Retrospective analysis of the prognostic factors of fetal corpus callosum dysplasia.

BACKGROUND: To analyze the genetic characteristics and long-term outcomes of fetuses with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC). METHODS: A total of 42 fetuses with DCC (n = 36) or PACC (n = 6) were retrospectively analyzed from January 2016 to December 2022 at the Peking University First Hospital. The cohort was categorized into isolated (15/42, 36%) and nonisolated groups (27/42, 64%), and differences in the genetic abnormalities and long-term outcomes between the two groups were analyzed. DCC was subdivided into short CC, thin CC, and thick CC. The outcomes of the three different types of DCC were analyzed and discussed. RESULTS: (1) Thirty-nine of the 42 cases underwent CMA (chromosomal microarray analysis) and CMA + WES (whole exome sequencing), with 13/15 cases in isolated group and 26/27 cases in nonisolated group. Only pathogenic or likely pathogenic (P/LP) variants were considered, identifying P/LP variants in 2/13 cases in isolated group and 12/26 cases in nonisolated group. There was no significant difference between the two groups (χ² = 3.566, P = 0.05897). (2) In the isolated group, 8 cases were terminated, and 7 cases were delivered. Postnatal follow-up detected 1 case of gross motor development delay one year after birth; no obvious abnormalities were found in the other six cases. In the nonisolated group, 21 cases were terminated, and 6 cases were delivered. Postnatal follow-up detected 4 cases of children with different degrees of language, motor and intelligence abnormalities; 1 case died 10 days after birth. No obvious abnormalities were observed in one case. Six cases (86%, 6/7) in the isolated group showed normal development, compared with 1 case (17%, 1/6) in the nonisolated group, with a significant difference (χ² = 6.198, P = 0.01279). (3) In DCC, the delivery rates of short CCs (18 cases), thin CCs (13 cases), and thick CCs (5 cases) were 17% (3/18), 54% (7/13), and 20% (1/5), respectively, with good outcomes observed in 0% (0/3), 71% (5/7), and 0% (0/1), respectively. P/LP variants were found in 6/17 cases of short CC, 3/12 cases of thin CC, and 2/5 cases of thick CC. CONCLUSIONS: Fetuses with DCC or PACC combined with other structural abnormalities had a poor long-term prognosis compared with the isolated group. Patients with thin CCs had a higher probability of a good prognosis than those with short or thick CCs.

Developmental Process and Symmetry of Fetal Sulci in the Mesial Area Assessed by Ultrasound: A Cohort Study in Chinese Population.

OBJECTIVE: We aimed to investigate the progression of cortical development in Chinese population and to determine the rate of isolated asymmetric cortical development. We also explored the outcomes of these fetuses and determined whether cortical asymmetry represents normal individual physiological variation. METHODS: Our observational cohort study included 456 healthy singleton pregnant women who visited Peking University First Hospital between September 2020 and December 2021. We evaluated the progression and symmetry of the parieto-occipital sulcus, calcarine sulcus, and cingulate sulcus using a scoring system during routine fetal ultrasound examinations. The outcomes of the included fetuses after birth were assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: The median gestational ages at which the parieto-occipital, calcarine, and cingulate sulci reached grade 1 were 22, 22, and 26 weeks, respectively. Among 456 included fetuses, 426 showed symmetric cortical development and 30 showed asymmetric cortical development during ultrasound examination. Fetuses with asymmetric cortical development underwent 'catch-up growth' and developed to the same grade in 2-6 weeks. All fetuses with symmetric or asymmetric cortical development had normal neurodevelopment after birth according to ASQ-3 assessment. CONCLUSION: The gestational age at which the parieto-occipital, calcarine, and cingulate sulci can be detected using ultrasound varies in different studies. Racial differences may be present in cortical development. Normal fetuses may physiologically have mildly asymmetric cortical development in the mesial area.

Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis.

Background: The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified. Case presentation: The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 µmol/L (normal < 15 µmol/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 µmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy's mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy. Conclusion: Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.

Enhancing early autism prediction based on electronic records using clinical narratives.

Recent work has shown that predictive models can be applied to structured electronic health record (EHR) data to stratify autism likelihood from an early age (<1 year). Integrating clinical narratives (or notes) with structured data has been shown to improve prediction performance in other clinical applications, but the added predictive value of this information in early autism prediction has not yet been explored. In this study, we aimed to enhance the performance of early autism prediction by using both structured EHR data and clinical narratives. We built models based on structured data and clinical narratives separately, and then an ensemble model that integrated both sources of data. We assessed the predictive value of these models from Duke University Health System over a 14-year span to evaluate ensemble models predicting later autism diagnosis (by age 4 years) from data collected from ages 30 to 360 days. Our sample included 11,750 children above by age 3 years (385 meeting autism diagnostic criteria). The ensemble model for autism prediction showed superior performance and at age 30 days achieved 46.8% sensitivity (95% confidence interval, CI: 22.0%, 52.9%), 28.0% positive predictive value (PPV) at high (90%) specificity (CI: 2.0%, 33.1%), and AUC4 (with at least 4-year follow-up for controls) reaching 0.769 (CI: 0.715, 0.811). Prediction by 360 days achieved 44.5% sensitivity (CI: 23.6%, 62.9%), and 13.7% PPV at high (90%) specificity (CI: 9.6%, 18.9%), and AUC4 reaching 0.797 (CI: 0.746, 0.840). Results show that incorporating clinical narratives in early autism prediction achieved promising accuracy by age 30 days, outperforming models based on structured data only. Furthermore, findings suggest that additional features learned from clinician narratives might be hypothesis generating for understanding early development in autism.

Predictive Value of Early Autism Detection Models Based on Electronic Health Record Data Collected Before Age 1 Year.

Importance: Autism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection. Objective: To quantify the predictive value of early autism detection models based on EHR data collected before age 1 year. Design, Setting, and Participants: This retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022. Main Outcomes and Measures: Prediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds. Results: Data from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity. Conclusions and Relevance: In this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.

Transvaginal ultrasound parameters to evaluate cervical favorability and predict the outcome of induction of labor.

OBJECTIVE: To compare the values of transvaginal ultrasound (TVU) and Bishop score (BS) for predicting outcomes of induction of labor (IOL). METHODS: The BS and TVU were assessed before IOL. TVU parameters included cervical length (CL) and E-Cervix comprising the cervical hard ratio (HR) and the mean strain level of internal os (IOS). Study end-points included the duration of the latent phase within 15 or 18 h and delivery within 24 h. RESULTS: In multivariable logistic regression models, at the first two end-points, the areas under the curve (AUCs) for CL with HR were 0.733 and 0.777, and the AUCs for CL with IOS were 0.754 and 0.787, respectively, The AUC for HR was 0.750 at the third end-point. With receiver operating characteristic (ROC) analysis, the best cut-off value for CL was ≤1.38 cm and that for IOS was ≥0.35. The AUCs of the TVU scoring system by the cut-off values for CL and IOS for the three end-points were 0.784, 0.833, and 0.855, respectively. The predicting values of both methods were better than those of the BS (AUC = 0.672, 0.694, and 0.687, respectively). CONCLUSION: Cervical length along with E-Cervix showed better predictive values for successful induction compared with the BS.

Corrigendum: Development and initial validation of a clinical measure to assess symptoms of post-stroke depression in stroke patients at the rehabilitation stage.

[This corrects the article DOI: 10.3389/fpsyg.2022.928257.].

Development and initial validation of a clinical measure to assess symptoms of post-stroke depression in stroke patients at the rehabilitation stage.

Background: The high incidence of post-stroke depression (PSD) during rehabilitation exerts a negative effect on the treatment and functional recovery of patients with stroke and increases the risk of mortality. It is necessary to screen PSD in the rehabilitation stage and thus provide effective intervention strategies. However, existing measurements used to assess PSD in the rehabilitation stage in patients with stroke lack specificity. This study aimed to develop a clinical measure to assess symptoms of PSD in the rehabilitation stage. Methods: The research team created the initial items through a literature review and semi-structured interviews of patients with stroke. Then, the symptom-related items were estimated by three panels: healthcare professionals (N = 41), Delphi experts (N = 15), and patients with stroke in the rehabilitation stage (N = 30). Results: The literature review and semi-structured interview produced 51 symptom-related items including six domains, and the items were reduced to 47 by the healthcare professionals. The symptom-related items were further reduced to 33 items by a two-round Delphi consultation. The initiative coefficients of the two Delphi rounds were 71.4 and 100%, the expert authority coefficients were both 0.85, Kendall's W were 0.152 and 0.408 (p < 0.01), and the coefficient of variation (CV) were 0.05-0.32 and 0.00-0.18, respectively. The item-level content validity index (I-CVI) was 0.53-1.00, the scale-level CVI/universal agreement (S-CVI/UA) was 0.26, and the S-CVI/average (S -CVI/Ave) was 0.85 for the first found Delphi consultation; the I-CVI was 0.67-1.00, the S-CVI/UA was 0.61, and the S-CVI/Ave was 0.97 for the second round Delphi consultation. All content validity indicators have been significantly improved compared with the first round. Using mean ≥ 4 and full score ≥ 0.5, combined with CV ≤ 0.16 as the item criteria, a clinical measure of PSD with 33 items and 6 dimensions (cognition, sleep, behavior, emotion, body, and guilt) was finally formed after two rounds. The patients with stroke made no further revisions after evaluation. Conclusion: The research team developed a specific tool with good content validity to assess the symptoms of PSD in the rehabilitation stage.

Stress and coping styles among nursing students during the initial period of the clinical practicum: A cross-section study.

Objectives: This study aimed to explore the level of stress, types of stressors, type of coping styles, and factors influencing stress levels and coping styles among nursing students during the initial period of the clinical practicum. Methods: A cross-sectional survey design was used. In September 2017, participants were recruited from a tertiary hospital in Zhejiang Province, China, using a convenience sampling method. A demographic characteristics questionnaire, the Intern Nursing Student Stressor Scale, and the Simple Coping Style Questionnaire were used to collect data. Data were analyzed using descriptive analysis, independent sample t-tests, one-way analysis of variance, Pearson's correlation analysis, and multiple linear regression analysis. Results: A total of 158 nursing students were recruited, most of whom were female, undergraduates, and from rural areas. The nursing students perceived a moderate level of stress during the initial period of the clinical practicum. The need for knowledge and skills was the most common source of stress. Positive coping styles were most commonly adopted. Nursing students who were undergraduates, only children, and chose nursing major involuntarily experienced higher stress levels than those who were junior college students, not only children, and chose nursing major voluntarily. Nursing undergraduates were more likely to use positive coping styles than junior college students. Male nursing students and those experiencing higher stress levels related to the "environment and equipment of the wards" and the "nature and content of the work" were more likely to use negative coping styles. Conclusion: Nursing educators should offer targeted guidance based on the stress reported during the clinical practicum and the demographic characteristics of the nursing students. Guidance should be provided to encourage nursing students to adopt effective coping strategies and reduce stress.

Comparing amniotic fluid mass spectrometry assays and amniocyte gene analyses for the prenatal diagnosis of methylmalonic aciduria.

BACKGROUND: Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However, the prenatal diagnosis of MMA using cultured amniocytes or chorionic villi to detect gene mutations is exclusively applicable to families with a definite genetic diagnosis. To evaluate the reliability of mass spectrometry assays for the prenatal diagnosis of MMA, we conducted a retrospective study of our 10 years' experience. MATERIALS AND METHODS: This retrospective compare study reviewed the medical records for maternal and fetuses data for 287 mothers with a family history of MMA from June 2010 to December 2020. Methylmalonate and propionylcarnitine in cell-free amniotic fluid were measured using a stable isotope dilution method (GC/MS) and MS/MS-based method (LC/MS/MS). Total homocysteine (tHcy) was measured by fluorescence polarization immunoassay. Depending on the presence of disease-causing gene mutations in probands, gene studies on amniocytes from 222 pregnant women were performed. RESULTS: For 222 fetuses of the families with definite genetic diagnosis, gene analyses were performed using cultured amniocytes. 52 fetuses were affected by MMA, whereas 170 were "unaffected". For GC/MS and LC/MS/MS, the specificity was 96.5% and 95.9%, sensitivity was 71.2% and 84.6%, respectively. The positive and negative predictive values were 86.0% and 91.6% and 86.3% and 95.3%, respectively. Propionylcarnitine/butyrylcarnitine ratio showed the highest accuracy and could thus serve as a sensitive indicator to identify those at a risk for MMA. When GC/MS and LC/MS/MS were performed in parallel, the specificity was 92.5% and sensitivity was 95.6%. When evaluating tHcy, the positive and negative predictive values were 95.0% and 96.1%, respectively. In 65 fetuses without family genetic diagnosis, 11 were finally confirmed to have MMA and 54 were "unaffected" by amniotic fluid biochemical assays. The 54 children showed normal urine organic acids and healthy development after birth. CONCLUSIONS: Amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel increased the accuracy of prenatal diagnosis of MMA. Propionylcarnitine is a more reliable marker than methylmalonic acid in amniotic fluid. Further, tHcy is recommended for the prenatal diagnosis of combined MMA and homocysteinemia.

Development and validation of the Health Education Adherence Scale for Stroke Patients: a cross-sectional study.

BACKGROUND: Due to the lack of health education adherence assessment tools for stroke patients, the assessment of health education adherence in this population is insufficient, which hinders the prevention and rehabilitation of stroke. This study aims to develop and validate a Health Education Adherence Scale for Stroke Patients (HEAS-SP). METHODS: A cross-sectional design with a purposive sampling method was used for this study. Six hundred and fifty-four eligible participants completed the demographic questionnaire and the HEAS-SP. The data collection lasted for 7 months, from March 1stto September 30th in 2019. Item analysis and exploratory and confirmatory factor analysis were employed to develop and validate the HEAS-SP. RESULTS: The item analysis, exploratory and confirmatory factor analysis resulted in a 20-item HEAS-SP with 4 domains: medication adherence, diet adherence, rehabilitation exercise adherence, and healthy lifestyle adherence. The four-domain model demonstrated acceptable model fit indexes and the 20-item HEAS-SP demonstrated acceptable reliability and validity. CONCLUSION: The 20-item HEAS-SP was shown to have acceptable reliability and validity for assessing health education adherence with respect to diet, medication, rehabilitation exercise and healthy lifestyle in stroke patients, making it a potential basis for developing targeted interventions for stroke patients.

Simpson-Golabi-Behmel syndrome in one of the Dichorionic-diamniotic twin: a case report and literature review.

BACKGROUND: Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked overgrowth syndrome. The main clinical manifestations are overgrowth and multiple malformations. CASE PRESENTATION: A 38-year-old Chinese woman was pregnant with dichorionic-diamniotic (DCDA) twins after in-vitro fertilization. Series of ultrasound examinations indicated that the measurements (abdominal circumference and estimated foetal weight) of one twin were significantly greater than those of the other one. The genetic testing results of the larger baby indicated of Simpson-Golabi-Behmel syndrome. CONCLUSION: SGBS is difficult to diagnose due to different clinical manifestations. Clinicians need to be more aware of typical SGBS's clinical findings and choose genetic testing methods individually to improve its prenatal diagnosis.

Neurodevelopmental outcomes in mild and moderate isolated ventriculomegaly originating in utero.

OBJECTIVE: To determine the differences in outcomes between mild and moderate isolated ventriculomegaly (IVM). METHODS: We conducted a prospective cohort study on 94 fetuses with IVM and evaluated the neurodevelopmental outcomes at 12 months of age using the ASQ-3 and BSID-I neurodevelopmental assessment tools. Progression of VM was defined as an increase in the width of the ventricular by at least 3 mm during sequential ultrasound monitoring. The population was divided into two groups according to ventricular width: mild (10-12 mm) and moderate (12.1-15 mm), which were further evaluated for VM progression in utero separately. RESULTS: Neurodevelopmental assessments at 12 months were the main form of evaluations. Neurodevelopmental impairment (NDI) was defined as a mental development index (MDI) or psychomotor development index (PDI) < 85. There were no significant differences in NDI values between the mild and moderate groups (p = .155). Compared with the non-in utero progression group (7.6%), the rate of NDI was significantly higher (p = .004) in the group with progression (33.3%). Using linear regression and correlation, no negative correlation was found between the maximum value of atrial diameter (AD) in utero and the PDI (r = -0.021, p = .914) or MDI (r = -0.073, p = .703) score. However, the maximum change in the AD in utero was negatively correlated with both PDI (r = -0.460, p = .011) and MDI (r=-0.422, p = .020) scores. CONCLUSION: There were likely no differences in neurodevelopmental outcomes between mild and moderate IVM. In fetuses with mild to moderate VM, intrauterine progression may be a poor prognostic factor for neurodevelopmental outcomes.

Correlation between mild fetal ventriculomegaly, chromosomal abnormalities, and copy number variations.

BACKGROUND: Lateral ventriculomegaly is the most common abnormality of the fetal nervous system. This study investigated the incidence of chromosomal abnormalities and copy number variations (CNVs) in fetuses with mild ventriculomegaly (MV) based on various ultrasonic manifestations, identifying their corresponding features via ultrasound examination. METHODS: A retrospective analysis was performed on ultrasound and neurosonogram (NSG) manifestations and genetic profiles of 334 cases with MV and invasive prenatal diagnosis. RESULTS: Three hundred thirty-four cases with fetal MV were assessed via karyotyping. Further chromosomal microarray analysis (CMA) was performed in 182 cases with normal chromosome karyotypes; pathogenic chromosomal copy number variations (CNVs) were found in eight cases with a prevalence of 4.4% (8/182). In this study, the incidence rate of pathogenic abnormalities of chromosomes and CNVs was 5.7% (19/334). Based on whether lateral ventriculomegaly was complicated with other ultrasonic features, the 334 patients were divided into two groups: (1) 175 cases exhibited isolated ventriculomegaly (IVM; 52.4%, 175/334 group A) including two (1.1%, 2/175) with pathogenic chromosomal karyotype abnormalities-both trisomy 21; (2) 159 cases exhibited non-isolated ventriculomegaly (N-IVM; 47.6%, 159/334) with pathogenic chromosomal abnormalities and CNVs detected in17 cases (10.7%, 17/159). The N-IVM group was further divided into two groups: 105 cases exhibited MV with undetermined ultrasonic abnormalities (31.4%, 105/334, group B) with pathogenic chromosomal abnormalities and CNVs detected in eight cases (7.6%, 8/105); 54 cases exhibited MV with structural malformations (16.2%, 54/334, group C) of which nine cases (16.7%, 9/54) presented both pathogenic chromosomal abnormalities and CNVs, and five cases (55.6%, 5/9) were diagnosed with various cortical malformations. The pathogenicity rates of the IVM and N-IVM groups were statistically different (χ2=14.159, p = 0.000). There were significant differences (χ2=7.992, p = 0.005) among groups A, B, and C. CONCLUSIONS: Combinations of various ultrasonic abnormalities significantly affect the risk of pathogenic chromosomal abnormalities and CNVs in fetuses with MV. Cases involving cortical malformations require particular attention to the occurrence of pathogenic genetic abnormalities. When fetal MV is detected, a comprehensive ultrasound examination focusing on undetermined ultrasonic abnormalities is critical. Fetal NSG should be conducted to detect potential cerebral cortical malformation easily missed by routine ultrasound.

Symptom clusters of early-stage poststroke depression: A mixed-methods study.

AIM: To identify the symptom clusters of early-stage poststroke depression (PSD) and provide an in-depth understanding of the symptoms. DESIGN: A mixed-methods study with a convenient sampling method was used. METHODS: A cross-sectional questionnaire survey in 231 stroke patients and semi-structured interviews in 14 stroke patients were conducted in the neurological department of a comprehensive hospital in Southeast China. Data from the questionnaire survey were analysed through descriptive and exploratory factor analyses; data from the semi-structured interview were transcribed verbatim and analysed through inductive content analysis. This study adheres to the GRAMMS checklist. RESULTS: Exploratory factor analysis revealed six symptom clusters of early-stage PSD that accounted for an ideal variance in PSD: nervous, wakefulness, emotional, dull, guilt and low mood. Further, inductive content analysis revealed five themes that were like the above symptom clusters, except for the dull symptom cluster.

Supercharging Imbalanced Data Learning With Energy-based Contrastive Representation Transfer.

Dealing with severe class imbalance poses a major challenge for many real-world applications, especially when the accurate classification and generalization of minority classes are of primary interest. In computer vision and NLP, learning from datasets with long-tail behavior is a recurring theme, especially for naturally occurring labels. Existing solutions mostly appeal to sampling or weighting adjustments to alleviate the extreme imbalance, or impose inductive bias to prioritize generalizable associations. Here we take a novel perspective to promote sample efficiency and model generalization based on the invariance principles of causality. Our contribution posits a meta-distributional scenario, where the causal generating mechanism for label-conditional features is invariant across different labels. Such causal assumption enables efficient knowledge transfer from the dominant classes to their under-represented counterparts, even if their feature distributions show apparent disparities. This allows us to leverage a causal data augmentation procedure to enlarge the representation of minority classes. Our development is orthogonal to the existing imbalanced data learning techniques thus can be seamlessly integrated. The proposed approach is validated on an extensive set of synthetic and real-world tasks against state-of-the-art solutions.

Significance of the ability to differentiate emotional prosodies for the early diagnosis and prognostic prediction of mild hypoxic-ischemic encephalopathy in neonates.

BACKGROUND: Perinatal brain injury affects around 300,000 neonates in China each year, early diagnosis and active intervention are also crucial for timely treatment and better prognoses. As hearing is the earliest as well as the most sensitive sense to develop in neonates, we propose that the ability to differentiate among different emotional prosodies may differ between neonates with and without brain injuries. METHODS: We enrolled full-term neonates admitted to the neonatology department of Peking University First Hospital from January 2016 to December 2016, conducted functional near-infrared spectroscopy (fNIRS) monitoring within 24 hr of admission, and analyzed changes in oxyhemoglobin (ΔHbO2 ) and deoxyhemoglobin (ΔHb) to study the ability of neonates to differentiate among emotional prosodies. The neonates were followed up to 36 months for neurological outcome evaluation. RESULTS AND CONCLUSIONS: We found that neonates showed the early ability to differentiate among emotional prosodies, responding most sensitively to positive emotions, and this ability may have been impaired following brain injury.

The cytomegalovirus UL146 gene product vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1.

The HCMV (human cytomegalovirus) encodes numerous proteins which function to evade the immune response, which allows the virus to replicate. Exploring the mechanisms of HCMV immune escape helps to find the strategy to inhibit HCMV replicate. CD8+ T cells play a critical role in the immune response to viral pathogens. However, the mechanisms of HCMV to evade the attack by CD8+ T cells remain largely unknown. Viral CXCL1 (vCXCL1) is the production of HCMV UL146 gene. Here, we found that vCXCL1 promoted the resistance of hepatic cells to CD8+ T cells. vCXCL1 increased the levels of PD-L1 protein expression and mRNA expression. VCXCL1 enhanced the binding of STAT3 transcription factor to the promoter of PD-L1 and increased the activity of PD-L1 promoter. Furthermore, down-regulation of PD-L1 reduced the effects of vCXCL1 on the resistance of hepatic cells to CD8+ T cells. Taken together, vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1. This finding might provide a new mechanism of HCMV immune escape.

Identification of Novel ARSA Mutations in Chinese Patients with Metachromatic Leukodystrophy.

OBJECTIVE: Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA) that leads to severe physiologic and developmental problems. Our study is aimed at elucidating the clinical and genetic characteristics of Chinese MLD patients. METHODS: Clinical data of 21 MLD patients was collected. All coding exons of ARSA and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. RESULTS: All 21 patients were diagnosed with MLD clinically and genetically, out of which 17 patients were late infantile and 4 were juvenile types. A total of 34 ARSA mutations, including 28 novel mutations (22 missense, 1 splicing, 1 nonsense, 3 small insertions, and 1 small deletion mutation) and 6 known mutations (5 missense and 1 small insertion mutation), were identified. Prenatal diagnosis was performed for four pedigrees. One fetus was a patient, two fetuses were carriers, and two were wild type. CONCLUSIONS: The present study discovered 28 novel ARSA mutations and widely expanded the mutation spectrum of ARSA. Four successful prenatal diagnoses provided critical information for MLD families.

Identification of novel ATP7A mutations and prenatal diagnosis in Chinese patients with Menkes disease.

Menkes disease (MD) is a fatal X-linked multisystem disease caused by mutations in ATP7A. In this study, clinical and genetic analysis was performed in 24 male MD patients. Development delay, seizures, kinky coarse hair, and dystonia were found in 24, 22, 24, and 24 patients, respectively. Serum ceruloplasmin/copper tested in 19 patients was low. Abnormal classic features of MD presented in the MRI/MRA of 19 patients. Seventeen mutations of ATP7A were identified in 22 patients. Twelve were novel mutations including three small deletion/insertion, one missense mutation, two nonsense mutations, three splicing-site mutations, and three gross deletions. Twenty-two patients were genetically diagnosed; neither point mutation nor deletion/duplication was found in two of them. c.2179G > A found in five patients might be a hot-spot mutation. Prenatal molecular diagnosis was performed for five unrelated fetuses (1 female and 4 male), which found four fetuses to be wild type and one male carried the same mutation as the proband. This study of the largest sample of Chinese MD patients examined to date discovered the unique phenotype and genotype spectrum in Chinese patients with 12 novel mutations of ATP7A, and that c.2179G > A might be a hot-spot mutation in MD patients. Five successful prenatal diagnosis contributed important information for MD families.