Quantitative Proteomics and Metabolomics of Culture Medium from Single Human Embryo Reveal Embryo Quality-Related Multiomics Biomarkers.

An effective tool to assess embryo quality in the assisted reproduction clinical practice will enhance successful implantation rates and mitigate high risks of multiple pregnancies. Potential biomarkers secreted into culture medium (CM) during embryo development enable rapid and noninvasive methods of assessing embryo quality. However, small volumes, low biomolecule concentrations, and impurity interference collectively preclude the identification of quality-related biomarkers in single blastocyst CM. Here, we developed a noninvasive trace multiomics approach to screen for potential markers in individual human blastocyst CM. We collected 84 CM samples and divided them into high-quality (HQ) and low-quality (LQ) groups. We evaluated the differentially expressed proteins (DEPs) and metabolites (DEMs) in HQ and LQ CM. A total of 504 proteins and 189 metabolites were detected in individual blastocyst CM. Moreover, 9 DEPs and 32 DEMs were identified in different quality embryo CM. We also categorized HQ embryos into positive implantation (PI) and negative implantation (NI) groups based on ultrasound findings on day 28. We identified 41 DEPs and 4 DEMs associated with clinical implantation outcomes in morphologically HQ embryos using a multiomics analysis approach. This study provides a noninvasive multiomics analysis technique and identifies potential biomarkers for clinical embryo developmental quality assessment.

Early stimulation and responsive care: A mediator of caregivers' depression on the suspected developmental delay of left-behind children in China.

BACKGROUND: Due to multiple factors, left-behind children in rural areas suffer from neurodevelopment delay and their caregivers suffer from depressive symptoms. This study aimed to analyze the effect of caregivers' depressive symptoms on left-behind children's neurodevelopment, with early stimulation and responsive care mediating. METHODS: We conducted a cross-sectional survey in five counties in China. A total of 904 left-behind children aged 0-3 and their primary caregivers were enrolled. The Zung Self-rating Depression Scale (ZSDS) was used to measure caregivers' depressive symptoms. The Ages and Stages questionnaires-third edition (ASQ-3), which contains five domains: communication (CM), gross motor (GM), fine motor (FM), problem-solving (CG), and personal social (PS), was used to screen children for suspected developmental delay (SDD). RESULTS: 31.4 % of left-behind children suffered from SDD, while 39.7 % of left-behind children's caregivers experienced depressive symptoms. Caregivers' ZSDS scores were positively correlated with the SDD on four domains (FM, GM, CG, and PS), while Early stimulation and responsive care was negatively correlated with the SDD on four domains (CM, FM, CG, and PS). LIMITATIONS: The cross-sectional design limited the ability to ascertain causal relations. Besides, the findings may not be generalized to all regions of China due to the heterogeneity of the study population. CONCLUSIONS: Left-behind children under three years old in rural China were at high risk of SDD, while a substantial proportion of their caregivers had depressive symptoms. Caregivers' depressive symptoms may negatively affect the SDD of left-behind children through caregivers providing less early stimulation and responsive care.

Multiplex Protein Profiling by Low-Signal-Loss Single-Cell Western Blotting with Fluorescent-Quenching Aptamers.

Single-cell western blotting (scWB) is a prevalent technique for high-resolution protein analysis on low-abundance cell samples. However, the extensive signal loss during repeated antibody stripping precludes multiplex protein detection. Herein, we introduce Fluorescent-quenching Aptamer-based Single-cell Western Blotting (FAS-WB) for multiplex protein detection at single-cell resolution. The minimal size of aptamer probes allows rapid in-gel penetration, diffusion, and elution. Meanwhile, the fluorophore-tagged aptamers, coordinated with complementary quenching strands, avoid the massive signal loss conventionally caused by antibody stripping during repeated staining. Such a strategy also facilitates multiplex protein analysis with a limited number of fluorescent tags. We demonstrated FAS-WB for co-imaging four biomarker proteins (EpCAM, PTK7, HER2, CA125) at single-cell resolution with lower signal loss and enhanced signal-to-noise ratio compared to conventional antibody-based scWB. Being more time-saving (less than 25 min per cycle) and economical (1/1000 cost of conventional antibody probes), FAS-WB offers a highly efficient platform for profiling multiplex proteins at single-cell resolution.

The relationship between home environment and early childhood development of left-behind children under 3 years in rural China.

BACKGROUND: Home environment provides stimulation and learning opportunities required for children's early development. However, few studies have focused on the effects of home environment on left-behind children's development in rural China. The study aimed to investigate the relationship between home environment and early childhood development of left-behind children under 3 years old in rural China. METHODS: Information about sociodemographic characteristics, caregivers' mental health, home environment and children's development was collected. Infant/Toddler Home Observation for Measurement of the Environment Inventory (IT-HOME) was used to assess home environment. Child's development was evaluated with the Chinese version of the Ages & Stages Questionnaire - third edition. RESULTS: Elevated caregivers' depressive symptoms were associated with a higher risk of total suspected development delay. An increase of one score in the IT-HOME resulted in a 7% decrease in total suspected development delay. Higher scores in the dimensions of involvement and variety were associated with a lower risk of suspected development delay adjusting for covariates. CONCLUSIONS: Our results have implications for home-based intervention aiming at promoting nurturing care as well as caregivers' mental health, which is required for early development of young left-behind children in rural areas of China.

The mitochondrial genome of Binodoxys acalephae (Hymenoptera: Braconidae) with unique gene rearrangement and phylogenetic implications.

BACKGROUND: Species in the subfamily Aphidiinae from the Braconidae of Hymenoptera are endoparasitic wasps that exclusively utilize aphids as hosts. Some Aphidiinae species are widely used as biological agents. However, there were only one species with determined complete mitochondrial genome from this subfamily. METHODS AND RESULTS: In this study, we sequenced and annotated the mitochondrial genome (mitogenome) of Binodoxys acalephae, which was 15,116 bp in size and contained 37 genes. The start codon of 13 protein-coding genes was ATN, and the complete stop codon TAA and TAG was widely assigned to 11 protein-coding genes. The lrRNA contains 43 stem-loop structures, and srRNA contains 25 stem-loop structures. Translocation and inversion of tRNA genes was found to be dominant in B. acalephae. In contrast to Aphidius gifuensis from the same subfamily Aphidiinae, inverted tRNALeu1 was translocated to the gene cluster between tRNALeu2 and COX2, and the control region between tRNAIle and tRNAMet was deleted in the mitogenome of B. acalephae. Within Braconidae, gene clusters tRNATrp-tRNACys-tRNATyr and CR-tRNAIle-tRNAGln-tRNAMet were hotspots for gene rearrangement. Phylogenetic analysis showed that both Bayesian and maximum-likelihood methods recovered the monophyly of Aphidiinae and suggested that Aphidiinae formed sister clades with the remaining subfamilies. The phylogenetic analyses of nine subfamilies supported the monophyly of Cyclostomes and Noncyclostomes in Braconidae. CONCLUSION: The arrangement of mitochondrial genes and the phylogenetic relationships among nine Braconidae subfamilies were constructed better to understand the diversity and evolution of Aphidiinae mitogenomes.

Prediction for pathological and immunohistochemical characteristics of triple-negative invasive breast carcinomas: the performance comparison between quantitative and qualitative sonographic feature analysis.

OBJECTIVE: Sonographic features are associated with pathological and immunohistochemical characteristics of triple-negative breast cancer (TNBC). To predict the biological property of TNBC, the performance using quantitative high-throughput sonographic feature analysis was compared with that using qualitative feature assessment. METHODS: We retrospectively reviewed ultrasound images, clinical, pathological, and immunohistochemical (IHC) data of 252 female TNBC patients. All patients were subgrouped according to the histological grade, Ki67 expression level, and human epidermal growth factor receptor 2 (HER2) score. Qualitative sonographic feature assessment included shape, margin, posterior acoustic pattern, and calcification referring to the Breast Imaging Reporting and Data System (BI-RADS). Quantitative sonographic features were acquired based on the computer-aided radiomics analysis. Breast cancer masses were manually segmented from the surrounding breast tissues. For each ultrasound image, 1688 radiomics features of 7 feature classes were extracted. The principal component analysis (PCA), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were used to determine the high-throughput radiomics features that were highly correlated to biological properties. The performance using both quantitative and qualitative sonographic features to predict biological properties of TNBC was represented by the area under the receiver operating characteristic curve (AUC). RESULTS: In the qualitative assessment, regular tumor shape, no angular or spiculated margin, posterior acoustic enhancement, and no calcification were used as the independent sonographic features for TNBC. Using the combination of these four features to predict the histological grade, Ki67, HER2, axillary lymph node metastasis (ALNM), and lymphovascular invasion (LVI), the AUC was 0.673, 0.680, 0.651, 0.587, and 0.566, respectively. The number of high-throughput features that closely correlated with biological properties was 34 for histological grade (AUC 0.942), 27 for Ki67 (AUC 0.732), 25 for HER2 (AUC 0.730), 34 for ALNM (AUC 0.804), and 34 for LVI (AUC 0.795). CONCLUSION: High-throughput quantitative sonographic features are superior to traditional qualitative ultrasound features in predicting the biological behavior of TNBC. KEY POINTS: • Sonographic appearances of TNBCs showed a great variety in accordance with its biological and clinical characteristics. • Both qualitative and quantitative sonographic features of TNBCs are associated with tumor biological characteristics. • The quantitative high-throughput feature analysis is superior to two-dimensional sonographic feature assessment in predicting tumor biological property.

Application of KTH-integrated nursing model in care of patients with multi-drug resistant tuberculosis.

OBJECTIVE: To evaluate the effect of the KTH-integrated nursing model of the knowledge-attitude-belief-practice model (KABP)-transtheoretical model (TTM)-as a health belief model (HBM) in nursing care of patients with multi-drug resistant tuberculosis (MDR-TB). METHODS: Using a prospective study method, 102 patients with MDR-TB were randomly divided into two groups according to a random number table. The control group (n=51) received conventional nursing care, and the study group (n=51) received a KTH-integrated nursing model. The sputum negative conversion rate, effective rate of lesion absorption, level of disease cognition, compliance, self-efficacy (general self-efficacy scale, GSES score), healthy behavior (health-promoting lifestyle profile, HPLP), and quality of life (GQOL-74 scale score) were compared between the two groups. RESULTS: Six months after enrollment, the sputum-negative conversion rate, total effective rate of lesion absorption, and total compliance rate of the study group were significantly higher than those of the control group (80.39% vs. 62.75%, 84.31% vs. 66.67%, 96.08% vs. 78.43%, P<0.05). 6 months after enrollment, the treatment plan, etiopathogenesis and harm, precautions, importance of treatment compliance, observation and follow-up, and total score of the study were all significantly higher than those of the control group (P<0.05). Six months after enrollment, the scores of GSES, HPLP and GQOL-74 in the study group were significantly higher than those of the control group (P<0.05). CONCLUSION: The implementation of a KTH integrated nursing model for patients with MDR-TB was beneficial to promote sputum-negative conversion and lesion absorption, and improved disease awareness, medication compliance, self-efficacy, healthy behavior, and quality of life.

Impact of parent-child separation on children's social-emotional development: a cross-sectional study of left-behind children in poor rural areas of China.

BACKGROUND: Parent-child separation is a considerable adversity for left-behind children (LBC), but there is little evidence on the association between detailed characteristics of parent-child separation and social-emotional development among LBC. This study examined the characteristics of parent-child separation and its impacts on developmental delay among under-3 LBC in poor rural China. METHODS: We used data from 811 LBC surveyed in five poor counties in rural China in 2018. Detailed characteristics of their parental migration were recalled by their primary caregivers in face-to-face interviews. The children's social-emotional development was measured by using the Ages and Stages Questionnaire: Social-Emotional. Logistic regression was employed to examine the association of detailed characteristics of parent-child separation with early social-emotional problems after adjusting for the children's and primary caregivers' sociodemographic characteristics. RESULTS: 287 (35.4%) children were left behind by fathers and cared for by mothers (FM-MC), while 524 (64.6%) were left behind by both parents and cared for by grandparents (PM-GC). The rate of social-emotional problems among LBC was 36.8% (PM-GC vs FM-MC: 40.6% vs 29.5%; aOR 1.51, 95% CI: 1.06 to 2.16). For paternal migration, the medians of the child's age at the first migration and average duration per migration were 3 months (IQR: 1 to 9 months) and 4.48 months (IQR: 2.38 to 7.54 months), respectively. For maternal migration, the corresponding values were 9 months (IQR: 6 to 13 months) and 4.65 months (IQR: 2.71 to 7.62 months), respectively. On average, LBC had been separated from fathers for 72% of their life due to paternal migration and from mothers for 52% of their life due to maternal migration. No significant association was found between the detailed characteristics of paternal migration and social-emotional development among LBC, while social-emotional problems among LBC were significantly associated with the proportion of cumulative duration of maternal migration in the child's lifetime (aOR 2.83; 95% CI: 1.13 to 7.10). CONCLUSIONS: LBC under 3 years had a high risk of social-emotional problems in poor rural China. Cumulative exposure to maternal migration may be detrimental to LBC's early social-emotional development. Programs are necessary to support these children as well as their families.

Quantitative Analysis and Automated Lung Ultrasound Scoring for Evaluating COVID-19 Pneumonia With Neural Networks.

As being radiation-free, portable, and capable of repetitive use, ultrasonography is playing an important role in diagnosing and evaluating the COVID-19 Pneumonia (PN) in this epidemic. By virtue of lung ultrasound scores (LUSS), lung ultrasound (LUS) was used to estimate the excessive lung fluid that is an important clinical manifestation of COVID-19 PN, with high sensitivity and specificity. However, as a qualitative method, LUSS suffered from large interobserver variations and requirement for experienced clinicians. Considering this limitation, we developed a quantitative and automatic lung ultrasound scoring system for evaluating the COVID-19 PN. A total of 1527 ultrasound images prospectively collected from 31 COVID-19 PN patients with different clinical conditions were evaluated and scored with LUSS by experienced clinicians. All images were processed via a series of computer-aided analysis, including curve-to-linear conversion, pleural line detection, region-of-interest (ROI) selection, and feature extraction. A collection of 28 features extracted from the ROI was specifically defined for mimicking the LUSS. Multilayer fully connected neural networks, support vector machines, and decision trees were developed for scoring LUS images using the fivefold cross validation. The model with 128×256 two fully connected layers gave the best accuracy of 87%. It is concluded that the proposed method could assess the ultrasound images by assigning LUSS automatically with high accuracy, potentially applicable to the clinics.

Correction to: How parental migration affects early social-emotional development of left-behind children in rural China: a structural equation modeling analysis.

The authors would like to correct errors in the publication of the original article. The errors described below and correct details provided.

How parental migration affects early social-emotional development of left-behind children in rural China: a structural equation modeling analysis.

OBJECTIVES: This study assessed the early social-emotional development of left-behind children (LBC) in rural China and determined the mediating factors linking parental migration to LBC's developmental outcome. METHODS: We used cross-sectional data of 845 LBC under 3 years old from five counties in rural China in 2018. Social-emotional problems were assessed by the ages and stages questionnaires: social-emotional. Family structure, function, and child nurturing care practices were measured to explore their roles in potential pathways of parental migration affecting early social-emotional development. RESULTS: 36.4% of LBC were identified with social-emotional problems; the rate was higher among LBC with migrant parents than those with migrant fathers (39.9% vs. 30.5%, adjusted OR: 1.40 [95% CI 1.01, 1.93]). Results of structural equation modeling reveal that caregivers' low education and depressive symptoms, poor migrant-caregiver communication, family poverty, and no assistant caregiving weakened home parenting environment, and then contributed to LBC's social-emotional problems. CONCLUSIONS: LBC in early childhood may be at a high risk of social-emotional problems, which are primarily caused by the transition of family structure and function and consequently weakened home environment.