bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
Authors: Fouqueray Pascale , Pirags Valdis , Inzucchi Silvio E. , Bailey Clifford J. , Schernthaner Guntram , Diamant Michaela , Lebovitz Harold E. 
Published: November 2012

OBJECTIVE
A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone.

RESEARCH DESIGN AND METHODS
A total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a day) or placebo added to a stable dose of metformin (1,500–2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio.

RESULTS
After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was −0.44% (P &lt; 0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (−0.91 mg/dL and −7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally well-tolerated with a comparable safety profile to metformin-placebo.

CONCLUSIONS
Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes.
Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults
Authors: Falvey Cherie M. , Rosano Caterina , Simonsick Eleanor M. , Harris Tamara , Strotmeyer Elsa S. , Satterfield Suzanne , Yaffe Kristine ,   for the Health ABC Study
Published: November 2012

OBJECTIVE
To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes.

RESEARCH DESIGN AND METHODS
MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV).

RESULTS
In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results.

CONCLUSIONS
In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.
Vitamin D Receptor Fok-I Polymorphism Modulates Diabetic Host Response to Vitamin D Intake
Authors: Neyestani Tirang R. , Djazayery Abolghassem , Shab-Bidar Sakineh , Eshraghian Mohammad Reza , Kalayi Ali , Shariátzadeh Nastaran , Khalaji Niloufar , Zahedirad Malihe , Gharavi A’zam , Houshiarrad Anahita , Chamari Maryam , Asadzadeh Sepideh 
Published: November 2012

OBJECTIVE
Interpopulation as well as interindividual variations in response to vitamin D intake commonly observed in subjects with type 2 diabetes may be related to genetic makeup. One of the candidate genes potentially responsible for this diversity is vitamin D receptor (VDR). This study aimed to investigate the interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse aspects of diabetic host response.

RESEARCH DESIGN AND METHODS
Glycemic status, lipid profiles, inflammatory biomarkers, and VDR Fok-I genotypes were determined in diabetic subjects (n = 140) who participated in a randomized controlled trial. Participants consumed two 250-mL bottles per day of yogurt drink (doogh) fortified with 500 IU vitamin D/250 mL for 12 weeks.

RESULTS
Mean serum 25(OH)D increased by ~30 nmol/L (P &lt; 0.001). The time × intervention effect was significant for 25(OH)D (P = 0.030), HDL (P = 0.011), high-sensitivity C-reactive protein (hsCRP) (P &lt; 0.001), interleukin (IL)-4 (P = 0.008), and IL-6 (P = 0.017) among the genotypic groups. The alleles were defined as ‘‘F’’ or ‘‘f’’ depending on the absence or presence of the restriction site, respectively. The least increment in 25(OH)D was in ff (23.0 ± 3.8 nmol/L) compared with Ff (31.2 ± 3.4 nmol/L) and FF (35.6 ± 2.7 nmol/L) (P for trend = 0.009), but only the difference between ff and FF was significant (P = 0.023). FF group had the largest decrement of both hsCRP and IL-6 compared with Ff (P &lt; 0.001 and P = 0.038) and ff (P = 0.010 and P = 0.048), respectively.

CONCLUSIONS
We concluded that those of VDR ff genotype may be regarded as “low responders” to vitamin D intake in terms of response of circulating 25(OH)D and certain inflammatory biomarkers. A nutrigenetic approach may, therefore, be needed to protect diabetic patients from vitamin D deficiency.
Association of Electrocardiographically Determined Left Ventricular Mass With Incident Diabetes, 1985–1986 to 2010–2011
Authors: Carnethon Mercedes R. , Ning Hongyan , Soliman Elsayed Z. , Lewis Cora E. , Schreiner Pamela J. , Sidney Stephen , Lloyd-Jones Donald M. 
Published: November 2012

OBJECTIVE
Electrocardiographic indices reflecting left ventricular hypertrophy are associated with incident diabetes in clinical populations at risk for coronary heart disease. We tested whether electrocardiographically determined left ventricular mass was positively associated with incident diabetes in a population sample.

RESEARCH DESIGN AND METHODS
Coronary Artery Risk Development in Young Adults (CARDIA) study participants (n = 4,739) were followed from 1985–1986 to 2010–2011 for incident diabetes. Validated sex- and race-specific formulas were applied to standard electrocardiograms to determine left ventricular mass.

RESULTS
Over 25 years, 444 participants developed diabetes (9.4%). After adjustment for demographic, behavioral, and clinical covariates, participants in the highest quartile of left ventricular mass index (LVMI) were twice as likely to develop diabetes than participants in the lower three quartiles (hazard ratio 2.61 [95% CI 2.16–3.17]). Neither Cornell voltage nor Cornell voltage product was associated with incident diabetes in fully adjusted models.

CONCLUSIONS
Electrocardiographically determined LVMI may be a useful noninvasive marker for identifying adults at risk for diabetes.
Early Prediction of Gestational Diabetes Mellitus in Vietnam
Authors: Tran Thach S. , Hirst Jane E. , Do My An T. , Morris Jonathan M. , Jeffery Heather E. 
Published: November 2012

OBJECTIVE
We aimed to compare the discriminative power of prognostic models for early prediction of women at risk for the development of gestational diabetes mellitus (GDM) using four currently recommended diagnostic criteria based on the 75-g oral glucose tolerance test (OGTT). We also described the potential effect of application of the models into clinical practice.

RESEARCH DESIGN AND METHODS
A prospective cross-sectional study of 2,772 pregnant women was conducted at a referral maternity center in Vietnam. GDM was determined by the American Diabetes Association (ADA), International Association of the Diabetes and Pregnancy Study Groups (IADPSG), Australasian Diabetes in Pregnancy Society (ADIPS), and World Health Organization (WHO) criteria. Prognostic models were developed using the Bayesian model averaging approach, and discriminative power was assessed by area under the curve. Different thresholds of predicted risk of developing GDM were applied to describe the clinical impact of the diagnostic criteria.

RESULTS
The magnitude of GDM varied substantially by the diagnostic criteria: 5.9% (ADA), 20.4% (IADPSG), 20.8% (ADIPS), and 24.3% (WHO). The ADA prognostic model, consisting of age and BMI at booking, had the best discriminative power (area under the curve of 0.71) and the most favorable cost-effective ratio if implemented in clinical practice. Selective screening of women for GDM using the ADA model with a risk threshold of 3% gave 93% sensitivity for identification of women with GDM with a 27% reduction in the number of OGTTs required.

CONCLUSIONS
A simple prognostic model using age and BMI at booking could be used for selective screening of GDM in Vietnam and in other low- and middle-income settings.
Testing achene germinationof Potamogeton praelongus Wulfen
Authors: Prausová Romana , Janová Jana , Šafářová Lenka 
Published: November 2012

Abstract
The goal of this work was to determine the best method of breaking the achene dormancy in Potamogeton praelongus Wulfen. The ways of breaking achene dormancy studied in this experiment included methods of achene storage, stratification, UVA radiation, anaerobic conditions, mechanical disruption of achenes?outer layers and their chemical disruption by NaClO. Nine different treatments of achenes were combined with two methods of achene storage. Particular achene treatments and storage conditions were proven to have a significant impact on breaking dormancy. Although the highest germination rate (83.3%) was achieved when the dormancy was broken chemically by long effect of 100% concentrations of Savo detergent (containing 5% NaClO), the growth of the sprouts was subsequently inhibited due to toxic effects of Savo. Thus the most successful treatment was based on changing temperature, e.g. 2.5 months of cold storage followed by 14 days at room temperature (germination rate 32.7%). This treatment was also most similar to the natural process. Germinated achenes were also found in Petri dishes exposed to UVA radiation, anaerobic conditions and chemical disruption of the outer layers. Results of these treatments were influenced by the storage method.
Fast characterisation of cell‐derived extracellular vesicles by nanoparticles tracking analysis, cryo‐electron microscopy, and Raman tweezers microspectroscopy
Authors: Tatischeff Irène , Larquet Eric , Falcón‐Pérez Juan M. , Turpin Pierre‐Yves , Kruglik Sergei G. 
Published: November 2012

The joint use of 3 complementary techniques, namely, nanoparticle tracking analysis (NTA), cryo‐electron microscopy (Cryo‐EM) and Raman tweezers microspectroscopy (RTM), is proposed for a rapid characterisation of extracellular vesicles (EVs) of various origins. NTA is valuable for studying the size distribution and concentration, Cryo‐EM is outstanding for the morphological characterisation, including observation of vesicle heterogeneity, while RTM provides the global chemical composition without using any exogenous label. The capabilities of this approach are evaluated on the example of cell‐derived vesicles of Dictyostelium discoideum, a convenient general model for eukaryotic EVs. At least 2 separate species differing in chemical composition (relative amounts of DNA, lipids and proteins, presence of carotenoids) were found for each of the 2 physiological states of this non‐pathogenic microorganism, that is, cell growth and starvation‐induced aggregation. These findings demonstrate the specific potency of RTM. In addition, the first Raman spectra of human urinary exosomes are reported, presumably constituting the primary step towards Raman characterisation of EVs for the purpose of human diseases diagnoses.
In vitro radiographic characteristics and biomechanical properties of the canine lumbar vertebral motion unit after lateral corpectomy, mini-hemilaminectomy and hemilaminectomy
Authors: de Vicente F. , Bernard F. , FitzPatrick D. , Moissonnier P. 
Published: November 2012

SummaryObjective: The purpose of this study was to assess the effect of three surgical procedures (left lateral corpectomy [LC], LC plus mini-hemilaminectomy [LC-MH], and LC plus hemilaminectomy [LC-H]) on the biomechanics and intervertebral collapse of a lumbar vertebral motor unit (VMU).Methods: Six canine cadaveric first and second lumbar vertebrae (L1-L2) VMU were retrieved. Range-of-motion (ROM) was measured while a custom-built mechanical simulator applied 3 Nm torque in lateral bending, flexion and extension to the intact VMU and following the three surgical procedures (LC, LC-MH, LC-H) performed sequentially. Radiographs were taken with and without 3 kg axial compression at each step.Results: Left lateral corpectomy and LC-MH significantly increased the ROM in left lateral bending and total lateral bending. A LC-H significantly increased the ventral, left, right, total lateral, and total dorsoventral ROM. Significant intervertebral collapse was observed after LC-H with and without axial compression, and after LC and LC-MH, but only with axial compression.Clinical significance: A LC induces significantly increased ROM in lateral bending to the side of the surgery and in total lateral ROM. Extending the LC to a LC-MH does not change the spinal column stability compared to LC alone, while it provides better access to the spinal canal. The LC-H further destabilizes the VMU. The finding of intervertebral collapse following these surgical procedures confirms the importance of the intervertebral disc and articular facet in the maintenance of spatial integrity.
Les modes de discours, interface entre texte et grammaire dans les langues de spécialité
Authors: Pic Elsa , Furmaniak Grégory 
Published: November 2012

Notre objectif est de présenter les apports que constituent pour l’étude grammaticale des langues de spécialité les « modes de discours » (Smith 2003). Nous montrons que, parce que les modes de discours sont définis à la fois formellement et sémantiquement, ils constituent un niveau d’analyse intermédiaire susceptible d’éclairer les rapports indirects entre les phénomènes grammaticaux de niveau phrastique et le fonctionnement pragmatico-discursif des textes. Les modes de discours possèdent deux avantages sur d’autres typologies existantes : leur caractère général les rend pertinents pour tout type de texte, y compris pour les textes vulgarisés, qui constituent la moitié de notre corpus, tandis que leur nombre réduit en fait un outil gérable et opératoire. Toutefois, le manque d’assise empirique du modèle de C. Smith ne lui permet pas de rendre compte d’un éventail suffisant de genres et de sous-genres et nécessite donc l’ajout de modes supplémentaires. En outre, bien que C. Smith attribue aux modes de discours des propriétés formelles et sémantico-pragmatiques, ce dernier aspect reste largement programmatique. C’est donc dans les théories françaises du discours que nous puisons pour pallier ces deux lacunes. Nous concluons par une analyse du hedging en discours spécialisé et en discours vulgarisé qui illustre la manière dont les modes de discours sont exploitables pour caractériser les propriétés linguistiques des textes.
Research in electronically-mediated communication in professional contexts – revisiting the past, preparing for the future
Authors: Gimenez Julio 
Published: November 2012

Cet article fait l’état des lieux des apports que l’étude du domaine de la communication véhiculée par l’électronique a eu en ce qui concerne notre compréhension de la nature et des objectifs de la communication en contexte professionnel. Il analyse les possibilités créées par les avancées technologiques récentes. L’article clôt sur un programme de recherches futures dans le domaine la communication véhiculée par l’électronique. Il met en avant la façon dont les thèmes ainsi que les activités dans ce programme peuvent être reliés aux quatre axes épistémologiques discutés lors du 33e colloque du GERAS : langue et discours, didactique, culture et technologie.
In Vitro Generation of Long-lived Human Plasma Cells
Authors: Cocco Mario , Stephenson Sophie , Care Matthew A. , Newton Darren , Barnes Nicholas A. , Davison Adam , Rawstron Andy , Westhead David R. , Doody Gina M. , Tooze Reuben M. 
Published: November 2012

Abstract
Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived unless supported by niche environments in which they may persist for years. No model system has linked B cell activation with niche function to allow the in vitro generation of long-lived PCs. Thus, the full trajectory of B cell terminal differentiation has yet to be investigated in vitro. In this article, we describe a robust model for the generation of polyclonal long-lived human PCs from peripheral blood B cells. After a proliferative plasmablast phase, PCs persist in the absence of cell division, with viability limited only by elective culture termination. Conservative predictions for PC life expectancy are 300 d, but with the potential for significantly longer life spans for some cells. These long-lived PCs are preferentially derived from memory B cells, and acquire a CD138high phenotype analogous to that of human bone marrow PCs. Analysis of gene expression across the system defines clusters of genes with related dynamics and linked functional characteristics. Importantly, genes in these differentiation clusters demonstrate a similar overall pattern of expression for in vitro and ex vivo PCs. In vitro PCs are fully reprogrammed to a secretory state and are adapted to their secretory load, maintaining IgG secretion of 120 pg/cell/day in the absence of XBP1 mRNA splicing. By establishing a set of conditions sufficient to allow the development and persistence of mature human PCs in vitro, to our knowledge, we provide the first platform with which to sequentially explore and manipulate each stage of human PC differentiation.
Potent Induction of Antibody-Secreting B Cells by Human Dermal-Derived CD14+ Dendritic Cells Triggered by Dual TLR Ligation
Authors: Matthews Katie , Chung Nancy P. Y. , Klasse Per Johan , Moore John P. , Sanders Rogier W. 
Published: November 2012

AbstractTargeting CD14+ dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naive B cells. In this study, we show that CD14+ DDCs express mRNA for TLRs 1–9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14+ DDCs, as shown by enhanced expression of B cell stimulatory cytokines (IL-6, IL-10, and TNF-α) and more pronounced phenotypic maturation. These combinations were resiquimod (R-848) plus polyinosinic-polycytidylic acid [Poly(I:C)], R-848 plus LPS, Pam3CSK4 plus Poly(I:C), and LPS plus Poly(I:C). We also found that selected TLR ligand pairs [R-848 plus either LPS or Poly(I:C)] were superior to individual agents at boosting the inherent capacity of CD14+ DDCs to induce naive B cells to proliferate and differentiate into CD27+ CD38+ B cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14+ DDCs also promoted the differentiation of Th1 (IFN-γ–secreting) CD4+ T cells, but not of Th2 or Th17 CD4+ T cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1.
Environmental and T Cell–Intrinsic Factors Limit the Expansion of Neonatal Follicular T Helper Cells but May Be Circumvented by Specific Adjuvants
Authors: Mastelic Béatris , Kamath Arun T. , Fontannaz Paola , Tougne Chantal , Rochat Anne-Françoise , Belnoue Elodie , Combescure Christophe , Auderset Floriane , Lambert Paul-Henri , Tacchini-Cottier Fabienne , Siegrist Claire-Anne 
Published: November 2012

Abstract
Follicular Th (TFH) cells have emerged as a new Th subset providing help to B cells and supporting their differentiation into long-lived plasma cells or memory B cells. Their differentiation had not yet been investigated following neonatal immunization, which elicits delayed and limited germinal center (GC) responses. We demonstrate that neonatal immunization induces CXCR5highPD-1high CD4+ TFH cells that exhibit TFH features (including Batf, Bcl6, c-Maf, ICOS, and IL-21 expression) and are able to migrate into the GCs. However, neonatal TFH cells fail to expand and to acquire a full-blown GC TFH phenotype, as reflected by a higher ratio of GC TFH/non-GC CD4+ T cells in immunized adults than neonates (3.8 × 10−3 versus 2.2 × 10−3, p = 0.01). Following the adoptive transfer of naive adult OT-II CD4+ T cells, OT-II TFH cells expand in the vaccine-draining lymph nodes of immunized adult but not infant recipients, whereas naive 2-wk-old CD4+ OT-II cells failed to expand in adult hosts, reflecting the influence of both environmental and T cell–intrinsic factors. Postponing immunization to later in life increases the number of TFH cells in a stepwise manner, in direct correlation with the numbers of GC B cells and plasma cells elicited. Remarkably, adjuvantation with CpG oligonucleotides markedly increased GC TFH and GC B cell neonatal responses, up to adult levels. To our knowledge, this is the first demonstration that the TFH cell development limits early life GC responses and that adjuvants/delivery systems supporting TFH differentiation may restore adultlike early life GC B cell responses.
B Lymphocyte–Induced Maturation Protein-1 Contributes to Intestinal Mucosa Homeostasis by Limiting the Number of IL-17–Producing CD4+ T Cells
Authors: Salehi Soofia , Bankoti Rashmi , Benevides Luciana , Willen Jessica , Couse Michael , Silva Joao S. , Dhall Deepti , Meffre Eric , Targan Stephan , Martins Gislâine A. 
Published: November 2012

Abstract
The transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) plays important roles in embryonic development and immunity. Blimp-1 is required for the differentiation of plasma cells, and mice with T cell–specific deletion of Blimp-1 (Blimp-1CKO mice) develop a fatal inflammatory response in the colon. Previous work demonstrated that lack of Blimp-1 in CD4+ and CD8+ T cells leads to intrinsic functional defects, but little is known about the functional role of Blimp-1 in regulating differentiation of Th cells in vivo and their contribution to the chronic intestinal inflammation observed in the Blimp1CKO mice. In this study, we show that Blimp-1 is required to restrain the production of the inflammatory cytokine IL-17 by Th cells in vivo. Blimp-1CKO mice have greater numbers of IL-17–producing TCRβ+CD4+cells in lymphoid organs and in the intestinal mucosa. The increase in IL-17–producing cells was not restored to normal levels in wild-type and Blimp-1CKO–mixed bone marrow chimeric mice, suggesting an intrinsic role for Blimp-1 in constraining the production of IL-17 in vivo. The observation that Blimp-1–deficient CD4+ T cells are more prone to differentiate into IL-17+/IFN-γ+ cells and cause severe colitis when transferred to Rag1-deficient mice provides further evidence that Blimp-1 represses IL-17 production. Analysis of Blimp-1 expression at the single cell level during Th differentiation reveals that Blimp-1 expression is induced in Th1 and Th2 but repressed by TGF-β in Th17 cells. Collectively, the results described here establish a new role for Blimp-1 in regulating IL-17 production in vivo.