bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a microglia phenotype supportive of remyelination
Authors: Olah Marta , Amor Sandra , Brouwer Nieske , Vinet Jonathan , Eggen Bart , Biber Knut , Boddeke Hendrikus W. G. M. 
Published: November 2011

AbstractIn multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome‐wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin‐induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelination‐supportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. © 2011 Wiley Periodicals, Inc.
A systematic review of the accuracy and clinical utility of the Addenbrooke's Cognitive Examination and the Addenbrooke's Cognitive Examination—Revised in the diagnosis of dementia
Authors: Crawford Stephanie , Whitnall Leigh , Robertson Joanne , Evans Jonathan J. 
Published: November 2011

ObjectivesTo review the evidence relating to the diagnostic accuracy and clinical utility of the Addenbrooke's Cognitive Examination (ACE) and its updated version, the Addenbrooke's Cognitive Examination—Revised (ACE‐R) in relation to the diagnosis of dementia.DesignA systematic search of relevant databases was conducted, covering the period 2000 to April 2010. Specific journals and reference lists were hand searched. Identified studies that fulfilled the inclusion criteria were reviewed using a tailored, methodological quality rating checklist.ResultsThe systematic search process identified nine studies for review (seven relating to the ACE, two on the ACE‐R). Strengths and weaknesses across studies are considered, and diagnostic accuracy measures are presented for six out of the nine studies.ConclusionThe evidence suggests that the ACE/ACE‐R is capable of providing information on a range of cognitive domains and of differentiating well between those with and those without cognitive impairment. Further research examining how the tools distinguish between dementia subtypes and mild cognitive impairment will further benefit the evidence base. Copyright © 2011 John Wiley & Sons, Ltd.
Eddy correlations for water flow in a single fracture with abruptly changing aperture
Authors: Qian Jiazhong , Liang Min , Chen Zhou , Zhan Hongbin 
Published: November 2011

AbstractFluid flow in single fractures with non‐uniform apertures is an important research subject in many disciplines. The abruptly changing aperture is a special case of such non‐uniformity. This paper simulates water flow in a single fracture with abruptly changing aperture (SF‐ACA) using the Lattice Boltzmann Method (LBM) and the Finite Volume Method (FVM). The flow occurs with the Reynolds number (Re) ranging from 5 to 900 and a ratio of aperture change (E) of 3 (E = D/d, where D and d are the larger and smaller apertures, respectively). For Re values between 5 and 100, both LBM and FVM can successfully simulate the eddy development in the expansion regime of an SF‐ACA. Flow with high Re values (up to 900) is simulated by FVM, which appears to be numerically more stable than LBM for high‐Re flow problems studied here. The flow symmetry in the expansion regime breaks at the Re value between 400 and 500. Our simulation result shows a linear relationship between l1/d and Re at low Re (5–100) or higher Re (110–900) values, where defined as the length from the location of abrupt expansion to the right edge of the first eddy along the flow direction. If considering the simulation results for the entire simulated range of Re (5–900), the l1/d–Re relationship is better described by a non‐linear logarithmical function. The l1/d approaches an asymptotic constant at large Re. Copyright © 2011 John Wiley & Sons, Ltd.
Height loss predicts subsequent hip fracture in men and women of the Framingham Study
Authors: Hannan Marian T , Broe Kerry E , Cupples L Adrienne , Dufour Alyssa B , Rockwell Margo , Kiel Douglas P 
Published: November 2011

Abstract
Although height is a risk factor for osteoporotic fracture, current risk assessments do not consider height loss. Height loss may be a simple measurement that clinicians could use to predict fracture or need for further testing. The objective was to examine height loss and subsequent hip fracture, evaluating both long-term adult height loss and recent height loss. Prospective cohort of 3081 adults from the Framingham Heart Study. Height was measured biennially since 1948, and cohort followed for hip fracture through 2005. Adult height loss from middle-age years across 24 years and recent height loss in elderly years were considered. Cox proportional hazard regression was used to estimate association between height loss and risk of hip fracture. Of 1297 men and 1784 women, mean baseline age was 66 years (SD = 7.8). Average height loss for men was 1.06 inches (0.76), and for women was 1.12 inches (0.84). A total of 11% of men and 15% of women lost ≥2 inches of height. Mean follow-up was 17 years, during which 71 men and 278 women had incident hip fractures. For each 1-inch of height loss, hazard ratio (HR) = 1.4 in men [95% confidence interval (CI): 1.00, 1.99], and 1.04 in women (95% CI: 0.88, 1.23). Men and women who lost ≥2 inches of height had increased fracture risk (compared with 0 to &lt;2 inches) of borderline significance: men HR = 1.8, 95% CI: 0.86, 3.61; women HR = 1.3, 95% CI: 0.90, 1.76. Recent height loss in elders significantly increased the risk of hip fracture, 54% in men and 21% in women (95% CI: 1.14, 2.09; 1.03, 1.42, respectively). Adult height loss predicted hip fracture risk in men in our study. Recent height loss in elderly men and women predicted risk of hip fracture. © 2012 American Society for Bone and Mineral Research
Height loss in older women: Risk of hip fracture and mortality independent of vertebral fractures
Authors: Hillier Teresa A , Lui Li-Yung , Kado Deborah M , LeBlanc ES , Vesco Kimberly K , Bauer Douglas C , Cauley Jane A , Ensrud Kristine E , Black Dennis M , Hochberg Marc C , Cummings Steven R 
Published: November 2011

Abstract
We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual-energy X-ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986–1988) and year 15 (2002–2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow-up occurred every 4 months for fractures and vital status (&gt;95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss &gt;5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self-reported height at age 25 (−40 years) to measured height age &gt;65 years (Year 0)] demonstrated consistent results. Height loss &gt;5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality—independent of incident VFx and BMD. © 2012 American Society for Bone and Mineral Research
RANK-dependent autosomal recessive osteopetrosis: Characterization of five new cases with novel mutations
Authors: Pangrazio Alessandra , Cassani Barbara , Guerrini Matteo M , Crockett Julie C , Marrella Veronica , Zammataro Luca , Strina Dario , Schulz Ansgar , Schlack Claire , Kornak Uwe , Mellis David J , Duthie Angela , Helfrich Miep H , Durandy Anne , Moshous Despina , Vellodi Ashok , Chiesa Robert , Veys Paul , Lo Iacono Nadia , Vezzoni Paolo , Fischer Alain , Villa Anna , Sobacchi Cristina 
Published: November 2011

Abstract
Autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder attributed to reduced bone resorption by osteoclasts. Most human AROs are classified as osteoclast rich, but recently two subsets of osteoclast-poor ARO have been recognized as caused by defects in either TNFSF11 or TNFRSF11A genes, coding the RANKL and RANK proteins, respectively. The RANKL/RANK axis drives osteoclast differentiation and also plays a role in the immune system. In fact, we have recently reported that mutations in the TNFRSF11A gene lead to osteoclast-poor osteopetrosis associated with hypogammaglobulinemia. Here we present the characterization of five additional unpublished patients from four unrelated families in which we found five novel mutations in the TNFRSF11A gene, including two missense and two nonsense mutations and a single-nucleotide insertion. Immunological investigation in three of them showed that the previously described defect in the B cell compartment was present only in some patients and that its severity seemed to increase with age and the progression of the disease. HSCT performed in all five patients almost completely cured the disease even when carried out in late infancy. Hypercalcemia was the most important posttransplant complication. Overall, our results further underline the heterogeneity of human ARO also deriving from the interplay between bone and the immune system, and highlight the prognostic and therapeutic implications of the molecular diagnosis. © 2012 American Society for Bone and Mineral Research
Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures
Authors: Donnelly Eve , Meredith Dennis S , Nguyen Joseph T , Gladnick Brian P , Rebolledo Brian J , Shaffer Andre D , Lorich Dean G , Lane Joseph M , Boskey Adele L 
Published: November 2011

Abstract
Reduction of bone turnover with bisphosphonate treatment alters bone mineral and matrix properties. Our objective was to investigate the effect of bisphosphonate treatment on bone tissue properties near fragility fracture sites in the proximal femur in postmenopausal women with osteoporosis. The mineral and collagen properties of corticocancellous biopsies from the proximal femur were compared in bisphosphonate-naive (−BIS, n = 20) and bisphosphonate-treated (+BIS, n = 20, duration 7 ± 5 years) patients with intertrochanteric (IT) and subtrochanteric (ST) fractures using Fourier transform infrared imaging (FTIRI). The mean values of the FTIRI parameter distributions were similar across groups, but the widths of the parameter distributions tended to be reduced in the +BIS group relative to the −BIS group. Specifically, the widths of the cortical collagen maturity and crystallinity were reduced in the +BIS group relative to those of the −BIS group by 28% (+BIS 0.45 ± 0.18 versus −BIS 0.63 ± 0.28, p = 0.03) and 17% (+BIS 0.087 ± 0.012 versus −BIS 0.104 ± 0.036, p = 0.05), respectively. When the tissue properties were examined as a function of fracture morphology within the +BIS group, the FTIR parameters were generally similar regardless of fracture morphology. However, the cortical mineral:matrix ratio was 8% greater in tissue from patients with atypical ST fractures (n = 6) than that of patients with typical (IT or spiral ST) fractures (n = 14) (Atypical 5.6 ± 0.3 versus Typical 5.2 ± 0.5, p = 0.03). Thus, although the mean values of the FTIR properties were similar in both groups, the tissue in bisphosphonate-treated patients had a more uniform composition than that of bisphosphonate-naive patients. The observed reductions in mineral and matrix heterogeneity may diminish tissue-level toughening mechanisms. © 2012 American Society for Bone and Mineral Research
Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity
Authors: Ge Chunxi , Yang Qian , Zhao Guisheng , Yu Hong , Kirkwood Keith L , Franceschi Renny T 
Published: November 2011

Abstract
RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase-mediated phosphorylation. However, the specific contribution of each kinase to RUNX2-dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P-RUNX2-specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcriptional activity. However, a clear preference for ERK1 versus p38α/β was found when the ability of these MAPKs to phosphorylate and activate RUNX2 was compared. Similarly, ERK1 preferentially bound to a consensus MAPK binding site on RUNX2 that was essential for the activity of either kinase. To assess the relative contribution of ERK1/2 and p38 to osteoblast gene expression, MC3T3-E1 preosteoblast cells were grown in control or ascorbic acid (AA)-containing medium ± BMP2/7. AA-induced gene expression, which requires collagen matrix synthesis, was associated with parallel increases in P-ERK and RUNX2-S319-P in the absence of any changes in P-p38. This response was blocked by ERK, but not p38, inhibition. Significantly, in the presence of AA, BMP2/7 synergistically stimulated RUNX2 S319 phosphorylation and transcriptional activity without affecting total RUNX2 and this response was totally dependent on ERK/MAPK activity. In contrast, although p38 inhibition partially blocked BMP-dependent transcription, it did not affect RUNX2 S319 phosphorylation, suggesting the involvement of other phosphorylation sites and/or transcription factors in this response. Based on this work, we conclude that extracellular matrix and BMP regulation of RUNX2 phosphorylation and transcriptional activity in osteoblasts is predominantly mediated by ERK rather than p38 MAPKs. © 2012 American Society for Bone and Mineral Research.
Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements
Authors: Liu X Sherry , Stein Emily M , Zhou Bin , Zhang Chiyuan A , Nickolas Thomas L , Cohen Adi , Thomas Valerie , McMahon Donald J , Cosman Felicia , Nieves Jeri , Shane Elizabeth , Guo X Edward 
Published: November 2011

Abstract
Osteoporosis is typically diagnosed by dual-energy X-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabecula segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by microfinite element analysis (µFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip, and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number, and plate–rod and rod–rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number, and connectivity were directly associated with bone stiffness. In contrast, rod volume, number, and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and µFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and µFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. © 2012 American Society for Bone and Mineral Research
Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?
Authors: Karasik David , Cheung Ching Lung , Zhou Yanhua , Cupples L Adrienne , Kiel Douglas P , Demissie Serkalem 
Published: November 2011

Abstract
Multiple musculoskeletal traits assessed by various methods at different skeletal sites serve as surrogates for osteoporosis risk. However, it is a challenge to select the most relevant phenotypes for genetic study of fractures. Principal component analyses (PCA) were conducted in participants of the Framingham Osteoporosis Study on 17 measures including bond mineral density (BMD) (hip and spine), heel ultrasound, leg lean mass (LLM), and hip geometric indices, adjusting for covariates (age, height, body mass index [BMI]), in a combined sample of 1180 men and 1758 women, as well as in each sex. Four principal components (PCs) jointly explained ∼69% of the total variability of musculoskeletal traits. PC1, explaining ∼33% of the total variance, was referred to as the component of “Bone strength,” because it included the hip and spine BMD as well as several hip cross-sectional properties. PC2 (20.5% variance) was labeled as “Femoral cross-sectional geometry;” PC3 (∼8% variance) captured only ultrasound measures; PC4, explaining ∼7% variance, was correlated with LLM and hip geometry. We then evaluated ∼2.5 mil SNPs for association with PCs 1, 2, and 4. There were genome-wide significant associations (p &lt; 5 × 10−8) between PC2 and HTR1E (that codes for one of the serotonin receptors) and PC4 with COL4A2 in women. In the sexes-combined sample, AKAP6 was associated with PC2 (p = 1.40 × 10−7). A single nucleotide polymorphism (SNP) in HTR1E was also associated with the risk of nonvertebral fractures in women (p = 0.005). Functions of top associated genes were enriched for the skeletal and muscular system development (p &lt; 0.05). In conclusion, multivariate combination provides genetic associations not identified in the analysis of primary phenotypes. Genome-wide screening for the linear combinations of multiple osteoporosis-related phenotypes suggests that there are variants with potentially pleiotropic effects in established and novel pathways to be followed up to provide further evidence of their functions. © 2012 American Society for Bone and Mineral Research
The Italian registry of therapeutic apheresis: Granulocyte–monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study
Authors: Passalacqua Stefano , Ferraro Pietro Manuel , Bresci Giampaolo , D'Ovidio Valeria , Astegiano Marco , Principi Mariabeatrice , Testa Roberto , D'Incà Renata , Valpiani Daniela , Armuzzi Alessandro , Sablich Renato , Cavallaro Flaminia , Costa Francesco , Di Leo Vincenza , Colombo Elisabetta , Santini Alessia , Aratari Annalisa , Lecis Pierenrico , Saladino Valeria , Riegler Gabriele , Marco Marino , Calella Francesca , Ricci Chiara , Guidi Maria Luisa , Repaci Giuseppe , Silla Michele 
Published: November 2011

AbstractLeukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte–monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered. © 2011 Wiley Periodicals, Inc.