bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Bone Mineral Density and Fracture Risk in Type 2 Diabetes as Skeletal Complications of Inadequate Glucose Control
Authors: Oei Ling , Zillikens M. Carola , Dehghan Abbas , Buitendijk Gabriëlle H.S. , Castaño-Betancourt Martha C. , Estrada Karol , Stolk Lisette , Oei Edwin H.G. , van Meurs Joyce B.J. , Janssen Joseph A.M.J.L. , Hofman Albert , van Leeuwen Johannes P.T.M. , Witteman Jacqueline C.M. , Pols Huibert A.P. , Uitterlinden André G. , Klaver Caroline C.W. , Franco Oscar H. , Rivadeneira Fernando 
Published: January 2013

OBJECTIVE
Individuals with type 2 diabetes have increased fracture risk despite higher bone mineral density (BMD). Our aim was to examine the influence of glucose control on skeletal complications.

RESEARCH DESIGN AND METHODS
Data of 4,135 participants of the Rotterdam Study, a prospective population-based cohort, were available (mean follow-up 12.2 years). At baseline, 420 participants with type 2 diabetes were classified by glucose control (according to HbA1c calculated from fructosamine), resulting in three comparison groups: adequately controlled diabetes (ACD; n = 203; HbA1c &lt;7.5%), inadequately controlled diabetes (ICD; n = 217; HbA1c ≥7.5%), and no diabetes (n = 3,715). Models adjusted for sex, age, height, and weight (and femoral neck BMD) were used to test for differences in bone parameters and fracture risk (hazard ratio [HR] [95% CI]).

RESULTS
The ICD group had 1.1–5.6% higher BMD, 4.6–5.6% thicker cortices, and −1.2 to −1.8% narrower femoral necks than ACD and ND, respectively. Participants with ICD had 47–62% higher fracture risk than individuals without diabetes (HR 1.47 [1.12–1.92]) and ACD (1.62 [1.09–2.40]), whereas those with ACD had a risk similar to those without diabetes (0.91 [0.67–1.23]).

CONCLUSIONS
Poor glycemic control in type 2 diabetes is associated with fracture risk, high BMD, and thicker femoral cortices in narrower bones. We postulate that fragility in apparently “strong” bones in ICD can result from microcrack accumulation and/or cortical porosity, reflecting impaired bone repair.
Influence of Adiposity on Insulin Resistance and Glycemia Markers Among U.K. Children of South Asian, Black African-Caribbean, and White European Origin
Authors: Nightingale Claire M. , Rudnicka Alicja R. , Owen Christopher G. , Wells Jonathan C.K. , Sattar Naveed , Cook Derek G. , Whincup Peter H. 
Published: January 2013

OBJECTIVE
Ethnic differences in type 2 diabetes risk between South Asians and white Europeans originate before adult life and are not fully explained by higher adiposity levels in South Asians. Although metabolic sensitivity to adiposity may differ between ethnic groups, this has been little studied in childhood. We have therefore examined the associations among adiposity, insulin resistance, and glycemia markers in children of different ethnic origins.

RESEARCH DESIGN AND METHODS
Cross-sectional study of 4,633 9- to 10-year-old children (response rate 68%) predominantly of South Asian, black African-Caribbean, and white European origin (n = 1,266, 1,176, and 1,109, respectively) who had homeostasis model assessments of insulin resistance (HOMA-IR), glycemia markers (HbA1c and fasting glucose), and adiposity (BMI, waist circumference, skinfold thicknesses, and bioimpedance [fat mass]).

RESULTS
All adiposity measures were positively associated with HOMA-IR in all ethnic groups, but associations were stronger among South Asians compared to black African-Caribbeans and white Europeans. For a 1-SD increase in fat mass percentage, percentage differences in HOMA-IR were 37.5% (95% CI 33.3–41.7), 29.7% (25.8–33.8), and 27.0% (22.9–31.2), respectively (P interaction &lt; 0.001). All adiposity markers were positively associated with HbA1c in South Asians and black African-Caribbeans but not in white Europeans; for a 1-SD increase in fat mass percentage, percentage differences in HbA1c were 0.04% (95% CI 0.03–0.06), 0.04% (0.02–0.05), and 0.02% (−0.00 to 0.04), respectively (P interaction &lt; 0.001). Patterns for fasting glucose were less consistent.

CONCLUSIONS
South Asian children are more metabolically sensitive to adiposity. Early prevention or treatment of childhood obesity may be critical for type 2 diabetes prevention, especially in South Asians.
One-Hour Glucose During an Oral Glucose Challenge Prospectively Predicts β-Cell Deterioration and Prediabetes in Obese Hispanic Youth
Authors: Kim Joon Young , Goran Michael I. , Toledo-Corral Claudia M. , Weigensberg Marc J. , Choi Myunghan , Shaibi Gabriel Q. 
Published: January 2013

OBJECTIVE
In adults, 1-h glucose during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes independent of fasting and 2-h glucose concentrations. The purpose of the current investigation was to examine the utility of elevated 1-h glucose levels to prospectively predict deterioration in β-cell function and the development of prediabetes in high-risk youth.

RESEARCH DESIGN AND METHODS
Obese Latino youth with a family history of type 2 diabetes (133 male and 100 female; age 11.1 ± 1.7 years) completed a baseline OGTT and were divided into two groups based upon a 1-h glucose threshold of 155 mg/dL (&lt;155 mg/dL, n = 151, or ≥155 mg/dL, n = 82). Youth were followed annually for up to 8 years for assessment of glucose tolerance, body composition by dual-energy X-ray absorptiometry, and insulin sensitivity, insulin secretion, and the disposition index by the frequently sampled intravenous glucose tolerance test.

RESULTS
Over time, the ≥155 mg/dL group exhibited a significantly greater decline in β-cell function compared with youth with a 1-h glucose &lt;155 mg/dL (β = −327.8 ± 126.2, P = 0.01). Moreover, this decline was independent of fasting or 2-h glucose and body composition. When the data were restricted to only participants with normal glucose tolerance at baseline, a 1-h glucose ≥155 mg/dL was independently associated with a 2.5 times greater likelihood of developing prediabetes during follow-up (95% CI 1.6–4.1, P = 0.0001).

CONCLUSIONS
These data suggest that a 1-h glucose ≥155 mg/dL during an OGTT is an independent predictor of β-cell deterioration and progression to prediabetes among obese Latino youth.
Sex-Specific Association of Fetuin-A With Type 2 Diabetes in Older Community-Dwelling Adults
Authors: Laughlin Gail A. , Barrett-Connor Elizabeth , Cummins Kevin M. , Daniels Lori B. , Wassel Christina L. , Ix Joachim H. 
Published: January 2013

OBJECTIVE
This study evaluated the sex-specific association of plasma fetuin-A levels with prevalent and incident type 2 diabetes in community-dwelling older adults.

RESEARCH DESIGN AND METHODS
Participants were 684 men and 1,058 women (median age, 71 years) whose fetuin-A levels, diabetes prevalence, and diabetes risk factors were evaluated in 1992–1996. The participants were followed for incident diabetes through 2010 (median follow-up, 9 years).

RESULTS
Women with impaired glucose tolerance had elevated fetuin-A levels compared with women with normal glucose tolerance (P = 0.019), but fetuin-A levels were not elevated in women with impaired fasting glucose. Fetuin-A did not vary by glucose tolerance status in men. There were significant interactions of fetuin-A by sex for prevalent (P = 0.007) and incident (P = 0.020) diabetes. For women, each SD (0.10 g/L) higher fetuin-A level was associated with a higher odds of prevalent diabetes (odds ratio [OR] 1.79, 95% CI 1.47–2.17) and greater risk of incident diabetes (hazard ratio [HR] 1.66, 95% CI 1.18–2.34), adjusting for age and estrogen therapy. These associations were not materially altered by adjustment for diabetes risk factors but were attenuated by adjusting for postchallenge glucose levels. Among men, although positive associations with prevalent (OR 1.15 [0.94–1.41]) and incident (HR 1.24 [0.93–1.65]) diabetes were suggested in age-adjusted models, risk estimates attenuated to one after multivariable adjustment.

CONCLUSIONS
Higher fetuin-A concentrations were independently associated with an increased risk of developing type 2 diabetes in older women but were not related to diabetes risk in older men. Fetuin-A may provide novel insights into mechanisms underlying sex differences in glucose homeostasis and diabetes risk in old age.
“These Noxious Microbes”: Pathological Dramaturgy in George Bernard Shaw’sToo True to Be Good
Authors: Wixson Christopher 
Published: January 2013

ABSTRACT:This essay charts the interdependency of form and content in Bernard Shaw’s Too True to Be Good (1931). In this late play, the playwright, building upon his well-known attacks against medical theory and practice, views class privilege, colonial relations, and dramatic structure itself through the lens of disease. Angrily taking the stage in act one, the unusual, acerbic Microbe inaugurates Shaw’s dissection of imperialist discourse and attempt to purge the theatrical textual body of its pathogenic conventions.
Honeggeriella complexa gen. et sp. nov., a heteromerous lichen from the Lower Cretaceous of Vancouver Island (British Columbia, Canada)
Authors: Matsunaga Kelly K. S. , Stockey Ruth A. , Tomescu Alexandru M. F. 
Published: January 2013

• Premise of the study: Colonists of even the most inhospitable environments, lichens are present in all terrestrial ecosystems. Because of their ecological versatility and ubiquity, they have been considered excellent candidates for early colonizers of terrestrial environments. Despite such predictions, good preservation potential, and the extant diversity of lichenized fungi, the fossil record of lichen associations is sparse. Unequivocal lichen fossils are rare due, in part, to difficulties in ascertaining the presence of both symbionts and in characterizing their interactions. This study describes an exceptionally well‐preserved heteromerous lichen from the Lower Cretaceous of Vancouver Island.• Methods: The fossil occurs in a marine carbonate concretion collected from the Apple Bay locality on Vancouver Island, British Columbia, and was prepared for light microscopy and SEM using the cellulose acetate peel technique.• Key results: The lichen, Honeggeriella complexa gen. et sp. nov., is formed by an ascomycete mycobiont and a chlorophyte photobiont, and exhibits heteromerous thallus organization. This is paired with a mycobiont‐photobiont interface characterized by intracellular haustoria, previously not documented in the fossil record.• Conclusions: Honeggeriella adds a lichen component to one of the richest and best characterized Early Cretaceous floras and provides a significant addition to the sparse fossil record of lichens. As a heteromerous chlorolichen, it bridges the >350 million‐year gap between previously documented Early Devonian and Eocene occurrences.
Valeur de marché et mesures comptables : les entreprises de la nouvelle économie française
Authors: Evraert Frédérique 
Published: January 2013

Résumé Cet article s’intéresse à l’évaluation des entreprises de la nouvelle économie française. Il examine le lien entre leur valeur de marché et les principaux paramètres de mesure de la situation financière décrits dans les états financiers : le résultat, les flux de trésorerie et les capitaux propres. Les exercices 2000-2002 servent de cadre temporel à l’analyse. Cette recherche s’inscrit dans la lignée des études visant à montrer la pertinence des mesures comptables et l’utilité de l’information financière pour expliquer les valorisations boursières des sociétés. La méthodologie utilisée est celle des études d’association. Les résultats testés à l’aide de trois modèles montrent l’intérêt du résultat de l’exercice et du résultat opérationnel dans l’explication des valeurs de marché des entreprises.
Stratégie comptable des dirigeants et parité d'échange : le cas des fusions françaises
Authors: Djama Constant , Boutant Jennifer 
Published: January 2013

Résumé Cet article s’intéresse à la détermination de la parité d’échange dans les opérations de fusion françaises et notamment à l’impact de la politique comptable des dirigeants des sociétés absorbantes sur cette parité. Les résultats de l’article suggèrent que les opérations de fusion-absorption françaises sont un contexte favorable à la gestion des résultats l’année qui précède la réalisation de l’opération. Ainsi, notre étude montre d’une part, que les dirigeants des sociétés absorbantes gèrent les résultats comptables l’année qui précède la fusion. Les ajustements discrétionnaires représentent environ 6,7 % du total de l’actif. D’autre part, cette gestion est influencée par plusieurs facteurs : l’actionnariat majoritaire de l’absorbante (famille(s), dirigeants, famille dirigeante, investisseurs institutionnels), l’influence des critères de nature comptable dans la détermination de la parité, la dilution du capital après la fusion, la réputation des auditeurs et la performance de la société absorbante.
EBV BILF1 Evolved To Downregulate Cell Surface Display of a Wide Range of HLA Class I Molecules through Their Cytoplasmic Tail
Authors: Griffin Bryan D. , Gram Anna M. , Mulder Arend , Van Leeuwen Daphne , Claas Frans H. J. , Wang Fred , Ressing Maaike E. , Wiertz Emmanuel 
Published: January 2013

AbstractCoevolution of herpesviruses and their hosts has driven the development of both host antiviral mechanisms to detect and eliminate infected cells and viral ploys to escape immune surveillance. Among the immune-evasion strategies used by the lymphocryptovirus (γ1-herpesvirus) EBV is the downregulation of surface HLA class I expression by the virally encoded G protein–coupled receptor BILF1, thereby impeding presentation of viral Ags and cytotoxic T cell recognition of the infected cell. In this study, we show EBV BILF1 to be expressed early in the viral lytic cycle. BILF1 targets a broad range of HLA class I molecules, including multiple HLA-A and -B types and HLA-E. In contrast, HLA-C was only marginally affected. We advance the mechanistic understanding of the process by showing that the cytoplasmic C-terminal tail of EBV BILF1 is required for reducing surface HLA class I expression. Susceptibility to BILF1-mediated downregulation, in turn, is conferred by specific residues in the intracellular tail of the HLA class I H chain. Finally, we explore the evolution of BILF1 within the lymphocryptovirus genus. Although the homolog of BILF1 encoded by the lymphocryptovirus infecting Old World rhesus primates shares the ability of EBV to downregulate cell surface HLA class I expression, this function is not possessed by New World marmoset lymphocryptovirus BILF1. Therefore, this study furthers our knowledge of the evolution of immunoevasive functions by the lymphocryptovirus genus of herpesviruses.
FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells
Authors: Seiler Frederik , Hellberg Jan , Lepper Philipp M. , Kamyschnikow Andreas , Herr Christian , Bischoff Markus , Langer Frank , Schäfers Hans-Joachim , Lammert Frank , Menger Michael D. , Bals Robert , Beisswenger Christoph 
Published: January 2013

Abstract
Bacterial pathogens are a leading cause of lung infections and contribute to acute exacerbations in patients with chronic respiratory diseases. The innate immune system of the respiratory tract controls and prevents colonization of the lung with bacterial pathogens. Forkhead box transcription factor family O (FOXO) transcription factors are key regulators of cellular metabolism, proliferation, and stress resistance. In this study, our aim was to investigate the role of FOXO transcription factors in innate immune functions of respiratory epithelial cells. We show that bacterial pathogens potently activate FOXO transcription factors in cultured human respiratory epithelial cells in vitro. Infection of mice with bacterial pathogens resulted in the activation of FOXO transcription factors in alveolar and bronchial epithelial cells in vivo. Active FOXO was also detectable in human bronchial tissue obtained from subjects with different infection-related lung diseases. Small interfering RNA–mediated knockdown of FOXO in bronchial epithelial cells resulted in reduced expression of factors of the innate immune system such as antimicrobial peptides and proinflammatory cytokines, both under basal conditions and upon infection. FOXO deficiency further affected internalization of Haemophilus influenzae in bronchial epithelial cells. Finally, we show that TLR3 activates innate immune responses in a FOXO-dependent manner. In conclusion, FOXO transcription factors are involved in the cellular responses to bacterial stimuli and act as central regulators of innate immune functions in respiratory epithelial cells.
Self Double-Stranded (ds)DNA Induces IL-1β Production from Human Monocytes by Activating NLRP3 Inflammasome in the Presence of Anti–dsDNA Antibodies
Authors: Shin Min Sun , Kang Youna , Lee Naeun , Wahl Elizabeth R. , Kim Sang Hyun , Kang Ki Soo , Lazova Rossitza , Kang Insoo 
Published: January 2013

AbstractThe pathogenic hallmark of systemic lupus erythematosus is the autoimmune response against self nuclear Ags, including dsDNA. The increased expression of the proinflammatory cytokine IL-1β has been found in the cutaneous lesion and PBMCs from lupus patients, suggesting a potential involvement of this cytokine in the pathogenesis of lupus. IL-1β is produced primarily by innate immune cells such as monocytes and can promote a Th17 cell response, which is increased in lupus. IL-1β production requires cleaving pro–IL-β into IL-1β by the caspase-1–associated multiprotein complex called inflammasomes. In this study we show that self dsDNA induces IL-1β production from human monocytes dependent on serum or purified IgG containing anti–dsDNA Abs by activating the nucleotide-binding oligomerization domain–like receptor family pyrin domain–containing 3 (NLRP3) inflammasome. Reactive oxygen species (ROS) and K+ efflux were involved in this activation. Knocking down the NLRP3 or inhibiting caspase-1, ROS, and K+ efflux decreased IL-1β production. Supernatants from monocytes treated with a combination of self dsDNA and anti–dsDNA Ab+ serum promoted IL-17 production from CD4+ T cells in an IL-1β–dependent manner. These findings provide new insights in lupus pathogenesis by demonstrating that self dsDNA together with its autoantibodies induces IL-1β production from human monocytes by activating the NLRP3 inflammasome through inducing ROS synthesis and K+ efflux, leading to the increased Th17 cell response.
IL-2R Signaling Is Essential for Functional Maturation of Regulatory T Cells during Thymic Development
Authors: Cheng Guoyan , Yu Aixin , Dee Michael J. , Malek Thomas R. 
Published: January 2013

Abstract
CD4+ Foxp3+ regulatory T cells (Tregs) are an independent cell lineage, and their developmental progression during thymic development depends on IL-2R signaling. However, the role of IL-2R signaling during thymic Treg development remains only partially understood. The current study assessed the contribution of IL-2 to the expansion and functional programming of developing Tregs. In the absence of IL-2Rβ signaling, predominantly CD4+ CD25− Foxp3lo T cells were found, and these cells exhibited somewhat lower expression of the proliferative marker Ki67. These immature Tregs, which represent products of failed development, were also found in normal mice and were characterized by markedly lower expression of several Treg functional molecules. Therefore, IL-2R is required for the progression, functional programming, and expansion of Tregs during thymic development. An IL-2R–signaling mutant that lowers STAT5 activation readily supported Treg functional programming, but Treg proliferation remained somewhat impaired. The requirement for IL-2 during thymic Treg expansion was best illustrated in mixed chimeras where the Tregs with mutant IL-2Rs were forced to compete with wild-type Tregs during their development. Tregs with impaired IL-2R signaling were more prevalent in the thymus than spleen in these competitive experiments. The general effectiveness of mutant IL-2Rs to support thymic Treg development is partially accounted for by a heightened capacity of thymic Tregs to respond to IL-2. Overall, our data support a model in which limiting IL-2R signaling is amplified by thymic Tregs to readily support their development and functional programming, whereas these same conditions are not sufficient to support peripheral Treg homeostasis.
T Cells Home to the Thymus and Control Infection
Authors: Nobrega Claudia , Nunes-Alves Cláudio , Cerqueira-Rodrigues Bruno , Roque Susana , Barreira-Silva Palmira , Behar Samuel M. , Correia-Neves Margarida 
Published: January 2013

AbstractThe thymus is a target of multiple pathogens. How the immune system responds to thymic infection is largely unknown. Despite being considered an immune-privileged organ, we detect a mycobacteria-specific T cell response in the thymus following dissemination of Mycobacterium avium or Mycobacterium tuberculosis. This response includes proinflammatory cytokine production by mycobacteria-specific CD4+ and CD8+ T cells, which stimulates infected cells and controls bacterial growth in the thymus. Importantly, the responding T cells are mature peripheral T cells that recirculate back to the thymus. The recruitment of these cells is associated with an increased expression of Th1 chemokines and an enrichment of CXCR3+ mycobacteria-specific T cells in the thymus. Finally, we demonstrate it is the mature T cells that home to the thymus that most efficiently control mycobacterial infection. Although the presence of mature T cells in the thymus has been recognized for some time, to our knowledge, these data are the first to show that T cell recirculation from the periphery to the thymus is a mechanism that allows the immune system to respond to thymic infection. Maintaining a functional thymic environment is essential to maintain T cell differentiation and prevent the emergence of central tolerance to the invading pathogens.
Identification of Pathogenic T Cell Epitopes Near Cathepsin Cleavage Sites in Thyroglobulin
Authors: Kolypetri Panayota , Jiang Hong , Carayanniotis George 
Published: January 2013

AbstractExperimental autoimmune thyroiditis, induced in mice after challenge with thyroglobulin (Tg), is known to be under the genetic control of the H2Ak locus. Because cathepsins are known to influence proteolytic processing of Tg in vivo, we examined in this study whether putative H2Ak-binding Tg epitopes, located near cathepsin cleavage sites within mouse Tg, have immunopathogenic properties. Cathepsin L, B, and D cleavage sites in mouse Tg were predicted based on homology with known cathepsin cleavage sites in rabbit Tg. We used an algorithm-based approach to identify H2Ak-binding motifs within 20-aa residue segments adjacent to cathepsin cleavage sites, and five 12mer peptides encompassing these sequences were synthesized. Two of them, p2369 (aa 2369–2380) and p2439 (aa 2439–2450) were immunogenic, eliciting significant proliferative T cell responses using lymph node cells from peptide-primed mice and production of IL-2 and IFN-γ in recall assays in vitro. Both peptides induced experimental autoimmune thyroiditis upon direct challenge of CBA/J mice with peptide in CFA and by adoptive transfer of peptide-primed lymph node cells into naive recipient hosts, but neither peptide was characterized as dominant.