Genetic and functional characterization of disease associations explains comorbidity

Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer's disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations

Diagnostic and prognostic value of long noncoding RNAs in sepsis: a systematic review and meta-analysis

To explore the potential of long noncoding RNA (lncRNA) as a diagnostic and prognostic biomarker for patients with sepsis. Literature was obtained from seven databases. Relevant data were examined by combining sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic orders ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve with their corresponding 95% confidence intervals (CI) using a bivariate model. Seventeen works of literature were included for meta-analysis. The meta-analysis determined that combined SEN was 0.76 (95% C.I.: 0.69–0.82), combined SPE was 0.84 (95% C.I.: 0.79–0.88), combined PLR was 4.81 (95% C.I.: 3.70–6.25), combined NLR was 0.28 (95% C.I.: 0.22–0.36), combined DOR was 17.02 (95% C.I.: 11.96–24.22), and AUC was 0.88 (95% C.I.: 0.84–0.90), however, for prognostic meta-analysis, combined SEN was 0.82 (95% C.I.: 0.73–0.86), combined SPE was 0.69 (95% C.I.: 0.54–0.81), combined PLR was 2.69 (95% C.I.: 1.82–3.97), combined NLR was 0.25 (95% C.I.: 0.10–0.35), combined DOR was 10.63 (95% C.I.: 7.13–15.87), and AUC was 0.84 (95% C.I.: 0.81–0.87). LncRNA possesses a significant diagnostic and prognostic ability for sepsis.</p

Aerosol delivery in models of pediatric high flow nasal oxygen and mechanical ventilation

Background: Aerosol drug delivery during high flow nasal oxygen (HFNO) and invasive mechanical ventilation (IMV) are key respiratory care strategies available for the treatment of pediatric patients. We aimed to quantify the impact of different HFNO and IMV set-ups on tracheal drug delivery via a vibrating mesh nebuliser (VMN). Methods: Percent tracheal dose via VMN was quantified during HFNO therapy and IMV in a benchtop model of a 9-month-old infant. Under HFNO, 3 cannula sizes were used at 3 flow rate settings with the VMN placed at the dry side of the humidifier. Under IMV, tracheal dose when VMN was placed at the dry side of the humidifier, 15 cm from the wye and between the wye and endotracheal tube (ETT) was assessed. Salbutamol at 2.5 mg/2.5 ml (1 mg/ml) was used for each test (N = 5). The impact of VMN refill on circuit pressure under HFNO and IMV was also assessed. Results: Tracheal dose was highest during HFNO with the largest cannula size (OPT318) set to the lowest flow rate setting of 2 L/min (liter per minute) (5.80 ± 0.17%). Increasing flow rate reduced tracheal drug delivery for all cannulas. For IMV, VMN on the dry side of the humidifier and between the wye and ETT gave optimal drug delivery (4.49 ± 0.14% vs. 4.43 ± 0.26% respectively). VMN refill did not impact circuit pressure for either HFNO therapy or IMV. Conclusions: Gas flow rate and cannula size during HFNO and VMN position during IMV has a significant effect on tracheal drug delivery in a pediatric setting.</p

Late Carboniferous bimodal volcanic rocks of the West Junggar Terrane, NW China: Implications for the postcollisional tectonic setting of the southwestern CAOB

The West Junggar terrain (WJT), as a crucial part of the Central Asian Orogenic Belt (CAOB), is distributed with numerous igneous rocks, which provide critical information for crustal growth. However, the closure of the Junggar Ocean (JO) and the beginning of the postcollisional tectonic stage of the WJT have been controversial. This study delimited the regional lithologic units based on remote sensing geological mapping and recognized a series of bimodal volcanic rocks (BVR) in Hala’alate Mountain of the WJT. LA-ICP‒MS zircon U‒Pb geochronology and geochemistry were used to discuss the petrogenesis of the BVR and determine the stage of regional tectonic evolution. Geochronological results yield crystallization ages of 302 ± 4 Ma, 298 ± 2 Ma, 304 ± 1 Ma, and 303 Ma±2Ma ± 2 Ma for the basaltic andesite, basaltbasalt, and two rhyolitic samples, respectively. Basalts and basaltic andesites are calc-alkaline, and display enrichment in light rare earth elements (LREEs) and large ion lithophile elements (LILEs) and depletion in high field strength elements (HFSEs). Notably, basaltic andesites in this area were once misjudged as sanukitoids owing to their low contents of Mg#, Ni, CrCr, and other characteristics that are inconsistent with the typical definition of sanukitoids. The rhyolites are A2-type granitoids with high SiO2 contents and are depleted in Nb, Ta, P, Ti, and Sr, showing enriched LREE patterns with negative Eu anomalies. These features indicate that the magma of the mafic end-member of the BVR is derived from the partial melting of the depleted lithospheric mantle, whereas the felsic end-member magma can be associated with the remelting of the lower crust due to the upwelling and underplating of mafic magma. In combination with previous studies of simultaneouslysimultaneous basic dykesdikes and felsic rocks, a postcollisional tectonic stage was proposed for the WTJ during the late Carboniferous, suggesting that the JO was closed.</p

A qRT-PCR analysis of nine randomly selected genes from <i>B</i>.<i>tabaci</i> that showed relative expressions at 24AP and 72AP.

<p>Black stands for the control and gray stands for a parasitized sample. The expression levels of the controls were regarded as 1. Error bars indicate standard deviations of the average from three replicates. The same letter above the error bar means that there was no significant difference at the 0.05 level by Duncan’s test.</p

Developmental-related genes differentially expressed in <i>B</i>. <i>tabaci</i> after being parasitized by <i>E</i>. <i>sophia</i>.

<p>Developmental-related genes differentially expressed in <i>B</i>. <i>tabaci</i> after being parasitized by <i>E</i>. <i>sophia</i>.</p

Metabolism-related genes differentially expressed in <i>B</i>. <i>tabaci</i> after being parasitized by <i>E</i>. <i>sophia</i>.

<p>Metabolism-related genes differentially expressed in <i>B</i>. <i>tabaci</i> after being parasitized by <i>E</i>. <i>sophia</i>.</p

Distribution of unigene lengths in the <i>B</i>. <i>tabaci</i> transcriptome.

<p><i>De novo</i> assembly of RNA-seq data produced 292,696 unigenes between 201–28,036bp in length.</p

GO annotation of differentially expressed genes at 24APand 72AP (level 2).

<p>At 24AP, the program categorized 390 unigenes in the cellular component category, 297 unigenes in the molecular function category, and 542 unigenes in the biological process category. At 72AP, the program categorized 732 unigenes in the cellular component category, 580 unigenes in the molecular function category, and 971 unigenes in the biological process category.</p

General information about genes that were differentially expressed in response to parasitization.

<p>The left figure shows the numbers of genes that were up-regulated and down-regulated at 24AP and 72AP. The right figure shows distribution of up-regulated (blue bars) and down-regulated (red bars) genes based on their fold change.</p