RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

Heart Murmur Classification Using a Capsule Neural Network.

The healthcare industry has made significant progress in the diagnosis of heart conditions due to the use of intelligent detection systems such as electrocardiograms, cardiac ultrasounds, and abnormal sound diagnostics that use artificial intelligence (AI) technology, such as convolutional neural networks (CNNs). Over the past few decades, methods for automated segmentation and classification of heart sounds have been widely studied. In many cases, both experimental and clinical data require electrocardiography (ECG)-labeled phonocardiograms (PCGs) or several feature extraction techniques from the mel-scale frequency cepstral coefficient (MFCC) spectrum of heart sounds to achieve better identification results with AI methods. Without good feature extraction techniques, the CNN may face challenges in classifying the MFCC spectrum of heart sounds. To overcome these limitations, we propose a capsule neural network (CapsNet), which can utilize iterative dynamic routing methods to obtain good combinations for layers in the translational equivariance of MFCC spectrum features, thereby improving the prediction accuracy of heart murmur classification. The 2016 PhysioNet heart sound database was used for training and validating the prediction performance of CapsNet and other CNNs. Then, we collected our own dataset of clinical auscultation scenarios for fine-tuning hyperparameters and testing results. CapsNet demonstrated its feasibility by achieving validation accuracies of 90.29% and 91.67% on the test dataset.

Polymorphisms in the promoter regions of RHD and RHCE genes in the Chinese Han population.

BACKGROUND AND OBJECTIVES: The Rh blood group system is the most polymorphic human blood group system. Previous studies have investigated variants in the RHD and RHCE promoter. The relevance of these variants to the Chinese Han population is further clarified in this study. MATERIALS AND METHODS: In total, 317 donors (223 Rh D-positive [D+], including 20 Del and 94 Rh D-negative [D-]) were randomly selected. The promoter regions and exon 1 of RHD and RHCE were amplified through polymerase chain reaction (PCR) whose products were directly sequenced using forward and reverse primers. RESULTS: Expected PCR products of the RHD promoter and exon 1 were amplified in 223 D+ individuals, including 20 Del individuals, and were absent in 81 of 94 D- individuals. Expected PCR products of RHCE were observed in all donors. Two single nucleotide variants (SNVs) were observed in the RHD promoter region. Moreover, 11 SNVs were observed in the promoter and exon 1 of RHCE. rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, rs2072931 and rs586178 with strong linkage disequilibria were significantly different between the D+ and D- groups. [A;C] was the most common haplotype in the RHD promoter (NC_000001.11:g.[-1033A>G;-831C>T]). [G;T;T;A;T;A;C;G;A;C;G] was the most predominant haplotype in both total and D- groups. In D+ individuals, [A;C;T;G;C;G;C;G;C;C;C] was the most frequent haplotype in the RHCE promoter (NC_000001.11:g.[-1080A>G;-958C>T;-390T>C;-378G>A;-369C>T;-296G>A;-144C>G;-132G>A;-122C>A;28C>T;48C>G]). CONCLUSION: We speculate that the SNVs/haplotypes found in this article cannot significantly affect gene expression. The present study findings should help elucidate the molecular basis of the polymorphic expression of RHD and RHCE promoter regions.

Structures of the human Wilson disease copper transporter ATP7B.

The P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive disorder of copper metabolism. Here, we present cryoelectron microscopy (cryo-EM) structures of human ATP7B in the E1 state in the apo, the putative copper-bound, and the putative cisplatin-bound forms. In ATP7B, the N-terminal sixth metal-binding domain (MBD6) binds at the cytosolic copper entry site of the transmembrane domain (TMD), facilitating the delivery of copper from the MBD6 to the TMD. The sulfur-containing residues in the TMD of ATP7B mark the copper transport pathway. By comparing structures of the E1 state human ATP7B and E2-Pi state frog ATP7B, we propose the ATP-driving copper transport model of ATP7B. These structures not only advance our understanding of the mechanisms of ATP7B-mediated copper export but can also guide the development of therapeutics for the treatment of WD.

Electrophysiological evidence for the characteristics of implicit self-schema and other-schema in patients with major depressive disorder: An event-related potential study.

Background: The significance of implicit self-schema and other-schema in major depressive disorder (MDD) is highlighted by both cognitive theory and attachment theory. The purpose of the current study was to investigate the behavioral and event-related potential (ERP) characteristics of implicit schemas in MDD patients. Methods: The current study recruited 40 patients with MDD and 33 healthy controls (HCs). The participants were screened for mental disorders using the Mini-International Neuropsychiatric Interview. Hamilton Depression Rating Scale-17 and Hamilton Anxiety Rating Scale-14 were employed to assess the clinical symptoms. Extrinsic Affective Simon Task (EAST) was conducted to measure the characteristics of implicit schemas. Meanwhile, reaction time and electroencephalogram data were recorded. Results: Behavioral indexes showed that HCs responded faster to positive self and positive others than negative self (t = -3.304, p = 0.002, Cohen's d = 0.575) and negative others (t = -3.155, p = 0.003, Cohen's d = 0.549), respectively. However, MDD did not show this pattern (p > 0.05). The difference in other-EAST effect between HCs and MDD was significant (t = 2.937, p = 0.004, Cohen's d = 0.691). The ERP indicators of self-schema showed that under the condition of positive self, the mean amplitude of LPP in MDD was significantly smaller than that in HCs (t = -2.180, p = 0.034, Cohen's d = 0.902). The ERP indexes of other-schema showed that HCs had a larger absolute value of N200 peak amplitude for negative others (t = 2.950, p = 0.005, Cohen's d = 0.584) and a larger P300 peak amplitude for positive others (t = 2.185, p = 0.033, Cohen's d = 0.433). The above patterns were not shown in MDD (p > 0.05). The comparison between groups found that under the condition of negative others, the absolute value of N200 peak amplitude in HCs was larger than that in MDD (t = 2.833, p = 0.006, Cohen's d = 1.404); under the condition of positive others, the P300 peak amplitude (t = -2.906, p = 0.005, Cohen's d = 1.602) and LPP amplitude (t = -2.367, p = 0.022, Cohen's d = 1.100) in MDD were smaller than that in HCs. Conclusion: Patients with MDD lack positive self-schema and positive other-schema. Implicit other-schema might be related to abnormalities in both the early automatic processing stage and the late elaborate processing stage, while the implicit self-schema might be related only to the abnormality in the late elaborate processing stage.

Acute-Onset Visual Impairment in Wilson's Disease: A Case Report and Literature Review.

Objective: We reported the case of a patient with Wilson's disease (WD) with acute-onset visual impairment and summarized previously reported cases to make physicians aware of the complicated clinical expressions of WD and improve diagnosis efficiency. Methods: The patient was recruited from the Second Affiliated Hospital of Zhejiang University School of Medicine. Clinical data, including cranial images, laboratory tests, and ophthalmic findings were obtained. The PubMed database was searched for published cases of WD with visual impairment. Results: We reported a 22-year-old male who presented with hand tremor, personality change, and acute-onset binocular vision blurring. WD was considered to be closely correlated with neuropsychiatric and ocular involvements. After low-copper diet and regular copper-chelation therapy, the related symptoms improved compared to before. Six WD cases of optic neuropathy have been reported, including ours. The patients usually had neurological and/or hepatic symptoms for a period without any treatment. All the reported cases manifested as acute episodes of visual changes, and the ocular manifestations improved after copper-chelation treatment. Conclusions: Excess copper accumulation may be a rare cause of visual impairment in patients with WD. While the etiology behind patients' acute-onset visual impairment remained uncertain, the possibility of WD should be considered through neuropsychiatric and hepatic symptoms, corneal K-F rings, decreased serum ceruloplasmin, and low likelihood or exclusion of other causes. Clinicians need to recognize this rare manifestation and give appropriate treatment to avoid misdiagnosis and unnecessary overtreatment.

Serum Neurofilament Light Chain in Wilson's Disease: A Promising Indicator but Unparallel to Real-Time Treatment Response.

BACKGROUND: Wilson's disease (WD) currently lacks a promising indicator that could reflect neurological impairment and monitor treatment outcome. We aimed to investigate whether serum neurofilament light chain (sNfL) functions as a candidate for disease assessment and treatment monitoring of WD. METHODS: We assessed preclinical and manifested WD patients' sNfL levels compared to controls and analyzed the differences between patients with various clinical symptoms. We then explored the correlation between clinical scales and sNfL levels. And repeated measurements were performed in 34 patients before and after treatment. RESULTS: WD patients with neurological involvement had significantly higher sNfL levels than both hepatic patients and controls. Positive correlations were found between Unified Wilson's Disease Rating Scale scores and sNfL and between semiquantitative magnetic resonance imaging scales and sNfL levels in WD patients. However, in the treatment follow-up analysis, the trend of sNfL before and after treatment disaccorded with clinical response. CONCLUSION: These findings suggest that sNfL levels can be an ideal indicator for the severity of neurological involvement but fail to evaluate change in disease condition after treatment. © 2022 International Parkinson and Movement Disorder Society.

Slow saturable absorption for optimal operation in a soliton comb laser.

In this article, we study how the choice of parameters of a slow saturable absorber (SSA) affects the stable operation of a soliton fiber comb laser. We show that a shorter recovery time for the SSA does not always lead to shorter modelocked pulses. Instead, increasing the cavity gain plays a critical role in generating stable modelocked pulses with higher energy and shorter durations. We find that more stable, shorter, and more energetic output pulses can be achieved with lower saturation energies of the SSA and/or higher anomalous dispersion within the cavity.

Prevalent Pathogenic Variants of ATP7B in Chinese Patients with Wilson's Disease: Geographical Distribution and Founder Effect.

Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the ATP7B gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (p < 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.