Machine learning and experimental analyses identified miRNA expression models associated with metastatic osteosarcoma.

Osteosarcoma (OS), as the most common primary bone cancer, has a high invasiveness and metastatic potential, therefore, it has a poor prognosis. This study identified early diagnostic biomarkers using miRNA expression profiles associated with osteosarcoma metastasis. In the first step, we used RNA-seq and online microarray data from osteosarcoma tissues and cell lines to identify differentially expressed miRNAs. Then, using seven feature selection algorithms for ranking, the first-ranked miRNAs were selected as input for five machine learning systems. Using network analysis and machine learning algorithms, we developed new diagnostic models that successfully differentiated metastatic osteosarcoma from non-metastatic samples based on newly discovered miRNA signatures. The results showed that miR-34c-3p and miR-154-3p act as the most promising models in the diagnosis of metastatic osteosarcoma. Validation for this model by RT-qPCR in benign tissue and osteosarcoma biopsies confirmed the lower expression of miR-34c-3p and miR-154-3p in OS samples. In addition, a direct correlation between miR-34c-3p expression, miR-154-3p expression and tumor grade was discovered. The combined values of miR-34c-3p and miR-154-3p showed 90 % diagnostic power (AUC = 0.90) for osteosarcoma samples and 85 % (AUC = 0.85) for metastatic osteosarcoma. Adhesion junction and focal adhesion pathways, as well as epithelial-to-mesenchymal transition (EMT) GO terms, were identified as the most significant KEGG and GO terms for the top miRNAs. The findings of this study highlight the potential use of novel miRNA expression signatures for early detection of metastatic osteosarcoma. These findings may help in determining therapeutic approaches with a quantitative and faster method of metastasis detection and also be used in the development of targeted molecular therapy for this aggressive cancer. Further research is needed to confirm the clinical utility of miR-34c-3p and miR-154-3p as diagnostic biomarkers for metastatic osteosarcoma.

Natural History of Secundum ASD in Preterm and Term Neonates: A Comparative Study.

Atrial septal defects (ASDs) are common in neonates. Although past studies suggest ASDs  ≥ 3 mm in term neonates (TNs) are less likely to close, there is paucity of data regarding the natural history in preterm neonates (PNs), information that would inform surveillance. We sought to compare spontaneous closure rates and need for intervention for ASDs in TNs/near term (≥ 36 weeks) versus PNs (< 36 weeks). We included all TNs and PNs who underwent echocardiography at ≤ 1 month between 2010 and 2018 in our institution with an ASD ≥ 3 mm, without major congenital heart disease, and with repeat echocardiogram(s). Spontaneous resolution was defined as size diminution to < 3 mm or closure. We included 156 TNs (mean gestational age at birth 38.6 ± 1.4 weeks) and 156 PNs (29.6 ± 3.7 weeks) with a mean age at follow-up of 16 ± 19 and 15 ± 21 months, respectively (p = 0.76). Based on maximum color Doppler diameter, in TNs, ASD resolution occurred in 95% of small (3-5 mm), 87% of moderate (5.1-8 mm), and 60% of large (> 8 mm) defects; whereas, in PNs, resolution occurred in 79% of small, 76% of moderate, and 33% of large ASDs. There was a significant association between size and ASD resolution in TNs (p = 0.003), but not PNs (p = 0.17). Overall, ASD resolution rate was higher in TNs (89%) versus PNs (78%) (p = 0.009), and fewer TNs (1%) compared to PNs (7%) required ASD intervention (p = 0.02). Most ASDs identified in TNs and PNs spontaneously resolve. PNs, however, demonstrate lower ASD resolution and higher intervention rates within all size groups. These data should inform follow-up of affected neonates.

Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.

As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.

The Cl Functionalized Aluminum Nitride (AlN) and Aluminum Phosphide (AlP) Nanocone Sheets as Hydrogen Selenide (H2Se) Sensor: a Density Functional Investigation.

The adsorption of H2Se molecule on AlN-NCS and AlP-NCS surfaces were investigated by using of DFT calculations. The potentials of Cl-functionalized AlN-NCS and AlP-NCS for H2Se adsorption were examined. All processes of H2Se-adsorption on considered nanocone sheets were exothermic reactions. The calculated |Ead| amount of complex H2Se with AlP-NCS was higher than AlN-NCS. The functionalization of considered nanocone sheets with Cl atom increase |Ead| amount of H2Se. Results reveal that, obtained Ead amounts of considered nanocone sheets have linear relationships with corresponding orbital energy amounts. Finally, the novel nanocone sheets with higher efficiency to adsorption of H2Se can be proposed.

Effects of cholinergic system of dorsal hippocampus of rats on MK-801 induced anxiolytic-like behavior.

RATIONALE: Some investigations have shown that the glutamate receptors play a critical role in cognitive processes such as learning and anxiety. OBJECTIVES: The possible involvement of the cholinergic system of the dorsal hippocampus in the anxiolytic-like response induced by MK-801, NMDA receptor antagonist, was investigated in the present study. METHODS: Male Wistar rats were used in the elevated plus maze apparatus to test the parameters: open arm time (%OAT), open arm entries (%OAE), close arm time (%CAT), close arm entries (%CAE) and other exploratory behaviors (locomotor activity, grooming, rearing and defecation) of anxiety-like response. RESULTS: The data indicated that intra-CA1 administration of MK-801 increased %OAT (2µg/rat) and %OAE (1 and 2µg/rat) while decreased %CAT and %CAE and did not alter other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, intra-hippocampal injections of mecamylamine, a cholinergic receptor antagonists (2µg/rat) and scopolamine (4µg/rat), by themselves, 5min before testing, increased %OAT and %OAE but decreased %CAT and %CAE and did not alter locomotor activity and other exploratory behaviors, suggesting an anxiolytic-like effect. On the other hand, intra-CA1 co-administration of an ineffective dose of scopolamine (3µg/rat), but not mecamylamine (1µg/rat), with an ineffective dose of MK-801 (0.5µg/rat) increased %OAT and %OAE and decreased %CAT and %CAE. The data may indicate the possible involvement of the cholinergic system of the CA1 in the anxiolytic-like response induced by MK-801.