Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to explore the epigenomic and transcriptomic effects of mutations in DNMT1. We show cell type-specific changes in gene expression and DNA methylation patterns. DNA methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia and NR2F1 for deafness and optic atrophy. Furthermore, ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the functions of DNMT1 and the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.

Association of Pseudomonas aeruginosa infection stage with lung function trajectory in children with cystic fibrosis.

BACKGROUND: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV1 decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection. METHODS: Participants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV1 adjusted for relevant covariates. Models contained interaction terms between age and Pa stage. RESULTS: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39-58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV1 decline and chronic Pa infection with the greatest FEV1 decline. The most rapid FEV1 decline and strongest association with Pa infection stage was seen in early adolescence (ages 12-15). CONCLUSIONS: Annual FEV1 decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV1 decline and improve survival.

Genetic background- and environment-independent QTL and candidate gene identification of appearance quality in three MAGIC populations of rice.

Many QTL have been identified for grain appearance quality by linkage analysis (LA) in bi-parental mapping populations and by genome-wide association study (GWAS) in natural populations in rice. However, few of the well characterized genes/QTL have been successfully applied in molecular rice breeding due to genetic background (GB) and environment effects on QTL expression and deficiency of favorable alleles. In this study, GWAS and LA were performed to identify QTL for five grain appearance quality-related traits using three multi-parent advanced generation inter-cross (MAGIC) populations. A total of 22 QTL on chromosomes 1-3, 5-8 were identified by GWAS for five traits in DC1, DC2 and 8way, and four combined populations DC12 (DC1+DC2), DC18 (DC1+8way), DC28 (DC2+8way) and DC128 (DC1+DC2+8way). And a total of 42 QTL were identified on all 12 chromosomes except 10 by LA in the three single populations. Among 20 QTL identified by GWAS in DC1, DC2 and 8way, 10, four and three QTL were commonly detected in DC18, DC28, and DC128, respectively. Similarly, among 42 QTL detected by LA in the three populations, four, one and two QTL were commonly detected in DC18, DC28, and DC128, respectively. There was no QTL mapped together in DC12 by both two mapping methods, indicating that GB could greatly affect the mapping results, and it was easier to map the common QTL among populations with similar GB. The 8way population was more powerful for QTL mapping than the DC1, DC2 and various combined populations. Compared with GWAS, LA can not only identify large-effect QTL, but also identify minor-effect ones. Among 11 QTL simultaneously detected by the two methods in different GBs and environments, eight QTL corresponded to known genes, including AqGL3b and AqGLWR3a for GL and GLWR, AqGW5a, AqGLWR5, AqDEC5 and AqPGWC5 for GW, GLWR, DEC and PGWC, and AqDEC6b and AqPGWC6b for DEC and PGWC, respectively. AqGL7, AqGL3c/AqGLWR3b, AqDEC6a/AqPGWC6a, and AqPGWC7 were newly identified and their candidate genes were analyzed and inferred. It was discussed to further improve grain appearance quality through designed QTL pyramiding strategy based on the stable QTL identified in the MAGIC populations.

Molecular mechanisms underlying iron and phosphorus co-limitation responses in the nitrogen-fixing cyanobacterium Crocosphaera.

In the nitrogen-limited subtropical gyres, diazotrophic cyanobacteria, including Crocosphaera, provide an essential ecosystem service by converting dinitrogen (N2) gas into ammonia to support primary production in these oligotrophic regimes. Natural gradients of phosphorus (P) and iron (Fe) availability in the low-latitude oceans constrain the biogeography and activity of diazotrophs with important implications for marine biogeochemical cycling. Much remains unknown regarding Crocosphaera's physiological and molecular responses to multiple nutrient limitations. We cultured C. watsonii under Fe, P, and Fe/P (co)-limiting scenarios to link cellular physiology with diel gene expression and observed unique physiological and transcriptional profiles for each treatment. Counterintuitively, reduced growth and N2 fixation resource use efficiencies (RUEs) for Fe or P under P limitation were alleviated under Fe/P co-limitation. Differential gene expression analyses show that Fe/P co-limited cells employ the same responses as single-nutrient limited cells that reduce cellular nutrient requirements and increase responsiveness to environmental change including smaller cell size, protein turnover (Fe-limited), and upregulation of environmental sense-and-respond systems (P-limited). Combined, these mechanisms enhance growth and RUEs in Fe/P co-limited cells. These findings are important to our understanding of nutrient controls on N2 fixation and the implications for primary productivity and microbial dynamics in a changing ocean.

Implementation of Standardized Care for the Medical Stabilization of Patients With Anorexia Nervosa.

Approaches to refeeding patients with anorexia nervosa for medical stabilization vary across institutions, and there is no established standard of care. This study assessed the impact of a refeeding pathway on hospital length of stay and transfer to the psychiatry unit. Methods: This quality improvement intervention sought to standardize care for adolescents with anorexia nervosa at a tertiary care, free-standing children's hospital from Spring 2017 to Fall 2018. The pathway specified admission criteria, nutritional advancement, activity restriction, laboratory monitoring, readiness to transfer to the psychiatry unit, and discharge criteria. Statistical process control analysis was utilized to identify system-level changes over time. We used linear regression to assess pre- and postpathway differences in length of stay and transfer to the psychiatry unit. Results: There were 161 patient encounters for anorexia nervosa admitted for medical stabilization. 84% of the sample were female with median age of 15.2 (IQR 14.0-17.0) years. There was no difference in hospital length of stay between the pre- and postpathway groups. There was a statistically significant increase in the proportion of patients transferred to the psychiatry unit over the study period. Conclusion: Clinical pathway use to deliver standardized care to achieve medical stability for patients with anorexia nervosa did not shorten hospital length of stay. Multiple potentially confounding medical and psychosocial factors may have contributed to this lack of improvement.

The overlap of medical child abuse and central sensitization in adolescents: An exploratory qualitative study.

BACKGROUND: Both medical child abuse (MCA) and central sensitization (CS) may present in adolescents with chronic pain, disability, high healthcare utilization, and unremarkable medical evaluations. OBJECTIVE: This study aimed to identify themes in the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. PARTICIPANTS AND SETTING: Participants were 28 adolescents (ages 13-18 years) with chronic pain referred to either the Child Abuse Pediatrics team or the Pediatric Pain Medicine team at a tertiary children's hospital between 2011 and 2019, and diagnosed with MCA or CS, respectively. METHODS: This was a qualitative, retrospective study. Qualitative themes were derived through a process of inductive content analysis utilizing open coding, grouping, and secondary review by an interdisciplinary panel of experts. The relative prevalence of each code, theme, and overarching category was examined between groups to identify areas of convergence and divergence. RESULTS: Several themes appeared to be more prevalent in the MCA group (n = 9) compared to the CS group (n = 19). These included sick identity, homeschooling, caregiver with mental health disorder, maternal catastrophizing, maternal misrepresentation, persistence in healthcare-seeking, mandated reports made, medical neglect, and unnecessary and harmful medical care. CONCLUSIONS: This exploratory work identified themes from the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. A visual reference, two illness scripts, and management recommendations are presented to aid pediatric providers in facilitating appropriate referrals for adolescents with chronic pain and disability out of proportion to diagnostic workup.

Digital nerve blocks: A systematic review and meta-analysis.

Study objective: Digital nerve blocks (DNBs) provide local anesthesia for minor procedures of the digits. Several DNB techniques have been described, but it is unclear which technique provides adequate anesthesia with the least pain. DNB techniques can be grouped into a dorsal approach, which requires 2 injections, versus 3 different types of volar approaches, which require a single injection. We performed a meta-analysis to compare DNB techniques with respect to time to anesthesia (TTA), duration of anesthesia (DOA), and pain of injection. We also reviewed data on degree and distribution of anesthesia and discuss the techniques preferred by study participants and clinicians performing injections. Data Sources: We searched MEDLINE, EMBASE, and CENTRAL databases with terms "digital block," "digital nerve block," "local anesthetic," "local anesthesia," "lidocaine," and/or "bupivacaine." Study Selection: Randomized controlled trials (RCTs) were prioritized, though high-quality prospective cohort studies were also eligible. All included studies evaluated DNB techniques or anesthetics. There were 23 papers (21 RCTs, 2 prospective descriptive studies) included. Data Extraction: DNBs studied included dorsal ring block, traditional dorsal block, transthecal block, modified transthecal block, and volar subcutaneous digital blocks. Outcomes measured included TTA, DOA, pain of injection scores, and degree of anesthesia. Results: Overall, mean TTA was 4.5 minutes (95% confidence interval [CI] 3.5, 5.6), mean DOA was 187 minutes (95% CI 104.3, 269.7), and mean pain score was 2.1 out of 10 (95% CI 1.3, 2.8) without significant differences between studies or techniques. Conclusions: There were no significant differences in the outcomes of TTA, DOA, and pain of injection between different DNB techniques. Single-injection volar approaches may be preferred by participants and clinicians over dorsal approaches that require 2 injections, particularly with respect to pain. However, 2-injection dorsal approaches may have better coverage of the proximal dorsal surface based on degree and distribution of anesthesia.

Association Between Language Use and ICU Transfer and Serious Adverse Events in Hospitalized Pediatric Patients Who Experience Rapid Response Activation.

Background: Hospitalized patients and caregivers who use a language other than English have worse health outcomes, including longer length of stay, more frequent readmissions, and increased rates of in-hospital adverse events. Children who experience clinical deterioration (as measured by a Rapid Response Team event) during a hospitalization are at increased risk for adverse events and mortality. Methods: We describe the results of a retrospective cohort study using hospital records at a free-standing, quaternary children's hospital, to examine the association of language of care with outcomes (transfer to intensive care, adverse event, mortality prior to discharge) following Rapid Response Team event, and whether increased interpreter use among patients who use a language other than English is associated with improved outcomes following Rapid Response Team event. Results: In adjusted models, Rapid Response Team events for patients who use a language other than English were associated with higher transfer rates to intensive care (RR 1.1, 95% CI 1.01, 1.21), but not with adverse event or mortality. Among patients who use a language other than English, use of 1-2 interpreted sessions per day was associated with lower transfer rates to intensive care compared to use of less than one interpreted session per day (RR 0.79, 95% 0.66, 0.95). Conclusion: Rapid Response Team events for hospitalized children of families who use a language other than English are more often followed by transfer to intensive care, compared with Rapid Response Team events for children of families who use English. Improved communication with increased interpreter use for hospitalized children who use a language other than English may lead to improvements in Rapid Response Team outcomes.

Implementation of various bowl designs in an HPDI natural gas engine focused on performance and pollutant emissions.

The air-fuel mixture preparation in pilot spray-ignited natural gas engines is primarily dominated by piston bowl profiles and fuel injection strategy. Piston bowl geometry is regarded as the crucial point in controlling engine pollutant emissions. In the present work, the SAGE combustion model was applied coupled with a general reaction kinetic mechanism. The engine model was validated with experimental data achieved from a Cummins ISX 400 engine, and good agreement between predicted and measured in-cylinder pressure and heat release rate was obtained. The influence of various piston bowl designs, including Mexican-hat geometry, double-lip geometry, bow geometry, and toroidal geometry, on the combustion process, engine performance, and pollutant emissions of a high-pressure direct-injection natural gas engine have been studied and analyzed numerically. The present study confirms the benefit of the piston bowl design as a beneficial tool to enhance the performance and pollutant emissions of the pilot diesel-ignited natural gas engine. Results showed that different chamber shapes slightly influence the combustion initiation, and the difference in in-cylinder pressure presents noticeable as the combustion continues. A higher turbulent kinetic energy improves the flow movement and facilitates the mixture formation in the cylinder. However, the combustion behavior is unwished caused by the improper injection angle of natural gas. Increasing the recess depth of combustion chambers reduces NOx formations at the price of sacrificing fuel economy. For the bow combustion chamber design, the NOx emission declined by 31.1%, while the indicated specific fuel consumption increased by 5.5% compared with the original engine. Although the indicated mean effective pressure and specific fuel consumption of the optimal double-lip geometry almost remain the same, NOx emissions can be reduced by 16.7% compared with the base design.

Racial and Ethnic Differences in Ondansetron Use for Acute Gastroenteritis in Children.

OBJECTIVES: There is limited research examining racial/ethnic disparities in antiemetic use for acute gastroenteritis (AGE). We assessed racial/ethnic differences in the care of children with AGE. METHODS: The Pediatric Health Information System was used to conduct a retrospective cohort study of children 6 months to 6 years old with AGE seen in participating emergency departments from 2016 to 2018. Cases were identified using International Classification of Diseases, Tenth Revision codes. The primary outcome was administration of ondansetron, secondary outcomes were administration of intravenous (IV) fluids and hospitalization, and primary predictor was race/ethnicity. Multivariable logistic regression followed by a mixed model adjusted for sex, age, insurance, and hospital to examine the association of race/ethnicity with each outcome. RESULTS: There were 78,019 encounters included; 24.8% of patients were non-Hispanic White (NHW), 29.0% non-Hispanic Black (NHB), 37.3% Hispanic, and 8.9% other non-Hispanic (NH) race/ethnicity. Compared with NHW patients, minority children were more likely to receive ondansetron (NHB: adjusted odds ratio, 1.36 [95% confidence interval, 1.2-1.55]; Hispanic: 1.26 [1.1-1.44]; other NH: 1.22 [1.07-1.4]). However, minority children were less likely to receive IV fluids (NHB: 0.38 [0.33-0.43]; Hispanic: 0.44 [0.36-0.53]; other NH: 0.51 [0.44-0.61]) or hospital admission (NHB: 0.37 [0.29-0.48]; Hispanic: 0.41 [0.33-0.5]; other NH: 0.52 [0.41-0.66]). Ondansetron use by hospital ranged from 73% to 95%. CONCLUSIONS: This large database analysis of emergency departments around the nation found that NHW patients were less likely to receive ondansetron but more likely to receive IV fluids and hospital admission than minority patients. These findings are likely multifactorial and may represent bias, social determinants of health, access to care, or illness severity among other possible causes.

Two co-dominant nitrogen-fixing cyanobacteria demonstrate distinct acclimation and adaptation responses to cope with ocean warming.

The globally dominant N2 -fixing cyanobacteria Trichodesmium and Crocosphaera provide vital nitrogen supplies to subtropical and tropical oceans, but little is known about how they will be affected by long-term ocean warming. We tested their thermal responses using experimental evolution methods during 2 years of selection at optimal (28°C), supra-optimal (32°C) and suboptimal (22°C) temperatures. After several hundred generations under thermal selection, changes in growth parameters, as well as N and C fixation rates, suggested that Trichodesmium did not adapt to the three selection temperature regimes during the 2-year evolution experiment, but could instead rapidly and reversibly acclimate to temperature shifts from 20°C to 34°C. In contrast, over the same timeframe apparent thermal adaptation was observed in Crocosphaera, as evidenced by irreversible phenotypic changes as well as whole-genome sequencing and variant analysis. Especially under stressful warming conditions (34°C), 32°C-selected Crocosphaera cells had an advantage in survival and nitrogen fixation over cell lines selected at 22°C and 28°C. The distinct strategies of phenotypic plasticity versus irreversible adaptation in these two sympatric diazotrophs are both viable ways to maintain fitness despite long-term temperature changes, and so could help to stabilize key ocean nitrogen cycle functions under future warming scenarios.

Major adverse kidney events after acute kidney injury in the pediatric intensive care unit: a propensity score-matched cohort study.

BACKGROUND: Acute kidney injury (AKI) in patients admitted to the pediatric intensive care unit (PICU) is associated with poor short-term and long-term outcomes. Greater awareness of long-term AKI-associated outcomes is needed to optimally plan follow-up and management after ICU discharge. We used propensity score methods to study associations between pediatric AKI and major adverse kidney outcomes, including mortality. METHODS: We included all children 6 months-18 years admitted to PICU at Seattle Children's Hospital from 7/1/2009 to 12/31/2018. Our primary outcome measure was Major Adverse Kidney Events at 30 days (MAKE30): creatinine > 200% of baseline, eGFR < 60 mL/min/1.73 m2, dialysis dependence, or mortality. Propensity scores for AKI development in PICU were generated using demographic, medical history, admission, and PICU hospitalization variables. Patients with AKI were matched to control patients without AKI. Logistic regression was used to test association between AKI status and MAKE30. RESULTS: In the unmatched cohort (n = 878), patients with AKI had lower platelet count (160 vs. 222) and higher PRISM III score (11 vs. 3.5). After propensity score matching, those with AKI vs. no AKI had similar PRISM III scores (9 vs. 10) and platelet count (163 vs. 159). AKI was significantly associated with MAKE30 after propensity score matching (OR: 2.97; 95% CI 1.82-4.84). CONCLUSIONS: Propensity score matching significantly reduced imbalance in baseline characteristics between those with and without AKI. After matching, AKI remained significantly associated with MAKE30. Patients who developed AKI were more likely to have abnormal kidney function at 30 and 90 days after ICU admission and may be at high risk for developing CKD in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

Child Abuse Pediatricians Assess a Low Likelihood of Abuse in Half of 2890 Physical Abuse Consults.

The aim of this study was to examine the frequency with which child abuse pediatricians (CAPs) assess consultations as low versus high likelihood of abuse. In this retrospective secondary analysis of data from the Examining Siblings to Recognize Abuse (ExSTRA) study, the likelihood of abuse score for 2890 consultations at 20 medical centers was collected. Descriptive statistics were used to examine the percentage of cases representing low versus high likelihood of abuse (i.e., score of 1-4 vs. 5-7 on a 7-point scale). Linear and logistic regression analyses were used to examine score variability between medical centers. Overall, fifty-three percent of cases were assessed as low likelihood of abuse, suggesting that CAPs were equally as likely to assess a high versus low likelihood of abuse. The percentage of cases representing low likelihood of abuse differed significantly (P < .001) between medical centers after controlling for patient age, sex, race/ethnicity, twin/triplet status, injury types, and injury severity. The variability between CAP assessments at different medical centers is discussed, along with potential contributors to this variability and directions for future work.

Socioeconomic status and parent perceptions about the costs and benefits of youth sport.

OBJECTIVES: Describe what costs and benefits parents across the socioeconomic spectrum weight most heavily when making decisions about sport participation for their children. METHOD: Cross-sectional survey of a nationally representative online panel of parents of children between the ages of 5 and 18 (n = 1025, 52% response rate). Parents rated the importance of a series of potential costs and benefits of youth sport and these responses were compared across tertiles of per capita family income. We first examined the association between family income tertiles and cost and benefit variables. Model-based cluster analysis was then used to identity homogeneous groups of responses to costs and benefits. RESULTS: In all income tertiles, the top two benefits of sport were the same: having fun and being physically active. Sport as a means of keeping children out of trouble was very important for 64% of low-income parents as compared to 40% of high-income parents. Obtaining a college athletic scholarship was very important for 26% of low-income parents, as compared to 8% of high-income parents. Relative rankings of potential costs were similar by income tertile, with risk of concussion and other injury and the impact of sport on schoolwork prioritized across tertiles. CONCLUSIONS: Parents prioritized fun and fitness in sport, and were concerned about injury and the impact of sport on academics. Lower income parents were the most likely to view keeping their child out of trouble, and the potential for a college athletics scholarship, as benefits of sport. Efforts to support parental decision making should be grounded in an understanding that family preferences are contextually constrained. While all parents should be appropriately informed about the potential costs and benefits they are weighting in their sports-related decision making, such family-focused efforts should be balanced with the recognition that structural change is needed to address income-related concerns about sport participation.

Qualification of ELISA and neutralization methodologies to measure SARS-CoV-2 humoral immunity using human clinical samples.

In response to the SARS-CoV-2 pandemic many vaccines have been developed and evaluated in human clinical trials. The humoral immune response magnitude, composition and efficacy of neutralizing SARS-CoV-2 are essential endpoints for these trials. Robust assays that are reproducibly precise, linear, and specific for SARS-CoV-2 antigens would be beneficial for the vaccine pipeline. In this work we describe the methodologies and clinical qualification of three SARS-CoV-2 endpoint assays. We developed and qualified Endpoint titer ELISAs for total IgG, IgG1, IgG3, IgG4, IgM and IgA to evaluate the magnitude of specific responses to the trimeric spike (S) antigen and total IgG specific to the spike receptor binding domain (RBD) of SARS-CoV-2. We also qualified a pseudovirus neutralization assay which evaluates functional antibody titers capable of inhibiting the entry and replication of a lentivirus containing the Spike antigen of SARS-CoV-2. To complete the suite of assays we qualified a plaque reduction neutralization test (PRNT) methodology using the 2019-nCoV/USA-WA1/2020 isolate of SARS-CoV-2 to assess neutralizing titers of antibodies in plasma from normal healthy donors and convalescent COVID-19 individuals.

MiR-361-5p/abca1 and MiR-196-5p/arhgef12 Axis Involved in γ-Sitosterol Inducing Dual Anti-Proliferative Effects on Bronchial Epithelial Cells of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD), a progressive and irreversible respiratory disease, becomes the third leading cause of death and results in enormous economic burden on healthcare costs and productivity loss worldwide by 2020. Thus, it is urgent to develop effective anti-COPD drugs. MATERIALS AND METHODS: In the present study, two published GEO profiles were used to re-analyze and ascertain the relationships between circulating miRNAs and bronchial epithelial cells (BECs) mRNAs in COPD. The microRNA levels of miR-361-5p and miR-196-5p in plasma of COPD patients and healthy volunteers were detected by qRT-PCR. Next, the effects of γ-sitosterol (GS) on the expression of miR-361-5p and miR-196-5p and cell proliferation were investigated in BEC and H292 cell lines. Finally, whether specific miRNA-mRNA pathways involved in the effect of GS on BECs was assayed using Western Blot, real-time PCR and immunofluorescence. RESULTS: miR-196-5p and miR-361-5p were, respectively, up- and down-regulated in COPD patients compared with healthy controls. Luciferase assays demonstrated that miR-361-5p and miR-196-5p were, respectively, targeting abca1 and arhgef12 3'UTR in BEAS-2B cells. GS significantly suppressed miR-196-5p and promoted miR-361-5p levels in BEAS-2B cells and inhibited BECs proliferation in vitro. GS promoted miR-361-5p expression, which inhibited BCAT1 mRNA and protein levels and weaken mTOR-pS6K pathway, resulted in anti-proliferation in BEAS-2B cells. In addition, RhoA was activated by ARHGEF12 due to the inhibitory effect of miR-196-5p on arhgef12-3'UTR which was partially abolished by GS suppressing miR-196-5p expression. Activated RhoA further activated ROCK1-PTEN pathway and finally inhibited mTOR pathway, resulting in induced BECs proliferation. The anti-proliferation effect of GS was not observed in H292 cells. CONCLUSION: These findings indicate that miR-361-5p/abca1 and miR-196-5p/arhgef12 axis mediated GS inducing dual anti-proliferation effects on BECs.

Construction of Consensus Genetic Map With Applications in Gene Mapping of Wheat (Triticum aestivum L.) Using 90K SNP Array.

Wheat is one of the most important cereal crops worldwide. A consensus map combines genetic information from multiple populations, providing an effective alternative to improve the genome coverage and marker density. In this study, we constructed a consensus map from three populations of recombinant inbred lines (RILs) of wheat using a 90K single nucleotide polymorphism (SNP) array. Phenotypic data on plant height (PH), spike length (SL), and thousand-kernel weight (TKW) was collected in six, four, and four environments in the three populations, and then used for quantitative trait locus (QTL) mapping. The mapping results obtained using the constructed consensus map were compared with previous results obtained using individual maps and previous studies on other populations. A simulation experiment was also conducted to assess the performance of QTL mapping with the consensus map. The constructed consensus map from the three populations spanned 4558.55 cM in length, with 25,667 SNPs, having high collinearity with physical map and individual maps. Based on the consensus map, 21, 27, and 19 stable QTLs were identified for PH, SL, and TKW, much more than those detected with individual maps. Four PH QTLs and six SL QTLs were likely to be novel. A putative gene called TraesCS4D02G076400 encoding gibberellin-regulated protein was identified to be the candidate gene for one major PH QTL located on 4DS, which may enrich genetic resources in wheat semi-dwarfing breeding. The simulation results indicated that the length of the confidence interval and standard errors of the QTLs detected using the consensus map were much smaller than those detected using individual maps. The consensus map constructed in this study provides the underlying genetic information for systematic mapping, comparison, and clustering of QTL, and gene discovery in wheat genetic study. The QTLs detected in this study had stable effects across environments and can be used to improve the wide adaptation of wheat cultivars through marker-assisted breeding.

Performance Evaluation of Precise Point Positioning for BeiDou-3 B1c/B2a Signals in the Global Range.

With the construction and development of the BeiDou navigation satellite system (BDS), the precise point positioning (PPP) performance of the BDS is worthy of research. In this study, observational data from 17 stations around the world across 20 days are used to comprehensively evaluate the PPP performance of BDS B1c/B2a signals. For greater understanding, the results are also compared with the Global Positioning System (GPS) and BDS PPP performance of different signals and system combinations. The evaluation found root mean square (RMS) values of the static PPP in the north (N), east (E), and upward (U) components, based on the B1c/B2a frequency of BDS-3, to be 6.9 mm, 4.7 mm, and 26.6 mm, respectively. Similar to the static positioning, the RMS values of kinematic PPP in the three directions of N, E, and U are 2.6 cm, 6.0 cm, and 8.5 cm, respectively. Besides this, the static PPP of BDS-3 (B1cB2a) and BDS-2 + BDS-3 (B1IB3I) have obvious system bias. Compared with static PPP, kinematic PPP is more sensitive to the number of satellites, and the coordinate accuracy in three dimensions can be increased by 27% with the combination of GPS (L1L2) and BDS. Compared with BDS-2+BDS-3 (B1IB3I), the convergence time of BDS-3 (B1CB2a) performs better in both static and kinematic modes. The antenna model does not show a significant difference in terms of the effect of the convergence speed, though the number of satellites observed has a certain influence on the convergence time.

Mental health comorbidities in adolescents and young adults with type 2 diabetes.

BACKGROUND: Screening for mental health comorbidities is recommended in adolescents and young adults (AYAs) with diabetes. There is a paucity of data on mental health comorbidities in AYAs with type 2 diabetes (T2D). OBJECTIVE: To assess rates of depression, suicidal ideation, and diabetes distress (DD) in AYAs with T2D overall and by sociodemographic and clinical factors. METHODS: AYAs with T2D ages 13-21 years seen in a pediatric diabetes clinic between March 2018 and June 2019 completed the Patient Health Questionnaire-9 (PHQ-9) for depression screening and the Problem Areas in Diabetes - teen version (PAID-T) survey to assess DD. Chi-square tests were used to assess whether rates of depression and DD were associated with participant characteristics. RESULTS: The sample consisted of 64 AYAs with T2D (58% female, mean age 15.8 ± 2.0 years, mean HbA1c 8.3% ± 2.6%, mean BMI z-score 2.2 ± 0.6, 59% on insulin). Overall, 31% of participants had high depression and/or DD. Twenty-two percent of participants reported high depressive symptoms and 9% endorsed suicidal ideation on the PHQ-9. There were no differences in rates of depression by sociodemographic factors. Twenty-three percent of participants reported high DD. Rates of DD were higher among those on insulin (p = 0.014) and on public health insurance (p = 0.014). CONCLUSIONS: Almost 1 in 3 AYAs with T2D endorsed depression and/or DD. Our findings support the importance of mental health screening in AYAs with T2D, as well as the need for strategies to address psychological comorbidities in this population.

Socioeconomic Inequities in Youth Participation in Physical Activity and Sports.

Access to opportunities for physical activity and sports, and therefore potential benefits of participation, are distributed inequitably. The aims of this study were to describe and compare youth experiences related to sport and physical activity by socioeconomic factors. A cross-sectional survey was conducted of students in 5-12th grades in King County, Washington, USA. Students were asked about physical activity and sports experiences and about demographic factors including family affluence, which was categorized as low, medium, and high. Participants were 1038 youth (50% girls, 58% non-White, and 32% from homes where languages other than English are spoken). Children from low-affluence families reported fewer days/week of physical activity, fewer sports sampled, and lower rates of ever playing sports. Greater proportions of children from low-affluence families reported these barriers to sports: (1) don't want to get hurt, (2) don't feel welcome on teams, (3) too expensive, and (4) transportation. Middle school children from high-affluence families had three times higher odds of meeting physical activity recommendations, and high-affluence high schoolers had three times higher odds of ever participating in sports compared to peers from low-affluence families. Socioeconomic status was inversely associated with outcomes related to youth physical activity and sports participation. The disproportionately reported barriers to sports participation are modifiable, and cross-sector solutions can help promote play equity.