bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men
Authors: Skattebo Øyvind , Calbet Jose A. L. , Rud Bjarne , Capelli Carlo , Hallén Jostein 
Published: May 2020

AbstractWe analysed the importance of systemic and peripheral arteriovenous O2difference (difference and a‐vfO2difference, respectively) and O2extraction fraction for maximal oxygen uptake (). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with. Articles (n = 17) publishing individual data (n = 154) on, maximal cardiac output (; indicator‐dilution or the Fick method),difference (catheters or the Fick equation) and systemic O2extraction fraction were identified. For the peripheral responses, group‐mean data (articles:n = 27; subjects:n = 234) on leg blood flow (LBF; thermodilution), a‐vfO2difference and O2extraction fraction (arterial and femoral venous catheters) were obtained.and two‐LBF increased linearly by 4.9‐6.0 L·min–1per 1 L·min–1increase in(R2 = .73 andR2 = .67, respectively; bothP < .001). Thedifference increased from 118‐168 mL·L–1from aof 2‐4.5 L·min–1followed by a reduction (second‐order polynomial:R2 = .27). After accounting for a hypoxemia‐induced decrease in arterial O2content with increasing(R2 = .17;P < .001), systemic O2extraction fraction increased up to ~90% (: 4.5 L·min–1) with no further change (exponential decay model:R2 = .42). Likewise, leg O2extraction fraction increased withto approach a maximal value of ~90‐95% (R2 = .83). Muscle O2diffusing capacity and the equilibration indexYincreased linearly with(R2 = .77 andR2 = .31, respectively; bothP < .01), reflecting decreasing O2diffusional limitations and accentuating O2delivery limitations. In conclusion, although O2delivery is the main limiting factor to, enhanced O2extraction fraction (≥90%) contributes to the remarkably highin endurance‐trained individuals.
Profiles of serum soluble programmed death‐1 and programmed death‐ligand 1 levels in chronic hepatitis B virus‐infected patients with different disease phases and after anti‐viral treatment
Authors: Xia Juan , Huang Rui , Chen Yuxin , Liu Yong , Wang Jian , Yan Xiaomin , Zhang Zhaoping , Wu Chao 
Published: May 2020

SummaryBackgroundSoluble programmed death‐1 (sPD‐1) and soluble programmed death‐ligand 1 (sPD‐L1) play a role in immune regulation of chronic hepatitis B virus (HBV) infection.AimTo investigate the profiles of serum sPD‐1 and sPD‐L1 in chronic HBV‐infected patients with different disease phases and after anti‐viral treatment.MethodsA total of 99 chronic HBV‐infected patients were enrolled and divided into HBeAg‐positive chronic HBV infection (EPI) group, HBeAg‐positive chronic hepatitis B (EPH) group, HBeAg‐negative chronic hepatitis B (ENH) group and HBeAg‐negative chronic HBV infection (ENI) group. Eleven healthy subjects were included as healthy controls (HCs). Thirty‐two EPH patients received anti‐viral treatment with nucleos(t)ide analogues and were followed up to 5 years. Serum sPD‐1 and sPD‐L1 levels were detected by Multiplex Immunoassays.ResultsSerum sPD‐1 and sPD‐L1 levels of chronic HBV infected patients were significantly higher than that of HCs (P < 0.01). Patients in EPH, ENH and EPI groups had higher serum sPD‐1 and sPD‐L1 levels than that in HCs (P < 0.01). After anti‐viral treatment, serum sPD‐1 and sPD‐L1 levels declined rapidly. EPH patients with HBeAg clearance after 2 years of anti‐viral treatment showed lower baseline HBeAg and sPD‐1 levels compared to those without HBeAg clearance.ConclusionsSerum sPD‐1 and sPD‐L1 levels varied among chronic HBV infected patients with different disease phases. Lower baseline sPD‐1 levels were associated with HBeAg clearance after 2 years of anti‐viral treatment in EPH patients.
Population pharmacokinetics of adalimumab biosimilar adalimumab‐adbm and reference product in healthy subjects and patients with rheumatoid arthritis to assess pharmacokinetic similarity
Authors: Kang Jia , Eudy‐Byrne Rena J. , Mondick John , Knebel William , Jayadeva Girish , Liesenfeld Karl‐Heinz 
Published: May 2020

AimsAdalimumab‐adbm is a monoclonal antibody developed as a biosimilar to adalimumab (Humira, AbbVie Inc.). The key objectives of this study were using a population pharmacokinetic (PPK) approach to assess pharmacokinetic (PK) similarity between adalimumab‐adbm and Humira in patients with active rheumatoid arthritis (RA), to quantify the effects of potential covariates on adalimumab PK and to assess the impact of switching treatment from Humira to adalimumab‐adbm on PK.MethodsA PPK model was firstly developed using intensive PK data from the phase‐1 study in healthy subjects (NCT02045979). PPK models were developed separately for phase‐3 base study (NCT02137226) and its extension study (NCT02640612) in patients with active RA.ResultsPPK models were developed for adalimumab from adalimumab‐adbm and Humira treatment in healthy subjects and RA patients. Weight and anti‐drug antibodies were found to be important predictors of adalimumab clearance. Adalimumab PK was similar between adalimumab‐adbm and Humira. The estimated effect of Humira on clearance, relative to the adalimumab‐adbm, was 1.02 (i.e., Humira has 0.02 greater clearance). Similarly, the effect of treatment arms (switching) on clearance was estimated to be 1.00 and 0.997 for Humira:Humira:BI and Humira:BI:BI arms, respectively, relative to the BI:BI:BI arm (BI refers to adalimumab‐adbm) in the phase‐3 extension study.ConclusionPK similarity between adalimumab‐adbm and Humira in patients with active RA was demonstrated using PPK approach. Adalimumab PK was also similar when switching treatment from Humira to adalimumab‐adbm at either week 24 or 48.
Clinical and neuroendocrine correlates of childhood maltreatment history in adults with bipolar disorder
Authors: Monteleone Alessio Maria , Cascino Giammarco , Marciello Francesca , D’Agostino Giulia , Caivano Vito , Monteleone Palmiero , Maj Mario 
Published: May 2020

AbstractObjectivesChildhood maltreatment has been associated to an increased risk of developing bipolar disorder (BD). A role of the hypothalamus‐pituitary‐adrenal (HPA) axis in mediating trauma‐related risk for adult psychopathology has been suggested but scarcely investigated in BD. Therefore, we explored the impact of childhood maltreatment on clinical features of BD and on the activity of the HPA axis.MethodsOne hundred and six patients participated in the study. On the basis of their history of childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), they were divided into a group with a history of childhood maltreatment (CM+) and a group without (CM−). Twenty‐nine participants (16 with a history of childhood trauma and 13 without) underwent the cortisol awakening response (CAR) test.ResultsSixty‐two patients had a history of childhood maltreatment and 44 had not. Maltreatment was significantly more frequent in females than males. CM+ patients showed a significant higher body mass index, a significant higher number of suicide attempts, and more severe mania symptoms than CM− ones. Logistic regression indicated a significant association between lifetime suicide attempts and any type of childhood maltreatment and between emotional abuse and the presence of psychotic symptoms or mixed mood episodes. CM+ individuals with BD exhibited a significantly reduced CAR with respect to CM− ones.DiscussionOur results add to literature findings showing a worse clinical course in BD patients with a history of childhood maltreatments and show for the first time that childhood trauma exposure is associated to an impaired CAR in adults with BD.
Testing polymineral post‐IR IRSLand quartzSAR‐OSLprotocols on Middle to Late Pleistocene loess at Batajnica, Serbia
Authors: Avram Anca , Constantin Daniela , Veres Daniel , Kelemen Szabolcs , Obreht Igor , Hambach Ulrich , Marković Slobodan B. , Timar‐Gabor Alida 
Published: May 2020

The loess–palaeosol sequence of Batajnica (Vojvodina region, Serbia) is considered as one of the most complete and thickest terrestrial palaeoclimate archives for the Middle and Late Pleistocene. In order to achieve a numerical chronology for this profile, four sets of ages were obtained on 18 individual samples. Equivalent doses were determined using theSARprotocol on fine (4–11 μm) and coarse (63–90 μm) quartz fractions, as well as on polymineral fine grains by using two elevated temperature infrared stimulation methods,pIRIR290andpIRIR225. We show that the upper age limit of coarse quartzOSLand polymineralpIRIR290andpIRIR225techniques is restricted to the Last Glacial/Interglacial cycle due to the field saturation of the natural signals. Luminescence ages on coarse quartz,pIRIR225andpIRIR290polymineral fine grains are in general agreement. Fine quartz ages are systematically lower than the coarse quartz andpIRIRages, the degree of underestimation increasing with age. Comparison between natural and laboratory dose response curves indicate the age range over which each protocol provides reliable ages. For fine and coarse quartz, the natural and laboratory dose response curves overlap up to ~150 and ~250 Gy, respectively, suggesting that theSARprotocol provides reliable ages up toc. 50 ka on fine quartz andc. 100 ka on coarse quartz. Using thepIRIR225andpIRIR290protocols, equivalent doses up to ~400 Gy can be determined, beyond which in the case of the former the natural dose response curve slightly overestimates the laboratory dose response curve. Our results suggest that the choice of the mineral and luminescence technique to be used for dating loess sediments should take into consideration the reported limited reliability.
Endurance exercise in seniors: Tonic, toxin or neither?
Authors: Eze‐Nliam Chete , Schiller Nelson B. , Hayami Doug , Ghahghaie Farzin , Bibby Dwight , Fang Qizhi , Marcus Gregory M. , Åström Aneq Meriam 
Published: May 2020

AbstractIntroductionCardiac adaptation to sustained exercise in the athletes is established. However, exercise‐associated effect on the cardiac function of the elderly has to be elucidated. The aim of this study was to analyse left (LV) and right ventricular (RV) characteristics at different levels of chronic exercise in the senior heart.Materials and methodsWe studied 178 participants in the World Senior Games (mean age 68 ± 8 years, 86 were men; 48%). Three groups were defined based on the type and intensity of sports: low‐, moderate‐ and high‐intensity level. Exclusion criteria were coronary artery disease, atrial fibrillation, valvular heart disease or uncontrolled hypertension. LV and RV size and function were evaluated with an echocardiogram.ResultsLV trans‐mitral inflow deceleration time decreased in parallel to the intensity of chronic exercise: 242 ± 54 ms in low‐, 221 ± 52 ms in moderate‐ and 215 ± 58 ms in high‐intensity level, p = .03. Left atrial volume index (LAVI) was larger in high‐intensity group, p = .001. The LAVI remained significantly larger when adjusting for age, gender, heart rate, hypertension and diabetes (p = .002). LV and RV sizes were larger in the high‐intensity group. LV ejection fraction and RV systolic function evaluated by tissue Doppler velocity, atrioventricular plane displacement and strain did not differ between groups.ConclusionLeft ventricular diastolic filling is not only preserved, but may also be enhanced in long‐term, top‐level senior athletes. Moreover, LV and RV systolic function remain unchanged at different levels of exercise. This supports the beneficial effects of endurance exercise participation in senior hearts.
Public Health Insurance and Farm Labor Supply: Evidence from China's Rural Health Insurance Reform
Authors: Luo Tianyuan , Escalante Cesar L. 
Published: May 2020

AbstractThis study examines the impact of China's public health insurance program on the farm employment decisions of the rural population. Using a difference‐in‐differences (DID) model, this study indicates that the public health insurance reform led to reallocation of the rural labor force out of the farm sector by reducing the farm employment and increasing the likelihood of rural residents working in both the farm and nonfarm sectors. This research finds that rural female residents who are of a younger age and in better health were more likely to leave farm employment when covered by public health insurance. Suggestive evidence also finds that such public health insurance reform increased the individual income of the farm population.
Exchange Rate Volatility, Heterogeneous Firms and Market Concentration
Authors: Lu Bing , Wang Yaqi , Tan Xiaofen 
Published: May 2020

AbstractWith the gradual promotion of market‐oriented reform of the RMB exchange rate, the fluctuation range of the RMB exchange rate is increasing. How to deal with the impact of exchange rate volatility on Chinese exports is an important challenge faced by China. This paper finds that although exchange rate volatility, as a whole, has a negative impact on exports, high‐productivity exporters are less prone to exchange rate volatility shock in both intensive and extensive margins. As high‐productivity firms are less affected by exchange rate risk, they account for larger market shares. This paper, from a new perspective, provides evidence that increasing productivity helps mitigate the negative impact of exchange volatility on exports.
How the Internet Promotes China's Exports: A Firm‐level Perspective
Authors: Mu Yifei , Chen Zhen , Ding Yibing , Wang Yuqing , Pang Bo 
Published: May 2020

AbstractThe development of information and communications technology (ICT), particularly the Internet, has reduced trade costs. However, it remains unclear whether these reduced costs are reflected in the “extensive margins” of firms’ exports (which refer to the probability of firms exporting) or the “intensive margins” (which refer to the value of firms’ export). To test this, we used the concepts of information cost and binary margins, an augmented trade model of firm heterogeneity, a two‐stage Heckman estimation, and data from the World Bank Enterprise Survey of Chinese firms in 2012. The results revealed that reduced trade costs from the use of ICT were positively related to extensive margins but that the connection with intensive margins was not significant. The results lead to the conclusion that reduced information costs related to a firm's exporting behavior were primarily reflected in variable trade costs. This study offers theoretical and empirical evidence for China's policies towards the Internet, which are relevant for the export of manufactured goods. The government should encourage the use of ICT to enhance firms’ export opportunities while facing current trade policy uncertainty.
Impact of right ventricular systolic function after heart transplantation on exercise capacity
Authors: Verset Lucas , Lavie‐Badie Yoan , Guitard Joëlle , Delmas Clément , Biendel‐Piquet Caroline , Cazalbou Stéphanie , Cariou Eve , Cron Christophe , Carrié Didier , Galinier Michel , Lairez Olivier , Fournier Pauline 
Published: May 2020

AbstractBackgroundRight ventricular (RV) systolic parameters are difficult to assess in heart transplant recipients (HTRs) compared to healthy people because of discordant data, and their impact on exercise capacity remains undefined. We sought to retrospectively assess the impact of RV systolic function on exercise capacity after heart transplantation.MethodsWe analyzed data from 61 HTRs who underwent transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), and exercise capacity assessment by 6‐minute walking test (6MWT) and cardiopulmonary exercise testing (CPET) at 1‐ and 2‐year follow‐ups.ResultsTransthoracic echocardiography RV longitudinal systolic function including tricuspid annular plan systolic excursion (TAPSE), peak systolic S′ wave tricuspid annular velocity (PSVtdi) and RV free wall longitudinal strain was decreased at 1 year (respectively, 15 ± 3 mm, 10 ± 3 cm/s, and −19 ± 5%) and at 2 years (respectively, 15 ± 3 mm, 10 ± 2 cm/s, and −20 ± 5%) with no significant difference between both evaluations; meanwhile, RV ejection fraction (RVEF) measured by CMR was preserved. Mean percentage of predicted peak oxygen consumption was altered, but improved between the first and second year (55 ± 18 vs 60 ± 18%, P = .038). PSVtdi was weakly correlated with 6MWT distance (r = .426, P = .017) and RVEF with the predicted distance at 6MWT (r = .410, P = .027) at the 1‐year follow‐up.ConclusionsDespite decreasing values, RV longitudinal systolic function has a weak impact on exercise capacity of HTRs. PSVtdi and RVEF are the most pertinent parameters to assess the impact of RV systolic function on exercise capacity after heart transplantation. These results should lead to redefine normal RV systolic function thresholds for HTRs.
Erythropoietin treatment in chronic phase chronic myeloid leukemia patients treated with frontline imatinib who developed late anemia
Authors: Cesini Laura , Frieri Camilla , Baratè Claudia , Sorà Federica , Bonifacio Massimiliano , Cerrano Marco , Cagnetta Antonia , Elena Chiara , Aprile Lara , Sgherza Nicola , Trawinska Malgorzata , Gozzini Antonella , Capodanno Isabella , Crugnola Monica , Carmosino Ida , Scalzulli Emilia , Ricci Federica , Bocchia Monica , Bergamaschi Micaela , Aguzzi Chiara , Sica Simona , Galimberti Sara , Breccia Massimo , Luciano Luigiana , Latagliata Roberto 
Published: May 2020

AbstractBackgroundRole of erythropoietin (EPO) in the treatment of late anemia in patients with Chronic Myeloid Leukemia (CML) is still undefined.MethodsFifty CML patients treated at 14 institutions with frontline imatinib for at least 12 months and in stable complete cytogenetic response who developed a late chronic anemia treated with EPO were retrospectively evaluated.ResultsMedian time from imatinib start to EPO treatment was 42.2 months [interquartile range (IQR) 20.8‐91.9]. Median Hb value at EPO starting time was 9.9 g/dL (IQR 8.9‐10.3): Eleven patients (22.0%) were transfusion dependent. Alpha‐EPO (40 000 UI weekly) was employed in 37 patients, beta‐EPO (30 000 UI weekly) in 9 patients, zeta‐EPO (40 000 UI weekly) in 2 patients, and darbepoetin (150 mcg/weekly) in the remaining 2 patients. On the whole, 41 patients (82.0%) achieved an erythroid response, defined as a stable (>3 months) improvement >1.5 g/dL of Hb level, and 9 patients (18.0%) indeed resulted resistant. Among responding patients, 10 relapsed after a median time from EPO start of 20.7 months (IQR 10.8‐63.7). No EPO‐related toxicity was observed.ConclusionsResults of EPO treatment for late chronic anemia during long‐lasting imatinib therapy are encouraging, with a high rate of response.
Hippocampal and prefrontal contributions to memory retrieval: Examination of immediate early gene, NMDA receptor and environmental interactions
Authors: Farina Francesca R. , Commins Seán 
Published: May 2020

AbstractAnimals can use a range of strategies to recall important locations. These include simple stimulus–response strategies and more complex spatial (place) strategies, which are thought to have distinct neural substrates. The hippocampus—and NMDA receptor activation therein—is considered to be crucial for spatial, but not response strategies. The medial prefrontal cortex has also been implicated in memory retrieval; however, evidence concerning its specific role is equivocal. Both hippocampal and prefrontal regions have been associated with flexible behavioural responding (e.g. when task demands change). Here, we investigated the use of spatial and non‐spatial strategies in the Morris water maze and their associated brain areas in rats using immediate early gene (IEG) imaging of Zif268 and c‐Fos. Specifically, we charted the involvement of hippocampal and prefrontal subregions during retrieval of spatial and non‐spatial memories. Behavioural flexibility was also examined using intact and partial cue configurations during recall. Results indicated that regions of both the hippocampus (area CA3) and prefrontal cortex (anterior cingulate cortex) were preferentially engaged in spatial memory recall compared to response learning. In addition, both spatial and non‐spatial memories were dependent on NMDA receptor activation. MK801 impaired recall performance across all groups and reduced IEG activation across hippocampal and prefrontal regions. Finally, IEG results revealed divergent patterns of Zif268 and c‐Fos activity and support the suggestion that Zif268 plays a functional role in the recall of long‐term memories.
Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia–reperfusion injury via PI3K/AKT/GSK3β pathway
Authors: Wang Jing , Liu Jing , Xie Liang , Cai Xiaomin , Ma Xiaohua , Gong Jianbin 
Published: May 2020

AbstractThe aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia–reperfusion injury via PI3K/AKT/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK‐MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, apoptosis, ROS production, cytometry, activities of AKT, GSK3β, and p‐38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK‐MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased AKT and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β‐specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation‐induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia–reperfusion injury via the PI3K/AKT/ GSK3β pathway.
The co‐existence of cold activity and thermal stability in an Antarctic GH42 β‐galactosidase relies on its hexameric quaternary arrangement
Authors: Mangiagalli Marco , Lapi Michela , Maione Serena , Orlando Marco , Brocca Stefania , Pesce Alessandra , Barbiroli Alberto , Camilloni Carlo , Pucciarelli Sandra , Lotti Marina , Nardini Marco 
Published: May 2020

To survive in cold environments, psychrophilic organisms produce enzymes endowed with high specific activity at low temperature. The structure of these enzymes is usually flexible and mostly thermolabile. In this work, we investigate the structural basis of cold adaptation of a GH42 β‐galactosidase from the psychrophilic Marinomonas ef1. This enzyme couples cold activity with astonishing robustness for a psychrophilic protein, for it retains 23% of its highest activity at 5 °C and it is stable for several days at 37 °C and even 50 °C. Phylogenetic analyses indicate a close relationship with thermophilic β‐galactosidases, suggesting that the present‐day enzyme evolved from a thermostable scaffold modeled by environmental selective pressure. The crystallographic structure reveals the overall similarity with GH42 enzymes, along with a hexameric arrangement (dimer of trimers) not found in psychrophilic, mesophilic, and thermophilic homologues. In the quaternary structure, protomers form a large central cavity, whose accessibility to the substrate is promoted by the dynamic behavior of surface loops, even at low temperature. A peculiar cooperative behavior of the enzyme is likely related to the increase of the internal cavity permeability triggered by heating. Overall, our results highlight a novel strategy of enzyme cold adaptation, based on the oligomerization state of the enzyme, which effectively challenges the paradigm of cold activity coupled with intrinsic thermolability.DatabaseStructural data are available in the Protein Data Bank database under the accession number 6Y2K.