Differentiating biliary atresia from other causes of neonatal cholestasis is challenging, particularly when cytomegalovirus (CMV) and biliary atresia occur simultaneously. We aimed to elucidate ...whether CMV infection would affect the differential diagnosis of biliary atresia and intrahepatic cholestasis.
This retrospective study was conducted among patients with neonatal cholestasis admitted to three tertiary hospitals between January 2010 and August 2019. The clinical characteristics, laboratory, and imaging findings were recorded. On the basis of the CMV serology results, the infants were classified into CMV-IgM (+) and CMV-IgM (−) groups. The clinical differences and diagnostic performances of routine predictors between biliary atresia and intrahepatic cholestasis were analyzed in each group. Finally, we compared the diagnostic performances of various tests in the two groups.
A total of 705 patients with neonatal cholestasis were enrolled: 215 (30.5%) patients were positive for CMV-IgM, among whom 97 had biliary atresia and 118 had CMV hepatitis; 490 infants were CMV-IgM (−), among whom 240 had biliary atresia and 250 had intrahepatic cholestasis. The diagnostic performances of stool color, direct bilirubin level, γ-glutamyl transpeptidase level, abnormal gallbladder, triangular cord sign, and hepatobiliary scintigraphy between CMV hepatitis and CMV-IgM (+) biliary atresia were similar to those between CMV-IgM (−) biliary atresia and CMV-IgM (−) intrahepatic cholestasis groups.
Our large-scale study showed a high prevalence of CMV infection in patients with neonatal cholestasis in China. The presence of CMV infection did not affect the routine predictors to discriminate biliary atresia and intrahepatic cholestasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Research on myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD) among Chinese children is relatively rare. Therefore, this study aimed to explore and analyze ...the clinical characteristics and prognoses of Chinese children with acquired demyelinating syndromes (ADSs) who tested positive or negative for MOG-Ab. Methods The clinical data of children with MOGAD who were treated in the Department of Neurology at Shanghai Children's Hospital from January 2017 to October 2021 were retrospectively collected. Results Among 90 children with ADSs, 30 were MOG-Ab-positive, and 60 were MOG-Ab-negative. MOG-Ab-positive children experienced more prodromal infections than did MOG-Ab-negative children (P < 0.05). Acute disseminated encephalomyelitis was the most common ADSs in both groups. There were ten cases of a rebound increase in MOG-Ab titers. There were significant differences in the MOG titer-related prognosis and disease time course between the disease relapse group and the non-relapse group (P < 0.01). Among the MOG-Ab-positive patients, the most affected brain areas detected via magnetic resonance imaging (MRI) were the temporal lobe, cerebellar hemispheres, brainstem, and periventricular lesions. The most common shapes of the lesions were commas, triangles, or patches. The average improvement time based on brain MRI was much longer in MOG-Ab-positive than in MOG-Ab-negative children (P < 0.05). The initial treatment time correlated with the disease time course, and the prognosis may be affected by the disease time course and serum MOG-Ab titer (P < 0.05). Conclusion The clinical characteristics and imaging features of ADSs differed between MOG-Ab-positive and MOG-Ab-negative children. In addition to existing treatment plans, additional diagnoses and treatment plans should be developed to reduce recurrence and improve the prognoses of children with MOGAD. Keywords: Myelin oligodendrocyte glycoprotein antibody, Acquired demyelinating syndromes, Clinical features, Prognosis, Children
Lysine acetyltransferase 6B (KAT6B) encodes a highly conserved histone acetyltransferase that regulates the expression of multiple genes and is essential for human growth and development.
We ...identified a novel frameshift variant c.3185del (p.leu1062Argfs*52) in a 5-year-old Chinese boy and further analyzed KAT6B expression and its interacting complexes and downstream products using real-time quantitative polymerase chain reaction (qPCR). Furthermore, we assessed its three-dimensional protein structure and compared the variant with other reported KAT6B variants.
The deletion changed the leucine at position 1062 into an arginine, resulting in translation termination after base 3340, which may have affected protein stability and protein-protein interactions. KAT6B mRNA expression levels in this case were substantially different from those of the parents and controls in the same age range. There were also significant differences in mRNA expression levels among affected children's parents. RUNX2 and NR5A1, downstream products of the gene, affect the corresponding clinical symptoms. The mRNA expression levels of the two in children were lower than those of their parents and controls in the same age range.
This deletion in KAT6B may affect protein function and cause corresponding clinical symptoms through interactions with key complexes and downstream products.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Proline-rich transmembrane protein 2 (PRRT2) plays an important role in the central nervous system and mutations in the gene are implicated in a variety of neurological disorders. This ...study aimed to summarize the clinical characteristics and gene expression analysis of neurological diseases related to the
PRRT2
gene and explore the clinical characteristics, therapeutic effects, and possible pathogenic mechanisms of related diseases.
Methods
We enrolled 10 children with
PRRT2
mutation-related neurological diseases who visited the Children's Hospital affiliated with the Shanghai Jiaotong University School of Medicine/Shanghai Children's Hospital between May 2017 and February 2022. Video electroencephalography (VEEG), cranial imaging, treatment regimens, gene results, and gene expression were analyzed. Genetic testing involved targeted sequencing or whole-exome genome sequencing (WES). We further analyzed the expression and mutation conservation of PRRT2 and synaptosome-associated protein 25 (SNAP25) in blood samples using quantitative polymerase chain reaction (qPCR) and predicted the protein structure. Summary analysis of the reported gene maps and domains was also performed.
Results
Ten children with
PRRT2
gene mutations were analyzed, and 4 mutations were identified, consisting of 2 new (c.518A > C, p.Glu173 Ala; c.879 + 112G > A, p.?) and two known (c. 649 dup, p. Arg217Profs * 8; c. 649 del, p. Arg217Glufs * 12) mutations. Among these mutations, one was
de novo
(P6), and three could not be determined because one parent refused genetic testing. The clinical phenotypes were paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), epilepsy, infantile spasms, and intellectual disability. The qPCR results showed that
PRRT2
gene expression levels were significantly lower in children and parent carriers than the control group. The
SNAP25
gene expression level of affected children was significantly lower (
P
≤ 0.001) than that of the control group. The mutation sites reported in this study are highly conserved in different species. Among the various drugs used, oxcarbazepine and sodium valproate were the most effective. All 10 children had a good disease prognosis, and 8 were completely controlled with no recurrence, whereas 2 had less severe and fewer seizures.
Conclusion
Mutation of
PRRT2
led to a significant decrease in its protein expression level and that of SNAP25, suggesting that the mutant protein may lead to the loss of its function and that of related proteins. This mutation site is highly conserved in most species, and there was no significant correlation between specific PRRT2 genotypes and clinical phenotypes. Asymptomatic carriers also have decreased gene expression levels, suggesting that more factors are involved.
The chromodomain helicase DNA-binding protein 2 (
) gene, is an ATPase and part of the
family of chromatin remodelers. Mutations in the
gene are inherited in an autosomal-dominant manner and can lead ...to intellectual disability, epilepsy, and autism. We investigated the clinical characteristics of
-related conditions and their possible pathogenesis.
We collected and analysed the clinical data of patients that were identified as having
mutations. Genetic testing was performed using targeted sequencing or whole-exome sequencing. We analysed the expression of
and repressor element 1-silencing transcription factor (
) in blood samples using quantitative PCR and the conservation of the mutations. The
mutations we identified were compared with the known mutations reported in the
-related literature.
Eight patients with
gene mutations were analysed. Six mutations were identified; four were unreported previously (c.670C>T; c.4012A>C; c.2416dup; c.1727-1728insAT), and two were known mutations: c.5035C>T (two cases) and c.4173dup (two cases). Among these mutations, seven were
mutations, and one could not be determined because the parents refused genetic testing. The clinical manifestations included mild or severe intellectual disability, epilepsy, and behavioural abnormalities. Quantitative PCR showed that the
gene expression levels among the patients, parents, and the controls were not significantly different. The levels of
gene expression in the patients were significantly higher than those of the controls; thus, mutation of the
gene led to an increase in the expression level of the
gene. The mutations reported were all located in conserved positions in different species. Among the various medications administered for treatment, valproate showed the best results for the treatment of epilepsy caused by
gene mutation.
Mutation in
did not lead to a significant decrease in its expression level, indicating that the clinical phenotype was unrelated to its expression level, and the mutant protein may retain some function. Most of the mutations relatively stable. In addition, the clinical manifestations from the same mutation in the
gene were different among the known cases; this may be related to the regulation of
or other regulatory factors.
Abstract
Recent advancements in spatial transcriptomics technology have revolutionized our ability to comprehensively characterize gene expression patterns within the tissue microenvironment, ...enabling us to grasp their functional significance in a spatial context. One key field of research in spatial transcriptomics is the identification of spatial domains, which refers to distinct regions within the tissue where specific gene expression patterns are observed. Diverse methodologies have been proposed, each with its unique characteristics. As the availability of spatial transcriptomics data continues to expand, there is a growing need for methods that can integrate information from multiple slices to discover spatial domains. To extend the applicability of existing single-slice analysis methods to multi-slice clustering, we introduce BiGATAE (Bipartite Graph Attention Auto Encoder) that leverages gene expression information from adjacent tissue slices to enhance spatial transcriptomics data. BiGATAE comprises two steps: aligning slices to generate an adjacency matrix for different spots in consecutive slices and constructing a bipartite graph. Subsequently, it utilizes a graph attention network to integrate information across different slices. Then it can seamlessly integrate with pre-existing techniques. To evaluate the performance of BiGATAE, we conducted benchmarking analyses on three different datasets. The experimental results demonstrate that for existing single-slice clustering methods, the integration of BiGATAE significantly enhances their performance. Moreover, single-slice clustering methods integrated with BiGATAE outperform methods specifically designed for multi-slice integration. These results underscore the proficiency of BiGATAE in facilitating information transfer across multiple slices and its capacity to broaden the applicability and sustainability of pre-existing methods.
Distinguishing biliary atresia from non-biliary atresia in patients with cholestasis is challenging, as these conditions have a similar clinical presentation. We developed and externally validated a ...screening model for biliary atresia and devised a web-based calculator for use in clinical settings.
A screening model was developed based on data from 227 cholestatic infants (82 and 145 with and without biliary atresia, respectively) and validated in 234 infants (90 and 144 with and without biliary atresia, respectively) admitted to three hospitals. Variables were selected from routine examination results using the least absolute shrinkage and selection operator method and entered into a logistic regression model to construct a biliary-atresia-risk-predicting equation. Cutoff values for risk stratification were estimated using model sensitivity, derived from the receiver-operating characteristic curves.
The final screening model included seven variables (i.e., weight at admission, clay-colored stools, γ-glutamyl transpeptidase and albumin levels at admission, abnormal gallbladder, triangular cord sign, and change in total bilirubin levels). The model generated an area under the curve of 0.94 with a sensitivity of 91.46 and specificity of 86.62 in the derivation cohort. This was confirmed in the validation cohort, as we found an area under the curve of 0.93 with a sensitivity of 93.1 and specificity of 80.15. Patients were stratified into three risk groups (low-, moderate-, and high-risk groups). Biliary atresia was excluded in the low-risk group. The high-risk group showed a higher detection rate of biliary atresia compared to the stool color screening method alone. This model was integrated into a user-friendly web-based system.
The screening tool had a high predictive value and may help in decision-making by physicians at tertiary and community hospitals.
•This study demonstrated that color-flavor congruency affected drink liking.•Congruency (vs. incongruency) of simultaneous colors and flavors enhanced liking.•Incongruency (vs. congruency) of ...successive colors and flavors increased alpha power.•The EEG results revealed the processing of conflict between color and flavor cues.
People often associate features or stimuli across senses, and these crossmodal correspondences also function as criteria for judging whether a pair of features or stimuli is crossmodally congruent or incongruent. We conducted two studies to examine whether the crossmodal congruency between a drink color and a flavor could also elicit more positive ratings of this drink. In Study 1, the experimental task was to simultaneously view a photo of a colored drink and to taste a beverage whose flavor was either congruent or incongruent with the color. Consequently, the color-flavor congruent drinks received more positive ratings than the color-flavor incongruent ones. In Study 2, we conducted an EEG experiment to investigate both behavioral and oscillatory brain responses to the crossmodal congruency between the successively presented color and flavor. The results of subjective ratings did not reveal any significant difference between the color-flavor congruent and incongruent stimuli. However, the time–frequency analyses on the EEG data revealed that rating the color-flavor incongruent beverages elicited greater alpha band power in the parietal region, compared to the color-flavor congruent stimuli. Collectively, these findings revealed the influence of color-flavor congruency on the subjective ratings of beverages, and demonstrated how this effect was modulated by the temporal synchrony of the color and flavor cues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Women scored higher than men on the centrality of visual product aesthetics (CVPA).•We examined the association between the CVPA and gray matter volume (GMV).•Women’s CVPA was positively correlated ...to GMV in the left mOFC and dorsal striatum.•Men’s CVPA scores were negatively correlated with GMV in the left mOFC.•Our results revealed gender difference in the association between the CVPA and GMV.
Visual aesthetics influence consumers’ perception, acquisition, and usage of products, but the level of significance that a commercial product’s visual aesthetics hold for each consumer varies from one person to another. Such individual difference is referred to as the centrality of visual product aesthetics (CVPA). Previous research has revealed that female adults scored higher than male adults in the self-reported CVPA scale. In order to identify the neuroanatomical correlates of this gender difference, we conducted a voxel-based morphometry (VBM) study to examine the association between the CVPA and gray matter volume (GMV) in a large sample of healthy adults from mainland China. The results revealed positive correlations between the female participants’ CVPA scores and the GMV in two brain areas liked to reward processing, namely the left medial orbitofrontal cortex (mOFC) and the left dorsal striatum. By contrast, the results revealed a negative correlation between the male participants’ CVPA scores and their GMV in the left mOFC. Collectively, these findings suggest that the level of significance that a commercial product’s visual aesthetics hold for consumers may be associated with the rewards that they are able to receive from them. These findings also provide empirical evidence about the neuroanatomical correlates of self-reported values.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To ensure the safe and efficient operation of electrical equipment, it is essential to study the micro-dynamic mechanisms and thermodynamic characteristics of the insulating oil emulsification ...process at the nanoscale. In this work, the behavior of water in insulating oil under various temperatures was visualized through a dynamic oil-water model using molecular dynamics (MD) simulations and in-situ observation. Quantitative analysis revealed temperature's influence on water droplet dynamics, exposing key details in nucleation and growth. The research findings indicate that the electrostatic shielding effect is critical in the nucleation process, and strong hydrogen bonding among water molecules promotes stable aggregate formation. Higher temperatures decrease the electrostatic shielding by the oil-water mixture and reduce molecular orderliness, decrease distances, and promote molecular collisions and nucleation. Furthermore, under sustained supersaturation, higher temperatures accelerate water molecules motion, boosting free water growth and facilitating the transition of water molecules from a free state to a dissolved state. The magnitude of nucleation rate was generally on the order of 10 35 m -3 ·s -1 and the growth rate was 0.3-1.8 m·s -1 in the simulated parameters range. These findings aid in understanding water issues in electrical equipment, improving design and operation for enhanced reliability and efficiency.
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