bluuebunny/crossref_metadata_2025_split huggingface dataset:
Essential Role of Apelin Signaling During Lymphatic Development in Zebrafish
Authors: Kim Jun-Dae , Kang Yujung , Kim Jongmin , Papangeli Irinna , Kang Hyeseon , Wu Jingxia , Park Hyekyung , Nadelmann Emily , Rockson Stanley G. , Chun Hyung J. , Jin Suk-Won 
Published: December 2013

Objective—
Apelin and its cognate receptor Aplnr/Apj are essential for diverse biological processes. However, the function of Apelin signaling in lymphatic development remains to be identified, despite the preferential expression of Apelin and Aplnr within developing blood and lymphatic endothelial cells in vertebrates. In this report, we aim to delineate the functions of Apelin signaling during lymphatic development.

Approach and Results—
We investigated the functions of Apelin signaling during lymphatic development using zebrafish embryos and found that attenuation of Apelin signaling substantially decreased the formation of the parachordal vessel and the number of lymphatic endothelial cells within the developing thoracic duct, indicating an essential role of Apelin signaling during the early phase of lymphatic development. Mechanistically, we found that abrogation of Apelin signaling selectively attenuates lymphatic endothelial serine–threonine kinase Akt 1/2 phosphorylation without affecting the phosphorylation status of extracellular signal–regulated kinase 1/2. Moreover, lymphatic abnormalities caused by the reduction of Apelin signaling were significantly exacerbated by the concomitant partial inhibition of serine–threonine kinase Akt/protein kinase B signaling. Apelin and vascular endothelial growth factor-C (VEGF-C) signaling provide a nonredundant activation of serine–threonine kinase Akt/protein kinase B during lymphatic development because overexpression of VEGF-C or apelin was unable to rescue the lymphatic defects caused by the lack of Apelin or VEGF-C, respectively.

Conclusions—
Taken together, our data present compelling evidence suggesting that Apelin signaling regulates lymphatic development by promoting serine–threonine kinase Akt/protein kinase B activity in a VEGF-C/VEGF receptor 3–independent manner during zebrafish embryogenesis.
Transient Global Amnesia and the Risk of Ischemic Stroke
Authors: Mangla Atul , Navi Babak B. , Layton Kelly , Kamel Hooman 
Published: December 2013

Background and Purpose—
Whether transient global amnesia (TGA) represents an arterial insult that heralds ischemic stroke remains unclear. Therefore, we examined stroke risk after TGA in a population-based cohort.

Methods—
After performing chart review at our institution to validate the International Classification of Diseases, 9th Edition, Clinical Modification diagnosis code for TGA, we used administrative claims data to identify all patients discharged from nonfederal California emergency departments or acute care hospitals between 2005 and 2010 with a primary discharge diagnosis of TGA. Patients with a primary discharge diagnosis of migraine, seizure, or transient ischemic attack were included as controls. Kaplan–Meier statistics were used to calculate rates of ischemic stroke, and Cox proportional hazards analyses were used to compare stroke risk among the 4 exposure groups while controlling for traditional stroke risk factors.

Results—
International Classification of Diseases, 9th Edition, Clinical Modification code 437.7 had a sensitivity of 86% and a specificity of 95% for TGA. The cumulative 1-year rate of stroke was 0.54% (95% confidence interval [CI], 0.36–0.81) after TGA, 0.22% (95% CI, 0.20–0.25) after migraine, 0.90% (95% CI, 0.83–0.97) after seizure, and 4.72% (95% CI, 4.60–4.85) after transient ischemic attack. After adjustment for demographic characteristics and stroke risk factors, TGA was not associated with stroke risk when compared with migraine (hazard ratio, 0.82; 95% CI, 0.61–1.10). The likelihood of stroke after TGA was lower than after seizure (hazard ratio, 0.57; 95% CI, 0.44–0.76) or transient ischemic attack (hazard ratio, 0.27; 95% CI, 0.20–0.35).

Conclusions—
Compared with patients diagnosed with migraine or seizure, patients diagnosed with TGA do not seem to face a heightened risk of stroke.
Predictability and Genesis of Hurricane Karl (2010) Examined through the EnKF Assimilation of Field Observations Collected during PREDICT
Authors: Poterjoy Jonathan , Zhang Fuqing 
Published: December 2013

Abstract
The genesis of Hurricane Karl (2010) is explored using analyses and forecasts from a cycling ensemble Kalman filter (EnKF) that assimilates routinely collected observations as well as dropsonde measurements that were taken during the Pre-Depression Investigation of Cloud Systems in the Tropics (PREDICT) field campaign. A total of 127 dropsonde observations were collected from six PREDICT flight missions over a 5-day period before and during Karl’s genesis. EnKF analyses that take into account the PREDICT dropsondes provide a detailed four-dimensional overview of the evolving kinematic and thermodynamic structure within the pregenesis disturbance. In particular, the additional field observations are found to increase the low- and midlevel circulation and column moisture in the EnKF analyses and reduce the position error of the low-level vortex. Deterministic forecasts from these analyses show a 24-h improvement in predicting genesis over a control experiment that omits the dropsonde observations. In ensemble forecasts for this event, the more accurate analyses translate into a higher confidence in predicting the intensification of Karl; that is, data assimilation experiments also suggest that initial condition errors at the mesoscale pose large challenges for predicting genesis, thus highlighting the need for improved observation networks and more advanced data assimilation methods.
Dynamics of an Equatorial River Plume: Theory and Numerical Experiments Applied to the Congo Plume Case
Authors: Vic Clément , Berger Henrick , Tréguier Anne-Marie , Couvelard Xavier 
Published: December 2013

Abstract
The Congo River has the second largest rate of flow in the world and is mainly responsible for the broad tongue of low-salinity water that is observed in the Gulf of Guinea. Despite their importance, near-equatorial river plumes have not been studied as thoroughly as midlatitude plumes and their dynamics remain unclear. Using both theory and idealized numerical experiments that reproduce the major characteristics of the region, the authors have investigated the dynamics of the Congo River plume and examine its sensitivity to different forcing mechanisms. It is found that near-equatorial plumes are more likely to be surface trapped than midlatitude plumes, and the importance of the β effect in describing the strong offshore extent of the low-salinity tongue during most of the year is demonstrated. It is shown that the buoyant plume constrained by the geomorphology is subject to the β pulling of nonlinear structures and wavelike equatorial dynamics. The wind is found to strengthen the intrinsic buoyancy-driven dynamics and impede the development of the coastal southward current, in coherence with observations.
Randomness, Symmetry, and Scaling of Mesoscale Eddy Life Cycles
Authors: Samelson R. M. , Schlax M. G. , Chelton D. B. 
Published: December 2013

Abstract
It is shown that the life cycles of nonlinear mesoscale eddies, a major component of low-frequency ocean physical variability, have a characteristic structure that differs fundamentally from that which would be expected on the basis of classical interpretations of ocean eddy evolution in terms of mean flow instability and equilibration followed by frictional, radiative, or barotropic decay, or of vortex merger dynamics in quasigeostrophic turbulent cascades. Further, it is found that these life cycles can be accurately modeled in terms of the large-amplitude excursions of a stochastic process. These conclusions, which apply in the corresponding global-mean context, follow from the examination of ensemble-mean and standard deviation time series of normalized eddy amplitude from an automated eddy identification and tracking analysis of a nearly two decade–merged satellite altimeter record of global sea surface height (SSH). The resulting series are found to have several striking and unexpected characteristics, including time-reversal symmetry and approximate self-similarity. Consistent results are obtained from a similar analysis of a 7-yr record of global SSH from a numerical ocean circulation model. The basic qualitative and quantitative statistical properties of these series can be remarkably well reproduced with an extremely simple stochastic model, in which the SSH increments between successive time points are random numbers, and the eddy life cycles are represented by excursions exceeding a given threshold. The stochastic model is found also to predict accurately the empirical autocorrelation structure of the underlying observed SSH field itself, when the autocorrelations are computed along long planetary (Rossby) wave characteristics.
A prospective evaluation of Dignity Therapy in advanced cancer patients admitted to palliative care
Authors: Houmann Lise J , Chochinov Harvey M , Kristjanson Linda J , Petersen Morten Aa , Groenvold Mogens 
Published: December 2013

Background: Dignity Therapy is a brief, psychosocial intervention for patients with incurable disease. Aim: To investigate participation in and evaluation of Dignity Therapy and longitudinal changes in patient-rated outcomes. Design: A prospective (pre/post) evaluation design was employed. Evaluation questionnaires were completed when patients received the generativity document (T1) and 2 weeks later (T2). Changes from baseline (T0) were measured in sense of dignity, Structured Interview for Symptoms and Concerns items, Patient Dignity Inventory, Hospital Anxiety and Depression Scale and European Organisation for Research and Treatment of Cancer QLQ-C15-PAL ( ClinicalTrials.gov number: NCT01507571). Setting/participants: Consecutive patients with incurable cancer, ≥18 years, informed of prognosis and not having cognitive impairment/physical limitations precluding participation were included at a hospice and a hospital palliative medicine unit. Results: Over 2 years, 80 of 341 eligible patients completed Dignity Therapy. At T1, 55 patients completed evaluations, of whom 73%–89% found Dignity Therapy helpful, satisfactory and of help to relatives; 47%–56% reported that it heightened their sense of purpose, dignity and will to live. Quality of life decreased (mean = −9 (95% confidence interval: −14.54; −2.49)) and depression increased (mean = 0.31 (0.06; 0.57)) on one of several depression measures. At T2 ( n = 31), sense of dignity (mean = −0.52 (−1.01; −0.02)) and sense of being a burden to others (mean = −0.26 (−0.49; −0.02)) improved. Patients with children and lower performance status, emotional functioning and quality of life were more likely to report benefit. Conclusions: This study adds to the growing body of evidence supporting Dignity Therapy as a valuable intervention in palliative care; a substantial subset of patients facing end of life found it manageable, relevant and beneficial.
The risk of radiation-induced breast cancers due to biennial mammographic screening in women aged 50–69 years is minimal
Authors: Hauge Ingrid Helen Ryste , Pedersen Kristin , Olerud Hilde Merete , Hole Eli Olaug , Hofvind Solveig 
Published: December 2013

Background The main aim of mammographic screening is to reduce the mortality from breast cancer. However, use of ionizing radiation is considered a potential harm due to the possible risk of inducing cancer in healthy women. Purpose To estimate the potential number of radiation-induced breast cancers, radiation-induced breast cancer deaths, and lives saved due to implementation of organized mammographic screening as performed in Norway. Material and Methods We used a previously published excess absolute risk model which assumes a linear no-threshold dose-response. The estimates were calculated for 100,000 women aged 50–69 years, a screening interval of 2 years, and with an assumed follow-up until the age of 85 or 105 years. Radiation doses of 0.7, 2.5, and 5.7 mGy per screening examination, a latency time of 5 or 10 years, and a dose and dose-rate effectiveness factor (DDREF) of 1 or 2 were applied. Results The total lifetime risk of radiation-induced breast cancers per 100,000 women was 10 (95% CI: 4–25) if the women were followed from the ages of 50 to 85 years, for a dose of 2.5 mGy, a latency time of 10 years, and a DDREF of 1. For the same parameter values the number of radiation-induced breast cancer death was 1 (95% CI: 0–2). The assumed number of lives saved is approximately 350. Conclusion The risk of radiation-induced breast cancer and breast cancer death due to mammographic screening is minimal. Women should not be discouraged from attending screening due to fear of radiation-induced breast cancer death.
Prevention of Cataracts by Statins
Authors: Kostis John B. , Dobrzynski Jeanne M. 
Published: December 2013

Background: Current data indicate a persisting concern about possible cataractogenecity of statins. Objective: To perform a meta-analysis of studies pertaining to statins and cataract. Methods: We identified 363 records by a systematic search of the MedLine, Web of Knowledge, Cochrane database, and ClinicalTrials.gov. After exclusion of duplicates, studies without cataract as an outcome, reviews, and animal or basic science studies, we analyzed 14 studies. Two end points were examined: clinical cataract (requiring extraction or reported by the patient) and lens opacities discovered by slit-lamp examination. Results: Using random effects meta-analysis, a statistically significant decrease in cataracts with statins was observed among studies examining clinical cataract (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71-0.93, P = .0022). Absolute risk reduction was 1.4% ± 0.015%, 95% CI 1.1%-1.7%, P < .0001, corresponding to 71, 95% CI 59-91, number needed to treat. The effect was larger for the harder end point of cataract extraction (OR 0.66, 95% CI 0.61-0.71, P < .0001). Metaregression indicated an increase in benefit with longer duration of statin use with OR varying from 0.54 for a treatment duration of 14 years to 0.95 for a treatment duration of 6 months. Older age was associated with lower benefit (OR 1.03 for persons in their 70s to OR 0.49 for persons in their 40s), and there were no differences by gender. Several sensitivity analyses confirmed the results. Limitations of this analysis include the combination of randomized and observational studies and imprecise ascertainment of exposure and incomplete adjustment for confounders in several observational studies. Conclusion: This meta-analysis indicates a clinically relevant protective effect of statins in preventing cataracts. The effect is more pronounced in younger patients and with longer duration of follow-up, while there is no difference by gender.
Smokers run increased risk of developing anti-natalizumab antibodies
Authors: Hedström AK , Alfredsson L , Lundkvist Ryner M , Fogdell-Hahn A , Hillert Jan , Olsson T 
Published: December 2013

Background: Smoking may contribute to the induction of neutralizing antibodies to interferon β-1a. Objective: In this study, we aimed to investigate the influence of smoking on the risk of developing antibodies to natalizumab, another biological drug in the treatment of multiple sclerosis. Methods: This report is based on 1338 natalizumab-treated multiple sclerosis patients included in either of two Swedish case-control studies in which information on smoking habits was collected. Using logistic regression, patients with different smoking habits were compared regarding risk of developing anti-natalizumab antibodies, by calculating odds ratios with 95% confidence intervals. Results: Compared with nonsmokers, the odds ratio of developing anti-natalizumab antibodies was 2.4 (95% CI 1.2–4.4) for patients who smoked at the time of screening, and a significant trend showed higher risk of developing antibodies with higher intensity of smoking. When smoking within two years prior to screening was considered, the odds ratio of developing anti-natalizumab antibodies was 2.7 (1.5–5.1). Interpretations: The finding strengthens our hypothesis of the lungs as immune-reactive organs on irritation in relation to autoimmune responses, and may also be of clinical relevance since antibodies against natalizumab abrogate the therapeutic effect of the treatment.
Analysis of Low-Field Magnetic Resonance Imaging Scanners for Evaluation of Knee Pathology Based on Arthroscopy
Authors: Lee Christopher S. , Davis Shane M. , McGroder Claire , Stetson William B. , Powell Scott E. 
Published: December 2013

Background: In recent years, few studies have evaluated low-field magnetic resonance imaging (MRI) diagnoses compared with intraoperative findings of the knee. Purpose: To determine the accuracy and sensitivity of low-field MRI scanners in diagnosing pathology of the menisci, cruciate ligaments, and osteochondral surfaces. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: MRI examinations without intra-articular contrast were performed on 379 patients for knee pathologies over a 4-year period. The MRI examinations were done using a 0.2-tesla scanner utilizing a dedicated knee coil and read by 1 of 3 board-certified, musculoskeletal fellowship–trained radiologists. Within a mean time of 50 days after MRI, all patients underwent knee arthroscopy performed by 1 of 2 sports fellowship–trained orthopaedic surgeons. Operative notes from the knee arthroscopies were then reviewed by a single independent observer, and the intraoperative findings were compared with the MRI reports. Results: For medial meniscus tears, the sensitivity, specificity, positive predictive value, and negative predictive value were 83%, 81%, 89%, and 71%, respectively. For lateral meniscus tears, the values were 51%, 93%, 84%, and 73%, respectively. For anterior cruciate ligament (ACL) tears, the values were 85%, 94%, 69%, and 97%, respectively. For osteochondral lesions, the values were 8%, 99%, 29%, and 94%, respectively. For posterior cruciate ligament (PCL) tears, the specificity and negative predictive value were 99% and 100%, respectively. Conclusion: Low-field MRI was an accurate tool for evaluation of medial meniscus and ACL tears. However, within the study population, it is not as effective in diagnosing lateral meniscus tears and showed a poor ability to detect osteochondral lesions. More information is needed to properly assess its ability to diagnose PCL tears.
The hemophilias and their clinical management
Authors: Josephson Neil 
Published: December 2013

Abstract
Outcomes for patients with hemophilia have improved dramatically over the past 50 years. With the increased availability of safe clotting factor concentrates, the primary focus in clinical management is now the prevention of long-term complications, most notably the debilitating hemophilic arthropathy that is associated with severe disease. This article reviews evidence-based approaches for managing both children and adults with hemophilia. Definitive evidence of improved clinical results from primary prophylaxis started in young patients with severe hemophilia A and a minimal bleeding history is presented. Furthermore, recent studies showing benefits for initiating prophylaxis in older adolescents and adults with established joint disease are examined. Inhibitors to factor VIII are the most problematic complication of factor replacement therapy. Patient-specific and treatment-related factors that contribute to the risk of inhibitor formation are discussed and controversies and clinical evidence related to approaches for tolerance induction are reviewed.
Strategies for induction, autologous hematopoietic stem cell transplantation, consolidation, and maintenance for transplantation-eligible multiple myeloma patients
Authors: McCarthy Philip L. , Hahn Theresa 
Published: December 2013

AbstractThere have been major advances in the past decade in the continuum of therapy for transplantation-eligible multiple myeloma patients. For patients requiring therapy, recommended induction treatment consists of triple drug regimens followed by the collection of hematopoietic stem cells. The question of early versus delayed transplantation is under investigation and may identify patients for whom early transplantation is optimal therapy and those for whom it may be delayed. For transplantation-eligible patients, high-dose melphalan remains the standard regimen. After transplantation, consolidation can be considered for patients with less than a complete remission. Maintenance therapy with bortezomib or lenalidomide (or both in very-high-risk patients) is a reasonable option for long-term disease control and improvement in overall survival. Incorporation of new agents into the continuum of multiple myeloma care should result in improved outcomes and long-term disease control.
Key clinical observations after 5-azacytidine and decitabine treatment of myelodysplastic syndromes suggest practical solutions for better outcomes
Authors: Saunthararajah Yogen 
Published: December 2013

AbstractClinical experience with 5-azacytidine and decitabine treatment of myelodysplastic syndromes (MDS), complemented by biological and pharmacological studies, has revealed compelling mechanism of action differences compared with traditional myeloid cancer treatment mainstays such as cytarabine. For example, 5-azacytidine and decitabine produce remissions and better overall survival in MDS with high-risk chromosome abnormalities at a surprisingly high rate, consistent with experimental observations that noncytotoxic DNA methyltransferase depletion by 5-azacytidine/decitabine can trigger cell cycle exit independently of p53, thus circumventing a basis for resistance to apoptosis-based DNA-damaging therapy. That responses cut across the chaotic genomic landscape of MDS highlights common threads in disease, such as high expression in myeloblasts of differentiation-driving transcription factors yet paradoxical epigenetic suppression of proliferation-terminating late-differentiation genes. Less toxic regimens (lower dosages but more frequent administration) of 5-azacytidine/decitabine have been more successful, underscoring the importance of preserving functionally normal stem cells, which are rendered more precious by attrition from age, previous cytotoxic treatments, and the disease process and are needed to relieve cytopenias, the cause of morbidity and mortality. Also emphasized is that there can be no therapeutic benefit, regardless of mutation or cytogenetic subtype, if DNA methyltransferase is not depleted by sufficient overlap between intracellular drug half-lives and S-phase entries of malignant cells. Improved understanding of mechanism-of-action differences demands new approaches, from historic (but not scientific) more-is-better and one-size-fits-all empiricism to pharmacodynamic-based designs and combinations directed not solely at suppressing malignant clones, but at improving therapeutic indices.
Focus on the epigenome in the myeloproliferative neoplasms
Authors: Kim Eunhee , Abdel-Wahab Omar 
Published: December 2013

Abstract
The discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferative neoplasms (MPNs) led to identification of tyrosine kinase activation as a predominant mechanism driving MPN pathogenesis. Despite this, the existence of additional genetic events that modify the MPN phenotype, predate JAK2 mutations, and/or contribute to leukemic transformation of MPNs has been suggested. Recently, mutations in several epigenetic modifiers have been described in patients with MPNs, including mutations in ASXL1, DNMT3A, EZH2, IDH1, IDH2, and TET2. Moreover, the mutant JAK2 itself has been shown recently to affect histone posttranslational modifications directly. Here we review the biological and clinical implications of epigenetic alterations in the pathogenesis of MPNs.