bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Adiponectin With Left Ventricular Mass in Blacks
Authors: Bidulescu Aurelian , Liu Jiankang , Musani Solomon K. , Fox Ervin R. , Samdarshi Tandaw E. , Sarpong Daniel F. , Vaccarino Viola , Wilson Peter W. , Arnett Donna K. , Din-Dzietham Rebecca , Taylor Herman A. , Gibbons Gary H. 
Published: August 2011

Background—
Blacks have a higher prevalence of left ventricular hypertrophy than whites. Several population-based studies have reported an inverse association between adiponectin and left ventricular mass (LVM); however, the relationship between adiponectin levels and LVM has yet to be defined in blacks. The Jackson Heart Study cohort provides an opportunity to test the hypothesis that the inverse association between adiponectin and LVM may be modified by risk factors common among blacks.

Methods and Results—

The study population included 2649 black Jackson Heart Study participants (mean age 51±12 years, 63% women, 51% obese, 54% with hypertension, and 16% with diabetes). Multiple linear and spline regression was used to assess the association, with adjustment for demographic, clinical, and behavioral covariates. Among all the participants, there was a statistically significant but modest inverse association between adiponectin and LVM index. Hypertension and insulin resistance emerged as statistically significant effect modifiers of this relationship. The inverse association present among the normotensive participants was explained by obesity measures such as the body mass index. Among participants with both hypertension and insulin resistance, there was a significant direct association between adiponectin and the LVM index after multivariable adjustment (β=1.55,
P
=0.04, per 1-SD increment in the adiponectin log value).

Conclusions—
The association between serum adiponectin and LVM among blacks in the Jackson Heart Study cohort was dependent on hypertension and insulin resistance status. Normotensive blacks exhibited an inverse adiponectin-LVM association, whereas participants with hypertension and insulin resistance had a direct association.
Single-Molecule Imaging of Bmp4 Dimerization on Human Periodontal Ligament Cells
Authors: Mi H.-W. , Lee M.-C. , Chiang Y.-C. , Chow L.-P. , Lin C.-P. 
Published: August 2011

We expressed bone morphogenetic protein 4 (BMP4) fused with enhanced green fluorescent protein (BMP4-EGFP) in the secretory pathways of producer cells. Fluorescent EGFP was acquired only after we interrupted the transport of BMP4-EGFP by culturing cells at a lower temperature (20°C), and the dynamics of BMP4-EGFP could be monitored by single-molecule microscopy. Western blotting analysis confirmed that exposure to low temperature helped the integrated formation of BMP4-EGFP fusion proteins. In this study, for the first time, we could image the fluorescently labeled BMP4 molecules localized on the plasma membrane of living hPDL cells. The one-step photobleaching with EGFP and the “blinking” behavior of quantum dots suggest that the fluorescent spots represent the events of single BMP4 molecules. Single-molecule tracking showed that the BMP receptors (BMPR) dimerize after BMP4 stimulation, or that a complex of one BMP4 molecule and a pre-formed BMPR dimer develops first, followed by the binding of the second BMP4 molecule. Furthermore, BMP4-EGFP enhanced the osteogenic differentiation of hPDL cells via signal transduction involving BMP receptors. This single-molecule imaging technique might be a valuable tool for the future development of BMP4 gene therapy and regenerative medicine mediated by hPDLs. Abbreviations: BMP4, bone morphogenetic protein 4; BMPR, BMP receptor; EGFP, enhanced green fluorescent protein; hPDL cells, human periodontal ligament cells; QDs, quantum dots; TIRFM, total internal reflection fluorescence microscopy; 293 cells, human embryonic kidney cells; oDM, osteogenic differentiation medium; HcoI, type I collagen; ALP, alkaline phosphatase; BSP, bone sialoprotein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.
Evolutionary design of a full-envelope full-authority flight control system for an unstable high-performance aircraft
Authors: Avanzini G , Minisci E A 
Published: August 2011

The use of an evolutionary algorithm in the framework of H∞ control theory is being considered as a means for synthesizing controller gains that minimize a weighted combination of the infinite norm of the sensitivity function (for disturbance attenuation requirements) and complementary sensitivity function (for robust stability requirements) at the same time. The case study deals with a complete full-authority longitudinal control system for an unstable high-performance jet aircraft featuring (i) a stability and control augmentation system and (ii) autopilot functions (speed and altitude hold). Constraints on closed-loop response are enforced, that representing typical requirements on airplane handling qualities, that makes the control law synthesis process more demanding. Gain scheduling is required, in order to obtain satisfactory performance over the whole flight envelope, so that the synthesis is performed at different reference trim conditions, for several values of the dynamic pressure, used as the scheduling parameter. Nonetheless, the dynamic behaviour of the aircraft may exhibit significant variations when flying at different altitudes, even for the same value of the dynamic pressure, so that a trade-off is required between different feasible controllers synthesized at different altitudes for a given equivalent airspeed. A multi-objective search is thus considered for the determination of the best suited solution to be introduced in the scheduling of the control law. The obtained results are then tested on a longitudinal non-linear model of the aircraft.
What is the relationship between diabetes and depression? A qualitative meta-synthesis of patient experience of co-morbidity
Authors: Gask Linda , Macdonald Wendy , Bower Peter 
Published: August 2011

Aims: To develop an explanatory framework concerning patient experience of diabetes and depression and the relationship between these disorders; to better understand how interventions and health services should be delivered for this group of patients. Methods: The study used meta-synthesis. Published qualitative studies were identified using a structured search, and themes synthesized across studies to develop a new explanatory framework. Results: Searches of three databases identified 5506 papers, and 22 were included. Diagnosis of diabetes and the impact of symptoms on functioning were associated with varied psychological reactions, not all of which are negative, and the concept of ‘depression’ only captures aspects of the experience. Similarly, the relationship between diabetes and relationships with professionals and family were variable, with relationships serving as both a buffer of the effects of diabetes and potentially as a cause of further difficulties for patients. Depression and other psychological states were significant barriers to effective coping. Definition of ‘self’ emerged as a key potential moderator of the relationship between depression and diabetes. Conclusions: The variability in psychological reactions to diabetes suggested three key clinical implications, reflecting increasing levels of complexity for practitioners.
Clinical complexity and the effectiveness of an intervention for depressed diabetes patients
Authors: Piette John D , Valenstein Marcia , Himle Joseph , Duffy Sonia , Torres Trissa , Vogel Mark , Richardson Caroline 
Published: August 2011

Objectives: In a trial completed in 2010, US patients with diabetes and depression were randomized to usual care or telephone cognitive behavioural therapy that emphasized physical activity. Twelve-month intervention effects were observed for blood pressure, depression, and pedometer-measured step-counts. This study examined variation in intervention effects across patient subgroups defined by a measure of clinical complexity. Methods: Three groups of patients were identified at baseline using the Vector Model of Complexity that recognizes socioeconomic, biological, behavioural, and other determinants of treatment response. Complexity-by-intervention interactions were examined using regression models. Results: Intervention effects for blood pressure, depression, and step-counts differed across complexity levels (each p < 0.01). Effects on Beck Depression Inventory scores were greater in the low-complexity group (−8.8) than in the medium- (−3.2) or high-complexity groups (−2.7). Physical activity effects also were greatest in the low-complexity group (increase of 1498 steps per day). In contrast, systolic blood pressure effects were greater among intervention patients with high complexity (−8.5 mmHg). Conclusions: This intervention had varying impacts on physical and mental health depending on patients' clinical complexity. Physical activity and depressive symptom gains may be more likely among less complex patients, although more complex patients may achieve cardiovascular benefits through decreased blood pressures.
Water-skiing biomechanics: a study of intermediate skiers
Authors: Runciman R J 
Published: August 2011

This research project was initiated to examine the water-skiing biomechanics of the intermediate skier. The hypothesis was that equipment used by the skier would have a significant effect on the loads that they encountered during skiing and on their athletic performance. Nine intermediate water skiers were instrumented and performed a series of standard water-skiing manoeuvres. Skiing participants, conditions, and equipment used for the study were chosen where possible to represent those typically encountered by the average intermediate skier. The results from the study showed that water-start rope loads of up to 2.45 times body weight were sometimes encountered and that average running rope loads of 0.35–0.41 times body weight were observed. The choice of equipment was found to make a statistically significant impact on the rope loads both for water starting and while skiing. The rope loads for starting and skiing were significantly lower when using a large square-tailed water ski that was included in this study. The intermediate skiers in this study achieved no statistically significant performance advantage when using competitive-style tapered water skis when compared with the square-tailed and larger water ski included in the study.
ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters
Authors: Huang Royston-Luke , Teo Ziqiang , Chong Han Chung , Zhu Pengcheng , Tan Ming Jie , Tan Chek Kun , Lam Chee Ren Ivan , Sng Ming Keat , Leong David Tai Wei , Tan Suet Mien , Kersten Sander , Ding Jeak Ling , Li Hoi Yeung , Tan Nguan Soon 
Published: August 2011

Abstract
Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted C-terminal fibrinogen-like domain of angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial because of the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with 3 novel binding partners, integrin α5β1, VE-cadherin, and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin α5β1-mediated Rac1/PAK signaling to weaken cell–cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies.
CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity
Authors: Sakakibara Keiichi , Saito Naoya , Sato Takuji , Suzuki Atsushi , Hasegawa Yoko , Friedman Jonathan M. , Kufe Donald W. , VonHoff Daniel D. , Iwami Tadahiko , Kawabe Takumi 
Published: August 2011

Abstract
CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time- and dose-dependent manner for a broad spectrum of cancer cells, including multiple myeloma cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in a competitive manner with LMB and vice versa. Mass spectrometric analysis shows that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528 but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate.
Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia: a nationwide study
Authors: Nielsen Sune F. , Bojesen Stig E. , Birgens Henrik S. , Nordestgaard Børge G. 
Published: August 2011

Abstract
Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1.2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer, and NHL, similar to patients with childhood leukemia.
Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice
Authors: Steinbicker Andrea U. , Bartnikas Thomas B. , Lohmeyer Lisa K. , Leyton Patricio , Mayeur Claire , Kao Sonya M. , Pappas Alexandra E. , Peterson Randall T. , Bloch Donald B. , Yu Paul B. , Fleming Mark D. , Bloch Kenneth D. 
Published: August 2011

AbstractBone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired mobilization of iron stores and the anemia of chronic disease. Two BMP type I receptors, Alk2 (Acvr1) and Alk3 (Bmpr1a), are expressed in murine hepatocytes. We report that liver-specific deletion of either Alk2 or Alk3 causes iron overload in mice. The iron overload phenotype was more marked in Alk3- than in Alk2-deficient mice, and Alk3 deficiency was associated with a nearly complete ablation of basal BMP signaling and hepcidin expression. Both Alk2 and Alk3 were required for induction of hepcidin gene expression by BMP2 in cultured hepatocytes or by iron challenge in vivo. These observations demonstrate that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type I BMP receptors, Alk2 and Alk3, are required for regulation of hepcidin gene expression in response to iron and BMP signaling.
12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation
Authors: Singh Nikhlesh K. , Kundumani-Sridharan Venkatesh , Rao Gadiparthi N. 
Published: August 2011

Abstract
To understand the mechanisms by which 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) activates Rac1 in the induction of angiogenesis, we studied the role of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase and αPix. 15(S)-HETE stimulated Rac1 in a sustained manner in human dermal microvascular endothelial cells (HDMVECs). Simvastatin, a potent inhibitor of HMG-CoA reductase, suppressed 15(S)-HETE–induced Rac1 activation in HDMVECs affecting their migration and tube formation. 15(S)-HETE by inducing HMG-CoA reductase expression caused increased farnesylation and membrane translocation of Rac1 where it became activated by Src-dependent αPix stimulation. Mevalonate rescued 15(S)-HETE–induced Rac1 farnesylation and membrane translocation in HDMVECs and the migration and tube formation of these cells from inhibition by simvastatin. Down-regulation of αPix inhibited 15(S)-HETE–induced HDMVEC migration and tube formation. Hind-limb ischemia induced Rac1 farnesylation and activation leading to increased angiogenesis and these effects were blocked by simvastatin and rescued by mevalonate in WT mice. In contrast, hind-limb ischemia failed to induce Rac1 farnesylation and activation as well as angiogenic response in 12/15-Lox−/− mice. Activation of Src and αPix were also compromised at least to some extent in 12/15-Lox−/− mice compared with WT mice in response to hind-limb ischemia. Together, these findings demonstrate for the first time that HMG-CoA reductase plays a determinant role in 12/15-Lox–induced angiogenesis.
Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand
Authors: Jain Ashish , Kovacs Joseph A. , Nelson David L. , Migueles Stephen A. , Pittaluga Stefania , Fanslow William , Fan Xiying , Wong Duane W. , Massey Justin , Hornung Ronald , Brown Margaret R. , Spinner Jacob J. , Liu Shuying , Davey Victoria , Hill Harry A. , Ochs Hans , Fleisher Thomas A. 
Published: August 2011

AbstractX-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell–dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-γ and TNF-α. Intracellular cytokine staining studies showed that both CD4+ and CD8+ T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell–immune function in patients with XHM.
EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*
Authors: Kempf Werner , Pfaltz Katrin , Vermeer Maarten H. , Cozzio Antonio , Ortiz-Romero Pablo L. , Bagot Martine , Olsen Elise , Kim Youn H. , Dummer Reinhard , Pimpinelli Nicola , Whittaker Sean , Hodak Emmilia , Cerroni Lorenzo , Berti Emilio , Horwitz Steve , Prince H. Miles , Guitart Joan , Estrach Teresa , Sanches José A. , Duvic Madeleine , Ranki Annamari , Dreno Brigitte , Ostheeren-Michaelis Sonja , Knobler Robert , Wood Gary , Willemze Rein 
Published: August 2011

AbstractPrimary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs.