bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between Fatigue, Perfectionism, and Functional Dysphonia
Authors: O’Hara James , Miller Tracey , Carding Paul , Wilson Janet , Deary Vincent 
Published: March 2011

ObjectivesIncreased levels of fatigue and perfectionism were noted during evaluation of cognitive behavioral therapy for the treatment of functional dysphonia. The investigators thus aimed to explore levels of general fatigue and perfectionism in patients with functional dysphonia and controls.Study designCase‐control study.SettingTeaching hospital, United Kingdom.Subjects and MethodsPatients recruited through speech therapy were asked to recruit a friend as a control, of the same sex and within 5 years of their age. An 11‐point fatigue questionnaire, previously validated on a normal population, was analyzed using both Likert (0123) and bimodal (0011) systems, with a score greater than 4 on the bimodal system implying substantial fatigue. A 35‐point perfectionism questionnaire was also completed and analyzed for “healthy” and “unhealthy” perfectionist traits.ResultsThere were 75 cases and 62 controls. The mean fatigue score in patients with functional dysphonia was 17.0 and 14.4 for the controls (Likert, P =. 009). Under the bimodal scoring system, the mean fatigue scores in functional dysphonia (5.10) and controls (3.01) were also significantly different (P =. 003). The mean perfectionism scores were 98.9 for patients with functional dysphonia and 91.2 for controls (P = 0.043).ConclusionsTo the investigators’ knowledge, this is the first substantial report that fatigue and perfectionism scores are significantly elevated in functional dysphonia. Functional dysphonia is shown to be analogous to other medically unexplained physical symptoms that are also marked by generic somatopsychic distress and for which multiple factors are implicated in their onset and maintenance. This has implications for both research and treatment.
Morphological and functional vascular changes induced by childhood obesity
Authors: Ciccone Marco Matteo , Miniello Vito , Marchioli Roberto , Scicchitano Pietro , Cortese Francesca , Palumbo Vincenzo , Primitivo Stefano Giuseppe , Sassara Marco , Ricci Gabriella , Carbonara Santa , Gesualdo Michele , Diaferio Lucia , Mercuro Giuseppe , De Pergola Giovanni , Giordano Paola , Favale Stefano 
Published: March 2011

Background: To investigate endothelial dysfunction and morphological vascular changes in childhood obesity. Methods: 93 overweight/obese children (body mass index 26 ± 5 kg/m2; median 26 kg/m2; interquartile range 22–28 kg/m2), mean age 10.9 ± 2.7 years, underwent a check-up of total, high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, together with ultrasound measures of flow-mediated dilatation, carotid intima-media thickness, and anterior-posterior diameter of the abdominal aorta. Results: The body mass index of overweight/obese children had a statistically significant linear relationship ( p < 0.05) with triglycerides, erythrocyte sedimentation rate, carotid intima-media thickness, anterior-posterior diameter of the abdominal aorta, and flow-mediated dilatation values. Conclusions: Overweight/obese children have an initial endothelial dysfunction and vascular damage, i.e., the first stage in the development of atherosclerosis.
The renaissance of interferon therapy for the treatment of myeloid malignancies
Authors: Kiladjian Jean-Jacques , Mesa Ruben A. , Hoffman Ronald 
Published: March 2011

AbstractIFNα has been used to treat malignant and viral disorders for more than 25 years. Its efficacy is likely the consequence of its broad range of biologic activities, including direct effects on malignant cells, enhancement of anti-tumor immune responses, induction of proapoptotic genes, inhibition of angiogenesis, and promotion of the cycling of dormant malignant stem cells. Because of the recent development of “targeted” therapies, the use of IFN has been dramatically reduced over the last decade. The increasing awareness of the multistep pathogenesis of many malignancies has suggested, however, that such an approach using target-specific agents is not universally effective. These observations have resulted in a number of recent clinical trials utilizing IFNα in patients with chronic myeloid leukemia (CML), systemic mast cell disease, hypereosinophilic syndrome and the Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) with promising outcomes. These reports provide evidence that IFNα, alone or in combination with other agents, can induce surprisingly robust molecular response rates and possibly improve survival. Although IFNα at present remains an experimental form of therapy for patients with myeloid malignancies, these promising results suggest that it may become again an important component of the therapeutic arsenal for this group of hematologic malignancies.
Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent
Authors: Gersh Kathryn C. , Zaitsev Sergei , Cines Douglas B. , Muzykantov Vladimir , Weisel John W. 
Published: March 2011

AbstractStudies in animal models have shown that plasminogen activators bound to erythrocytes (RBC-PA) have an extended lifetime in the circulation and are safer than free PAs. RBC-PAs incorporate into nascent thrombi, which are focally lysed from within, an attractive thromboprophylactic option. In static systems, RBC-PAs cleave surrounding fibrin fibers, forming pores larger than the cells themselves, and move around the pore edges, enlarging them until eventual clot dissolution. We hypothesized that under flow in blood vessels, RBC-PAs form functional patent channels before clot dissolution. Here we used perfusion chambers to study clot lysis by RBC-PAs under static versus arterial and venous flow conditions. We found that flow decelerates bulk clot lysis but quickly generates patent channels filled with passing RBCs, via pore enlargement and merging in the direction of flow. Formation of such channels by RBC-PAs may help rescue ischemic tissue before bulk dissolution of potentially occlusive clots.
Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor
Authors: Waters Emily K. , Genga Ryan M. , Schwartz Michael C. , Nelson Jennifer A. , Schaub Robert G. , Olson Karen A. , Kurz Jeffrey C. , McGinness Kathleen E. 
Published: March 2011

AbstractHemophilia A and B are caused by deficiencies in coagulation factor VIII (FVIII) and factor IX, respectively, resulting in deficient blood coagulation via the intrinsic pathway. The extrinsic coagulation pathway, mediated by factor VIIa and tissue factor (TF), remains intact but is negatively regulated by tissue factor pathway inhibitor (TFPI), which inhibits both factor VIIa and its product, factor Xa. This inhibition limits clot initiation via the extrinsic pathway, whereas factor deficiency in hemophilia limits clot propagation via the intrinsic pathway. ARC19499 is an aptamer that inhibits TFPI, thereby enabling clot initiation and propagation via the extrinsic pathway. The core aptamer binds tightly and specifically to TFPI. ARC19499 blocks TFPI inhibition of both factor Xa and the TF/factor VIIa complex. ARC19499 corrects thrombin generation in hemophilia A and B plasma and restores clotting in FVIII-neutralized whole blood. In the present study, using a monkey model of hemophilia, FVIII neutralization resulted in prolonged clotting times as measured by thromboelastography and prolonged saphenous-vein bleeding times, which are consistent with FVIII deficiency. ARC19499 restored thromboelastography clotting times to baseline levels and corrected bleeding times. These results demonstrate that ARC19499 inhibition of TFPI may be an effective alternative to current treatments of bleeding associated with hemophilia.
IMiD immunomodulatory compounds block C/EBPβ translation through eIF4E down-regulation resulting in inhibition of MM
Authors: Li Shirong , Pal Rekha , Monaghan Sara A. , Schafer Peter , Ouyang Hongjiao , Mapara Markus , Galson Deborah L. , Lentzsch Suzanne 
Published: March 2011

AbstractImmunomodulatory derivatives of thalidomide (IMiD compounds), such as pomalidomide and lenalidomide, are highly active in multiple myeloma (MM) treatment. However, the precise mechanisms of action and resistance in MM are unresolved. Here we show that IMiD compounds down-regulate CCAAT/enhancer-binding protein-β (C/EBPβ) resulting in abrogation of cell proliferation. Overexpression of C/EBPβ rescued MM cells from IMiD-induced inhibition of proliferation, indicating that C/EBPβ is critical in mediating antiproliferative effects. IMiD-induced decrease of C/EBPβ protein led to impaired transcription of interferon regulatory factor 4 (IRF4). Down-regulation of IRF4 by lenalidomide was confirmed by longitudinal studies of bone marrow samples from 23 patients obtained before and during lenalidomide treatment using CD138+/IRF4+ double labeling. In contrast to down-regulation of C/EBPβ protein, IMiD compounds did not alter C/EBPβ mRNA levels or protein stability, suggesting translational regulation of C/EBPβ. We could demonstrate that C/EBPβ protein expression is under eIF4E-translational control in MM. Furthermore, inhibition of the eIF4E-C/EBPβ axis by IMiD compounds was not observed in IMiD-resistant MM cells. However, targeting translation at a different level by inhibiting eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation overcame resistance, suggesting that this pathway is critical and might be a target to overcome drug resistance.
Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy
Authors: Wang Hongjie , Madhusudhan Thati , He Tao , Hummel Björn , Schmidt Simone , Vinnikov Ilya A. , Shahzad Khurrum , Kashif Muhammed , Muller-Krebs Sandra , Schwenger Vedat , Bierhaus Angelika , Rudofsky Gottfried , Nawroth Peter P. , Isermann Berend 
Published: March 2011

AbstractWhereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.
HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients
Authors: Zerr Danielle M. , Fann Jesse R. , Breiger David , Boeckh Michael , Adler Amanda L. , Xie Hu , Delaney Colleen , Huang Meei-Li , Corey Lawrence , Leisenring Wendy M. 
Published: March 2011

AbstractHuman herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.
Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis
Authors: Fos José , Pabst Thomas , Petkovic Vibor , Ratschiller Daniel , Mueller Beatrice U. 
Published: March 2011

Abstract
CCAAT/enhancer binding protein-α (CEBPA) mutations in acute myeloid leukemia (AML) patients with a normal karyotype (NK) confer favorable prognosis, whereas NK-AML patients per se are of intermediate risk. This suggests that blocked CEBPA function characterizes NK-AML with favorable outcome. We determined the prognostic significance of CEBPA DNA binding function by enzyme-linked immunosorbent assay in 105 NK-AML patients. Suppressed CEBPA DNA binding was defined by 21 good-risk AML patients with inv(16) or t(8;21) (both abnormalities targeting CEBPA) and 8 NK-AML patients with dominant-negative CEBPA mutations. NK-AML patients with suppressed CEBPA function showed a better overall survival (P = .0231) and disease-free survival (P = .0069) than patients with conserved CEBPA function. Suppressed CEBPA DNA binding was an independent marker for better overall survival and disease-free survival in a multivariable analysis that included FLT3-ITD, NPM1 and CEBPA mutation status, white blood cell count, age and lactate dehydrogenase. These data indicate that suppressed CEBPA function is associated with favorable prognosis in NK-AML patients.
Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia
Authors: Barsam Sarah J. , Psaila Bethan , Forestier Marc , Page Lemke K. , Sloane Peter A. , Geyer Julia T. , Villarica Glynis O. , Ruisi Mary M. , Gernsheimer Terry B. , Beer Juerg H. , Bussel James B. 
Published: March 2011

AbstractThis study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 109/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P = .001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r2 = −0.578, P = .015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect.
Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia
Authors: Montes Rosa , Ayllón Verónica , Gutierrez-Aranda Ivan , Prat Isidro , Hernández-Lamas M. Carmen , Ponce Laura , Bresolin Silvia , te Kronnie Geertruy , Greaves Mel , Bueno Clara , Menendez Pablo 
Published: March 2011

AbstractInfant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency. Our limited understanding of transformation by MLL-AF4 is reflected in murine models, which do not accurately recapitulate the human disease. Human models for MLL-AF4 disease do not exist. Hematopoietic stem or progenitor cells (HSPCs) represent probable targets for transformation. Here, we explored in vitro and in vivo the impact of the enforced expression of MLL-AF4 in human cord blood-derived CD34+ HSPCs. Intrabone marrow transplantation into NOD/SCID-IL2Rγ−/− mice revealed an enhanced multilineage hematopoietic engraftment, efficiency, and homing to other hematopoietic sites on enforced expression of MLL-AF4. Lentiviral transduction of MLL-AF4 into CD34+ HSPCs increased the in vitro clonogenic potential of CD34+ progenitors and promoted their proliferation. Consequently, cell cycle and apoptosis analyses suggest that MLL-AF4 conveys a selective proliferation coupled to a survival advantage, which correlates with changes in the expression of genes involved in apoptosis, sensing DNA damage and DNA repair. However, MLL-AF4 expression was insufficient to initiate leukemogenesis on its own, indicating that either additional hits (or reciprocal AF4-MLL product) may be required to initiate ALL or that cord blood-derived CD34+ HSPCs are not the appropriate cellular target for MLL-AF4-mediated ALL.
The impact of inflammatory licensing on heme oxygenase-1–mediated induction of regulatory T cells by human mesenchymal stem cells
Authors: Mougiakakos Dimitrios , Jitschin Regina , Johansson C. Christian , Okita Riki , Kiessling Rolf , Le Blanc Katarina 
Published: March 2011

Abstract
Mesenchymal stem cells (MSCs) are characterized by their manifold immunomodulatory and regenerative properties. The stress-responsive, cytoprotective, and immunoregulatory molecule heme oxygenase-1 (HO-1) was recently identified as a key contributor for MSC-mediated suppression of alloactivated T cells. As HO-1 has also been implicated in the induction of regulatory T cells (Tregs), we sought to examine its impact on MSC-driven promotion of Tregs. Human MSCs were shown to induce, in a HO-1–dependent fashion, IL-10+ Tr1 and transforming growth factor-β+ Th3 Treg-subsets in allo- and T-cell receptor-activated lymphocytes. Because inflammatory stimuli modulate (“license”) human MSCs, we were interested in whether an in vitro alloreactive micro-milieu within mixed lymphocyte reactions (MLRs) alters the HO-1 expression. We observed a substantial down-regulation of HO-1 facilitated by yet unidentified soluble factor(s) produced in an MLR, and most probably occurring at the level of its major transcription-factor NF-E2–related factor 2. Interestingly, HO-1 lost its impact regarding suppressiveness, Treg induction, and promotion of IL-10 production for MSCs, which were prelicensed in an MLR environment. Taken together, we show that HO-1 produced by human MSCs beyond its direct suppressive function promotes formation of Tr1 and Th3 Tregs and IL-10 production, functions, which are taken over by other molecules, among them COX-2, after an alloreactive priming.
Clonal immunoglobulin DNA in the plasma of patients with AIDS lymphoma
Authors: Wagner-Johnston Nina D. , Gellert Lan , Gocke Christopher D. , Lemas Victor M. , Lee Jeannette , Martínez-Maza Otoniel , Ambinder Richard F. 
Published: March 2011

Abstract
Immunoglobulin (Ig) gene rearrangements are used to define clonality of suspected B-lineage malignancy in tissue samples. To determine whether such rearrangements could be identified in plasma, we screened plasma from 14 consecutive patients with AIDS-related lymphoma with multiplex Ig primers. Clonally rearranged Ig DNA was detected in plasma from 7 of 14 patients. Patients in whom clonal Ig DNA remained detectable after combination chemotherapy died with lymphoma. Tumor was available from 1 patient, and the IgH amplification products from plasma and tumor were sequenced and confirmed to be identical. Ig DNA rearrangements in plasma may be useful as a lymphoma-specific tumor marker, and failure to clear clonal Ig DNA may identify patients at high risk for failure of standard therapy.
Observation of strong anisotropic forbidden transitions in (001) InGaAs/GaAs single-quantum well by reflectance-difference spectroscopy and its behavior under uniaxial strain
Authors: Yu Jin-Ling , Chen Yong-Hai , Tang Chen-Guang , Jiang ChongYun , Ye Xiao-Ling 
Published: March 2011

AbstractThe strong anisotropic forbidden transition has been observed in a series of InGaAs/GaAs single-quantum well with well width ranging between 3 nm and 7 nm at 80 K. Numerical calculations within the envelope function framework have been performed to analyze the origin of the optical anisotropic forbidden transition. It is found that the optical anisotropy of this transition can be mainly attributed to indium segregation effect. The effect of uniaxial strain on in-plane optical anisotropy (IPOA) is also investigated. The IPOA of the forbidden transition changes little with strain, while that of the allowed transition shows a linear dependence on strain.PACS 78.66.Fd, 78.20.Bh, 78.20.Fm
An aeroponic culture system for the study of root herbivory on Arabidopsis thaliana
Authors: Vaughan Martha M , Tholl Dorothea , Tokuhisa James G 
Published: March 2011

Abstract

Background
Plant defense against herbivory has been studied primarily in aerial tissues. However, complex defense mechanisms have evolved in all parts of the plant to combat herbivore attack and these mechanisms are likely to differ in the aerial and subterranean environment. Research investigating defense responses belowground has been hindered by experimental difficulties associated with the accessibility and quality of root tissue and the lack of bioassays using model plants with altered defense profiles.

Results
We have developed an aeroponic culture system based on a calcined clay substrate that allows insect herbivores to feed on plant roots while providing easy recovery of the root tissue. The culture method was validated by a root-herbivore system developed for Arabidopsis thaliana and the herbivore Bradysia spp. (fungus gnat). Arabidopsis root mass obtained from aeroponically grown plants was comparable to that from other culture systems, and the plants were morphologically normal. Bradysia larvae caused considerable root damage resulting in reduced root biomass and water absorption. After feeding on the aeroponically grown root tissue, the larvae pupated and emerged as adults. Root damage of mature plants cultivated in aeroponic substrate was compared to that of Arabidopsis seedlings grown in potting mix. Seedlings were notably more susceptible to Bradysia feeding than mature plants and showed decreased overall growth and survival rates.

Conclusions
A root-herbivore system consisting of Arabidopsis thaliana and larvae of the opportunistic herbivore Bradysia spp. has been established that mimics herbivory in the rhizosphere. Bradysia infestation of Arabidopsis grown in this culture system significantly affects plant performance. The culture method will allow simple profiling and in vivo functional analysis of root defenses such as chemical defense metabolites that are released in response to belowground insect attack.