Multi-branch convolutional neural network for identification of small non-coding RNA genomic loci

Genomic regions that encode small RNA genes exhibit characteristic patterns in their sequence, secondary structure, and evolutionary conservation. Convolutional Neural Networks are a family of algorithms that can classify data based on learned patterns. Here we present MuStARD an application of Convolutional Neural Networks that can learn patterns associated with user-defined sets of genomic regions, and scan large genomic areas for novel regions exhibiting similar characteristics. We demonstrate that MuStARD is a generic method that can be trained on different classes of human small RNA genomic loci, without need for domain specific knowledge, due to the automated feature and background selection processes built into the model. We also demonstrate the ability of MuStARD for inter-species identification of functional elements by predicting mouse small RNAs (pre-miRNAs and snoRNAs) using models trained on the human genome. MuStARD can be used to filter small RNA-Seq datasets for identification of novel small RNA loci, intra- and inter- species, as demonstrated in three use cases of human, mouse, and fly pre-miRNA prediction. MuStARD is easy to deploy and extend to a variety of genomic classification questions. Code and trained models are freely available at gitlab.com/RBP_Bioinformatics/mustard.peer-reviewe

GAINESIS: Generative Artificial Intelligence NEtlists SynthesIS

A significant problem in the field of hardware security consists of hardware trojan (HT) viruses. The insertion of HTs into a circuit can be applied for each phase of the circuit chain of production. HTs degrade the infected circuit, destroy it or leak encrypted data. Nowadays, efforts are being made to address HTs through machine learning (ML) techniques, mainly for the gate-level netlist (GLN) phase, but there are some restrictions. Specifically, the number and variety of normal and infected circuits that exist through the free public libraries, such as Trust-HUB, are based on the few samples of benchmarks that have been created from circuits large in size. Thus, it is difficult, based on these data, to develop robust ML-based models against HTs. In this paper, we propose a new deep learning (DL) tool named Generative Artificial Intelligence Netlists SynthesIS (GAINESIS). GAINESIS is based on the Wasserstein Conditional Generative Adversarial Network (WCGAN) algorithm and area–power analysis features from the GLN phase and synthesizes new normal and infected circuit samples for this phase. Based on our GAINESIS tool, we synthesized new data sets, different in size, and developed and compared seven ML classifiers. The results demonstrate that our new generated data sets significantly enhance the performance of ML classifiers compared with the initial data set of Trust-HUB

Low Morning Serum Cortisol Levels in Children with Tonsillar Hypertrophy and Moderate-to-Severe OSA

Background: Hypertrophic tonsillar tissue in children with obstructive sleep apnea (OSA) has enhanced expression of glucocorticoid receptors, which may reflect low endogenous cortisol levels. We have evaluated the effect of the interaction between tonsillar hypertrophy and OSA severity on morning serum cortisol levels. Methods: Children with and without snoring underwent polysomnography, tonsillar size grading, and measurement of morning serum cortisol. Results: Seventy children (2-13 years old) were recruited: 30 with moderate-to-severe OSA (apnea-hypopnea index [AHI] > 5 episodes/h), 26 with mild OSA (AHI > 1 and <= 5), and 14 controls (no snoring; AHI <= 1). Tonsillar hypertrophy was present in 56.7%, 53.8%, and 42.9% of participants in each group, respectively. Application of a general linear model demonstrated a significant effect of the interaction between severity of OSA and tonsillar hypertrophy on cortisol levels (P = 0.04), after adjustment for obesity, gender, and age. Among children with tonsillar hypertrophy, subjects with moderate-to-severe OSA (n = 17; AHI 14.7 +/- 10.6), mild OSA (n = 14; AHI 2.3 +/- 1.2), and control participants (n = 6; AHI 0.7 +/- 0.2) were significantly different regarding cortisol levels (P = 0.02). Subjects with moderate-to-severe OSA had lower cortisol (16.9 +/- 8.7 mcg/dL) than those with mild OSA (23.3 +/- 4.2; P = 0.01) and those without OSA (controls) (23.6 +/- 5.3 mcg/dL; P = 0.04). In contrast, children with normal-size tonsils and moderate-to-severe OSA, mild OSA, and controls did not differ in cortisol levels. Conclusions: Children with moderate-to-severe obstructive sleep apnea and the phenotype of hypertrophic tonsils have reduced morning serum cortisol levels and potentially decreased glucocorticoid inhibitory effects on tonsillar growth

Theoretical Elucidation of a Classic Reaction: Protonation of the Quadruple Bond of the Octachlorodimolybdate(II,II) [Mo₂Cl₈]^4– Anion

The protonation reaction of the unbridged quadruple metal–metal bond of [Mo₂Cl₈]^4– anion producing the triply bonded hydride [Mo₂(μ-H)­(μ-Cl)₂Cl₆]^3– is studied by accurate Density Functional Theory computations. The reactant, product, stable intermediates, and transition states are located on the potential energy surface. The water solvent is explicitly included in the calculations. Full reaction profiles are calculated and compared to experimental data. The mechanism of the reaction is fully elucidated. This involves two steps. The first is a proton transfer from an oxonium ion to the quadruple bond, being rate determining. The second, involves the internal rearrangement of chlorine atoms and is much faster. Activation energies with a mean value of 19 kcal/mol are calculated, in excellent agreement with experimental values

Right-sided Chest Leads in Exercise Testing for Detection of Coronary Restenosis

Background: The incorporation of right-sided chest leads (V(3)R through V(5)R) into standard exercise testing has been reported to improve its diagnostic utility. Hypothesis: The purpose of this study was to evaluate any improvement in the ability of exercise testing in detecting restenosis, using additional V(3)R through V(5)R leads, in asymptomatic patients undergoing percutaneous coronary intervention (PCI) in the right coronary artery (RCA) or/and left circumflex (LCX). Methods: We studied 172 consecutive patients (54 +/- 7 years old, 106 males) undergoing PCI in RCA or/and LCX. A treadmill test had been performed before PCI. Six months later, all patients underwent a second treadmill test and arteriography in order to detect silent ischemia due to restenosis. Recordings during exercise were obtained with the standard 12-leads plus V(3)R through V(5)R. Results: Out of 172 patients, 106 had stenosis in RCA, 35 in LCX, and 31 in both vessels while 6 months later, restenosis was detected in 8 (for RCA), 3 (for LCX), and 3 (for both vessels) patients respectively. Sensitivity, specificity, positive prognostic value, negative prognostic value, and accuracy of exercise testing performed post PCI were ameliorated using V(3)R through V5R (79% vs 57%, 97% vs 80%, 69% vs 21%, 98% vs 95%, and 95% vs 78% respectively, P < .05 for all except negative prognostic value). Maximal exercise-induced ST-segment deviation (in mm) was not changed post PCI in 12 leads (1.4 +/- 0.2 vs 1.5 +/- 0.2, P = NS) while it was decreased in V(3)R through V(5)R (0.2 +/- 0.2 vs 1.2 +/- 0.3, P < .01) Conclusions: The addition of V(3)R through V(5)R improves the diagnostic ability of standard exercise testing in detecting silent ischemia due to restenosis in patients undergoing PCI in RCA or/and LCX

Low-grade albuminuria in children with obstructive sleep apnea

Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apneahypopnea index<1episodeh1; n=31); (ii) mild obstructive sleep apnea (snoring, apneahypopnea index=15episodesh1; n=71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apneahypopnea index>5episodes.h1; n=27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio>median value in the control group (1.85mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.112.6); P=0.04 and 1.5 (0.63.7); 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r=0.31, P=0.01; and r=0.43, P<0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea

Accuracy of the sleep clinical record for the diagnosis of pediatric moderate-to-severe obstructive sleep apnea syndrome

Purpose The sleep clinical record (SCR) has been used to diagnose obstructive sleep apnea syndrome (OSAS) in children when access to polysomnography (PSG) is limited. Our aim was to determine the best SCR score that could facilitate diagnosis of moderate-to-severe OSAS in children with snoring. Methods Healthy children with history of snoring, who were referred for PSG, were prospectively recruited. The SCR score was calculated. Receiver operating characteristic curves (ROCs) were plotted to determine the area under curve (AUC), and the optimum SCR cutoff value was determined using the Youden index (J). Results Two hundred and seventy-three children were recruited (mean age 6.3 +/- 2.5 years; median obstructive apnea-hypopnea index 1.5 episodes/h; range 0-61.1). The mean SCR score was 6.9 +/- 3.6. Forty-six children had moderate-to-severe OSAS. Subjects with moderate-to-severe OSAS had a significantly higher mean SCR score (10.2 +/- 2.9) than those with mild OSAS (6.2 +/- 3.3; P < 0.001). Based on the plotted ROC, the AUC was 0.811 (95% confidence interval: 0.747-0.876; P < 0.001). Calculation of J, based on its ROC coordinates, indicated that the optimum cutoff SCR score to predict moderate-to-severe OSAS was 8.25, corresponding to a sensitivity of 83% and a specificity of 70%. Conclusion Among children with history of snoring, an SCR score above 8.25 can identify those with moderate-to-severe OSAS

Inflammatory markers and plaque morphology: An optical coherence tomography study

Background: OCT with its unique image resolution is the ideal method to detect culprit lesion characteristics in different clinical presentations. The identification of inflammatory markers related to plaque characteristics may be of clinical importance. Methods: Thirty-two patients with acute coronary syndromes (ACS) and fourteen patients with stable angina pectoris (SAP) were enrolled in this study. Culprit lesion morphology was assessed by optical coherence tomography (OCT) in patients with ACS and SAP. The possible relations between serum levels of high sensitivity-C reactive protein (hs-CRP) and interleukin-18 (IL-18) with plaque characteristics were investigated in those patients. Results: Plaque rupture and thin-cap fibroatheroma (TCFA) were detected more frequently in ACS patients compared with SAP patients, (78.6% vs. 14.3%, p<0.001, 92.9% vs. 14.3%, p<0.001, respectively). Higher levels of serum hs-CRP and IL-18 were found in patients with plaque rupture vs. those with no plaque rupture (median value: 19.2 mg/L vs. 1.6 mg/L, p<0.001 and 219.5 pg/ml vs. 127.5 pg/ml, p=0.001 respectively), and TCFA vs. those without TCFA (median value: 15.2 mg/L vs. 1.6 mg/L, p=0.004 and 209.0 pg/ml vs. 153.2 pg/ml, p=0.03 respectively). Serum hs-CRP was the only independent predictor of plaque rupture (p=0.02, odds ratio 1.1, 95% confidence interval 1.0 to 1.2). A cut-off value of hs-CRP>4.5 mg/L could detect ruptured plaque with a sensitivity of 91.7% and a specificity of 77.8%. Conclusions: OCT detected plaque rupture and TCFA more frequent in ACS patients compared with SAP. Elevated hs-CRP and IL-18 were positively related to plaque instability and rupture. (C) 2010 Elsevier Ireland Ltd. All rights reserved