Artificial Intelligence in Intensive Care Medicine

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis

Comment by InpharmD Researcher

The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties. In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response.

Plasma arginine-vasopressin (AVP) analysis can help in the differential diagnosis of the polyuria-polydipsia syndrome (PPS), even if such investigation is hampered by technical difficulties, conversely to its surrogate copeptin. This study aims to enlarge the existing data on normal copeptin levels in childhood, to evaluate the correlation between copeptin, serum sodium and plasma and urine osmolality, and to assess the utility of the copeptin analysis in the diagnostic work-up of PPS in the paediatric age.

Background

A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM.

Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis.

A weighted gene coexpression network was constructed, and the genes were divided into 66 modules. The enriched functions and candidate pathway modules included interferon-γ, type I interferon, cellular response to interferon-γ, neutrophil activation, neutrophil degranulation, neutrophil-mediated immunity and neutrophil activation involved in the immune response. A total of 22 hub genes were identified. The Mann-Whitney U test was performed on these 22 genes using the three datasets of muscle samples and one dataset of whole blood samples, and two genes significantly differentially expressed in all datasets were obtained: VCAM1 and LY96. Receiver operating characteristic curve analysis determined that VCAM1 and LY96 gene expression can distinguish PM from healthy controls (the area under the curve [AUC] was greater than 0.75). Logistic regression analysis was performed on the combination of LY96 and VCAM1. The accuracy, sensitivity, specificity, and AUC of the combination reached 1.0. GSEA of VCAM1 and LY96 revealed their relation to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. CMap research revealed a few compounds with the potential to counteract the effects of the dysregulated molecular signature in PM.

To identify the candidate genes of PM, microarray datasets GSE128470, GSE3112, GSE39454 and GSE125977 were obtained from the Gene Expression Omnibus database. The gene network of GSE128470 was constructed, and WGCNA was used to divide genes into different modules. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied to the most PM-related modules. The datasets were used to verify the expression profile and diagnostic capabilities of the hub genes. Additionally, gene set enrichment analysis (GSEA) was carried out. Moreover, gene signatures were then used as a search query to explore the connectivity map (CMap).

Relevant Prescribing Information

We used WGCNA to observe all aspects of PM, which helped to elucidate the molecular mechanisms of PM onset and progression and provide candidate targets for the diagnosis and treatment of PM. Key Points • Four microarray datasets were analysed in patients with polymyositis and healthy controls, and VCAM1 and LY96 were significant genes in all datasets. • GSEA of VCAM1 and LY96 revealed that they were mainly related to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. • CMap found a few compounds such as dimethyloxalylglycine and HNMPA-(AM)3 with the potential to counteract the effects of the dysregulated molecular signature in PM. The purpose of our present study was to, for the first time, identify key genes associated with postpartum depression (PPD) and discovery the potential molecular mechanisms of this condition. Methods: First, microarray expression profiles GSE45603 dataset were acquired from the Gene Expression Omnibus (GEO) in National Center for Biotechnology Information (NCBI). The weighted gene co-expression network analysis (WGCNA) was performed to identify the top three modules from differentially expressed genes (DEGs). Furthermore, cross-validated differential gene expression analysis of the top three modules and DEGs was used to identify the hub genes. Gene set enrichment analysis (GSEA) was conducted to identify the potential functions of the hub genes. We conducted a Receiver Operator Characteristic (ROC) curve to verify the diagnostic efficiencies of the hub genes. Lastly, GSE44132 dataset was used to search the association between the methylation profiles of the hub genes and susceptibility to PPD.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Table 1 for your response.

Enter title in bold, with all first words capitalized, and without a reference number
Design	Objective terms describing the type of study (randomized, uncontrolled, retrospective, placebo-controlled, cross-over, etc.); N= (total subjects)
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Baseline Characteristics		A	B
	Age, years
	Female
	White
	---
	Include relevant baseline characteristics that will provide a general (big picture) view of the patients in the study.
Results	Endpoint	A	B	p-Value
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	Serious Adverse Events: (or those deemed high risk; if not listed in study, use N/A or “Not disclosed”)
	Percentage that Discontinued due to Adverse Events: (if not listed in study, use N/A or “Not disclosed”)
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