bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Makes Patients with Fibromyalgia Feel Better? Correlations Between Patient Global Impression of Improvement and Changes in Clinical Symptoms and Function: A Pooled Analysis of 4 Randomized Placebo-controlled Trials of Duloxetine
Authors: HUDSON JAMES I. , ARNOLD LESLEY M. , BRADLEY LAURENCE A. , CHOY ERNEST H. S. , MEASE PHILIP J. , WANG FUJUN , AHL JONNA , WOHLREICH MADELAINE M. 
Published: October 2009

Objective.To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I).Methods.Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings.Results.Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r ≥ 0.5 or r ≤ −0.5) with endpoint PGI-I. Moderate correlation with endpoint PGI-I (0.30 ≤ r < 0.5 or −0.5 < r ≤ −0.30) included changes in variables that assessed physical functioning, depression, anxiety, fatigue, and several variables related to impact on daily living. Independent predictor variables of endpoint PGI-I identified by stepwise linear regression included assessments for pain, physical function, vitality, anxiety, social function, and tender point thresholds.Conclusion.In addition to pain reduction, what makes patients with FM feel better may include improvement in fatigue, physical functioning, mood, and impact on daily living. An assessment of these domains may be important in clinical trials of FM and in the management of patients with FM.
Research Education for Clinical Nurses: A Pilot Study to Determine Research Self-Efficacy in Critical Care Nurses
Authors: Swenson-Britt Evelyn , Reineck Carol 
Published: October 2009

Background:
Translating research into practice is essential to providing care that promotes both cost-efficient and effective health care delivery. Nurses practicing in the intensive care unit are in need of education that can build research self-efficacy and promote understanding and the ability to apply research findings.

Methods:
This pilot study evaluated the Critical Reading of Research Publications Plus course with intensive care unit nurses to determine whether this experience would affect their research self-efficacy. The Nursing Research Self-Efficacy Scale was administered before and after the course.

Results:

Paired
t
tests showed a significant increase on three of the four subscales in research self-efficacy.

Conclusion:
This study shows that using a course along with mentors may increase the research self-efficacy of practicing nurses.

J Contin Educ Nurs
2009;40(10):454–461.
Amino Acid Deprivation Links BLIMP-1 to the Immunomodulatory Enzyme Indoleamine 2,3-Dioxygenase
Authors: Barnes Nicholas A. , Stephenson Sophie J. , Tooze Reuben M. , Doody Gina M. 
Published: October 2009

Abstract
Catabolism of tryptophan by IDO1 plays an important role in the control of immune responses. Activation of the eukaryotic initiation factor 2α (eIF2α) kinase general control nonderepressible-2 (GCN2) following tryptophan depletion is a major pathway mediating this effect. However, immunomodulatory target genes of GCN2 activation are poorly defined. The transcriptional repressor B lymphocyte-induced maturation protein-1 (BLIMP-1) is a target of the eIF2α kinase1, protein kinase-like ER kinase (PERK) during the unfolded protein response of the endoplasmic reticulum. Thus, BLIMP-1 might also be a mediator of the GCN2 stress response pathway activated by IDO1 and tryptophan depletion. Indeed, in human monocytes BLIMP-1 mRNA and protein are up-regulated in response to both a pharmacological activator of GCN2 and tryptophan-depletion generated by IDO1-transfected cells. This suggests a functional role for BLIMP-1 in the immunomodulatory effects of the IDO1-GCN2 axis. BLIMP-1 has been shown to repress IFN-γ-regulated promoters. As IDO1 is itself highly responsive to IFN-γ, we hypothesized that BLIMP-1 functions in a feedback loop to regulate IDO1 expression. We found that BLIMP-1 binds to IFN-responsive sites in the IDO1 promoter and represses IFN-dependent IDO1 activation. We propose that BLIMP-1 acts in a negative feedback loop to successfully balance the outcome of tolerance vs inflammation.
The Lupus Susceptibility Locus Sle1 Breaches Peripheral B Cell Tolerance at the Antibody-Forming Cell and Germinal Center Checkpoints
Authors: Vuyyuru Raja , Mohan Chandra , Manser Tim , Rahman Ziaur S. M. 
Published: October 2009

Abstract
We have described a line of VH knock-in mice termed HKIR in which the transgenic Igh locus partially encodes “dual-reactive” antichromatin and anti-p-azophenylarsonate (Ars) BCRs. HKIR B cells termed canonical, expressing a particular Vκ L chain, evade central tolerance by down-regulating BCR levels. Canonical HKIR B cells can be recruited into the primary germinal center (GC) and Ab-forming cell (AFC) compartments via Ars immunization. However, their participation in the GC response rapidly wanes and they do not efficiently contribute to the memory compartment, indicating that they are regulated by a GC tolerance checkpoint. We analyzed the influence of the Sle1 genetic interval, shown to break tolerance of chromatin-reactive B cells, on the behavior of HKIR B cells during the anti-Ars response. Canonical B cells from congenic HKIR.Sle1 mice gave rise to elevated short and long-lived AFC responses, and the attenuated GC and memory responses characteristic of these B cells were relieved in adoptive, wild-type recipients. HKIR GC B cells containing Sle1 expressed increased levels of Bcl-2 and c-FLIP and decreased levels of Fas RNA compared with HKIR controls, suggesting direct alteration of the regulation of the GC response by Sle1. High titers of canonical and anti-dsDNA Abs spontaneously developed in many aged HKIR.Sle1 mice. Together, these data indicate that Sle1 perturbs the action of peripheral tolerance checkpoints operative on antinuclear Ag B cells in both the AFC and GC pathways in a cell autonomous fashion.
The α-Isoform of p38 MAPK Specifically Regulates Arthritic Bone Loss
Authors: Böhm Christina , Hayer Silvia , Kilian Anita , Zaiss Mario M. , Finger Susann , Hess Andreas , Engelke Klaus , Kollias George , Krönke Gerhard , Zwerina Jochen , Schett Georg , David Jean-Pierre 
Published: October 2009

Abstract
Pharmacological inhibitors have provided evidence for the key role of p38 MAPK in osteoclast differentiation and in inflammation-induced bone loss. However, these inhibitors block more than one of the four p38 isoforms, usually p38α and p38β, and sometimes also other kinases such as JNK3. We show in this study that p38α is the main p38 isoenzyme expressed in the osteoclast precursors and in the mature osteoclasts. p38α as well as its downstream substrates were phosphorylated in osteoclast progenitors stimulated by TNF-α. Using Mx-cre-mediated conditional gene inactivation we demonstrated that mice lacking p38α were protected against TNF-α-induced bone destruction at the site of inflammation as well as against TNF-α-mediated systemic bone loss. The bone protection was associated to decreased osteoclast numbers in vivo as well as a decreased IL-1β expression in the inflamed tissue and in the isolated monocytes. The phenotype was cell autonomous because, similarly to p38α-deficient cells, knockdown of p38α in monocytes resulted in a decreased osteoclast differentiation in vitro. It was not caused by major changes in RANKL-mediated ERK or JNK activation but rather associated to an increased NF-κB activation caused by a decrease in IκBα recovery. Thus, our data show that developing specific inhibitors of the α-isoenzyme of p38 would be beneficial for the treatment of inflammation-induced bone destruction as observed in rheumatoid arthritis.
RANKL Is Necessary and Sufficient to Initiate Development of Antigen-Sampling M Cells in the Intestinal Epithelium
Authors: Knoop Kathryn A. , Kumar Nachiket , Butler Betsy R. , Sakthivel Senthilkumar K. , Taylor Rebekah T. , Nochi Tomonori , Akiba Hisaya , Yagita Hideo , Kiyono Hiroshi , Williams Ifor R. 
Published: October 2009

Abstract
Microfold cells (M cells) are specialized epithelial cells situated over Peyer’s patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-κB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have &lt;2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-mediated neutralization of RANKL in adult wild-type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.
Ethanol Augments RANTES/CCL5 Expression in Rat Liver Sinusoidal Endothelial Cells and Human Endothelial Cells via Activation of NF-κB, HIF-1α, and AP-1
Authors: Yeligar Samantha M. , Machida Keigo , Tsukamoto Hidekazu , Kalra Vijay K. 
Published: October 2009

AbstractChronic alcohol consumption leads to liver inflammation and cirrhosis. Alcoholic liver disease patients have increased levels of hepatic RANTES/CCL5. However, less is known about the molecular mechanisms for ethanol-induced RANTES up-regulation. In this study, we observed that liver sinusoidal endothelial cells derived from ethanol-fed rats (E-rLSECs) showed severalfold increases in RANTES and hypoxia-inducible factor 1α (HIF-1α) mRNAs compared with control rLSECs (C-rLSECs). Similar effects were seen in acute ethanol treatment of isolated rLSECs and human dermal microvascular endothelial cells. Ethanol-induced RANTES mRNA expression required ethanol metabolism, p38 MAPK, HIF-1α, and JNK-2, but not JNK-1. EMSA experiments showed increased HIF-1α binding to wild-type hypoxia response elements (HREs; −31 to −9 bp) within the RANTES promoter in response to ethanol. RANTES promoter analysis showed that cis elements proximal to the transcription start site, HRE-1 (nt −22 to −19), HRE-2 (nt −32 to −29), and AP-1 (nt −250 to −244) were required for ethanol-mediated RANTES expression. These results were corroborated by chromatin immunoprecipitation assays showing augmented HIF-1α binding to HRE-1. Additionally, promoter analysis revealed c-Jun, c-Jun/c-Fos, and JunD, but not JunB, bound to the AP-1 site of the RANTES promoter. Ethanol-mediated activation of NF-κB led to HIF-1α activation and concomitant RANTES expression. Plasma of ethanol-fed c-Junflox/flox-Mx-1-Cre mice showed attenuated levels of RANTES compared with ethanol-fed control mice, supporting the role of c-Jun in ethanol-induced RANTES expression. Our studies showed that ethanol-mediated RANTES/CCL5 expression occurs via HIF-1α activation independently of hypoxia. The identification of HIF-1α and AP-1 in ethanol-induced RANTES expression provides new strategies to ameliorate ethanol-induced inflammatory responses.
Pulmonary IL-17E (IL-25) Production and IL-17RB+ Myeloid Cell-Derived Th2 Cytokine Production Are Dependent upon Stem Cell Factor-Induced Responses during Chronic Allergic Pulmonary Disease
Authors: Dolgachev Vladislav , Petersen Bryan C. , Budelsky Alison L. , Berlin Aaron A. , Lukacs Nicholas W. 
Published: October 2009

Abstract
In the present studies local neutralization of allergen-induced stem cell factor (SCF) leads to decreased production of Th2 cytokines, a reduction in inflammation, allergen-specific serum IgE/IgG1, and attenuation of severe asthma-like responses. The local blockade of pulmonary SCF also resulted in a significant reduction of IL-17E (IL-25). Sorted cell populations from the lung indicated that IL-25 was produced from c-kit+ cells, whereas Th2 cytokine production was primarily from c-kit− cell populations. SCF stimulated c-kit+ eosinophils produced IL-25, whereas bone marrow-derived mast cells did not. Using 4get mice that contain a IL-4-IRES-eGFP that when transcribed coexpress GFP and IL-4, our studies identified cells that comprised a CD11b+, GR1+, Ly6C+/−, c-kit−, CD4−, CD11c−, MHC class IIlow cell population as a source of IL-4 in the lung after chronic allergen challenge. In the bone marrow a similar cell was identified with approximately a third of the IL-4+ cells also expressing c-kit+. The pulmonary and bone marrow IL-4+ cell populations were significantly reduced upon local pulmonary anti-SCF treatment. Subsequently, when IL-25R was examined during the chronic allergen responses the expression was found on the IL-4+ myeloid cell population that expressed CD11b+GR1+. Interestingly, the IL-25R+ cells in the bone marrow were also all CD11b+GR1+, similar to the lung cells, but they were also all c-kit+, potentially suggesting a maturation of the bone marrow cell once it enters the lung and/or is stimulated by SCF. Overall, these studies suggest a complex relationship between SCF, bone marrow-derived IL-25-responsive myeloid cells, Th2 cytokines, and chronic allergic disease.
Targeted Inhibition of the Complement Alternative Pathway with Complement Receptor 2 and Factor H Attenuates Collagen Antibody-Induced Arthritis in Mice
Authors: Banda Nirmal K. , Levitt Brandt , Glogowska Magdalena J. , Thurman Joshua M. , Takahashi Kazue , Stahl Gregory L. , Tomlinson Stephen , Arend William P. , Holers V. Michael 
Published: October 2009

Abstract
The alternative pathway (AP) of complement is required for the induction of collagen Ab-induced arthritis (CAIA) in mice. The objective of this study was to examine the effect of a recombinant AP inhibitor containing complement receptor 2 and factor H (CR2-fH) on CAIA in mice. CR2 binds to tissue-fixed activation fragments of C3, and the linked fH is a potent local inhibitor of the AP. CAIA was induced in C57BL/6 mice by i.p. injections of 4 mAb to type II collagen (CII) on day 0 and LPS on day 3. PBS or CR2-fH (250 or 500 μg) were injected i.p. 15 min after the mAb to CII on day 0 and 15 min after LPS on day 3; the mice were sacrificed on day 10. The disease activity score (DAS) was decreased significantly (p &lt; 0.001) in both groups receiving CR2-fH compared with the PBS. Histology scores for inflammation, pannus, bone damage, and cartilage damage decreased in parallel with the DAS. C3 deposition in the synovium and cartilage was significantly reduced (p &lt; 0.0001) in the mice treated with CR2-fH. In vitro studies with immune complexes containing type II collagen and mAb to CII showed that CR2-fH specifically inhibited the AP with minimal effect on the classical pathway (CP) and no effect on the lectin pathway (LP). The relative potency of CR2-fH in vitro was superior to mAbs to factor B and C5. Thus, CR2-fH specifically targets and inhibits the AP of complement in vitro and is effective in CAIA in vivo.
Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits
Authors: Boullier Séverine , Tanguy Myriam , Kadaoui Khalil A. , Caubet Cécile , Sansonetti Philippe , Corthésy Blaise , Phalipon Armelle 
Published: October 2009

Abstract
Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer’s patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer’s patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer’s patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-α, IL-6, Cox-2, and IFN-γ, was observed, consistent with preserved morphology. In contrast, in Peyer’s patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA.
Role of the Receptor for the Globular Domain of C1q Protein in the Pathogenesis of Hepatitis C Virus-Related Cryoglobulin Vascular Damage
Authors: Sansonno Domenico , Tucci Felicia Anna , Ghebrehiwet Berhane , Lauletta Gianfranco , Peerschke Ellinor I. B. , Conteduca Vincenza , Russi Sabino , Gatti Pietro , Sansonno Loredana , Dammacco Franco 
Published: October 2009

Abstract
Mixed cryoglobulinemia (MC) is a lymphoproliferative disorder observed in ∼10 to 15% of hepatitis C virus (HCV)-infected patients. Circulating, nonenveloped HCV core protein, which has been detected in cryoprecipitable immune complexes, interacts with immunocytes through the receptor for the globular domain of C1q protein (gC1q-R). In this study, we have evaluated circulating gC1q-R levels in chronically HCV-infected patients, with and without MC. These levels were significantly higher in MC patients than in those without MC and in healthy controls and paralleled specific mRNA expression in PBL. Soluble gC1q-R circulates as a complexed form containing both C1q and HCV core proteins. Higher serum gC1q-R levels negatively correlated with circulating concentrations of the C4d fragment. The presence of sequestered C4d in the vascular bed of skin biopsies from MC patients was indicative of in situ complement activation. In vitro studies showed that release of soluble gC1q-R is regulated by HCV core-mediated inhibition of cell proliferation. Our results indicate that up-regulation of gC1q-R expression is a distinctive feature of MC, and that dysregulated shedding of C1q-R molecules contributes to vascular cryoglobulin-induced damage via the classic complement-mediated pathway.
Decorating Liquid Crystal Surfaces with Proteins for Real‐Time Detection of Specific Protein–Protein Binding
Authors: Hartono Deny , Xue Chang‐Ying , Yang Kun‐Lin , Yung Lin‐Yue Lanry 
Published: October 2009

AbstractHere, a novel method of immobilizing proteins with well‐defined orientation directly on liquid crystal surfaces that allow subsequent real‐time imaging of specific protein–protein binding events on these surfaces is reported. Self‐assembly of nitrilotriacetic acid terminated amphiphiles loaded with Ni2+ ions at aqueous‐liquid crystal interface creates a surface capable of immobilizing histidine‐tagged ubiquitin through complex formation between Ni2+ and histidine. When these surfaces containing immobilized histidine‐tagged ubiquitin are exposed to anti‐ubiquitin antibody, the spatial and temporal of specific protein–protein binding events trigger orientational transitions of liquid crystals. As a result, sharp liquid crystal optical switching from dark to bright can readily be observed under polarized lighting. The protein–protein binding can be observed within seconds and only requires nanogram quantities of proteins. This work demonstrates a simple strategy to immobilize proteins with well‐defined orientation on liquid crystal surfaces for real‐time and label‐free detection of specific protein–protein binding events, which may find use in biomedical diagnostics.
Foldable Printed Circuit Boards on Paper Substrates
Authors: Siegel Adam C. , Phillips Scott T. , Dickey Michael D. , Lu Nanshu , Suo Zhigang , Whitesides George M. 
Published: October 2009

AbstractThis paper describes several low‐cost methods for fabricating flexible electronic circuits on paper. The circuits comprise i) metallic wires (e.g., tin or zinc) that are deposited on the substrate by evaporation, sputtering, or airbrushing, and ii) discrete surface‐mountable electronic components that are fastened with conductive adhesive directly to the wires. These electronic circuits—like conventional printed circuit boards—can be produced with electronic components that connect on both sides of the substrate. Unlike printed circuit boards made from fiberglass, ceramics, or polyimides, however, paper can be folded and creased (repeatedly), shaped to form three‐dimensional structures, trimmed using scissors, used to wick fluids (e.g., for microfluidic applications) and disposed of by incineration. Paper‐based electronic circuits are thin and lightweight; they should be useful for applications in consumer electronics and packaging, for disposable systems for uses in the military and homeland security, for applications in medical sensing or low‐cost portable diagnostics, for paper‐based microelectromechanical systems, and for applications involving textiles.
Neutral Tridentate PNP Ligands and Their Hybrid Analogues: Versatile Non‐Innocent Scaffolds for Homogeneous Catalysis
Authors: van der Vlugt Jarl Ivar , Reek Joost N. H. 
Published: October 2009

AbstractLigands in coordination chemistry and homogeneous catalysis are traditionally “static” spectators that do not actively participate in the catalytic cycle. However, such classic systems do not provide additional “handles” that could facilitate or trigger alternative productive reaction pathways. Recent advances in the use of novel nitrogen‐centered pincer systems have unveiled interesting opportunities for cooperative catalysis. The chemistry of pyridine‐derived, neutral ligands is discussed, with a specific focus on their non‐innocent behavior and potential as facilitators for metal‐mediated organic transformations. This overview should provide inspiration and an incentive to incorporate non‐innocent ligands and their metal complexes within old and new homogeneously catalyzed reactions.