive integrated moving average (SARIMA) model and a non-linear autoregressive neural network with exogenous input (NARNNX) model to understand the future epidemiological patterns of TB morbidity. Methods We develop a SARIMA-NARNNX hybrid model for forecasting future levels of TB incidence based on data containing 255 observations from January 1997 to March 2018 in mainland China, and the ultimate simulating and forecasting performances were compared with the basic SARIMA, non-linear autoregressive neural network (NARNN) and error-trend-seasonal (ETS) approaches, as well as the SARIMA-generalised regression neural network (GRNN) and SARIMA-NARNN hybrid techniques. Results In terms of the root mean square error, mean absolute error, mean error rate and mean absolute percentage error, the identified best-fitting SARIMA-NARNNX combined model with 17 hidden neurons and 4 feedback delays had smaller values in both in-sample simulating scheme and the out-of-sample forecasting scheme than the preferred single SARIMA(2,1,3)(0,1,1) 12 model, a NARNN with 19 hidden neurons and 6 feedback delays and ETS(M,A,A), and the best-performing SARIMA-GRNN and SARIMA-NARNN models with 32 hidden neurons and 6 feedback delays. Every year, there was an obvious high-risk season for the notified TB cases in March and April. Importantly, the epidemic levels of TB from 2006 to 2017 trended slightly downward. According to the projection results from 2018 to 2025, TB incidence will continue to drop by 3.002% annually but will remain high. Conclusions The new SARIMA-NARNNX combined model visibly outperforms the other methods. This hybrid model should be used for forecasting the long-term epidemic patterns of TB, and it may serve as a beneficial and effective tool for controlling this disease.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
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