SAERMA: Stacked Autoencoder Rule Mining Algorithm for the Interpretation of Epistatic Interactions in GWAS for Extreme Obesity

One of the most important challenges in the analysis of high-throughput genetic data is the development of efficient computational methods to identify statistically significant Single Nucleotide Polymorphisms (SNPs). Genome-wide association studies (GWAS) use single-locus analysis where each SNP is independently tested for association with phenotypes. The limitation with this approach, however, is its inability to explain genetic variation in complex diseases. Alternative approaches are required to model the intricate relationships between SNPs. Our proposed approach extends GWAS by combining deep learning stacked autoencoders (SAEs) and association rule mining (ARM) to identify epistatic interactions between SNPs. Following traditional GWAS quality control and association analysis, the most significant SNPs are selected and used in the subsequent analysis to investigate epistasis. SAERMA controls the classification results produced in the final fully connected multi-layer feedforward artificial neural network (MLP) by manipulating the interestingness measures, support and confidence, in the rule generation process. The best classification results were achieved with 204 SNPs compressed to 100 units (77% AUC, 77% SE, 68% SP, 53% Gini, logloss=0.58, and MSE=0.20), although it was possible to achieve 73% AUC (77% SE, 63% SP, 45% Gini, logloss=0.62, and MSE=0.21) with 50 hidden units - both supported by close model interpretation

Echocardiography and pulse contour analysis to assess cardiac output in trauma patients.

Echocardiography is a valuable technique to assess cardiac output (CO) in trauma patients, but it does not allow a continuous bedside monitoring. Beat-to-beat CO assessment can be obtained by other techniques, including the pulse contour method MostCare. The aim of our study was to compare CO obtained with MostCare (MC-CO) with CO estimated by transthoracic echocardiography (TTE-CO) in trauma patients. METHODS: Forty-nine patients with blunt trauma admitted to an intensive care unit and requiring hemodynamic optimization within 24 hours from admission were studied. TTE-CO and MC-CO were estimated simultaneously at baseline, after a fluid challenge and after the start of vasoactive drug therapy. RESULTS: One hundred sixteen paired CO values were obtained. TTE-CO values ranged from 2.9 to 7.6 L·min-1, and MC-CO ranged from 2.8 to 8.2 L·min-1. The correlation between the two methods was 0.94 (95% confidence interval [CI] = 0.89 to 0.97; p<0.001). The mean bias was -0.06 L·min-1 with limits of agreements (LoA) of -0.94 to 0.82 L·min-1 (lower 95% CI, -1.16 to -0.72; upper 95% CI, 0.60 to 1.04) and a percentage error of 18%. Changes in CO showed a correlation of 0.91 (95% CI = 0.87 to 0.95; p<0.001), a mean bias of - 0.01 L·min-1 with LoA of -0.67 to 0.65 L·min-1 (lower 95% CI, -0.83 to -0.51; upper 95% CI, 0.48 to 0.81). CONCLUSION: CO measured by MostCare showed good agreement with CO obtained by transthoracic echocardiography. Pulse contour analysis can complement echocardiography in evaluating hemodynamics in trauma patients

An Investigation into the Biological Effects of Indirect Potable Reuse Water Using Zebrafish Embryos

© 2021 The Authors. Advanced treatment technologies are being assessed as a proactive measure to assist with the transformation of treated wastewater into a source of water for potable water production. We investigated the biological effects along an advanced water treatment pilot plant, using zebrafish embryos throughout early development. The study compared phenotypic observations with global transcriptome responses, enabling us to keep an open mind about the chemicals that might influence the biological activity. There was no evidence of acute toxicity at any treatment stage, but skeletal, cardiovascular and pigmentation changes occurred in a small proportion of embryos along the treatment process, and in a tap water; not detected in the aquarium water control. Reverse osmosis (RO) reduced the concentration of measured chemical contaminants in the water the most, while eliminating the occurrence of abnormalities detected in fish embryos. Conversely, advanced oxidation reversed the benefits of RO treatment by increasing the frequency of teratogenic and sub-lethal abnormalities seen. Using the molecular responses of zebrafish embryos to different IPR water, we report the bioactivity within the water at different stages of advanced treatment and associate these to perturbed biological functions. Transcriptomic analysis revealed alterations to the retinoid system, which was consistent with the observed teratogenic effects. Changes to tryptophan metabolism (associated with the production of melatonin required for the control of normal circadian rhythms) and somatolactin-beta (associated with normal pigmentation in fish) were also found. We show that underexplored forms of biological activity occur in treated wastewater effluent, and/or may be created depending on the type of advanced treatment process used. By integrating the available analytical chemistry we highlight chemical groups associated to this response. Our study shows that more detailed and in-depth characterisation of chemicals and biological pathways associated with advanced treatment water systems are needed to mitigate possible risks to downstream organisms.Thames Water Utilities Ltd

Are periodontitis and psoriasis associated? A pre-clinical murine model

Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. Materials and Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm(2)]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-alpha) were collected. Results: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm(2)) compared to the control group (p &lt;.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p &lt;.05). Conclusions: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation

The solar chromosphere at high resolution with IBIS. I. New insights from the Ca II 854.2 nm line

(Abridged) Aims: In this paper, we seek to establish the suitability of imaging spectroscopy performed in the Ca II 854.2 nm line as a means to investigate the solar chromosphere at high resolution. Methods: We utilize monochromatic images obtained with the Interferometric BIdimensional Spectrometer (IBIS) at multiple wavelengths within the Ca II 854.2 nm line and over several quiet areas. We analyze both the morphological properties derived from narrow-band monochromatic images and the average spectral properties of distinct solar features such as network points, internetwork areas and fibrils. Results: The spectral properties derived over quiet-Sun targets are in full agreement with earlier results obtained with fixed-slit spectrographic observations, highlighting the reliability of the spectral information obtained with IBIS. Furthermore, the very narrowband IBIS imaging reveals with much clarity the dual nature of the Ca II 854.2 nm line: its outer wings gradually sample the solar photosphere, while the core is a purely chromospheric indicator. The latter displays a wealth of fine structures including bright points, akin to the Ca II H2V and K2V grains, as well as fibrils originating from even the smallest magnetic elements. The fibrils occupy a large fraction of the observed field of view even in the quiet regions, and clearly outline atmospheric volumes with different dynamical properties, strongly dependent on the local magnetic topology. This highlights the fact that 1-D models stratified along the vertical direction can provide only a very limited representation of the actual chromospheric physics.Comment: 13 pages, 8 figures. Accepted in A&A. Revised version after referee's comments. New Fig. 1 and 7. Higher quality figures in http://www.arcetri.astro.it/~gcauzzi/papers/ibis.caii.pd

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA