The efficacy of using a multiparametric magnetic resonance imaging-based radiomics model to distinguish glioma recurrence from pseudoprogression.

OBJECTIVE: The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner. METHODS: A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy. RESULTS: Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93-1). CONCLUSION: The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment.

Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.

BACKGROUND: The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. METHODS: Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. RESULTS: The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. CONCLUSION: Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.

In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperform those modified at the nucleobase. Our in vivo validation using hamster models further bolsters the promise of this nucleoside tailoring approach, positioning it as a valuable asset in the development of innovative antiviral drugs.

Yak IGFBP3 promotes hepatocyte proliferation through PI3K-Akt signaling pathway.

IGFBP3 (Insulin-like growth factor binding protein 3) constitutes a crucial constituent of the insulin-like growth factor (IGF), which are intimately associated with the organism's growth and development processes. Despite its significance, the precise function of IGFBP3 in yak liver development remains largely unexplored. In the present study, we systematically examined the expression profile of IGFBP3 in the liver tissues of yaks across various growth stages, elucidated its influence on the activity of yak hepatocytes, and probed its effects on murine liver development. A comparative analysis revealed that the expression of IGFBP3 was significantly higher in the liver tissue of 5-year-old yaks compared to their 15-month-old and 1-day-old counterparts (P < 0.01). To further validate its biological function, pET-28a-BgIGFBP3 prokaryotic expression vector was constructed. Upon exposing yak hepatocytes to varying concentrations of Bos grunniens (Bg) IGFBP3 protein, we observed augmented cellular activities and elevated colony formation rates. Moreover, our investigation revealed the upregulation of key genes within the PI3K-Akt signaling pathway, including ERBB2, IRS1, PIK3R1, AKT1, RAF1, MAP2K2, and MAPK3, in both yak hepatocyte cultures and murine models. These findings collectively indicate that BgIGFBP3 promotes the proliferation of yak hepatocytes and enhances murine liver development by modulating the PI3K-Akt signaling pathway. The functional relevance of BgIGFBP3 was substantiated through in vivo and in vitro experiments, thereby underscoring its potential as a regulatory factor in liver development processes.

The Functions of Phasic Wing-Tip Folding on Flapping-Wing Aerodynamics.

Insects produce a variety of highly acrobatic maneuvers in flight owing to their ability to achieve various wing-stroke trajectories. Among them, beetles can quickly change their flight velocities and make agile turns. In this work, we report a newly discovered phasic wing-tip-folding phenomenon and its aerodynamic basis in beetles. The wings' flapping trajectories and aerodynamic forces of the tethered flying beetles were recorded simultaneously via motion capture cameras and a force sensor, respectively. The results verified that phasic active spanwise-folding and deployment (PASFD) can exist during flapping flight. The folding of the wing-tips of beetles significantly decreased aerodynamic forces without any changes in flapping frequency. Specifically, compared with no-folding-and-deployment wings, the lift and forward thrust generated by bilateral-folding-and-deployment wings reduced by 52.2% and 63.0%, respectively. Moreover, unilateral-folding-and-deployment flapping flight was found, which produced a lateral force (8.65 mN). Therefore, a micro-flapping-wing mechanism with PASFD was then designed, fabricated, and tested in a motion capture and force measurement system to validate its phasic folding functions and aerodynamic performance under different operating frequencies. The results successfully demonstrated a significant decrease in flight forces. This work provides valuable insights for the development of flapping-wing micro-air-vehicles with high maneuverability.

Revitalization of Diluent Amide-Based Electrolyte for Building High-Voltage Lithium-Metal Batteries.

Hitherto, highly concentrated electrolyte is the overarching strategy for revitalizing the usage of amide - in lithium-metal batteries (LMBs), which simultaneously mitigates the reactivity of amide toward Li and regulates uniform Li deposition via forming anion-solvated coordinate structure. However, it is undeniable that this would bring the cost burden for practical electrolyte preparation, which stimulates further electrolyte design toward tailoring anion-abundant Li+ solvation structure in stable amide electrolytes under a low salt content. Herein, a distinct method is conceived to design anions-enriched Li+ solvation structure in dilute amide-electrolyte (1 m Li-salt concentration) with the aid of integrating perfluoropolyethers (PFPE-MC) with anion-solvating ability and B/F-involved additives. The optimized electrolyte based on N,N-Dimethyltrifluoroacetamide (FDMAC) exhibits outstanding compatibility with Li and NCM622 cathode, facilitates uniform Li deposition along with robust solid electrolyte interphase (SEI) formation. Accordingly, both the lab-level LMB coin cell and practical pouch cell based on this dilute FDMAC electrolyte deliver remarkable performances with improved capacity and cyclability. This work pioneers the feasibility of diluted amide as electrolyte in LMB, and provides an innovative strategy for highly stable Li deposition via manipulating solvation structure within diluent electrolyte, impelling the electrolyte engineering development for practical high-energy LMBs.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

Prenatal diagnosis and outcomes in fetuses with duplex kidney.

OBJECTIVE: Duplex kidney is a relatively frequent form of urinary system abnormality. This study aimed to elucidate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) for duplex kidney and the perinatal outcomes of duplex kidney fetuses. METHODS: This retrospective cohort study included 63 patients with duplex kidney diagnosed using antenatal ultrasound between August 2013 and January 2023. We reviewed the clinical characteristics, genetic test results, and pregnancy outcomes of the patients. RESULTS: Among the 63 cases based on the inclusion criteria, the CMA detected seven (11.1%) clinically significant variants and nine variants of uncertain significance (VUS), and the pathogenic/likely pathogenic (P/LP) copy number variations (CNVs) in the recurrent region that were associated with prenatal duplex kidney included 17q12, 17p13.3, and 22q11.2. No significant disparity was observed in the CMA detection rate between the unilateral and bilateral groups, or between the isolated and non-isolated groups. WES identified three (50%) P/LP single-gene variants in six fetuses with duplex kidney. We detected the following pathogenic genes in the duplex kidney fetuses: KMT2D, SMPD4, and FANCI. Pregnancy termination in cases where clinically significant variants were detected by genetic testing was different in statistical significance from that in cases with negative results (9/10, 90.0% vs 8/48, 16.7%, P < 0.001). CONCLUSION: This study elucidated the value of CMA and WES for fetal duplex kidney, proving that CMA and WES may be useful tools in prenatal diagnosis and genetic counseling.

High-Entropy Mn/Fe-Based Layered Cathode with Suppressed P2-P'2 Transition and Low-Strain for Fast and Stable Sodium Ion Storage.

Mn/Fe-based layered oxides are deemed to be a highly suitable cathode for sodium-ion batteries (SIBs) due to their high capacity and abundant Mn/Fe resources, but they still suffer from a complicated phase transition and large volume variation. To conquer these problems, high-entropy Mn/Fe-based layered oxide P2-Na0.67Mn0.5Fe0.334Cu0.045Mg0.014Ti0.014Al0.014Zr0.014Sn0.014O2 (Mn-Fe-HEO) is rationally designed and fabricated. When used as a cathode for SIB, high-entropy Mn-Fe-HEO exhibits much higher reversible capacity and better rate capability than low-entropy Na0.67Mn0.5Fe0.334Cu0.164O2 (Mn-Fe-LEO) within a wide voltage range of 1.5-4.3 V. Ex situ X-ray diffraction combined with diffusion kinetics tests and microstructural characterizations demonstrate that high-entropy enhanced structural stability effectively prevents the Jahn-Teller distortion of Mn3+, stabilizes the Na+ diffusion channels, and enables the smooth transfer of more working Na+. These lead to a stable and fast redox electrochemistry in high-entropy Mn-Fe-HEO. This work deepens the understanding of the relationship between high-entropy structure and performance and provides important guidance for the rational design of future high-entropy layered cathodes.

3D human ear modelling with parameterization technique and variation analysis.

Anthropometry is vital to provide design references when seeking proper product fit. Nowadays, 3D anthropometry is widely used to provide more size and shape details for improving product designs. However, 3D ear anthropometry is still at an explorative stage, considering the complex ear morphology and other technical obstacles. The proposed research method in this study is applicable to analyse the 3D point cloud of the entire external ear. With the cross-parameterisation technique, the dataset was used to explore the morphological characteristics of the ear. Ear dimensions were automatically extracted and further analysed to explore the gender and symmetry differences using two-way ANOVA. The 3D ear models were investigated through Principal Component Analysis (PCA). The most significant variation was found in the helix and concha region, and the overall ear size is the second important factor determining ear variance. The statistical models were generated as 3D design references for ear-related products.Practitioner summary: This study revealed the morphological variations of the entire 3D external ear with a parameterised 3D ear dataset. Based on the PCA findings, a set of statistical models were generated as design references for product evaluation digitally or physically.

Journey to inpatient hospice care: A qualitative study on the decision-making process of Chinese family caregivers of persons with terminal cancer.

OBJECTIVE: To understand family caregivers' decision-making process to place their family members with terminal cancer in inpatient hospice care, especially in the social-cultural contexts whereby the caregivers have a dominant say about the care of their seriously ill family members. METHODS: A qualitative study with a phenomenological approach was undertaken to understand the lived experience of caregivers of persons with terminal cancer in the decision-making process. Semi-structured qualitative interviews were conducted with a purposive sample of 17 caregivers in Shanghai, China. Thematic analysis was used to analyze the data. RESULTS: The caregivers underwent a winding and socioculturally mediated four-stage process. The stages are (i) trigger for alternatives: lost hope for a cure, (ii) meandering the see-saw process, (iii) the last straws: physical limitations and witnessing unbearable suffering, and (iv) the aftermath: acceptance versus lingering hope. Caregivers' attitudes towards death and their family members with advanced cancer expressed care wishes influence the state of the aftermath. CONCLUSIONS: Chinese sociocultural values and beliefs about caregiving and death provide insightful explanations for the observed process. PRACTICAL IMPLICATIONS: Training healthcare professionals in cultural competence, developing an effective hospice referral system, and delivering socioculturally acceptable death education are critical interventions to facilitate better decision-making experiences.

Functional analysis of a novel splice site variant in the ASAH1 gene.

BACKGROUND: Acid ceramidase (ACDase) deficiency is an ultrarare autosomal recessive lysosomal disorder caused by pathogenic N-acylsphingosine amidohydrolase (ASAH1) variants. It presents with either Farber disease (FD) or spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). OBJECTIVE: The study aims to identify a novel splice site variant in a hydrops fetus that causes ASAH1-related disorder, aid genetic counseling, and accurate prenatal diagnosis. METHODS: We report a case of hydrops fetalis with a novel homozygous mutation in ASAH1 inherited from non-consanguineous parents. We performed copy number variation sequencing (CNV-Seq) and whole exome sequencing (WES) on the fetus and family, respectively. Minigene splicing analyses were conducted to confirm the pathogenic variants. RESULTS: WES data revealed a splice site variant of the ASAH1 (c.458-2A>T), which was predicted to affect RNA splicing. Minigene splicing analyses found that the c.458-2A>T variant abolished the canonical splicing of intron 6, thereby activating two cryptic splicing products (c.456_458ins56bp and c.458_503del). CONCLUSIONS: Overall, we identified a novel splice site variant in the mutational spectrum of ASAH1 and its aberrant effect on splicing. These findings highlight the importance of ultrasonic manifestation and family history of fetal hydrops during ASAH1-related disorders and could also aid genetic counseling and accurate prenatal diagnosis. To the best of our knowledge, this is the shortest-lived account of ASAH1-related disorders in utero with severe hydrops fetalis.

Facile fabrication and antibacterial properties of chitosan/acrylamide/gold nanocomposite hydrogel incorporated with Chaetomium globosium extracts from Gingko biloba leaves.

Microorganisms are a unique part of our ecosystem because they affect the survival of living organisms. Although pathogenic microorganisms could be detrimental to the plants, animals, and humans, beneficial microbes have provided significant improvement in the growth and development of living organisms. In this study, the fungus Chaetomium globosium was isolated from the medicinal tree Gingko biloba, and then incorporated into a polymerization system to fabricate chitosan/acrylamide/gold (CS/Am/Au) nanocomposite hydrogels. The as-prepared hydrogel displayed increased mechanical strength due to the reinforcement of Au (gold) nanocomposites within the hydrogel matrix. Also, the equilibrium pH responsive swelling rates of the hydrogels gradually increased as the pH increases due to partial acid and basic hydrolysis occurring in the hydrogel as well as formation of hydrogen bond. In addition, the hydrogel demonstrated promising antibacterial activities against selected gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa) bacterial strains with an average MIC90 of 0.125 mg/mL at a dosage of 1.0 mg/L. The obtained results are quite promising towards resolving several health challenges and advancing the pharmaceutical industries.

Prenatal diagnosis of polycystic renal diseases: diagnostic yield, novel disease-causing variants, and genotype-phenotype correlations.

BACKGROUND: Polycystic renal disease is a frequent congenital anomaly of the kidneys, but research using chromosomal microarray analysis and exome sequencing in fetuses with polycystic renal disease remains sparse, with most studies focusing on the multisystem or genitourinary system. OBJECTIVE: This study aimed to assess the detection rate of detectable genetic causes of fetal polycystic renal disease at different levels, novel disease-causing variants, and genotype-phenotype correlations. STUDY DESIGN: This study included 220 fetal polycystic renal disease cases from January 2014 to June 2022. Cases were divided into the following 3 groups: isolated multicystic dysplastic kidneys, nonisolated multicystic dysplastic kidneys, and suspected polycystic kidney disease group. We reviewed data on maternal demographics, ultrasonographic results, chromosomal microarray analysis/exome sequencing results, and pregnancy outcomes. RESULTS: In our cohort, chromosomal microarray analysis identified 19 (8.6%) fetuses carrying chromosomal abnormalities, and the most common copy number variation was 17q12 microdeletion (7/220; 3.2%). Furthermore, 94 families chose to perform trio-exome sequencing testing, and 21 fetuses (22.3%) were found to harbor pathogenic/likely pathogenic variants. There was a significant difference in the live birth rate among the 3 groups (91/130 vs 46/80 vs 1/10; P<.001). Among 138 live birth cases, 106 (78.5%) underwent postnatal ultrasound review, of which 95 (89.6%) had a consistent prenatal-postnatal ultrasound diagnosis. CONCLUSION: For both isolated and nonisolated polycystic renal disease, our data showed high detection efficiency with both testing tools. The detection of novel pathogenic variants expands the known disease spectrum of polycystic renal disease-associated genes while enriching our understanding of the genotype-phenotype correlation. Therefore, we consider it feasible to perform chromosomal microarray analysis+exome sequencing testing in fetal polycystic renal disease. Moreover, prenatal-postnatal ultrasound concordance was greater, the live birth rate was higher, and prognosis was better when known genetic disorders were excluded, indicating that genetic testing results significantly influenced pregnancy decisions.

Isolation, characterization, and phylogenetic analysis of two new porcine parvovirus 1 isolates from Northern China.

Porcine parvovirus (PPV) is a pathogen of infectious reproductive disease, which can cause stillbirth, mummification, embryo death, and infertility (SMEDI) syndrome in pigs. The objective of this study was to gain new insights into the evolution and phylogeny of the PPV1 genome. In this study, we isolated two new PPV1 (HLJ202108-Y and SDLC202109) from northern China and sequenced their whole genomes. The new isolates were found to have three amino acid substitutions (K195R, K562R, and S578P) in nonstructural protein 1. The VP2 amino acid site contained nine nonsynonymous substitutions, including six substitutions of the Kresse strain corresponding to the NADL-2 strain and three substitutions of A414S, S436T, and N555K. Genetic evolution analysis was conducted on 107 reference sequences available in the GenBank database, and 4-5 PPV1 taxa were defined. The new isolates were in the same phylogenetic cluster as strain 27a. The changes in the cluster, specifically marker amino acids, and their potential role in enhancing pathogenicity are discussed in this study. Furthermore, the evolutionary tree map results showed that the strains in China were evolving in two directions: one was becoming increasingly similar to early NADL-2 strains, while the other was evolving toward 27a-like strains. We also compared the proliferation ability of the isolated strains in susceptible cells by analyzing the multistep growth curves. The results showed that the virulence titer of the mutant strain was high. In summary, this study introduced the latest changes in PPV and discussed the virus characteristics that were considered to affect virulence.

Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing.

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling. Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses. Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes. Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.

Postmarket safety profile of suicide/self-injury for GLP-1 receptor agonist: a real-world pharmacovigilance analysis.

BACKGROUND: Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database. METHODS: The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis. RESULTS: A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak. CONCLUSIONS: The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

Prenatal diagnosis and perinatal outcomes of twin pregnancies disharmonious for one fetus with nuchal translucency above the 95th percentile.

OBJECTIVE: To assess prenatal diagnosis and pregnancy outcomes in twin pregnancies where one fetus has nuchal translucency (NT) above the 95th percentile. METHOD: In this retrospective analysis, 130 twin pregnancies (260 fetuses) in which one twin had an NT measurement above the 95th percentile while that of the other twin was normal were analyzed. Prenatal diagnostic results such as G bands, chromosomal microarray analysis, ultrasound findings, and pregnancy outcomes were reviewed. RESULTS: Karyotype analysis and CMA results revealed that 15 (15.6 percent, 15/96) fetuses exhibited chromosomal abnormalities and that 13 fetuses were Variant of Uncertain Significance. Chromosome abnormalities were detected at a rate of 8.9% (5/56) in the DCT group and 25.0% (10/40) in the MCT group (p = 0.033, X2 = 4.571). 2 fetuses in DCT (3.9 percent, 2/51) and 4 fetuses in MCT (13.3 percent, 4/30) (p = 0.187) revealed structural abnormalities among the cases with normal prenatal diagnosis. Fetuses in the DCT group had an overall survival rate of 75.4 percent (95/126), whereas those in the MCT group had a survival rate of 60.4 percent (81/134) (p = 0.01, X2 = 6.636). According to the findings of Logistics regression analysis, NT thickening, maternal age and method of conception were all significant risk factors for chromosome abnormalities. CONCLUSION: In twin pregnancies with one fetus with NT above the 95th percentile, the prevalence of fetal structural abnormalities of the MCT group and the DCT group were comparable. Pregnant women's age and mode of pregnancy are risk factors for chromosomal abnormalities.

Chromosome Microarray Analysis and Exome Sequencing: Implementation in Prenatal Diagnosis of Fetuses with Digestive System Malformations.

(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential.