Adaptive Reflection Detection and Control Strategy of Pointer Meters Based on YOLOv5s.

Reflective phenomena often occur in the detecting process of pointer meters by inspection robots in complex environments, which can cause the failure of pointer meter readings. In this paper, an improved k-means clustering method for adaptive detection of pointer meter reflective areas and a robot pose control strategy to remove reflective areas are proposed based on deep learning. It mainly includes three steps: (1) YOLOv5s (You Only Look Once v5-small) deep learning network is used for real-time detection of pointer meters. The detected reflective pointer meters are preprocessed by using a perspective transformation. Then, the detection results and deep learning algorithm are combined with the perspective transformation. (2) Based on YUV (luminance-bandwidth-chrominance) color spatial information of collected pointer meter images, the fitting curve of the brightness component histogram and its peak and valley information is obtained. Then, the k-means algorithm is improved based on this information to adaptively determine its optimal clustering number and its initial clustering center. In addition, the reflection detection of pointer meter images is carried out based on the improved k-means clustering algorithm. (3) The robot pose control strategy, including its moving direction and distance, can be determined to eliminate the reflective areas. Finally, an inspection robot detection platform is built for experimental study on the performance of the proposed detection method. Experimental results show that the proposed method not only has good detection accuracy that achieves 0.809 but also has the shortest detection time, which is only 0.6392 s compared with other methods available in the literature. The main contribution of this paper is to provide a theoretical and technical reference to avoid circumferential reflection for inspection robots. It can adaptively and accurately detect reflective areas of pointer meters and can quickly remove them by controlling the movement of inspection robots. The proposed detection method has the potential application to realize real-time reflection detection and recognition of pointer meters for inspection robots in complex environments.

A copy number variation genotyping method for aneuploidy detection in spontaneous abortion specimens.

OBJECTIVE: Chromosomal abnormalities such as aneuploidy have been shown to be responsible for causing spontaneous abortion. Genetic evaluation of abortions is currently underperformed. Screening for aneuploidy in the products of conception can help determine the etiology. We designed a high-throughput ligation-dependent probe amplification (HLPA) assay to examine aneuploidy of 24 chromosomes in miscarriage tissues and aimed to validate the performance of this technique. METHODS: We carried out aneuploidy screening in 98 fetal tissue samples collected from female subjects with singleton pregnancies who experienced spontaneous abortion. The mean maternal age was 31.6 years (range: 24-43), and the mean gestational age was 10.2 weeks (range: 4.6-14.1). HLPA was performed in parallel with array comparative genomic hybridization, which is the gold standard for aneuploidy detection in clinical practices. The results from the two platforms were compared. RESULTS: Forty-nine out of ninety-eight samples were found to be aneuploid. HLPA showed concordance with array comparative genomic hybridization in diagnosing aneuploidy. CONCLUSION: High-throughput ligation-dependent probe amplification is a rapid and accurate method for aneuploidy detection. It can be used as a cost-effective screening procedure in clinical spontaneous abortions. © 2016 John Wiley & Sons, Ltd.

SNPscan as a high-performance screening tool for mutation hotspots of hearing loss-associated genes.

In the present study, to assess the feasibility of the SNPscan technique for mutation screening in patients with nonsyndromic hearing loss (NSHL) and neonatus in China, the SNPscan technique was compared with the SNaPshot screening system. Chinese patients (162) with NSHL were used as the experimental group and 276 children without HL were used as the control group, respectively. SNPscan detected molecular defects in 112 patients (68.5%). In this technique, 83 patients (51.2%) with homozygous or compound heterozygous had confirmed molecular etiology in the GJB2, SLC26A4, and MT-RNR1 genes. By contrast, SNaPshot detected molecular defects in 103 patients (63.6%). In this method, 72 subjects (44.4%) with HL were confirmed to have NSHL caused by these mutations. This study demonstrates that SNPscan performs equally well or better than earlier routine genotyping method for genetic hearing loss, with possibility of detecting a larger variety of mutation.

A modified multiplex ligation-dependent probe amplification method for the detection of 22q11.2 copy number variations in patients with congenital heart disease.

BACKGROUND: Copy number variations (CNVs) of chromosomal region 22q11.2 are associated with a subset of patients with congenital heart disease (CHD). Accurate and efficient detection of CNV is important for genetic analysis of CHD. The aim of the study was to introduce a novel approach named CNVplex®, a high-throughput analysis technique designed for efficient detection of chromosomal CNVs, and to explore the prevalence of sub-chromosomal imbalances in 22q11.2 loci in patients with CHD from a single institute. RESULTS: We developed a novel technique, CNVplex®, for high-throughput detection of sub-chromosomal copy number aberrations. Modified from the multiplex ligation-dependent probe amplification (MLPA) method, it introduced a lengthening ligation system and four universal primer sets, which simplified the synthesis of probes and significantly improved the flexibility of the experiment. We used 110 samples, which were extensively characterized with chromosomal microarray analysis and MLPA, to validate the performance of the newly developed method. Furthermore, CNVplex® was used to screen for sub-chromosomal imbalances in 22q11.2 loci in 818 CHD patients consecutively enrolled from Shanghai Children's Medical Center. In the methodology development phase, CNVplex® detected all copy number aberrations that were previously identified with both chromosomal microarray analysis and MLPA, demonstrating 100% sensitivity and specificity. In the validation phase, 22q11.2 deletion and 22q11.2 duplication were detected in 39 and 1 of 818 patients with CHD by CNVplex®, respectively. Our data demonstrated that the frequency of 22q11.2 deletion varied among sub-groups of CHD patients. Notably, 22q11.2 deletion was more commonly observed in cases with conotruncal defect (CTD) than in cases with non-CTD (P<0.001). With higher resolution and more probes against selected chromosomal loci, CNVplex® also identified several individuals with small CNVs and alterations in other chromosomes. CONCLUSIONS: CNVplex® is sensitive and specific in its detection of CNVs, and it is an alternative to MLPA for batch screening of pathogenetic CNVs in known genomic loci.

Loss-of-function mutations in filaggrin gene associate with psoriasis vulgaris in Chinese population.

Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent linkage analysis and immunohistochemical studies suggest the possible contribution of FLG to psoriatic susceptibility. However, no susceptibility variant in FLG gene associated with psoriasis (OMIM #177900) has been identified. In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in two IV patients and four apparently normal family members. We also genotyped p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous mutation in two patients, while no homozygous variant was found in 500 control individuals. After sequencing the entire coding region of FLG gene in 441 psoriasis patients, we identified another five mutations (p.R826X, p.W2583X, c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X was significantly associated with psoriasis (P < 0.05). Our data thus indicates an association of FLG with psoriasis in Chinese population.

Intelligent phase-transition MnO2 single-crystal shell enabling a high-capacity Li-rich layered cathode in Li-ion batteries.

Layered, Li-rich Mn-based oxides (LLMOs) are the most promising next-generation, high-energy batteries due to their relatively high specific capacities and high voltages. However, the practical application of LLMO cathodes is limited by low initial coulombic efficiencies (CEs) and poor cycling performance. Herein, we used the reaction of KMnO4 and MnSO4 under hydrothermal conditions to grow a nano-SCMO shell on the LLMO material surface (SCMO@LLMO). The unique particle/sheet compound structure of the SCMO shell is beneficial to the electrochemical reaction. SCMO has good Li storage characteristics and excellent surface structure stability in the single-crystal phase which further improves the reversible capacity, CE, and cyclic stability of the LLMO cathode. Therefore, the optimal coated sample (feedstock: 2 M KMnO4, SCMO@LLMO-2.0) exhibits a good initial discharge capacity (238.2 mA h g-1 at 1C and 173.8 mA h g-1 at 5C), initial CE (89.6% at 1C and 86.5% at 5C), and cycling performance (capacity retention of 84.67% at 1C and 62.72% at 5C after 200 cycles). This work adopts a hydrothermal method to synthesize a nano-single crystal composite material, laying a foundation for the preparation of the SCMO@LLMO cathodes for LLMO primary battery cathodes with high electrochemical performance.

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

PURPOSE: Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. METHODS: We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. RESULTS: The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. CONCLUSIONS: Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

A rapid improved multiplex ligation detection reaction method for the identification of gene mutations in hereditary hearing loss.

Hearing loss (HL) is a common sensory disorder. More than half of HL cases can be attributed to genetic causes. There is no effective therapy for genetic HL at present, early diagnosis to reduce the incidence of genetic HL is important for clinical intervention in genetic HL. Previous studies have identified 111 nonsyndromic hearing loss genes. The most frequently mutated genes identified in NSHL patients in China include GJB2, SLC26A4, and the mitochondrial gene MT-RNR1. It is important to develop HL gene panels in Chinese population, which allow for etiologic diagnosis of both SHL and NSHL. In this study, a total of 220 unrelated Han Chinese patients with bilateral progressive SNHL and 50 unrelated healthy controls were performed Single nucleotide polymorphism (SNP) genotyping using an improved multiplex ligation detection reaction (iMLDR) technique, is to simultaneously detect a total of 32 mutations in ten HL genes, covering all currently characterized mutations involved in the etiology of nonsyndromic or syndromic hearing loss in the Chinese population. The 49 positive samples with known mutations were successfully detected using the iMLDR Technique. For 171 SNHL patients, gene variants were found in 57 cases (33.33%), among which, 30 patients carried mutations in GJB2, 14 patients carried mutations in SLC26A4, seven patients carried mutations in GJB3, and six patients carried mutations in MT-RNR1. The molecular etiology of deafness was confirmed in 12.9% (22/171) of patients carried homozygous variants. These results were verified by Sanger sequencing, indicating that the sensitivity and specificity of the iMLDR technique was 100%. We believe that the implementation of this population-specific technology at an efficient clinical level would have great value in HL diagnosis and treatment.

The Association between Metabolic Syndrome and Morbid Events in Type 2 Diabetes after a 7-Year Community Management: Beijing Community Diabetes Study 17.

BACKGROUND: To examine the association between morbid events and metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM). METHODS: A prospective, longitudinal, multicenter study was conducted at 13 community health centers associated with Beijing Tongren Hospital. From 2008 to 2015, there have been 3,525 T2DM patients being managed based on the Chinese guideline for T2DM. The morbid events included macrovascular events, diabetic kidney disease, ophthalmologic events, cancer, and all-cause death. RESULTS: At baseline, there were 2,708 people with MS and 817 without MS. After a seven-year management, there were 351 (12.96%) events in MS people and 74 (9.06%) events in people without MS (p = 0.003). The prevalence of macrovascular events (6.06%) was much higher in MS people than in people without MS (3.79%, p = 0.013). Cox regression analysis showed an association between MS and morbid events even after adjusting for confounding variables (adjusted hazard ratio = 1.44). MS was also associated with macrovascular events (adjusted hazard ratio = 1.96). The occurrence of morbid events and macrovascular events was increased when the numbers of metabolic abnormalities were 1, 2, 3, and 4 (p < 0.001). There was no continuously statistically significant difference in the cumulative prevalence of morbid events between patients with MS and patients without MS during the first five years. However, after six or seven years, the cumulative prevalence of morbid events in patients with MS was continuously significantly higher than that in patients without MS (11.00% vs. 8.20%, 12.96% vs. 9.06%, p < 0.05). CONCLUSIONS: T2DM with MS had higher incidence of morbid events, especially cardiovascular events, even after integrated management. The occurrence of morbid and macrovascular events increased as the number of metabolic abnormalities increased. MS was associated with increased risk of morbid events by 44% and macrovascular events by 96%. It would take at least six years to observe the association between MS and morbid events in T2DM.

The effects of cardiovascular risk factor combined anti-platelet therapy and the risk of cerebrovascular events in patients with T2DM in an urban community over 96-months follow-up: The Beijing communities diabetes study 19.

OBJECTIVE: We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. METHODS: A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. RESULTS: During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. CONCLUSIONS: This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. TRIAL REGISTRATION: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

The effects of AER and eGFR on outcomes of CVD in patients with T2DM in an urban community over 8 years of multifactorial treatment: the Beijing Communities Diabetes Study 18.

OBJECTIVE: It is well known that diabetic kidney disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). In this study, the effects of urine albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population of T2DM. METHODS: The study was carried out using recorded information of a cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were enrolled in an 8 years prospective study and received multifactorial intervention. The risk of CVD outcomes was assessed according to chronic kidney disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2). The effects of AER and eGFR on risk of CVD onset were also analyzed. RESULTS: During the follow-up period (median 6.8 years), 71 CVD events occurred. At baseline, those with AER ≥300 mg/d and coexisting eGFR 60-89 mL/min/1.73 m2 or <60 mL/min/1.73 m2 showed increased risk for CVD outcomes when compared with "no chronic kidney disease" (AER <30 mg/d and eGFR ≥90 mL/min/1.73 m2). The increased CVD risk was observed in patients who progressed to AER ≥30 mg/d during the follow-up period, whereas patients who progressed to eGFR <90 mL/min/1.73 m2 alone showed no increased CVD risk. During the follow-up period, after multifactorial intervention, 8.7% patients with microalbuminuria and 1.8% patients with overt nephropathy reversed to normoalbuminuria or microalbuminuria. CONCLUSION: AER is a more sensitive predictor than eGFR for CVD outcomes in T2DM patients. Overt nephropathy can be reversed after multifactorial intervention.

A New Genetic Diagnostic for Enlarged Vestibular Aqueduct Based on Next-Generation Sequencing.

Enlarged vestibular aqueduct (EVA) is one of the most common congenital inner ear malformations and accounts for 1-12% of sensorineural deafness in children and adolescents. Multiple genetic defects contribute to EVA; therefore, early molecular diagnosis is critical for EVA patients to ensure that the most effective treatment strategies are employed. This study explored a new genetic diagnosis method for EVA and applied it to clinic diagnoses of EVA patients. Using next-generation sequencing technology, we set up a multiple polymerase chain reaction enrichment system for target regions of EVA pathogenic genes (SLC26A4, FOXI1, and KCNJ10). Forty-six EVA samples were sequenced by this system. Variants were detected in 87.0% (40/46) of cases, including three novel variants (SLC26A4 c.923_929del, c.1002-8C>G, and FOXI1 c.519C>A). Biallelic potential pathogenic variants were detected in 27/46 patient samples, leading to a purported diagnostic rate of 59%. All results were verified by Sanger sequencing. Our target region capture system was validated to amplify and measure SLC26A4, FOXI1, and KCNJ10 in one reaction system. The result supplemented the mutation spectrum of EVA. Thus, this strategy is an economic, rapid, accurate, and reliable method with many useful applications in the clinical diagnosis of EVA patients.

Mutation analysis of the NRXN1 gene in a Chinese autism cohort.

Autism is a brain developmental disorder characterized by impaired social interaction and communication, as well as restricted and repetitive behaviors. The neurexin-1(NRXN1) gene mapped on chromosome 2p16.3 encodes neurexin, a cell adhesion molecule and receptor in the vertebrate nervous system. Rare de novo alterations and copy number variations (CNVs) suggested neurexin-1 as a candidate gene for the pathogenesis of autism, but data on the gene mutation of neurexin-1 in Chinese Han population with autism are limited. By direct sequencing, we analyzed the entire coding regions and associated splice junctions of neurexin-1 in 313 Chinese autism patients. For exons in which non-synonymous variants were identified, sequencing was performed in 500 healthy controls. We identified 22 variants in the neurexin-1 coding regions, including 7 missense variants, 3 deletions, and 12 synonymous mutations. Among them, 3 missense and 3 synonymous variants were not reported in the dbSNP database and absent in 500 control subjects; whereas 4 missense variants, 3 deletions and 3 synonymous mutations were not reported in the dbSNP database but were identified in the control subjects. However, there is no significant association of these mutations with autism risk. Interestingly, there was a statistically significant association of neurexin-1 SNP P300P (rs2303298) with risk of autism (26.2% vs. 13.8%; χ(2) = 22.487; p = 3.45E-006; OR = 2.152 (1.559-2.970)). Our data suggest a possible association of neurexin-1 with autism risk in Chinese Han population, warranting further large-scale study on this gene.

A novel locus for congenital simple microphthalmia family mapping to 17p12-q12.

PURPOSE: To investigate the etiology in a family with autosomal-dominant congenital simple microphthalmia of Chinese origin. METHODS: A whole-genome scan was performed by using 382 microsatellite DNA markers after the exclusion of reported candidates linked to microphthalmia. Additional fluorescent markers were genotyped for fine mapping. To find out the novel predisposing gene, 14 candidate genes including CRYBA1 and NCOR1 were selected to screen for the mutation by the PCR direct-sequencing method. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed to find out the pathogenetic copy number variation, as well. RESULTS: The most statistically significant linkage results were obtained at D17S1824 (maximum LOD score, 4.97, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene to a 21.57-cM interval between loci D17S900 and D17S1872 of chromosome 17, region p12-q12. However, no mutation or CNV (copy number variation) was identified to be responsible for the microphthalmia phenotype of this pedigree. CONCLUSIONS: A novel suggestive linkage locus for congenital microphthalmia was detected in a Chinese family. This linkage region provides a target for susceptibility gene identification.

Genetic screening for mutations in the Nrdp1 gene in Parkinson disease patients in a Chinese population.

Strong evidence has shown that a defect in the Parkin gene is known to be a common, genetic cause of Parkinson disease (PD). The E3 ubiquitin ligase Nrdp1 is shown to interact with the N terminal of Parkin (the first 76 amino acids) and catalyze degradation of Parkin via the ubiquitin-proteasome pathway, suggesting that Nrdp1 may be involved in the development of PD via the regulation of Parkin, We believe we are the first to have screened PD patients for mutations in the Nrdp1 gene to determine the association between these variants and PD. By direct sequencing, we analysed the entire coding regions and 5' UTR of Nrdp1 in 209 Chinese PD patients and 302 unrelated healthy individuals. No variant was detected in the coding regions (exons 3-7); only 2 variants (c.-206 T > A and c.-208-8 A > G) were identified in the 5' UTR (exon 2) and intron 1. Furthermore, a study of the allelic and genotypic association between patients and controls showed no significant association between the c.-206 T > A polymorphism and PD; c.-208-8 A > G was identified in one PD patient and not in controls. Our data do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population.