bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Vascular Response Patterns During Exercise in Left Ventricular Systolic Dysfunction Predict Exercise Capacity and Outcomes
Authors: Lewis Gregory D. , Murphy Ryan M. , Shah Ravi V. , Pappagianopoulos Paul P. , Malhotra Rajeev , Bloch Kenneth D. , Systrom David M. , Semigran Marc J. 
Published: February 2011

Background—
Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized.

Methods and Results—

Sixty consecutive patients with LVSD (age 60±12 years, left ventricular ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 W), LVSD subjects, compared with controls, had greater augmentation in mean PAPs (15±1 versus 5±1 mm Hg), transpulmonary gradients (5±1 versus 1±1 mm Hg), and effective pulmonary artery elastance (0.05±0.02 versus −0.03±0.01 mm Hg/mL,
P
<0.0001 for all). A linear increment in PAP relative to work (0.28±0.12 mm Hg/W) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07±0.02 mm Hg/W,
P
<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41±0.16 mm Hg/W) followed by a plateau. The plateau pattern, compared with a linear pattern, was associated with reduced peak V
o
2
(10.6±2.6 versus 13.1±4.0 mL · kg
−1
· min
−1
,
P
=0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 versus 9.7±5.0 g/m
2
,
P
=0.002), and increased mortality (hazard ratio 8.1, 95% CI 2.7 to 23.8,
P
<0.001).

Conclusions—
A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets.

Clinical Trial Information—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00309790.
Comparison of Mass Spectrometry and Clinical Assay Measurements of Circulating Fragments of B-Type Natriuretic Peptide in Patients With Chronic Heart Failure
Authors: Miller Wayne L. , Phelps Mary A. , Wood Christina M. , Schellenberger Ute , Van Le Anh , Perichon Regis , Jaffe Allan S. 
Published: February 2011

Background—
Multiple B-type natriuretic peptide (BNP) fragments circulate in patients with heart failure (HF) but the types and relative quantities, particularly in relation to bioactive BNP 1-32, remain poorly defined. The purpose of the study was to relate clinically available BNP values with quantitative information on the concentration of pre-secretion and post-processed fragments of BNP detected by mass spectrometry.

Methods and Results—

Seventy Class I–IV patients were prospectively enrolled with blood drawn into tubes containing a preservative to protect against BNP degradation. Samples were analyzed by quantitative mass spectrometry (MS) immunoassay for intact BNP 1-32 and its fragments. Clinical BNP 1-2 was measured by standard clinical laboratory methods. ProBNP 1-108, corin, and clinically measured BNP levels were elevated, but MS BNP 1-32 levels were low and differed from clinical BNP (
P
=0.01). Intact MS BNP 1-32 correlated modestly with clinical BNP (
r
=0.46,
P
<0.001). MS BNP fragments 3-32, 4-32, and 5-32 demonstrated the best associations with clinical BNP; fragment 5-32 with a correlation coefficient of
r
=0.81 (
P
<0.001).

Conclusions—
ProBNP 1-108 is measured by clinical BNP assays and contributes to the cumulative results of the BNP assay. However, the observation that clinically measured BNP correlates best with MS degradation fragments and relatively poorly with MS BNP 1-32 suggests that a significant component of circulating clinical BNP is composed of such fragments that are known to demonstrate little biological activity. There appear to be multiple pathways involved in the dysregulation of proBNP in HF, and both the processing of proBNP and the downstream degradation to BNP 1-32 appear to be critical.
Early Predictive Biomarkers for Lesion After Transient Cerebral Ischemia
Authors: Berthet Carole , Lei Hongxia , Gruetter Rolf , Hirt Lorenz 
Published: February 2011

Background and Purpose—
Despite the improving imaging techniques, it remains challenging to predict the outcome early after transient cerebral ischemia. The aim of this study was thus to identify early metabolic biomarkers for outcome prediction.

Methods—
We modeled transient ischemic attacks and strokes in mice. Using high-field MR spectroscopy, we correlated early changes in the neurochemical profile of the ischemic striatum with histopathologic alterations at a later time point.

Results—
A significant increase in glutamine was measured between 3 hours and 8 hours after all ischemic events followed by reperfusion independently of the outcome and can thus be considered as an indicator of recent transient ischemia. On the other hand, a reduction of the score obtained by summing the concentrations of N-acetyl aspartate, glutamate, and taurine was a good predictor of an irreversible lesion as early as 3 hours after ischemia.

Conclusions—
We identified biomarkers of reversible and irreversible ischemic damage, which can be used in an early predictive evaluation of stroke outcome.
Thrombolysis With Intravenous Tissue Plasminogen Activator Predicts a Favorable Discharge Disposition in Patients With Acute Ischemic Stroke
Authors: Ifejika-Jones Nneka L. , Harun Nusrat , Mohammed-Rajput Nareesa A. , Noser Elizabeth A. , Grotta James C. 
Published: February 2011

Background and Purpose—
Acute ischemic stroke patients who receive recombinant tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal to no disability at 3 months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, inpatient rehabilitation, a skilled nursing facility, or subacute care. There are no studies assessing the role of recombinant tissue plasminogen activator use as a predictor of poststroke discharge disposition.

Methods—
We conducted a retrospective analysis of all patients with ischemic stroke who presented within the original three hour window for intravenous thrombolysis, and who were admitted to the University of Texas Houston Medical School Stroke Service at Memorial Hermann Hospital - Texas Medical Center between January 2004 and October 2009. Baseline demographics and National Institute of Health Stroke Scale score were collected. Cerebrovascular disease risk factors were used for risk stratification in the multivariate regression.

Results—

Out of 2225 patients with acute ischemic stroke, 1019 were discharged to home, 719 to inpatient rehabilitation, 371 to a skilled nursing facility and 116 to subacute care. Patients who received recombinant tissue plasminogen activator therapy were more likely to be discharged home compared to the other levels of care (
P
<0.0001; OR, 1.945; 95% CI, 1.538 to 2.459). Considering post-acute inpatient rehabilitation versus skilled nursing facility/subacute care and disposition at a skilled nursing facility versus subacute care, there were no differences in disposition between patients who received recombinant tissue plasminogen activator therapy. Inpatient Rehabilitation versus Skilled Nursing Facility or Subacute Care (
P
= 0.123); Skilled Nursing Facility versus Subacute Care (
P
= 0.605).

Conclusions—
Patients who receive intravenous recombinant tissue plasminogen activator as treatment for acute ischemic stroke are more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge.
Retrieving the Fraction of Ground Flashes from Satellite Lightning Imager Data Using CONUS-Based Optical Statistics
Authors: Koshak W. J. , Solakiewicz R. J. 
Published: February 2011

Abstract
A retrieval method is introduced for estimating the fraction of ground flashes in a set of N flashes observed from either a low earth-orbiting or geostationary satellite lightning imager. The methodology exploits the fact that mean optical characteristics of ground and cloud flashes differ, and hence a properly posed equation set for mean conditions of a set of N observed flashes can be mathematically inverted to estimate the ground flash fraction (and hence the cloud flash-to-ground flash ratio). Explicit analytic expressions for the retrieval errors are derived, and numerical tests of the retrieval method are provided to quantify retrieval accuracy. It has been found that the retrieval method works best when only one optimum optical parameter is used (the single-characteristic solution approach) rather than a mixture of optical parameters (the multiple-characteristic solution approach); that is, the suboptimum optical parameters in the mix degrade retrieval accuracy. Since the retrieval method uses conterminous United States (CONUS)-averaged values of the lightning optical measurements, retrieval errors tend to be smallest in geographical regions whose specific mean lightning optical measurements are closest to the CONUS mean values. The rms ground flash fraction retrieval errors for 52 widely distributed regions across CONUS ranged from as low as 0.061 to 0.111, depending on the true ground flash fraction sought.
Cost Burden of Chronic Rhinosinusitis
Authors: Bhattacharyya Neil , Orlandi Richard R. , Grebner Jeff , Martinson Melissa 
Published: February 2011

ObjectiveTo quantify the cost burden and utilization of health care for chronic rhinosinusitis (CRS).Study DesignHistorical cohort study.SettingAcademic medical centers.MethodsMedical claims data from 2003 to 2008 were analyzed. Patients were defined as having chronic sinus disease if they had a minimum of 2 CRS‐related diagnoses with either computed tomography scanning or endoscopy performed between diagnoses. The prevalence and costs of CRS from the payer perspective (reimbursements) were determined.ResultsMore than 4.4 million patients with an average of 3.1 years of eligibility and at least 1 diagnosis of acute rhinosinusitis (ARS) or CRS were studied. A total of 5.5% (95% confidence interval [CI], 5.4%‐5.6%) of those with ARS were diagnosed with CRS in the subsequent 4 years. Among patients with chronic disease, after 12 months, 39% were still consuming care for CRS, and after 24 months, nearly 28% were still doing so. Of the CRS patients whose diagnosis was confirmed with endoscopy or radiology, 46.2% underwent endoscopic sinus surgery (ESS). In the year prior to ESS, patient care costs averaged $2449 ($2341‐$2556). The ESS procedure plus 45‐day postprocedure debridement and medical therapy costs averaged $7726 ($7554‐$7898). In the year following the 45‐day postprocedure period, consumption dropped by $885 (P <. 0001). In the second year following ESS, therapy costs dropped an additional $446 (P <. 0001).ConclusionsA significant proportion of CRS patients require ongoing treatment of their sinus disease for years. Sinus surgery appears to reduce consumption of rhinosinusitis‐related health care, but costs related to the procedure are significant.
Does Prosthesis Diameter Matter?
Authors: Starmer Heather M. , Agrawal Nishant , Koch Wayne , Richmon Jeremy , Webster Kimberly , Gourin Christine G. 
Published: February 2011

ObjectiveTo assess the impact of tracheoesophageal voice prosthesis diameter and treatment status on prosthesis‐related complications.Study DesignHistorical cohort study.SettingSingle academic medical institution.Subjects and MethodsPatients who underwent total laryngectomy (TL) between 1996 and 2008 were divided into 2 subgroups according to prosthesis diameter: 16F (n = 19) and 20/22F (n = 71). Each patient only used 1 diameter of prosthesis. Time to leakage through the prosthesis, number of episodes of leakage around the prosthesis, number of prosthesis dislodgements, and length changes after the first 6 months were chosen as outcomes of interest.ResultsAnalysis included 90 patients. Analysis of selected complications by prosthesis diameter revealed no significant differences for time to leakage through the prosthesis, number of leaks around the prosthesis, or dislodgement. Larger diameter prosthesis use was associated with a greater number of length changes (P =. 008). Multivariable regression analysis did not find any significant association between prosthesis‐specific complications and prosthesis diameter when controlling for other variables. Prior radiation was associated with an increased number of size changes (β = 2.0, P =. 004) and a decrease in time to leakage through the prosthesis (β = −4.4, P =. 048), after controlling for other variables.ConclusionsProsthesis diameter is not associated with an increased prevalence of certain voice prosthesis complications in laryngectomy patients, regardless of initial treatment modality, whereas prior radiation or chemoradiation is associated with complications. These data suggest that factors affecting tissue health, rather than prosthesis size, may be more responsible for prosthesis complications.
MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia
Authors: Vargova Karin , Curik Nikola , Burda Pavel , Basova Petra , Kulvait Vojtech , Pospisil Vit , Savvulidi Filipp , Kokavec Juraj , Necas Emanuel , Berkova Adela , Obrtlikova Petra , Karban Josef , Mraz Marek , Pospisilova Sarka , Mayer Jiri , Trneny Marek , Zavadil Jiri , Stopka Tomas 
Published: February 2011

Abstract
Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of miR-155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription.
Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism
Authors: Nitta Eriko , Yamashita Masayuki , Hosokawa Kentaro , Xian MingJi , Takubo Keiyo , Arai Fumio , Nakada Shinichiro , Suda Toshio 
Published: February 2011

Abstract
Telomerase reverse transcriptase (TERT) contributes to the prevention of aging by a largely unknown mechanism that is unrelated to telomere lengthening. The current study used ataxia-telangiectasia mutated (ATM) and TERT doubly deficient mice to evaluate the contributions of 2 aging-regulating molecules, TERT and ATM, to the aging process. ATM and TERT doubly deficient mice demonstrated increased progression of aging and had shorter lifespans than ATM-null mice, while TERT alone was insufficient to affect lifespan. ATM-TERT doubly null mice show in vivo senescence, especially in hematopoietic tissues, that was dependent on p16INK4a and p19ARF, but not on p21. As their HSCs show decreased stem cell activities, accelerated aging seen in these mice has been attributed to impaired stem cell function. TERT-deficient HSCs are characterized by reactive oxygen species (ROS) fragility, which has been suggested to cause stem cell impairment during aging, and apoptotic HSCs are markedly increased in these mice. p38MAPK activation was indicated to be partially involved in ROS-induced apoptosis in TERT-null HSCs, and BCL-2 is suggested to provide a part of the protective mechanisms of HSCs by TERT. The current study demonstrates that TERT mitigates aging by protecting HSCs under stressful conditions through telomere length-independent mechanisms.
RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5
Authors: Zhu Yuan Xiao , Tiedemann Rodger , Shi Chang-Xin , Yin Holly , Schmidt Jessica E. , Bruins Laura A. , Keats Jonathan J. , Braggio Esteban , Sereduk Chris , Mousses Spyro , Stewart A. Keith 
Published: February 2011

Abstract
The molecular target(s) cooperating with proteasome inhibition in multiple myeloma (MM) remain unknown. We therefore measured proliferation in MM cells transfected with 13 984 small interfering RNAs in the absence or presence of increasing concentrations of bortezomib. We identified 37 genes, which when silenced, are not directly cytotoxic but do synergistically potentiate the growth inhibitory effects of bortezomib. To focus on bortezomib sensitizers, genes that also sensitized MM to melphalan were excluded. When suppressed, the strongest bortezomib sensitizers were the proteasome subunits PSMA5, PSMB2, PSMB3, and PSMB7 providing internal validation, but others included BAZ1B, CDK5, CDC42SE2, MDM4, NME7, RAB8B, TFE3, TNFAIP3, TNK1, TOP1, VAMP2, and YY1. The strongest hit CDK5 also featured prominently in pathway analysis of primary screen data. Cyclin-dependent kinase 5 (CDK5) is expressed at high levels in MM and neural tissues with relatively low expression in other organs. Viral shRNA knockdown of CDK5 consistently sensitized 5 genetically variable MM cell lines to proteasome inhibitors (bortezomib and carfilzomib). Small-molecule CDK5 inhibitors were demonstrated to synergize with bortezomib to induce cytotoxicity of primary myeloma cells and myeloma cell lines. CDK5 regulation of proteasome subunit PSMB5 was identified as a probable route to sensitization.
Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1
Authors: Rajkumar S. Vincent , Harousseau Jean-Luc , Durie Brian , Anderson Kenneth C. , Dimopoulos Meletios , Kyle Robert , Blade Joan , Richardson Paul , Orlowski Robert , Siegel David , Jagannath Sundar , Facon Thierry , Avet-Loiseau Hervé , Lonial Sagar , Palumbo Antonio , Zonder Jeffrey , Ludwig Heinz , Vesole David , Sezer Orhan , Munshi Nikhil C. , San Miguel Jesus ,   on behalf of the International Myeloma Workshop Consensus Panel 1
Published: February 2011

Abstract
It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript.
Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3
Authors: Dimopoulos Meletios , Kyle Robert , Fermand Jean-Paul , Rajkumar S. Vincent , San Miguel Jesus , Chanan-Khan Asher , Ludwig Heinz , Joshua Douglas , Mehta Jayesh , Gertz Morie , Avet-Loiseau Hervé , Beksaç Meral , Anderson Kenneth C. , Moreau Philippe , Singhal Seema , Goldschmidt Hartmut , Boccadoro Mario , Kumar Shaji , Giralt Sergio , Munshi Nikhil C. , Jagannath Sundar ,   on behalf of the International Myeloma Workshop Consensus Panel 3
Published: February 2011

AbstractA panel of members of the 2009 International Myeloma Workshop developed guidelines for standard investigative workup of patients with suspected multiple myeloma. Both serum and urine should be assessed for monoclonal protein. Measurement of monoclonal protein both by densitometer tracing and/by nephelometric quantitation is recommended, and immunofixation is required for confirmation. The serum-free light chain assay is recommended in all newly diagnosed patients with plasma cell dyscrasias. Bone marrow aspiration and/or biopsy along with demonstration of clonality of plasma cells are necessary. Serum β2-microglobulin, albumin, and lactate dehydrogenase are necessary for prognostic purposes. Standard metaphase cytogenetics and fluorescent in situ hybridization for 17p, t(4;14), and t(14;16) are recommended. The skeletal survey remains the standard method for imaging screening, but magnetic resonance imaging frequently provides valuable diagnostic and prognostic information. Most of these tests are repeated during follow-up or at relapse.
Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor–induced thrombocytopenia
Authors: Bishton Mark J. , Harrison Simon J. , Martin Benjamin P. , McLaughlin Nicole , James Chloé , Josefsson Emma C. , Henley Katya J. , Kile Benjamin T. , Prince H. Miles , Johnstone Ricky W. 
Published: February 2011

Abstract
Histone deacetylase inhibitor (HDACI)–induced thrombocytopenia (TCP) is a major dose-limiting toxicity of this new class of drugs. Using preclinical models to study the molecular and biologic events that underpin this effect of HDACI, we found that C57BL/6 mice treated with both the HDAC1/2-selective HDACI romidepsin and the pan-HDACI panobinostat developed significant TCP. HDACI-induced TCP was not due to myelosuppression or reduced platelet lifespan, but to decreased platelet release from megakaryocytes. Cultured primary murine megakaryocytes showed reductions in proplatelet extensions after HDACI exposure and a dose-dependent increase in the phosphorylation of myosin light chain 2 (MLC2). Phosphorylation of MLC to phospho-MLC (pMLC) and subsequent proplatelet formation in megakaryocytes is regulated by the Rho-GTPase proteins Rac1, CDC42, and RhoA. Primary mouse megakaryocytes and the human megakaryoblastic cell line Meg-01 showed reductions in Rac1, CDC42, and RhoA protein levels after treatment with HDACIs. We were able to overcome HDACI-induced TCP by administering the mouse-specific thrombopoietin (TPO) mimetic AMP-4, which improved platelet numbers to levels similar to untreated controls. Our report provides the first detailed account of the molecular and biologic processes involved in HDACI-mediated TCP. Moreover, our preclinical studies provide evidence that dose-limiting TCP induced by HDACIs may be circumvented using a TPO mimetic.