Predicting Adverse Neonatal Outcomes for Preterm Neonates with Multi-Task Learning

Diagnosis of adverse neonatal outcomes is crucial for preterm survival since it enables doctors to provide timely treatment. Machine learning (ML) algorithms have been demonstrated to be effective in predicting adverse neonatal outcomes. However, most previous ML-based methods have only focused on predicting a single outcome, ignoring the potential correlations between different outcomes, and potentially leading to suboptimal results and overfitting issues. In this work, we first analyze the correlations between three adverse neonatal outcomes and then formulate the diagnosis of multiple neonatal outcomes as a multi-task learning (MTL) problem. We then propose an MTL framework to jointly predict multiple adverse neonatal outcomes. In particular, the MTL framework contains shared hidden layers and multiple task-specific branches. Extensive experiments have been conducted using Electronic Health Records (EHRs) from 121 preterm neonates. Empirical results demonstrate the effectiveness of the MTL framework. Furthermore, the feature importance is analyzed for each neonatal outcome, providing insights into model interpretability

S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia

ABSTRACT Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited. Using a neonatal mouse model of BPD, we show that hyperoxia increases activity and expression of a mediator of endogenous bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p, predicted in silico and shown in this study in vitro to suppress expression of GSNO reductase, was decreased in hyperoxia-exposed pups. Both pretreatment with aerosolized GSNO and inhibition of GSNO reductase attenuated airway hyperresponsiveness in vivo among juvenile and adult mice exposed to neonatal hyperoxia. Our data suggest that neonatal hyperoxia exposure causes detrimental effects on airway hyperreactivity through microRNA-342-3p-mediated upregulation of GSNO reductase expression. Furthermore, our data demonstrate that this adverse effect can be overcome by supplementing its substrate, GSNO, or by inhibiting the enzyme itself. Rates of BPD have not improved over the past two decades; nor have new therapies been developed. GSNO-based therapies are a novel treatment of the respiratory problems that patients with BPD experience

Collagen VI Deficiency Results in Structural Abnormalities in the Mouse Lung

Collagen VI (COL6) is known for its role in a spectrum of congenital muscular dystrophies, which are often accompanied by respiratory dysfunction. However, little is known regarding the function of COL6 in the lung. We confirmed the presence of COL6 throughout the basement membrane region of mouse lung tissue. Lung structure and organization were studied in a previously described Col6a1-/- mouse, which does not produce detectable COL6 in the lung. The Col6a1-/- mouse displayed multiple histopathologic alveolar and airway abnormalities. The airspaces of Col6a1-/- lungs appeared simplified, with larger (29%; P\ua0<\ua00.01) and fewer (31%; P\ua0<\ua00.001) alveoli. These airspace abnormalities included a reduction in isolectin B4+ alveolar capillaries and surfactant protein C-positive alveolar epithelial type-II cells. Alterations in lung function consistent with these histopathologic changes were evident. Col6a1-/- mice also displayed multiple airway changes, including increased branching (59%; P\ua0<\ua00.001), increased mucosal thickness (34%; P\ua0<\ua00.001), and increased epithelial cell density (13%; P\ua0<\ua00.001). Comprehensive transcriptome analysis revealed that the loss of COL6 is associated with reductions in integrin-paxillin-phosphatidylinositol 3-kinase signaling in\ua0vivo. In\ua0vitro, COL6 promoted steady-state phosphorylated paxillin levels and reduced cell density (16% to 28%; P\ua0<\ua00.05) at confluence. Inhibition of phosphatidylinositol 3-kinase, or its downstream effectors, resulted in increased cell density to a level similar to that seen on matrices lacking COL6

Analyzing the Cryptome: Uncovering Secret Sequences

The mammalian cryptome consists of bioactive peptides generated by the proteolysis of precursor proteins. It is speculated that the cryptide repertoire increases the complexity of the proteome by an order of magnitude. Cryptides have been found to function in a wide range of processes including neuronal signaling, antigen presentation, and the inflammatory response. Due to their potential as therapeutic agents, there has been an increasing interest in studying cryptides. In this review, we discuss different approaches for discovering these hidden peptides and how proteomic tools can be utilized to aid in their identification and characterization

The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery.

The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease. PAPERCLIP