Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and Histologic Features of Chronic Hepatitis C Virus Infection After Blood Transfusion in Japanese Children

Objective. To characterize the clinical and histologic features of chronic hepatitis C virus (HCV) infection after blood transfusion in Japanese children. Study Design. We studied 231 children with a history of blood product transfusion. Patients were divided into two groups: 116 patients with a history of malignant disease (group 1), 115 patients who had undergone open heart surgery (group 2). We examined changes in serum alanine aminotransferase (ALT) activity and HCV markers, and patients' clinical course. Moreover, in 38 patients in whom the time of HCV infection could be defined, we examined liver histology. Results. The proportions of patients in each group who were anti-HCV-positive were 35 out of 116 (30%) and 20 out of 115 (17%), respectively. Of the anti-HCV-positive patients, the proportions of HCV RNA-positive patients in each group were 30 out of 35 (86%) and 12 out of 20 (60%), respectively. Levels of ALT activity in patients with HCV infection varied widely for several years after blood transfusion; thereafter ALT activity fell to <100 IU/L in 2 groups. Serum ALT activity in patients who were HCV RNA-negative became normal. With regard to liver histology, there were no differences in the grade of necroinflammation or stage of fibrosis in patients with different durations of infection or when patients were analyzed according to the presence or absence of malignant disease. Patients mostly had grade 2–4 inflammation and stage 1–2 fibrosis. Thus, chronic hepatitis C was a morphologically mild disease in most children in this study. Conclusions. Sixty percent to 80% of children with HCV infection in this study developed chronic hepatitis C. However, examination of liver histology findings in children with chronic hepatitis C showed only mild changes.
Mechanisms of Inducible Nitric Oxide Synthase–Mediated Vascular Dysfunction

Objective—Inducible nitric oxide synthase (iNOS) is expressed in arteries during inflammation and may contribute to vascular dysfunction. Effects of gene transfer of iNOS to carotid arteries were examined in vitro in the absence of systemic inflammation to allow examination of mechanisms by which iNOS impairs contraction and relaxation. Methods and Results—After gene transfer of iNOS with an adenovirus (AdiNOS), constrictor responses to phenylephrine (PE) and U46619 were impaired. After AdiNOS, inhibition of soluble guanylate cyclase (sGC) with 1H-[1,2,4]oxadiazolo-[4,3,2]quinoxalin-1-one (ODQ) reduced the EC50 for PE from 4.33±0.78 &mgr;mol/L to 1.15±0.43 &mgr;mol/L (mean±SEM). These results imply that iNOS impairs contraction by activation of the NO/cGMP pathway. Relaxation to acetylcholine (ACh) also was impaired after AdiNOS. Sepiapterin (300 &mgr;mol/L), the precursor for tetrahydrobiopterin (BH4), improved relaxation to Ach. Because BH4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH4. Next, we examined effects of expression of iNOS in endothelium and adventitia. Selective expression of iNOS in endothelium, but not adventitia, impaired contraction to phenylephrine and relaxation to acetylcholine. Conclusions—We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia.
Alcohol-related disorders in first- and second-generation immigrants in Sweden: a national cohort study.

AIMS The risk of alcohol-related disorders in first- and second-generation immigrants in Sweden were investigated and compared with the Swedish majority population to assess how alcohol habits are modified over generations in a new society. DESIGN Register study based on multivariate analyses of demographic data, including information on country of birth, from the Swedish Population and Housing Census of 1985 linked to data on hospital admissions for alcohol-related disorders during 1990-99 in the National Hospital Discharge Register. PARTICIPANTS The study population consisted of a national cohort of 1.25 million youth born 1968-79 and 1.47 million adults born 1929-65. RESULTS First- and second-generation immigrants from Finland had higher relative risks (RRs) for hospital admission because of an alcohol-related disorder compared to the Swedish majority population (socio-economic adjusted RRs 2.1 and 1.9, respectively), while first-generation immigrants born in southern Europe, the Middle East and other non-European countries had lower risks. Second-generation immigrants with heritage in southern Europe, the Middle East and other non-European countries had socio-economic adjusted RRs that were higher relative to the first generation immigrants but lower relative to the Swedish majority population. Intercountry adoptees had the highest adjusted RR (2.5). CONCLUSIONS Patterns of alcohol abuse in the country of origin are strong determinants of alcohol-related disorders in first-generation immigrants. The patterns in second-generation immigrants are influenced by parental countries of origin as well as patterns in the majority population. The Finnish minority and intercountry adoptees are of particular concern in prevention.
Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury

BACKGROUND An association between stress-induced hyperglycemia (SIH) and increased mortality has been demonstrated following trauma. Experimental animal model data regarding the association between hyperglycemia and outcomes following traumatic brain injury (TBI) are inconsistent, suggesting that hyperglycemia may be harmful, neutral, or beneficial. The purpose of this study was to examine the effects of SIH versus diabetic hyperglycemia (DH) on severe TBI. METHODS Admission glycosylated hemoglobin (HbA1c), glucose levels, and comorbidity data were collected during a 4-year period from September 2009 to December 2013 for patients with severe TBI (i.e., admission Glasgow Coma Scale [GCS] score of 3–8 and head Abbreviated Injury Scale [AIS] score ≥ 3). Diabetes mellitus was determined by patient history or admission HbA1c of 6.5% or greater. SIH was determined by the absence of diabetes mellitus and admission glucose of 200 mg/dL or greater. A Cox proportional hazards model adjusted for age, sex, injury mechanism, and Injury Severity Score (ISS) was used to calculate hazard ratios (HRs) and associated 95% confidence intervals (CIs) for the association between SIH and the outcomes of interest. RESULTS During the study period, a total of 626 patients were included in the study group, having severe TBI defined by both GCS score of 3 to 8 and head AIS score being 3 or greater and also had available HbA1c and admission glucose levels. A total of 184 patients were admitted with hyperglycemia; 152 patients (82.6%) were diagnosed with SIH, and 32 patients (17.4%) were diagnosed with DH. When comparing patients with severe TBI adjusted for age, sex, injury mechanism, ISS, Revised Trauma Score (RTS), and lactic acid greater than 2.5 mmol/L, patients with SIH had a 50% increased mortality (HR, 1.49; 95% CI, 1.13–1.95) compared with the nondiabetic normoglycemia patients. DH patients did not have a significant increase in mortality (HR, 0.94; 95% CI, 0.56–1.58). CONCLUSION SIH is associated with higher mortality after severe TBI. This association was not observed among patients with DH, which suggests that hyperglycemia related to diabetes is of less importance compared with SIH in terms of mortality in the acute trauma and TBI patient. Further research is warranted to identify mechanisms causing SIH and subsequent worse outcomes after TBI. LEVEL OF EVIDENCE Prognostic/epidemiologic study, leve III.
East–West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort

Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists. Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.
Stem Cells , Tissue Engineering and Hematopoietic Elements Tumorigenic Potential of Mononucleated Small Cells of Hodgkin Lymphoma Cell Lines

Tumor cells with tumorigenic potential are limited to a small cell population known as cancer stem cells (CSCs). CSCs yield both CSCs and non-CSCs, whereas non-CSCs do not yield CSCs. CSCs have not been identified in any malignant lymphomas. Hodgkin lymphoma (HL) is a mostly B-cell neoplasm that can be diagnosed by the presence of multinucleated (ReedSternberg; RS) cells admixed with Hodgkin cells with distinct nucleoli and various inflammatory cells. Here, the tumorigenic potential of cells with a single nucleus (S) and cells with multiple nuclei (M), which may be equivalent to Hodgkin and RS cells, respectively, was examined in HL cell lines L1236 and L428. Cultures of single S cells yielded both S and M cells, whereas M cell cultures yielded only M cells. When either cultured in methylcellulose or inoculated into NOD/SCID mice, the colony number and tumor size were both larger in S than in M cells. Concentrations of intracellular reactive oxygen species (ROS) were at low levels in a portion of S cells that abundantly expressed FoxO3a, a transcription factor that regulates ROS-degrading enzymes. In clinical samples of HL, FoxO3a was expressed in mononuclear Hodgkin cells but not in multinucleated RS cells. These findings suggest that smaller cells or Hodgkin cells that show low-ROS concentrations and high FoxO3a expression levels might be candidates for HL CSCs. (Am J Pathol 2010, 177:3081–3088; DOI: 10.2353/ajpath.2010.100089)
Agile requirements: opportunity or oxymoron?

We show that, in today's world, a requirement without agility is just as bad as agility without requirements. We have discovered a consensus that systems analysis and requirements definition, in particular, have fallen on hard times. Ten or 15 years ago we taught people structured analysis, information engineering, data modeling, and working with computer-aided software engineering tools to turn those requirements into running programs. Rather than understanding the user's business and information needs, some agile approaches attempt to give users what they say they want as quickly as possible. Every system of consequence needs good requirements. Without good requirements, the project risks increase dramatically. The better the requirements, the better people understand what they're trying to build (or acquire).
Galectin Binding to Mgat5-Modified N-Glycans Regulates Fibronectin Matrix Remodeling in Tumor Cells

ABSTRACT Oncogenic signaling stimulates the dynamic remodeling of actin microfilaments and substrate adhesions, essential for cell spreading and motility. Transformation is associated with increased expression of β1,6GlcNAc-branched N-glycans, products of Golgi β1,6-acetylglucosaminyltransferase V (Mgat5) and the favored ligand for galectins. Herein we report that fibronectin fibrillogenesis and fibronectin-dependent cell spreading are deficient in Mgat5−/− mammary epithelial tumor cells and inhibited in Mgat5+/+ cells by blocking Golgi N-glycan processing with swainsonine or by competitive inhibition of galectin binding. At an optimum dosage, exogenous galectin-3 added to Mgat5+/+ cells activates focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K), recruits conformationally active α5β1-integrin to fibrillar adhesions, and increases F-actin turnover. RGD peptide inhibits PI3K-dependent fibronectin matrix remodeling and fibronectin-dependent cell motility, while galectin-3 stimulates and overrides the inhibitory effects of RGD. Antibodies to the galectin-3 N-terminal oligomerization domain stimulate α5β1 activation and recruitment to fibrillar adhesions in Mgat5+/+ cells, an effect that is blocked by disrupting galectin-glycan binding. Our results demonstrate that fibronectin polymerization and tumor cell motility are regulated by galectin-3 binding to branched N-glycan ligands that stimulate focal adhesion remodeling, FAK and PI3K activation, local F-actin instability, and α5β1 translocation to fibrillar adhesions.
Large-scale implementation of electric road systems: Associated costs and the impact on CO2 emissions

Abstract This study investigates a large-scale implementation of an electric road system (ERS) in Norway and Sweden by identifying: (i) which roads; (ii) how much of the road network; and (iii) which vehicle types are beneficial to electrify based on an analysis of current road traffic volumes, CO2 emissions mitigation potential, and infrastructure investment costs. All the European (E) and National (N) roads in Norway and Sweden were included, while assuming different degrees of electrification in terms of the fraction of the road length with an ERS, prioritizing roads with high-traffic loads. The results show that implementing an ERS already for 25% of the E- and N-road lengths could result in electrification of 70% of the traffic on these roads, as well as 35% of the total vehicle kilometers in Norway and Sweden. The ERS will then connect some of the larger cities with ERS. Installation of ERS on all the E- and N-roads in the two countries would cover more than 60% of the CO2 emissions from all heavy traffic assuming all vehicles run on electricity. For roads with an average daily traffic of >6800 and >1200 vehicles per day, the costs of infrastructure investment are ∼0.03 €2016 per vkm and ∼0.15 €2016 per vkm, respectively. Thereby, for roads with high traffic volumes using an ERS, the total driving cost per km using an ERS (0.23–0.55 €2016 per vkm) does not seem to be an issue. Light vehicles appear to be important bringing down the ERS infrastructure cost.
Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease

We previously suggested that gut bacteria may be involved in the onset of Kawasaki disease (KD). In this study, we evaluated the production of heat shock proteins (hsps) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD in the acute phase and from 15 age‐matched control children. We identified 13 strains of Gram‐negative microbes from patients with KD; these microbes produced large amounts of hsp60 and induced pro‐inflammatory cytokine production by peripheral blood mononuclear cells. The Gram‐negative microbes also elicited endogenous hsp60 production, leading to the secretion of anti‐inflammatory intereukin‐10 (IL‐10). We also identified 18 strains of Gram‐positive cocci that had superantigenic properties and which induced the expansion of Vβ2 T cells in vitro. All bacteria identified in this study were antibiotic resistant. These data suggest that sAg and hsps produced by gut bacteria might be involved in KD.
Two cholinesterase activities and genes are present in amphioxus.

To obtain information about the evolution of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the vertebrates, we investigated the cholinesterase (ChE) activity of the cephalochordate amphioxus (Branchiostoma floridae and Branchiostoma lanceolatum). On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that amphioxus possesses two ChE activities and two ChE genes. Two covalent inhibitors of cholinesterases were able to pharmacologically isolate the two activities as drug-sensitive ChE and drug-resistant ChE. Kinetically, in terms of substrate specificity, the drug-sensitive ChE resembles vertebrate AChE, and the drug-resistant ChE resembles the BuChE of cartilaginous and bony fish or the intermediate ChE of protostome invertebrates. We also used the polymerase chain reaction with degenerate oligonucleotide primers and genomic DNA to obtain clones of 1,574 and 1,011 bp corresponding to two cholinesterase genes from amphioxus, which we designated as ChE1 and ChE2. ChE2 codes for an enzyme with an acyl-binding pocket sequence, a portion of the protein that plays an important role in determining substrate specificity, typical of invertebrate ChE. ChE1, which contains a 503-bp intron, encodes a protein with a novel acyl binding site. Phylogenetic analysis of the sequences suggests that the two genes are a result of a duplication event in the lineage leading to amphioxus. We discuss the relevance of our results to the evolution of the cholinesterases in the chordates. Previously, we reported that amphioxus contained a single cholinesterase activity with properties intermediate to AChE and BuChE (Pezzementi et al. [1991] In: Cholinesterases: Structure, Function, Mechanism, Genetics and Cell Biology. J. Massoulié et al., eds. ACS: Washington, D.C., pp. 24-31).
Prospects for knowledge exchange in health policy and management: Institutional and epistemic boundaries

Objectives: There have been calls for greater exchange between research and practice in health care policy and management, but little empirical research on what commissioners of research and researchers themselves consider appropriate, good quality research knowledge. This paper addresses this gap, considering the views of commissioners and producers of policy and management research in health care and other fields. Methods: Qualitative semi-structured interviews with 18 commissioners and producers of research, in central government, the NHS and other commissioning organizations, and in universities and independent sector providers. Results: Commissioners and producers agreed that research often fails to fulfil policy-makers’ and managers’ needs, and that greater interaction is required to improve this relationship. However, they offered differing accounts of the nature of research knowledge (as a ‘product’ or a ‘mindset’), and of what constitutes value, validity and originality in research, reflecting the differing priorities and pressures faced by the two groups. Conclusions: Efforts to promote greater interaction between research, policy and practice, and more critical, reflexive engagement between policy-makers, managers and researchers, are likely to face significant obstacles given these competing constructions of research knowledge and their reinforcement by divergent priorities.
Social Capital and the Collective Management of Resources

The proposition that natural resources need protection from the destructive actions of people is widely accepted. Yet communities have shown in the past and increasingly today that they can collaborate for long-term resource management. The term social capital captures the idea that social bonds and norms are critical for sustainability. Where social capital is high in formalized groups, people have the confidence to invest in collective activities, knowing that others will do so too. Some 0.4 to 0.5 million groups have been established since the early 1990s for watershed, forest, irrigation, pest, wildlife, fishery, and microfinance management. These offer a route to sustainable management and governance of common resources.
Generation of Hoxc13 knockout pigs recapitulates human ectodermal dysplasia–9

Atrichia and sparse hair phenotype cause distress to many patients. Ectodermal dysplasia-9 (ED-9) is a congenital condition characterized by hypotrichosis and nail dystrophy without other disorders, and Hoxc13 is a pathogenic gene for ED-9. However, mice carrying Hoxc13 mutation present several other serious disorders, such as skeletal defects, progressive weight loss and low viability. Mouse models cannot faithfully mimic human ED-9. In this study, we generated an ED-9 pig model via Hoxc13 gene knockout through single-stranded oligonucleotides (c.396C > A) combined with CRISPR/Cas9 and somatic cell nuclear transfer. Eight cloned piglets with three types of biallelic mutations (five piglets with Hoxc13c.396C > A/c.396C > A, two piglets with Hoxc13c.396C > A/c.396C > A + 1 and one piglet with Hoxc13Δ40/Δ40) were obtained. Hoxc13 was not expressed in pigs with all three mutation types, and the expression levels of Hoxc13-regulated genes, namely, Foxn1, Krt85 and Krt35, were decreased. The hair follicles displayed various abnormal phenotypes, such as reduced number of follicles and disarrayed hair follicle cable without normal hair all over the body. By contrast, the skin structure, skeleton phenotype, body weight gain and growth of Hoxc13 knockout pigs were apparently normal. The phenotypes of Hoxc13 mutation in pigs were similar to those in ED-9 patients. Therefore, Hoxc13 knockout pigs could be utilized as a model for ED-9 pathogenesis and as a hairless model for hair regeneration research. Moreover, the hairless pigs without other major abnormal phenotypes generated in this study could be effective models for other dermatological research because of the similarity between pig and human skins.
A Sequence-Based Map of Arabidopsis Genes with Mutant Phenotypes1,212

The classical genetic map of Arabidopsis contains 462 genes with mutant phenotypes. Chromosomal locations of these genes have been determined over the past 25 years based on recombination frequencies with visible and molecular markers. The most recent update of the classical map was published in a special genome issue ofScience that dealt with Arabidopsis (D.W. Meinke, J.M. Cherry, C. Dean, S.D. Rounsley, M. Koornneef [1998] Science 282: 662–682). We present here a comprehensive list and sequence-based map of 620 cloned genes with mutant phenotypes. This map documents for the first time the exact locations of large numbers of Arabidopsis genes that give a phenotype when disrupted by mutation. Such a community-based physical map should have broad applications in Arabidopsis research and should serve as a replacement for the classical genetic map in the future. Assembling a comprehensive list of genes with a loss-of-function phenotype will also focus attention on essential genes that are not functionally redundant and ultimately contribute to the identification of the minimal gene set required to make a flowering plant.