Designing an automated prototype tool for preservation quality metadata extraction for ingest into digital repository

We present a viable framework for the automated extraction of preservation quality metadata, which is adjusted to meet the needs of, ingest to digital repositories. It has three distinctive features: wide coverage, specialisation and emphasis on quality. Wide coverage is achieved through the use of a distributed system of tool repositories, which helps to implement it over a broad range of document object types. Specialisation is maintained through the selection of the most appropriate metadata extraction tool for each case based on the identification of the digital object genre. And quality is sustained by introducing control points at selected stages of the workflow of the system. The integration of these three features as components in the ingest of material into digital repositories is a defining step ahead in the current quest for improved management of digital resources

Issues in digital preservation: towards a new research agenda

Digital Preservation has evolved into a specialized, interdisciplinary research discipline of its own, seeing significant increases in terms of research capacity, results, but also challenges. However, with this specialization and subsequent formation of a dedicated subgroup of researchers active in this field, limitations of the challenges addressed can be observed. Digital preservation research may seem to react to problems arising, fixing problems that exist now, rather than proactively researching new solutions that may be applicable only after a few years of maturing. Recognising the benefits of bringing together researchers and practitioners with various professional backgrounds related to digital preservation, a seminar was organized in Schloss Dagstuhl, at the Leibniz Center for Informatics (18-23 July 2010), with the aim of addressing the current digital preservation challenges, with a specific focus on the automation aspects in this field. The main goal of the seminar was to outline some research challenges in digital preservation, providing a number of "research questions" that could be immediately tackled, e.g. in Doctoral Thesis. The seminar intended also to highlight the need for the digital preservation community to reach out to IT research and other research communities outside the immediate digital preservation domain, in order to jointly develop solutions

Effect of a Small Selective Inhibitor of C-Jun N-Terminal Kinase on the Inducible mRNA Expression of Interleukin-6 and Interleukin-18

BACKGROUND: The expression of many inducible genes, involved in cell growth and differentiation as cytokine genes are regulated by receptor-activated intracellular signalling pathways, including the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase pathway. AIM: We examined the involvement of the JNK signalling pathway in the regulation of the inducible interleukin-6 (IL-6) and interleukin-18 (IL-18) gene expression at the transcriptional level. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with lipopolysaccharide (LPS) and C3 binding glycoprotein (C3bgp) with or without SP600125 and cultured for 6 h. After mRNA isolation, a qRT-PCR was performed. RESULTS: Regarding IL-6 and IL-18 mRNA expression, donors were divided into two groups of high and low responders. SP600125 inhibited significantly IL-6 mRNA transcription in the high responder group and did not influence the transcription level in the low responder group. Concerning IL-18 mRNA, we detect the significant effect of SP600125 on the inducible mRNA in high responder group upon C3bgp stimulation. CONCLUSION: JNK transduction pathway is involved in the production of IL-6 mRNA, after LPS and C3bgp stimulation. We suggest that the inhibition of JNK may be beneficial only for higher responding patients during the treatment of inflammatory and autoimmune diseases

Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study

Background: Patients with primary hyperparathyroidism (PHPT) have increased mortality risk predominantly attributed to cardiovascular disease. Taking the risk factors for cardiovascular disease into account, such as overweight, atherogenic dyslipidaemia, carbohydrate metabolism disorders and insulin resistance (IR), investigation on the the study of the state of carbohydrate and lipid metabolism in patients with PHPT will help to shed light on the pathogenic mechanisms of the disease and, perhaps, to complement the algorithm for selecting treatment strategies for patients with PHPT. Aims: To study the prevalence of carbohydrate and lipid metabolism disorders among patients with PHPT and to identify the relationship between these two disorders with the indicators of mineral metabolism. Materials and methods: A case-control study of a total of age-matched 256 female patients, 220 patients with PHPT and 36 healthy individuals. The group patients with PHPT were sub-divided into two groups, symptomatic and mild form of PHPT. To verify the form of PHPT, ultrasound examinations of the parathyroid glands and kidneys, two-energy x-ray absorptiometry, biochemical studies (concentration of total and ionised calcium, serum phosphorus and the activity of alkaline phosphatase) and assessment of parathyroid hormone concentration were performed. The relationship between form of PHPT and body weight were evaluated retrospectively according to the survey. Among the 109 participants with PHPT (symptomatic PHPT: 82 patients; mild PHPT: 27 patients) and healthy individuals, the biochemical and hormonal parameters of fat (lipid spectrum of blood) and carbohydrate metabolism (content of immunoreactive insulin, HOMA index, presence of fasting glycemia disorder, glucose tolerance disorders and type 2 diabetes mellitus) were evaluated. Results: The symptomatic PHPT was associated with low body mass index (BMI) while the mild PHPT with high BMI. During an oral glucose tolerance test, the postprandial glycemia in symptomatic PHPT was significantly higher than that in mild PHPT (p = 0.036). The content of immunoreactive insulin in the symptomatic PHPT was not correlated with the concentration of parathyroid hormone, but positively correlated with the concentration of ionised calcium in the blood (r = 0.31; p = 0.006). Patients with PHPT showed a direct positive correlation between BMI and IR index (r = 0.67; p < 0.001). It is shown that patients with PHPT have increased LDL content in the blood, and the actual blood lipid concentration is associated with the state of kidney function. Conclusions: The obtained data confirm the relationship between phosphorus–calcium metabolism disorders in PHPT and carbohydrate and lipid metabolism disorders. Prospective, controlled studies are warranted to better elucidate the causal relationships of mineral, carbohydrate and fat metabolism disorders in PHPT

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits

The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits. The pharmacokinetic behaviour of cytisine is studied in male and female New Zealand rabbits after oral and intravenous administration. Cytisine is administered orally (dose of 5 mg/kg b.w.) under fasting condition (12 hours) and intravenously (dose 1 mg/kg b.w.) in the marginal ear vein. Cytisine serum concentrations are measured using a highly selective and sensitive validated HPLC method with UV detection. Linearity of the method is in the range 12–2 400 µg/L; accuracy and precision are both within ± 10%, and the limit of detection is 4 µg/L. Selectivity and stability are also validated. Basic pharmacokinetic parameters of cytisine after single oral and intravenous administration are calculated using TOPFIT software. Pharmacokinetic analysis suggests a rapid but incomplete absorption of cytisine after oral administration

Small Deletions of SATB2 Cause Some of the Clinical Features of the 2q33.1 Microdeletion Syndrome

Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome. Clinical features of this syndrome include severe mental retardation, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. The commonly deleted region contains at least seven genes. Haploinsufficiency of one of these genes, SATB2, a DNA-binding protein that regulates gene expression, has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In this study we describe three individuals with smaller microdeletions of this region, within 2q33.1. The deletions ranged in size from 173.1 kb to 185.2 kb and spanned part of SATB2. Review of clinical records showed similar clinical features among these individuals, including severe developmental delay and tooth abnormalities. Two of the individuals had behavioral problems. Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature. Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome

MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization

© 2018 The Author(s). The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of bidirectionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and the polycomb repressive complex 2 (PRC2) to the bidirectionally active loci. The exosome degrades the ncRNAs, whereas PRC2 induces heterochromatin and transcriptional silencing through EZH2. Moreover, this multicomponent RNA-protein complex, which we named MiCEE, tethers the regulated genes to the perinucleolar region and thus is required for proper nucleolar organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bidirectionally expressed genes and global genome organization