A novel MED12 pathogenic variant in a female fetus with facial cleft and cardiac defects identified in the first trimester.

Trio exome sequencing was performed on a female fetus with an increased nuchal translucency, along with nasal bone hypoplasia, suspected cleft palate and abnormal outflow tract of the heart. A de novo heterozygous variant c.5500_5507del, p.(Tyr1834Argfs × 58) in the MED12 gene was detected. Loss-of-function variants in MED12 in females are associated with Hardikar syndrome (HS). A follow-up ultrasound at 15+5 weeks of gestation identified multiple fetal anomalies including bilateral cleft lip and palate, diaphragmatic hernia, atrioventricular septal defect, persistent truncus arteriosus, and bilateral renal pelvis dilation. Fetal autopsy confirmed the prenatal sonographic findings, and the MED12 variant was discussed by our multidisciplinary team to be the cause of fetal anomalies. Our case is the first prenatal one in which HS was diagnosed due to first trimester structural malformations. This case report presents another example of early identification of a major anomaly which allows earlier genetic diagnosis and more time for clinical management.

Plant species diversity and functional diversity relations in the degradation process of desert steppe in an arid area of northwest China.

Species and functional diversity play a major role in the stability and sustainability of grassland ecosystems. However, changes in species and functional diversity during grassland degradation in arid areas as well as the underlying mechanisms remain unclear. In this study, we surveyed the vegetation and soil properties of arid regions across a degradation gradient to explore the shifts in species and functional diversity in plant communities, their relationships and key determinants during desert steppe degradation. Our results found significant variability in species diversity and functional diversity across degradation stages. Species diversity (Shannon-Wiener index (H), and Pielou index) and functional diversity (functional evenness (FEve) index, and Rao's quadratic entropy (RaoQ) index) tended to increase initially and then decrease with increasing grassland degradation. The Patrick index, Simpson index, functional richness (FRic) index, functional divergence (FDiv) index, and functional dispersion (FDis) index declined as grassland degradation increased. The relationships between species diversity and functional diversity indices at different stages of degradation in the desert steppe were inconsistent. From no to heavy degradation grasslands, the correlation between species diversity and functional diversity gradually weakened. Specifically, there was a significant correlation between Patrick (R) and FRic indices (R2 > 0.7) on both non-degraded and light degraded grasslands, but there was no significant correlation between R and FRic indices in moderately and heavily degraded grasslands (R2 < 0.7), and R2 gradually decreased. Redundancy analysis and partial least squares path modeling showed that grassland degradation has a significant direct effect on the species diversity and functional diversity. In addition grassland degradation has direct and indirect effects on the species diversity through soil available nitrogen, organic matter and total nitrogen. Functional diversity is directly or indirectly affected by species diversity, soil available nitrogen, organic matter and total nitrogen, soil moisture content, soil bulk density, and pH value. In summary, the relationship between species and functional diversity indices gradually weakened from areas with no degradation to heavy degradation in arid desert grasslands. Our study reveals the patterns and relationships between species diversity and functional diversity throughout the process of grassland degradation, demonstrating a gradual decrease in ecosystem stability and sustainability as degradation advances. Our results have significant implications for the restoration of grassland degradation and the management of ecosystem services in arid steppe regions.

Knowledge, attitude, and practice toward postpartum depression among the pregnant and lying-in women.

BACKGROUND: Postpartum depression (PPD) is considered an important public health problem, and early recognition of PPD in pregnant and lactating women is critical. This study investigated the knowledge, attitude, and practice (KAP) toward PPD among pregnant and lying-in women. METHODS: This cross-sectional study was conducted at Binzhou Medical University Hospital between September 2022 and November 2022 and included pregnant and lying-in women as study participants. A questionnaire was designed by the researchers that included demographic data and knowledge, attitude, and practice dimensions. Correlations between knowledge, attitude, and practice scores were evaluated by Pearson correlation analysis. Factors associated with practice scores were identified by multivariable logistic regression. RESULTS: All participants scored 6.27 ± 2.45, 36.37 ± 4.16, and 38.54 ± 7.93 93 from three sub-dimensions of knowledge, attitudes, and practices regarding PPD, respectively, with statistical differences in the three scores by age, education, and job status (p < 0.05). There were no significant differences between maternal (6.24 ± 2.34, 36.67 ± 3.82 and 38.31 ± 7.27, respectively) and pregnant women (6.30 ± 2.49, 36.00 ± 4.53 and 38.83 ± 8.69, respectively) in the total scores of knowledge, attitude, and practice dimensions. According to the results of multivariate logistic regression, the knowledge (OR = 1.235[1.128-1.353], P < 0.001) and attitude (OR = 1.052[1.005-1.102], P = 0.030) dimension scores were factors influencing the practice dimension scores. CONCLUSION: The KAP of pregnant and lying-in women toward PPD is low. This study suggests that maternal awareness of PPD should be increased through the knowledge and attitudinal dimensions. Preventing PPD in pregnant and lying-in women can be achieved by improving both dimensions, thus enhancing practice.

Insights into the mechanism of the deterioration of mainstream partial nitritation/anammox under low residual ammonium.

Residual ammonium is a critical parameter affecting the stability of mainstream partial nitritation/anammox (PN/A), but the underlying mechanism remains unclear. In this study, mainstream PN/A was established and operated with progressively decreasing residual ammonium. PN/A deteriorated as the residual ammonium decreased to below 5 mg/L, and this was paralleled by a significant loss in anammox activity in situ and an increasing nitrite oxidation rate. Further analysis revealed that the low-ammonium condition directly decreased anammox activity in situ via two distinct mechanisms. First, anammox bacteria were located in the inner layer of the granular sludge, and thus were disadvantageous when competing for ammonium with ammonium-oxidizing bacteria (AOB) in the outer layer. Second, the complete ammonia oxidizer (comammox) was enriched at low residual ammonium concentrations because of its high ammonium affinity. Both AOB and comammox presented kinetic advantages over anammox bacteria. At high residual ammonium concentrations, nitrite-oxidizing bacteria (NOB) were effectively suppressed, even when their maximum activity was high due to competition for nitrite with anammox bacteria. At low residual ammonium concentrations, the decrease in anammox activity in situ led to an increase in nitrite availability for nitrite oxidation, facilitating the activation of NOB despite the dissolved oxygen limitation (0.15-0.35 mg/L) for NOB persisting throughout the operation. Therefore, the deterioration of mainstream PN/A at low residual ammonium was primarily triggered by a decline in anammox activity in situ. This study provides novel insights into the optimized design of mainstream PN/As in engineering applications.

Fetal Rhabdomyoma Leads to Family Diagnosis of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder characterized by the growth of numerous noncancerous tumors in many parts of the body. It is highly variable in clinical presentations, including a wide range of cognitive, behavioral, and psychiatric manifestations. Of all the possible manifestations, cognitive and behavioral problems are the greatest concern to parents and physicians. In this study, two fetuses were identified to have rhabdomyomas by prenatal ultrasound. Carefully inquired familial medical history revealed other symptoms of TSC such as skin lesions or psychiatric problems in family members in the two families. Both fetuses and family members with positive clinical symptoms were confirmed to carry a familial TSC2 variant. Our study indicates that fetal echocardiography is not just the evaluation of the fetal heart. When fetal cardiac rhabdomyomas are diagnosed, a full family medical history and clinical assessment for TSC in family members should be undertaken.

Megacystis in the First Trimester as an Unreported Sonographic Finding of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Confirmed by Whole-exome Sequencing.

A pregnant woman was revealed to have fetal univentricular heart and megacystis by a routine first-trimester ultrasound. Chorionic villus sampling with the use of karyotyping and microarray found no causative etiologies. A further investigation with whole-exome sequencing (WES) demonstrated a FOXF1 variant. Autopsy confirmed the prenatal findings, and a histological study of the lungs showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This study indicates that although ultrasound itself has no ability of the identification of pulmonary histological malformations associated with ACDMPV, the early markers of univentricular heart and megacystis might alert clinicians to consider this genetic disorder which is facilitated considerably by the increasingly used WES in prenatal diagnosis.

Adducted Thumb in the First Trimester of Pregnancy: An Early Clue to Prenatal Diagnosis of L1 Syndrome.

A pregnant woman was revealed to have an unusual position of the fetal hand by a routine 12-week ultrasound. Bilateral adducted thumbs and a male phenotype were confirmed by another ultrasound at 14 weeks' gestation. A structural survey at 18 weeks revealed fetal hydrocephalus with severe bilateral ventriculomegaly. The pregnancy was terminated, and postnatal examination with trio exome sequencing detected a hemizygous deletion (1,511 bp in size) variant of L1CAM gene in the fetus, inherited from the mother. The fetus was diagnosed as L1 syndrome (X-linked hydrocephalus). A family study found that this was a familial mutant allele. This study demonstrates that fetal hand abnormalities can be identified in the first trimester. Adducted thumbs might indicate the maldevelopment of the fetal brain, and therefore, examination of fetal hands and fingers should be integrated into fetal anomaly scans.

Transcriptomic Landscape of von Economo Neurons in Human Anterior Cingulate Cortex Revealed by Microdissected-Cell RNA Sequencing.

The von Economo neurons (VENs) are specialized large bipolar projection neurons with restricted distribution in the human brain, and they are far more abundant in humans than in non-human primates. However, VEN functions remain elusive due to the difficulty of isolating VENs and dissecting their connections in the brain. Here, we combined laser-capture-microdissection with RNA sequencing to describe the transcriptomic profile of VENs from human anterior cingulate cortex (ACC). Using pyramidal neurons as reference cells, we identified 344 genes with VEN-associated expression differences, including 215 higher and 129 lower expression genes. Functional enrichment and protein-protein interaction network analyses showed that these genes with VEN-associated expression differences are involved in VEN morphogenesis and functions, such as dendrite branching and axon myelination, and many of them are associated with human social-emotional disorders. With the use of in situ hybridization and immunohistochemistry assays, we validated four novel VEN markers (VAT1L, CHST8, LYPD1, and SULF2). Collectively, we generated a full-spectrum expression profile of VENs from human ACC, greatly enlarging the pool of genes with VEN-associated expression differences that can help researchers to understand the role of VENs in normal and disordered human brains.

Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: Benefit for prenatal counseling and pregnancy management.

OBJECTIVE: The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar. METHOD: Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel. RESULTS: Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks. CONCLUSION: Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases.

[Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency].

OBJECTIVE: To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them. METHODS: The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies. RESULTS: Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated. CONCLUSION: Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.

Promotion of partial nitritation-anammox process by improving granule proportion.

For enhancing the partial nitritation-anammox (PN/A) process, the effects of granule fraction on system performance were investigated in this study. Two sequencing batch reactors (SBRs) were inoculated with PN/A biomass with a floc mass fraction of 53%. In SBR1, when the nitrogen removal rate (NRR) was stable, flocculent sludge was gradually discharged from the reactor using a screen, and the granule fraction was therefore increased. However, nitrogen removal was not improved and finally deteriorated due to the loss of nitritation activity. In SBR2, most flocculent sludge was eliminated and granular proportion was maintained at over 90% by controlling a short settling and decanting time. NRR was low initially but gradually improved to 1.23 kg N/(m3·d), which was 54% higher than SBR1. Ammonium oxidation activities of flocs and granules were respectively measured. Results suggested that the increase of nitritation activity in the granules was the main reason for the improvement of nitrogen removal in SBR2.

[Genotype and phenotype analysis of a child with partial 18q deletion syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of a child with chromosome 18q deletion syndrome. METHODS: G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on the child with abnormal phenotypes. Genotype-phenotype correlation was explored following accurate mapping of the breakpoints on chromosome 18q. SNP array was also performed on the genome DNA derived from peripheral venous blood samples from both parents. RESULTS: Chromosomal analysis revealed that the child has a karyotype of 46, XY, del(18) (q23). SNP array analysis detected a 9.855 Mb deletion (chr18: 68 158 880-78 014 123) at 18q22.2q23. Mapping of the breakpoints suggested that the deletion has overlapped with that of distal chromosome 18q deletion syndrome and encompassed several critical regions for this syndrome. SNP array performed on parental samples suggested that the 18q22.2q23 deletion was de novo in origin. FISH analysis of peripheral blood sample from the child confirmed the presence of 18qter deletion. CONCLUSION: The phenotype of this child may be attributed to the deletion of distal 18q22.2q23, which has encompassed several critical regions for the 18q deletion syndrome.

Determine the operational boundary of a pilot-scale single-stage partial nitritation/anammox system with granular sludge.

The partial nitritation/anammox (PN/A) process has been applied to ammonium-rich wastewater treatment, but the operational boundary has not been well determined for long-term stability. This pilot-scale study was targeted at a single-stage PN/A process using a sequencing batch reactor (SBR) (volume: 53 m(3)) and granulated activated sludge. The maximum nitrogen removal rate reached 0.83 kg N/(m(3)·d). Microbial analysis suggested that ammonium oxidizing bacteria were mainly present in small sludge flocs while anammox bacteria were prone to grow in large sludge granules. The PN/A performance was enhanced when dissolved oxygen (DO) was increased from 0.25 to 0.76 mg/L, and deteriorated at DO higher than 1.15 mg/L. The PN/A was inhibited at free ammonia (FA) over 77.0 mg/L. High DO or FA concentrations inhibited anammox activity and further induced high and inhibitory nitrite concentrations. Therefore, appropriate DO and FA concentrations should be controlled to achieve single-stage PN/A in SBRs.

[Improved identification for 5p deletion syndrome and partial trisomy 11q presented in a fetus by SNP array].

OBJECTIVE: To investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q. METHODS: G-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results. RESULTS: Karyotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result. CONCLUSION: SNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.