bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Different Metabolic Syndrome Definitions Predict Cerebrovascular Events and Coronary Heart Disease Independent of Their Components?
Authors: Hadaegh Farzad , Mohebi Reza , Cheraghi Leila , Tohidi Maryam , Moghaddam Nahid Beladi , Bozorogmanesh Mohammadreza , Sheikholeslami Farhad , Azizi Fereidoun 
Published: March 2012

Background and Purpose—
The purpose of this study was to examine whether metabolic syndrome (MetS), applying different definitions, predicts incident coronary heart disease (CHD) and cerebrovascular events (CVAs) independent of its components.

Methods—
Among 2548, aged ≥50 years, World Health Organization, International Diabetes Federation, and Joint Interim Statement criteria were used to define MetS. Cox proportional hazards regression was implemented to estimate hazard ratios of incident CVA and CHD.

Results—
During 9.3 years of follow-up, 72 and 343 cases of CVA and CHD events occurred. The multivariate hazard ratios (95% CI) of incident CVA and CHD were 2.71 (1.57–4.68) and 2.07 (1.63–2.64) for MetS as defined by the Joint Interim Statement, respectively. There was no difference among the 3 definitions of MetS regarding the prediction of the CVA incidence. However, MetS as defined by the Joint Interim Statement predicted CHD better than the International Diabetes Federation definition. After adjustment for components, MetS lost its association with CHD and CVA; in this model, the elevated blood pressure and high fasting plasma glucose (International Diabetes Federation definition) showed significant risk for CVA events; regarding CHD events, the elevated blood pressure, high fasting plasma glucose, and, for World Health Organization definition, obesity and dyslipidemia remained as predictors.

Conclusions—
All definitions of MetS were associated with CVA and CHD events. After adjusting its components, MetS lost its association with incident CVA and CHD; however, elevated blood pressure for both CVA and CHD events and high fasting plasma glucose for CHD events remained as independent predictors in all definitions.
Does Passive Smoking Have an Effect on Nasal Mucociliary Clearance?
Authors: Habesoglu Mehmet , Demir Kadri , Yumusakhuylu Ali Cemal , Sahin Yilmaz Asli , Oysu Cagatay 
Published: March 2012

ObjectiveThe aim of this study is to review the literature about nasal mucociliary clearance (MCC) and passive smoking in otorhinolaryngology by clearly explaining their relationship in a cross‐sectional study.Study Design and SettingThis cross‐sectional study was conducted at the Umraniye Education and Research Hospital in Turkey. Umraniye Education and Research Hospital Ethical Committee approved the study, and informed consents of the patients were obtained.MethodsOur study consisted of patients who presented to the Ear‐Nose‐Throat Department of Istanbul Umraniye Education and Research Hospital between February 2011 and July 2011. Three groups of subjects were evaluated: 15 passive smokers (group 1), 17 active smokers (group 2), and 15 healthy matched controls (group 3). All patients were asked to answer our questions regarding their smoking history, and nasal MCC time was assessed for all individuals of the 3 groups.ResultsThe mean MCC value was 23.59 ± 12.41 in the smoking group, 12.6 ± 4.67 in the passive smoking group, and 6.4 ± 1.55 in the healthy group. The comparison of MCC values between the smoking group and passive smoking group and between the smoking group and healthy group revealed statistically significant differences (P <. 01). There was also a significant difference between the MCC values of the passive smoking group and the healthy group (P <. 01). In addition, we compared MCC values according to exposure number of cigarettes.ConclusionIn this study, we conclude that passive smoking affects nasal MCC. Both active and passive smoking increases nasal MCC time when compared with healthy controls.
Ultrasonographic Assessment of Humeral Retrotorsion in Baseball Players
Authors: Myers Joseph B. , Oyama Sakiko , Clarke John P. 
Published: March 2012

Background: Recently, clinicians and researchers started using diagnostic ultrasound to measure humeral torsion as an alternative to radiological assessments in overhead-throwing athletes and other clinical populations. Ultrasound appears to be a reliable, nonradiological alternative, but ultrasound assessment has not been validated against computed tomography (CT), the current gold standard. Purpose: This study aimed to establish the validity of an ultrasound assessment of humeral torsion by comparing data obtained using both ultrasound and CT, the current standard. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Humeral torsion was measured using both ultrasound and CT in 24 collegiate-aged baseball players. Comparisons between the assessments were made using both regression and Bland-Altman plots. Reliability and precision were also established. Results: A strong relationship existed between humeral torsion variables obtained with ultrasound and CT ( R = .797, R2 = .635, P < .001). The ultrasound assessment yielded reliability coefficients ranging from .991 to .997, with approximately 1° of measurement error. The CT method’s reliability coefficients ranged from .805 to .933, with approximately 3.5° of measurement error. Conclusion: There was a strong relationship between humeral torsion obtained with ultrasound and CT, the current standard of assessment. Ultrasound provides a reliable, valid alternative to CT for obtaining an indication of the amount of humeral torsion in the upper extremity.
Dynamic Sagittal Plane Trunk Control During Anterior Cruciate Ligament Injury
Authors: Sheehan Frances T. , Sipprell William H. , Boden Barry P. 
Published: March 2012

Background: Recent studies have demonstrated that trunk control likely plays a role in anterior cruciate ligament (ACL) injury. Yet, the majority of ACL research remains focused on the lower limb, with limited information on the trunk position at the time of injury. Hypotheses: Athletes experiencing a noncontact ACL injury after a 1-legged landing position their center of mass (COM) more posterior from the base of support (BOS) at initial ground contact in comparison with uninjured athletes. The distance from the COM to the BOS (COM_BOS) is larger in female, as compared with male, athletes during 1-legged landing. Study Design: Case control study; Level of evidence, 3. Methods: Movie captures of 20 athletes performing a 1-legged landing maneuver resulting in a torn ACL were compared with matched (for gender, sport, and activity just before landing) movie captures of 20 athletes performing a similar maneuver that did not result in an ACL disruption (controls). The COM_BOS, trunkG angle, and limbG angle (both relative to the gravity vector) were measured in the sagittal plane at initial ground-foot contact. A 2-way ANOVA (injury status × gender) was used to examine the hypotheses. Results: There was a significant difference in all 3 measures based on injury status but not on gender. The COM_BOS, normalized by femur length, and limbG angle were greater (Δ = 0.9, P < .001 and Δ = 16°, P = .004, respectively), and the trunkG angle was smaller (Δ = 12°, P = .016) in the participants who sustained an ACL injury as compared with controls. The average COM was calculated as 38 cm more posterior relative to the BOS in the participants who sustained an ACL injury as compared with controls. Conclusion: Landing with the COM far posterior to the BOS may be a risk factor for noncontact ACL injury and potentially can be addressed in prevention programs.
Sulfasalazine prevents the increase in TGF-β, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat
Authors: Chávez E , Castro-Sánchez L , Shibayama M , Tsutsumi V , Moreno MG , Muriel P 
Published: March 2012

It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor κB (NFκB) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl4)-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl4 (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl4 + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-β (TGF-β) and nuclear translocation of NFκB. SF was capable to inhibit the ALT and γ-GTP elevated levels induced with the CCl4 administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl4. Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-β, the nuclear translocation of NFκB and the activity of COX-2, all induced with the administration of CCl4 in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NFκB and consequently the expression of TGF-β and the activity of COX-2.
Characteristics of multiple sclerosis in aboriginals living in British Columbia, Canada
Authors: Saeedi Jameelah , Rieckmann Peter , Yee Irene , Tremlett Helen ,   and the UBC MS clinic neurologists
Published: March 2012

Objectives: The objectives of this study were to identify and describe the demographic and clinical characteristics of multiple sclerosis (MS) in aboriginals in British Columbia (BC), Canada and compare these findings with non-aboriginal MS patients. Methods: This retrospective chart and database review accessed patient information from the linked BC-wide MS clinical and genetics databases. Data gathered included: demographics (age, sex and ethnicity); clinical characteristics (MS onset date, disease course and disability scores (Expanded Disability Status Scale [EDSS]). Aboriginals were identified via the database linkage augmented by physician and nurse recall. Two non-aboriginal comparator groups with definite MS were selected. Group one included all definite MS patients in the BC MS database, and group two comprised MS patients matched by sex, age at onset and initial disease course. Patient characteristics were compared using the Student’s t-test, chi-squared test, and Kaplan–Meier survival analysis was used to examine disease progression (time to sustained and confirmed EDSS 6) Results: We identified 26 aboriginals with MS, of which 19/26 (73%) were female, 23/26 (89%) had relapsing-onset MS and a mean onset age of 31.1 years. There were no significant differences between the MS aboriginals and the non-matched ( n = 5708) comparator group with respect to age, sex or disease course ( p > 0.1), However, aboriginals progressed more rapidly to EDSS 6 from disease onset ( p < 0.001) when compared with the matched and unmatched comparator groups. Conclusion: We identified a small, but important cohort of aboriginals with MS; being the largest identified to date. There was evidence of more rapid MS progression in aboriginals compared with non-aboriginals.
Effect of gender on late-onset multiple sclerosis
Authors: Bove Riley M , Healy Brian , Augustine Ann , Musallam Alexander , Gholipour Taha , Chitnis Tanuja 
Published: March 2012

Objectives: We aimed to examine the incidence and disease course of late-onset multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic cohort, stratified based on gender and race, since both have been reported as important modifiers of disease outcomes in MS. Methods: Patients with LOMS and AOMS were compared in terms of demographic characteristics and disease course characteristics. Combined effects were investigated with a logistic regression model. Time from disease onset to sustained Expanded Disability Status Scale (EDSS) score of 6 was investigated using an extension of log-rank test appropriate for interval-censored data. Results: Some 7.96% of 4273 patients studied had an onset of MS after the age of 50 years (LOMS), and 1.33% experienced an onset after age 60. Progressive onset was more common in LOMS relative to AOMS. The proportion of women with progressive-onset disease was similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared with males; however, it was similar between males and females in the LOMS group. Conclusions: Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.
Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis
Authors: Doré Louis C. , Chlon Timothy M. , Brown Christopher D. , White Kevin P. , Crispino John D. 
Published: March 2012

AbstractThere are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than one-third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression; and in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we show that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification.
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma
Authors: Leonard John P. , LaCasce Ann S. , Smith Mitchell R. , Noy Ariela , Chirieac Lucian R. , Rodig Scott J. , Yu Jian Q. , Vallabhajosula Shankar , Schoder Heiko , English Patricia , Neuberg Donna S. , Martin Peter , Millenson Michael M. , Ely Scott A. , Courtney Rachel , Shaik Naveed , Wilner Keith D. , Randolph Sophia , Van den Abbeele Annick D. , Chen-Kiang Selina Y. , Yap Jeffrey T. , Shapiro Geoffrey I. 
Published: March 2012

AbstractMantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1–dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3-deoxy-3[18F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUVmax), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUVmax and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.
Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity
Authors: Ndhlovu Lishomwa C. , Lopez-Vergès Sandra , Barbour Jason D. , Jones R. Brad , Jha Aashish R. , Long Brian R. , Schoeffler Eric C. , Fujita Tsuyoshi , Nixon Douglas F. , Lanier Lewis L. 
Published: March 2012

AbstractNatural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. This effect is achieved through a complex mosaic of inhibitory and activating receptors expressed by NK cells that ultimately determine the magnitude of the NK-cell response. The T-cell immunoglobulin– and mucin domain–containing (Tim)–3 receptor was initially identified as a T-helper 1–specific type I membrane protein involved in regulating T-cell responses. Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. Tim-3 protein is expressed on essentially all mature CD56dimCD16+ NK cells and is expressed heterogeneously in the immature CD56brightCD16– NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56brightCD16− NK cells after stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a maturation marker on NK cells. Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. However, when Tim-3 was cross-linked with antibodies it suppressed NK cell–mediated cytotoxicity. These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3.
Acute myeloid leukemia in the real world: why population-based registries are needed
Authors: Juliusson Gunnar , Lazarevic Vladimir , Hörstedt Ann-Sofi , Hagberg Oskar , Höglund Martin 
Published: March 2012

Abstract
Population-based registries may provide data complementary to that from basic science and clinical intervention studies, all of which are essential for establishing recommendations for the management of patients in the real world. The same quality criteria apply for the evidence-based label, and both high representation and good data quality are crucial in registry studies. Registries with high coverage of the target population reduce the impact of selection on outcome and the subsequent problem with extrapolating data to nonstudied populations. Thus, data useful for clinical decision in situations not well covered by clinical studies can be provided. The potential clinical impact of data from population-based studies is exemplified with analyses from the Swedish Acute Leukemia Registry containing more than 3300 acute myeloid leukemia (AML) patients diagnosed between 1997 and 2006 with a median follow-up of 6.2 years on (1) the role of intensive combination chemotherapy for older patients with AML, (2) the impact of allogeneic stem cell transplantation on survival of younger patients with AML, and (3) the continuing problem with early deaths in acute promyelocytic leukemia. We also present the first Web-based dynamic graph showing the complex interaction between age, performance status, the proportion of patients given intensive treatment, early death rate, complete remission rate, use of allogeneic transplants, and overall survival in AML (non-AML).
Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice
Authors: Kil Laurens P. , de Bruijn Marjolein J. W. , van Nimwegen Menno , Corneth Odilia B. J. , van Hamburg Jan Piet , Dingjan Gemma M. , Thaiss Friedrich , Rimmelzwaan Guus F. , Elewaut Dirk , Delsing Dianne , van Loo Pieter Fokko , Hendriks Rudi W. 
Published: March 2012

AbstractOn antigen binding by the B-cell receptor (BCR), B cells up-regulate protein expression of the key downstream signaling molecule Bruton tyrosine kinase (Btk), but the effects of Btk up-regulation on B-cell function are unknown. Here, we show that transgenic mice overexpressing Btk specifically in B cells spontaneously formed germinal centers and manifested increased plasma cell numbers, leading to antinuclear autoantibody production and systemic lupus erythematosus (SLE)–like autoimmune pathology affecting kidneys, lungs, and salivary glands. Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant. B cells overexpressing wild-type Btk were selectively hyperresponsive to BCR stimulation and showed enhanced Ca2+ influx, nuclear factor (NF)–κB activation, resistance to Fas-mediated apoptosis, and defective elimination of selfreactive B cells in vivo. These findings unravel a crucial role for Btk in setting the threshold for B-cell activation and counterselection of autoreactive B cells, making Btk an attractive therapeutic target in systemic autoimmune disease such as SLE. The finding of in vivo pathology associated with Btk overexpression may have important implications for the development of gene therapy strategies for X-linked agammaglobulinemia, the immunodeficiency associated with mutations in BTK.
Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study
Authors: Levine John E. , Logan Brent R. , Wu Juan , Alousi Amin M. , Bolaños-Meade Javier , Ferrara James L. M. , Ho Vincent T. , Weisdorf Daniel J. , Paczesny Sophie 
Published: March 2012

Abstract
Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet–derived 3-α, a gastrointestinal tract–specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874.