EsATAC: an easy-to-use systematic pipeline for ATAC-seq data analysis

Summary ATAC-seq is rapidly emerging as one of the major experimental approaches to probe chromatin accessibility genome-wide. Here, we present ‘esATAC’, a highly integrated easy-to-use R/Bioconductor package, for systematic ATAC-seq data analysis. It covers essential steps for full analyzing procedure, including raw data processing, quality control and downstream statistical analysis such as peak calling, enrichment analysis and transcription factor footprinting. esATAC supports one command line execution for preset pipelines and provides flexible interfaces for building customized pipelines. Availability and implementation esATAC package is open source under the GPL-3.0 license. It is implemented in R and C++. Source code and binaries for Linux, MAC OS X and Windows are available through Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/esATAC.html). Supplementary information Supplementary data are available at Bioinformatics online. Document type: Articl

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma

Background: Adolescents and young adults (AYAs) diagnosed with cancer between ages 15 and 45 years may exhibit unique biologic and genomic characteristics as well as clinical features, resulting in differences in clinical characters and drug resistance. However, compared to other solid cancers, relatively few studies have been conducted in this age group in cholangiocarcinoma (CCA). This study is performed to investigate the clinical and molecular features of AYAs with CCA. Methods: Three cohorts, including the external dataset (TCGA and MSKCC) and the perihilar CCA databank of Chinese tertiary hospitals, were contained in this study. Pathway and process enrichment analysis had been carried out with the following ontology sources: KEGG Pathway, GO Biological Processes, Reactome Gene Sets, Canonical Pathways, and CORUM. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism (version 7.0; GraphPad Software, La Jolla, California) and R studio (version 3.6.1; R studio, Boston, Massachusetts). Results: Compared to older adults, AYAs with CCA presented with worse overall survival, although the difference was not significant. Specific to patients with stage IV CCAs who underwent chemotherapy, AYAs were associated with significantly poorer overall survival (OS) (p = 0.03, hazards ratio (HR) 3.01, 95% confidence interval (CI) 1.14-4.91). From the anatomical perspective, more extrahepatic CCA was detected in the AYA group. Microsatellite instability (MSI) occurred in 3% of older patients in the present study. Nevertheless, none of the AYAs had MSI status. In this study, AYAs gained an enhanced frequency of additional sex combs like 1 (ASXL1) (p = 0.02) and KMT2C (p = 0.02) mutation than their older counterparts. Besides ASXL1 and KMT2C, the genes enriched in AYAs with CCA were analyzed by pathway and process enrichment analysis. And those genes were found to be associated with poorer differentiation, deubiquitination, and WNT signal pathway. Moreover, AYAs were relevant to poor differentiation and advanced tumor stage. Conclusion: This study offered a preliminary landscape of the clinical and molecular features of early-onset biliary cancers. Further studies including more samples are essential to investigate whether ASXL1 and KMT2C could be considered as potentially targetable genomic signatures for young patients

A user-centred collective system design approach for Smart Product-Service Systems:A case study on fitness product design

Emerging technologies have significantly contributed to the evolution of traditional product-service systems (PSS) into smart PSS. This transformation demands a fresh perspective and a more inventive design approach. In response, this study proposes a new User-Centred Collective System Design (CSD) framework and process for Smart PSS design, aiming to enhance stakeholder engagement during the entire design process, thus promoting highly effective and creative design solutions. A case study, titled ‘Next-G Smart Fitness PSS Design’, was carried out to test and implement this approach, contrasting the results of the CSD method with a designer-centred method. The outcomes showed a marked improvement in product novelty and user desirability of the design outcomes when using the proposed design framework. The proposed CSD framework could offer beneficial insights and user-centric viewpoints for practitioners dealing with complex challenges linked to smart PSS design

Synchronous right hepatectomy and cesarean section in a pregnant lady with hepatocellular carcinoma

AbstractINTRODUCTIONCancer in pregnancy is rare and hepatocellular carcinoma (HCC) during pregnancy is even rarer. Due to limited experience, management of these patients remains challenging.PRESENTATION OF CASEA 33-year old pregnant lady presented with HCC at 28 weeks of gestation. She underwent synchronous cesarean section and right hepatectomy at 32 weeks of gestation. The post-operative course was uneventful. She was discharged home on day 10 after surgery. Histolopathology confirmed HCC. The surgical resection margins were clear. At a follow-up of 3 months after surgery, the mother was disease free and the infant was well.DISCUSSIONHCC during pregnancy is extremely rare. The experience in its management and outcomes are lacking. In managing any patient diagnosed with a malignant neoplasm in pregnancy, both the mother and the fetus have to be considered.CONCLUSIONWith adequate preoperative assessment and a good management strategy, good results can be obtained for both the mother and the baby for a pregnant patient with HCC

Vocal cord dysfunction diagnosed by four-dimensional dynamic volume computed tomography in patients with difficult-to-treat asthma: A case series

Patients with asthma may also have vocal cord dysfunction (VCD), which leads to poor control of the asthma. Once patients are diagnosed with difficult-to-treat asthma with poor control, VCD should be excluded or treated accordingly. The gold standard for diagnosis of VCD is to perform a laryngoscopy. However, this procedure is invasive and may not be suitable for patients with difficult-to-treat asthma. Four-dimensional (4D) dynamic volume computed tomography (CT) is a noninvasive method for quantification of laryngeal movement, and can serve as an alternative for the diagnosis of VCD. Herein, we present a series of five cases with difficult-to-treat asthma patients who were diagnosed with VCD by 4D dynamic volume CT. Clinicians should be alert to the possibility of VCD when poor control is noted in patients with asthma. Early diagnosis by noninvasive 4D dynamic volume CT can decrease excessive doses of inhaled corticosteroids

Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway

Purpose: To investigate the effect of lipoxin A4 (LXA4) on the expressions of protein and mRNA of alveolar epithelial sodium channel (ENaC) in normal and lipopolysaccharide (LPS)-stimulated A549 cells.Methods: A549 cell-lines were randomized into 11 groups (N = 8) and treated. EnaC level was evaluated by Western blot. Total RNA was extracted and reverse-transcribed and then levels of ENaC mRNA, cGMP and cAMP in the cells were determined.Results: LXA4 (10-7mol/L) increased the expressions of α-subunit of ENaC relative to LPS group. In addition, LXA4 significantly up-regulated the expression of mRNAs of α, β and γ subunits of ENaC (p &lt; 0.01). The level of cAMP was increased in LXA4 group, but significantly reduced in LPS group relative to control group (p &lt; 0.05). However, treatment with LXA4 annulled the increased cAMP concentration, compared with LPS group (p &lt; 0.05)Conclusion: These results show that LXA4 influences ENaC up-regulation in normal and LPS stimulated A549 alveolar epithelial cells.Keywords: Acute lung injury, Alveolar epithelial sodium channel, Lipoxin A4, AhR, cAMP, cGM

Psychological distress among health professional students during the COVID-19 outbreak

This work was supported by the National Natural Science Foundation of China (No. 81801359 to Dr Lu), Swedish Research Council (No. 2018-00648 to Dr Lu), West China Hospital COVID-19 Epidemic Science and Technology Project (No. HX-2019-nCoV-019 to Dr Zhang), and Sichuan University Emergency Grant (No. 2020scunCoVyingji1005 to Dr Zhang). Publisher Copyright: © 2020 BMJ Publishing Group. All rights reserved.Background: Due to the drastic surge of COVID-19 patients, many countries are considering or already graduating health professional students early to aid professional resources. We aimed to assess outbreak-related psychological distress and symptoms of acute stress reaction (ASR) in health professional students and to characterize individuals with potential need for interventions. Methods: We conducted a prospective cohort study of 1442 health professional students at Sichuan University, China. At baseline (October 2019), participants were assessed for childhood adversity, stressful life events, internet addiction, and family functioning. Using multivariable logistic regression, we examined associations of the above exposures with subsequent psychological distress and ASR in response to the outbreak. Results: 384 (26.63%) participants demonstrated clinically significant psychological distress, while 160 (11.10%) met criteria for a probable ASR. Individuals who scored high on both childhood adversity and stressful life event experiences during the past year were at increased risks of both distress (ORs 2.00-2.66) and probable ASR (ORs 2.23-3.10), respectively. Moreover, internet addiction was associated with elevated risks of distress (OR 2.05, 95% CI 1.60-2.64) and probable ASR (OR 2.15, 95% CI 1.50-3.10). By contrast, good family functioning was associated with decreased risks of distress (OR 0.43, 95% CI 0.33-0.55) and probable ASR (OR 0.48, 95% CI 0.33-0.69). All associations were independent of baseline psychological distress. Conclusions: Our findings suggest that COVID-19 related psychological distress and high symptoms burden of ASR are common among health professional students. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.Peer reviewe

Increased brain iron in patients with thyroid-associated ophthalmopathy: a whole-brain analysis

BackgroundTo investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM).MethodsForty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs.ResultsCompared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%).ConclusionPatients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO