bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study
Authors: Kanias Tamir , Lanteri Marion C. , Page Grier P. , Guo Yuelong , Endres Stacy M. , Stone Mars , Keating Sheila , Mast Alan E. , Cable Ritchard G. , Triulzi Darrell J. , Kiss Joseph E. , Murphy Edward L. , Kleinman Steve , Busch Michael P. , Gladwin Mark T. 
Published: June 2017

Key Points
Genetic and biological variability in blood donors may impact RBC predisposition to hemolysis during cold storage and after transfusion. Male sex, Asian or African American racial background, and older age (>45 years) are significant modifiers of hemolysis.
Urban green and grey space in relation to respiratory health in children
Authors: Tischer Christina , Gascon Mireia , Fernández-Somoano Ana , Tardón Adonina , Lertxundi Materola Aitana , Ibarluzea Jesus , Ferrero Amparo , Estarlich Marisa , Cirach Marta , Vrijheid Martine , Fuertes Elaine , Dalmau-Bueno Albert , Nieuwenhuijsen Mark J. , Antó Josep M. , Sunyer Jordi , Dadvand Payam 
Published: June 2017

We assessed the effect of three different indices of urban built environment on allergic and respiratory conditions.This study involved 2472 children participating in the ongoing INMA birth cohort located in two bio-geographic regions (Euro-Siberian and Mediterranean) in Spain. Residential surrounding built environment was characterised as 1) residential surrounding greenness based on satellite-derived normalised difference vegetation index (NDVI), 2) residential proximity to green spaces and 3) residential surrounding greyness based on urban land use patterns. Information on wheezing, bronchitis, asthma and allergic rhinitis up to age 4 years was obtained from parent-completed questionnaires. Logistic regression and generalised estimating equation modelling were performed.Among children from the Euro-Siberian region, higher residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing. In the Mediterranean region, higher residential proximity to green spaces was associated with a reduced risk for bronchitis. A higher amount of residential surrounding greyness was found to increase the risk for bronchitis in this region.Associations between indices of urban residential greenness and greyness with respiratory diseases differ by region. The pathways underlying these associations require further exploration.
Predicting risk of undiagnosed COPD: development and validation of the TargetCOPD score
Authors: Haroon Shamil , Adab Peymane , Riley Richard D. , Fitzmaurice David , Jordan Rachel E. 
Published: June 2017

Chronic obstructive pulmonary disease (COPD) is greatly underdiagnosed worldwide and more efficient methods of case-finding are required. We developed and externally validated a risk score to identify undiagnosed COPD using primary care records.We conducted a retrospective cohort analysis of a pragmatic cluster randomised controlled case-finding trial in the West Midlands, UK. Participants aged 40–79 years with no prior diagnosis of COPD received a postal or opportunistic screening questionnaire. Those reporting chronic respiratory symptoms were assessed with spirometry. COPD was defined as presence of relevant symptoms with a post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. A risk score was developed using logistic regression with variables available from electronic health records for 2398 participants who returned a postal questionnaire. This was externally validated among 1097 participants who returned an opportunistic questionnaire to derive the c-statistic, and the sensitivity and specificity of cut-points.A risk score containing age, smoking status, dyspnoea, prescriptions of salbutamol and prescriptions of antibiotics discriminated between patients with and without undiagnosed COPD (c-statistic 0.74, 95% CI 0.68–0.80). A cut-point of ≥7.5% predicted risk had a sensitivity of 68.8% (95% CI 57.3–78.9%) and a specificity of 68.8% (95% CI 65.8.1–71.6%).A novel risk score using routine data from primary care electronic health records can identify patients at high risk for undiagnosed symptomatic COPD. This score could be integrated with clinical information systems to help primary care clinicians target patients for case-finding.
Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD
Authors: Naz Shama , Kolmert Johan , Yang Mingxing , Reinke Stacey N. , Kamleh Muhammad Anas , Snowden Stuart , Heyder Tina , Levänen Bettina , Erle David J. , Sköld C. Magnus , Wheelock Åsa M. , Wheelock Craig E. 
Published: June 2017

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
PTH monitoring after total parathyroidectomy with forearm auto-transplantation: Potential for spuriously high levels from grafted forearm
Authors: Khalil Diana , Kerr Paul D. 
Published: June 2017

Background We have identified a cause of falsely elevated parathyroid hormone (PTH) levels after total parathyroidectomy with forearm auto-transplantation (TPT-ATx). Our cases highlight the need to draw PTH samples remotely, away from forearm graft sites, to ensure accurate levels. Case presentations We report on four patients who were referred to our surgical team at an academic tertiary care center for what was perceived to be recurrent hyperparathyroidism 2–5 years following total parathyroidectomy with auto-transplantation. Further evaluation revealed highly discrepant results in these patients depending on where the blood was drawn, with spuriously high levels in blood drawn from the grafted arm (Range 337–3885 ng/l), and much lower levels when blood was drawn remotely away from the graft site (Range 9–242 ng/l). The difference in PTH level between the grafted forearm and remote site for these patients ranged between 328 and 3643 ng/l. Over the period these cases were accrued (2008–2012), 89 patients underwent TPT-ATx in our institution. Therefore, our case report series suggests that this phenomenon will be evident to a clinically important extent in at least 4% of patients. Conclusions One can acquire spuriously high PTH levels from grafted forearms, leading to the false diagnosis of recurrent hyperparathyroidism. We recommend PTH levels be drawn remotely from graft sites to ensure accurate systemic levels are reflected.
Adipose tissue macrophages develop from bone marrow–independent progenitors in Xenopus laevis and mouse
Authors: Hassnain Waqas Syed F , Noble Anna , Hoang Anh C , Ampem Grace , Popp Manuela , Strauß Sarah , Guille Matthew , Röszer Tamás 
Published: June 2017

Abstract
ATMs have a metabolic impact in mammals as they contribute to metabolically harmful AT inflammation. The control of the ATM number may have therapeutic potential; however, information on ATM ontogeny is scarce. Whereas it is thought that ATMs develop from circulating monocytes, various tissue-resident Mϕs are capable of self-renewal and develop from BM-independent progenitors without a monocyte intermediate. Here, we show that amphibian AT contains self-renewing ATMs that populate the AT before the establishment of BM hematopoiesis. Xenopus ATMs develop from progenitors of aVBI. In the mouse, a significant amount of ATM develops from the yolk sac, the mammalian equivalent of aVBI. In summary, this study provides evidence for a prenatal origin of ATMs and shows that the study of amphibian ATMs can enhance the understanding of the role of the prenatal environment in ATM development.
Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals
Authors: Rivera Margarita , Locke Adam E. , Corre Tanguy , Czamara Darina , Wolf Christiane , Ching-Lopez Ana , Milaneschi Yuri , Kloiber Stefan , Cohen-Woods Sara , Rucker James , Aitchison Katherine J. , Bergmann Sven , Boomsma Dorret I. , Craddock Nick , Gill Michael , Holsboer Florian , Hottenga Jouke-Jan , Korszun Ania , Kutalik Zoltan , Lucae Susanne , Maier Wolfgang , Mors Ole , Müller-Myhsok Bertram , Owen Michael J. , Penninx Brenda W. J. H. , Preisig Martin , Rice John , Rietschel Marcella , Tozzi Federica , Uher Rudolf , Vollenweider Peter , Waeber Gerard , Willemsen Gonneke , Craig Ian W. , Farmer Anne E. , Lewis Cathryn M. , Breen Gerome , McGuffin Peter 
Published: June 2017

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.ConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children’s Oncology Group Trial AAML0531
Authors: Lamba Jatinder K. , Chauhan Lata , Shin Miyoung , Loken Michael R. , Pollard Jessica A. , Wang Yi-Cheng , Ries Rhonda E. , Aplenc Richard , Hirsch Betsy A. , Raimondi Susana C. , Walter Roland B. , Bernstein Irwin D. , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil 
Published: June 2017

Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy. Patients and Methods CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children’s Oncology Group AAML0531 trial. Results The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P < 1.0E−6) and with lower diagnostic leukemic cell surface CD33 intensity ( P < 1.0E−6). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P < .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype. Conclusion Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO.
Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer
Authors: Choueiri Toni K. , Plimack Elizabeth , Arkenau Hendrik-Tobias , Jonasch Eric , Heng Daniel Y.C. , Powles Thomas , Frigault Melanie M. , Clark Edwin A. , Handzel Amir A. , Gardner Humphrey , Morgan Shethah , Albiges Laurence , Pal Sumanta Kumar 
Published: June 2017

PurposePatients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status.Patients and MethodsPatients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients.ResultsOf 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P < .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema.ConclusionThese data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.
Effect of APOE ε Genotype on Lipoprotein(a) and the Associated Risk of Myocardial Infarction and Aortic Valve Stenosis
Authors: Kritharides Leonard , Nordestgaard Børge G , Tybjærg-Hansen Anne , Kamstrup Pia R , Afzal Shoaib 
Published: June 2017

Abstract

Context
APOE ε2/3/4 genotypes affect plasma lipoprotein(a); however, the effects of APOE genotypes on the prediction of myocardial infarction and aortic valve stenosis by lipoprotein(a) are unknown.

Objective
We tested the hypothesis that APOEε2/3/4 genotype affects plasma lipoprotein(a), the contribution of plasma apoE levels to this association as well as the associated risk of myocardial infarction and aortic valve stenosis.

Design and Outcome Measures
In 46,615 individuals from the general population, we examined plasma lipoprotein(a), APOE ε2/3/4, and incidence of myocardial infarction (n = 1807) and aortic valve stenosis (n = 345) over 37 years of follow-up (range: 0.3 to 38 years).

Results
Compared with ε33, age- and sex-adjusted lipoprotein(a) concentrations were lower by 15% in ε23, by 24% in ε24, and by 36% in ε22; adjusted for plasma apolipoprotein E, corresponding values were 22%, 28%, and 62%. These reductions were independent of LPA genotypes. Compared with ε2 carriers with lipoprotein(a) ≤50 mg/dL, the hazard ratio for myocardial infarction was 1.26 (95% confidence interval: 1.06 to 1.49) for ε2 noncarriers with lipoprotein(a) ≤50 mg/dL, 1.68 (1.21 to 2.32) for ε2 carriers with lipoprotein(a) &gt;50 mg/dL, and 1.92 (1.59 to 2.32) for ε2 noncarriers with lipoprotein(a) &gt;50 mg/dL (interaction, P = 0.57); corresponding values for aortic valve stenosis were 1.05 (0.74 to 1.51), 1.49 (0.72 to 3.08), and 2.04 (1.46 to 2.26) (interaction, P = 0.50). Further adjustment for APOE ε2/3/4 genotype had minimal influence on these risk estimates.

Conclusions
APOE ε2 is a strong genetic determinant of low lipoprotein(a) concentrations but does not modify the causal association of lipoprotein(a) with myocardial infarction or aortic valve stenosis.
The Social Scope of Roman Identity in Byzantium: An Evidence-Based Approach
Authors: KALDELLIS Anthony 
Published: June 2017

Η ΚΟΙΝΩΝΙΚΗ ΕΜΒΕΛΕΙΑ ΤΗΣ ΡΩΜΑΪΚΗΣ ΤΑΥΤΟΤΗΤΑΣ ΣΤΟ ΒΥΖΑΝΤΙΟ: ΜΙΑ ΠΡΟΣΕΓΓΙΣΗ ΒΑΣΕΙ ΤΩΝ ΓΡΑΠΤΩΝ ΠΗΓΩΝ Έχουν προταθεί προσφάτως αντίθετες ερμηνείες αναφορικά με την κοινή διαπίστωση ότι οι Βυζαντινοί «αυτοαποκαλούνται Ρωμαίοι». Σύμφωνα με μία άποψη, το Βυζάντιο ήταν ρωμαϊκό έθνος-κράτος, ενώ αντιθέτως έχει υποστηριχθεί επίσης ότι η ρωμαϊκή ταυτότητα ήταν αποκλειστικότητα μιας αριθμητικά περιορισμένης «ελίτ». Το παρόν άρθρο χαρτογραφεί για πρώτη φορά την κοινωνική εμβέλεια της ρωμαϊκής ταυτότητας, όπως προκύπτει από τις γραπτές πηγές: ποιούς εννοούσαν οι Βυζαντινοί και οι Άραβες συγγραφείς, όταν χρησιμοποιούσαν τον όρο «Ρωμαίοι»; Οι Ρωμαίοι ήταν ένα στενό κοινωνικό-οικονομικό στρώμα ή είχαν συνείδηση ότι αποτελούσαν το μεγαλύτερο μέρος του πληθυσμού της αυτοκρατορίας; Από την ανάλυση των κειμένων προκύπτει ότι η ρωμαϊκή ταυτότητα δεν περιοριζόταν στην πολιτικοκοινωνική ελίτ της αυτοκρατορίας, αλλά αφορούσε σε όλα σχεδόν τα κοινωνικά στρώματα, τόσο στην Κωνσταντινούπολη όσο και στην επαρχία. Η αντίθετη ερμηνεία περί ελίτ βασίζεται σε παραπλανητικές σύγχρονες θεωρίες και όχι στις πρωτογενείς πηγές.
Monitoring respiration and oxygen saturation in patients during the first night after elective bariatric surgery: A cohort study
Authors: Wickerts Liselott , Forsberg Sune , Bouvier Frederic , Jakobsson Jan G. 
Published: June 2017

Background: Obstructive sleep apnoea and obese hypoventilation is not uncommon in patients with obesity. Residuals effect from surgery/anaesthesia and opioid analgesics may worsen respiration during the first nights after bariatric surgery. The aim of this observational study was to monitor respiration on the first postoperative night following elective bariatric surgery. Methods: This observational study aimed to determine the incidence and severity of hypo/apnoea in low risk obsess patients undergoing elective bariatric surgery in general anesthaesia. Patients with known or suspected sleep respiratory disturbances was not included. ESS was scored prior to surgery. Oxygen desaturation was analyzed by continuous respiratory monitoring. Mean oxygen saturation (SpO2), nadir SPo2, apnoea/hypopnea index and oxygen desaturation index was assess by standard tools. Results: 45 patients were monitored with portable polygraphy equipment (Embletta, ResMed) during the first postoperative night at the general ward following elective laparoscopic bariatric surgery. The prop ESS was 0-5 in 22, 6-10 in 14 and 11-16 in 6 of the patients studied (missing data 3). Mean SpO2 was 93%; 10 patients had a mean SpO2 of less than 92% and 4 of less than 90%. The lowest mean SpO2 was 87%. There were 16 patients with a nadir SpO2 of less than 85%, lowest nadir SpO2 being 63%. An Apnoea Hypo/apnoea Index (AHI) > 5 was found in 2 patients only (AHI 10 and 6), and an Oxygen Desaturation index (ODI) > 5 was found in 3 patients (24, 10 and 6, respectively). 3 patients had more prolonged (> 30 seconds) apnoea with nadir SpO2 81%, 83% and 86%. ESS score and type of surgery did not impact on respiration/oxygenation during the observation period. Conclusions: A low mean SpO2 and episodes of desaturation were not uncommon during the first postoperative night following elective bariatric surgery in patients without history of night time breathing disturbance. AHI and/or ODI of more than 5 were only rarely seen. Night-time respiration monitoring provided seemingly sparse additional information. Further studies are need to assess risk factors and potential impact of the desaturation episodes that occurs during sleep.
Pilot Metal Workload in Flight Operation: A case study of Indonesian Civilian Pilot
Authors: Saputra Abadi Dwi 
Published: June 2017

This type of activity or work with high stress level and requires more concentration and attention, in this case is the aircraft operation. Thereby mental workload is the most dominant than the physical workload. And this is what should have been a concern, because if mental workload endured by pilot is excessive, it will lower down the quality of work and lead to work safety; in this case the aircraft operation. Subjective Workload Assessment Technique (SWAT) method is used to measure mental workload value, this method consists of three dimensions with their levels, there are: time, mental effort, and psychological stress load. The aim of this study was to know the mental workload of the pilot of an aircraft in flight dimensions: phases of time, phase of flight, terrain condition, and weather, and identifies what factors the most dominant for build of mental workload. The results of studies showed that pilot mental workload will increase when a pilot faced with flight conditions do at early morning (00.00-05:59 am), during weekend and enters the peak season period, and the aircraft will be landing procedures, and also in case of change of wind conditions in flight, and will increasingly when pilot exposed to aircraft operating with route condition which has a land surface is mountainious. This study also showed that the time dimension factor (T) significantly affects the mental workload of pilots, indicating that they put more emphasis on this factor when they are considering workloads.