bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis
Authors: Barnaby Douglas P , Fernando Shannon M , Ferrick Kevin J , Herry Christophe L , Seely Andrew J E , Bijur Polly E , Gallagher E John 
Published: August 2017

ObjectiveTo examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration.MethodsThis is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration.Results466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups.ConclusionsWhile we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.
Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows
Authors: Dalbøge Annett , Frost Poul , Andersen Johan Hviid , Svendsen Susanne Wulff 
Published: August 2017

ObjectivesWe aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate if exposure to hand-arm vibration (HAV) is an independent risk factor.MethodsWe used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003–2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register-based occupational codes (1993–2007) to a general population job exposure matrix to obtain year-by-year exposure intensities on measurement scales for force, upper arm elevation >90° and repetition and expert rated intensities of exposure to HAV. For 10-year exposure time windows, we calculated the duration of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures.ResultsWe found indications of safe exposure intensities for repetition (median angular velocity <45°/s), while force exertion ≥10% of maximal voluntary electrical activity and upper arm elevation >90° >2 min/day implied an increased risk reaching ORs of 1.7 and 1.5 after 10 years at low intensities. No associations were found for HAV.ConclusionsWe found indications of safe exposure intensities for repetition. Any intensities of force and upper arm elevation >90° above minimal implied an increased risk across 10-year exposure time windows. No independent associations were found for HAV.
Dynamic motion modes of high temperature superconducting maglev on a 45-m long ring test line
Authors: Lei W. Y. , Qian N. , Zheng J. , Jin L. W. , Zhang Y. , Deng Z. G. 
Published: August 2017

With the development of high temperature superconducting (HTS) maglev, studies on the running stability have become more and more significant to ensure the operation safety. An experimental HTS maglev vehicle was tested on a 45-m long ring test line under the speed from 4 km/h to 20 km/h. The lateral and vertical acceleration signals of each cryostat were collected by tri-axis accelerometers in real time. By analyzing the phase relationship of acceleration signals on the four cryostats, several typical motion modes of the HTS maglev vehicle, including lateral, yaw, pitch and heave motions were observed. This experimental finding is important for the next improvement of the HTS maglev system.
Samples from the Lomonosov Ridge place new constraints on the geological evolution of the Arctic Ocean
Authors: Knudsen C. , Hopper J. R. , Bierman P. R. , Bjerager M. , Funck T. , Green P. F. , Ineson J. R. , Japsen P. , Marcussen C. , Sherlock S. C. , Thomsen T. B. 
Published: August 2017

Abstract

A number of rock samples were collected from two dredge positions on the Lomonosov Ridge at water depths of 2–3.5 km. The dredge samples are dominated by sediments deformed and metamorphosed under greenschist-facies conditions 470 myr ago according to
40
Ar/
39
Ar dating of metamorphic muscovite. This shows that the Lomonosov Ridge was involved in a major Mid-Ordovician orogenic event that correlates with early arc–terrane accretion observed in northern Ellesmere Island, Svalbard, and other parts of the Caledonian belt. Detrital zircon age spectra of these metasediments span the Mesoproterozoic–Palaeoproterozoic with a main peak at around 1.6 Ga, and a pattern similar to that known from Caledonian metasedimentary rocks in East Greenland and northern Norway, as well as from Cambrian sediments in Estonia and Palaeozoic sediments on Novaya Zemlya. A second population of dredge samples comprises undeformed, non-metamorphic sandstones and siltstones. Detrital zircons in these sediments span the Palaeoproterozoic with a few Archaean zircons. Both rock types are covered by an up to 8 Ma ferromanganese crust and are evaluated to represent outcrop, and apatite fission-track data from three of the rock samples indicate that exposure at the seabed corresponds to a regional event of uplift and erosion that affected the Arctic in the Late Miocene. The data from the Lomonosov Ridge suggest that the 470 Ma orogenic event extended from Scotland and northern Scandinavia into the Arctic, including Svalbard, the Pearya Terrane and the Chukchi Borderlands.
α1A-Subtype adrenergic agonist therapy for the failing right ventricle
Authors: Cowley Patrick M. , Wang Guanying , Joshi Sunil , Swigart Philip M. , Lovett David H. , Simpson Paul C. , Baker Anthony J. 
Published: August 2017

Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg−1·day−1). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α1A-subtype is a potential therapeutic target to treat the failing RV. NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α1A-adrenergic receptor subtype agonist A61603. Chronic A61603 treatment improved RV contraction and reduced multiple indexes of RV injury, suggesting that the α1A-subtype is a therapeutic target to treat RV failure.
Dasatinib Reversibly Disrupts Endothelial Vascular Integrity by Increasing Non-Muscle Myosin II Contractility in a ROCK-Dependent Manner
Authors: Kreutzman Anna , Colom-Fernández Beatriz , Jiménez Ana Marcos , Ilander Mette , Cuesta-Mateos Carlos , Pérez-García Yaiza , Arévalo Cristina Delgado , Brück Oscar , Hakanen Henna , Saarela Jani , Ortega-Carrión Alvaro , de Rosendo Ana , Juanes-García Alba , Steegmann Juan Luis , Mustjoki Satu , Vicente-Manzanares Miguel , Muñoz-Calleja Cecilia 
Published: August 2017

Abstract
Purpose: Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which is frequently used to treat chronic myeloid leukemia. Although very effective, patients taking dasatinib often display severe adverse effects, including pleural effusions and increased risk of bleeding primarily in the gastrointestinal tract. The actual causes of these side effects are currently undetermined. We hypothesize that endothelial cells (ECs) that line the inner walls of blood vessels and control the traffic to the underlying tissues might be involved.
Experimental Design: The effects of TKIs on ECs were studied by various assays, such as real-time cell impedance measurements, live-cell microscopy, wound healing, Western blot, and an in vivo model.
Results: Dasatinib uniquely causes a profound, dose-dependent disorganization of the EC monolayers. Dasatinib promoted the disassembly of cell–cell contacts, altered cell–matrix contacts, and further altered the wound healing. A key observation is that this effect is fully reversible after drug washout. In line with these in vitro observations, intraperitoneal administration of dasatinib to mice caused significant vascular leakage in the intestine. The underlying molecular mechanism of dasatinib-induced reorganization of the actin involves ROCK activation, which increases the amount of the phosphorylation of myosin light chain and consequently activates the non-muscle myosin II.
Conclusions: Our data are consistent with a scenario in which dasatinib triggers a transient increase in vascular leakage that probably contributes to adverse effects such as bleeding diathesis and pleural effusions. Clin Cancer Res; 23(21); 6697–707. ©2017 AACR.
p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy
Authors: Moreno-Smith Myrthala , Lakoma Anna , Chen Zaowen , Tao Ling , Scorsone Kathleen A. , Schild Linda , Aviles-Padilla Kevin , Nikzad Rana , Zhang Yankai , Chakraborty Rikhia , Molenaar Jan J. , Vasudevan Sanjeev A. , Sheehan Vivien , Kim Eugene S. , Paust Silke , Shohet Jason M. , Barbieri Eveline 
Published: August 2017

Abstract
Purpose: mTORC1 inhibitors are promising agents for neuroblastoma therapy; however, they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling.
Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the antitumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first- and second-generation MDM2 inhibitors to reactivate p53.
Results: Nongenotoxic p53 activation suppresses mTOR activity. Moreover, p53 reactivation via RG7388, a second-generation MDM2 inhibitor, strongly enhances the in vivo antitumor activity of temsirolimus. Single-agent temsirolimus does not elicit apoptosis, and tumors rapidly regrow after treatment suspension. In contrast, our combination therapy triggers a potent apoptotic response in wild-type p53 xenografts and efficiently blocks tumor regrowth after treatment completion. We also found that this combination uniquely led to p53-dependent suppression of survivin whose ectopic expression is sufficient to rescue the apoptosis induced by our combination.
Conclusions: Our study supports a novel highly effective strategy that combines RG7388 and temsirolimus in wild-type p53 neuroblastoma, which warrants testing in early-phase clinical trials. Clin Cancer Res; 23(21); 6629–39. ©2017 AACR.
Defective Cyclin B1 Induction in Trastuzumab-emtansine (T-DM1) Acquired Resistance in HER2-positive Breast Cancer
Authors: Sabbaghi MohammadA , Gil-Gómez Gabriel , Guardia Cristina , Servitja Sonia , Arpí Oriol , García-Alonso Sara , Menendez Silvia , Arumi-Uria Montserrat , Serrano Laia , Salido Marta , Muntasell Aura , Martínez-García Maria , Zazo Sandra , Chamizo Cristina , González-Alonso Paula , Madoz-Gúrpide Juan , Eroles Pilar , Arribas Joaquin , Tusquets Ignasi , Lluch Ana , Pandiella Atanasio , Rojo Federico , Rovira Ana , Albanell Joan 
Published: August 2017

AbstractPurpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2-positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance.Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3, and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions. Genetic modifications to up- or downregulate cyclin B1 were conducted. Effects of T-DM1 on cyclin B1 levels, proliferation, and apoptosis were assayed in human HER2-positive breast cancer explants.Results: We obtained three cell lines with different levels of acquired T-DM1 resistance (HCC1954/TDR, HCC1419/TDR, and SKBR3/TDR cells). HER2 remained amplified in the resistant cells. Binding to HER2 and intracellular uptake of T-DM1 were maintained in resistant cells. T-DM1 induced cyclin B1 accumulation in sensitive but not resistant cells. Cyclin B1 knockdown by siRNA in parental cells induced T-DM1 resistance, while increased levels of cyclin B1 by silencing cdc20 partially sensitized resistant cells. In a series of 18 HER2-positive breast cancer fresh explants, T-DM1 effects on proliferation and apoptosis paralleled cyclin B1 accumulation.Conclusions: Defective cyclin B1 induction by T-DM1 mediates acquired resistance in HER2-positive breast cancer cells. These results support the testing of cyclin B1 induction upon T-DM1 treatment as a pharmacodynamic predictor in HER2-positive breast cancer. Clin Cancer Res; 23(22); 7006–19. ©2017 AACR.
Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice
Authors: Pajic Marina , Blatter Sohvi , Guyader Charlotte , Gonggrijp Maaike , Kersbergen Ariena , Küçükosmanoğlu Aslι , Sol Wendy , Drost Rinske , Jonkers Jos , Borst Piet , Rottenberg Sven 
Published: August 2017

Abstract
Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.
Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1−/−;p53−/− mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells.
Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1-mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G0-like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1-mutated mouse mammary tumors.
Conclusions: Our data show that targeting G0-like cells is crucial for the eradication of BRCA1/p53–deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020–33. ©2017 AACR.
Cutaneous analgesia before transradial access for coronary intervention to prevent radial artery spasm
Authors: Tatlı Ersan , Yılmaztepe Mustafa Adem , Vural Mustafa Gökhan , Tokatlı Alptuğ , Aksoy Murat , Ağaç Mustafa Tarık , Çakar Mehmet Akif , Gündüz Huseyin , Akdemir Ramazan 
Published: August 2017

Aim: Transradial access (TRA) for coronary intervention is increasingly used in current clinical practice. The aim of the present study was to evaluate the hypothesis that cutaneous analgesia before TRA for coronary intervention at a puncture site 30 minutes before puncture can reduce patient discomfort and the incidence of radial artery spasm (RAS). Methods: Patients (n=104) undergoing planned coronary interventions using TRA were prospectively randomized to receive either 1 mL of 1% lidocaine subcutaneously (n=52) (control group) or subcutaneous lidocaine plus 5% lidocaine cream (n=52) cutaneously 30 minutes before puncture (treatment group). The primary endpoint was angiographically or clinically confirmed RAS. Secondary endpoints were the occurrence of patient discomfort in the forearm during the procedure and access-site crossover to the femoral artery. Patient discomfort was quantified with a visual analogue scale (VAS) score. Results: Fifty-two patients in the treatment group (60.5±9.4 years of age and 16 female) and 52 patients in the control group (60.4±9.7 years of age and 16 female) were included in the final analysis. Radial artery spasm occurrence decreased in the treatment group compared to the control group (26.9% vs 9.6%; p=0.04) accompanied by a VAS score of 3.7±1.8 in the treatment group and 4.9±2.0 in the control group; p=0.02. The access site crossover rate did not differ between the groups (7.6% vs 21.1%; p=0.09). Conclusion: Cutaneous analgesia before TRA for coronary interventions is associated with a substantial reduction in the RAS and the procedure-related level of patient discomfort.
Differences between central nervous system infection and neuropsychiatric systemic lupus erythematosus in patients with systemic lupus erythematosus
Authors: Fang Hongli , Lan Likang , Qu Yanzhou , Zhang Qiankun , Lv Jin 
Published: August 2017

Objective Neuropsychiatric systemic lupus erythematosus (NPSLE) is a manifestation of systemic lupus erythematosus (SLE). Central nervous system (CNS) infection is a consequence of intensive immunosuppressive therapy that patients with SLE might undergo. This study aimed to compare the differences between NPSLE and CNS infections in patients with SLE. Methods Patients with SLE and NPSLE or CNS infections were retrospectively reviewed. Clinical manifestations, laboratory test results, and prognoses were recorded. The independent sample t-test or chi-square test was used to compare data. Results Patients with CNS infections (n = 20) had more serious headache, high fever (>39.0°C), and vomiting compared with patients with NPSLE (n = 48). Patients with CNS infections also had a larger prednisone dose at the time of symptom onset, larger cumulative dosages over the preceding year, lower SLE Disease Activity Index (SLEDAI) scores, higher rate of nephritis, lower albumin levels, higher C-reactive protein (CRP) levels, higher 24-h-urine protein levels, higher cerebrospinal fluid (CSF) white blood cell levels, and lower protein and glucose levels than those with NPSLE. Conclusions For patients with SLE presenting with CNS symptoms, serious headache, high fever, a high dose of corticosteroids, low SLEDAI scores, and abnormal CSF are more important indicators for CNS infections than NPSLE.
The Organization of Working Time: Developing an Understanding and Action Plan to Promote Workers’ Health in a Seasonal Work Context: L'organisation temporelle du travail: la comprendre pour développer des actions favorisant la santé des travailleuses en contexte de travail saisonnier
Authors: Major Marie-Eve , Vézina Nicole 
Published: August 2017

Despite the health problems associated with irregular schedules and long working hours, few studies have focused on the temporal dimension of work in seasonal working contexts. Through the monitoring of sixteen seasonal workers in the crab-processing industry over a two-year period, this study aimed to better understand their working reality and to provide a detailed picture of the temporal dimension of seasonal work as experienced by these workers. Observations of the work activity, interviews, and analysis of official documents were carried out. The findings reveal that the organization of working time and working conditions are very restrictive. These constraints are linked not only to the work environment and management but also to various public policies and ministerial directives. Methodological elements essential for the study of the organization of working time have been identified and could contribute to a better understanding of temporal constraints experienced by seasonal workers. Résumé Malgré les problèmes de santé associés aux horaires non standards et aux longues heures de travail, peu d'études se sont attardées à dégager un portrait de la dimension temporelle du travail en contexte de travail saisonnier. Par le suivi de 16 travailleuses saisonnières de l'industrie de la transformation du crabe pendant deux années, cette étude visait à mieux comprendre leur réalité de travail et à dresser un portrait détaillé de la dimension temporelle du travail saisonnier tel que vécu par ces travailleuses. Des observations du travail, des entretiens et l'analyse de documents ont été réalisés. Les résultats révèlent une organisation temporelle et des conditions de travail fort contraignantes pour ces travailleuses liées, entre autres, à l'environnement et à la gestion du travail, mais également à diverses politiques publiques et consignes ministérielles. Des éléments méthodologiques essentiels pour l'étude des temps de travail ont également été identifiés et contribueront à mieux cerner les contraintes temporelles des situations de travail vécues par les travailleuses saisonnières.