Optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies: A single-center retrospective cohort study

ObjectiveTo explore the optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies.MethodsA retrospective cohort study in a university hospital which included twins delivered from February 2013 to September 2020. Restrictive cubic spline (RCS) model was applied to the trend of intertwin birthweight difference (BWD) with the risk of preeclampsia. Logistic regression and subgroup analysis were performed to find the cut-off with statistical significance and clinical meaningfulness.ResultsA total of 2,631 women pregnant with twins were enrolled. RCS showed a nonlinear upward trend of preeclampsia with BWD, and the BWD of 15% was the initial rising point. With the confounders adjusted, only the group with BWD ≥ 25% was found to be significantly associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 2.44; 95% confidence interval [CI]: 1.74–3.42). Additionally, subgroup analysis showed that both monochorionic (MC) and small for gestational age (SGA) twins were more likely to complicate with preeclampsia.ConclusionThe growth discordance of 15% during pregnancy may be the preventive point of preeclampsia, and 25% may be the interventional point

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Dynamical Behaviors of Stochastic Reaction-Diffusion Cohen-Grossberg Neural Networks with Delays

This paper investigates dynamical behaviors of stochastic Cohen-Grossberg neural network with delays and reaction diffusion. By employing Lyapunov method, Poincaré inequality and matrix technique, some sufficient criteria on ultimate boundedness, weak attractor, and asymptotic stability are obtained. Finally, a numerical example is given to illustrate the correctness and effectiveness of our theoretical results

Dynamical Behaviors of Stochastic Reaction-Diffusion Cohen-Grossberg Neural Networks with Delays

This paper investigates dynamical behaviors of stochastic Cohen-Grossberg neural network with delays and reaction diffusion. By employing Lyapunov method, Poincaré inequality and matrix technique, some sufficient criteria on ultimate boundedness, weak attractor, and asymptotic stability are obtained. Finally, a numerical example is given to illustrate the correctness and effectiveness of our theoretical results

Examination of the adoption intention of new energy vehicles from the perspective of functional attributes and media richness

Drawing on the theory of media richness, this paper aims to explore the impact of media richness on consumers' adoption intention through their perception of new energy vehicle (NEV) function attributes, and assess the moderation roles of brand familiarity and locus of control. A structural equation model is applied to analyze the data collected from 427 respondents. Empirical results demonstrate that consumers' perception of an electric attribute (i.e., charging efficiency) and two intelligent attributes (i.e., car networking and self-driving) are determinants of their adoption intention of NEVs. The other electric attribute (range) is trivial in consumers' perception. We also find that low, medium, and high-richness media significantly affect consumers' perception of NEVs' functional attributes. Compared to the high-richness, medium-richness correlates significantly with two types of NEV functional attributes. Regarding moderating effects, consumer familiarity with NEV's brand negatively impacts the relationship between media richness and adoption intention. Furthermore, low and medium-richness media effectively stimulate individuals with external control to adopt NEV, while high-richness media adversely influence individuals with internal control

Quantitative proteomic analysis of serum from pregnant women carrying a fetus with conotruncal heart defect using isobaric tags for relative and absolute quantitation (iTRAQ) labeling.

To identify differentially expressed proteins from serum of pregnant women carrying a conotruncal heart defects (CTD) fetus, using proteomic analysis.The study was conducted using a nested case-control design. The 5473 maternal serum samples were collected at 14-18 weeks of gestation. The serum from 9 pregnant women carrying a CTD fetus, 10 with another CHD (ACHD) fetus, and 11 with a normal fetus were selected from the above samples, and analyzed by using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry(2D LC-MS/MS). The differentially expressed proteins identified by iTRAQ were further validated with Western blot.A total of 105 unique proteins present in the three groups were identified, and relative expression data were obtained for 92 of them with high confidence by employing the iTRAQ-based experiments. The downregulation of gelsolin in maternal serum of fetus with CTD was further verified by Western blot.The identification of differentially expressed protein gelsolin in the serum of the pregnant women carrying a CTD fetus by using proteomic technology may be able to serve as a foundation to further explore the biomarker for detection of CTD fetus from the maternal serum

Types of congenital heart defects included in this study.

<p>Types of congenital heart defects included in this study.</p

Identification of the protein gelsolin as being differentially expressed in maternal sera of pregnant women carrying a CTD fetus.

<p>(A) Identification of the protein gelsolin in maternal serum by iTRAQ and 2D LC-MS/MS. (i) The peptide quantitation information of gelsolin was derived from the intensities of three iTRAQ reporter ions. Reporter ions 118,119 were used to label sera from pregnant women carrying CTD and ACHD fetuses, respectively. Reporter ion 121 was used to label normal controls. (ii)The representative MS/MS spectrum of a peptide from gelsolin. (B). The Western blot validated the relative expression of GSN, A2M, CERU, ATRN, PZP in maternal serum samples(i), and confirmed relative decreased level of maternal serum gelsolin in CTD group compared with normal controls (ii). n = 9 in CTD group, n = 11 in normal control.*<i>p</i> = 0.008.</p

Maternal serum proteins showed differently expression in CTD group and ACHD group compared to normal control (CON).

<p>Maternal serum proteins showed differently expression in CTD group and ACHD group compared to normal control (CON).</p

Western blot and IHC analyses confirmed the relative expression of GSN in fetal heart tissues with CTD.

<p>(A) Western blot analysis examined the relative expression of GSN, and confirmed that the GSN protein was downregulated in heart tissues of CTD fetuses compared with normal controls. n = 4, respectively. *<i>p</i> = 0.004. (B) IHC demonstrated the dark brown immunostaining was weaker in the CTD heart tissues than the normal controls (i, normal control, 23 gestational weeks, ii, CTD 23 gestational weeks; iii normal control, 25 gestational weeks, iv, CTD 25 gestational weeks). n = 4, respectively. Magnification was set at 400×.</p