bluuebunny/crossref_metadata_2025_split huggingface dataset:
PK‐guided personalized prophylaxis with Nuwiq® (human‐cl rhFVIII) in adults with severe haemophilia A
Authors: Lissitchkov T. , Rusen L. , Georgiev P. , Windyga J. , Klamroth R. , Gercheva L. , Nemes L. , Tiede A. , Bichler J. , Knaub S. , Belyanskaya L. , Walter O. , Pasi K. J. 
Published: April 2017

IntroductionNuwiq® (human‐cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell‐line.Aims/MethodsThis study (NuPreviq) was a prospective, open‐label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72‐h pharmacokinetic (PK) phase; (ii) a 1–3 month standard prophylaxis phase; and (iii) a 6‐month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two‐ or one‐compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied.ResultsThe median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed‐free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment‐related serious or severe adverse events.ConclusionPK‐guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.
Effects of glutinous and nonglutinous sorghums on Saccharomyces cerevisiae fermentation for Chinese liquor making
Authors: Wu Qun , Cao Shuai , Xu Yan 
Published: April 2017

SummaryThis work investigated the effect of sorghum, including Chinese glutinous (S1 and S2) and nonglutinous (S3 and S4), Canadian nonglutinous cultivars (S5 and S6), on fermentation of Saccharomyces cerevisiae MT and FJ, the representative strains for Chinese liquor fermentation with glutinous and nonglutinous sorghums as materials, respectively. S. cerevisiae MT and FJ exhibited a longer stationary phase in glutinous and nonglutinous cultivars, respectively. Fat and tannin contents in sorghums were, respectively, negatively related with ethanol and esters production by both MT and FJ. FJ produced the most amount of flavour compounds in nonglutinous cultivars, while MT showed no preference on sorghum cultivars, as it produced most flavour compounds in both S1 and S3. Moreover, sorghums showed different characteristics on flavour production. The nonglutinous cultivars S3 and S4 were correlated with most of the acids, aromatic compounds and terpenoids, while S5 and S6 were correlated with most of the esters.
Corrosion of ISG fibers in alkaline solutions
Authors: Trivelpiece Cory L. , Rice Jarrett A. , Clark Nicholas L. , Kabius Bernd , Jantzen Carol M. , Pantano Carlo G. 
Published: April 2017

AbstractThe corrosion behavior of glass fibers synthesized from the International Simple Glass (ISG) reference ingot, an international High‐Level Waste (HLW) borosilicate glass standard, is reported. Bundles of glass fibers were submerged in 120 mL of four different solutions of initial pH values (pHi) of 9.5, 10.5, 11.5, and 12.5 for static corrosion testing. While all the experiments reached a residual corrosion rate after ~50 days, which remained approximately constant for the duration of the pHi 9.5‐11.5 experiments, the pHi 12.5 experiment underwent a Stage II→III dissolution transition after 57 days. This transition was preceded by a decrease in the Al concentration in solution followed by an increase in B and Si concentration in the leachate. Zeolite NaP2 was observed to form on these fibers via scanning electron microscopy and X‐ray diffraction—the crystallinity of the fibers was estimated to be ~40%‐45% (relative to amorphous component) after the Stage II→III transition. Transmission electron microscopy cross‐sectional imaging of sampled fibers revealed several porous layers on the pHi 9.5‐11.5 samples, and a more aggressive alteration mechanism in the pHi 12.5 fibers. Potential markers that indicate a transition from Stage II→Stage III corrosion are shown to occur based on experimental observations.
Genetic and morphometric data demonstrate alternative consequences of secondary contact inClitarchusstick insects
Authors: Myers Shelley S. , Holwell Gregory I. , Buckley Thomas R. 
Published: April 2017

AbstractAimComparisons of independent secondary contact events provide insights into allopatric speciation. The geographic distribution ofClitarchusstick insects across northern New Zealand corresponds to islands that existed in the Pliocene. Subsequent joining to the mainland provided multiple opportunities for secondary contact. We address the hypothesis that secondary contact has similar effects on parental species, across two peninsulas, due to the simultaneous removal of allopatric barriers.LocationNorthland, New ZealandMethodsWe explore how genetic structure relates to morphological variation and biogeographical history ofClitarchus hookeriandC. tepaki. MitochondrialDNAsequences were used to reconstruct phylogenetical relationships. Population structure was estimated using 14 microsatellite markers. We analysed genital morphology and genetic structure within a biogeographical context to identify the consequences of independent secondary contact events.ResultsGeographical patterns of genital shape indicate two independent hybrid swarms occur betweenC. hookeriandC. tepaki. Haplotype distributions and Bayesian cluster analyses revealC. tepakifrom the Aupouri Peninsula are distinguished fromC. hookerion the basis of both genetic structure and morphology.Clitarchus tepakion the Karikari Peninsula did not group phylogenetically or through Bayesian clustering withC. tepakifrom the Aupouri Peninsula. We observed a hybrid swarm along the Aupouri Peninsula.Main conclusionsClitarchusspecies were separated on Pliocene islands and then subsequently made independent secondary contact as land connections formed.Clitarchus tepakion the Aupouri Peninsula maintained genetic integrity; whereas we hypothesize genetic swamping has occurred on Karikari Peninsula. Our data demonstrate different outcomes of independent secondary contact events.
Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies
Authors: Zhou Jing‐dong , Zhang Ting‐juan , Li Xi‐xi , Ma Ji‐chun , Guo Hong , Wen Xiang‐mei , Zhang Wei , Yang Lei , Yan Yang , Lin Jiang , Qian Jun 
Published: April 2017

AbstractPromoter hypermethylation‐mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia‐free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML). Moreover, ID4 methylation was significantly decreased in the follow‐up paired AML patients who achieved complete remission (CR) after induction therapy. Importantly, ID4 methylation was increased during MDS progression to AML and chronic phase (CP) progression to blast crisis (BC) in chronic myeloid leukaemia (CML). Epigenetic studies showed that ID4 methylation might be one of the mechanisms silencing ID4 expression in myeloid leukaemia. Functional studies in vitro showed that restoration of ID4 expression could inhibit cell proliferation and promote apoptosis in both K562 and HL60 cells. These findings indicate that ID4 acts as a tumour suppressor in myeloid malignancies, and ID4 methylation is a potential biomarker in predicting disease progression and treatment outcome.
Oral infection with Porphyromonas gingivalis induces peri‐implantitis in a murine model: Evaluation of bone loss and the local inflammatory response
Authors: Tzach‐Nahman Rinat , Mizraji Gabriel , Shapira Lior , Nussbaum Gabriel , Wilensky Asaf 
Published: April 2017

AbstractAimPeri‐implantitis is a major health concern, with unclear pathogenesis, and with no accessible animal models. Our aim was to establish a mouse model for peri‐implantitis and to investigate mediators of inflammation.Materials and MethodsMice were divided into implanted versus non‐implanted groups. Implants were inserted immediately following the extraction of the upper first molar. Four weeks following implantation, implanted and non‐implanted mice were challenged with either Porphyromonas gingivalis or vehicle (eight mice in each subgroup, 32 mice in total). Alveolar bone loss and expression of inflammatory mediators in the soft tissue were assessed 42 days following infection.ResultsPorphyromonas gingivalis infection induced greater bone loss around implants than around teeth. In non‐infected animals, the presence of the implant correlated with elevated expression of Il‐10, Foxp3 and Rankl/Opg ratio, while Tnf‐α levels were decreased relative to tissue around teeth. Six weeks following infection, Tnf‐α increased significantly while the expression of Foxp3 decreased in the tissue around the implants. No significant differences in anti‐ or pro‐inflammatory mediators were found around teeth of infected, relative to non‐infected mice.ConclusionsOral infection with P. gingivalis of mice with implants induced bone loss and a shift in gingival cytokine expression. This mouse model enables exploration of the pathogenesis of peri‐implantitis and testing of novel treatments.
Non‐surgical treatment of peri‐implant mucositis and peri‐implantitis at two‐piece zirconium implants: A clinical follow‐up observation after up to 3 years
Authors: John Gordon , Becker Jürgen , Schmucker Andrea , Schwarz Frank 
Published: April 2017

AbstractObjectivesTo assess the long‐term clinical outcomes following non‐surgical therapy of peri‐implant diseases at two‐piece zirconium implants.Material and MethodsA total of 27 patients suffering from either (i) peri‐implant mucositis (n = 24 implants), or (ii) peri‐implantitis (n = 16 implants) completed a mean follow‐up period of 32.8 ± 2.85 months (median: 34 months). The initial treatment procedures included (i) mechanical debridement + local antiseptic therapy using chlorhexidine digluconate (MD + CXH), or (ii) Er:YAG laser monotherapy (ERL). The primary outcome was disease resolution (i.e. absence of bleeding on probing (BOP) at mucositis sites/absence of BOP and probing pocket depths (PD) ≥6 mm at peri‐implantitis sites).ResultsResolution of peri‐implant mucositis and peri‐implantitis was obtained in 7/14 (50.0%; p = .003) and 5/13 (38.5%; p = .001) of the patients investigated. This corresponded to 54.2% (13/24) and 50.0% (8/16) at the implant level respectively.ConclusionBoth MD + CHX and ERL were effective on the long‐term, but failed to achieve a complete disease resolution.
Saliva and plasma levels of cardiac‐related biomarkers in post‐myocardial infarction patients
Authors: Rathnayake Nilminie , Buhlin Kåre , Kjellström Barbro , Klinge Bjorn , Löwbeer Christian , Norhammar Anna , Rydén Lars , Sorsa Timo , Tervahartiala Taina , Gustafsson Anders ,   the PAROKRANK Steering Committee
Published: April 2017

AbstractAimTo relate cardiac biomarkers, such as cystatin C and growth differentiation factor‐15 (GDF‐15) in saliva to myocardial infarction (MI) and to periodontal status, and to investigate the relation between salivary and plasma cardiac biomarkers.Materials and MethodsTwo hundred patients with MI admitted to coronary care units and 200 matched controls without MI were included. Dental examination and collection of blood and saliva samples was performed 6–10 weeks after the MI for patients and in close proximity thereafter for controls. Analysing methods: ARCHITECT i4000SR, Immulite 2000 XPi or ELISA.ResultsThe mean age was 62 ± 8 years and 84% were male. Total probing pocket depth, fibrinogen, white blood cell counts and HbA1c were higher in patients than controls. GDF‐15 levels correlated with most of the included clinical variables in both study groups. No correlation was found between plasma and saliva levels of cystatin C or GDF‐15.ConclusionSalivary cystatin C and GDF‐15 could not differentiate between MI patients and controls.
Frequency‐dependent selection acting on the widely fluctuating sex ratio of the aphid Prociphilus oriens
Authors: Li Y. , Akimoto S. 
Published: April 2017

AbstractFrequency‐dependent selection is a fundamental principle of adaptive sex ratio evolution in all sex ratio theories but has rarely been detected in the wild. Through long‐term censuses, we confirmed large fluctuations in the population sex ratio of the aphid Prociphilus oriens and detected frequency‐dependent selection acting on these fluctuations. Fluctuations in the population sex ratio were partly attributable to climatic factors during the growing season. Climatic factors likely affected the growth conditions of host plants, which in turn led to yearly fluctuations in maternal conditions and sex ratios. In the process of frequency‐dependent selection, female proportion higher or lower than ca. 60% was associated with a reduction or increase in female proportion, respectively, the next year. The rearing of aphid clones in the laboratory indicated that mothers of each clone produced an increasing number of females as maternal size increased. However, the mean male number was not related to maternal size, but varied largely among clones. Given genetic variance in the ability to produce males among clones, selection should favour clones that can produce more numerous males in years with a high female proportion. Population‐level sex allocation to females was on average 71%–73% for three localities and more female‐biased when maternal conditions were better. This tendency was accounted for by the hypothesis of competition among foundresses rather than the hypothesis of local mate competition. We conclude that despite consistent operation of frequency‐dependent selection, the sex ratio continues to fluctuate because environmental conditions always push it away from equilibrium.
Anthropogenic spreading ofanguillid herpesvirus 1by stocking of infected farmed European eels,Anguilla anguilla(L.), in the Schlei fjord in northern Germany
Authors: Kullmann B , Adamek M , Steinhagen D , Thiel R 
Published: April 2017

AbstractThe Schlei fjord in northern Germany is the recipient water of a comprehensive eel,Anguilla anguilla(L.), stocking programme. Since 2015, stocked eels become alizarin red S marked, but to date no control mechanism is implemented in this stock enhancement measure to prevent anthropogenic spreading of diseases. Consequentially, it was possible that farmed stocking cohorts of 2015 and 2016 (in total ca. 1040 kg) were subsequently tested positive foranguillid herpesvirus 1(AngHV1). For this study, 100 eels [total length (TL) 24.3–72.9 cm, age ca. 1–6 years] were caught in 2016 and investigated with regard to AngHV1 infection, parasite load (Anguillicoloides crassus) and body conditions. 68% of the eels were found to be virus positive while larger specimens were more often infected. In addition, a fitted generalized linear model (area under the curve = 0.741) demonstrated that an increase in individual TL is accompanied with an increased risk of clinically relevant virus loads.Anguillicoloides crassusturned out to be an important stressor for eels, because parasite and virus load revealed a significant positive correlation. The results of this study evidently show the urgent need of a disease containment strategy for eel stocking programmes.
Stepwise application of fibrosis index based on four factors, red cell distribution width–platelet ratio, and aspartate aminotransferase–platelet ratio for compensated hepatitis B fibrosis detection
Authors: Chen Yong‐Peng , Hu Xiao‐Min , Liang Xie‐Er , Huang Li‐Wen , Zhu You‐Fu , Hou Jin‐Lin 
Published: April 2017

AbstractBackground and AimFibrosis index based on four factors (FIB‐4) and aspartate aminotransferase–platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width–platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB‐4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis.MethodsA total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut‐offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB‐4, and APRI were statistically analyzed.ResultsThe Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB‐4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume–platelet ratio, respectively. The proportion of patient determined as cirrhosis or non‐cirrhosis was 65.9% by transient elastography, 36.9% by FIB‐4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB‐4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively.ConclusionsIn source‐limited settings without transient elastography, stepwise applying FIB‐4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.
Impact of gluten consumption in patients with functional dyspepsia: A case–control study
Authors: Du Lijun , Shen Jinhua , Kim John J , He Huiqin , Chen Binrui , Dai Ning 
Published: April 2017

AbstractBackground and AimDietary factors and immune dysfunction may induce symptoms in patients with functional dyspepsia (FD). The aim of the study was to evaluate whether gluten consumption impacts symptom onset in patients with FD and to evaluate for possible histologic alterations in the duodenum of patients with FD.MethodsWe prospectively enrolled 101 patients newly diagnosed with FD and 31 asymptomatic controls. Specific FD symptoms and gluten consumption patterns were evaluated by self‐reported questionnaires. Tight junction protein (claudin‐1) expression and presence of intraepithelial lymphocyte (IEL) infiltration in the bulb (D1) and second portion (D2) of the duodenum were assessed by immunohistochemistry.ResultsWheat bun consumption had higher frequency (P = 0.047) and increased average consumption (P = 0.01) scores in patients with FD compared with the control group. Of the 101 patients with FD, early satiety (P = 0.03) was associated with increased wheat bun consumption frequency score. On histologic evaluation, claudin‐1 expression was decreased in D1 (0.003 ± 0.001 vs 0.012 ± 0.002, P = 0.003) and D2 (0.002 ± 0.0004 vs 0.012 ± 0.001, P < 0.001), while duodenal IEL counts were increased in D1 (15.5 ± 7.8 vs 3.1 ± 2.5, P < 0.001) and D2 (20.6 ± 7.7 vs 5.8 ± 3.4, P < 0.001) among patients with FD compared with the control group. Finally, Helicobacter pylori infection was associated with increased IELs in D1 (20.6 ± 7.0 vs 14.2 ± 7.4, P = 0.001) among patients with FD.ConclusionsAmong patients with FD, gluten‐rich food may lead to symptom onset, specifically early satiety. Intestinal epithelial barrier dysfunction characterized by decreased claudin‐1 expression and mucosal immune activation demonstrated by IEL infiltration may contribute to the pathogenesis of FD.
Integrating Backcasting and Eco‐Design for the Circular Economy: The BECE Framework
Authors: Mendoza Joan Manuel F. , Sharmina Maria , Gallego‐Schmid Alejandro , Heyes Graeme , Azapagic Adisa 
Published: April 2017

SummaryThe circular economy (CE) is essential for decoupling economic growth from resource consumption and environmental impacts. However, effective implementation requires a systemic change across supply chains, involving both technological and nontechnological innovations. Frameworks are beginning to emerge to foster CE thinking in organizations. However, literature review carried out as part of this research has revealed gaps in their ability to fulfil CE requirements. Furthermore, few frameworks provide support on how CE requirements may be implemented. To address these issues, this article presents a new framework, BECE (backcasting and eco‐design for the circular economy), to ensure that businesses can implement CE requirements more readily. BECE empowers organizations to tackle the CE holistically by embedding the concept into corporate decision making and by bringing operational and systems thinking together, thus increasing the likelihood of successful implementation. The potential of the BECE framework was tested through a pilot workshop focusing on the development of a CE business model through redesign of products and supply chains. Using vacuum cleaners as an illustrative case study, several product design and supply‐chain alternatives were identified, including the development of scenarios and action plans for their implementation at the business level. Although the case study focuses on a particular product, the BECE framework is generic and applicable across different products and business sectors.
Coming Full Circle: Why Social and Institutional Dimensions Matter for the Circular Economy
Authors: Moreau Vincent , Sahakian Marlyne , van Griethuysen Pascal , Vuille François 
Published: April 2017

SummaryIn light of the environmental consequences of linear production and consumption processes, the circular economy (CE) is gaining momentum as a concept and practice, promoting closed material cycles by focusing on multiple strategies from material recycling to product reuse, as well as rethinking production and consumption chains toward increased resource efficiency. Yet, by considering mainly cost‐effective opportunities within the realm of economic competitiveness, it stops short of grappling with the institutional and social predispositions necessary for societal transitions to a CE. The distinction of noncompetitive and not‐for‐profit activities remains to be addressed, along with other societal questions relating to labor conditions, wealth distribution, and governance systems. In this article, we recall some underlying biophysical aspects to explain the limits to current CE approaches. We examine the CE from a biophysical and social perspective to show that the concept lacks the social and institutional dimensions to address the current material and energy throughput in the economy. We show that reconsidering labor is essential to tackling the large share of dissipated material and energy flows that cannot be recovered economically. Institutional conditions have an essential role to play in setting the rules that differentiate profitable from nonprofitable activities. In this context, the social and solidarity economy, with its focus on equity with respect to labor and governance, provides an instructive and practical example that defies the constraints related to current institutional conditions and economic efficiency. We show how insights from the principles of the social and solidarity economy can contribute to the development of a CE by further defining who bears the costs of economic activities.