Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralizing Interleukin-4 Prevents Transplant Arteriosclerosis Mediated by Indirect Pathway T Cells Under CD40-CD154 Costimulation Blockade

Introduction. Blockade of the CD40-CD154 costimulatory pathway can prolong allograft survival, but does not prevent the development of transplant arteriosclerosis in several models. In this study, we investigated the mechanisms of CD40-CD154-independent transplant arteriosclerosis in major histocompatibility complex (MHC)-class I-mismatched aortic allografts. Methods. MHC class I-mismatched CBK (H2k+Kb) donor aortas were transplanted into CBA (H2k) recipients who can only recognize the graft through CD8+ T cells and CD4+ T cells responding to the class I MHC mismatch through the indirect pathway of allorecognition. Recipients were treated with anti-CD154 antibody (MR1) alone or in combination with anti-CD8 (YTS169) or anti-interleukin (IL)-4 (11B11) antibodies. Grafts were analyzed by histology on days 30 and 60 and for intragraft mRNA expression on day 14 after transplantation. Results. Repeated treatment with anti-CD154 alone or in combination with anti-CD8 antibody did not prevent intimal proliferation compared with untreated controls (65%±6%, 62%±9%, and 71%±7% luminal occlusion, respectively, 60 days after transplantation). In both treatment groups, the expression of IL-4, IL-5, and eotaxin was increased compared with control grafts, and an eosinophilic infiltration was observed. Neutralizing IL-4 in combination with CD40-CD154 blockade and CD8+ T-cell depletion abrogated transplant arteriosclerosis (9%±4% luminal occlusion 60 days after transplantation). Conclusion. Prolonged treatment with anti-CD154 was not able to prevent the development of transplant arteriosclerosis in MHC class I-mismatched aortic allografts, in the presence or absence of CD8+ T cells. This CD40-CD154 pathway resistant transplant arteriosclerosis was mediated by IL-4, because neutralizing IL-4 in addition to CD40-CD154 costimulation blockade and CD8+ T-cell depletion prevented its development.
Social media and libraries

Libraries are the early pioneers in using social media, Social media has the potential to facilitate much closer relationships between libraries and their patrons – wherever users are based, and however they choose to learn about and access library services and resources. Social media can be an effective tool for building and engaging community. In this article we discussed about the social media its growth, applications in library and information services, advantages of the social media in libraries and the challenges encountered. Current usage of social media by the library community generally remains ad hoc and somewhat experimental, but the uptake of these tools is accelerating, and they will play an important role in library service in the future.
Influence of the Presidential Inaugural Address on Audience Perceptions of Candidate Image and the State of the Nation

This study asks whether and how the presidential inaugural address influences American audiences. The current study explores how the 2017 Presidential Inaugural Address of Donald Trump influences audiences. Two areas were studied: Candidate image and the state of the nation. I hypothesized that participants who watched the address would have different attitudes regarding candidate image and the state of the nation compared to non-viewers. I also hypothesized that viewers of the address who voted for Donald Trump would respond differently to candidate image and the state of the nation when compared with those who did not vote for Trump. With one exception, none of the findings was significant. That is, attitudes of inaugural address viewers and non-viewers were similar, and attitudes of those who voted for the president and those who did not vote for the president were also similar. The exception was noted between those who voted for the candidate and oppositional voters: Those who voted for Donald Trump reported the nation is headed “in the right direction” while dissenters disagreed.
Uveitis in a tertiary ophthalmology centre in Thailand

Purpose: To determine the aetiology and clinical characteristics of patients with uveitis in a tertiary ophthalmology centre in northern Thailand. Methods: Standard ophthalmological examination and laboratory screening blood tests were performed in 200 consecutive new patients with uveitis. Patients were classified according to the location and aetiology of the uveitis. Specific clinical characteristics were recorded. Design: Prospective case series. Results: The case series included 106 male and 94 female patients with a mean age of 38 years. HIV-associated uveitis was noted in 31% (62/200), and included mostly patients with cytomegalovirus retinitis (85%, 53/62). In the non-HIV group, the most common anatomical type was anterior uveitis (34%, 47/138). Infectious uveitis was diagnosed in 22% (30/138) of non-HIV patients, and toxoplasmosis was the most common infection (12/138, 8.7%). The most common non-infectious clinical entities were Vogt–Koyanagi–Harada disease (20%, 22/108) and HLA-B27-associated acute anterior uveitis (9%, 10/108). Conclusions: The spectrum of uveitis in northern Thailand included 27% of HIV-infected patients with cytomegalovirus retinitis. Causes of non-HIV uveitis were similar to those often observed in the Far East, but the specific prevalences of these disorders were distinct from that found in India and Japan.
A Review of Physical Activity and Circulating miRNA Expression: Implications in Cancer Risk and Progression

The role of circulating miRNAs (c-miRNAs) in carcinogenesis has garnered considerable scientific interest. miRNAs may contribute actively to cancer development and progression, making them potential targets for cancer prevention and therapy. Lifestyle factors such as physical activity (PA) have been shown to alter c-miRNA expression, but the subsequent impact on cancer risk and prognosis is unknown. To provide a better understanding of how PA reduces the risk of cancer incidence and improves patient outcomes, we conducted a review of the impact of PA on c-miRNA expression, which includes a comprehensive synthesis of studies examining the impacts of acute and chronic exercise on expression of c-miRNAs. While the variability in methods used to assess miRNA expression creates challenges in comparing and/or synthesizing the literature, results to date suggest that the circulating form of several miRNAs known for playing a role in cancer (c-miR-133, c-miR-221/222, c-miR-126, and c-let-7) are altered by both acute and chronic PA. Additional research should develop standardized procedures for assessing both c-miRNA and PA measurement to improve the comparability of research results regarding the direction and amplitude of changes in c-miRNAs in response to PA. Cancer Epidemiol Biomarkers Prev; 27(1); 11–24. ©2017 AACR.
Propositions, challenges and dilemmas of the Virtual Organisation - a social capital-based analysis

Virtual Organisations (VO) are regarded as the appropriate organisational form to facilitate innovation. Much has been written about the structural characteristics and propositions of virtual organisations, but their inherent limitations remain largely unaddressed. Hence, there is a significant gap between the propositions in the literature and the number of successful VO examples in practice. We argue for a more realistic view of the VO, its goals, structural propositions, limitations and challenges. VO are flexible and volatile organisational arrangements with only little formal structures and management mechanisms. While this is a promising proposition on an organisational level, it challenges cooperation on the project and team level. Especially complex and innovative tasks need effective social structures to enable interpersonal cooperation in knowledge-intensive tasks. Based on a conceptual analysis of its structure and by applying social capital theory we are able to identify inherent contradictions and challenges of the VO, which result from a mismatch between task requirements on the project level and its characteristics on the organisational level. Organisational virtualisation in terms of inter-firm cooperation and technological virtualisation in terms of intensive usage of ICT challenge the emergence of social capital as a prerequisite for effective team-level collaboration. At the same time social capital can be seen as a solution to the problems of the VO, given that management finds ways to promote its emergence in the VO. We present some ideas of how to facilitate the emergence of social capital in the VO.
Computer‐Based Exercise Program

&NA; Effects of a 12‐week intervention on mood and fatigue in pediatric patients with cancer BACKGROUND: Increasing rates of survival present a new set of physical and psychological challenges for children dealing with side effects during cancer treatment. Physical activity has been shown to be an effective strategy to reduce several side effects. OBJECTIVES: The purpose of this pilot study was to determine the benefits of a 12‐week computer‐based exercise intervention on perceived physical, motivational, and fatigue syndrome and psychological state. METHODS: Nine inpatient and outpatient pediatric patients with cancer participated in a 12‐week intervention consisting of supervised computer‐based exercise sessions. Participants completed measures assessing mood and fatigue pre‐ and postintervention. FINDINGS: The intervention was feasible and provided preliminary evidence for the benefits on mood and fatigue in pediatric patients with cancer. The results promote the effectiveness of physical activity in pediatric oncology and call for continuing research in pediatric patients with cancer where sedentary behavior and the associated side effects are a growing concern.
[Troglitazone suppresses ICAM-1 and MMP-9 expressions by up-regulating PPARγ in HeLa cells].

OBJECTIVE To investigate the effect of troglitazone, a proliferator-activated receptor-γ (PPARγ) agonist, on the expressions of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteainse-9 (MMP-9) and cell proliferation in HeLa cells. METHODS MTT assay was used to measure the cell viability at different time points (0, 24, 48 and 72 h) after exposure to troglitazone. RT-PCR and Western blotting were employed to detect the mRNA and protein expressions of ICAM-1, MMP-9 and PPARγ in the cells. Electrophoretic mobility shift assay (EMSA) was performed to assess the changes in DNA binding activity of PPARγ. RESULTS The viability of HeLa cells were time-dependently inhibited by troglitazone, which also significantly reduced the mRNA and protein expressions of ICAM-1 and MMP-9 and increased PPARγ expression. The effects of troglitazone in inhibiting the cell viability and reducing ICAM-1 and MMP-9 expressions were antagonized by the application of the PPARγ antagonist GW9662. The result of EMSA also showed significantly increased DNA binding activity of PPARγ in the cells exposed to troglitazone. CONCLUSION The PPARγ agonist troglitazone can inhibit the expression of ICAM-1 and MMP-9 in HeLa cells by up-regulating PPARγ.
Coastal Eutrophication Thresholds: A Matter of Sediment Microbial Processes

Abstract In marine sediments, the major anaerobic mineralization processes are Fe(III) oxide reduction and sulfate reduction. In this article, we propose that the two alternative microbial mineralization pathways in sediments exert decisively different impacts on aquatic ecosystems. In systems where iron reduction dominates in the recently deposited sediment layers, the fraction of Fe(III) oxides that is dissolved to Fe(II) upon reduction will ultimately be transported to the oxic layer, where it will be reoxidized. Phosphorus, which is released from Fe(III) oxides and decomposing organic matter from the sediment, will be largely trapped by this newly formed Fe(III) oxide layer. Consequently, there are low concentrations of phosphorus in near-bottom and productive water layers and primary production tends to be limited by phosphorus (State 1). By contrast, in systems where sulfate reduction dominates, Fe(III) oxides are reduced by sulfides. This chemical reduction leads to the formation and permanent burial of iron as solid iron sulfides that are unable to capture phosphorus. In addition, the cycling of iron is blocked, and phosphorus is released to overlying water. Owing to the enrichment of phosphorus in water, the nitrogen : phosphorus ratio is lowered and nitrogen tends to limit algal growth, giving an advantage to nitrogen-fixing blue-green algae (State 2). A major factor causing a shift from State 1 to State 2 is an increase in the flux of labile organic carbon to the bottom sediments; upon accelerating eutrophication a critical point will be reached when the availability of Fe(III) oxides in sediments will be exhausted and sulfate reduction will become dominant. Because the reserves of Fe(III) oxides are replenished only slowly, reversal to State 1 may markedly exceed the time needed to reduce the flux of organic carbon to the sediment. A key factor affecting the sensitivity of a coastal system to such a regime shift is formed by the hydrodynamic alterations that decrease the transport of O2 to the near-bottom water, e.g., due to variations in salinity and temperature stratification.
Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice.

BACKGROUND The development of dependence may have significant motivational consequences regarding continued use and abuse of ethanol. We have developed a mouse model of ethanol dependence and repeated withdrawals that demonstrates sensitization of seizures and other symptoms of withdrawal. It is unclear whether such experience influences ethanol drinking behavior. The present series of experiments were designed to examine whether repeated cycles of chronic ethanol exposure and withdrawal has an impact on subsequent motivation to voluntarily self-administer ethanol. METHODS With the use of a modified sucrose-fading procedure, adult male C57BL/6J mice were trained to drink 15% (v/v) ethanol in a limited access procedure (2 hr/day). The animals were not food or water deprived at any time during the experiments. Once stable baseline intake was established, mice were exposed to four cycles of 16 hr of ethanol vapor (or air) in inhalation chambers separated by 8-hr periods of withdrawal. At 32 hr after the last cycle of ethanol exposure, all mice were tested for ethanol intake under limited access conditions for 5 consecutive days. The animals then received a second series of chronic ethanol exposure and withdrawal followed by another 5-day test period for ethanol drinking. RESULTS Stable daily baseline intake was established in mice that drank 15% ethanol combined with 5% sucrose (experiment 1), 15% ethanol alone (experiment 2), 5% sucrose alone (experiment 3), or 15% ethanol when presented as a choice with water (experiment 4). After repeated cycles of chronic ethanol exposure and withdrawal experience, consumption of ethanol solutions increased over baseline levels and in comparison with control (air-exposed) groups. However, sucrose consumption did not change in mice that were trained to drink 5% sucrose. The increase in ethanol consumption after chronic ethanol exposure and withdrawal experience resulted in a significant increase in resultant blood ethanol levels. CONCLUSIONS Once the positive reinforcing properties of ethanol were established, chronic ethanol exposure and withdrawal experience resulted in a significant increase in voluntary ethanol drinking that yielded a >2-fold increase in resultant blood ethanol levels. This increase in ethanol intake occurred whether ethanol was presented in combination with sucrose, alone (unadulterated), or as a choice with tap water. Furthermore, this effect seems to be selective for ethanol in that animals that were trained to drink a sucrose solution did not exhibit a change in their intake after similar chronic ethanol exposure. As such, this model may be useful in studying the mechanisms and conditions in which chronic ethanol treatment influences motivation to resume drinking after a period of abstinence (relapse).
Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

Background Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. Objectives We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). Methods A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Statistical methods Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. Results The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. Conclusions This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.
An environmental audit tool suitable for use in homelike facilities for people with dementia

Aim: To compare an assessment tool developed for use on contemporary homelike environments, the Environmental Audit Tool (EAT), with the gold standard assessments for residential facilities for people with dementia, the Special Care Unit Environmental Quality Scale (SCUEQS) and the global score of the Therapeutic Environment Screening Survey for Nursing Homes (TESS‐NH).
Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret.

BACKGROUND & AIMS Marijuana and other cannabinoids are effective anti-emetics. Despite ongoing controversy over their usage, the receptor distribution and the site of the anti-emetic action of these compounds are not known. Our aim was to investigate whether the cannabinoid 1 receptor (CB1r) and endocannabinoids play a role in the anti-emetic action of cannabinoids. METHODS Ferrets were given an emetic stimulus and the number of episodes of retching and vomiting were observed after administration of CB1r agonists and a CB1r antagonist. CB1r and fatty acid amide hydrolase (FAAH), which degrades endocannabinoids, were localized by immunohistochemistry. RESULTS CB1r and FAAH were localized in the dorsal vagal complex, consisting of the area postrema, nucleus of the solitary tract, and the dorsal motor nucleus of the vagus in the brainstem. CB1r was found in the myenteric plexus of the stomach and duodenum. Activation of CB1r by the agonists (delta)(9)-tetrahydrocannabinol, WIN 55,212-2, and methanandamide inhibited emesis and their action was reversed by a selective CB1r antagonist, which alone had no effect, but potentiated vomiting in response to an emetic stimulus. CONCLUSIONS CB1r mediates the anti-emetic action of cannabinoids in the dorsal vagal complex. Endocannabinoids are a novel neuroregulatory system involved in the control of emesis.
How to cope with dissonant heritage: a way towards sustainable tourism development

ABSTRACT The UNESCO World Summit at Johannesburg in 2002, can be considered a watershed moment for promoting cultural diversity and defining cultural sustainability. Involving community residents is often regarded as best practice when fostering sustainability, though dissonant heritage problems may arise. We connect the issue of dissonance with contrasting interpretations of the past, specifically in the context of promoting heritage places linked to ideologies that are contrary to the principles enshrined in the Universal Declaration of Human Rights. We focus on buildings constructed during the interwar years in Predappio and Forlì, which are closely tied to Italian dictator Benito Mussolini, and now represent an “ambivalent and largely unwanted past”. Using a LISREL (Linear Structural Relations) model to analyse residents’ attitude towards tourism around these dissonant heritage sites, we show that without a proper cultural policy as the creation of the European cultural route named ATRIUM (Architecture of Totalitarian Regimes of the 20th Century in Europe's Urban Memory Route), residents view tourism unfavourably, rendering it unsustainable.
GLP-1 Mediates Antiapoptotic Effect by Phosphorylating Bad through a β-Arrestin 1-mediated ERK1/2 Activation in Pancreatic β-Cells

Strategies based on activating GLP-1 receptor (GLP-1R) are intensively developed for the treatment of type 2 diabetes. The exhaustive knowledge of the signaling pathways linked to activated GLP-1R within the β-cells is of major importance. In β-cells, GLP-1 activates the ERK1/2 cascade by diverse pathways dependent on either Gαs/cAMP/cAMP-dependent protein kinase (PKA) or β-arrestin 1, a scaffold protein. Using pharmacological inhibitors, β-arrestin 1 small interfering RNA, and islets isolated from β-arrestin 1 knock-out mice, we demonstrate that GLP-1 stimulates ERK1/2 by two temporally distinct pathways. The PKA-dependent pathway mediates rapid and transient ERK1/2 phosphorylation that leads to nuclear translocation of the activated kinases. In contrast, the β-arrestin 1-dependent pathway produces a late ERK1/2 activity that is restricted to the β-cell cytoplasm. We further observe that GLP-1 phosphorylates the cytoplasmic proapoptotic protein Bad at Ser-112 but not at Ser-155. We find that the β-arrestin 1-dependent ERK1/2 activation engaged by GLP-1 mediates the Ser-112 phosphorylation of Bad, through p90RSK activation, allowing the association of Bad with the scaffold protein 14-3-3, leading to its inactivation. β-Arrestin 1 is further found to mediate the antiapoptotic effect of GLP-1 in β-cells through the ERK1/2-p90RSK-phosphorylation of Bad. This new regulatory mechanism engaged by activated GLP-1R involving a β-arrestin 1-dependent spatiotemporal regulation of the ERK1/2-p90RSK activity is now suspected to participate in the protection of β-cells against apoptosis. Such signaling mechanism may serve as a prototype to generate new therapeutic GLP-1R ligands.