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Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

Abstract Background Deafness autosomal dominant 2A (DFNA2A) is related to non‐syndromic genetic hearing impairment. The KCNQ4 (Potassium Voltage‐Gated Channel Subfamily Q Member 4) can lead to DFNA2A. In this study, we report a case of autosomal dominant non‐syndromic hearing loss with six family members as caused by a novel variant in the KCNQ4 gene. Methods The whole‐exome sequencing (WES) and pure tone audiometry were performed on the proband of the family. Sanger sequencing was conducted on family members to determine if the novel variant in the KCNQ4 gene was present. Evolutionary conservation analysis and computational tertiary structure protein prediction of the wild‐type KCNQ4 protein and its variant were then performed. In addition, voltage‐gated channel activity of the wild‐type KCNQ4 protein and its variant were tested using whole‐cell patch clamp. Results It was observed that the proband had inherited autosomal dominant, non‐syndromic sensorineural hearing loss as a trait. A novel co‐segregating heterozygous missense variant (c.902C>A, p.Ala301Asp) of the KCNQ4 gene was identified in the proband and other five affected family members. This variant was predicted to cause an alanine‐to‐aspartic acid substitution at position 301 in the KCNQ4 protein. The alanine at position 301 is well conserved across different species. Whole‐cell patch clamp showed that there was a significant difference between the WT protein currents and the mutant protein currents in the voltage‐gated channel activity. Conclusion In the present study, performing WES in conjunction with Sanger sequencing enhanced the detection of a novel, potentially causative variant (c301 A>G; p.Ala301Asp) in exon 6 of the KCNQ4 gene. Therefore, our findings contributed to the mutation spectrum of the KCNQ4 gene and may be useful in the diagnosis and gene therapy of deafness autosomal dominant 2A.

To investigate highway vehicle lane-changing behavior, we utilized the publicly available naturalistic driving dataset, HighD, to extract the movement data of vehicles involved in lane changes and their proximate counterparts. We employed univariate and multivariate Cox proportional hazards models alongside random survival forest models to analyze the influence of various factors on lane change duration, assess their statistical significance, and compare the performance of multiple random survival forest models. Our findings indicate that several variables significantly impact lane change duration, including the standard deviation of lane-changing vehicles, lane-changing vehicle speed, distance to the following vehicle in the target lane, lane-changing vehicle length, and distance to the following vehicle in the current lane. Notably, the standard deviation and vehicle length act as protective factors, with increases in these variables correlating with longer lane change durations. Conversely, higher lane-changing vehicle speeds and shorter distances to following vehicles in both the current and target lanes are associated with shorter lane change durations, indicating their role as risk factors. Feature variable selection did not substantially improve the training performance of the random survival forest model based on our findings. However, validation set evaluation showed that careful feature variable selection can enhance model accuracy, leading to improved AUC values. These insights lay the groundwork for advancing research in predicting lane-changing behaviors, understanding lane-changing intentions, and developing pre-emptive safety measures against hazardous lane changes.

Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1. Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH.

Objectives: This study aims to investigate whether circulating ADAMTS13 activity can offer insights into the mechanism of pathophysiological changes in deep medullary veins (DMVs). Methods: This study was conducted on a community cohort of elderly individuals in Shanghai. Plasma von Willebrand factor (VWF) levels and ADAMTS13 activity were measured. A validated DMV score described the overall burden of DMV on the brain. Through ordinal regression models, we investigated the correlation between VWF levels, ADAMTS13 activity, and increasing severity of DMV score while adjusting for demographics and cardiovascular risk factors. Results: The study enrolled 262 subjects according to the inclusion criteria. The mean VWF level (1.35 ± 0.25) was higher in the DMV group than in the group without DMV (1.25 ± 0.30) (p = 0.025), and ADAMTS13 activity (83.76 ± 7.96) was relatively lower. After adjusting for age, sex, alcohol consumption, smoking, hypertension, and diabetes, reduced ADAMTS13 activity [β = −7.78; 95 % CI (−10.21, −5.35) p