bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect profile of paracetamol, Δ9‐THC and promethazine using an evoked pain test battery in healthy subjects
Authors: van Amerongen G. , Siebenga P. , de Kam M.L. , Hay J.L. , Groeneveld G.J. 
Published: April 2018

AbstractBackgroundA battery of evoked pain tasks (PainCart) was developed to investigate the pharmacodynamic properties of novel analgesics in early‐phase clinical research. As part of its clinical validation, compounds with different pharmacological mechanisms of actions are investigated. The aim was to investigate the analgesic effects of classic and nonclassic analgesics compared to a sedating negative control in a randomized placebo‐controlled crossover study in 24 healthy volunteers using the PainCart.MethodsThe PainCart consisted of pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain. Subjective scales for cognitive functioning and psychotomimetic effects were included. Subjects were administered each of the following oral treatments: paracetamol (1000 mg), Δ9‐THC (10 mg), promethazine (50 mg) or matching placebo. Pharmacodynamic measurements were performed at baseline and repeated up to 10 h postdose.ResultsParacetamol did not show a significant reduction in pain sensation or subjective cognitive functioning compared to placebo. Promethazine induced a statistically significant reduction in PTT for cold pressor and pressure stimulation. Furthermore, reduced subjective alertness was observed. Δ9‐THC showed a statistically significant decrease in PTT for electrical and pressure stimulation. Δ9‐THC also demonstrated subjective effects, including changes in alertness and calmness, as well as feeling high and psychotomimetic effects.ConclusionsThis study found a decreased pain tolerance due to Δ9‐THC and promethazine, or lack thereof, using an evoked pain task battery. Pain thresholds following paracetamol administration remained unchanged, which may be due to insufficient statistical power. We showed that pain thresholds determined using this pain test battery are not driven by sedation.SignificanceThe multimodal battery of evoked pain tasks utilized in this study may play an important role in early‐phase clinical drug development. This battery of pain tasks is not sensitive to the effects of sedation alone, and thus suitable to investigate the analgesic potential of novel analgesic compounds.
The Multidimensional Symptom Index: A new patient‐reported outcome for pain phenotyping, prognosis and treatment decisions
Authors: Walton D.M. , Marsh J. 
Published: April 2018

AbstractBackgroundThere are few patient‐reported outcomes routinely used that capture frequency and interference of different pain‐related symptoms on a single scale. The purpose of this study was to describe the development and initial validation of the new Multidimensional Symptom Index (MSI).MethodsItems were generated from patient interviews of the experience of chronic pain. Health valuations were created from rankings of 82 healthy subjects for each of 120 symptom (×10) × frequency (×3) × interference (×4) combinations using preference‐based health valuations (0–100). Ranks for each symptom combination were then used in scale scoring. A sample of 300 patients with acute or chronic pain subsequently completed the MSI and a battery of other tools. Exploratory (EFA) and Confirmatory (CFA) factor analyses were triangulated with theory to arrive at the factor structure. Convergent validity was tested against established measures.ResultsHealth rankings resulted in scores of 0–12 for each of the 10 symptom types. Factor analyses revealed two factors: MSI Somatic Symptoms and MSI Non‐Somatic Symptoms. The MSI also quantified number of symptoms experienced (/10), mean frequency (/3) and mean interference (/4). The indices showed appropriate associations with the established PROs.ConclusionsThe MSI is a new symptom‐focused PRO that allows patient phenotyping and may have value for screening, prognosis and evaluating change.SignificanceThis article presents the development and psychometric properties of a new measure of pain and related symptom frequency and interference. This measure could aid clinicians in establishing clinically relevant pain phenotypes for screening, prognosis and treatment decisions.
Simultaneous Determination of Homovanillic and Vanillylmandelic Acid by HPLC Using a Coulometric Detector with Renewable Glassy Carbon Microbeads Based Working Electrode
Authors: Mika Jan , Barek Jiří , Zima Jiří , Moreira Josino Costa , Dejmková Hana 
Published: April 2018

AbstractHomovanilic (HVA) and vanillylmandelic (VMA) acid are catecholamines metabolites commonly used as cancer biomarkers. New method for simultaneous determination of both these metabolites is presented, using recently developed flow‐through coulometric detector based on glassy carbon microbeads. This application presents the potential opportunities of the above mentioned coulometric detector for the simultaneous determination of mixture of substances in complicated matrix in combination with gradient chromatography. Optimum conditions were set as follows: mobile phase consisting of acetonitrile (eluent A) and ten time diluted B‐R buffer pH 3 (eluent B) with gradient program 5 % A (2 min), 5 % A to 25 % A (8 min), 25 % A (4 min), 25 % A to 95 % A (1 min), and 95 % A (4 min); flow rate of mobile phase 0.7 mL min−1, detection potential +1.3 V, and injection volume 20 μL. Calibration dependences of both metabolites were linear from concentration 100 μmol L−1 to their quantitation limits (i.e. 0.6 μmol L−1 for HVA and 1.3 μmol L−1 for VMA, respectively). Standard addition method was applied for the determination of these analytes in human urine. Obtained results are in agreement with results of HPLC method with UV detector.
Low and high prices can improve covariance forecasts: The evidence based on currency rates
Authors: Fiszeder Piotr 
Published: April 2018

AbstractIn this paper we introduce a new specification of the BEKK model, where its parameters are estimated with the use of closing and additionally low and high prices. In an empirical application, we show that the use of additional information related to low and high prices in the formulation of the BEKK model improved the estimation of the covariance matrix of returns and increased the accuracy of covariance and variance forecasts based on this model, compared with using closing prices only. This analysis was performed for the following three most heavily traded currency pairs in the Forex market: EUR/USD, USD/JPY, and GBP/USD. The main result obtained in this study is robust to the applied forecast evaluation criterion. This issue is important from a practical viewpoint, because daily low and high prices are available with closing prices for most financial series.
Brain PET substrate of impulse control disorders in Parkinson's disease: A metabolic connectivity study
Authors: Verger Antoine , Klesse Elsa , Chawki Mohammad B. , Witjas Tatiana , Azulay Jean‐Philippe , Eusebio Alexandre , Guedj Eric 
Published: April 2018

AbstractImpulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F‐fluorodeoxyglucose positron emission tomography. SPM‐T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p < .005, uncorrected; k > 130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation.
Impact of Medicare Advantage penetration and hospital competition on technical efficiency of nursing care in US intensive care units
Authors: Min Ari , Scott Linda D. , Park Chang , Vincent Catherine , Ryan Catherine J. , Lee Taewha 
Published: April 2018

SummaryThis study aimed to evaluate technical efficiency of US intensive care units and determine the effects of environmental factors on technical efficiency in providing quality of nursing care. Data were obtained from the 2014 National Database of Nursing Quality Indicators and the Centers for Medicare and Medicaid Services. Data envelopment analysis was used to estimate technical efficiency for each intensive care unit. Multilevel modeling was used to determine the effects of environmental factors on technical efficiency. Overall, Medicare Advantage penetration and hospital competition in a market did not create pressure for intensive care units to become more efficient by reducing their inputs. However, these 2 environmental factors showed positive influences on technical efficiency in intensive care units with certain levels of technical efficiency. The implications of the study results for management strategies and health policy may vary according to the levels of technical efficiency in intensive care units. Further studies are needed to examine why and how intensive care units with particular levels of technical efficiency are differently affected by certain environmental factors.
Gold‐Catalyzed Polycyclization Toward Natural Products Synthesis
Authors: Toullec Patrick Y. , Michelet Véronique 
Published: April 2018

AbstractOver the last years, gold catalysis has gained considerable significance in organic synthesis, since it allows atom economy and synthetic efficiency for the transformation of relatively simple substrates into valuable, highly complex molecular architectures. The gold‐catalyzed polycyclization reactions of alkynes and enynes have been particularly successful toward the synthesis of natural products. This review highlights the recent developments in polycyclization area according to the key gold‐catalyzed step.
Diversification of 6‐bromo‐2‐substituted Pyridine Derivatives via Suzuki‐Miyaura Cross‐Coupling
Authors: Lambert Abigail E. , Carrick Jesse D. 
Published: April 2018

The functionalized pyridine ring is a ubiquitous moiety in numerous research areas including materials, natural products, as well as agrochemicals and is a strategic synthon for heteroaromatic synthetic method development. Pyridinyl ligand scaffolds are also frequently incorporated into the study of metal complexes for pharmaceutical applications or separation science. Convergent access to advanced synthons is critical to experimentally defining structure activity relationships and improvement of molecular performance in the aforementioned areas. The current work describes an efficient catalyst/ligand combination for accessing 2‐acetyl‐ and 2‐procarbonyl substituted pyridines via Suzuki‐Miyaura cross‐coupling with various organotrifluoroborates. Twenty examples are described with carbonyl and procarbonyl functional groups which afford subsequent access to diversified unsymmetric ketones. Substrate scope and limitation in addition to a scale up experiment are reported.
Linkage and retention in HCV care for HIV‐infected populations: early data from the DAA era
Authors: Sacks‐Davis Rachel , Doyle Joseph S , Rauch Andri , Beguelin Charles , Pedrana Alisa E , Matthews Gail V , Prins Maria , van der Valk Marc , Klein Marina B , Saeed Sahar , Lacombe Karine , Chkhartishvili Nikoloz , Altice Frederick L , Hellard Margaret E 
Published: April 2018

AbstractIntroductionThere is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV‐infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co‐infected populations in the context of implementation science theory.MethodsHCV elimination initiatives and studies in HIV co‐infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks.ResultsSeven HCV elimination initiatives and studies were identified in HIV co‐infected populations, mainly operating in high‐income countries. Four were focused mainly on HCV elimination in HIV‐infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV‐infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV‐infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%).ConclusionsEarly results from emerging research on HCV elimination in HIV‐infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have initiated treatment, completion and SVR rates are promising. More data are required in order to evaluate the effectiveness of these elimination programmes in the long term, assess which intervention components are effective, and whether they need to be tailored to particular population groups.
Approaches for simplified HCV diagnostic algorithms
Authors: Fourati Slim , Feld Jordan J , Chevaliez Stéphane , Luhmann Niklas 
Published: April 2018

AbstractIntroductionIn the light of the advances in HCV antiviral therapy, global control of HCV infection becomes feasible but depends on the capacity of countries to identify infected people and to offer them treatment. To achieve the WHO goal which targets a diagnosis rate of 90% by 2030, simplification of screening and diagnosis will be crucial.MethodsPublished literature, unpublished data and expert consensus were used to determine key parameters, including point‐of‐care, rapid diagnostic testing, screening, the use of HCV core Ag and dried blood spots; starting from 2008 until November 2017. In addition, a manual search was undertaken to detect relevant papers or websites related to specific data from countries which underwent or are planning a programme of HCV elimination.ResultsSeveral strategies have been developed and evaluated these last years to simplify and facilitate access to screening and diagnosis, the development of reliable HCV core antigen tests and new nucleic acid amplification technologies for use in decentralized settings. In high prevalence settings, a one‐step screening and diagnosis strategy could simplify diagnostic algorithms provided the cost is reduced. Finally, genotyping may no longer be required in the context of availability of pangenotypic antiviral therapy.ConclusionsDespite relevant advances in HCV screening and diagnosis, the overall diagnosis package is still too expensive today and efforts must be made to allow generalized implementation of reliable tests in low and middle income countries. These efforts will be key factors to foster a real public health approach to HCV elimination.
Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo
Authors: Aulakh Gurpreet K , Petri Björn , Wojcik Katarzyna M , Colarusso Pina , Lee James J , Patel Kamala D 
Published: April 2018

Abstract
Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment.
FAK inhibitor affects eosinophil recruitment in vivo using a new eosinophil reporter animal.
Altered fecal microbiota composition in all male aggressor‐exposed rodent model simulating features of post‐traumatic stress disorder
Authors: Gautam Aarti , Kumar Raina , Chakraborty Nabarun , Muhie Seid , Hoke Allison , Hammamieh Rasha , Jett Marti 
Published: April 2018

AbstractThe bidirectional role of gut–brain axis that integrates the gut and central nervous system activities has recently been investigated. We studied “cage‐within‐cage resident‐intruder” all‐male model, where subject male mice (C57BL/6J) are exposed to aggressor mice (SJL albino), and gut microbiota‐derived metabolites were identified in plasma after 10 days of exposure. We assessed 16S ribosomal RNA gene from fecal samples collected daily from these mice during the 10‐day study. Alpha diversity using Chao indices indicated no change in diversity in aggressor‐exposed samples. The abundance profile showed the top phyla were Firmicutes and Bacteroidetes, Tenericutes, Verrucomicrobia, Actinobacteria and Proteobacteria, respectively. The phyla Firmicutes and Bacteroidetes are vulnerable to PTSD‐eliciting stress and the Firmicutes/Bacteroidetes ratio increases with stress. Principal coordinate analysis showed the control and aggressor‐exposed samples cluster separately where samples from early time points (day 1‐3) clustered together and were distinct from late time points (day 4‐9). The genus‐based analysis revealed all control time points clustered together and aggressor‐exposed samples had multiple clusters. The decrease in proportion of Firmicutes after aggressor exposure persisted throughout the study. The proportion of Verrucomicrobia immediately decreased and was significantly shifted at most of the later time points. The genus Oscillospira, Lactobacillus, Akkermansia and Anaeroplasma are the top four genera that differed between control and stressor‐exposed mice. The data showed immediate effect on microbiome composition during a 10 day time period of stress exposure. Studying the longitudinal effects of a stressor is an important step toward an improved mechanistic understanding of the microbiome dynamics.
Post‐translational cleavage pattern of Lupinus angustifolius γ‐conglutin
Authors: Czubiński Jarosław , Montowska Magdalena , Fornal Emilia 
Published: April 2018

AbstractBACKGROUNDProtein post‐translational modifications are a key element for the functional diversity of the proteome. The modifications generally refer to the addition of functional groups to certain proteins; however, proteolytic cleavage is also one of the relevant events during protein maturation. γ‐Conglutin is a unique protein fraction present in lupin seeds that is marked by numerous unusual properties. This protein fraction undergoes very complex post‐translational maturation. Unfortunately, the precise mechanism of γ‐conglutin post‐translational processing is not yet fully understood.RESULTSTwo independent methods were used to study γ‐conglutin post‐translational cleavage processing. Edman N‐terminal sequencing indicates that the signal peptide is processed at Tyr34, while α‐ and β‐subunit cleavage takes place between Ser295 and Ser296. High‐resolution mass spectrometry revealed a great diversity of N‐terminal sequences of γ‐conglutin α‐subunit. However, most abundant peptides also began from Tyr34. Mass spectrometric analyses additionally confirmed the subunit cleavage position between two serine residues.CONCLUSIONSThe results indicate that the proteolytic processing of γ‐conglutin signal peptide is not precise. On the other hand, the post‐translational cleavage between α‐ and β‐subunits of γ‐conglutin is very conserved. Interestingly, the results also indicate that proteolytic processing leading to the formation of two subunits of γ‐conglutin is incomplete, leaving a certain amount of the protein in an uncut form. © 2018 Society of Chemical Industry
Improved survival for extremity soft tissue sarcoma treated in high‐volume facilities
Authors: Abarca Tyler , Gao Yubo , Monga Varun , Tanas Munir R. , Milhem Mohammed M. , Miller Benjamin J. 
Published: April 2018

Background and ObjectivesThe purpose of this investigation was to determine the effect of hospital volume on treatment decisions, treatment results, and overall patient survival in extremity soft tissue sarcoma.MethodsThe National Cancer Database was used to identify patients ≥18 years of age with non‐metastatic soft tissue sarcoma of the extremity treated with surgery. Patients in high‐ and low‐volume centers were matched by propensity score and placed into two equal comparative groups of 2437 patients each.ResultsChemotherapy was used at a higher rate in high‐volume centers (22% vs 17%, P < 0.001) and external beam radiation usage was similar (55% vs 52%, P = 0.108). There was a lower incidence of positive margins in high‐volume centers (12% vs 17%, P < 0.001). There was no significant difference in the rates of limb salvage surgery or readmissions at high‐volume hospitals compared to low‐volume. In a multivariate Cox proportional hazards model, low‐volume facilities demonstrated diminished overall survival at all time points (hazard ratio at 5 years = 1.24, 95%CI 1.10‐1.39).ConclusionsTreatment at high‐volume hospitals was associated with fewer positive margins and increased overall survival at 2, 5, and 10 years. Continued efforts should focus on optimizing the balance between patient access to specialty care and experience of the treating center.