bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans
Authors: van der Valk Fleur M. , Bekkering Siroon , Kroon Jeffrey , Yeang Calvin , Van den Bossche Jan , van Buul Jaap D. , Ravandi Amir , Nederveen Aart J. , Verberne Hein J. , Scipione Corey , Nieuwdorp Max , Joosten Leo A.B. , Netea Mihai G. , Koschinsky Marlys L. , Witztum Joseph L. , Tsimikas Sotirios , Riksen Niels P. , Stroes Erik S.G. 
Published: August 2016

Background:
Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis might be mediated through this pathway.

Methods:

In vivo imaging techniques including magnetic resonance imaging,
18
F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography were used to measure subsequently atherosclerotic burden, arterial wall inflammation, and monocyte trafficking to the arterial wall. Ex vivo analysis of monocytes was performed with fluorescence-activated cell sorter analysis, inflammatory stimulation assays, and transendothelial migration assays. In vitro studies of the pathophysiology of Lp(a) on monocytes were performed with an in vitro model for trained immunity.

Results:
We show that subjects with elevated Lp(a) (108 mg/dL [50–195 mg/dL]; n=30) have increased arterial inflammation and enhanced peripheral blood mononuclear cells trafficking to the arterial wall compared with subjects with normal Lp(a) (7 mg/dL [2–28 mg/dL]; n=30). In addition, monocytes isolated from subjects with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation (n=15). In vitro studies show that Lp(a) contains OxPL and augments the proinflammatory response in monocytes derived from healthy control subjects (n=6). This effect was markedly attenuated by inactivating OxPL on Lp(a) or removing OxPL on apolipoprotein(a).

Conclusions:
These findings demonstrate that Lp(a) induces monocyte trafficking to the arterial wall and mediates proinflammatory responses through its OxPL content. These findings provide a novel mechanism by which Lp(a) mediates cardiovascular disease.

Clinical Trial Registration:

URL:
http://www.trialregister.nl
. Unique identifier: NTR5006 (VIPER Study).
The 2015 Plains Elevated Convection at Night Field Project
Authors: Geerts Bart , Parsons David , Ziegler Conrad L. , Weckwerth Tammy M. , Biggerstaff Michael I. , Clark Richard D. , Coniglio Michael C. , Demoz Belay B. , Ferrare Richard A. , Gallus William A. , Haghi Kevin , Hanesiak John M. , Klein Petra M. , Knupp Kevin R. , Kosiba Karen , McFarquhar Greg M. , Moore James A. , Nehrir Amin R. , Parker Matthew D. , Pinto James O. , Rauber Robert M. , Schumacher Russ S. , Turner David D. , Wang Qing , Wang Xuguang , Wang Zhien , Wurman Joshua 
Published: August 2016

Abstract
The central Great Plains region in North America has a nocturnal maximum in warm-season precipitation. Much of this precipitation comes from organized mesoscale convective systems (MCSs). This nocturnal maximum is counterintuitive in the sense that convective activity over the Great Plains is out of phase with the local generation of CAPE by solar heating of the surface. The lower troposphere in this nocturnal environment is typically characterized by a low-level jet (LLJ) just above a stable boundary layer (SBL), and convective available potential energy (CAPE) values that peak above the SBL, resulting in convection that may be elevated, with source air decoupled from the surface. Nocturnal MCS-induced cold pools often trigger undular bores and solitary waves within the SBL. A full understanding of the nocturnal precipitation maximum remains elusive, although it appears that bore-induced lifting and the LLJ may be instrumental to convection initiation and the maintenance of MCSs at night.
To gain insight into nocturnal MCSs, their essential ingredients, and paths toward improving the relatively poor predictive skill of nocturnal convection in weather and climate models, a large, multiagency field campaign called Plains Elevated Convection At Night (PECAN) was conducted in 2015. PECAN employed three research aircraft, an unprecedented coordinated array of nine mobile scanning radars, a fixed S-band radar, a unique mesoscale network of lower-tropospheric profiling systems called the PECAN Integrated Sounding Array (PISA), and numerous mobile-mesonet surface weather stations. The rich PECAN dataset is expected to improve our understanding and prediction of continental nocturnal warm-season precipitation. This article provides a summary of the PECAN field experiment and preliminary findings.
The Relationship between Age of Air and the Diabatic Circulation of the Stratosphere
Authors: Linz Marianna , Plumb R. Alan , Gerber Edwin P. , Sheshadri Aditi 
Published: August 2016

AbstractThe strength of the Brewer–Dobson circulation is difficult to estimate using observations. Trends in the age of stratospheric air, deduced from observations of transient tracers, have been used to identify trends in the circulation, but there are ambiguities in the relationship between age and the strength of the circulation. This paper presents a steady-state theory and a time-dependent extension to relate age of air directly to the diabatic circulation of the stratosphere. In steady state, it is the difference between the age of upwelling and downwelling air through an isentrope and not the absolute value of age that is a measure of the strength of the diabatic circulation through that isentrope. For the time-varying case, expressions for other terms that contribute to the age budget are derived. An idealized atmospheric general circulation model with and without a seasonal cycle is used to test the time-dependent theory and to find that these additional terms are small upon annual averaging. The steady-state theory holds as well for annual averages of a seasonally varying model as for a perpetual-solstice model. These results are a step toward using data to quantify the strength of the diabatic circulation.
Evaluating Land–Atmosphere Coupling Using a Resistance Pathway Framework
Authors: Hirsch A. L. , Pitman A. J. , Haverd V. 
Published: August 2016

Abstract
This paper presents a methodology for examining land–atmosphere coupling in a regional climate model by examining how the resistances to moisture transfer from the land to the atmosphere control the surface turbulent energy fluxes. Perturbations were applied individually to the aerodynamic resistance from the soil surface to the displacement height, the aerodynamic resistance from the displacement height to the reference level, the stomatal resistance, and the leaf boundary layer resistance. Only perturbations to the aerodynamic resistance from the soil surface to the displacement height systematically affected 2-m air temperature for the shrub and evergreen boreal forest plant functional types (PFTs). This was associated with this resistance systematically increasing the terrestrial and atmospheric components of the land–atmosphere coupling strength through changes in the partitioning of the surface energy balance. Perturbing the other resistances did contribute to changing the partitioning of the surface energy balance but did not lead to systematic changes in the 2-m air temperature. The results suggest that land–atmosphere coupling in the modeling system presented here acts mostly through the aerodynamic resistance from the soil surface to the displacement height, which is a function of both the friction velocity and vegetation height and cover. The results show that a resistance pathway framework can be used to examine how changes in the resistances affect the partitioning of the surface energy balance and how this subsequently influences surface climate through land–atmosphere coupling. Limitations in the present analysis include grid-scale rather than PFT-scale analysis, the exclusion of resistance dependencies, and the linearity assumption of how temperature responds to a resistance perturbation.
Haemoglobin variants may cause significant differences in haemoglobin A1c as measured by high-performance liquid chromatography and enzymatic methods in diabetic patients: a cross-sectional study
Authors: Otabe Shuichi , Nakayama Hitomi , Ohki Tsuyoshi , Soejima Eri , Tajiri Yuji , Yamada Kentaro 
Published: August 2016

Background We aimed to determine whether the discrepancy between haemoglobin A1c values determined by high-performance liquid chromatography and enzymatic haemoglobin A1c measurements in diabetic patients was clinically relevant. Methods We randomly recruited 1421 outpatients undergoing diabetic treatment and follow-up who underwent at least three haemoglobin A1c measurements between April 2014 and March 2015 at our clinic. In 6369 samples, haemoglobin A1c was simultaneously measured by HA-8160 and MetaboLead (enzymatic assay), and the values were compared. Results haemoglobin A1c measurements by high-performance liquid chromatography and enzymatic assay were strongly correlated (correlation coefficient: 0.9828, linear approximation curve y = 0.9986x − 0.2507). Mean haemoglobin A1c (6.8 ± 1.0%) measured by high-performance liquid chromatography was significantly higher than that measured by enzymatic assay (6.5 ± 1.0%, P < 0.0001). During the sample processing, four (0.3%) subjects presented consistently lower haemoglobin A1c values (<0.7%) by high-performance liquid chromatography than those from enzymatic assay. Of these, three had Hb Toranomon [β112 (G14) Cys→Trp]. The fourth had Hb Ube-2 [α68 (E17) Asn→Asp]. One other subject presented consistently higher haemoglobin A1c values (>1%) by high-performance liquid chromatography than those from enzymatic assay and was diagnosed with a −77 (T > C) mutation in the δ-globin gene. These unrelated asymptomatic subjects had normal erythrocyte profiles, without anaemia. Conclusions We showed that haemoglobin A1c values measured by high-performance liquid chromatography were significantly higher than those measured by enzymatic assay in diabetic subjects. However, when an oversized deviation (>0.7%) between glycaemic control status and haemoglobin A1c is apparent, clinicians should check the methods used to measure haemoglobin A1c and consider the possible presence of a haemoglobin variant.
Post-standardization of routine creatinine assays: are they suitable for clinical applications
Authors: Jassam Nuthar , Weykamp Cas , Thomas Annette , Secchiero Sandra , Sciacovelli Laura , Plebani Mario , Thelen Marc , Cobbaert Christa , Perich Carmen , Ricós Carmen , Paula Faria A , Barth Julian H 
Published: August 2016

IntroductionReliable serum creatinine measurements are of vital importance for the correct classification of chronic kidney disease and early identification of kidney injury. The National Kidney Disease Education Programme working group and other groups have defined clinically acceptable analytical limits for creatinine methods. The aim of this study was to re-evaluate the performance of routine creatinine methods in the light of these defined limits so as to assess their suitability for clinical practice.MethodIn collaboration with the Dutch External Quality Assurance scheme, six frozen commutable samples, with a creatinine concentration ranging from 80 to 239  μmol/L and traceable to isotope dilution mass spectrometry, were circulated to 91 laboratories in four European countries for creatinine measurement and estimated glomerular filtration rate calculation. Two out of the six samples were spiked with glucose to give high and low final concentrations of glucose.ResultsResults from 89 laboratories were analysed for bias, imprecision (%CV) for each creatinine assay and total error for estimated glomerular filtration rate. The participating laboratories used analytical instruments from four manufacturers; Abbott, Beckman, Roche and Siemens. All enzymatic methods in this study complied with the National Kidney Disease Education Programme working group recommended limits of bias of 5% above a creatinine concentration of 100  μmol/L. They also did not show any evidence of interference from glucose. In addition, they also showed compliance with the clinically recommended %CV of ≤4% across the analytical range. In contrast, the Jaffe methods showed variable performance with regard to the interference of glucose and unsatisfactory bias and precision.ConclusionJaffe-based creatinine methods still exhibit considerable analytical variability in terms of bias, imprecision and lack of specificity, and this variability brings into question their clinical utility. We believe that clinical laboratories and manufacturers should work together to phase out the use of relatively non-specific Jaffe methods and replace them with more specific methods that are enzyme based.
Bone turnover marker reference intervals in young females
Authors: Callegari Emma T , Gorelik Alexandra , Garland Suzanne M , Chiang Cherie Y , Wark John D 
Published: August 2016

Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16–25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230–1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27–131  µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers’ relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.
Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer
Authors: Shetty Praveenkumar , Patil Vidya S , Mohan Rajashekar , D’souza Leonard Clinton , Bargale Anil , Patil Basavaraj R , Dinesh US , Haridas Vikram , Kulkarni Shrirang P 
Published: August 2016

BackgroundAnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression.MethodsSecretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model.ResultsAnnexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 ± 60.59 ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 ± 118.81 pg/mL) were highly significant compared with normal (14.92 ± 17.33 pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the breast cancer phenotypes as compared with normal ( P < 0.001).ConclusionThe specific expression pattern of annexinA2 and HB-EGF in triple-negative breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.
Integrating across policy sectors: how the wider public impacts on the drafting process of EU trans-border healthcare
Authors: Hartlapp Miriam 
Published: August 2016

Policy-making in the EU has been depicted as being starkly fragmented: initiatives are drafted in separate Directorates-General of the EU Commission, discussed in specific policy communities and decided upon in sectoral European Parliament Committees and Council formations. At the same time, we see growing numbers of complex policy problems that require cross-sectorally integrated solutions. This article argues that there are good grounds to expect policy-making in the EU Commission to favour fragmented solutions, while diffuse public interests will tend to push for integrated policies. However, it is only under specific constellations that the EU Commission will respond to these interests. The argument will be demonstrated using case study material on three policy instruments that address trans-border healthcare policy. While the Coordination of Social Security Systems Regulation and the Services in the Internal Market Directive favour largely fragmented solutions, the Patient Mobility Directive takes a more integrated approach. Points for practitioners Today, complex policy problems often demand integrated policy solutions that cut across organizational borders and areas of responsibility. At the same time, decision-making is often easier if policy solutions remain fragmented. Internal coordination is an important means for public administrations to reach integrated instead of fragmented policy solutions. Periods with high public attention are more likely to lead to more integrated policy solutions, since policy-makers will seize internal coordination to anticipate the interests of a wider public that is following the policy-making process. Evidence is provided from drafting processes inside the EU Commission on trans-border healthcare acts.
Patient perceptions of weight loss
Authors: Nelson David A , Ruffalo Leslie A , Dyer Alexandra J , Nelson Karen H 
Published: August 2016

Objectives The prevalence of overweight and obese individuals in the United States is growing, and primary health care represents a setting in which providers may address weight with their patients. However, many providers and medical trainees feel ill-prepared to address the full scope of complexities associated with weight loss. This study sought to investigate patients’ perceptions of the barriers and facilitators they encountered in their weight loss journeys. The results of the mixed-methods study will be used to inform a better understanding among providers and medical students of how to address weight loss with their patients. This study was approved by the institutional review board of Medical College of Wisconsin. Methods Participants were selected from patient panels at a Family Medicine Residency Program. Participants who enrolled in the study completed a survey that collected attitudes and behaviors about weight loss and demographics. The patients also participated in a 60- to 90-min guided interview. Interviews were transcribed verbatim and analyzed using open-coding techniques and principles of grounded theory. Results To date, five participants completed the study. All were female with a mean age of 52 years. Two primary themes emerged from a grounded theory model. The first theme centered on individual’s knowledge, attitudes, and behaviors to lost weight. The second theme emphasized that societal relationships serve as both a barrier and a facilitator to weight loss. Conclusion The overarching conclusion of this study is that individuals often have the knowledge to make positive health behaviors changes, but multiple factors may prohibit this from occurring. When a supportive environment exists, healthy behavior changes are more attainable. Physicians, mid-level providers, and medical trainees and even medical systems can provide appropriate support to join the patient on their weight loss journey.
The elephant in the room
Authors: White-Davis Tanya , Stein Emma , Karasz Alison 
Published: August 2016

Objectives For centuries, the concept of race, a uniquely pervasive social construct, has often complicated dialogue and interactions between groups of people. This study assessed perceptions and attitudes of faculty and trainees with varied racial backgrounds within graduate medical and psychology programs. Self-reported responses addressed potential barriers and facilitating factors required for meaningful conversations about race. Methods A brief 18-question survey was developed and administered electronically to three professional and academic Listservs within a large metropolitan city in northeast United States. Quantitative and qualitative analysis were conducted using SPSS Statistical Software and Text analyzer. Results Results revealed that among participants ( N = 57) a majority experienced cross-racial supervision, and more than half indicated engaging in conversations about race within supervision. Respondents endorsed lack of comfort and lack of opportunity/time as significant barriers to discussing race within supervision. When race-related dialogues occurred, a majority of supervisees and supervisors found it beneficial. Most Supervisors of Colora actively initiated these conversations in supervision, while White supervisees endorsed the least benefit from these conversations. Contrary to our expectations, few respondents endorsed limited training as a barrier. Discussion The current study revealed cross-racial dialogues about race may be occurring frequently in supervisory relationships. Supervisees of Color reported benefiting from these dialogues, in contrast to their White counterparts, who endorsed the least benefit. Lack of comfort in supervisory relationships appears to be a significant barrier to having these conversations. Therefore, it is important for supervisors to create supervisory relationships emphasizing safety and comfort. Directions for future research are discussed.