Miracle-dz/UniFAR-FTUs huggingface dataset:
Curcumin Suppresses the Induction of Indoleamine 2,3-Dioxygenase by Blocking the Janus-activated Kinase-Protein Kinase Cδ-STAT1 Signaling Pathway in Interferon-γ-stimulated Murine Dendritic Cells*

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step in the degradation of tryptophan and is strongly induced in interferon-γ (IFNγ)-stimulated dendritic cells (DCs). IDO has recently been established as a key enzyme in T-cell suppression-mediated immune tolerance to tumors. STAT1 phosphorylation appears to play an important role in the control of IDO expression by IFNγ, but the precise regulatory mechanism remains obscure. Here we present a novel mechanism of IFNγ-induced IDO expression in bone marrow-derived dendritic cells. In addition, we demonstrate that curcumin, an active component of turmeric, significantly inhibited the induction of IDO expression and activity by IFNγ. We found that curcumin suppressed STAT1 activation by directly inhibiting Janus-activated kinase 1/2 and protein kinase Cδ phosphorylation in bone marrow-derived DCs, suppressing the subsequent translocation and binding of STAT1 to the GAS element of the IRF-1 promoter. Coincident with these inhibitory effects on IFNγ-induced IDO expression, curcumin reversed IDO-mediated suppression of T-cell responses. Our results, thus, suggest that down-regulation of IDO in DCs is an important immunomodulatory property of curcumin that may be exploited therapeutically in the control of cancers.
Time‐efficient fast spin echo imaging at 4.7 T with low refocusing angles

An implementation of fast spin echo at 4.7 T designed for versatile and time‐efficient T2‐weighted imaging of the human brain is presented. Reduced refocusing angles (α < 180°) were employed to overcome specific absorption rate (SAR) constraints and their effects on image quality assessed. Image intensity and tissue contrast variations from heterogeneous RF transmit fields and incidental magnetization transfer effects were investigated at reduced refocusing angles. We found that intraslice signal variations are minimized with refocusing angles near 180°, but apparent gray/white matter contrast is independent of refocusing angle. Incidental magnetization transfer effects from multislice acquisitions were shown to attenuate white matter intensity by 25% and gray matter intensity by 15% at 180°; less than 5% attenuation was seen in all tissues at flip angles below 60°. We present multislice images acquired without excess delay time for SAR mitigation using a variety of protocols. Subsecond half Fourier acquisition single‐shot turbo spin echo (HASTE) images were obtained with a novel variable refocusing angle echo train (20° < α < 58°) and high‐resolution scans with a voxel volume of 0.18 mm3 were acquired in 6.5 min with refocusing angles of 100°. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Simulation of Multiple Reflecting Structures Using a Nonparaxial Bidirectional Split-Step Finite Difference Method

We present simulation of nonparaxial waves in multiple reflecting structures, using a recently proposed bidirectional method based on a finite difference split-step nonparaxial scheme. Simulation of finite beams in volume Bragg gratings, through high reflection coatings and tilted fiber Bragg gratings are presented. Comparisons are made with experimental, analytical, and other numerical methods to demonstrate its accuracy and efficiency. The method is noniterative and the propagation matrices are evaluated analytically making it computationally very efficient. The method has very high accuracy for modeling reflection of nonparaxial beams and can simulate large longitudinal index discontinuities efficiently without using special modifications.
Changes in Utilization and Discard of Hepatitis C–Infected Donor Livers in the Recent Era

The impact of interferon (IFN)‐free direct‐acting antiviral (DAA) hepatitis C virus (HCV) treatments on utilization and outcomes associated with HCV‐positive deceased donor liver transplantation (DDLT) is largely unknown. Using the Scientific Registry of Transplant Recipients, we identified 25 566 HCV‐positive DDLT recipients from 2005 to 2015 and compared practices according to the introduction of DAA therapies using modified Poisson regression. The proportion of HCV‐positive recipients who received HCV‐positive livers increased from 6.9% in 2010 to 16.9% in 2015. HCV‐positive recipients were 61% more likely to receive an HCV‐positive liver after 2010 (early DAA/IFN era) (aRR:1.451.611.79, p < 0.001) and almost three times more likely to receive one after 2013 (IFN‐free DAA era) (aRR:2.582.853.16, p < 0.001). Compared to HCV‐negative livers, HCV‐positive livers were 3 times more likely to be discarded from 2005 to 2010 (aRR:2.692.993.34, p < 0.001), 2.2 times more likely after 2010 (aRR:1.802.162.58, p < 0.001) and 1.7 times more likely after 2013 (aRR:1.371.682.04, p < 0.001). Donor HCV status was not associated with increased risk of all‐cause graft loss (p = 0.1), and this did not change over time (p = 0.8). Use of HCV‐positive livers has increased dramatically, coinciding with the advent of DAAs. However, the discard rate remains nearly double that of HCV‐negative livers. Further optimization of HCV‐positive liver utilization is necessary to improve access for all candidates.
Feed premix: a difficult matrix for the accurate determination of trace elements – the outcome of IMEP-114 and IMEP-36

This paper presents the outcome of two proficiency tests (IMEP-114/36) running in parallel, which focused on the determination of total As, Cd, Pb, Hg and Sn in feed premixes. Both exercises aimed to test the performance of laboratories measuring trace elements in feed, in compliance with Directive 2002/32/EC of the European Parliament and of the Council on undesirable substances in animal feed. IMEP-114 was run for the European Union National Reference Laboratories, while IMEP-36 was open to all food control laboratories that wished to participate. In total 80 laboratories from 37 countries registered to both proficiency tests, from which 75 laboratories reported results. The test material used in this exercise was commercially available feed premix, which was processed, bottled, labelled and dispatched to participants. The performance of the participating laboratories was similar in both proficiency tests and was very good in the case of total Cd and less satisfactory for total As and total Pb. For total Sn only one-third of the participants reported results, from which 33% performed satisfactorily. Thirty-four participants reported results for total Hg, although the expert laboratories stated that the mass fraction for that measurand was below the limit of detection of the method used. An evaluation of the reasons that could be at the basis of unsatisfactory results has been carried out and is presented here.
Morphological and immunophenotypic analysis of basal-like carcinoma of the breast

Breast carcinomas present a heterogeneous group of tumours varying greatly with regard to histopathological classification, prognosis and treatment options. Recent research has identified a subtype of breast carcinoma that is associated with a poor prognosis and is most commonly found to be grade 3; these tumours are termed basal-like tumours due to their differentiation towards basal cell types. Sixty cases of grade 3 ductal carcinomas not otherwise specified (NOS) were stained using immunohistochemical techniques with a panel of antibodies. All cases were subjected to immunohistochemical and morphological analyses, and tumours were classified as either basal-like or ductal NOS. Statistical analysis accompanied by sensitivity and specificity values showed cytokeratin 5 and vimentin to be the most useful antibodies for diagnosing the basal-like tumour. Morphological analysis found that a high mitotic count and presence of necrosis could be associated with the basal-like phenotype. Results of this study have facilitated the development of an algorithm to allow identification and diagnosis of this tumour type.
Impact of Cognitive Behavior Therapy on Health-Related Quality of Life Among Adult Hypnotic Users With Chronic Insomnia

Results were combined from representative surveys of health related quality of life (HRQoL; n = 11,877; age range = 16–104) with data from a randomized controlled trial of cognitive behavior therapy for chronic insomnia (n = 209; age range = 31–92). Secondary analyses of scores from the SF-36 measure of HRQoL were conducted in order: (a) to compare the health related quality of life profiles of adult hypnotic users with chronic insomnia with those of population norms, and (b) to assess the impact of cognitive behavior therapy (CBT) for insomnia on HRQoL outcomes over 6 months. Compared with the primary care reference values, HRQoL among the trial participants at baseline was generally poorer. The magnitude of these decrements reduced markedly with advancing age. In the evaluation of the CBT intervention, statistically significant differences in SF-36 scores in favor of the intervention were present for physical functioning, emotional role limitation, and mental health over 6 months. Overall, this study shows that the SF-36 can play an important role in describing HRQoL in this patient group, and in the evaluation of interventions within this group.
Reduction of Low Space Harmonics for the Fractional Slot Concentrated Windings Using a Novel Stator Design

Using magnetic flux barriers in the stator yoke of electric machines with fractional slots, tooth-concentrated winding, it is possible to reduce or even to cancel some space harmonics of low order in the air-gap flux density resulting in lower rotor losses induced by the armature reaction field. In this paper, this new technique is applied during the design and analysis of two permanent magnet machines with different 12-teeth/10-poles concentrated windings. Considering the main machine performances, such as the electromagnetic torque, machine losses, and also the field-weakening capability, the new stator design shows significant advantages over the conventional design. According to the new technique, a prototype machine is built and some measurement results are given.
MicroRNA-346 Mediates Tumor Necrosis Factor &agr;–Induced Downregulation of Gut Epithelial Vitamin D Receptor in Inflammatory Bowel Diseases

Background:We recently reported that the gut epithelial vitamin D receptor (VDR) signaling inhibits colitis through inhibition of intestinal epithelial cell apoptosis, and the level of colonic epithelial VDR is markedly reduced in patients with inflammatory bowel diseases (IBD). VDR downregulation promotes colitis, but the mechanism underlying VDR downregulation in IBD is unknown. Methods:VDR expression was analyzed in colon cancer cells under proinflammatory cytokine treatment. VDR as a target of miR-346 was confirmed using colon cancer cell culture. The relationship among inflammation, miR-346, and VDR was assessed in human IBD biopsies and experimental colitis models. Results:We showed that tumor necrosis factor &agr; (TNF-&agr;) suppresses VDR expression while simultaneously upregulating miR-346 in human colon cancer cells. Further studies demonstrated that miR-346 inhibits VDR by a specific target sequence in the 3′ untranslated region of the human VDR transcript, and blockade of miR-346 with a hairpin inhibitor abrogates the ability of TNF-&agr; to inhibit VDR, confirming that TNF-&agr; downregulates VDR by inducing miR-346. Consistently, in human IBD biopsies, the reduction of epithelial VDR is associated with increased immune cell infiltration and elevation of TNF-&agr; and miR-346. In an experimental model of colitis, mucosal VDR expression is reduced over time with the progression of colitis, inversely correlated with the induction of TNF-&agr; and miR-346 in the mucosa. Conclusions:These data suggest that during mucosal inflammation TNF-&agr; induces miR-346, which downregulates epithelial VDR. Mucosal VDR reduction in turn compromises the integrity of the mucosal epithelial barrier, further driving mucosal inflammation and colitis development.
Reversal of myelofibrosis by hydroxyurea

Abstract: Bone marrow morphology in 39 symptomatic patients with myeloproliferative disorders (polycythaemia vera 15, essential thrombocythaemia 14, idiopathic myelofibrosis 9, myeloproliferative syndrome 1) and elevated platelet counts was studied before and after a median of 18 months of continuous treatment with hydroxyurea. We found a significant reduction of bone marrow fibrosis, believed to be mediated by suppression of thrombopoiesis by hydroxyurea.
How case-study research can help to explain implementation of the nurse practitioner role.

AIM To discuss how case-study research was undertaken to explain the implementation of the nurse practitioner role in a Canadian province. BACKGROUND In Canada, the nurse practitioner role was only recently introduced and one of the last provinces to implement it was British Columbia. At this time, no studies of the role's implementation in the province had been published and, although nurses refer to case studies more frequently in their research, the literature lacks concise explanations of the methodologies involved in creating them. DATA SOURCES A case study of the implementation of the nurse practitioner role, including participant interviews and document review. RESEARCH METHODOLOGY The development of an explanatory, single case study with embedded units of analysis in line with Yin's (2009) approach to case-study research. DISCUSSION This article provides an overview of case-study research methodology and examples from a case study undertaken by the author. CONCLUSION The use of case studies provides nurse researchers with opportunities to engage with phenomena of interest in their settings and so is suited to the complex nature of nursing practice. IMPLICATIONS FOR PRACTICE OR RESEARCH: Case-study research enables researchers to study areas of interest thoroughly and in the context in which they occur.
Nasal carriage of Streptococcus pneumoniae serotypes and Staphylococcus aureus in Streptococcus pneumoniae-vaccinated and non-vaccinated young children

SUMMARY Since the implementation of Streptococcus pneumoniae (SPn) conjugate vaccination (PCV), non-vaccine types have prevailed in invasive pneumococcal disease (IPD), and an increase in Staphylococcus aureus (SA) burden has been suggested. Here, we assess the epidemiology of SA and SPn nasal carriage in 620 children at day-care centres; 141 of these children had received 1–4 PCV7 doses. A higher vaccine dosage was associated with non-vaccine-type SPn carriage. Of all SPn isolates, 45% were PCV7 types, 1% were additional PCV10 types and 22% were the three additional PCV13 types. SA carriage was inversely associated with vaccine-type SPn carriage. SPn serotype 19A showed higher SA co-carriage rates compared to other SPn serotypes. PCV7 implementation does not prevent children from being part of the IPD-related SPn transmission chain. These results contribute to the monitoring of SA- and SPn-related disease and add to the debate on the current national vaccination policy that recently included a change from PCV7 to PCV10.
The Market of Ideas as the Center of the IS Field

The center of the IS field is presented as a market of ideas, an intellectual exchange related to the design and management of information technologies in organized human enterprise. In this view, the IS field is a loosely coupled system operating through weak social ties across intellectual communities. A loosely coupled system can operate towards contradictory goals of both plasticity and stability in the search for new research opportunities and generation of valid knowledge. The market of ideas allows reconciliation of rigor and relevance, technical and social, design and explanation. It lowers the barriers of established disciplinary regimes and institutions, and facilitates scholarship in fields where conditions change quickly. It helps to balance exploration and exploitation in an effort to avoid competency traps. Limitations of the metaphor are considered.
Denuding and centrifugation of maturing bovine oocytes alters oocyte spindle integrity and the ability of cytoplasm to support parthenogenetic and nuclear transfer embryo development

The effects of cumulus cell removal and centrifugation of maturing bovine oocytes on nuclear maturation and subsequent embryo development after parthenogenetic activation and nuclear transfer were examined. Removal of cumulus cells at 4, 8, and 15 hr after in vitro maturation (IVM) or the centrifugation of denuded oocytes had no effect on maturation rates. Oocytes treated at 0 hr of IVM had a lower expulsion rate (50%) of the first polar body (PB1). The removal of cumulus cells and centrifugation affected the pattern of spindle microtubule distribution and division of chromosomes. There were almost no spindle microtubules allocated to PB1 and the spindles were swollen in anaphase I and telophase I oocytes. Approximately 20% of PB1 oocytes contained tripolar or multipolar spindles. After activation, oocytes denuded with or without centrifugation at 8 hr of IVM resulted in the lowest rate of development (3.0%). Denuded oocytes at 4, 15, and 24 hr of IVM with centrifugation or not resulted in similar blastocyst development rates (9.6%–13.2%). However, centrifugation of oocytes denuded at the beginning of IVM resulted in lower blastocyst development rate (8.1%, P < 0.05) than the noncentrifuged oocytes (17.3%). After nuclear transfer, the blastocyst development rates of oocytes denuded and centrifuged at 0, 4, and 8 hr of IVM were not different when compared to the same patch of noncentrifuged oocytes. However, oocytes denuded and centrifuged at 15 hr of IVM resulted in lower (P < 0.05) blastocyst development rates than the noncentrifuged oocytes. The results of this study suggest that removal of cumulus cells and centrifugation of denuded oocytes affect the spindle pattern. Embryo development of denuded and centrifuged oocytes may differ depending on the time of removal of cumulus cells. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
A prospective study of widowhood and changes in symptoms of depression in a community sample of the elderly

Synopsis This survey examines changes in depressive symptomatology (CES-D) during bereavement in 1046 elderly subjects, of whom 139 became widowed during follow-up. Depression scores increased during the first year of bereavement, but generally returned to pre-widowhood levels thereafter. However, depression scores remained elevated among young-old widows (65–74year-olds) well after the first year of widowhood. Using cut-off scores, rates of high depressive symptoms remained somewhat elevated over baseline levels. Increases in depression scores during bereavement were not explained by socio-economic variables, health habits and health status. It is concluded that particularly young-old widows are at risk of developing chronic depressive symptomatology during bereavement that may warrant clinical attention.
Controlling sleeping sickness – a review

SUMMARY Following a period characterized by severe epidemics of sleeping sickness, restoration of effective control and surveillance systems has raised the question of eliminating the disease from sub-Saharan Africa. Given sufficient political and financial support, elimination is now considered a reasonable aim in countries reporting zero or less than 100 cases per year. This success may lead health authorities across the affected region to downgrade the disease from ‘neglected’ to simply being ignored. In view of the significant levels of under-reporting of sleeping sickness mortality in rural communities, this could be a short-sighted policy. Loss of capacity to deal with new epidemics, which can arise as a consequence of loss of commitment or civil upheaval, would have serious consequences. The present period should be seen as a clear opportunity for public-private partnerships to develop simpler and more cost-effective tools and strategies for sustainable sleeping sickness control and surveillance, including diagnostics, treatment and vector control.
The nonrandom distribution of facial hemangiomas.

OBJECTIVE To map sites of occurrence of facial infantile hemangiomas and correlate these with pattern of tumor growth, clinical complications, and proximity to structural and developmental landmarks. DESIGN A retrospective medical record review of 205 patients diagnosed with facial infantile hemangioma. SETTING Arkansas Children's Hospital, Little Rock, a 250-bed teaching hospital affiliated with the University of Arkansas for Medical Sciences. PATIENTS Based on their clinical photographs, 232 of the hemangiomas were mapped on a facial schematic. Each lesion was encoded with a number reflective of its location, and this number was shared by other lesions occurring at the same site. Frequencies of complicating ulceration and airway obstruction were determined by medical record review. RESULTS Two patterns of tumor growth were evident among the hemangiomas analyzed: focal (177 lesions [76.3%]) and diffuse (55 lesions [23.7%]). The focal hemangiomas mapped to 22 sites of occurrence, all near lines of mesenchymal or mesenchymal-ectodermal embryonic fusion. The 55 diffuse hemangiomas showed a segmental tissue distribution and thus were designated as frontonasal (15 lesions [27%]), maxillary (19 lesions [35%]), or mandibular (21 lesions [38%]). Ulceration was 3 times more common in patients with diffuse hemangiomas (21 [51%] of 41) than in patients with focal hemangiomas (28 [17%] of 164). Airway obstruction was characteristic of diffuse mandibular hemangiomas. CONCLUSIONS Facial infantile hemangiomas occurred in 2 distinct patterns of tissue involvement: a focal type with a tumorlike appearance and a less common diffuse type with a plaquelike appearance. The diffuse lesions were more likely to be complicated by ulceration or airway obstruction and showed a strikingly segmental distribution pattern. Focal hemangiomas, in contrast, showed a predilection for regions of embryological fusion.
The effects of IL-5 on airway physiology and inflammation in rats.

BACKGROUND There is evidence that the cytokine IL-5 is a prominent feature of airway inflammation in asthma. OBJECTIVE The aim of this study was to determine whether exogenous IL-5 could cause changes in lung physiology, the early and late airway response after antigen challenge, and airway inflammation in rats that do not have a propensity to develop these changes after sensitization and challenge. METHOD AND RESULTS Intratracheal administration of IL-5 to ovalbumin sensitized Brown Norway SSN rats increased the airway responsiveness to methacholine (AHR) 20 hours after administration of IL-5 at the same time as an increase in neutrophils occurred in the lung lavage. This effect was dose dependent and was not caused by endotoxin. Concurrent intratracheal administration of 50 ng of anti-IL-5 monoclonal antibody with 10 microg of recombinant human IL-5 decreased the AHR and neutrophil influx. Pretreatment with 3 microg of IL-5 had no effect on the early and late airway response or on AHR after ovalbumin challenge. However, IL-5 increased lung re-sistance 20 hours after antigen challenge. Although total lung cells and differential counts did not differ significantly 8 hours after antigen challenge, the blood lymphocyte CD4/CD8 ratio decreased in IL-5 pretreated rats (P <.05). In addition, in situ hybridization showed a significant increase in cells within the airway wall expressing IL-4 and IL-5 mRNA in IL-5 treated/challenged rats compared to controls (P <.05). CONCLUSION The intratracheal administration of IL-5 causes only part of the physiologic changes that are associated with asthma. Other factors are necessary to obtain the complete asthma phenotype.