bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of Using Plasma Rather Than Serum in First and Second Trimester Multiple Marker Down's Syndrome Screening
Authors: Lambert-Messerlian Geralyn M , Palomaki Glenn E , Eklund Elizabeth E , Kloza Edward M , Neveux Louis M , Phipps Maureen G , Canick Jacob A 
Published: April 2013

Objective To compare maternal plasma with serum for measuring markers currently used in first and second trimester screening for Down's syndrome. Setting A laboratory-based investigation of two sample types in assays used in prenatal screening for Down's syndrome. Methods A paired data-set included both plasma and serum from 101 pregnant women. A nested case/control data-set included only plasma samples from 34 first and 23 second trimester Down's syndrome pregnancies, each matched with six euploid controls. Analyte levels were measured and converted to multiples of the median (MoM). Results In the paired data-set, each of the five analytes (alphafetoprotein, unconjugated estriol, human chorionic gonadotropin, inhibin-A and pregnancy-associated plasma protein A) in serum and plasma was highly correlated (r > 0.970) and after conversion to MoM, the resulting distributions were equivalent ( P > 0.7). In the matched data-set, plasma-based median MoM levels in cases were consistent with the published serum counterparts for all markers. Conclusions This study provides strong evidence that current serum-based prenatal screening can be performed equally well using plasma samples. This may prove useful, especially if secondary screening using a DNA-based test requires maternal plasma.
β-Blocker Use and Incidence of Chronic Obstructive Pulmonary Disease Exacerbations
Authors: Farland Michelle Z , Peters Cassey J , Williams Juli D , Bielak Kenneth M , Heidel R Eric , Ray Shaunta' M 
Published: April 2013

BACKGROUND β-Adrenergic antagonist (β-blocker) use in patients with chronic obstructive pulmonary disease (COPD) has been avoided as a result of potential risk of pulmonary adverse effects. However, recent studies indicate that β-blocker use in patients with COPD can decrease outpatient visits and either decrease or have no effect on the number of hospitalizations. Long-term treatment with β-blockers has been shown to increase survival and decrease exacerbations in patients with COPD. OBJECTIVE To assess the impact of β-blocker use on the incidence of exacerbations in patients with COPD. METHODS In a retrospective cohort study of patients with COPD from 2 academic primary care practice sites who were seen in 2010, patients were identified using International Classification of Diseases, 9th revision, Clinical Modification codes for COPD and reviewing active medication lists for COPD-specific medications (tiotropium). Patients were classified as either a β-blocker user or a nonuser. Primary outcomes were incidence and severity of COPD exacerbations. Secondary outcomes included COPD exacerbations distinguished by β-blocker cardioselectivity and all-cause hospitalizations. RESULTS The study enrolled 412 patients. Of those, 166 patients were β-blocker users and 246 were β-blocker nonusers. β-Blocker users were less likely to have a COPD exacerbation (OR 0.61, 95% CI 0.40–0.93) and had fewer mild exacerbations (OR 0.56; 95% CI 0.34–0.89). There was no significant difference in COPD exacerbations based on β-blocker cardioselectivity (OR 0.84, 95% CI 0.38–1.83). When controlled for, using a backwards stepwise logistic regression, β-blocker use was a variable in the model that predicted exacerbations but alone was not statistically significant (adjusted OR 0.62, 95% CI 0.39–1.01). CONCLUSIONS Patients with COPD prescribed a β-blocker were significantly less likely to have a COPD exacerbation and had fewer mild COPD exacerbations.
Individual Optimal Frequency in Whole-Body Vibration: Effect of Protocol, Joint Angle, and Fatiguing Exercise
Authors: Carlucci Flaminia , Felici Francesco , Piccinini Alberto , Haxhi Jonida , Sacchetti Massimo 
Published: April 2013

AbstractCarlucci, F, Felici, F, Piccinini, A, Haxhi, J, and Sacchetti, M. Individual optimal frequency in whole-body vibration: effect of protocol, joint angle, and fatiguing exercise.J Strength Cond Res30(12): 3503–3511, 2016—Recent studies have shown the importance of individualizing the vibration intervention to produce greater effects on the neuromuscular system in less time. The purpose of this study was to assess the individual optimal vibration frequency (OVF) corresponding to the highest muscle activation (RMSmax) during vibration at different frequencies, comparing different protocols. Twenty-nine university students underwent 3 continuous (C) and 2 random (R) different vibrating protocols, maintaining a squat position on a vibration platform. The C protocol lasted 50 seconds and involved the succession of ascending frequencies from 20 to 55 Hz, every 5 seconds. The same protocol was performed twice, having the knee angle at 120° (C) and 90° (C90), to assess the effect of joint angle and after a fatiguing squatting exercise (CF) to evaluate the influence of fatigue on OVF assessment. In the random protocols, vibration time was 20 seconds with a 2-minute (R2) and a 4-minute (R4) pauses between tested frequencies. Muscle activation and OVF values did not differ significantly in the C, R2, and R4 protocols. RMSmaxwas higher in C90 (p< 0.001) and in CF (p= 0.04) compared with the C protocol. Joint angle and fatiguing exercise had no effect on OVF. In conclusion, the shorter C protocol produced similar myoelectrical activity in the R2 and the R4 protocols, and therefore, it could be equally valid in identifying the OVF with considerable time efficiency. Knee joint angle and fatiguing exercise had an effect on surface electromyography response during vibration but did not affect OVF identification significantly.
Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma
Authors: Hermsen Ilse G C , Haak Harm R , de Krijger Ronald R , Kerkhofs Thomas M A , Feelders Richard A , de Herder Wouter W , Wilmink Hanneke , Smit Jan W A , Gelderblom Hans , de Miranda Noel F C C , van Eijk Ronald , van Wezel Tom , Morreau Hans 
Published: April 2013

BackgroundAdrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first-line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinical importance. The epidermal growth factor receptor (EGFR) has been implicated in the development of one-third of all malignancies. EGFR pathway members in ACC have been investigated, however, without available clinical data and relation to survival.MethodsIn this study, mutation status of EGFR and downstream signalling pathways was evaluated in 47 ACC patients on mitotane using direct sequencing, a TaqMan allele-specific assay and immunohistochemistry. Archival formalin-fixed paraffin-embedded tumour tissue was used for all analyses. Patient data were obtained anonymously, after coupling with the collected tumour tissue.ResultsOne BRAF, two EGFR TK domain (c.2590G>A, p.864A>T) and 11 TP53, but no PIK3CA or KRAS, mutations were found. No relationship was found between mutation status, immunostaining and mitotane response or survival.ConclusionIn conclusion, our data suggest that the role of EGFR tyrosine kinase inhibitors in ACC is limited. Treatment with EGFR monoclonal antibodies on the other hand might be beneficial for a larger group of patients. The possible efficacy of this therapy in ACC should be evaluated in future trials.
The Pleasure of the Spectator
Authors: Ubersfeld Anne 
Published: April 2013

Brecht's optimism: for him, pleasure and knowledge go hand in hand; knowing and enjoying are but one. … He uses the word pleasure, but he also, impudently, refers to sensual pleasure [jouissance], which means much more. One can say almost anything about the spectator's pleasure, and the most contradictory formulas can appear valid: the pleasure of liking and of disliking; the pleasure of understanding and of not understanding; the pleasure of maintaining an intellectual distance and of being carried away by one's emotions; the pleasure of following a story ("and what happens next?" the child asks) and of looking at a tableau; the pleasure of laughing and of crying; the pleasure of dreaming and of knowing; the pleasure of enjoying oneself and of suffering; the pleasure of desiring and of being protected from passions. … One can continue forever this little game of oppositions'.
>Role Constraints versus Self-Identity in La tejedora de sueiios and Anillos para una dama
Authors: Rogers Elizabeth 
Published: April 2013

In this study I would like to elaborate on this dilemma of role demands versus personal desires as it relates to two twentieth-century Spanish dramas. While both of these dramas are based on the mythic stories of legendary heroes, Ulysses and the Cid, the focus is nevertheless not on the heroes themselves, but rather on their wives, Penelope and Jimena. Both women have come to be prototype figures who represent the loyal, faithful, passive but supportive wife whose love for her husband is exemplary and unquestioned. In La tejedora de suenos (The Weaver of Dreams) (1952), Antonio Buero Vallejo asks what life might have been like for Penelope during Ulysses' twenty-year absence, whereas Antonio Gala in Anillos para una dama (Rings for a Lady) (1973) speculates on Jimena's life after the Cid's death.
Book Reviews
Authors: Parkin Andrew , Leland Charles , Laughlin Karen , Schlueter June , Jacobs Barry , Gale Steven , Hinden Michael , Innes Christopher 
Published: April 2013

James Simmons, Sean O'Casey, reviewed by Andrew Parkin Robert G. Lowery And Patricia Angelin, eds., My Very Dear Sean: George Jean Nathan to Sean O'Casey, Letters and Articles, reviewed by Andrew Parkin Thomas Postwait, ed., William Archer on Ibsen: The Major Essays, 1889-1919, reviewed by Charles Leland Helene Keyssar, Feminist Theatre: An Introduction to Plays a/Contemporary British and American Women, reviewed by Karen Laughlin Elizabeth J. Natalle, Feminist Theatre: A Study in Persuasion, reviewed by Karen Laughlin Lise-Lone Marker and Frederick J. Marker, Ingmar Bergman: Four Decades in the Theater, reviewed by Barry Jacobs C.W.E. Bigsby, A Critical Introduction to Twentieth-Cemury American Drama, Volume Two: Williams/Miller/Albee, reviewed by June Schlueter Leslie Kane, The Language a/Silence: On the Unspoken and Unspeakable in Modern Drama, reviewed by Stepven H. Gale Judith E. Barlow, Final Acts: The Creation of Three Late O'Neill Plays, reviewed by Michael Hinden George Rowell and Anthony Jackson, The Repertory Movement: A History of Regional Theatre ill Britain, reviewed by Christopher Innes
The Snark and the Orchard: A Polemical Afterword
Authors: Bryden Ronald 
Published: April 2013

We need a new way of talking about plays. For more than half a century, universities have been teaching drama as a subject distinct from literature — Carnegie Tech began it in 1914, Yale followed in 1925, and most English-speaking universities got on the bandwagon during the boom in higher education after World War II. The rationale for creating all those drama departments was that plays could not be known by reading their texts: the text is to a play what a blueprint is to a building, and the play itself comes to life only in performance. The problem is that no drama department has yet found a way of staging more than ten or twelve plays in the eight months of an academic year — you can just squeeze in four major productions. with six weeks of rehearsal, and six or eight studio productions. This means that a bachelor of arts in drama emerges from a four-year program having studied perhaps fifty plays in performance. The rest of hi s or her knowledge of the drama of the world comes from reading play texts as literature, just like people in departments of English and Comparative Literature.
Ilario Doria, le gambros génois de Manuel II Palaiologos : beau-frère ou gendre ?
Authors: Ganchou Thierry 
Published: April 2013

The Genoese Ilario Doria is thought to be the son-in-law of Manuel II, that is, the husband of the latter’s natural daughter Zambia Palaiologina. This information comes exclusively from patriarchal chronicles of the 16th century, whereas contemporary Greek sources call Ilario simply Manuel’s gambros,
an ambiguous word which means both son-in-law and brother-in-law. The anonymous authors of the patriarchal chronicles chose the former meaning. But contemporary western documents always present Ilario as Manuel’s brother-in-law : cognatus, levir or sororius. Ilario was thus manuel’s gambros
through the latter’s sister, not his daughter. he had married a natural daughter of John V whose name is unknown, the name zambia given in the patriarchal chronicles being in fact that of Ilario’s eldest daughter who married an ottoman prince.
Quelles pratiques pour une connaissance fondée sur l'action ? Le cas dune recherche-action en contrôle
Authors: Pastorelli Ivan 
Published: April 2013

Les recherches-actions permettent de comprendre en profondeur un contexte organisationnel particulier, mais le chercheur a dans ce cadre une double contrainte de légitimité : celle de l’organisation, qui le rémunère pour résoudre un problème perçu, et celle de ses pairs, qui le jugent à sa capacité à produire des connaissances scientifiques. La conciliation de ses deux objectifs lui impose alors de se doter d’un dispositif apte à « objectiver des informations subjectives. » Grâce à une recherche de ce type menée dans un établissement subissant de sa tutelle une réforme de ses modes de gestion, nous avons montré l’inexistence des leviers d’action organisationnels sur lesquels pensait pouvoir s’appuyer la tutelle, et mis en évidence des effets pervers remettant en cause les objectifs même de cette réforme.
Local “On-Demand” Generation and Function of Antigen-Specific Foxp3+ Regulatory T Cells
Authors: McPherson Scott W. , Heuss Neal D. , Gregerson Dale S. 
Published: April 2013

Abstract
Extrathymically derived regulatory T cells (iTregs) protect against autoimmunity to tissue-specific Ags. However, whether Ag-specific iTreg generation and function is limited to secondary lymphoid tissue or whether it can occur within the tissue-specific local environment of the cognate Ag remains unresolved. Mice expressing β-galactosidase (βgal) on a retina-specific promoter (βgal mice) in conjunction with mice expressing GFP and diphtheria toxin (DTx) receptor (DTR) under control of the Foxp3 promoter, and βgal-specific TCR transgenic (BG2) mice were used to examine this question. Local depletion (ocular DTx), but not systemic depletion (i.p. DTx), of βgal-specific iTregs enhanced experimental autoimmune uveoretinitis induced by activated βgal-specific effector T cells. Injections of small amounts of βgal into the anterior chamber of the eye produced similar numbers of βgal-specific iTregs in the retina whether the mouse was depleted of pre-existing, circulating Tregs. Taken together, these results suggest that protection from tissue-specific autoimmunity depends on the function of local Ag-specific iTregs and that the retina is capable of local, “on-demand” iTreg generation that is independent of circulating Tregs.
Acidic Amino Acid Residues in the Juxtamembrane Region of the Nucleotide-Sensing TLRs Are Important for UNC93B1 Binding and Signaling
Authors: Kim Jihee , Huh Jiwon , Hwang Misun , Kwon Eun-Hye , Jung Da-Jung , Brinkmann Melanie M. , Jang Myoung Ho , Ploegh Hidde L. , Kim You-Me 
Published: April 2013

Abstract
TLRs are divided into two groups based on their subcellular localization patterns. TLR1, 2, 4, 5, and 6 are expressed on the cell surface, whereas the nucleotide-sensing TLRs, such as TLR3, 7, 8, and 9 stay mainly inside cells. The polytopic membrane protein UNC93B1 physically interacts with the nucleotide-sensing TLRs and delivers them from the endoplasmic reticulum to endolysosomes, where the TLRs recognize their ligands and initiate signaling. In cells with nonfunctional UNC93B1, the nucleic acid–sensing TLRs fail to exit the endoplasmic reticulum and consequently do not signal. However, the detailed molecular mechanisms that underlie the UNC93B1-mediated TLR trafficking remain to be clarified. All nucleotide-sensing TLRs contain acidic amino acid residues in the juxtamembrane region between the leucine-rich repeat domain and the transmembrane segment. We show that the D812 and E813 residues of TLR9 and the D699 and E704 residues of TLR3 help to determine the interaction of these TLRs with UNC93B1. Mutation of the acidic residues in TLR3 and TLR9 prevents UNC93B1 binding, as well as impairs TLR trafficking and renders the mutant receptors incapable of transmitting signals. Therefore, the acidic residues in the juxtamembrane region of the nucleotide-sensing TLRs have important functional roles.
Hemorrhagic Shock Augments Nlrp3 Inflammasome Activation in the Lung through Impaired Pyrin Induction
Authors: Xu Peng , Wen Zongmei , Shi Xueyin , Li Yuehua , Fan Liyan , Xiang Meng , Li Aijun , Scott Melanie J. , Xiao Guozhi , Li Song , Billiar Timothy R. , Wilson Mark A. , Fan Jie 
Published: April 2013

Abstract
Hemorrhagic shock (HS) promotes the development of systemic inflammatory response syndrome and organ injury by activating and priming the innate immune system for an exaggerated inflammatory response through, as of yet, unclear mechanisms. IL-1β also plays an important role in the development of post-HS systemic inflammatory response syndrome and active IL-1β production is tightly controlled by the inflammasome. Pyrin, a protein of 781 aa with pyrin domain at the N-terminal, negatively regulates inflammasome activation through interaction with nucleotide-binding oligomerization domain–like receptor protein (NLRP). Expression of pyrin can be induced by LPS and cytokines, and IL-10 is a known potent inducer of pyrin expression in macrophages. In the current study, we tested the hypothesis that HS downregulates IL-10 and therefore decreases pyrin expression to promote inflammasome activation and subsequent IL-1β processing and secretion in the lungs. Our results show that LPS, while activating Nlrp3 inflammasome in the lungs, also induced pyrin expression, which in turn suppressed inflammasome activation. More importantly, LPS-mediated upregulation of IL-10 enhanced pyrin expression, which serves, particularly in later phases, as a potent negative-feedback mechanism regulating inflammasome activation. However, HS-mediated suppression of IL-10 expression in alveolar macrophages attenuated the upregulation of pyrin in alveolar macrophages and lung endothelial cells and thereby significantly enhanced inflammasome activation and IL-1β secretion in the lungs. This study demonstrates a novel mechanism by which HS suppresses negative-feedback regulation of Nlrp3 inflammasome to enhance IL-1β secretion in response to subsequent LPS challenge and so primes for inflammation.
Lymphotoxin β Receptor Regulates the Development of CCL21-Expressing Subset of Postnatal Medullary Thymic Epithelial Cells
Authors: Lkhagvasuren Enkhsaikhan , Sakata Mie , Ohigashi Izumi , Takahama Yousuke 
Published: April 2013

Abstract
Medullary thymic epithelial cells (mTECs) play a pivotal role in the establishment of self-tolerance in T cells by ectopically expressing various tissue-restricted self-Ags and by chemoattracting developing thymocytes. The nuclear protein Aire expressed by mTECs contributes to the promiscuous expression of self-Ags, whereas CCR7-ligand (CCR7L) chemokines expressed by mTECs are responsible for the attraction of positively selected thymocytes. It is known that lymphotoxin signals from the positively selected thymocytes preferentially promote the expression of CCR7L rather than Aire in postnatal mTECs. However, it is unknown how lymphotoxin signals differentially regulate the expression of CCR7L and Aire in mTECs and whether CCR7L-expressing mTECs and Aire-expressing mTECs are distinct populations. In this study, we show that the majority of postnatal mTECs that express CCL21, a CCR7L chemokine, represent an mTEC subpopulation distinct from the Aire-expressing mTEC subpopulation. Interestingly, the development of CCL21-expressing mTECs, but not Aire-expressing mTECs, is impaired in mice deficient in the lymphotoxin β receptor. These results indicate that postnatal mTECs consist of heterogeneous subsets that differ in the expression of CCL21 and Aire, and that lymphotoxin β receptor regulates the development of the CCL21-expressing subset rather than the Aire-expressing subset of postnatal mTECs.
CD43-Mediated IFN-γ Production by CD8+ T Cells Promotes Abdominal Aortic Aneurysm in Mice
Authors: Zhou Hui-fang , Yan Huimin , Cannon Judy L. , Springer Luke E. , Green Jonathan M. , Pham Christine T. N. 
Published: April 2013

AbstractCD43 is a glycosylated surface protein abundantly expressed on lymphocytes. Its role in immune responses has been difficult to clearly establish, with evidence supporting both costimulatory and inhibitory functions. In addition, its contribution to disease pathogenesis remains elusive. Using a well-characterized murine model of elastase-induced abdominal aortic aneurysm (AAA) that recapitulates many key features of the human disease, we established that the presence of CD43 on T cells is required for AAA formation. Moreover, we found that IFN-γ–producing CD8+ T cells, but not CD4+ T cells, promote the development of aneurysm by enhancing cellular apoptosis and matrix metalloprotease activity. Reconstitution with IFN-γ–producing CD8+ T cells or recombinant IFN-γ promotes the aneurysm phenotype in CD43−/− mice, whereas IFN-γ antagonism abrogates disease in wild-type animals. Furthermore, we showed that the presence of CD43 with an intact cytoplasmic domain capable of binding to ezrin-radixin-moesin cytoskeletal proteins is essential for optimal in vivo IFN-γ production by T cells and aneurysm formation. We have thus identified a robust physiologic role for CD43 in a relevant animal model and established an important in vivo function for CD43-dependent regulation of IFN-γ production. These results further suggest that IFN-γ antagonism or selective blockade of CD43+CD8+ T cell activities merits further investigation for immunotherapy in AAA.
IL-22 Deficiency Alters Colonic Microbiota To Be Transmissible and Colitogenic
Authors: Zenewicz Lauren A. , Yin Xiaochen , Wang Guoyang , Elinav Eran , Hao Liming , Zhao Liping , Flavell Richard A. 
Published: April 2013

Abstract
IL-22 is a good candidate to play a critical role in regulating gut microbiota because it is an important inducer of antimicrobial peptides and mucins in the gut. However, whether IL-22 participates in immune homeostasis by way of modulating gut microbiota remains to be elucidated. In this study, we find, through 16S rRNA gene-pyrosequencing analysis, that healthy IL-22–deficient mice had altered colonic microbiota, notably with decreased abundance of some genera, including Lactobacillus, and increased levels of others. Mice harboring this altered microbiota exhibited more severe disease during experimentally induced colitis. Interestingly, this altered gut microbiota can be transmitted to cohoused wild-type animals along with the increased susceptibility to this colitis, indicating an important role for IL-22 in shaping the homeostatic balance between immunity and colonic microbiota for host health.