bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates of Delayed Recognition and Treatment of Acute Type A Aortic Dissection
Authors: Harris Kevin M. , Strauss Craig E. , Eagle Kim A. , Hirsch Alan T. , Isselbacher Eric M. , Tsai Thomas T. , Shiran Hadas , Fattori Rossella , Evangelista Arturo , Cooper Jeanna V. , Montgomery Daniel G. , Froehlich James B. , Nienaber Christoph A. ,   for the International Registry of Acute Aortic Dissection (IRAD) Investigators
Published: October 2011

Background—
In acute aortic dissection, delays exist between presentation and diagnosis and, once diagnosed, definitive treatment. This study aimed to define the variables associated with these delays.

Methods and Results—

Acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and January 2007 were evaluated for factors contributing to delays in presentation to diagnosis and in diagnosis to surgery. Multiple linear regression was performed to determine relative delay time ratios (DTRs) for individual correlates. The median time from arrival at the emergency department to diagnosis was 4.3 hours (quartile 1–3, 1.5–24 hours; n=894 patients) and from diagnosis to surgery was 4.3 hours (quartile 1–3, 2.4–24 hours; n=751). Delays in acute aortic dissection diagnosis occurred in female patients; those with atypical symptoms that were not abrupt or did not include chest, back, or any pain; patients with an absence of pulse deficit or hypotension; or those who initially presented to a nontertiary care hospital (all
P
<0.05). The largest relative DTRs were for fever (DTR=5.11;
P
<0.001) and transfer from nontertiary hospital (DTR=3.34;
P
<0.001). Delay in time from diagnosis to surgery was associated with a history of previous cardiac surgery, presentation without abrupt or any pain, and initial presentation to a nontertiary care hospital (all
P
<0.001). The strongest factors associated with operative delay were prolonged time from presentation to diagnosis (DTR=1.35;
P
<0.001), race other than white (DTR=2.25;
P
<0.001), and history of coronary artery bypass surgery (DTR=2.81;
P
<0.001).

Conclusions—
Improved physician awareness of atypical presentations and prompt transport of acute aortic dissection patients could reduce crucial time variables.
Wnt Signaling Mediates Pathological Vascular Growth in Proliferative Retinopathy
Authors: Chen Jing , Stahl Andreas , Krah Nathan M. , Seaward Molly R. , Dennison Roberta J. , Sapieha Przemyslaw , Hua Jing , Hatton Colman J. , Juan Aimee M. , Aderman Christopher M. , Willett Keirnan L. , Guerin Karen I. , Mammoto Akiko , Campbell Matthew , Smith Lois E.H. 
Published: October 2011

Background—
Ischemic proliferative retinopathy, characterized by pathological retinal neovascularization, is a major cause of blindness in working-age adults and children. Defining the molecular pathways distinguishing pathological neovascularization from normal vessels is critical to controlling these blinding diseases with targeted therapy. Because mutations in Wnt signaling cause defective retinal vasculature in humans with some characteristics of the pathological vessels in retinopathy, we investigated the potential role of Wnt signaling in pathological retinal vascular growth in proliferative retinopathy.

Methods and Results—

In this study, we show that Wnt receptors (Frizzled4 and low-density lipoprotein receptor–related protein5 [Lrp5]) and activity are significantly increased in pathological neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Loss of Wnt coreceptor Lrp5 and downstream signaling molecule dishevelled2 significantly decreases the formation of pathological retinal neovascularization in retinopathy. Loss of Lrp5 also affects retinal angiogenesis during development and formation of the blood-retinal barrier, which is linked to significant downregulation of tight junction protein claudin5 in
Lrp5
−/−
vessels. Blocking claudin5 significantly suppresses Wnt pathway–driven endothelial cell sprouting in vitro and developmental and pathological vascular growth in retinopathy in vivo.

Conclusions—
These results demonstrate an important role of Wnt signaling in pathological vascular development in retinopathy and show a novel function of Cln5 in promoting angiogenesis.
Role of fiber/matrix interphases on dielectric, friction, and mechanical properties of glass fiber-reinforced epoxy composites
Authors: Kechaou B. , Salvia M. , Benzarti K. , Turki C. , Fakhfakh Z. , Tréheux D. 
Published: October 2011

This study compares the mechanical, tribological, and dielectric properties of glass fiber-reinforced epoxy (GFRE), presenting various fiber/matrix adhesions. Three GFRE composites were studied. The only difference between them is in the initial preparation of fibers which is intentionally simplified compared to the complex sizings used in industry. Thus, fibers treated with aminosilane or silicone coupling agents were compared with fibers simply washed with deionized water. The dielectric measurements show the leading role of interfacial bonding in the trapping or diffusion of electric charges. To obtain high mechanical properties, a fiber treatment that contributes to the diffusion of electric charges along the fiber/matrix interface is preferred. In addition, after friction, a modification of the dielectric properties in all materials is observed, and the trapping or the diffusion of the charges along the interfaces can make it possible to lower the friction coefficient, or the wear.
In Vivo Analysis of Coracoclavicular Ligament Kinematics During Shoulder Abduction
Authors: Izadpanah Kaywan , Weitzel Elizabeth , Honal Matthias , Winterer Jan , Vicari Marco , Maier Dirk , Jaeger Martin , Kotter Elmar , Hennig Jürgen , Weigel Matthias , Südkamp Norbert P. 
Published: October 2011

Background: Anatomic reconstruction of the coracoclavicular ligaments for the treatment of acromioclavicular joint separations provides superior biomechanical stability compared with other procedures. Clavicular and coracoidal footprints of the conoid ligament (CL) and the trapezoid ligament (TL) are well described. So far, little is known about their kinematics and the changes of the coracoclavicular distance during shoulder abduction. Hypothesis: The coracoclavicular distance along the coracoclavicular ligaments changes significantly with shoulder abduction and weightbearing. Study Design: Descriptive laboratory study. Methods: With use of an open magnetic resonance imaging scanner, the shoulders of 13 healthy volunteers were examined in supine and sitting positions. Three-dimensional magnetic resonance images of the shoulders were obtained in 30° increments of abduction (0°-120°). A manual segmentation of the scapula, the clavicle, and the coracoclavicular ligaments was performed. The insertion points of the coracoclavicular ligaments were identified, and automated measures along the ligamentous course were carried out. Results: During transfer from the lying to sitting position, the coracoclavicular distance showed significant lengthening of 3 mm along the center of the CL, which significantly increased another 3 mm during shoulder abduction to a total lengthening of 6 mm. In the supine position, the coracoclavicular distance along the TL did not elongate significantly. In the sitting position, the distance along the medial portion of the TL shortened significantly, whereas the distance along the center portion did not elongate significantly during shoulder abduction. Conclusion: The distances between the coracoclavicular insertion points depend on both patient and shoulder positioning. To prevent overconstraining of the graft, the CL should be fixated during 90° to 120° of shoulder abduction in a sitting position. Isometric reconstruction of the TL can be achieved if precise fixation of the graft at the centers of the conoidal and clavicular footprints is performed.
Assessment and Management of Sport-Related Concussions in United States High Schools
Authors: Meehan William P. , d’Hemecourt Pierre , Collins Christy L. , Comstock R. Dawn 
Published: October 2011

Background: Little existing data describe which medical professionals and which medical studies are used to assess sport-related concussions in high school athletes. Purpose: To describe the medical providers and medical studies used when assessing sport-related concussions. To determine the effects of medical provider type on timing of return to play, frequency of imaging, and frequency of neuropsychological testing. Study Design: Descriptive epidemiology study. Methods: All concussions recorded by the High School Reporting Information Online (HS RIO) injury surveillance system during the 2009 to 2010 academic year were included. χ2 analyses were conducted for categorical variables. Fisher exact test was used for nonparametric data. Logistic regression analyses were used when adjusting for potential confounders. Statistical significance was considered for P < .05. Results: The HS RIO recorded 1056 sport-related concussions, representing 14.6% of all injuries. Most (94.4%) concussions were assessed by athletic trainers (ATs), 58.8% by a primary care physician. Few concussions were managed by specialists. The assessment of 21.2% included computed tomography. Computerized neuropsychological testing was used for 41.2%. For 50.1%, a physician decided when to return the athlete to play; for 46.2%, the decision was made by an AT. After adjusting for potential confounders, no associations between timing of return to play and the type of provider (physician vs AT) deciding to return the athlete to play were found. Conclusion: Concussions account for nearly 15% of all sport-related injuries in high school athletes. The timing of return to play after a sport-related concussion is similar regardless of whether the decision to return the athlete to play is made by a physician or an AT. When a medical doctor is involved, most concussions are assessed by primary care physicians as opposed to subspecialists. Computed tomography is obtained during the assessment of 1 of every 5 concussions occurring in high school athletes.
Δ12-prostaglandin J3, an omega-3 fatty acid–derived metabolite, selectively ablates leukemia stem cells in mice
Authors: Hegde Shailaja , Kaushal Naveen , Ravindra Kodihalli C. , Chiaro Christopher , Hafer Kelsey T. , Gandhi Ujjawal H. , Thompson Jerry T. , van den Heuvel John P. , Kennett Mary J. , Hankey Pamela , Paulson Robert F. , Prabhu K. Sandeep 
Published: October 2011

AbstractTargeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ12-PGJ3, a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia. IP administration of Δ12-PGJ3 to mice infected with Friend erythroleukemia virus or those expressing the chronic myelogenous leukemia oncoprotein BCR-ABL in the hematopoietic stem cell pool completely restored normal hematologic parameters, splenic histology, and enhanced survival. More importantly, Δ12-PGJ3 selectively targeted leukemia stem cells (LSCs) for apoptosis in the spleen and BM. This treatment completely eradicated LSCs in vivo, as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplantations. Given the potency of ω-3 polyunsaturated fatty acid–derived CyPGs and the well-known refractoriness of LSCs to currently used clinical agents, Δ12-PGJ3 may represent a new chemotherapeutic for leukemia that targets LSCs.
Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia
Authors: Staffas Anna , Kanduri Meena , Hovland Randi , Rosenquist Richard , Ommen Hans Beier , Abrahamsson Jonas , Forestier Erik , Jahnukainen Kirsi , Jónsson Ólafur G. , Zeller Bernward , Palle Josefine , Lönnerholm Gudmar , Hasle Henrik , Palmqvist Lars , Ehrencrona Hans ,   on behalf of the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
Published: October 2011

Abstract
Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information.
Quantitative trait mapping reveals a regulatory axis involving peroxisome proliferator-activated receptors, PRDM16, transforming growth factor-β2 and FLT3 in hematopoiesis
Authors: Avagyan Serine , Aguilo Francesca , Kamezaki Kenjiro , Snoeck Hans-Willem 
Published: October 2011

AbstractHematopoiesis is the process whereby BM HSCs renew to maintain their number or to differentiate into committed progenitors to generate all blood cells. One approach to gain mechanistic insight into this complex process is the investigation of quantitative genetic variation in hematopoietic function among inbred mouse strains. We previously showed that TGF-β2 is a genetically determined positive regulator of hematopoiesis. In the presence of unknown nonprotein serum factors TGF-β2, but not TGF-β1 or -β3, enhances progenitor proliferation in vitro, an effect that is subject to mouse strain-dependent variation mapping to a locus on chr.4, Tb2r1. TGF-β2–deficient mice show hematopoietic defects, demonstrating the physiologic role of this cytokine. Here, we show that TGF-β2 specifically and predominantly cell autonomously enhances signaling by FLT3 in vitro and in vivo. A coding polymorphism in Prdm16 (PR-domain-containing 16) underlies Tb2r1 and differentially regulates transcriptional activity of peroxisome proliferator-activated receptor-γ (PPARγ), identifying lipid PPAR ligands as the serum factors required for regulation of FLT3 signaling by TGF-β2. We furthermore show that PPARγ agonists play a FLT3-dependent role in stress responses of progenitor cells. These observations identify a novel regulatory axis that includes PPARs, Prdm16, and TGF-β2 in hematopoiesis.
Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer
Authors: Brugger Wolfram , Triller Nadja , Blasinska-Morawiec Maria , Curescu Stefan , Sakalauskas Raimundas , Manikhas Georgy Moiseevich , Mazieres Julien , Whittom Renaud , Ward Carol , Mayne Karen , Trunzer Kerstin , Cappuzzo Federico 
Published: October 2011

Purpose The phase III, randomized, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study found that erlotinib maintenance therapy extended progression-free survival (PFS) and overall survival in patients with advanced non–small-cell lung cancer (NSCLC) who had nonprogressive disease following first-line platinum-doublet chemotherapy. This study included prospective analysis of the prognostic and predictive value of several biomarkers. Patients and Methods Mandatory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor (EGFR) protein expression by using immunohistochemistry (IHC), EGFR gene copy number by using fluorescent in situ hybridization (FISH), and EGFR and KRAS mutations by using DNA sequencing. An EGFR CA simple sequence repeat in intron 1 (CA-SSR1) polymorphism was evaluated in blood. Results All 889 randomly assigned patients provided tumor samples. EGFR IHC, EGFR FISH, KRAS mutation, and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy. A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation–positive subgroup (hazard ratio [HR], 0.10; P < .001). Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup (HR, 0.78; P = .0185). KRAS mutation status was a significant negative prognostic factor for PFS. Conclusion This large prospective biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy. No other biomarkers were predictive for outcomes with erlotinib, although the study was not powered for clinical outcomes in biomarker subgroups. EGFR IHC–positive KRAS mutations were prognostic for reduced PFS. The study demonstrated the feasibility of prospective tissue collection for biomarker analyses in NSCLC.
Second Cancer Risk After Chemotherapy for Hodgkin's Lymphoma: A Collaborative British Cohort Study
Authors: Swerdlow Anthony J. , Higgins Craig D. , Smith Paul , Cunningham David , Hancock Barry W. , Horwich Alan , Hoskin Peter J. , Lister T. Andrew , Radford John A. , Rohatiner Ama Z.S. , Linch David C. 
Published: October 2011

Purpose We investigated the long-term risk of second primary malignancy after chemotherapy for Hodgkin's lymphoma (HL) in a much larger cohort than any yet published, to our knowledge. Patients and Methods We followed 5,798 patients with HL treated with chemotherapy in Britain from 1963 to 2001—of whom 3,432 also received radiotherapy—to assess second primary malignancy risks compared with general population-based expectations. Results Second malignancies occurred in 459 cohort members. Relative risk (RR) of second cancer was raised after chemotherapy alone (RR, 2.0; 95% CI, 1.7 to 2.4) but was much lower than after combined modalities (RR, 3.9; 95% CI, 3.5 to 4.4). After chemotherapy alone, there were significantly raised risks of lung cancer, non-HL, and leukemia, each contributing approximately equal absolute excess risk. After combined modalities, there were raised risks of these and several other cancers. Second cancer risk peaked 5 to 9 years after chemotherapy alone, but it remained raised for 25 years and longer after combined modalities. Risk was raised after each common chemotherapy regimen except, based on limited numbers and follow-up, adriamycin, bleomycin, vinblastine, and dacarbazine. The age and time-course relations of lung cancer differed between chemotherapy alone and combined modalities. Conclusion Although chemotherapy alone leads to raised risk of second malignancy, this risk is lower and affects fewer anatomic sites than that after combined modalities, and it is slight if at all after 15 years follow-up. The mechanism of lung cancer etiology may differ between chemotherapy and radiotherapy.
Cisplatin, Irinotecan, and Bevacizumab for Untreated Extensive-Stage Small-Cell Lung Cancer: CALGB 30306, a Phase II Study
Authors: Ready Neal E. , Dudek Arkadiusz Z. , Pang Herbert H. , Hodgson Lydia D. , Graziano Stephen L. , Green Mark R. , Vokes Everett E. 
Published: October 2011

Purpose The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in patients with extensive-stage small-cell lung cancer (ES-SCLC). Patients and Methods Patients with ES-SCLC received cisplatin 30 mg/m2 and irinotecan 65 mg/m2 on days 1 and 8 plus bevacizumab 15 mg/kg on day 1 every 21 days for six cycles on this phase II study. The primary end point was to differentiate between 50% and 65% 12-month survival rates. Results Seventy-two patients were enrolled between March 2005 and April 2006; four patients canceled, and four were ineligible. Grade 3 or 4 toxicities included neutropenia (25%), all electrolyte (23%), diarrhea (16%), thrombocytopenia (10%), fatigue (10%), nausea (10%), hypertension (9%), anemia (9%), infection (7%), vascular access thrombosis (2%), stroke (2%), and bowel perforation (1%). Three deaths (5%) occurred on therapy as a result of pneumonitis (n = 1), stroke (n =1), and heart failure (n = 1). Complete response, partial response, and stable disease occurred in three (5%), 45 (70%), and 11 patients (17%), respectively. Progressive disease occurred in one patient (2%). Overall response rate was 75%. Median progression-free survival (PFS) was 7.0 months (95% CI, 6.4 to 8.4 months). Median overall survival (OS) was 11.6 months (95% CI, 10.5 to 15.1 months). Hypertension ≥ grade 1 was associated with improved OS after adjusting for performance status (PS) and age (hazard ratio [HR], 0.55; 95% CI, 0.31 to 0.97; P = .04). Lower vascular endothelial growth factor levels correlated with worse PFS after adjusting for age and PS (HR, 0.90; 95% CI, 0.83 to 0.99; P = .03). Conclusion PFS and OS times were higher compared with US trials in ES-SCLC with the same chemotherapy. However, the primary end point of the trial was not met. Hypertension was associated with improved survival after adjusting for age and PS.
Prediction of Early Death After Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia With Pretreatment Risk Scores: A Novel Paradigm for Treatment Assignment
Authors: Walter Roland B. , Othus Megan , Borthakur Gautam , Ravandi Farhad , Cortes Jorge E. , Pierce Sherry A. , Appelbaum Frederick R. , Kantarjian Hagop A. , Estey Elihu H. 
Published: October 2011

Purpose Outcome in acute myeloid leukemia (AML) worsens with age, at least in part because of higher treatment-related mortality (TRM) in older patients. Eligibility for intensive AML treatment protocols is therefore typically based on age as the implied principal predictor of TRM, although other health- and disease-related factors modulate this age effect. Patients and Methods We empirically defined TRM using estimated weekly hazard rates in 3,365 adults of all ages administered intensive chemotherapy for newly diagnosed AML. We used the area under the receiver operator characteristic curve (AUC) to quantify the relative effects of age and other covariates on TRM in a subset of 2,238 patients. In this approach, an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is analogous to a coin flip. Results Regardless of age, risk of death declined once 4 weeks had elapsed from treatment start, suggesting that patients who die during this time comprise a qualitatively distinct group. Performance status (PS) and age were the most important individual predictors of TRM (AUCs of 0.75 and 0.65, respectively). However, multicomponent models were significantly more accurate in predicting TRM (AUC of 0.83) than PS or age alone. Elimination of age from such multicomponent models only minimally affected their predictive accuracy (AUC of 0.82). Conclusion These data suggest that age is primarily a surrogate for other covariates, which themselves add significantly to predictive accuracy, thus challenging the wisdom of using age as primary or sole basis for assignment of intensive, curative intent treatment in AML.