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Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants, with significant mortality and long-term morbidity among survivors. Multiple NEC definitions exist, but no formal head-to-head evaluation has been performed. We hypothesized that contemporary definitions would perform better in evaluation metrics than Bell's and range features would be more frequently identified as important than yes/no features.

Two hundred and nineteen patients from the University of Iowa hospital with NEC, intestinal perforation, or NEC concern were identified from a 10-year retrospective cohort. NEC presence was confirmed by a blinded investigator. Evaluation metrics were calculated using statistics and six supervised machine learning classifiers for current NEC definitions. Feature importance evaluation was performed on each decision tree classifier.

Newer definitions outperformed Bell's staging using both standard statistics and most machine learning classifiers. The decision tree classifier NEC utilized and should be expounded upon with a larger and more diverse patient cohort.

This article is the first formal head-to-head evaluation of current available definitions of NEC. Non-Bell NEC definitions may be more effective in identifying NEC based on findings from traditional measures of diagnostic performance and machine learning techniques. Nine features were identified as important for diagnosis from the definitions evaluated within the decision tree when performing supervised classification machine learning. This article serves as a preliminary study to formally evaluate the definitions of NEC utilized and should be expounded upon with a larger and more diverse patient cohort.

We determine trends in fatal pediatric drug overdose from 1999 to 2018 and describe the influence of contextual factors and policies on such overdoses.

Combining restricted CDC mortality files with data from other sources, we conducted between-county multilevel models to examine associations of demographic and socioeconomic characteristics with pediatric overdose mortality and a fixed-effects analysis to identify how changes in contexts and policies over time shaped county-level fatal pediatric overdoses per 100,000 children under 12 years.

Pediatric overdose deaths rose from 0.08/100,000 children in 1999 to a peak of 0.19/100,000 children in 2016, with opioids accounting for an increasing proportion of deaths. Spatial patterns of pediatric overdose deaths are heterogenous. Socioeconomic characteristics are not associated with between-county differences in pediatric overdose mortality. Greater state expenditures on public welfare (B = -0.099; CI [-0.193, -0.005]) and hospitals (B = -0.222; CI [-.437, -.se is necessary.

Pediatric fatalities from psychoactive substances have risen within the U.S. since 1999. Higher levels of state spending on public welfare and hospitals are significantly associated with lower pediatric overdose mortality rates. The implementation of Good Samaritan laws is significantly associated with lower pediatric overdose mortality rates. We identified no county-level sociodemographic factors associated with pediatric overdose mortality. The findings indicate that a multi-faceted approach to the reduction of pediatric overdose is necessary.

The use of corticosteroids in Kawasaki disease (KD) is still controversial. The aim of this study was to investigate the safety and effectiveness of modified methylprednisolone (mPSL) regimen as an initial treatment for refractory KD.

This is a real-world observational study. We identified refractory KD with a self-developed scoring system. Patients were divided into the intravenous immunoglobulin (IVIG) + mPSL group and the IVIG group. Clinical outcomes and changes in coronary arteries after the treatment during a 12-week period were observed. Propensity-score matching was used to analyze those patients with similar baseline characteristics.

Of a total of 168 patients, 104 patients were assigned into the IVIG group and 64 patients into the IVIG + mPSL group. The therapeutic response rate of the IVIG + mPSL group was significantly higher than that of the IVIG group (98.4 vs 76.0%, P < 0.05). The IVIG + mPSL group had a shorter duration of fever and a higher rate of C-reactive protein decline than thekg/day, once a day for 3-5 days, then oral prednisone was tapered over 3-5 weeks in 5-7 days steps) as an intensive initial treatment can decrease LCX dilation in high-risk IVIG-resistant KD patients. Our self-developed scoring system has been proven validated and can be used to identify high-risk IVIG-resistant KD patients in North China. The present study provides an alternative therapeutic regimen for high-risk refractory KD patients.Tumor necrosis factor (TNF) inhibitors have improved a lot the treatment of numerous diseases, with the well-known example of rheumatoid arthritis (RA). In the early 2000s, postmarketing data quickly revealed an alarming number of severe tuberculosis (TB) under such treatment. These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization. The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma, with changes in cellular interactions, cytokine, and chemokine production. In addition to the role of TNF in granuloma, the interleukin (IL)-12/interferon (IFN)-γ pathway is required for an efficient host defense against TB. Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin (BCG) reaction or full TB. Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain. When TNF inhibitors are initiated, this transiently increases this risk of TB, through effects on cellular interactions in a latent TB granuloma. At a later stage, when a better control disease activity is obtained, the risk of TB is reduced but not abrogated. Given the clear benefit from TNF inhibition, latent TB infection screening at baseline is essential for an optimal safety.To explore the association between methylation level and transcript level of TNF receptor-associated factor 5 (TRAF5) gene with ankylosing spondylitis (AS) in Chinese Han population. Methylation and mRNA expression level of the TRAF5 gene were tested in 98 patients and 98 healthy controls. Among the 21 CpG sites, methylation levels at eight sites were significantly different between AS patients and healthy controls. However, only three sites remained significantly different after the correction by the Benjamini-Hochberg method. Compared with controls, the CpG island of TRAF5 gene promoter was highly methylated in AS patients, and the relative mRNA expression level of TRAF5 was significantly reduced in AS patients. And the mRNA level was negatively correlated with the methylation level of TRAF5 gene in AS patients (rs = -0.453, P  less then  0.001). Subgroup analyses indicated that there was no significant difference in the level of methylation between groups of different status of HLA-B27 and medications in AS patients. Multiple linear regression showed that disease-modifying antirheumatic drugs could reduce methylation levels of AS patients after adjusting for the effects of other drugs. In conclusion, the hypermethylation of the TRAF5 might contribute to the pathogenesis of AS, but many open questions remain.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. It thrives in a malnourished environment; however, little is known about the mechanisms by which PDAC cells actively promote aerobic glycolysis to maintain their metabolic needs. Gene Expression Omnibus (GEO) was used to identify differentially expressed miRNAs. The expression pattern of miR-30d in normal and PDAC tissues was studied by in situ hybridization. The role of miR-30d/RUNX1 in vitro and in vivo was evaluated by CCK8 assay and clonogenic formation as well as transwell experiment, subcutaneous xenograft model and liver metastasis model, respectively. Glucose uptake, ATP and lactate production were tested to study the regulatory effect of miR-30d/RUNX1 on aerobic glycolysis in PDAC cells. Quantitative real-time PCR, western blot, Chip assay, promoter luciferase activity, RIP, MeRIP, and RNA stability assay were used to explore the molecular mechanism of YTHDC1/miR-30d/RUNX1 in PDAC. Here, we discover that miR-30d expression was remarkably decreased in PDAC tissues and associated with good prognosis, contributed to the suppression of tumor growth and metastasis, and attenuation of Warburg effect. Mechanistically, the m6A reader YTHDC1 facilitated the biogenesis of mature miR-30d via m6A-mediated regulation of mRNA stability. Then, miR-30d inhibited aerobic glycolysis through regulating SLC2A1 and HK1 expression by directly targeting the transcription factor RUNX1, which bound to the promoters of the SLC2A1 and HK1 genes. Moreover, miR-30d was clinically inversely correlated with RUNX1, SLC2A1 and HK1, which function as adverse prognosis factors for overall survival in PDAC tissues. Overall, we demonstrated that miR-30d is a functional and clinical tumor-suppressive gene in PDAC. Our findings further uncover that miR-30d is a novel target for YTHDC1 through m6A modification, and miR-30d represses pancreatic tumorigenesis via suppressing aerobic glycolysis.Two new dipimprinine alkaloids dipimprinine E (1) and dipimprinine F (2) were isolated from Streptomyces sp. 44414B. The structure was elucidated by extensive spectroscopic analysis, including ESI-MS, HR-MS, and 1D and 2D NMR experiments. Dipimprinines F (2) showed cytotoxic activities against three tumor cell lines, including A-875, Hep G2, and H-460, with IC50 values of 26.4, 0.5, and 9.0 μg ml-1, respectively.SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242-244 deletion (242-244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242-244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. selleck chemical Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.