bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience With the Atrium Advanta Covered Stent for Aortic Obstruction
Authors: OHNO NAOKI , CHATURVEDI RAJIV , LEE KYONG‐JIN , HORLICK ERIC M. , OSTEN MARK D. , BENSON LEE N. 
Published: August 2013

AbstractIntroductionWe sought to assess the efficacy, safety and clinical outcomes of the Advanta V12™ covered stent in management of coarctation of the aorta (CoA).Materials and MethodsStent functionality was assessed by review of angiographic imaging, clinical data at admission, discharge and at the last clinic visit, stent configuration on chest roentgenogram, radiation exposure, and complications.ResultsBetween October 2009 and February 2012, 17 patients underwent stent implantation. There were 9–12, 2–14, and 6–16 mm diameter stents deployed. Balloon angioplasty after implantation was required in 2 patients. Mean percent recoil in the middle of the stent for the 12, 14, and 16 mm implants was 14%, 24%, and 24%, respectively. There was improvement in CoA diameter from 6.6 ± 3.2 to 11.5 ± 1.7 mm (P < 0.0001) and a reduction in the peak pressure gradient from 23.1 ± 10.1 to 0.8 ± 3.3 mmHg (P < 0.0001). No patient had a symptomatic complication. Left arm cuff blood pressure fell 24 hours after implantation and left arm to leg blood pressure gradient fell to <20 mmHg in all (P < 0.0001). Follow‐up was a median 242 days and at the last clinic visit there were no statistically different findings from discharge. Five children (33%) required antihypertensive medications but 3 were off medication at latest follow‐up. Three patients (18%) required reintervention.ConclusionThe implantation of the Advanta™ V12 stent for the treatment of CoA is safe and effective in the early term. However, further study is required to determine longer‐term stent efficacy.
An ORF1‐rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture
Authors: Johne R. , Reetz J. , Ulrich R. G. , Machnowska P. , Sachsenröder J. , Nickel P. , Hofmann J. 
Published: August 2013

SummaryHepatitis E is an increasingly reported disease in industrialized countries. Studies on the replication cycle of hepatitis E virus (HEV) are hampered due to the lack of efficient and robust cell culture systems for this virus. We describe the successful isolation of HEV derived from a chronically infected kidney transplant patient held under immunosuppressive therapy. Inoculation of serum sample 47832 onto the human lung carcinoma cell line A549 resulted in the replication of the virus as shown by RT‐qPCR. This novel human‐derived HEV strain is closely related to a wild boar‐derived genotype 3 strain, which did not replicate in A549 cells. It carries a 186 nucleotide insertion in the hypervariable ORF1‐region, derived from two parts of its ORF1. By passaging of the infected cells, a cell line continuously producing HEV particles was generated as demonstrated by RT‐qPCR, immuno‐electron microscopy, density gradient centrifugation and immunohistochemistry. Replication of the produced virus was demonstrated after its inoculation onto fresh A549 cells and two consecutive passages, whereas heating at 65 °C for 2 min abolished its infectivity. Several point mutations scattered along the whole genome were present in the HEV strain from the second passage; however, the ORF1 insertion was still present. Previously, cell culture isolation of two other HEV strains carrying insertions in their hypervariable regions, but originating from human ribosomal protein genes, has been described. The findings may indicate that cell culture adaptation of is mostly dependent on the length and position of the insertion, rather than from the sequence itself.
Alpha‐1 Acid Glycoprotein Reduces Hepatic Leukocyte Recruitment in Murine Models of Either Early Endotoxemia or Early Sepsis
Authors: McCurdy Teresa R. , Patrick Amanda L. , Eltringham‐Smith Louise J. , Bhakta Varsha , Sheffield William P. , Fox‐Robichaud Alison E. 
Published: August 2013

AbstractObjectiveTo characterize the effect of systemically administered AGP on early leukocyte recruitment in the livers of endotoxemic or septic mice and to determine whether this is influenced by LPS sequestration.MethodsEndotoxemia was induced in C57Bl/6 mice via intraperitoneal injection of LPS. Sepsis was induced in mice by cecal ligation and perforation. AGP (165 mg/kg) or saline (20 mL/kg) or HAS (200 mg/kg) was administered immediately after surgery or LPS injection and the hepatic microcirculation was examined by intravital microscopy at four hour.ResultsLeukocyte adhesion in the PSV was reduced by treatment with AGP in mice subjected to either LPS or CLP protocols compared to either saline or HAS treatment. AGP‐treated mice also had significantly higher sinusoidal flow in both models. Pre‐incubation of LPS with AGP reduced the ability of LPS to recruit leukocytes to the liver microcirculation.ConclusionsAGP was more effective in limiting hepatic inflammation and maintaining perfusion than saline or HAS, in both endotoxemic and septic mice. AGP sequestration of LPS may contribute to its anti‐inflammatory effects.
Mechanisms of action of otilonium bromide (OB) in human cultured smooth muscle cells and rat colonic strips
Authors: Martínez‐Cutillas M. , Gil V. , Gallego D. , Mañé N. , Martín M. T. , Jiménez M. 
Published: August 2013

AbstractBackgroundThe pharmacological properties of otilonium bromide (OB) have been investigated using different experimental models, techniques, and conditions, and consequently, the results are not always easy to compare. The aim of the present work was to investigate the pharmacological properties of OB in human cultured colonic smooth muscle cells (HCSMCs), which is the main target of the drug ‘in vivo’. Rat colonic strips were used to confirm the pharmacological properties.MethodsHuman cultured colonic smooth muscle cells were studied using the calcium imaging technique. Microelectrodes and muscle bath experiments were performed in rat colonic strips.Key ResultsOtilonium bromide (OB) concentration dependently inhibited nifedipine‐sensitive calcium transients induced by KCl (EC50 = 3.6 μM) and BayK8644 (EC50 = 4.0 μM). All the following experiments were performed in the presence of nifedipine. In HCSMC, carbachol‐induced calcium transients were inhibited by OB (EC50 = 8.4 μM). Carbachol evoked 1—a smooth muscle depolarization (10 mV) that was antagonized by 100 μM OB; and 2—a contraction that was inhibited by OB (EC50 = 13.0 μM). ‘Non‐nitrergic (L‐NNA 1 mM) non‐purinergic (MRS2500 1 μM)’ conditions were used to elicit endogenous excitatory responses. Electrical field stimulation caused 1—an atropine‐sensitive excitatory junction potential that was inhibited by OB (EC50 = 8.9 μM) and 2—an atropine‐sensitive contraction that was inhibited by OB (EC50 = 7.3 μM). In HCSMC, neurokinin A (NKA) and CaCl2 induced calcium transients that were inhibited by OB (NKA: EC50 = 11.7 μM; CaCl2: EC50 = 17.5 μM).Conclusions & InferencesOtilonium bromide causes inhibition of L‐/T‐type calcium channels, muscarinic, and tachykininergic responses that acting together explain the pharmacological properties of the compound.
Nonsteroidal Anti‐Inflammatory Drugs, Gastroprotection, and Benefit–Risk
Authors: Moore Robert Andrew , Derry Sheena , Simon Lee S. , Emery Paul 
Published: August 2013

AbstractBackgroundGastroprotective agents (GPA) substantially reduce morbidity and mortality with long‐term nonsteroidal anti‐inflammatory drugs (NSAIDs) and aspirin.ObjectiveTo evaluate efficacy of NSAIDs, protection against NSAID‐induced gastrointestinal harm, and balance of benefit and risk.MethodsFree text searches of PubMed (December 2012) supplemented with “related citation” and “cited by” facilities on PubMed and Google Scholar for patient requirements, NSAID effectiveness, pain relief benefits, gastroprotective strategies, adherence to gastroprotection prescribing, and serious harm with NSAIDs and GPA.ResultsPatients want 50% reduction in pain intensity and improved fatigue, distress, and quality of life. Meta‐analyses of NSAID trials in musculoskeletal conditions had bimodal responses with good pain relief or little. Number needed to treat (NNTs) for good pain relief were 3 to 9. Proton pump inhibitors (PPI) and high‐dose histamine‐2 receptor antagonists (H2RA) provided similar gastroprotection, with no conclusive evidence of greater PPI efficacy compared with high‐dose H2RA. Prescriber adherence to guidance on use of GPA with NSAIDS was 49% in studies published since 2005; patient adherence was less than 100%. PPI use at higher doses over longer periods is associated with increased risk of serious adverse events, including fracture; no such evidence was found for H2RA. Patients with chronic conditions are more willing to accept risk of harm for successful treatment than their physicians.ConclusionGuidance on NSAIDs use should ensure that patients have a good level of pain relief and that gastroprotection is guaranteed for the NSAID delivering good pain relief. Fixed‐dose combinations of NSAID plus GPA offer one solution.
Diabetes, physical activity participation and exercise capacity in patients with schizophrenia
Authors: Vancampfort Davy , De Hert Marc , Sweers Kim , De Herdt Amber , Detraux Johan , Probst Michel 
Published: August 2013

AimThe aim of this study was to determine if in schizophrenia patients the presence of diabetes is associated with lower physical activity participation and lower exercise capacity compared to patients with pre‐diabetes and to patients without (pre‐) diabetes.MethodsSchizophrenia patients without (pre‐)diabetes (n = 86) were compared with pre‐diabetic (n = 10) and diabetic patients (n = 10). Patients were assessed on physical activity participation using the Baecke physical activity questionnaire and on exercise capacity using a 6‐min walk test (6MWT).ResultsThe three groups were similar in age, sex, mean antipsychotic medication dose, negative and depressive symptoms and smoking behavior. Distance achieved on the 6MWT, however, was approximately 15% shorter (P < 0.05) in patients withdiabetes than in patients without (pre‐)diabetes (500.3 ± 76.9 m vs 590.7 ± 101.8 m). Patients with diabetes were also significantly less physically active (P < 0.05). No differences between diabetic and pre‐diabetic patients were found. Pre‐diabetic patients had a higher body mass index (BMI) than non‐diabetic patients (30.0 ± 7.3 vs 24.3 ± 4.3, P < 0.05). An interaction effect with BMI for differences in Baecke (F = 29.9, P < 0.001) and 6MWT (F = 13.0, P < 0.001) scores was seen between diabetic and non‐diabetic patients on univariate ANCOVA.ConclusionThe additive burden of diabetes might place patients with schizophrenia at an even greater risk for functional limitations in daily life.
Development of a Tumor‐Specific Photoactivatable Doxorubicin Prodrug
Authors: Girotti Albert W. , Minotti Giorgio 
Published: August 2013

AbstractThis is a retrospective highlight on the publication by Ibsen and coworkers: Localized In Vivo Activation of a Photoactivatable Doxorubicin Prodrug in Deep Tumor Tissue, which appeared in a preceding issue of Photochem. Photobiol. (2013, 89:698–708). The authors describe the synthesis and properties of a novel doxorubicin (DOX) prodrug, DOX‐PCB, which contains a photocleavable linker group. Systemic administration of the prodrug to a tumor‐bearing animal followed by LED/fiber optic 365 nm light delivery allowed active DOX to be released site specifically in the tumor area. This elegant and timely study provides compelling evidence that photocleavable DOX‐PCB can eliminate many of the toxic side effects of DOX that have plagued clinical use of this highly effective antitumor drug for many years.
Moderate alcohol intake is related to increased heart rate variability in young adults: Implications for health and well‐being
Authors: Quintana Daniel S. , Guastella Adam J. , McGregor Iain S. , Hickie Ian B. , Kemp Andrew H. 
Published: August 2013

AbstractEpidemiological literature indicates that the relationship between alcohol consumption and health outcomes reflects a J‐shaped curve such that moderate alcohol consumption confers a protective effect in comparison to abstinence, while heavy consumption is associated with poorer health. While heart rate variability (HRV) may underpin the relationship between drinking and poor health in heavy drinkers, it is unclear whether HRV is increased in moderate, habitual drinkers relative to nonhabitual drinkers. HRV and drinking habits were assessed in 47 volunteers. Results supported hypotheses suggesting that moderate, habitual drinking increases HRV. Although not supported by a significant interaction between drinking group and sex, planned follow‐up analysis also revealed that these findings may be specific to males. Regardless, results highlight HRV as a candidate mechanism for the findings reported in the epidemiological literature.
Nonaffective motivation modulates the sustained LPP (1,000–2,000 ms)
Authors: Gable Philip A. , Adams David L. 
Published: August 2013

AbstractPast work has demonstrated that the sustained late positive potential (LPP) is modulated by motivational demands of affective content. The current experiment sought to investigate how motivational demands in nonaffective tasks would modulate the sustained LPP. Using a modified oddball paradigm, participants either counted the number of appearances of a nonaffective target or determined the duration length of the target. Results showed that targets in both the counted and duration tasks produced larger LPPs in the early window (400–1,000 ms) than the neutral standard. Only the duration target produced larger LPPs in the late time window (1,000–2,000 ms) than the neutral standard. These results suggest that the late LPP is a measure of persistent motivated attentional processing and can be modulated by nonaffective motivation.
Knowledge and Reasoning in Spatial Analysis
Authors: Hall Andreas , Ahonen‐Rainio Paula , Virrantaus Kirsi 
Published: August 2013

AbstractReasoning is an essential part of any analysis process. Especially in visual analytics, the quality of the results depends heavily on the knowledge and reasoning skills of the analyst. In this study, we consider how to make the results transparent by visualizing the reasoning and the knowledge, so that persons from outside can trace and verify them. The focus of this study is in spatial analysis and a case study was carried out on a process of off‐road mobility analysis. In the case study, linked views of a map and a PCP were identified as reasoning artifacts. The knowledge used by the analyst was formed by these artifacts and the tangible pieces of information identified in them, along with the mental models of the analyst′s mind. To make the results transparent, the tangible pieces of information were marked with sketches and the mental models were presented in causal graphs because it was found that causality was central to the reasoning process in the case study. The causal graph allows the reasoning of the analyst to be studied, as well as traced back to its origin.
Priority Structures in Deontic Logic
Authors: van Benthem Johan , Grossi Davide , Liu Fenrong 
Published: August 2013

AbstractThis article proposes a systematic application of recent developments in the logic of preference to a number of topics in deontic logic. The key junction is the well‐known Hansson conditional for dyadic obligations. These conditionals are generalized by pairing them with reasoning about syntactic priority structures. The resulting two‐level approach to obligations is tested first against standard scenarios of contrary‐to‐duty obligations, leading also to a generalization for the Kanger‐Anderson reduction of deontic logic. Next, the priority framework is applied to model two intuitively different sorts of deontic dynamics of obligations, based on information changes and on genuine normative events. In this two‐level setting, we also offer novel takes on vexed issues such as the Chisholm paradox and modelling strong permission. Finally, the priority framework is shown to provide a unifying setting for the study of operations on norms as such, in particular, adding or deleting individual norms, and even merging whole norm systems in different manners.
A generalised model for individualising a treatment recommendation based on group-level evidence from randomised clinical trials
Authors: Marcucci Maura , Sinclair John C 
Published: August 2013

ObjectivesRandomised controlled trials report group-level treatment effects. However, an individual patient confronting a treatment decision needs to know whether that person's expected treatment benefit will exceed the expected treatment harm. We describe a flexible model for individualising a treatment decision. It individualises group-level results from randomised trials using clinical prediction guides.MethodsWe constructed models that estimate the size of individualised absolute risk reduction (ARR) for the target outcome that is required to offset individualised absolute risk increase (ARI) for the treatment harm. Inputs to the model include estimates for the individualised predicted absolute treatment benefit and harm, and the relative value assigned by the patient to harm/benefit. A decision rule recommends treatment when the predicted benefit exceeds the predicted harm, value-adjusted. We also derived expressions for the maximum treatment harm, or the maximum relative value for harm/benefit, above which treatment would not be recommended.ResultsFor the simpler model, including one kind of benefit and one kind of harm, the individualised ARR required to justify treatment was expressed as required ARRtarget(i)=ARIharm(i) × RVharm/target(i). A complex model was also developed, applicable to treatments causing multiple kinds of benefits and/or harms. We demonstrated the applicability of the models to treatments tested in superiority trials (either placebo or active control, either fixed harm or variable harm) and non-inferiority trials.ConclusionsIndividualised treatment recommendations can be derived using a model that applies clinical prediction guides to the results of randomised trials in order to identify which individual patients are likely to derive a clinically important benefit from the treatment. The resulting individualised prediction-based recommendations require validation by comparison with strategies of treat all or treat none.
A prospective, multicenter pilot study investigating the utility of flat detector derived parenchymal blood volume maps to estimate cerebral blood volume in stroke patients
Authors: Fiorella David , Turk Aquilla , Chaudry Imran , Turner Raymond , Dunkin Jared , Roque Clemente , Sarmiento Marily , Deuerling-Zheng Yu , Denice Christine M , Baumeister Marlene , Parker Adrian T , Woo Henry H 
Published: August 2013

PurposeNewer flat panel angiographic detector (FD) systems have the capability to generate parenchymal blood volume (PBV) maps. The ability to generate these maps in the angiographic suite has the potential to markedly expedite the triage and treatment of patients with acute ischemic stroke. The present study compares FP-PBV maps with cerebral blood volume (CBV) maps derived using standard dynamic CT perfusion (CTP) in a population of patients with stroke.Methods56 patients with cerebrovascular ischemic disease at two participating institutions prospectively underwent both standard dynamic CTP imaging followed by FD-PBV imaging (syngo Neuro PBV IR; Siemens, Erlangen, Germany) under a protocol approved by both institutional review boards. The feasibility of the FD system to generate PBV maps was assessed. The radiation doses for both studies were compared. The sensitivity and specificity of the PBV technique to detect (1) any blood volume deficit and (2) a blood volume deficit greater than one-third of a vascular territory, were defined using standard dynamic CTP CBV maps as the gold standard.ResultsOf the 56 patients imaged, PBV maps were technically adequate in 42 (75%). The 14 inadequate studies were not interpretable secondary to patient motion/positioning (n=4), an injection issue (n=2), or another reason (n=8). The average dose for FD-PBV was 219 mGy (median 208) versus 204 mGy (median 201) for CT-CBV. On CT-CBV maps 26 of 42 had a CBV deficit (61.9%) and 15 (35.7%) had a deficit that accounted for greater than one-third of a vascular territory. FD-PBV maps were 100% sensitive and 81.3% specific to detect any CBV deficit and 100% sensitive and 62.9% specific to detect any CBV deficit of greater than one-third of a territory.ConclusionsPBV maps can be generated using FP systems. The average radiation dose is similar to a standard CTP examination. PBV maps have a high sensitivity for detecting CBV deficits defined by conventional CTP. PBV maps often overestimate the size of CBV deficits. We hypothesize that the FP protocol initiates PBV imaging prior to complete saturation of the blood volume in areas perfused via indirect pathways (ie, leptomeningeal collaterals), resulting in an overestimation of CBV deficits, particularly in the setting of large vessel occlusion.
Epithelial–Mesenchymal Transition and Tumor Suppression Are Controlled by a Reciprocal Feedback Loop between ZEB1 and Grainyhead-like-2
Authors: Cieply Benjamin , Farris Joshua , Denvir James , Ford Heide L. , Frisch Steven M. 
Published: August 2013

Abstract
Epithelial–mesenchymal transition (EMT) in carcinoma cells enhances malignant progression by promoting invasion and survival. EMT is induced by microenvironmental factors, including TGF-β and Wnt agonists, and by the E–box-binding transcription factors Twist, Snail, and ZEB. Grainyhead-like-2 (GRHL2), a member of the mammalian Grainyhead family of wound-healing regulatory transcription factors, suppresses EMT and restores sensitivity to anoikis by repressing ZEB1 expression and inhibiting TGF-β signaling. In this study, we elucidate the functional relationship between GRHL2 and ZEB1 in EMT/MET and tumor biology. At least three homeodomain proteins, Six1, LBX1, and HoxA5, transactivated the ZEB1 promoter, in the case of Six1, through direct protein–promoter interaction. GRHL2 altered the Six1–DNA complex, inhibiting this transactivation. Correspondingly, GRHL2 expression prevented tumor initiation in xenograft assays, sensitized breast cancer cells to paclitaxel, and suppressed the emergence of CD44highCD24low cells (defining the cancer stem cell phenotype in the cell type studied). GRHL2 was downregulated in recurrent mouse tumors that had evolved to an oncogene-independent, EMT-like state, supporting a role for GRHL2 downregulation in this phenotypic transition, modeling disease recurrence. The combination of TGF-β and Wnt activation repressed GRHL2 expression by direct interaction of ZEB1 with the GRHL2 promoter, inducing EMT. Together, our observations indicate that a reciprocal feedback loop between GRHL2 and ZEB1 controls epithelial versus mesenchymal phenotypes and EMT-driven tumor progression. Cancer Res; 73(20); 6299–309. ©2013 AACR.