bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood pressure and calf muscle oxygen extraction during plantar flexion exercise in peripheral artery disease
Authors: Luck J. Carter , Miller Amanda J. , Aziz Faisal , Radtka John F. , Proctor David N. , Leuenberger Urs A. , Sinoway Lawrence I. , Muller Matthew D. 
Published: April 2017

Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects 200 million people worldwide. Although PAD primarily affects large arteries, it is also associated with microvascular dysfunction, an exaggerated blood pressure (BP) response to exercise, and high cardiovascular mortality. We hypothesized that fatiguing plantar flexion exercise that evokes claudication elicits a greater reduction in skeletal muscle oxygenation (SmO2) and a higher rise in BP in PAD compared with age-matched healthy subjects, but low-intensity steady-state plantar flexion elicits similar responses between groups. In the first experiment, eight patients with PAD and eight healthy controls performed fatiguing plantar flexion exercise (from 0.5 to 7 kg for up to 14 min). In the second experiment, seven patients with PAD and seven healthy controls performed low-intensity plantar flexion exercise (2.0 kg for 14 min). BP, heart rate (HR), and SmO2 were measured continuously using near-infrared spectroscopy (NIRS). SmO2 is the ratio of oxygenated hemoglobin to total hemoglobin, expressed as a percent. At fatigue, patients with PAD had a greater increase in mean arterial BP (18 ± 2 vs. vs. 10 ± 2 mmHg, P = 0.029) and HR (14 ± 2 vs. 6 ± 2 beats/min, P = 0.033) and a greater reduction in SmO2 (−54 ± 10 vs. −12 ± 4%, P = 0.001). However, both groups had similar physiological responses to low-intensity, nonpainful plantar flexion exercise. These data suggest that patients with PAD have altered oxygen uptake and/or utilization during fatiguing exercise coincident with an augmented BP response. NEW & NOTEWORTHY In this laboratory study, patients with peripheral artery disease performed plantar flexion exercise in the supine posture until symptoms of claudication occurred. Relative to age- and sex-matched healthy subjects we found that patients had a higher blood pressure response, a higher heart rate response, and a greater reduction in skeletal muscle oxygenation as determined by near-infrared spectroscopy. Our data suggest that muscle ischemia contributes to the augmented exercise pressor reflex in peripheral artery disease.
Expression of Neuroendocrine Factor VGF in Lung Cancer Cells Confers Resistance to EGFR Kinase Inhibitors and Triggers Epithelial-to-Mesenchymal Transition
Authors: Hwang Wen , Chiu Yu-Fan , Kuo Ming-Han , Lee Kuan-Lin , Lee An-Chun , Yu Chia-Cherng , Chang Junn-Liang , Huang Wen-Chien , Hsiao Shih-Hsin , Lin Sey-En , Chou Yu-Ting 
Published: April 2017

AbstractMutations in EGFR drive tumor growth but render tumor cells sensitive to treatment with EGFR tyrosine kinase inhibitors (TKI). Phenotypic alteration in epithelial-to-mesenchymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma. However, the mechanism underlying this resistance remains unclear. Here we report that high expression of a neuroendocrine factor termed VGF induces the transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subset of lung adenocarcinoma cells. VGF silencing resensitized EGFR-mutated lung adenocarcinoma cells to TKI. Conversely, overexpression of VGF in sensitive cells conferred resistance to TKIs and induced EMT, increasing migratory and invasive behaviors. Correlation analysis revealed a significant association of VGF expression with advanced tumor grade and poor survival in patients with lung adenocarcinoma. In a mouse xenograft model of lung adenocarcinoma, suppressing VGF expression was sufficient to attenuate tumor growth. Overall, our findings show how VGF can confer TKI resistance and trigger EMT, suggesting its potential utility as a biomarker and therapeutic target in lung adenocarcinoma. Cancer Res; 77(11); 3013–26. ©2017 AACR.
Impact of fibrinogen carbamylation on fibrin clot formation and stability
Authors: Jaisson Stéphane , Gillery Philippe , Scavenius Carsten , Spriet Endy , Nyhaug Anne , Roberts Helen , Chapple Iain , Hellvard Annelie , Delaleu Nicolas , Mydel Piotr , Binder Veronika , Bergum Brith 
Published: April 2017

SummaryCarbamylation is a non-enzymatic post-translational modification induced upon exposure of free amino groups to urea-derived cyanate leading to irreversible changes of protein charge, structure and function. Levels of carbamylated proteins increase significantly in chronic kidney disease and carbamylated albumin is considered as an important biomarker indicating mortality risk. High plasma concentrations and long half-life make fibrinogen a prime target for carbamylation. As aggregation and cross-linking of fibrin monomers rely on lysine residues, it is likely that carbamylation impacts fibrinogen processing. In this study we investigated carbamylation levels of fibrinogen from kidney disease patients as well as the impact of carbamylation on fibrinogen cleavage by thrombin, fibrin polymerisation and cross-linking in vitro. In conjunction, all these factors determine clot structure and stability and thus control biochemical and mechanical properties. LC-MS/MS analyses revealed significantly higher homocitrulline levels in patient fibrinogen than in fibrinogen isolated from control plasma. In our in vitro studies we found that although carbamylation does not affect thrombin cleavage per se, it alters fibrin polymerisation kinetics and impairs cross-linking and clot degradation. In addition, carbamylated fibrin clots had reduced fiber size and porosity associated with decreased mechanical stability. Using mass spectroscopy, we discovered that N-terminally carbamylated fibrinopeptide A was generated in this process and acted as a strong neutrophil chemoattractant potentially mediating recruitment of inflammatory cells to sites of fibrin(ogen) turnover. Taken together, carbamylation of fibrinogen seems to play a role in aberrant fibrin clot formation and might be involved in haemostatic disorders associated with chronic inflammatory diseases.
On-clopidogrel platelet reactivity as predictor for long-term clinical outcome in patients after planned discontinuation of clopidogrel
Authors: Bömicke Timo , Valina Christian , Stratz Christian , Amann Michael , Neumann Franz-Josef , Hochholzer Willibald 
Published: April 2017

SummaryIt is unknown whether the known association of high on-treatment platelet reactivity (HTPR) with worse clinical outcome in patients on clopidogrel following coronary stent implantation persists after planned discontinuation of clopidogrel. This study investigated the association of HTPR with major ischaemic events after planned discontinuation of clopidogrel. Consecutive patients undergoing elective coronary stent implantation after loading with clopidogrel 600 mg were followed for up to seven years (n=765). Platelet reactivity was tested on day 1 after coronary intervention. Clopidogrel was continued for six months after implantation of drug-eluting stents and for one month if only bare-metal stents were used. The combined primary endpoint was death of any cause or non-fatal myocardial infarction (MACE). HTPR was found in 217 of 765 patients (28%). During a median follow-up of 5.7 years, the primary endpoint occurred in 145 subjects after planned discontinuation of clopidogrel. Patients with HTPR showed a higher incidence of MACE after discontinuation of clopidogrel. There was a significant interaction of HTPR and time following discontinuation of clopidogrel beyond one year (p for interaction 0.08). Landmark analyses confirmed that the association of HTPR and MACE was only significant within the first year (HR: 2.93, 95%-CI 1.13–7.60, p=0.03), but not beyond the first year following discontinuation of clopidogrel (HR: 1.19, 95%-CI 0.82–1.72, p=0.37). In conclusion, patients with HTPR persist to be at high risk for death or myocardial infarction even following planned discontinuation of clopidogrel. However, this association was only significant for the first year following discontinuation of clopidogrel.
Textural Composition: Aesthetics, Techniques, and Spatialization for High-Density Loudspeaker Arrays
Authors: Hagan Kerry L. 
Published: April 2017

This article documents a personal journey of compositional practice that led to the necessity for working with high-density loudspeaker arrays (HDLAs). I work with textural composition, an approach to composing real-time computer music arising from acousmatic and stochastic principles in the form of a sound metaobject. Textural composition depends upon highly mobile sounds without the need for trajectory-based spatialization procedures. In this regard, textural composition is an intermediary aesthetic—between “tape music” and real-time computer music, between sound objects and soundscape, and between point-source and trajectory-based, mimetic spatialization. I begin with the aesthetics of textural composition, including the musical and sonic spaces it needs to inhabit. I then detail the techniques I use to create textures for this purpose. I follow with the spatialization technique I devised that supports the aesthetic requirements. Finally, I finish with an example of an exception to my techniques, one where computational requirements and the HDLA required me to create a textural composition without my real-time strategies.
Reduced-Order Modeling of Stratospheric Winds and Its Application in High-Altitude Balloon Trajectory Simulations
Authors: Ramesh Sai Sudha , Lim Kian Meng , Lee Heow Pueh , Khoo Boo Cheong 
Published: April 2017

AbstractThe knowledge of weather conditions at the stratosphere is important for the planning and execution of high-altitude balloon flights, which require an accurate modeling of weather data over a period of time. Various methods based on statistical analysis, artificial neural networks, and cluster analysis have been employed to model the temporal variation of weather parameters. In the present study, a proper orthogonal decomposition (POD) method has been used to study the spatial as well as temporal variations of wind data in Singapore. The use of POD facilitates a compact representation of the weather dataset and aids in faster computation of wind profiles for use in balloon trajectory simulation. Further, the results reveal the existence of the quasi-biennial oscillation phenomenon, which is characteristic of equatorial easterly–westerly winds. This phenomenon enables the development of a Fourier prediction model, which can be used in real-time balloon trajectory simulations. The Fourier model is observed to be sensitive to wind velocity fluctuations, especially in the vicinity of alternating wind directions. However, it provides a reasonable projection of balloon trajectory, which can be used in preliminary planning and testing of high-altitude flights. Thus, a prior knowledge of wind profiles based on POD or a Fourier model aids in balloon station keeping. A simple case of altitude-controlled balloon flight is presented, and the results highlight the advantages of the present method in balloon station keeping.
Statistics and Meteorology of Air Pollution Episodes over the South African Highveld Based on Satellite–Model Datasets
Authors: Jury Mark R. 
Published: April 2017

AbstractThe meteorological conditions associated with air pollution episodes on South Africa’s Highveld were studied using Ozone Monitoring Instrument (OMI) and Atmospheric Infrared Sounder (AIRS) satellite estimates, MERRA2 reanalysis model products, and in situ weather data. Surface-layer sulfur dioxide (SO2) and nitrogen dioxide (NO2) display high concentrations during winter (May–July) and provide a focus for statistical analysis of monthly and daily time series. Highveld area-averaged monthly model SO2 was temporally correlated with boundary layer height (correlation coefficient of −0.76) and temperature lapse rate (+0.65) for the period of 1980–2015, but relationships with winds were weak. Daily Highveld area-averaged satellite NO2 was related to dewpoint temperature (−0.59) and exhibited pulsing in the range of 7–24 days for 2005–15. High concentrations of these short-lived locally generated air pollutants were found over and southeast of Johannesburg as a result of urban and industrial emissions. The spatial regression of daily NO2 onto regional sea level air pressure fields for May–July over 2005–15 revealed the slow eastward movement of an anticyclone. At the climatic time scale, Pacific Ocean La Niña conditions favored an increase of May–July SO2 concentrations when sea surface temperatures in the equatorial Atlantic Ocean were warmer than normal. The meteorological pattern underlying the highest-ranked air pollution event of 18–25 July 2008 was characterized by sharp anticyclonic curvature of low-level winds that induce subsidence and consequently a stable lapse rate and low dewpoint temperature (−5°C). The wind vorticity exerted a stronger influence on dispersion than did the surface divergence. This new understanding will underpin better air-quality forecasts over the South African Highveld.
Potential Predictability during a Madden–Julian Oscillation Event
Authors: Jones Charles , Dudhia Jimy 
Published: April 2017

The Madden–Julian oscillation (MJO) is an important source of predictability. The boreal 2004/05 winter is used as a case study to conduct predictability experiments with the Weather Research and Forecasting (WRF) Model. That winter season was characterized by an MJO event, weak El Niño, strong North Atlantic Oscillation, and extremely wet conditions over the contiguous United States (CONUS). The issues investigated are as follows: 1) growth of forecast errors in the tropics relative to the extratropics, 2) propagation of forecast errors from the tropics to the extratropics, 3) forecast error growth on spatial scales associated with MJO and non-MJO variability, and 4) the relative importance of MJO and non-MJO tropical variability on predictability of precipitation over CONUS. Root-mean-square errors in forecasts of normalized eddy kinetic energy (NEKE) (200 hPa) show that errors in initial conditions in the tropics grow faster than in the extratropics. Potential predictability extends out to about 4 days in the tropics and 9 days in the extratropics. Forecast errors in the tropics quickly propagate to the extratropics, as demonstrated by experiments in which initial conditions are only perturbed in the tropics. Forecast errors in NEKE (200 hPa) on scales related to the MJO grow slower than in non-MJO variability over localized areas in the tropics and short lead times. Potential predictability of precipitation extends to 1–5 days over most of CONUS but to longer leads (7–12 days) over regions with orographic precipitation in California. Errors in initial conditions on small scales relative to the MJO quickly grow, propagate to the extratropics, and degrade forecast skill of precipitation.
Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis
Authors: Cohen Jeffrey A , Imrey Peter B , Planchon Sarah M , Bermel Robert A , Fisher Elizabeth , Fox Robert J , Bar-Or Amit , Sharp Susan L , Skaramagas Thomai T , Jagodnik Patricia , Karafa Matt , Morrison Shannon , Reese Koc Jane , Gerson Stanton L , Lazarus Hillard M 
Published: April 2017

Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0–6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1–2 × 106 MSCs/kg were thawed and administered IV. Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1–3 passages) was 1.9 × 106 MSCs/kg (range, 1.5–2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
Development of a Pharmacist REferral Program in a primary cARE clinic (PREPARE): A prospective cross-sectional study
Authors: Barry Arden R. 
Published: April 2017

Background:Increasing demand for ambulatory health care services has led to the development of primary care multidisciplinary teams that include pharmacists. The objective of this study was to characterize referrals to a pharmacist in a primary care clinic (PCC) based in Chilliwack, British Columbia.Methods:This prospective cross-sectional study included all patients referred to the PCC pharmacist over 12 months (May 2015 to April 2016). Data regarding the source/reason for referral, patient demographics, medical problems/medications and number/category of identified drug therapy concerns (DTCs) were collected.Results:A total of 137 referrals were received. Mean age was 60 years and 59% were female. Twenty patients (15%) did not attend their appointment. Fifty-eight percent were new clinic patients identified using a Medication Risk Assessment Questionnaire (MRAQ), 30% were from PCC clinicians and 12% were from community family physicians. The most common reason for referral was for a medication review (82%). Median number of medical problems and medications per patient were 7 (interquartile range [IQR] 5) and 11 (IQR 7.5), respectively. A total of 460 DTCs were identified (median 4 per patient, IQR 3.5), of which 34% were medication without an indication and 28% an untreated indication.Discussion and Conclusion:The most common source of referrals to a PCC pharmacist was for medication reviews of new patients using an MRAQ. Most referred patients had multiple medical problems and polypharmacy, and few were referred for disease-specific management. The number of DTCs per patient was variable and, despite polypharmacy being commonplace, almost one-third of patients had an untreated indication.
Demonstration of therapeutic window of Cerebrolysin in embolic stroke: A prospective, randomized, blinded, and placebo-controlled study
Authors: Zhang Li , Chopp Michael , Lu Mei , Zhang Talan , Li Chao , Winter Stefan , Brandstaetter Hemma , Doppler Edith , Meier Dieter , Pabla Pardeep , Zhang Zheng G 
Published: April 2017

Background and aims In an effort to characterize the effects of Cerebrolysin for treatment of stroke that are essential for successful clinical translation, we have demonstrated that Cerebrolysin dose dependently enhanced neurological functional recovery in experimental stroke. Here, we conduct a prospective, randomized, placebo-controlled, blinded study to examine the therapeutic window of Cerebrolysin treatment of rats subjected to embolic stroke. Methods Male Wistar rats age 3–4 months (n = 100) were subjected to embolic middle cerebral artery occlusion. Animals were randomized to receive saline or Cerebrolysin daily for 10 consecutive days starting 4, 24, 48, and 72 h after middle cerebral artery occlusion. Neurological outcome was measured weekly with a battery of behavioral tests (adhesive removal test, modified neurological severity score (mNSS), and foot-fault test). Global test was employed to assess Cerebrolysin effect on neurological recovery with estimation of mean difference between Cerebrolysin and control-treated groups and its 95% confidence interval in the intent-to-treat population, where a negative value of the mean difference and 95% confidence interval < 0 indicated a significant treatment effect. All rats were sacrificed 28 days after middle cerebral artery occlusion and infarct volume was measured. Results Cerebrolysin treatment initiated within 48 h after middle cerebral artery occlusion onset significantly improved functional outcome; mean differences and 95% confidence interval were −11.6 (−17.7, −5.4) at 4 h, −7.1 (−13.5, −0.8) at 24 h, −8.4 (−14.2, −8.6) at 48 h, and −4.9 (−11.4, 1.5) at 72 h. There were no differences on infarct volume and mortality rate among groups. Conclusions With a clinically relevant rigorous experimental design, our data demonstrate that Cerebrolysin treatment effectively improves stroke recovery when administered up to 48 h after middle cerebral artery occlusion.
Segmenting subregions of the human hippocampus on structural magnetic resonance image scans: An illustrated tutorial
Authors: Dalton Marshall A. , Zeidman Peter , Barry Daniel N. , Williams Elaine , Maguire Eleanor A. 
Published: April 2017

Background: The hippocampus plays a central role in cognition, and understanding the specific contributions of its subregions will likely be key to explaining its wide-ranging functions. However, delineating substructures within the human hippocampus in vivo from magnetic resonance image scans is fraught with difficulties. To our knowledge, the extant literature contains only brief descriptions of segmentation procedures used to delineate hippocampal subregions in magnetic resonance imaging/functional magnetic resonance imaging studies. Methods: Consequently, here we provide a clear, step-by-step and fully illustrated guide to segmenting hippocampal subregions along the entire length of the human hippocampus on 3T magnetic resonance images. Results: We give a detailed description of how to segment the hippocampus into the following six subregions: dentate gyrus/Cornu Ammonis 4, CA3/2, CA1, subiculum, pre/parasubiculum and the uncus. Importantly, this in-depth protocol incorporates the most recent cyto- and chemo-architectural evidence and includes a series of comprehensive figures which compare slices of histologically stained tissue with equivalent 3T images. Conclusion: As hippocampal subregion segmentation is an evolving field of research, we do not suggest this protocol is definitive or final. Rather, we present a fully explained and expedient method of manual segmentation which remains faithful to our current understanding of human hippocampal neuroanatomy. We hope that this ‘tutorial’-style guide, which can be followed by experts and non-experts alike, will be a practical resource for clinical and research scientists with an interest in the human hippocampus.