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The type-I error rate from the random intercept LMEM was closer to 0.05, but it might be under 0.05 and coverage probability might be over 95%. The GEE independent model performed worst and the LMEM with both random intercept and slope might not converge.

To estimate marginal exposure-outcome association with bivariate continuous outcomes, the random intercept LMEM may be preferred. It has the best coverage probability of 95% CI and is the only model with correct type-I error rates in this study. However, it may have low power and overly wide CI in studies with small sample size or low inter-eye correlation.

To estimate marginal exposure-outcome association with bivariate continuous outcomes, the random intercept LMEM may be preferred. It has the best coverage probability of 95% CI and is the only model with correct type-I error rates in this study. However, it may have low power and overly wide CI in studies with small sample size or low inter-eye correlation.

To explore the experiences of nurses and coordinators in the PRIMROSE childhood obesity prevention trial, and to understand the factors that might help to improve the outcome of future primary prevention of obesity.

Using a qualitative approach, data were obtained by interviewing nine intervention nurses and three regional study coordinators. All participants were female. The interviews were transcribed and analysed using content analysis.

Two themes emerged

 ; and

. The importance of support, encouragement, briefer and simpler intervention, and adaptation of the training in motivational interviewing to the setting was emphasized. Stress and lack of time were major barriers to deliver the intervention as intended.

Although the PRIMROSE intervention was developed in collaboration with representatives from the child health services, and additional research funding was provided to compensate for time spent working with the trial, nurses experienced stress and time constraints. .

Although the PRIMROSE intervention was developed in collaboration with representatives from the child health services, and additional research funding was provided to compensate for time spent working with the trial, nurses experienced stress and time constraints. .Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children's Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1β were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.

Hybrid imaging (e.g., positron emission tomography [PET]/computed tomography [CT], PET/magnetic resonance imaging [MRI]) helps one to visualize and quantify morphological and physiological tumor characteristics in a single study. The noninvasive characterization of tumor heterogeneity is essential for grading, treatment planning, and following-up oncological patients. However, conventional (CONV) image-based parameters, such as tumor diameter, tumor volume, and radiotracer activity uptake, are insufficient to describe tumor heterogeneities. Here, radiomics shows promise for a better characterization of tumors. Nevertheless, the validation of such methods demands imaging objects capable of reflecting heterogeneities in multi-modality imaging. We propose a phantom to simulate tumor heterogeneity repeatably in PET, CT, and MRI.

The phantom consists of three 50-ml plastic tubes filled partially with acrylic spheres of S1 1.6mm, S2 50%(1.6 mm)/50%(6.3mm), or S3 6.3-mm diameter. The spheres were fixed to the bo a COV of 10% or less. In particular, CONV, histogram, and gray-level run length matrix features showed high repeatability for all the phantom regions and imaging modalities. Several of repeatable texture features allowed the image-based discrimination of the different phantom regions (p<0.05). However, depending on the feature, different pattern discrimination capabilities were found for the different imaging modalities.

The proposed phantom appears suitable for simulating heterogeneities in PET, CT, and MRI. We demonstrate that it is possible to select radiomic features for the readout of the phantom. Most of these features had been shown to be relevant in previous clinical studies.

The proposed phantom appears suitable for simulating heterogeneities in PET, CT, and MRI. We demonstrate that it is possible to select radiomic features for the readout of the phantom. Most of these features had been shown to be relevant in previous clinical studies.COVID-19 has been proposed to be an endothelial disease, as endothelial damage and oxidative stress contribute to its systemic inflammatory and thrombotic events. Polyphenols, natural antioxidant compounds appear as promising agents to prevent and treat COVID-19. Polyphenols bind and inhibit the F1 Fo -ATP synthase rotary catalysis. An early target of polyphenols may be the ectopic F1 Fo -ATP synthase expressed on the endothelial plasma membrane. Among the pleiotropic beneficial action of polyphenols in COVID-19, modulation of the ecto-F1 Fo -ATP synthase, lowering the oxidative stress produced by the electron transfer chain coupled to it, would not be negligible.Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neuhi), but low levels of CD8+ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. Tacedinaline chemical structure To study specifically the mechanisms related to Neuhi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.Gastrointestinal (GI) motility requires coordination among several cell types in the intestinal epithelium and the neuromuscular apparatus. A disruption in GI motility was primarily attributed to disruption of this coordinated effort among different host cells, but recent studies have begun to uncover how the products of gut microbiota can alter GI motility by modulating the function of different host cells and the interactions among them. In this issue of the JCI, Chen, Qiu, et al. used a reverse translation approach, isolating a Shigella sp. - peristaltic contraction-inhibiting bacterium (PIB) - from a cohort of patients with intractable constipation. They identified an ω-3 polyunsaturated fatty acid (PUFA), docosapentaenoic acid (DPA), produced by this Shigella variant, as an important driver of constipation using a series of microbiologic, biochemical, and genetic manipulations combined with in vitro and in vivo studies. This finding advances the field, given that production of DPA is rare in the human gut and appears to have a distinct effect on GI physiology.Individuals with Down syndrome (DS) have more than 100-fold increased risk of acute megakaryoblastic leukemia (AMKL), but its pathogenesis is poorly understood. In this issue of the JCI, Arkoun et al. engineered stepwise DS-AMKL-associated mutations in GATA1, MPL, and SMC3 in human induced pluripotent stem cell (iPSC) clones from individuals with DS to dissect how each mutation affects gene expression control and megakaryocytic differentiation. The authors showed that the mutations cooperatively promote progression from transient myeloproliferative disorder to DS-AMKL. This study highlights the importance of mutation order and context in the perturbations of transcriptional and differentiation pathways involved in the evolution of hematologic malignancies, which will be critical for the development of preventative and therapeutic interventions.The metabolic dependencies of cancer cells have substantial potential to be exploited to improve the diagnosis and treatment of cancer. Creatine riboside (CR) is identified as a urinary metabolite associated with risk and prognosis in lung and liver cancer. However, the source of high CR levels in patients with cancer as well as their implications for the treatment of these aggressive cancers remain unclear. By integrating multiomics data on lung and liver cancer, we have shown that CR is a cancer cell-derived metabolite. Global metabolomics and gene expression analysis of human tumors and matched liquid biopsies, together with functional studies, revealed that dysregulation of the mitochondrial urea cycle and a nucleotide imbalance were associated with high CR levels and indicators of a poor prognosis. This metabolic phenotype was associated with reduced immune infiltration and supported rapid cancer cell proliferation that drove aggressive tumor growth. CRhi cancer cells were auxotrophic for arginine, revealing a metabolic vulnerability that may be exploited therapeutically. This highlights the potential of CR not only as a poor-prognosis biomarker but also as a companion biomarker to inform the administration of arginine-targeted therapies in precision medicine strategies to improve survival for patients with cancer.