bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating a Simple Discharge Planning Tool Following Hospital Admission for an Isolated Lower Limb Fracture
Authors: Kimmel Lara A. , Holland Anne E. , Simpson Pam M. , Edwards Elton R. , Gabbe Belinda J. 
Published: April 2014

Background
Early, accurate prediction of discharge destination from the acute hospital assists individual patients and the wider hospital system. The Trauma Rehabilitation and Prediction Tool (TRaPT), developed using registry data, determines probability of inpatient rehabilitation discharge for patients with isolated lower limb fractures.

Objective
The aims of this study were: (1) to prospectively validatate the TRaPT, (2) to assess whether its performance could be improved by adding additional demographic data, and (3) to simplify it for use as a bedside tool.

Design
This was a cohort, measurement-focused study.

Methods
Patients with isolated lower limb fractures (N=114) who were admitted to a major trauma center in Melbourne, Australia, were included. The participants' TRaPT scores were calculated from admission data. Performance of the TRaPT score alone, and in combination with frailty, weight-bearing status, and home supports, was assessed using measures of discrimination and calibration. A simplified TRaPT was developed by rounding the coefficients of variables in the original model and grouping age into 8 categories. Simplified TRaPT performance measures, including specificity, sensitivity, and positive and negative predictive values, were evaluated.

Results
Prospective validation of the TRaPT showed excellent discrimination (C-statistic=0.90 [95% confidence interval=0.82, 0.97]), a sensitivity of 80%, and specificity of 94%. All participants able to weight bear were discharged directly home. Simplified TRaPT scores had a sensitivity of 80% and a specificity of 88%.

Limitations
Generalizability may be limited given the compensation system that exists in Australia, but the methods used will assist in designing a similar tool in any population.

Conclusions
The TRaPT accurately predicted discharge destination for 80% of patients and may form a useful aid for discharge decision making, with the simplified version facilitating its use as a bedside tool.
Treadmill Training After Surgical Removal of a Spinal Tumor in Infancy
Authors: Heathcock Jill C. , Christensen Catie , Bush Karah , Butler Marisa , Buehner Jeffrey J. , Basso D. Michele 
Published: April 2014

Background and PurposeStep training on a treadmill is a common intervention for adult and pediatric patients with spinal cord injuries (SCI). Treadmill training has not been used as an intervention for infants and toddlers with SCI before walking onset. This case report describes the intervention and stepping behaviors on a treadmill and overground of a toddler after the surgical removal of a rare spinal tumor resulting in SCI.Case DescriptionThe toddler presented with an inability to step on the left, rare stepping on the right, and an apparent lack of sensation in the lower extremities. After spinal tumor excision at 5.5 weeks of age, step training on a treadmill and overground occurred once per week from 15 to 35 months of age in addition to traditional physical therapy.OutcomesIndependent symmetrical stepping emerged both on and off the treadmill over 20 months. Improvements in the number and pattern of steps occurred with training. Walking speed increased, and milestones important to overground walking developed.DiscussionIndependent steps developed during the intervention with little motor development of the lower extremities during the first year of life. Furthermore, improvements in stepping alternation, standing, and walking occurred despite no evidence of sensation in the lower extremities.
Altered brain connectivity in sagittal craniosynostosis
Authors: Beckett Joel S. , Brooks Eric D. , Lacadie Cheryl , Wyk Brent Vander , Jou Roger J. , Steinbacher Derek M. , Constable R. Todd , Pelphrey Kevin A. , Persing John A. 
Published: April 2014

Object
Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC.

Methods
Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite.

Results
Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC < control group) in mean diffusivity were localized to the right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: −6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates −31, −61, 34), posterior cingulate cortex (MNI coordinates 13, −52, 18), precuneus (MNI coordinates 10, −55, 54), left and right parahippocampus (MNI coordinates −13, −52, 2 and MNI coordinates 11, −50, 2, respectively), lingual (MNI coordinates −11, −86, −10), and fusiform gyri (MNI coordinates −30, −79, −18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices (MNI coordinates −5, −35, 34 and MNI coordinates 6, −42, 39, respectively) were negatively correlated to right hemisphere precuneus (MNI coordinates 6, −71, 46), while the left ventromedial prefrontal cortex (MNI coordinates 6, 34, −8) was negatively correlated to right middle frontal gyrus (MNI coordinates 40, 4, 33). All group comparisons (sNSC vs controls) were conducted at a whole brain–corrected threshold of p < 0.05.

Conclusions
This study demonstrates altered neocortical structural and functional connectivity in sNSC that may, in part or substantially, underlie the neuropsychological deficits commonly reported in this population. Future studies combining analysis of multimodal MRI and clinical characterization data in larger samples of participants are warranted.
André Mazon et les études slaves : Introduction
Authors: Gonneau Pierre 
Published: April 2014

André Mazon et les études slaves
Introduction

André Mazon passed away on july 13th 1967. This issue of the Revue des études slaves takes a look back at a distinguished man who actively studied and traveled the Slavic world for more than sixty years, through wars, revolutions and academic turmoils. In France, he was instrumental to the development of Slavic studies with his teaching first at Strasbourg University, then at the Collège de France, and with his many publications. He was also as an organizer, a long-time head of the Institut d’études slaves, a pillar of the redaction of the Revue des études slaves, and an untiring defender of scientific relations with other slavists. Jean Breuillard draws a complete picture of Mazon’s legacy as a linguist. Robert Roudet revisits the famous controversy Mazon raised by his skepticism about the authenticity of the Slovo o Polku Igoreve, uniting against himself Roman Jakobson and Dmitrij Lixačev. Antoine Marès shows us Mazon practising his ‘religion of exchanges’ and maintaining or restoring scientific ties with the Slavic countries, in spite of their ideological transformations. Vladislav Rjéoutski studies the particular case of relations with Soviet Russia. Finally, Edward L. Keenan gives us the point of view of a disciple of Roman Jakobson who nevertheless shares Mazon’s views about the Slovo.
Sur le pas de la porte
Authors: Tuset Annabelle 
Published: April 2014

A travers l’histoire clinique de Soufiane, adolescent issu de migrants présentant des troubles du comportement graves, l’auteur tentera d’établir un lien entre un investissement particulier de l’espace géographique (espace où le corps prend nécessairement place) : appréhension de l’espace de la ville, de la consultation ou de l’école mais aussi de la maison, et une impossibilité d’investissement de l’espace interne. La notion de la formation de l’identité, élaboration fondamentale à l’adolescence, apparaissant en arrière-plan tout au long du trajet de Soufiane.
Cutting Edge: Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells Suppress Autoimmunity while Establishing Transplantation Tolerance
Authors: Adeegbe Dennis , Bayer Allison L. , Levy Robert B. , Malek Thomas R. 
Published: April 2014

Abstract
An important unresolved question with regard to T regulatory (Treg) cell specificity and suppressive activity is whether allogeneic Treg cells inhibit self-reactive T cells. In the present study, this issue was addressed using IL-2Rβ-deficient mice that develop rapid lethal autoimmunity due to impaired production of Treg cells. We show that adoptive transfer of completely MHC-mismatched Treg cells into IL-2Rβ−/− mice resulted in life-long engraftment of the donor cells, which exhibited skewed reactivity toward host alloantigens, and prevented autoimmunity. Thus, Treg cells that underwent thymic selection by peptide/MHC class II complexes distinct from those recognized by autoreactive T cells, still effectively suppress autoimmunity. Remarkably, when such animals were skin grafted, they exhibited dominant tolerance to those grafts bearing MHC molecules that were shared with donor Treg cells. Collectively, these data demonstrate that effective engraftment by allogeneic Treg cells controls autoimmunity and results in permissive conditions for long-term acceptance of allografts.
Transgenic Galectin-1 Induces Maturation of Dendritic Cells That Elicit Contrasting Responses in Naive and Activated T Cells
Authors: Perone Marcelo J. , Larregina Adriana T. , Shufesky William J. , Papworth Glenn D. , Sullivan Mara L. G. , Zahorchak Alan F. , Stolz Donna Beer , Baum Linda G. , Watkins Simon C. , Thomson Angus W. , Morelli Adrian E. 
Published: April 2014

AbstractDendritic cells (DC) are professional APC that control the balance between T cell immunity and tolerance. Genetic engineering of DC to regulate the outcome of the immune response is an area of intense research. Galectin (gal)-1 is an endogenous lectin that binds to glycoproteins and exerts potent regulatory effects on T cells. Consequently, gal-1 participates in central deletion of thymocytes and exerts therapeutic effects on experimental models of T cell-mediated autoimmune disorders and graft-vs-host disease. Together, these observations strongly indicate that engineering DC to express transgenic (tg) gal-1 may be beneficial to treat T cell-mediated disorders. In this study, we have investigated the impact of the expression of high levels of tg gal-1 on maturation/activation of DC and on their T cell stimulatory function. Murine DC were transduced with a recombinant adenovirus encoding hu gal-1 (gal-1-DC). Tg gal-1 was exported by a nonclassical pathway through exosomes and was retained on the DC surface inducing segregation of its ligand CD43. Expression of tg gal-1 triggered activation of DC determined by induction of a more mature phenotype, increased levels of mRNA for proinflammatory cytokines, and enhanced ability to stimulate naive T cells. Conversely, gal-1-DC induced rapid apoptosis of activated T cells. In vivo, gal-1-DC increased significantly the sensitization phase of contact hypersensitivity assays while inducing a drastic inhibition of the elicitation phase by triggering apoptosis of activated T cells in the dermis. Gal-1-DC represent a novel tool to control differentially the afferent and efferent arms of the T cell response.
IL-2 Is Required for the Activation of Memory CD8+ T Cells via Antigen Cross-Presentation
Authors: Blachère Nathalie E. , Morris Heather K. , Braun Deborah , Saklani Hélène , Di Santo James P. , Darnell Robert B. , Albert Matthew L. 
Published: April 2014

AbstractDendritic cells (DCs) are capable of capturing exogenous Ag for the generation of MHC class I/peptide complexes. For efficient activation of memory CD8+ T cells to occur via a cross-presentation pathway, DCs must receive helper signals from CD4+ T cells. Using an in vitro system that reflects physiologic recall memory responses, we have evaluated signals that influence helper-dependent cross-priming, while focusing on the source and cellular target of such effector molecules. Concerning the interaction between CD4+ T cells and DCs, we tested the hypothesis that CD40 engagement on DCs is critical for IL-12p70 (IL-12) production and subsequent stimulation of IFN-γ release by CD8+ T cells. Although CD40 engagement on DCs, or addition of exogenous IL-12 are both sufficient to overcome the lack of help, neither is essential. We next evaluated cytokines and chemokines produced during CD4+ T cell/DC cross talk and observed high levels of IL-2 produced within the first 18–24 h of Ag-specific T cell engagement. Functional studies using blocking Abs to CD25 completely abrogated IFN-γ production by the CD8+ T cells. Although required, addition of exogenous IL-2 did not itself confer signals sufficient to overcome the lack of CD4+ T cell help. Thus, these data support a combined role for Ag-specific, cognate interactions at the CD4+ T cell/DC as well as the DC/CD8+ T cell interface, with the helper effect mediated by soluble noncognate signals.
Chronic Immune Therapy Induces a Progressive Increase in Intratumoral T Suppressor Activity and a Concurrent Loss of Tumor-Specific CD8+ T Effectors in her-2/neu Transgenic Mice Bearing Advanced Spontaneous Tumors
Authors: Nair Raji E. , Kilinc Mehmet O. , Jones Stacy A. , Egilmez Nejat K. 
Published: April 2014

AbstractA single intratumoral injection of IL-12 and GM-CSF-encapsulated microspheres induces the complete regression of advanced spontaneous tumors in her-2/neu transgenic mice. However, tumor regression in this model is transient and long-term cure is not achieved due to recurrence. Posttherapy molecular analysis of immune activation/suppression markers within the tumor microenvironment demonstrated a dramatic up-regulation of IFN-γ and a concomitant down-regulation of Forkhead/winged-helix protein 3 (Foxp3), TGFβ, and IL-10 expression. Therapy-induced reversion of immune suppression was transient since all three markers of suppression recovered rapidly and surpassed pretherapy levels by day 7 after treatment, resulting in tumor resurgence. Repeated treatment enhanced short-term tumor regression, but did not augment long-term survival. Serial long-term analysis demonstrated that although chronic stimulation enhanced the IFN-γ response, this was countered by a parallel increase in Foxp3, TGFβ, and IL-10 expression. Analysis of tumor-infiltrating T lymphocyte populations showed that the expression of Foxp3 and IL-10 was associated with CD4+CD25+ T cells. Repeated treatment resulted in a progressive increase in tumor-infiltrating CD4+CD25+Foxp3+ T suppressor cells establishing their role in long-term neutralization of antitumor activity. Analysis of tumor-infiltrating CD8+ T cells demonstrated that although treatment enhanced IFN-γ production, antitumor cytotoxicity was diminished. Monitoring of CD8+ T cells that specifically recognized a dominant MHC class I her-2/neu peptide showed a dramatic increase in tetramer-specific CD8+ T cells after the first treatment; however, continuous therapy resulted in the loss of this population. These results demonstrate that both enhanced suppressor activity and deletion of tumor-specific T cells are responsible for the progressive loss of efficacy that is associated with chronic immune therapy.
Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells
Authors: Yu Xue-Zhong , Liang Yaming , Nurieva Roza I. , Guo Fei , Anasetti Claudio , Dong Chen 
Published: April 2014

AbstractICOS, a CD28 family member expressed on activated CD4+ and CD8+ T cells, plays important roles in T cell activation and effector function. Here we studied the role of ICOS in graft-vs-host disease (GVHD) mediated by CD4+ or CD8+ T cells in allogeneic bone marrow transplantation. In comparison of wild-type and ICOS-deficient T cells, we found that recipients of ICOS−/− CD4+ T cells exhibited significantly less GVHD morbidity and delayed mortality. ICOS−/− CD4+ T cells had no defect in expansion, but expressed significantly less Fas ligand and produced significantly lower levels of IFN-γ and TNF-α. Thus, ICOS−/− CD4+ T cells were impaired in effector functions that lead to GVHD. In contrast, recipients of ICOS−/− CD8+ T cells exhibited significantly enhanced GVHD morbidity and accelerated mortality. In the absence of ICOS signaling, either using ICOS-deficient donors or ICOS ligand-deficient recipients, the levels of expansion and Tc1 cytokine production of CD8+ T cells were significantly increased. The level of expansion was inversely correlated with the level of apoptosis, suggesting that increased ability of ICOS−/− CD8+ T cells to induce GVHD resulted from the enhanced survival and expansion of those cells. Our findings indicate that ICOS has paradoxical effects on the regulation of alloreactive CD4+ and CD8+ T cells in GVHD.
The CC Chemokine MCP-1 Stimulates Surface Expression of CX3CR1 and Enhances the Adhesion of Monocytes to Fractalkine/CX3CL1 via p38 MAPK
Authors: Green Simone R. , Han Ki Hoon , Chen Yiming , Almazan Felicidad , Charo Israel F. , Miller Yury I. , Quehenberger Oswald 
Published: April 2014

AbstractThe membrane-anchored form of CX3CL1 has been proposed as a novel adhesion protein for leukocytes. This functional property of CX3CL1 is mediated through CX3CR1, a chemokine receptor expressed predominantly on circulating white blood cells. Thus far, it is still uncertain at what stage of the trafficking process CX3CR1 becomes importantly involved and how the CX3CR1-dependent adhesion of leukocytes is regulated during inflammation. The objective of this study was to examine the functional effects of chemokine stimulation on CX3CR1-mediated adhesion of human monocytes. Consistent with previous reports, our data indicate that the activity of CX3CR1 on resting monocytes is sufficient to mediate cell adhesion to CX3CL1. However, the basal, nonstimulated adhesion activity is low, and we hypothesized that like the integrins, CX3CR1 may require a preceding activation step to trigger firm leukocyte adhesion. Compatible with this hypothesis, stimulation of monocytes with MCP-1 significantly increased their adhesion to immobilized CX3CL1, under both static and physiological flow conditions. The increase of the adhesion activity was mediated through CCR2-dependent signaling and obligatory activation of the p38 MAPK pathway. Stimulation with MCP-1 also induced a rapid increase of CX3CR1 protein on the cell surface. Inhibition of the p38 MAPK pathway prevented this increase of CX3CR1 surface expression and blunted the effect of MCP-1 on cell adhesion, indicating a causal link between receptor surface density and adhesion activity. Together, our data suggest that a chemokine signal is required for firm CX3CR1-dependent adhesion and demonstrate that CCR2 is an important regulator of CX3CL1-dependent leukocyte adhesion.
The Complementarity Determining Region 2 of BV8S2 (Vβ8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR
Authors: Pyż Elwira , Naidenko Olga , Miyake Sachiko , Yamamura Takashi , Berberich Ingolf , Cardell Susanna , Kronenberg Mitchell , Herrmann Thomas 
Published: April 2014

AbstractInvariant NKT cells (iNKT cells) are characterized by a semi-invariant TCR comprising an invariant α-chain paired with β-chains with limited BV gene usage which are specific for complexes of CD1d and glycolipid Ags like α-galactosylceramide (α-GalCer). iNKT cells can be visualized with α-GalCer-loaded CD1d tetramers, and the binding of mouse CD1d tetramers to mouse as well as to human iNKT cells suggests a high degree of conservation in recognition of glycolipid Ags between species. Surprisingly, mouse CD1d tetramers failed to stain a discrete cell population among F344/Crl rat liver lymphocytes, although comprised iNKT cells are indicated by IL-4 and IFN-γ secretion after α-GalCer stimulation. The arising hypothesis that rat iNKT TCR recognizes α-GalCer only if presented by syngeneic CD1d was then tested with the help of newly generated rat and mouse iNKT TCR-transduced cell lines. Cells expressing mouse iNKT TCR reacted to α-GalCer presented by rat or mouse CD1d and efficiently bound α-GalCer-loaded mouse CD1d tetramers. In contrast, cells expressing rat iNKT TCR responded only to α-GalCer presented by syngeneic CD1d and bound mouse CD1d tetramers only poorly or not at all. Finally, CD1d-dependent α-GalCer reactivity and binding of mouse CD1d tetramers was tested for cells expressing iNKT TCR comprising either rat or mouse AV14 (Vα14) α-chains and wild-type or mutated BV8S2 (Vβ8.2) β-chains. The results confirmed the need of syngeneic CD1d as restriction element for rat iNKT TCR and identified the CDR2 of BV8S2 as an essential site for ligand recognition by iNKT TCR.
Local Amplification of Glucocorticoids by 11β-Hydroxysteroid Dehydrogenase Type 1 Promotes Macrophage Phagocytosis of Apoptotic Leukocytes
Authors: Gilmour James S. , Coutinho Agnes E. , Cailhier Jean-François , Man Tak Yung , Clay Michael , Thomas Graham , Harris Hayley J. , Mullins John J. , Seckl Jonathan R. , Savill John S. , Chapman Karen E. 
Published: April 2014

AbstractGlucocorticoids promote macrophage phagocytosis of leukocytes undergoing apoptosis. Prereceptor metabolism of glucocorticoids by 11β-hydroxysteroid dehydrogenases (11β-HSDs) modulates cellular steroid action. 11β-HSD type 1 amplifies intracellular levels of active glucocorticoids in mice by reactivating corticosterone from inert 11-dehydrocorticosterone in cells expressing the enzyme. In this study we describe the rapid (within 3 h) induction of 11β-HSD activity in cells elicited in the peritoneum by a single thioglycolate injection in mice. Levels remained high in peritoneal cells until resolution. In vitro experiments on mouse macrophages demonstrated that treatment with inert 11-dehydrocorticosterone for 24 h increased phagocytosis of apoptotic neutrophils to the same extent as corticosterone. This effect was dependent upon 11β-HSD1, as 11β-HSD1 mRNA, but not 11β-HSD2 mRNA, was expressed in these cells; 11-dehydrocorticosterone was ineffective in promoting phagocytosis by Hsd11b1−/− macrophages, and carbenoxolone, an 11β-HSD inhibitor, prevented the increase in phagocytosis elicited in wild-type macrophages by 11-dehydrocorticosterone. Importantly, as experimental peritonitis progressed, clearance of apoptotic neutrophils was delayed in Hsd11b1−/− mice. These data point to an early role for 11β-HSD1 in promoting the rapid clearance of apoptotic cells during the resolution of inflammation and indicate a novel target for therapy.