Relative Mediastinal Displacement Index (RMDI): A Prenatal MRI Indicator of Adverse Events in Fetuses With Isolated Left Congenital Diaphragmatic Hernia.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), has partly improved congenital diaphragmatic hernia (CDH) outcomes, yet the overall morbidity and mortality remain high. Existing prenatal indicators for CDH fetuses are operator-dependent, time-consuming, or less accurate, a new simple and accurate indicator to indicate adverse events in CDH patients is needed. PURPOSE: To propose and assess the association of a new MRI parameter, the relative mediastinal displacement index (RMDI), with adverse events including in-hospital deaths or the need for ECMO in fetuses with isolated left CDH (iLCDH). STUDY TYPE: Retrospective analysis. SUBJECTS: One hundred thirty-nine fetuses were included in the iLCDH group (24 with adverse events and 115 without) and 257 fetuses were included in the control group from two centers in Guangzhou. FIELD STRENGTH/SEQUENCE: 3.0 T, T2WI-TRUFI; 1.5 T, T2WI-FIESTA. ASSESSMENT: Three operators independently measured the → DL $$ \underset{\mathrm{DL}}{\to } $$ , → DR $$ \underset{\mathrm{DR}}{\to } $$ , and DH on the axial images. The calculation formula of the RMDI was ( → DL $$ \underset{\mathrm{DL}}{\to } $$ + → DR $$ \underset{\mathrm{DR}}{\to } $$ )/DH . STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Chi-square test, Chi-square test continuity correction, Fisher's test, linear regression analysis, logistic regression analysis, intraclass correlation coefficient, receiver operating characteristic curve analysis, and Delong test. A P value <0.05 was considered statistically significant. RESULTS: The RMDI did not change with gestational age in the iLCDH group (with [P = 0.189] and without [P = 0.567] adverse events) and the control group (P = 0.876). There were significant differences in RMDI between the iLCDH group (0.89 [0.65, 1.00]) and the control group (-0.23 [-0.34, -0.16]). In the iLCDH group, RMDI was the only indicator left for indicating adverse events, and the best cutoff value was 1.105. Moreover, there was a significant difference in diagnostic accuracy between the RMDI (AUC = 0.900) and MSA (AUC = 0.820), LHR (AUC = 0.753), o/e LHR (AUC = 0.709), and o/e TFLV (AUC = 0.728), respectively. DATA CONCLUSION: The RMDI is expected to be a simple and accurate tool for indicating adverse events in fetuses with iLCDH. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

A joint brain extraction and image quality assessment framework for fetal brain MRI slices.

Brain extraction and image quality assessment are two fundamental steps in fetal brain magnetic resonance imaging (MRI) 3D reconstruction and quantification. However, the randomness of fetal position and orientation, the variability of fetal brain morphology, maternal organs around the fetus, and the scarcity of data samples, all add excessive noise and impose a great challenge to automated brain extraction and quality assessment of fetal MRI slices. Conventionally, brain extraction and quality assessment are typically performed independently. However, both of them focus on the brain image representation, so they can be jointly optimized to ensure the network learns more effective features and avoid overfitting. To this end, we propose a novel two-stage dual-task deep learning framework with a brain localization stage and a dual-task stage for joint brain extraction and quality assessment of fetal MRI slices. Specifically, the dual-task module compactly contains a feature extraction module, a quality assessment head and a segmentation head with feature fusion for simultaneous brain extraction and quality assessment. Besides, a transformer architecture is introduced into the feature extraction module and the segmentation head. We utilize a multi-step training strategy to guarantee a stable and successful training of all modules. Finally, we validate our method by a 5-fold cross-validation and ablation study on a dataset with fetal brain MRI slices in different qualities, and perform a cross-dataset validation in addition. Experiments show that the proposed framework achieves very promising performance.

Two Chinese Patients of Auriculocondylar Syndrome 2: A Novel PLCB4 Splicing Variant and 5-Year Follow-up.

OBJECTIVE: Auriculocondylar syndrome (ARCND) is a set of rare craniofacial malformations characterized by variable micrognathia, ear malformations, and mandibular condyle hypoplasia, and other accompanying features with phenotypic complexity. ARCND2 caused by pathogenic variants in the PLCB4 gene is a very rare disease with less than 50 patients reported and only 36 different variants of the PLCB4 gene recorded in HGMD. This study aims to enrich the patient resources, clinical data and mutational spectrum of ARCND2. DESIGN: Case series study. SETTING: Guangzhou Women and Children's Medical Center and Guangdong Women and Children Hospital. PATIENTS: Two Chinese patients with ARCND2. MAIN OUTCOME MEASURES: Clinical, radiological and molecular findings. RESULTS: Both the two patients presented with craniofacial and ear malformations, and feeding difficulties. Whole exome sequencing identified two different variants of the PLCB4 gene in these two patients with a heterozygous allele and a de novo mode of inheritance respectively. Patient 1 carried a known pathogenic c.1861C > T(p.Arg621Cys) missense variant, whereas Patient 2 had a novel c.225 + 1G > A splicing variant. Sanger sequencing confirmed the presence of PLCB4 variants in the proband and absence in the unaffected parents. These two PLCB4 variants were suggested as disease-causing candidates for these two patients. During a 5-year follow-up, Patient 2 gradually manifested crowded teeth, underweight, motor delay and intellectual disability. CONCLUSIONS: In this study, we report two Chinese patients with ARCND2, describe their clinical and mutational features, and share a 5-year follow-up of one patient. Our study adds two additional patients to ARCND2, reveals a novel PLCB4 variant, and expands the phenotypic and genotypic spectrum.

Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports.

BACKGROUND: Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops. CASE PRESENTATION: We report two cases of prenatally diagnosed TAM. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5-8%) of trisomy 21 mosiacism by Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (FISH). In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases. CONCLUSION: It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family.

Rare genetic skeletal disorders (GSDs) remain the major problem in orthopedics and result in significant morbidity in patients, but the causes are highly diverse. Precise molecular diagnosis will benefit management and genetic counseling. This study aims to share the diagnostic experience on a three-generation Chinese family with co-occurrence of spondyloepiphyseal dysplasia (SED) and X-linked hypophosphatemia (XLH), and evaluate the therapeutic effects of two third-generation siblings. The proband, his younger brother, and mother presented with short stature, skeletal problems, and hypophosphatemia. His father, paternal grandfather, and aunt also manifested short stature and skeletal deformities. Whole exome sequencing (WES) of proband-brother-parents initially only found the proband and his younger brother had a pathogenic c.2833G > A(p.G945S) variant in the COL2A1 gene inherited from their father. Re-analysis of WES uncovered the proband and his younger brother also harbored a pathogenic ex.12 del variant in the PHEX gene transmitted from their mother. Sanger sequencing, agarose gel electrophoresis, and quantitative polymerase chain reaction proved these results. The proband and his younger brother were confirmed to have a paternally inherited SED and a maternally inherited XLH. During a 2.8-year follow-up, these two siblings remained short stature and hypophosphatemia, but their radiographic signs and serum bone alkaline phosphatase levels were improved with treatment of oral phosphate and calcitriol. Our study presents the first report of co-occurrence of SED and XLH, shows the possibility that two different rare GSDs co-exist in a single patient, and alerts clinicians and geneticists to be cautious about this condition. Our study also suggests that next-generation sequencing has limit in detecting exon-level large deletions.

A Miniaturized Piezoelectric MEMS Accelerometer with Polygon Topological Cantilever Structure.

This work proposes a miniaturized piezoelectric MEMS accelerometer based on polygonal topology with an area of only 868 × 833 µm2. The device consists of six trapezoidal cantilever beams with shorter fixed sides. Meanwhile, a device with larger fixed sides is also designed for comparison. The theoretical and finite element models are established to analyze the effect of the beam's effective stiffness on the output voltage and natural frequency. As the stiffness of the device decreases, the natural frequency of the device decreases while the output signal increases. The proposed polygonal topology with shorter fixed sides has higher voltage sensitivity than the larger fixed one based on finite element simulations. The piezoelectric accelerometers are fabricated using Cavity-SOI substrates with a core piezoelectric film of aluminum nitride (AlN) of about 928 nm. The fabricated piezoelectric MEMS accelerometers have good linearity (0.99996) at accelerations less than 2 g. The measured natural frequency of the accelerometer with shorter fixed sides is 98 kHz, and the sensitivity, resolution, and minimum detectable signal at 400 Hz are 1.553 mV/g, 1 mg, and 2 mg, respectively. Compared with the traditional trapezoidal cantilever with the same diaphragm area, its output voltage sensitivity is increased by 22.48%.

Paternal De Novo Variant of TAOK1 in a Fetus With Structural Brain Abnormalities.

A dilated lateral ventricle is a relatively common finding on prenatal ultrasound, and the causes are complex. We aimed to explore the etiology of a fetus with a dilated lateral ventricle. Trio whole-exome sequencing was performed to detect causative variants. A de novo variant of TAOK1 (NM_020791.2: c.227A>G) was detected in the proband and evaluated for potential functional impacts using a variety of prediction tools. Droplet digital polymerase chain reaction was used to exclude the parental mosaicism and to verify the phasing of the de novo variant. Based on peripheral blood analysis, the parents did not exhibit mosaicism at this site, and the de novo variant was paternally derived. Here, we describe a fetus with a de novo likely pathogenic variant of TAOK1 who had a dilated lateral ventricle and a series of particular phenotypes. This case expands the clinical spectrum of TAOK1-associated disorders. We propose a method for solving genetic disorders in which the responsible genes have not yet gone through ClinGen curation, particularly for prenatal cases.

Congenital soft tissue Ewing's sarcoma: A case report of pre- and postnatal magnetic resonance imaging findings.

RATIONALE: Most congenital soft tissue masses are benign. Ewing's sarcoma (ES) is a highly malignant tumor that commonly occurs in children and adolescents and rarely occurs during the fetal period. Cases of congenital soft tissue ES with magnetic resonance imaging (MRI) findings are scarce. To the best of our knowledge, no previous reports have described the pre- and postnatal MRI findings of ES. PATIENT CONCERNS: We present a case of congenital soft tissue ES arising in the body wall, which was examined using MRI during the prenatal and neonatal periods. DIAGNOSES: Malignancy was suspected by diffusion-weighted imaging, which demonstrated restricted diffusion within the mass even during the fetal period. ES was confirmed via histopathological examination after birth. INTERVENTIONS: The patient initially underwent conservative treatment for suspected hemangioma. Tumorrectomy was undergone after three weeks based on previously dissatisfied therapeutic effects. OUTCOMES: The patient died of multiple distant metastases despite undergoing postoperative chemotherapy and metastasectomies. LESSONS: Fetal or neonatal soft tissue ES may be clinically misdiagnosed as a hemangioma. It is important to suspect this through an imaging approach such as diffusion-weighted imaging.

A novel non-sense variant in the OFD1 gene caused Joubert syndrome.

Background: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis. Methods: Whole-exome sequencing and Sanger sequencing were performed to screen the causative gene variants in a suspected JBS family. RNA-seq and protein model prediction were performed to clarify the potential pathogenic mechanism. A more comprehensive review of previously reported cases with OFD1 variants is presented and may help to establish a genotype-phenotype. Results: We identified a novel non-sense variant in the OFD1 gene, OFD1 (NM_003611.3): c.2848A>T (p.Lys950Ter). Sanger sequencing confirmed cosegregation among this family. RNA-seq confirmed that partial degradation of mutant transcripts, which was predicted to be caused by the non-sense-mediated mRNA decay (NMD) mechanism, may explain the reduction in the proportion of mutant transcripts. Protein structure prediction of the non-sense variant transcript revealed that this variant may lead to a change in the OFD1 protein structure. Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease.

Congenital Visceral Vascular Variation Causing Gastrointestinal Hemorrhage: A Case Report.

Variations in the visceral vasculature are often encountered, but rarely cause clinical symptoms. We report a 12-year-old girl with portal hypertension caused by congenital variations in visceral vessels. The clinical manifestations included gastrointestinal hemorrhage and ascites. The common hepatic artery and splenic artery stem shared the same trunk from the aorta, and the common hepatic artery was directly connected with the main portal vein to form an arteriovenous fistula. In addition, the left hepatic artery and the left gastric artery shared a common trunk termed the "hepatic-gastric trunk" which originated from the anterior wall of the aorta, while the right hepatic artery originated from the superior mesenteric artery and supplied the right liver. The patient was treated with interventional embolization and remained in good condition throughout the follow-up and at the time of publication.

Prenatal diagnosis of midgut volvulus with jejunal atresia by ultrasonography.

Prenatal midgut volvulus is difficult to diagnose, and it is particularly difficult to evaluate the degree of rotation, which may be related to prognosis. We present a rare case of prenatal midgut volvulus with a 720° rotation around the superior mesenteric artery diagnosed based on ultrasonography, and jejunal atresia was noted at the same time. This condition was supported by prenatal magnetic resonance imaging and the subsequent postnatal operation. To the best of our knowledge, there is no previous literature describing similar ultrasound findings in the prenatal period. Recognition of the color Doppler ultrasound imaging findings can help elucidate the relationship among the twisted vessels of midgut volvulus during the prenatal examination.

User performance effects with graphical icons and training for elderly novice users: A case study on automatic teller machines.

This study investigated the effects with training and graphical icons on task performance for elderly novice users on automatic teller machines (ATMs). 124 elderly novice users who had no prior ATM experience participated in the training and test of ATM usage. Participants in the control group (n = 62) were training to use the traditional text-based ATM interface meanwhile those in the experimental group (n = 62) were training to use the alternative ATM interface with graphical icons. They were asked to learn how to perform three major tasks of ATMs. A test immediately following the training and a test one month after training was carried out. Task completion score was used for measuring user performance. The results showed although training could help elderly novice users succeed in learning to use ATMs, they still had a significant decline in user performance in the test one month later compared with the immediate test. Participants of the experimental group outperformed those of the control group in both the immediate test and one month test after training, especially in the latter. The finding suggested graphical icons could help to improve the learning and retention of ATM usage for elderly novice users, especially the latter, which would compensate for the drawback of training and reduce forgetting rate to some extent. Well-designed graphical icons could benefit elderly novice users much from learning phase to retention phase. The findings of this study can be applied to guide the design and development of ATMs or other public technology devices considering elderly novice users.