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Abstract Optical genome mapping (OGM) offers high consistency in simultaneously detecting structural and copy number variants. This study aimed to retrospectively evaluate the efficacy and potential applications of OGM in preconception genetic counseling. Herein, 74 samples from 37 families were included, and their results of OGM were compared to conventional methods, namely karyotyping (KT) and chromosomal microarray analysis (CMA), which identified 27 variants across 16 positive families. Notably, OGM achieved a concordance rate of 94.7% and 100% with KT and CMA, respectively, presenting an overall concordance of 96.3%, as it missed detecting a centromeric translocation. Additionally, OGM detected two cryptic balanced translocations and a small deletion in three families that were missed by conventional methods, improving the diagnostic rate by 5.4%, along with assisting in the diagnoses of six families (16.2%) by identifying complex rearrangements and confirming cryptic translocations. The combination of KT with OGM yielded the highest diagnostic rate in all families. Overall, the findings of this study present the notable potential of OGM for its application, combined with KT per requirement, in clinical settings to improve the efficiency and accuracy of diagnoses and rapid screening of individuals seeking preconception genetic counseling.

Abstract Background Kagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. Case presentation The woman’s two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. Conclusions Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Abstract Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

Abstract Background Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases are detected prenatally, and the final diagnosis cannot be made until pathology is completed after birth. Here, we present a case of disseminated form IM (DFIM) with a diagnosis established on prenatal genetic grounds. Case presentation A woman at 23 weeks of gestation was referred for ultrasound evaluation of fetal kidney abnormality. Generalized masses in the skin and muscle of the fetus developed at 28 weeks. Prenatal genetic testing identified the pathogenic heterozygous variant c.1681C > T (p.R561C) of the PDGFRB gene inherited from the asymptomatic father. Intrauterine demise occurred at 31 weeks. Autopsy confirmed DFIM with involvement of the heart and kidney. All cases of prenatally detected IM were reviewed, revealing an association of high mortality with DFIM. Conclusions Prenatal IM diagnosis is difficult. Initial detection is always based on ultrasound. DFIM has high mortality. The germline p.R561C mutation in PDGFRB may cause fetal demise due to severe visceral involvement of IM. Prenatal genetic testing provides a diagnosis before pathological results are available, leading to better counseling and management of pregnancy with a fetus with IM.

Abstract Background Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort. Methods In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports. Results In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P = 0.0130). Conclusions Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes.

Objective: Mosaicism is a common biological phenomenon in organisms and has been reported in many types of chromosome abnormalities, including the absence of heterozygosity (AOH). Due to the detection limitations of the sequencing approach, mosaic AOH events are rarely assessed in clinical cases. Herein, we report the performance of mosaic AOH identification using a low-pass (5~8-fold) WGS method (termed ‘CMA-seq’, an abbreviation for ‘Chromosome Analysis by Sequencing’) in fetal genetic diagnosis. Methods: Thirty AOH-negative, eleven constitutional AOH, and three mosaic AOH samples were collected as training data sets to develop the algorithm and evaluate the suitable thresholds for distinguishing mosaic AOH. Twenty-four new chromosomal aberrant cases, along with sixteen constitutional AOH samples, which were previously ascertained via the SNP-array-based method, were used as a validation data set to measure the performance in terms of sensitivity and specificity of this algorithm. Results: A new statistic, ‘D-value’, was implemented to identify and distinguish constitutional and mosaic AOH events. The reporting thresholds for constitutional and mosaic AOH were also established. In the validation set consisting of 24 new cases, seven constitutional AOH cases and 1 mosaic AOH case were successfully identified, indicating that the results were consistent with those of the SNP-array-based method. The results of all sixteen constitutional AOH validation samples also met the threshold requirements. Conclusions: In this study, we developed a new bioinformatic algorithm to accurately distinguish mosaic AOH from constitutional AOH by low-pass WGS. However, due to the small sample size of the training data set, the algorithm proposed in this manuscript still needs further refinements.

Objective Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population.Methods A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival.Results During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery.Conclusion EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

Objective: Absence of homozygosity (AOH) is a genetic characteristic known to cause human diseases mainly through autosomal recessive or imprinting mechanisms. The importance and necessity of accurate AOH detection has become more clinically significant in recent years. However, it remains a challenging task for sequencing-based methods thus far. Methods: In this study, we developed and optimized a new bioinformatic algorithm based on the assessment of minimum sequencing coverage, optimal bin size, the Z-score threshold of four types of allele count and the frequency for accurate genotyping using 28 AOH negative samples, and redefined the AOH detection cutoff value. We showed the performance of chromosome analysis by five-fold coverage whole genome sequencing (CMA-seq) for AOH identification in 27 typical prenatal/postnatal AOH positive samples, which were previously confirmed by chromosomal microarray analysis with single nucleotide polymorphism array (CMA/SNP array). Results: The blinded study indicated that for all three forms of AOH, including whole genomic AOH, single chromosomal AOH and segmental AOH, and all kinds of sample types, including chorionic villus sampling, amniotic fluid, cord blood, peripheral blood and abortive tissue, CMA-seq showed equivalent detection power to that of routine CMA/SNP arrays (750K). The subtle difference between the two methods is that CMA-seq is prone to detect small inconsecutive AOHs, while CMA/SNP array reports it as a whole. Conclusion: Based on our newly developed bioinformatic algorithm, it is feasible to detect clinically significant AOH using CMA-seq in prenatal diagnosis.

Next-generation sequencing (NGS) is emerging as a new method for the detection of clinically significant copy number variants (CNVs). In this study, we developed and validated rapid CNV-sequencing (rCNV-seq) for clinical application in prenatal diagnosis. Low-pass whole-genome sequencing was performed on PCR libraries prepared from amniocyte genomic DNA. From 10–40 ng of input DNA, PCR-free libraries consistently produced sequencing data with high unique read mapping ratios, low read redundancy, low coefficient of variation for all chromosomes and high genomic coverage. In validation studies, reliable and accurate CNV detection using PCR-free-based rCNV-seq was demonstrated for a range of common trisomies and sex chromosome aneuploidies as well as microdeletion and duplication syndromes. In reproducibility studies, CNV copy number and genomic intervals closely matched those defined by chromosome microarray analysis. Clinical testing of genomic DNA samples from 217 women referred for prenatal diagnosis identified eight samples (3.7%) with known chromosome disorders. We conclude that PCR-free-based rCNV-seq is a sensitive, specific, reproducible and efficient method that can be used in any NGS-based diagnostic laboratory for detection of clinically significant CNVs.

Adding an anti-corrosion coating to the surface of magnesium (Mg) alloy is an effective means to improve its corrosion resistance, but it is particularly important to enhance the bonding force between the anti-corrosion coating and the Mg matrix. Epoxy resin coating is considered the most cost-effective approach from an industrial standpoint, while the hindering the wider utilization of Mg alloys with epoxy coating in the realm of engineering materials are due to their insufficient adhesion between Mg matrix and the epoxy coating. Here, we demonstrated a simple method for forming an epoxy resin/mineralized film composite coating. The mineralized products coatings were applied to the surface of Mg-3Nd alloy, via a direct reaction between Mg and 15 wt% Na2CO3 solution. Due to the inherent lamellar structure of alkaline magnesium carbonate mineralization film, the mechanical interlocking between the epoxy resin and the Mg substrate are remarkably strengthened. Therefore, this simple surface treatment method is promising to improve the adhesion between the epoxy resin and the matrix. Moreover, the effects of mineralized products coating on the corrosion resistance of Mg with epoxy coating were researched. It was observed that the corrosion resistance of Mg alloy with composite coatings are significantly enhanced. Such an investigation aims to provide a new method for developing a cost-effective and robust epoxy resin/mineralized film composite coating protection structure of Mg alloys in practical applications.

Understanding the corrosion behavior of Mg alloys in the Cl− environments is crucial to preventing catastrophic accidents in their facilities due to their poor corrosion. The microstructures and corrosion behaviors of the Mg-4Gd-2Nd alloy under different heat-treatment conditions were investigated. The content of Mg41Nd5 in the alloy decreased significantly with increasing heat-treatment temperature. It was found that the formation of solid solution atomic oxides separates the lamellar Mg(OH)2 during the corrosion process of Mg alloys. With the increase of solid solution atomic oxides, lamellar Mg(OH)2 is no longer clustered and laid flat on the alloy surface. The loose Mg(OH)2 corrosion product film is eroded by Cl− and converted to the rod-like Mg2Cl(OH)3·4H2O, which lead to the detachment of the loose lamellar Mg(OH)2 in pieces. Furthermore, the corrosion products of the as-extruded alloy fall off in large blocks, whereas the corrosion products of the heat-treated alloys fall off in small pieces. Therefore, 540 °C-treated specimen exhibits best corrosion resistance.

The Mg-Al alloys exhibit poor corrosion resistance when they exposed to Cl ^- attack. To solve this problem, Erbium (Er) and Manganese (Mn) are added to the Mg-4Al alloy and the Mg-4Al-6Er-0.3Mn is T4 treated to enhance the corrosion resistance of the alloy. Then the corrosion behaviors of the as-extruded alloy and the T4 alloy are investigated in this paper. It is found that the effective cathode Mg _17 Al _12 is significantly reduced in the alloy due to the precipitation of Mg _17 Al _12 being suppressed by Al _2 Er and the dissolution of the Mg _17 Al _12 in the alloy. It is observed that the corrosion products transform from needle-like to tetrahedral-shaped corrosion products during the transformation process, which leads to severe pit corrosion. The results show that the T4 treatment can delay the transformation of the morphologies of the corrosion products, thereby improved the alloy corrosion resistance during the early stages of corrosion.

Taking an oxygen-rich side-blown lead melting furnace made by a company as the research object, the three-dimensional design software Solidworks was used to construct a model at an equal scale, and established a physical model which is in line with the actual system. Based on the determination of the physical properties of the slag phase and metal phase in the furnace, the VOF multiphase flow model and standard turbulence model in FLUENT were used to simulate the gas–liquid multiphase flow. By adjusting the different inclination angles of the spray gun, we analyzed the distribution changes of key indicators, such as the flow field, average turbulent kinetic energy and gas content in the furnace. At the same time, it was found that the turbulent kinetic energy in the middle of the furnace was large, which could strengthen the winding effect of the material and the best arrangement. The gas content of the upper part of the oxygen gun was high, and the gas content in the middle of the furnace was higher than that in the wall area on both sides and showed a gradual downward trend. If the inclination angle of the spray gun is too small, the agitation of the lower melting area is not strong enough, On the contrary, if the inclination angle is too large, the local flow rate of the sedimentation area increases and the gas content is low. The optimal tilt angle of the spray gun is between 10° and 15°.

Background: Karyotyping is considered the gold standard for the genome-wide detection of genomic imbalances in prenatal diagnosis, but it has a number of inherent limitations, namely the time required to culture cell and the limited resolution(5 ~ 10 Mb). Although fluorescence in situ hybridization (FISH) can also be used as a rapid prenatal diagnosis for common aneuploidies, it is labor intensive, requires prior knowledge of the regions of interest, and can only be used to diagnose one or a few genomic regions simultaneously. Array comparative genomic hybridization (aCGH) can overcome the resolution, the locus-specific, and the time limitations of the karyotyping and FISH techniques and is currently the most powerful method for detecting chromosomal alterations in pre and postnatal clinical cases. Several investigations have suggested that the aCGH testing should be considered a firsttier test for the diagnosis of cytogenetic aberrations in the fetus. Results: This study used karyotyping, FISH, sequence-tagged site (STS) analysis and aCGH to diagnose a case of de novo duplication of chromosome 21q22.12-q22.3 with other concomitant deletion and duplication of small fragments in 21q associated with Down syndrome prenatally. Conclusions: FISH, aCGH and STS analysis are useful in prenatal investigation of the nature of de novo alterations of small fragments of the chromosome. [ABSTRACT FROM AUTHOR]

The demand for high performance lithium-ion batteries (LIBs) is increasing due to widespread use of portable devices and electric vehicles. Silicon (Si) is one of the most attractive candidate anode materials for next generation LIBs. However, the high-volume change (>300%) during lithium ion alloying/de-alloying leads to poor cycle life. When Si is used as the anode, conductive carbon is needed to provide the necessary conductivity. However, the traditional carbon coating method could not overcome the challenges of pulverization and unstable Solid Electrolyte Interphase (SEI) layer during long-term cycling. Since 2010, Si/Graphene composites have been vigorously studied in hopes of providing a material with better cycling performance. This paper reviews current progress of Si/Graphene nanocomposites in LIBs. Different fabrication methods have been studied to synthesize Si/Graphene nanocomposites with promising electrochemical performances. Graphene plays a key enabling role in Si/Graphene anodes. However, the desired properties of graphene for this application have not been systematically studied and understood. Further systematic investigation of the desired graphene properties is suggested to better control the Si/Graphene anode performance.

Millimeter-wave (MMW) imaging techniques have been used for the detection of concealed weapons and contraband carried by personnel. However, the future application of the new technology may be limited by its large number of antennas. In order to reduce the complexity of the hardware, a novel MMW imaging method based on compressive sensing (CS) is proposed in this paper. The MMW images can be reconstructed from the significantly undersampled backscattered data via the CS approach. Thus the number of antennas and the cost of system can be further reduced than those based on the traditional imaging methods that obey the Nyquist sampling theorem. The effectiveness of the proposed method is validated by numerical simulations as well as by real measured data of objects.