bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action integréee pour la valorisation et le respect des Indiens dans la communauté indigène Nambikwara – District de Comodoro, Mato grosso
Authors: Nogueira Marta Cristina de Jesus Aparecida , Metello Humberto da Silva , Nascimento Lucelma Aparecida , Rosa Deocleciano Bittencourt 
Published: March 2014

Ce travail présente un ensemble d’actions interdisciplinaires et hautement durables qui peuvent rendre viable une amélioration de la qualité de vie de la communauté indigène Nambikwara, dans le District de Comodoro, située dans la région Nord-Ouest de l’État de Mato Grosso, en mazonie Légale du Brésil, par l’intégration dans notre société sans perte de son identité culturelle, car si si l’indien vit d’une façon simple et humble, il peut comprendre notre monde à partir d’un ensemble de signifiés propres. Dans la Constitution Fédérale du Brésil de 1988, il est assuré aux Indiens le droit de maintenir leur dignité culturelle et est établi en devoir d’État la mission de protéger cette population. Ont ainsi été ouverts plusieurs chemins vers la reconnaissance des différences culturelles qui existent dans notre société, et l’importance de gérer les études, recherches, modèles éducatifs et pratiques pédagogiques qui puissent satisfaire les nécessités basiques des communautés indigènes, pas seulement à Comodoro, mais dans tout le Brésil.
La récupération des déchets à Buenos Aires : un travail de l’âge global
Authors: Carré Marie-Noëlle 
Published: March 2014

À Buenos Aires (Argentine), la récupération des déchets recyclables a mis à jour de nouvelles dynamiques de travail et d’organisation économique et sociale intrinsèquement liées aux processus de métropolisation intervenus dans les années 1990. Depuis la fin de la crise de 2001, cette activité s’est pérennisée, interrogeant par la même occasion les conditions de son inscription durable dans les territoires métropolitains. En partant de l’hypothèse que la récupération consiste en un travail de l’âge global, il s’agira de mettre en évidence ses caractéristiques et les difficultés que rencontrent les acteurs de la métropole pour la consolider dans les cadres politico-administratifs existants. De fait, autant sa précarité que ses modalités innovantes sont liées à son double ancrage dans les territoires locaux et dans les réseaux économiques et informationnels globaux, ce qui permet de la définir comme une activité hybride. Dans ces conditions, l’inscription dans les dynamiques métropolitaines brouille la dichotomie entre la mondialisation « par le haut » et « par le bas » retenue pour différencier les circuits formels et informels. La récupération des déchets au XXIe siècle est née de la concentration des investissements directs étrangers, de l’accroissement des contrastes socio-économique et des transformations morphologiques de Buenos Aires. Mais elle n’existerait pas non plus si elle ne fonctionnait pas selon des réseaux capillaires, et dans une profonde informalité. Les récupérateurs et les décideurs urbains sont donc amenés à inventer des arrangements pour prendre en compte les enjeux sociaux, économiques, environnementaux et territoriaux nouveaux de cette activité. L’expression la plus intéressante et novatrice de ce processus est l’émergence de la sélection des déchets recyclables comme un service exclusif de première classe pour les territoires métropolitains plus que comme un service de base pour toute l’agglomération.
NKT Cells Determine Titer and Subtype Profile of Virus-Specific IgG Antibodies during Herpes Simplex Virus Infection
Authors: Raftery Martin J. , Wolter Eike , Fillatreau Simon , Meisel Helga , Kaufmann Stefan H. E. , Schönrich Günther 
Published: March 2014

Abstract
Invariant NKT cells (iNKT cells) are innate lymphocytes that recognize lipid-derived Ags presented by the MHC class I–related protein CD1d. In this study, we analyzed the role of iNKT cells in the generation of Abs against HSV type 1 (HSV-1). In sera from healthy hman donors, we found a correlation between HSV-1–specific IgG titers and proportions of CD4+ iNKT cells. In HSV-1–infected iNKT cell–deficient mice, the amount of specific IgM and IgG Abs were significantly reduced compared with wild-type mice. Moreover, iNKT cell–deficient mice were unable to upregulate CD1d on B cells and failed to establish an IFN-γ–driven subtype profile of HSV-1–specific IgG Abs. In spleens of HSV-1–infected wild-type mice, the percentage of iNKT cells expressing CCR6, a marker for inflammatory iNKT cells secreting IFN-γ, was significantly decreased at 6 mo postinfection, suggesting that these cells were released from the spleen to other tissues. Finally, in vitro experiments showed that in the absence of CD1d-restricted cells, HSV-1 induced markedly lower IFN-γ production in splenocytes from naive mice. Taken together, our results indicate that iNKT cells shape the Ab response to HSV-1 infection and provide a basis for rational development of antiviral vaccines.
Altered Expression of Oligodendrocyte and Neuronal Marker Genes Predicts the Clinical Onset of Autoimmune Encephalomyelitis and Indicates the Effectiveness of Multiple Sclerosis–Directed Therapeutics
Authors: Evangelidou Maria , Karamita Maria , Vamvakas Sotiris-Spyros , Szymkowski David E. , Probert Lesley 
Published: March 2014

Abstract
Experimental autoimmune encephalomyelitis (EAE) is a valuable model for studying immunopathology in multiple sclerosis (MS) and for exploring the interface between autoimmune responses and CNS tissue that ultimately leads to lesion development. In this study, we measured gene expression in mouse spinal cord during myelin oligodendrocyte gp35–55 peptide–induced EAE, using quantitative RT-PCR, to identify gene markers that monitor individual hallmark pathological processes. We defined a small panel of genes whose longitudinal expression patterns provided insight into the timing, interrelationships, and mechanisms of individual disease processes and the efficacy of therapeutics for the treatment of MS. Earliest transcriptional changes were upregulation of Il17a and sharp downregulation of neuronal and oligodendrocyte marker genes preceding clinical disease onset, whereas neuroinflammatory markers progressively increased as symptoms and tissue lesions developed. EAE-induced gene-expression changes were not altered in mice deficient in IKKβ in cells of the myeloid lineage compared with controls, but the administration of a selective inhibitor of soluble TNF to mice from the day of immunization delayed changes in the expression of innate inflammation, myelin, and neuron markers from the presymptomatic phase. Proof of principle that the gene panel shows drug screening potential was obtained using a well-established MS therapeutic, glatiramer acetate. Prophylactic treatment of mice with glatiramer acetate normalized gene marker expression, and this correlated with the level of therapeutic success. These results show that neurons and oligodendrocytes are highly sensitive to CNS-directed autoimmunity before the development of clinical symptoms and immunopathology and reveal a role for soluble TNF in mediating the earliest changes in gene expression.
Mechanistic Target of Rapamycin Complex 1 Expands Th17 and IL-4+ CD4−CD8− Double-Negative T Cells and Contracts Regulatory T Cells in Systemic Lupus Erythematosus
Authors: Kato Hiroshi , Perl Andras 
Published: March 2014

Abstract
The mechanistic target of rapamycin (mTOR) is activated in CD4−CD8− double-negative (DN) T cells and its blockade is therapeutic in systemic lupus erythematosus (SLE) patients. Murine studies showed the involvement of mTOR complex 1 (mTORC1) and 2 (mTORC2) in the differentiation of Th1/Th17 cells and Th2 cells, respectively. In this study, we investigated the roles of mTORC1 and mTORC2 in T cell lineage development in SLE and matched healthy control (HC) subjects. mTORC1 activity was increased, whereas mTORC2 was reduced, as assessed by phosphorylation of their substrates phosphorylated S6 kinase 1 or phosphorylated S6 ribosomal protein and phosphorylated Akt, respectively. Rapamycin inhibited mTORC1 and enhanced mTORC2. IL-4 expression was increased in freshly isolated CD8+ lupus T cells (SLE: 8.09 ± 1.93%, HC: 3.61 ± 0.49%; p = 0.01). DN T cells had greater IL-4 expression than CD4+ or CD8+ T cells of SLE patients after 3-d in vitro stimulation, which was suppressed by rapamycin (control: 9.26 ± 1.48%, rapamycin: 5.03 ± 0.66%; p &lt; 0.001). GATA-3 expression was increased in CD8+ lupus T cells (p &lt; 0.01) and was insensitive to rapamycin treatment. IFN-γ expression was reduced in all lupus T cell subsets (p = 1.0 × 10−5) and also resisted rapamycin. IL-17 expression was increased in CD4+ lupus T cells (SLE: 3.62 ± 0.66%, HC: 2.29 ± 0.27%; p = 0.019), which was suppressed by rapamycin (control: 3.91 ± 0.79%, rapamycin: 2.22 ± 0.60%; p &lt; 0.001). Frequency of regulatory T cells (Tregs) was reduced in SLE (SLE: 1.83 ± 0.25%, HC: 2.97 ± 0.27%; p = 0.0012). Rapamycin inhibited mTORC1 in Tregs and promoted their expansion. Neutralization of IL-17, but not IL-4, also expanded Tregs in SLE and HC subjects. These results indicate that mTORC1 expands IL-4+ DN T and Th17 cells, and contracts Tregs in SLE.
Molecular Mechanisms of TLR2-Mediated Antigen Cross-Presentation in Dendritic Cells
Authors: Shen Kuan-Yin , Song Ying-Chyi , Chen I-Hua , Leng Chih-Hsiang , Chen Hsin-Wei , Li Hui-Ju , Chong Pele , Liu Shih-Jen 
Published: March 2014

Abstract
Cross-presentation is a key function of dendritic cells (DCs), which present exogenous Ags on MHC class I molecules to prime CTL responses. The effects of TLR triggering on the cross-presentation of exogenous Ags by DCs remain unclear. In this study, we used synthetic dipalmitoylated peptides and TLR2 agonist–conjugated peptides as models to elucidate the mechanisms of TLR2-mediated cross-presentation. We observed that the internalization of dipalmitoylated peptides by bone marrow–derived DCs was facilitated by TLR2 via clathrin-mediated endocytosis. The administration of these dipalmitoylated peptide-pulsed bone marrow–derived DCs eliminated established tumors through TLR2 signaling. We further demonstrated that the induction of Ag-specific CTL responses and tumor regression by dipalmitoylated peptides was TAP independent. In addition, presentation of dipalmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). The endocytosed dipalmitoylated peptide also passed rapidly from early endosome Ag-1–positive endosomes to RAS-related GTP-binding protein 7 (Rab7)–associated late endosomes compared with their nonlipidated counterparts. Furthermore, we found that dipalmitoylated peptide–upregulated Rab7 expression correlated with Ag presentation via the TLR2/MyD88 pathway. Both JNK and ERK signaling pathways are required for upregulation of Rab7. In summary, our data suggest that TLR2-mediated cross-presentation occurs through the upregulation of Rab7 and a TAP-independent pathway that prime CTL responses.
Heterocomplex Formation between MBL/Ficolin/CL-11–Associated Serine Protease-1 and -3 and MBL/Ficolin/CL-11–Associated Protein-1
Authors: Rosbjerg Anne , Munthe-Fog Lea , Garred Peter , Skjoedt Mikkel-Ole 
Published: March 2014

Abstract
The activity of the complement system is tightly controlled by many fluid-phase and tissue-bound regulators. Mannose-binding lectin (MBL)/ficolin/collectin-11–associated protein-1 (MAP-1) is a recently discovered plasma protein that acts as an upstream inhibitor of the lectin complement pathway (LCP). It has previously been shown that MAP-1 can compete with the MBL/ficolin/collectin-11–associated serine proteases (MASPs) in binding to MBL and the ficolins. However, this mechanism may only partly explain the inhibitory complement effect of MAP-1. We hypothesized that MAP-1 is also involved in heterocomplex formation with the MASPs thereby breaking the stoichiometry of the activation complexes of the LCP, which could represent an alternative mechanism of MAP-1–mediated complement inhibition. We assessed the heterocomplex formation with ELISA, size-exclusion chromatography, and immunoblotting using both recombinant proteins and serum/plasma. We found that rMAP-1 can engage in heterocomplexes with rMASP-1 and rMASP-3 in a calcium-dependent manner. Moreover, we discovered that rMASP-1 and rMASP-3 also form heterocomplexes under these conditions. Complexes containing both MAP-1 and MASP-1 or -3 were detected in normal human serum and plasma, and depletion of the LCP recognition molecules from ficolin-3–deficient human serum showed that free circulating heterocomplexes also exist in the blood, although the major part appears to be associated with the LCP recognition molecules. Altogether, these findings suggest that MASPs can associate in various combinations and bring new perspectives to the complexity of lectin pathway–driven complement activation.
The Spectrum of Cervical Glandular Neoplasia and Issues in Differential Diagnosis
Authors: Loureiro Joana , Oliva Esther 
Published: March 2014

Context.—Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems with a variety of benign (more common) as well as other malignant mimics, the latter setting often being represented by secondary involvement by endometrioid endometrial carcinoma especially in small samplings.Objective.—To highlight key histologic features and immunohistochemical markers that may be helpful in the distinction of in situ endocervical carcinoma from benign glandular proliferations, and those that separate different subtypes of invasive endocervical carcinoma, as well as invasive carcinoma from other carcinomas secondarily involving the cervix and nonneoplastic proliferations of the cervix.Conclusions.—Clinical and morphologic features as well as immunohistochemistry results should be used in conjunction in the differential diagnosis of glandular proliferations of the cervix, as correct interpretation has major clinical consequences for the patient in most instances (especially benign versus malignant). Immunohistochemical markers should be used as part of a panel of antibodies, as exceptions may occur to the usual pattern of staining, and if used singly, they may mislead the pathologist to establish a wrong diagnosis.
Fluorescence Immunophenotyping and Interphase Cytogenetics (FICTION) Detects BCL6 Abnormalities, Including Gene Amplification, in Most Cases of Nodular Lymphocyte-Predominant Hodgkin Lymphoma
Authors: Bakhirev Alexei G. , Vasef Mohammad A. , Zhang Qian-Yun , Reichard Kaaren K. , Czuchlewski David R. 
Published: March 2014

Context.— BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells.
Objective.—To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis.
Design.—We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers.
Results.— BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION.
Conclusions.—To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.
Biopsies of Facial Dermatoses Made Simple
Authors: Al-Mohammedi Faisal , Crawford Richard I. , Martinka Magdalena 
Published: March 2014

Context.—Biopsy of the face is rarely done for inflammatory skin diseases, unless the entire process is confined to the face.
Objective.—We hypothesized that facial dermatitis has a differential diagnosis that is more limited than the differential diagnosis of inflammatory skin diseases that affect other parts of the body. To our knowledge, the classification of inflammatory skin diseases occurring on the face has never been conducted before in the English literature.
Design.—The most-recent 100 facial biopsies of inflammatory skin conditions were retrieved from our files, and the cases were categorized into the main inflammatory skin patterns.
Results.—Forty-seven cases (47%) were categorized as interface dermatitis, 2 cases (2%) as psoriasiform dermatitis, 11 cases (11%) as spongiotic dermatitis, 16 cases (16%) as diffuse and nodular dermatitis, 8 cases (8%) as perivascular dermatitis, 14 cases (14%) as folliculitis and perifolliculitis, 1 case (1%) as panniculitis, and 1 case (1%) as fibrosing dermatitis. The number of diagnostic entities represented within each of these patterns was small.
Conclusions.—We believe that facial dermatitis should have its own more-circumscribed differential diagnosis. From a practical viewpoint, many of the inflammatory skin diseases that affect other parts of the body should be excluded from the differential diagnosis after the tissue is determined to be from a facial skin biopsy, and others should not be considered unless the biopsy is from the face.
Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura
Authors: Barrows Brad D. , Teruya Jun 
Published: March 2014

Context.—Acquired thrombotic thrombocytopenic purpura (A-TTP) is a rare but significant disease requiring rapid diagnosis and treatment. The diagnosis is often difficult because of variability in the presence of specific clinical criteria. The primary etiology of A-TTP involves inhibitors directed against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Literature has shown that the ADAMTS13 activity assay is sensitive and specific for identifying cases of A-TTP, and application of this test as an on-site screening method has not been fully explored.
Objective.—Our objective is to determine if the ADAMTS13 activity assay can be used as a successful, on-site diagnostic modality to rapidly identify cases of A-TTP and prevent unnecessary use of prophylactic therapeutic plasma exchange.
Design.—A retrospective analysis was performed including 152 patients with clinically suspected A-TTP, screened using the ADAMTS13 activity assay. Results were correlated with potential therapeutic plasma exchange treatment for all cases highly suspicious for A-TTP and evaluated for unnecessary patient morbidity and financial cost.
Results.—The ADAMTS13 activity assay had an overall sensitivity and specificity of 100% and 99%, respectively. The positive predictive value was 91% and the negative predictive value was 100%. In 95% of the studies ordered, A-TTP was ruled out, leading to decreased patient morbidity and $1.7 million of potential treatment costs avoided.
Conclusion.—Implementation of the fluorescence energy transfer–based ADAMTS13 activity assay as a point-of-care laboratory study decreased patient morbidity while also directing more efficient employment of therapeutic plasma exchange in cases of suspected A-TTP.
Determination of HER2/neu Status: A Pilot Study Comparing HER2/neu Dual In Situ Hybridization DNA Probe Cocktail Assay Performed on Cell Blocks to Immunohistochemisty and Fluorescence In Situ Hybridization Performed on Histologic Specimens
Authors: Hartman Adria K. , Gorman Blythe K. , Chakraborty Subhendu , Mody Dina R. , Schwartz Mary R. 
Published: March 2014

Context.—Validation of new methodologies for determining human epidermal growth factor receptor 2 gene (HER2/neu) amplification status is crucial for advancing the standard of care and determining treatment for patients with primary and/or metastatic breast carcinoma.Objective.—To compare results of HER2/neu gene amplification status by 2-color chromogenic in situ hybridization (ISH) on cell block material to HER2/neu status by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) in the corresponding resection specimen or previous biopsy specimen.Design.—Formalin, thrombin, and Cellient cell blocks were prepared from cytologic samples obtained from resection specimens from 27 patients with invasive breast carcinoma. In situ hybridization was performed on cell block sections from 18 of the collected cases, on both the Ventana BenchMark ULTRA and the Ventana BenchMark XT, and the HER2/neu gene amplification status was determined. This was then compared to the HER2/neu status by IHC and/or FISH in the resection specimen or previous biopsy specimen.Results.—Comparison of HER2/neu status by ISH on the quantifiable cell block sections showed 100% correlation with the HER2/neu status determined by IHC or FISH in the corresponding histologic specimens. The results from thrombin and formalin cell blocks were statistically superior to the results from Cellient cell blocks on both Ventana instruments.Conclusions.—While further validation and study are needed, preliminary results show that the HER2/neu gene amplification status of breast carcinomas can reliably be determined on thrombin and formalin cell block material by using ISH. More consistent staining and better signal integrity was obtained with the Ventana BenchMark ULTRA than the BenchMark XT.
Pathology Training in Informatics: Evolving to Meet a Growing Need
Authors: Sinard John H. , Powell Suzanne Z. , Karcher Donald S. 
Published: March 2014

Context.—The mechanics of the practice of medicine in general and of pathology in particular is evolving rapidly with the rise in the use of electronic information systems for managing the care of individual patients, including the ordering and reporting of laboratory tests, maintaining the health of served populations, and documenting the full range of health care activities. Pathologists currently in practice and those in training need to acquire additional skills in informatics to be prepared to maintain a central role in patient care.Objective.—To summarize the evolving landscape of pathology informatics, with particular attention to the preparation of pathologists for this discipline and to the possible influence of the new subspecialty certification in clinical informatics.Data Sources.—Most of the information discussed is drawn from the authors' direct experience with informatics, resident and fellow education, and the organizations supporting these activities in pathology.Conclusions.—The increasing reliance of medical practice on electronic health records and other clinical information systems is creating a greater need for physicians skilled in the use and management of these tools. The establishment of clinical informatics as a formal subspecialty in medicine will likely help secure a role for physicians within information management structures at health care institutions. Pathologists must actively engage in informatics to assure that our specialty is appropriately recognized and represented in this growing discipline.