Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until sympto...Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.展开更多
Spinocerebellar ataxias （SCAs） are a group of genetic disorders characterized by slowly progressive incoordina- tion of gait and are often associated with poor coordination of the hands, speech, and eye movements. F...Spinocerebellar ataxias （SCAs） are a group of genetic disorders characterized by slowly progressive incoordina- tion of gait and are often associated with poor coordination of the hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. The genetic forms of ataxia are diagnosed by family history, physical examina- tion, neuroimaging, and molecular genetic testing. At present, 36 SCA subtypes including 27 pathogenic genes have been identified [1]. Different subtypes of SCAs have clear distribution differences among ethnic populations, and SCA8 is an infrequent entity worldwide, which has mostly been reported in Japanese, but has never been reported in Chinese [2]. SCAB involves bidirectional expression based on the total number of both the （CTA）n and （CTG）n expansion transcripts in ATXN8OS. The pathogenesis of this disorder is complex and the spectrum of clinical presentations is broad. It is predominantly characterized by drawn-out slowness of speech and gait instability, followed by slowly progressive ataxia, with disease onset typically occurring in adulthood [3]. How- ever, the lowest full-penetrance allele for SCA8 onset remains elusive and the current understanding of the phenotypic and genotypic features of SCA8 is limited. Since SCA8 has not yet been reported in the Chinese population and is scantily reported in a small proportion of pedigrees so far, clinical knowledge is still developing. Moreover, the boundary between the normal and patho- genic alleles of SCA8 is uncertain. Here we report the clinical and molecular genetic characteristics of 3 Chinese SCA8 families and have identified 51 CTA/CTG repeats within ATXN8OS, probably the shortest pathogenic allele for SCA8.展开更多
Abnormal driving behavior identification( ADBI) has become a research hotspot because of its significance in driver assistance systems. However,current methods still have some limitations in terms of accuracy and reli...Abnormal driving behavior identification( ADBI) has become a research hotspot because of its significance in driver assistance systems. However,current methods still have some limitations in terms of accuracy and reliability under severe traffic scenes. This paper proposes a new ADBI method based on direction and position offsets,where a two-factor identification strategy is proposed to improve the accuracy and reliability of ADBI. Self-adaptive edge detection based on Sobel operator is used to extract edge information of lanes. In order to enhance the efficiency and reliability of lane detection,an improved lane detection algorithm is proposed,where a Hough transform based on local search scope is employed to quickly detect the lane,and a validation scheme based on priori information is proposed to further verify the detected lane. Experimental results under various complex road conditions demonstrate the validity of the proposed ADBI.展开更多
The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/s...The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/snRNA-seq)techniques,there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features.In this study,we build a unified liver cell atlas uniLIVER(http://lifeome.net/database/uniliver)by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets.Moreover,we introduce LiverCT,a machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of“variant”cellular states analogous to the sequence variants in genomic analysis.Applying LiverCT on liver cancer datasets,we find that the“deviated”states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma,and the enrichments of tumor cells with the hepatocyte-cholangiocyte“intermediate”states significantly indicate poor prognosis.Besides,we find that the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis.This reference atlas mapping framework can also be extended to any other tissues.展开更多
基金supported by the funds for the construction of key medical disciplines in Shenzhen.
文摘Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.
基金supported by grants from the National Natural Science Foundation of China(81301486 and81672095)
文摘Spinocerebellar ataxias （SCAs） are a group of genetic disorders characterized by slowly progressive incoordina- tion of gait and are often associated with poor coordination of the hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. The genetic forms of ataxia are diagnosed by family history, physical examina- tion, neuroimaging, and molecular genetic testing. At present, 36 SCA subtypes including 27 pathogenic genes have been identified [1]. Different subtypes of SCAs have clear distribution differences among ethnic populations, and SCA8 is an infrequent entity worldwide, which has mostly been reported in Japanese, but has never been reported in Chinese [2]. SCAB involves bidirectional expression based on the total number of both the （CTA）n and （CTG）n expansion transcripts in ATXN8OS. The pathogenesis of this disorder is complex and the spectrum of clinical presentations is broad. It is predominantly characterized by drawn-out slowness of speech and gait instability, followed by slowly progressive ataxia, with disease onset typically occurring in adulthood [3]. How- ever, the lowest full-penetrance allele for SCA8 onset remains elusive and the current understanding of the phenotypic and genotypic features of SCA8 is limited. Since SCA8 has not yet been reported in the Chinese population and is scantily reported in a small proportion of pedigrees so far, clinical knowledge is still developing. Moreover, the boundary between the normal and patho- genic alleles of SCA8 is uncertain. Here we report the clinical and molecular genetic characteristics of 3 Chinese SCA8 families and have identified 51 CTA/CTG repeats within ATXN8OS, probably the shortest pathogenic allele for SCA8.
基金Supported by the National Natural Science Foundation of China(No.61304205,61502240)Natural Science Foundation of Jiangsu Province(BK20141002)+1 种基金Innovation and Entrepreneurship Training Project of College Students(No.201710300051,201710300050)Foundation for Excellent Undergraduate Dissertation(Design) of Naning University of Information Science & Technology
文摘Abnormal driving behavior identification( ADBI) has become a research hotspot because of its significance in driver assistance systems. However,current methods still have some limitations in terms of accuracy and reliability under severe traffic scenes. This paper proposes a new ADBI method based on direction and position offsets,where a two-factor identification strategy is proposed to improve the accuracy and reliability of ADBI. Self-adaptive edge detection based on Sobel operator is used to extract edge information of lanes. In order to enhance the efficiency and reliability of lane detection,an improved lane detection algorithm is proposed,where a Hough transform based on local search scope is employed to quickly detect the lane,and a validation scheme based on priori information is proposed to further verify the detected lane. Experimental results under various complex road conditions demonstrate the validity of the proposed ADBI.
基金funded by the National Key Research and Development Program of China(No.2021YFF1200901)the National Natural Science Foundation of China(Nos.61721003,62133006,and 92268104)。
文摘The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/snRNA-seq)techniques,there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features.In this study,we build a unified liver cell atlas uniLIVER(http://lifeome.net/database/uniliver)by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets.Moreover,we introduce LiverCT,a machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of“variant”cellular states analogous to the sequence variants in genomic analysis.Applying LiverCT on liver cancer datasets,we find that the“deviated”states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma,and the enrichments of tumor cells with the hepatocyte-cholangiocyte“intermediate”states significantly indicate poor prognosis.Besides,we find that the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis.This reference atlas mapping framework can also be extended to any other tissues.
基金the financial support from National Key Research and Development Program of China(2021YFC2900500)Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(52161135301).
