Biomedical and biophysical limits to mathematical modeling of pulmonary system mechanics: a scoping review on aerosol and drug delivery.

Undoubtedly, the construction of the biomechanical geometry systems with the help of computer tomography (CT) and magnetic resonance imaging (MRI) has made a significant advancement in studying in vitro numerical models as accurately as possible. However, some simplifying assumptions in the computational studies of the respiratory system have caused errors and deviations from the in vivo actual state. The most important of these hypotheses is how to generate volume from the point cloud exported from CT or MRI images, not paying attention to the wall thickness and its effect in computational fluid dynamic method, statistical logic of aerosol trap in software; and most importantly, the viscoelastic effect of respiratory tract wall in living tissue pointed in the fluid-structure interaction method. So that applying the viscoelastic dynamic mesh effect in the form of the moving deforming mesh can be very effective in achieving more appropriate response quality. Also, changing the volume fraction of the pulmonary extracellular matrix constituents leads to changes in elastic modulus (storage modulus) and the viscous modulus (loss modulus) of lung tissue. Therefore, in the biomedical computational methods where the model wall is considered flexible, the viscoelastic properties of the texture must be considered correctly

Investigation of the Upper Respiratory Tract of a Male Smoker with Laryngeal Cancer by Inhaling Air Associated with Various Physical Activity Levels

Smokers are at a higher risk of laryngeal cancer, which is a type of head and neck cancer in which cancer cells proliferate and can metastasize to other tissues after a tumor has formed. Cigarette smoke greatly reduces the inhaled air quality and can also lead to laryngeal cancer. In this study, the upper airway of a 70-year-old smoker with laryngeal cancer was reconstructed by taking a CT scan using Mimics software. To solve the governing equations, computational fluid dynamics (CFD) with a pressure base approach was used with the help of Ansys 2021 R1 software. As a result, the maximum turbulence intensity occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum turbulence intensity was 1.1, 3.5, and 6.1, respectively. The turbulence intensity in the respiratory system is crucial because it demonstrates the ability to transfer energy. The maximum wall shear stress (WSS) also occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum WSS was 0.62 Pa, 5.4 Pa, and 12.4 Pa, respectively. The WSS index cannot be calculated in vivo and should be calculated in vitro. Excessive WSS in the epiglottis is inappropriate and can lead to an airway obstruction. Furthermore, real mathematical modeling outcomes provide an approach for future prevention, treatment, and management planning by forecasting the zones prone to an acceleration of disease progression. In this regard, accurate computational modeling leads to pre-visualization in surgical planning to define the best reformative techniques to determine the most probable patient condition consequences

Cancer somatic mutations cluster in a subset of regulatory sites predicted from the ENCODE data

Background: Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. The ENCODE project has mapped potential regulatory sites across the complete genome in many cell types, and these regions have been shown to harbour many of the somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. The ENCODE data suggests a very large number of regulatory sites, and methods are needed to identify those that are most relevant and to connect them to the genes that they control. Methods: Predictive models of gene expression were developed by integrating the ENCODE data for regulation, including transcription factor binding and DNase1 hypersensitivity, with RNA-seq data for gene expression. A penalized regression method was used to identify the most predictive potential regulatory sites for each transcript. Known cancer somatic mutations from the COSMIC database were mapped to potential regulatory sites, and we examined differences in the mapping frequencies associated with sites chosen in regulatory models and other (rejected) sites. The effects of potential confounders, for example replication timing, were considered. Results: Cancer somatic mutations preferentially occupy those regulatory regions chosen in our models as most predictive of gene expression. Conclusion: Our methods have identified a significantly reduced set of regulatory sites that are enriched in cancer somatic mutations and are more predictive of gene expression. This has significance for the mechanistic interpretation of cancer mutations, and the understanding of genetic regulation

STELLAR: fast and exact local alignments

<p>Abstract</p> <p>Background</p> <p>Large-scale comparison of genomic sequences requires reliable tools for the search of local alignments. Practical local aligners are in general fast, but heuristic, and hence sometimes miss significant matches.</p> <p>Results</p> <p>We present here the local pairwise aligner STELLAR that has full sensitivity for <it>ε</it>-alignments, i.e. guarantees to report all local alignments of a given minimal length and maximal error rate. The aligner is composed of two steps, filtering and verification. We apply the SWIFT algorithm for lossless filtering, and have developed a new verification strategy that we prove to be exact. Our results on simulated and real genomic data confirm and quantify the conjecture that heuristic tools like BLAST or BLAT miss a large percentage of significant local alignments.</p> <p>Conclusions</p> <p>STELLAR is very practical and fast on very long sequences which makes it a suitable new tool for finding local alignments between genomic sequences under the edit distance model. Binaries are freely available for Linux, Windows, and Mac OS X at <url>http://www.seqan.de/projects/stellar</url>. The source code is freely distributed with the SeqAn C++ library version 1.3 and later at <url>http://www.seqan.de</url>.</p

Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.

Translog, a web browser for studying the expression divergence of homologous genes

<p>Abstract</p> <p>Background</p> <p>Increasing amount of data from comparative genomics, and newly developed technologies producing accurate gene expression data facilitate the study of the expression divergence of homologous genes. Previous studies have individually highlighted factors that contribute to the expression divergence of duplicate genes, e.g. promoter changes, exon structure heterogeneity, asymmetric histone modifications and genomic neighborhood conservation. However, there is a lack of a tool to integrate multiple factors and visualize their variety among homologous genes in a straightforward way.</p> <p>Results</p> <p>We introduce Translog (a web-based tool for Transcriptome comparison of homologous genes) that assists in the comparison of homologous genes by displaying the loci in three different views: promoter view for studying the sharing/turnover of transcription initiations, exon structure for displaying the exon-intron structure changes, and genomic neighborhood to show the macro-synteny conservation in a larger scale. CAGE data for transcription initiation are mapped for each transcript and can be used to study transcription turnover and expression changes. Alignment anchors between homologous loci can be used to define the precise homologous transcripts. We demonstrate how these views can be used to visualize the changes of homologous genes during evolution, particularly after the 2R and 3R whole genome duplication.</p> <p>Conclusion</p> <p>We have developed a web-based tool for assisting in the transcriptome comparison of homologous genes, facilitating the study of expression divergence.</p

Clinical features of headache associated with mobile phone use: a cross-sectional study in university students

<p>Abstract</p> <p>Background</p> <p>Headache has been reported to be associated with mobile phone (MP) use in some individuals. The causal relationship between headache associated with MP use (HAMP) and MP use is currently undetermined. Identifying the clinical features of HAMP may help in clarifying the pathophysiology of HAMP and in managing symptoms of individuals with HAMP. The aim of the present study is to describe the clinical features of HAMP.</p> <p>Methods</p> <p>A 14-item questionnaire investigating MP use and headache was administered to 247 medical students at Hallym University, Korea. Individual telephone interviews were subsequently conducted with those participants who reported HAMP more than 10 times during the last 1 year on the clinical features of HAMP. We defined HAMP as a headache attack during MP use or within 1 hour after MP use.</p> <p>Results</p> <p>In total, 214 (86.6%) students completed and returned the questionnaire. Forty (18.9%) students experienced HAMP more than 10 times during the last 1 year in the questionnaire survey. In subsequent telephone interviews, 37 (97.4%) interviewed participants reported that HAMP was triggered by prolonged MP use. HAMP was usually dull or pressing in quality (30 of 38, 79.0%), localised ipsilateral to the side of MP use (32 of 38, 84.2%), and associated with a burning sensation (24 of 38, 63.2%).</p> <p>Conclusion</p> <p>We found that HAMP usually showed stereotyped clinical features including mild intensity, a dull or pressing quality, localisation ipsilateral to the side of MP use, provocation by prolonged MP use and often accompanied by a burning sensation.</p