Disorders of sexual development (DSD) are estimated to occur in 1 of 4500 births. Since the genetic etiology of DSD is highly heterogeneous, obtaining a definitive molecular diagnosis by single gene test is challenging. Utilizing a high-throughput sequencing upfront is proposed as an efficient approach to aid in the diagnosis. This study aimed to examine the diagnostic yield of next-generation sequencing in DSD. 32 DSD patients that previously received clinical examinations and single gene tests were selected, with or without a diagnosis. Prior single gene tests were masked, and then samples went through targeted next-generation sequencing of 80 genes from which the diagnostic yield was assessed. A likely diagnosis, with pathogenic or likely pathogenic variants identified, was obtained from nine of the 32 patients (i.e., 28.1%, versus 10% by single gene tests). In another five patients (15.6%), variants of uncertain significance were found. Among 18 variants identified (i.e., 17 single nucleotide variants and one small deletion), eight had not been previously reported. This study supports the notion that next-generation sequencing can be an efficient tool in the clinical diagnosis and variant discovery in DSD.

Developmental delay (DD) and intellectual disability (ID) are frequently associated with a broad spectrum of additional phenotypes. Chromosomal microarray analysis (CMA) has been recommended as a first-tier test for DD/ID in general, whereas the diagnostic yield differs significantly among DD/ID patients with different comorbid conditions. To investigate the genotype-phenotype correlation, we examined the characteristics of identified pathogenic copy number variations (pCNVs) and compared the diagnostic yields among patient subgroups with different co-occurring conditions. This study is a retrospective review of CMA results generated from a mixed cohort of 710 Chinese patients with DD/ID. A total of 247 pCNVs were identified in 201 patients (28%). A large portion of these pCNVs were copy number losses, and the size of copy number losses was generally smaller than gains. The diagnostic yields were significantly higher in subgroups with co-occurring congenital heart defects (55%), facial dysmorphism (39%), microcephaly (34%) or hypotonia (35%), whereas co-occurring conditions of skeletal malformation (26%), brain malformation (24%) or epilepsy (24%) did not alter the yield. In addition, the diagnostic yield nominally correlated with ID severity. Varied yields exist in DD/ID patients with different phenotypic presentation. The presence of comorbid conditions can be among factors to consider when planning CMA.

Background: To summarize the relationship between different MMUT gene mutations and the response to vitamin B12 in MMA.Methods: This was a retrospective study of patients diagnosed with mut‐type MMA. All patients with mut‐type MMA were tested for responsiveness to vitamin B12.Results: There were 81, 27, and 158 patients in the completely responsive, partially responsive, and nonresponsive groups, respectively, and the proportions of symptom occurrence were 30/81 (37.0%), 21/27 (77.8%), and 131/158 (82.9%), respectively (p < .001). The median levels of posttreatment propionyl carnitine (C3), C3/acetyl carnitine (C2) ratio in the blood, and methylmalonic acid in the urine were all lower than pretreatment, and the median level of C3/C2 ratio in the completely responsive group was within the normal range. In 266 patients, 144 different mutations in the MMUT gene were identified. Patients with the mutations of c.1663G>A, c.2080C>T, c.1880A>G, c.1208G>A, etc. were completely responsive and with the mutations of c.1741C>T, c.1630_1631GG>TA, c.599T>C, etc. were partially responsive. The proportions of healthy/developmental delay outcomes in the three groups were 63.0%/23.5%, 33.3%/40.7%, and 13.3%/60.1%, respectively (p < .001).Conclusion: Different mutations in the MMUT gene are associated with the effect of vitamin B12 treatment.

Fractal dimension, as a common nonlinear dynamics metric, is extensively applied in biomedicine, fault diagnosis, underwater acoustics, etc. However, traditional fractal dimension can only analyze the complexity of the time series given a single channel at a particular scale. To characterize the complexity of multichannel time series, multichannel information processing was introduced, and multivariate Higuchi fractal dimension (MvHFD) was proposed. To further analyze the complexity at multiple scales, multivariate multiscale Higuchi fractal dimension (MvmHFD) was proposed by introducing multiscale processing algorithms as a technology that not only improved the use of fractal dimension in the analysis of multichannel information, but also characterized the complexity of the time series at multiple scales in the studied time series data. The effectiveness and feasibility of MvHFD and MvmHFD were verified by simulated signal experiments and real signal experiments, in which the simulation experiments tested the stability, computational efficiency, and signal separation performance of MvHFD and MvmHFD, and the real signal experiments tested the effect of MvmHFD on the recognition of multi-channel mechanical signals. The experimental results show that compared to other indicators, A achieves a recognition rate of 100% for signals in three features, which is at least 17.2% higher than for other metrics.

Background: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, with cblC (cblC-MMA) and mut (mut-MMA) being the predominant subtypes. The present study aimed to investigate the prognostic manifestations and their possible influence in patients with these two subtypes. Methods: A national multicenter retrospective study of patients with cblC-MMA and mut-MMA between 2004 and 2022 was performed. We compared the clinical features between patients with two subtypes or diagnosed with or without newborn screening (NBS) and further explored the potentially influential factors on the prognosis. Results: The 1617 enrolled MMA patients included 81.6% cblC-MMA patients and 18.4% mut-MMA patients, with an overall poor prognosis rate of 71.9%. These two subtypes of patients showed great differences in poor prognostic manifestations. The role of NBS in better outcomes was more pronounced in cblC-MMA patients. Predictors of outcomes are “pre-treatment onset”, “NBS”, variants of c.80A > G and c.482G > A and baseline levels of propionylcarnitine and homocysteine for cblC-MMA; “pre-treatment onset”, “responsive to vitB12”, variants of c.914T > C and baseline propionylcarnitine and propionylcarnitine/acetylcarnitine ratio for mut-MMA. Besides, prognostic biochemical indicators have diagnostic value for poor outcomes in mut-MMA. Conclusions: The study provided potential predictors of the long-term outcome of patients with cblC-MMA and mut-MMA. Impact: Predictors of outcomes are “pre-treatment onset”, “NBS”, MMACHC variants of c.80A > G and c.482G > A and baseline propionylcarnitine and homocysteine for cblC-MMA, “pre-treatment onset”, “responsive to vitB12”, MMUT variants of c.914T > C and baseline propionylcarnitine and propionylcarnitine/acetylcarnitine ratio for mut-MMA. This study with larger sample sizes effectively validated the prediction power and emphasized the importance of NBS in improving the outcomes of both MMA subtypes. The study enhances understanding of the phenotypic and prognostic variations of MMA disease and the predictors will help in the improvement of diagnosis and treatment strategies to achieve a better prognosis for MMA.

The ship-radiated noise (SN) is easily affected by other hydroacoustic objects or complex ocean noise when it spreads through water. In order to reduce the impact from the environment, a denoising method for SN based on optimized variational mode decomposition with snake optimization (SO-VMD) and dual-threshold criteria of correlation coefficient (CC) is proposed in this paper. The first step is to optimize the parameter combination, that is, decomposition number K and penalty factor α, of variational mode decomposition (VMD) by snake optimization (SO) with envelope entropy (EE). Then, the input signal using the optimized results is decomposed and the intrinsic mode functions (IMFs) are obtained. After that, the IMFs are classified into three classes with the dual-threshold criteria of CC, including signal components, signal-noise components, and noise components. Finally, all the signal components and the processed signal-noise components denoised by wavelet threshold (WT) are reconstructed together. Simulations performed in this paper demonstrate that SO is the more appropriate optimization for VMD and the proposed method has the more outstanding performance in denoising different kinds of test signals. In addition, experiments on measured SNs show that the proposed method is effective and accurate in denoising.