scholarly journals RNA sequencing of a large number of psoriatic patients identifies 131 novel miRNAs and 11 miRNAs associated with disease severity

2021 ◽  
Author(s):  
Å.Ø. Solvin ◽  
K. Chawla ◽  
L.C. Olsen ◽  
K. Danielsen ◽  
M. Jenssen ◽  
...  
Keyword(s):  
Disease Severity ◽  
Functional Enrichment ◽  
Psoriatic Skin ◽  
Comprehensive Overview ◽  
Specific Expression ◽  
Functional Studies ◽  
Differentially Expressed Mirnas ◽  
Skin Biopsies ◽  
Meta Analyses ◽  
And Control

AbstractBackgroundMicroRNAs are small regulatory molecules that are dysregulated in psoriasis. Despite previous efforts, much is unknown about the regulatory mechanisms of psoriasis genetics and their contributions to disease development and activity.ObjectivesTo globally characterize the miRNAome of psoriatic skin in a large sample of psoriatic cases and controls for increased understanding of psoriasis pathophysiology.MethodsSkin biopsies from psoriatic cases (n=75) and non-psoriatic controls (n=57) were RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n=24, controls, n=20), increasing the number of psoriatic cases four-fold from previously published studies. Differential expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell specific analyses were performed.ResultsWe identified 439 significantly differentially expressed miRNAs (DEMs), of which 131 were novel and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in all psoriatic skin. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells.ConclusionsWe have provided the most comprehensive overview of the miRNome in psoriatic skin to date and identified a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

scholarly journals Identification of miRNA-target gene regulatory networks in liver fibrosis based on bioinformatics analysis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11910
Author(s):  
Yang Tai ◽  
Chong Zhao ◽  
Jinhang Gao ◽  
Tian Lan ◽  
Huan Tong
Keyword(s):  
Immune Response ◽  
Liver Cirrhosis ◽  
Bioinformatics Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Hub Genes ◽  
Differentially Expressed Mirnas ◽  
And Control

Background Liver cirrhosis is one of the leading causes of death worldwide. MicroRNAs (miRNAs) can regulate liver fibrosis, but the underlying mechanisms are not fully understood, and the interactions between miRNAs and mRNAs are not clearly elucidated. Methods miRNA and mRNA expression arrays of cirrhotic samples and control samples were acquired from the Gene Expression Omnibus database. miRNA-mRNA integrated analysis, functional enrichment analysis and protein-protein interaction (PPI) network construction were performed to identify differentially expressed miRNAs (DEMs) and mRNAs (DEGs), miRNA-mRNA interaction networks, enriched pathways and hub genes. Finally, the results were validated with in vitro cell models. Results By bioinformatics analysis, we identified 13 DEMs between cirrhotic samples and control samples. Among these DEMs, six upregulated (hsa-miR-146b-5p, hsa-miR-150-5p, hsa-miR-224-3p, hsa-miR-3135b, hsa-miR-3195, and hsa-miR-4725-3p) and seven downregulated (hsa-miR-1234-3p, hsa-miR-30b-3p, hsa-miR-3162-3p, hsa-miR-548aj-3p, hsa-miR-548x-3p, hsa-miR-548z, and hsa-miR-890) miRNAs were further validated in activated LX2 cells. miRNA-mRNA interaction networks revealed a total of 361 miRNA-mRNA pairs between 13 miRNAs and 245 corresponding target genes. Moreover, PPI network analysis revealed the top 20 hub genes, including COL1A1, FBN1 and TIMP3, which were involved in extracellular matrix (ECM) organization; CCL5, CXCL9, CXCL12, LCK and CD24, which participated in the immune response; and CDH1, PECAM1, SELL and CAV1, which regulated cell adhesion. Functional enrichment analysis of all DEGs as well as hub genes showed similar results, as ECM-associated pathways, cell surface interaction and adhesion, and immune response were significantly enriched in both analyses. Conclusions We identified 13 differentially expressed miRNAs as potential biomarkers of liver cirrhosis. Moreover, we identified 361 regulatory pairs of miRNA-mRNA and 20 hub genes in liver cirrhosis, most of which were involved in collagen and ECM components, immune response, and cell adhesion. These results would provide novel mechanistic insights into the pathogenesis of liver cirrhosis and identify candidate targets for its treatment.

scholarly journals Artificial Intelligence-Based Wearable Robotic Exoskeletons for Upper Limb Rehabilitation: A Review

Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 2146
Author(s):  
Manuel Andrés Vélez-Guerrero ◽  
Mauro Callejas-Cuervo ◽  
Stefano Mazzoleni
Keyword(s):  
Artificial Intelligence ◽  
Upper Limb ◽  
Main Trend ◽  
Motor Rehabilitation ◽  
Rehabilitation Process ◽  
Upper Limb Rehabilitation ◽  
Multiple Sensors ◽  
Meta Analyses ◽  
Limb Rehabilitation ◽  
And Control

Processing and control systems based on artificial intelligence (AI) have progressively improved mobile robotic exoskeletons used in upper-limb motor rehabilitation. This systematic review presents the advances and trends of those technologies. A literature search was performed in Scopus, IEEE Xplore, Web of Science, and PubMed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology with three main inclusion criteria: (a) motor or neuromotor rehabilitation for upper limbs, (b) mobile robotic exoskeletons, and (c) AI. The period under investigation spanned from 2016 to 2020, resulting in 30 articles that met the criteria. The literature showed the use of artificial neural networks (40%), adaptive algorithms (20%), and other mixed AI techniques (40%). Additionally, it was found that in only 16% of the articles, developments focused on neuromotor rehabilitation. The main trend in the research is the development of wearable robotic exoskeletons (53%) and the fusion of data collected from multiple sensors that enrich the training of intelligent algorithms. There is a latent need to develop more reliable systems through clinical validation and improvement of technical characteristics, such as weight/dimensions of devices, in order to have positive impacts on the rehabilitation process and improve the interactions among patients, teams of health professionals, and technology.

scholarly journals 10 Years of Pulsed-Xenon Ultraviolet Disinfection

2020 ◽  
Vol 41 (S1) ◽  
pp. s438-s438
Author(s):  
Mark Stibich ◽  
Sarah Simmons ◽  
Deborah Passey
Keyword(s):  
Relative Risk ◽  
Meta Analysis ◽  
Outcome Studies ◽  
Uv Disinfection ◽  
Clostridioides Difficile ◽  
Environmental Effectiveness ◽  
Meta Analyses ◽  
Hospital Acquired ◽  
And Control ◽  
Effectiveness Studies

Background: Ultraviolet light (UV) disinfection using low-pressure mercury lamps has been around since the 1940s. The advent of pulsed-xenon UV for hospital use in 2010 has provided a nontoxic and novel technology for hospital disinfection with the first data presented at the 2010 SHEA Decennial. The purpose of this systematic review and meta-analysis is to examine the current body of evidence for pulsed xenon UV disinfection. Methods: The literature search criteria included the following: research conducted in domestic and international settings using pulsed-xenon for surface disinfection, published between 2000 and 2019, and reporting on environmental effectiveness or hospital-acquired reductions (HAIs). We searched PubMed, Google Scholar, and Web of Science. The meta-analysis included 24 studies: 12 HAI outcome studies and 12 environmental effectiveness studies. Meta-analyses were conducted by calculating the percentage reductions for environmental effectiveness, and for the HAI outcome studies, we used a random-effects model to pool the relative risk of HAI. The outcome studies used 272 and 299 months of data for the experimental and control groups, respectively. Results: There was an overall benefit of using pulsed-xenon UV. The overall relative risk of infection decreased compared to the control arm (RR, 0.64; 95% CI, 0.54–0.76). The percentage reductions in environmental studies were as follows: Clostridioides difficile (94.8%), methicillin-resistant Staphylococcus aureus (91.5%), vancomycin-resistant Enterococcus (99.2%), and aerobic bacteria (94.2%). Conclusions: Overall, pulsed-xenon UV was effective for reducing environmental contamination and had the ability to significantly reduce HAIs.Funding: Xenex, Inc., funded this study.Disclosures: Mark Stibich receives a salary from Xenex and is a shareholder of Xenex. Deborah Passey receives a salary from Xenex Disinfection Services.

scholarly journals Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

2021 ◽  
Vol 10 (2) ◽  
pp. 359 ◽  
Author(s):  
Trinidad Montero-Vilchez ◽  
María-Victoria Segura-Fernández-Nogueras ◽  
Isabel Pérez-Rodríguez ◽  
Miguel Soler-Gongora ◽  
Antonio Martinez-Lopez ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Water Loss ◽  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Diagnostic Tools ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Healthy Controls

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

scholarly journals miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1480
Author(s):  
Hiresh Ayoubian ◽  
Joana Heinzelmann ◽  
Sebastian Hölters ◽  
Oybek Khalmurzaev ◽  
Alexey Pryalukhin ◽  
...  
Keyword(s):  
Microarray Data ◽  
Expression Patterns ◽  
Hpv Infection ◽  
Differentially Expressed ◽  
Histological Subtypes ◽  
Specific Expression ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Differentially Expressed Mirnas ◽  
The Impact

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

scholarly journals Role for Human SIRT2 NAD-Dependent Deacetylase Activity in Control of Mitotic Exit in the Cell Cycle

2003 ◽  
Vol 23 (9) ◽  
pp. 3173-3185 ◽  
Author(s):  
Sylvia C. Dryden ◽  
Fatimah A. Nahhas ◽  
James E. Nowak ◽  
Anton-Scott Goustin ◽  
Michael A. Tainsky
Keyword(s):  
Cell Cycle ◽  
Protein A ◽  
Proteasome Inhibitors ◽  
26S Proteasome ◽  
Functional Studies ◽  
Cellular Life ◽  
Subsequent Decrease ◽  
Subsequent Degradation ◽  
Phosphorylation Cascade ◽  
And Control

ABSTRACT Studies of yeast have shown that the SIR2 gene family is involved in chromatin structure, transcriptional silencing, DNA repair, and control of cellular life span. Our functional studies of human SIRT2, a homolog of the product of the yeast SIR2 gene, indicate that it plays a role in mitosis. The SIRT2 protein is a NAD-dependent deacetylase (NDAC), the abundance of which increases dramatically during mitosis and is multiply phosphorylated at the G2/M transition of the cell cycle. Cells stably overexpressing the wild-type SIRT2 but not missense mutants lacking NDAC activity show a marked prolongation of the mitotic phase of the cell cycle. Overexpression of the protein phosphatase CDC14B, but not its close homolog CDC14A, results in dephosphorylation of SIRT2 with a subsequent decrease in the abundance of SIRT2 protein. A CDC14B mutant defective in catalyzing dephosphorylation fails to change the phosphorylation status or abundance of SIRT2 protein. Addition of 26S proteasome inhibitors to human cells increases the abundance of SIRT2 protein, indicating that SIRT2 is targeted for degradation by the 26S proteasome. Our data suggest that human SIRT2 is part of a phosphorylation cascade in which SIRT2 is phosphorylated late in G2, during M, and into the period of cytokinesis. CDC14B may provoke exit from mitosis coincident with the loss of SIRT2 via ubiquitination and subsequent degradation by the 26S proteasome.

scholarly journals What we know, what we do not know, and where are we heading? Efficacy and acceptability of psychological interventions for depression

2015 ◽  
Vol 25 (4) ◽  
pp. 301-308 ◽  
Author(s):  
N. Solomonov ◽  
J. P. Barber
Keyword(s):  
Randomized Clinical Trials ◽  
Behavioural Therapy ◽  
Drop Out ◽  
Interpersonal Therapy ◽  
Problem Solving Therapy ◽  
Cognitive Behavioural ◽  
Treatment Of Depression ◽  
Personalised Treatment ◽  
Meta Analyses ◽  
And Control

In the past several decades, increasing evidence supports the efficacy of psychotherapies for depression. The vast majority of findings from meta-analyses, randomized clinical trials (RCTs) and naturalistic studies have demonstrated that well-established psychotherapies (behavioural activation, problem-solving therapy, psychodynamic therapy, cognitive-behavioural therapy, interpersonal therapy and emotion-focused therapy) are superior to no-treatment and control conditions, and are in most cases equally effective in treating depression. However, despite this abundant support for psychotherapies, studies have also consistently shown high drop-out rates, high percentages of non-respondent patients who experience treatment failures, and mixed findings regarding the enduring effects of psychotherapy. Thus, there is a need to develop more personalised treatment models tailored to patients’ needs. A new integrative sequential stepwise approach to the treatment of depression is suggested.

Stable transfer and restricted expression of a cloned class I gene encoding a secreted transplantation-like antigen

1985 ◽  
Vol 5 (6) ◽  
pp. 1295-1300
Author(s):  
Y Barra ◽  
K Tanaka ◽  
K J Isselbacher ◽  
G Khoury ◽  
G Jay
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Class I ◽  
Regulatory Sequences ◽  
Transcriptional Enhancer ◽  
Gene Encoding ◽  
Specific Expression ◽  
Tissue Specific ◽  
Functional Studies ◽  
I Gene

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.

A framework to guide the implementation of lean management in emergency department

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Anna Tiso ◽  
Maria Crema ◽  
Chiara Verbano
Keyword(s):  
Emergency Department ◽  
Literature Review ◽  
Descriptive Analysis ◽  
Lean Management ◽  
Comprehensive Overview ◽  
Content Type ◽  
Managerial Practices ◽  
Prisma Statement ◽  
Meta Analyses ◽  
Tools And Techniques

PurposeThe paper aims at enriching the knowledge of the application of lean management (LM) in emergency department (ED), structuring the methodology for implementing LM projects and summarizing the relevant dimensions of LM adoption in ED.Design/methodology/approachIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic literature review has been performed, extracting a database of 34 papers. To answer the research purpose, a descriptive and content analyses have been carried out.FindingsThe descriptive analysis demonstrates that the dealt topic is worldwide emerging and multidisciplinary as it arouses interest by medical and engineering communities. Despite the heterogeneity in the adopted methodology, a framework can be grasped from the literature review. It points out the phases and activities, the tools and techniques and the enablers to be considered for guiding the developing of LM project in ED.Originality/valueThis paper provides a comprehensive overview on how to adopt LM in ED, contributing to fill in the gap emerged in the literature. From a practical perspective, this paper provides healthcare managers with a synthesis of the best managerial practices and guidelines in developing a LM project in ED.

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