bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating antibody‐dependent cellular cytotoxicity of epidermal growth factor receptor‐specific heavy‐chain antibodies through hinge engineering
Authors: D'Eall Calvin , Pon Robert A , Rossotti Martin A , Krahn Natalie , Spearman Maureen , Callaghan Deborah , van Faassen Henk , Hussack Greg , Stetefeld Jörg , Butler Michael , Durocher Yves , Zhang Jianbing , Henry Kevin A , Tanha Jamshid 
Published: January 2019

AbstractHuman IgG1 and IgG3 antibodies (Abs) can mediate Ab‐dependent cellular cytotoxicity (ADCC), and engineering of the Ab Fc (point mutation; defucosylation) has been shown to affect ADCC by modulating affinity for FcRγIIIa. In the absence of a CH1 domain, many camelid heavy‐chain Abs (HCAbs) naturally bear very long and flexible hinge regions connecting their VHH and CH2 domains. To better understand the influence of hinge length and structure on HCAb ADCC, we produced a series of hinge‐engineered epidermal growth factor receptor (EGFR)‐specific chimeric camelid VHH‐human Fc Abs and characterized their affinities for recombinant EGFR and FcRγIIIa, their binding to EGFR‐positive tumor cells, and their ability to elicit ADCC. In the case of one chimeric HCAb (EG2‐hFc), we found that variants bearing longer hinges (IgG3 or camelid hinge regions) showed dramatically improved ADCC in comparison with a variant bearing the human IgG1 hinge, in similar fashion to a variant with reduced CH2 fucosylation. Conversely, an EG2‐hFc variant bearing a truncated human IgG1 upper hinge region failed to elicit ADCC. However, there was no consistent association between hinge length and ADCC for four similarly engineered chimeric HCAbs directed against distinct EGFR epitopes. These findings demonstrate that the ADCC of some HCAbs can be modulated simply by varying the length of the Ab hinge. Although this effect appears to be heavily epitope‐dependent, this strategy may be useful to consider during the design of VHH‐based therapeutic Abs for cancer.
Recognising and managing dying patients in the acute hospital setting: can we do better?
Authors: Gunasekaran Bharathy , Scott Caroline , Ducharlet Kathryn , Marco David , Mitchell Imogen , Weil Jennifer 
Published: January 2019

AbstractHealthcare professionals have limited formal end‐of‐life care training despite the large proportion of hospital deaths. A retrospective review of 201 acute hospital deaths revealed 166 (82.6%) had documentation to suggest the patient was dying but this was performed late with a median time between documentation and death of 0.84 days. Furthermore, 132 (66%) patients received an intervention in the final 48 h of life. This highlights the need to improve the recognition and management of dying patients in acute hospitals.
Management of frail older people with acute illness
Authors: Mudge Alison M. , Hubbard Ruth E. 
Published: January 2019

AbstractFrailty status is intrinsically related to every aspect of older patients’ hospital journeys: the way in which they present to hospital, their health status at admission, vulnerability to complications in hospital and rate of recovery after an acute insult. In younger people, hospitalisation is usually the result of a serious illness or injury, such as sepsis or major trauma. Management can be underpinned by evidence‐based algorithms relating to the precipitating insult and recovery usually follows a predictable trajectory. In older people who are frail, on the other hand, admission to hospital may be triggered by an illness that may seem minor, such as a viral infection, which causes a geriatric syndrome. A fall or delirium with no major precipitant should be considered an indicator of frailty. Promptly recognising the acute illness and the increased risk for hospital‐associated complications is essential for providing safe systems of care for frail older people. Early consideration of health assets and engagement of families and community services can have an important role in successful recovery during and beyond the hospital stay. Effective decision‐making about clinical interventions can benefit from explicit assessment of frailty status and consideration of patient priorities.
The impact of international migration on the public pension system: The case of Portugal
Authors: Alves José , Craveiro Daniela , Garcia Maria Teresa Medeiros , Albuquerque Paula 
Published: January 2019

AbstractThis article analyses the impact of replacement migration on the financial sustainability of the old‐age pension system in Portugal, a country with one of the largest ageing populations in Europe. We do this using demographic forecasts and prospective exercises for the evolution of the Portuguese economy. During the 2015–2060 period, our results evidence the positive impacts of international migration on old‐age pension system financial balances, reaching over 3 per cent of GDP after 2045. Moreover, even when taking into considering the low dynamics for the Portuguese economy, replacement migration is an important input to improve pension system financial sustainability.
Synthesis of highly pure and dense 0.9(KNbO3)‐0.1(BaNi1/2Nb1/2O3‐δ) ceramic with superior magnetic properties
Authors: Tiwari Rajender Prasad , Hashmi Syed Zimad Husain , Sharma Raghav , Khan Saif Ahmad , Birajdar Balaji 
Published: January 2019

AbstractResidual NiO phase is generally detected in 0.9(KNbO3)–0.1(BaNi1/2Nb1/2O3‐δ) (KBNNO) synthesized using NiO as a nickel precursor by solid‐state reaction. In this work, NiO phase is found to exist in the form of the residual NiO particles with a size of 100‐200 nm using energy dispersive X‐ray elemental mapping. These NiO residual particles are eliminated by using nickel acetate as a nickel precursor and a 100% perovskite phase KBNNO is successfully synthesized at as low as 600°C temperature. Furthermore, using the two‐step sintering technique, 100% relative density is achieved in this material. The nickel acetate–based KBNNO shows a robust ferromagnetism with the saturation magnetization of 11.42 memu/g and the remanent magnetization of 3.89 memu/g which is 38 times higher than that of previously reported value in NiO‐based KBNNO. Thus, a highly pure and fully dense KBNNO ceramic with superior magnetic properties is obtained using nickel acetate and by the two‐step sintering method. This is a key step forward in the processing of KBNNO and is likely to have a significant impact on other physical properties of this newly invented and promising photovoltaic perovskite material.
Training young adults with intellectual disability to read critically on the internet
Authors: Delgado Pablo , Ávila Vicenta , Fajardo Inmaculada , Salmerón Ladislao 
Published: January 2019

AbstractBackgroundYoung people with intellectual disability (ID) are becoming frequent Internet users, but they present difficulties selecting reliable Internet sources.MethodsThe present authors tested an instructional programme aimed at increasing skills to evaluate information from the Internet of 33 young adult students with intellectual disability enrolled in special needs education (19.4 years). The programme was composed of different web pages that provided conflicting views on a controversial topic. Students participated in small group discussions supported with Wh‐question graphic organizers and contrasting cases during seven sessions.ResultsDifferences between pre‐ and post‐tests indicated that the programme is effective in increasing students’ ability to select trustworthy web pages, and to use source characteristics to justify such selection by means of supervised instruction.ConclusionPromoting Internet use in a safe way might increase the opportunities of young people with intellectual disability to make choices and self‐determined decisions about their life (Handbook of research‐based practices for educating students with intellectual disability, 2016, New York, NY: Taylor & Francis).
Electrophysiological characteristics of the earliest activation site in idiopathic right ventricular outflow tract arrhythmias under mini‐electrode mapping
Authors: Liu Menghui , Jiang Jingzhou , Su Chen , Li Jie , Chen Xumiao , Ma Yuedong , Feng Chong , Liu Jun , Dong Yugang , Tang Anli , He Jiangui , Wang Lichun 
Published: January 2019

AbstractIntroductionRight ventricular outflow tract ventricular arrhythmias (RVOT VAs) often originate in the voltage‐transitional zone. The target electrogram could be compromised by the architecture of the roving catheter. Mini‐electrodes could improve the mapping resolution, especially in low‐voltage areas. The aim was to assess the electrophysiological characteristics of the earliest activation site (EAS) of RVOT VAs during mapping using mini‐electrodes.Methods and ResultsTwenty‐seven patients with RVOT‐type VAs were mapped using Orion mini‐electrodes and the Rhythmia mapping system. Bipolar and unipolar electrograms were analyzed and compared with conventional ablation catheter recordings. Twenty‐five patients (25 of 27) were successfully mapped and ablated at the RVOT. At the EAS, all 25 (100%) patients exhibited local sharp potentials (spiky potential) at the VAs, and 88% (22 of 25) individuals showed reverse late potentials in adjacent sinus beats on the bipolar mini‐electrode recordings. Related unipolar electrograms manifested 20% “q‐plateau‐QS,” 76% “gross QS,” and 4% “late QS” patterns related to spiky potential voltages and advanced times. Compared with electrograms recorded by ablation catheter, bipolar mini‐electrode recordings exhibited significantly shorter spiky potential durations (P = 0.001) and a significantly increased incidence of the reverse late potentials (P = 0.041). Unipolar mini‐electrode recordings had a lower incidence ratio of “late QS” patterns (P = 0.039).ConclusionCompared with ablation catheter mapping, mini‐electrodes improved the mapping resolution of the EAS of RVOT VAs and exhibited shorter spiky potential durations and reduced incidence of “later QS” unipolar patterns.
Deficiency of TPPP2, a factor linked to oligoasthenozoospermia, causes subfertility in male mice
Authors: Zhu Feng , Yan Peipei , Zhang Jingjing , Cui Yiqiang , Zheng Meimei , Cheng Yiwei , Guo Yueshuai , Yang Xiaoyu , Guo Xuejiang , Zhu Hui 
Published: January 2019

AbstractOligoasthenozoospermia is a major cause of male infertility; however, its etiology and pathogenesis are unclear and may be associated with specific gene abnormalities. This study focused on Tppp2 (tubulin polymerization promoting protein family member 2), whose encoded protein localizes in elongating spermatids at stages IV‐VIII of the seminiferous epithelial cycle in testis and in mature sperm in the epididymis. In human and mouse sperm, in vitro inhibition of TPPP2 caused significantly decreased motility and ATP content. Studies on Tppp2 knockout (KO) mice demonstrated that deletion of TPPP2 resulted in male subfertility with a significantly decreased sperm count and motility. In Tppp2−/− mice, increased irregular mitochondria lacking lamellar cristae, abnormal expression of electron transfer chain molecules, lower ATP levels, decreased mitochondrial membrane potential and increased apoptotic index were observed in sperm, which could be the potential causes for its oligoasthenozoospermia phenotype. Moreover, we identified a potential TPPP2‐interactive protein, eEf1b (eukaryotic translation elongation factor 1 beta), which plays an important role in protein translation extension. Thus, TPPP2 is probably a potential pathogenic factor in oligoasthenozoospermia. Deficiency of TPPP2 might affect the translation of specific proteins, altering the structure and function of sperm mitochondria, and resulting in decreased sperm count, motility and fertility.
Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA‐C associated antigenic epitope in vitro
Authors: Niepiekło‐Miniewska W. , Mpakali A. , Stratikos E. , Matusiak Ł. , Narbutt J. , Lesiak A. , Kuna P. , Wilczyńska K. , Nowak I. , Wiśniewski A. , Zwolińska K. , Ponińska J. , Płoski R. , Szepietowski J.C. , Kuśnierczyk P. 
Published: January 2019

AbstractBackgroundAtopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA‐C molecules. Here, we found an association of HLA‐C*05:01 allele with AD. KIR‐HLA‐C interactions are affected by peptides presented by HLA‐C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes.ObjectivePossible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD.MethodsPeripheral blood DNA isolation from 318 patients and 549 controls. PCR‐SSO or PCR‐SSP for HLA‐C typing; TaqMan Genotyping Assay for ERAP typing.ResultsOnly one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N‐terminally extended precursor LIVDRPVTLV of the HLA‐C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1‐negative individuals, not protected by this KIR.ConclusionAssociations of HLA‐C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA‐C*05:01 molecule was found.
Understanding FEV1 for the purpose of cystic fibrosis registry comparisons: Does bias in annual review FEV1 affect between‐centre comparison within the UK? An analysis of registry data
Authors: Hoo Zhe Hui , Campbell Michael J. , Walters Stephen J. , Wildman Martin J. 
Published: January 2019

AbstractRationale, aims, and objectiveWe previously demonstrated that annual review %FEV1 underestimates lung health of adults with CF compared with %FEV1 captured during periods of clinical stability. This has implications in the comparisons against registries with encounter‐based FEV1, such as the United States. It is uncertain whether this bias affects between‐centre comparison within the United Kingdom. Previous funnel plot analyses have identified variation in annual review %FEV1 according to centre size; hence, we investigated whether paired differences between annual review and best %FEV1 also vary according to centre size.MethodsThis registry analysis included 18 adult CF centres in the United Kingdom with ≥80% completeness for best FEV1 data in 2014. Mean discrepancy between annual review and best %FEV1 is a surrogate for the extent by which annual review %FEV1 underestimates lung health, and was plotted against centre size. A local polynomial regression (LOESS) curve was used to explore the relationship between the two variables. An appropriate model is fitted based on the LOESS curve to determine the strength of relationship between discrepancies in %FEV1 and centre size.ResultsThere is an inverted U‐shaped relationship between mean discrepancies in %FEV1 and centre size. A regression of the paired mean difference in %FEV1 against centre size showed a significant improvement in the goodness of fit for a quadratic model (R2 = 23.8% for a quadratic model compared with 0.4% for a linear one; P = 0.048 for the quadratic term).ConclusionsAnnual review %FEV1 underestimated lung health of adults from small and large centres in the United Kingdom to a greater extent compared with medium‐sized centres. A plot of %FEV1 against centre size (eg, funnel plot comparison) would be affected by systematic bias in annual review %FEV1. Therefore, annual review %FEV1 is an unreliable metric to compare health outcomes of adult CF centres within the United Kingdom.
Subcutaneous thermal sensor microchip validation in vervet monkeys (Chlorocebus pygerythrus) during normothermic and hypothermic situations
Authors: Navarro‐Serra Ana , Sanz‐Cabañes Héctor 
Published: January 2019

AbstractBackgroundInternal temperature data are essential for clinical evaluation in veterinary medicine. During the last decade, new thermometry devices have been developed. Identification microchips with a temperature sensor offer double utility to clinicians by satisfying animal identification regulations and providing a non‐invasive method for temperature measurement.MethodsDuring this study, 26 healthy vervet monkeys (Chlorocebus pygerythrus) were implanted with a subcutaneous temperature transponding microchip. For each monkey, internal temperature measurements from the microchip and from an anaesthetic monitor (rectal sensor) were recorded every 5 minutes during an anaesthetic procedure.ResultsIn this study, there were 83 paired samples obtained under normothermic conditions and another 72 paired samples obtained under hypothermic conditions, with interclass correlation coefficients of 0.79 and 0.69, respectively, between the two temperature measurement approaches.ConclusionMeasurements obtained using the examined microchip thermal sensor exhibited good and excellent correlation with rectal temperature measurements under hypothermic and normothermic conditions, respectively.
How Collective Engagement Creates Competitive Advantage for Organizations: A Business‐Level Model of Shared Vision, Competitive Intensity, and Service Performance
Authors: Eldor Liat 
Published: January 2019

AbstractWe argue that collective engagement can serve as a unique value‐creation capacity at the business level by linking shared vision and service performance. We also propose that competitive intensity will be a market indicator by which management can enhance the effect of shared vision on collective engagement, and indirectly strengthen service performance (through collective engagement). Furthermore, we argue that this distinctive value‐creation capability, embedded in collective engagement, generates competitive advantage; specifically, one that competing organizations will struggle to replicate. We examine our moderated‐mediation model by using a three‐time‐point method derived from five different sources in 198 retail‐service branches. Our findings indicate that collective engagement, fueled by shared organizational vision, improves service performance. Furthermore, as this conditional indirect effect of shared vision on service quality and customer satisfaction was solely generated through collective engagement rather than other mechanisms (i.e., commitment and involvement), it creates a competitive advantage for engagement‐oriented organizations.
Molecular diversity of the 5S nuclear ribosomal DNA inCampeiostachyswithStHYhaplome constitution
Authors: Yang Cai‐Rong , Baum Bernard R. , Johnson Douglas A. , Zhang Hai‐Qin , Zhou Yong‐Hong 
Published: January 2019

AbstractTo detect the genomic constitutions and investigate the evolutionary relationships betweenCampeiostachysDrobov andElymusL. species, we have cloned and analyzed 271 5S nuclear ribosomal DNA sequences from 27 accessions of these species, mostly of Chinese origin. We identified LongH1, ShortS1, and LongY1 unit classes in nineCampeiostachysorElymusspecies. The identification of the three orthologous unit classes was confirmed by the neighbor‐joining tree of each unit class from PAUP and the phylogeny tree of three unit classes from MrBayes. The results suggested that theseElymusspecies compriseStYHhaplomes and should be included inCampeiostachys. The phylogeny tree showed a clear separation between theS1 unit class andY1 unit class. However,Y1 unit class sequences formed a sister clade to theS1 unit class, implying that although theStandYhaplomes might have some affinity, they are distinct from one another. The phylogeny tree also indicated that the five species in sect.Turczaninovia(C. dahuricavar.cylindrica,C. dahuricavar.dahurica,C. dahuricavar.tangutorum,E. purpuraristatus, andE. dahuricusTurcz. ex Griseb. var.violeusC. P. Wang & H. L. Yang) might share a more recent common ancestor, whereas the four species in sect.Elymus(C. nutans,E. breviaristatus(Keng) Keng ex Keng f.,E. sinosubmuticus(Keng) Keng f., andE. atratus(Nevski) Hand.‐Mazz.) share a close relationship. By identifying only one type of unit class for each haplome, we propose that the 5S nuclear ribosomal DNA sequences of species withinCampeiostachysmight have undergone haplome‐specific concerted evolution.
Pharmacodynamic evaluation of the effects of oral melatonin on expression of the T‐cell cytokines interleukin‐2 and interferon gamma in the dog
Authors: Peace Anna C. , Kumar Santosh , Wills Robert , Mackin Andrew , Hoh Crystal M. , Archer Todd 
Published: January 2019

AbstractObjectiveTo determine the effects of exogenous melatonin administration on activated whole blood expression of the T‐cell cytokines interleukin‐2 (IL‐2) and interferon gamma (INF‐γ) in dogs.AnimalsTen healthy dogs.ProceduresHeparinized whole blood was collected from 10 dogs for analysis of cytokine expression before administration of melatonin (baseline). Each dog was then administered melatonin at a dosage of approximately 1 mg/kg,PO, q 12 hr for 14 days. On day 14, whole blood was again collected from each dog at the time points of trough (0 hr) and 6 hr postmelatonin administration to evaluate the effects of melatonin on cytokine expression. At all evaluated time points, analysis of activated whole blood expression ofmRNAcoding for bothIL‐2 andIFN‐γ was performed using quantitative reverse transcription polymerase chain reaction to determine whether a difference existed for any time point. Blood melatonin concentrations were also measured at comparable time points.ResultsA statistical difference in the expression of either cytokine was not appreciated at any time point, despite attainment of expected blood concentrations of the drug.Conclusions and Clinical RelevanceResults indicate that melatonin therapy does not significantly affectIL‐2 orIFN‐γ expression in healthy dogs. While melatonin is thought to have an effect on the immune system in dogs, it does not appear this effect is through altering T‐cellIL‐2 orIFN‐γ expression. Further studies investigating the effects of melatonin on the immune system of dogs are warranted.
How deep is the conflict between molecular and fossil evidence on the age of angiosperms?
Authors: Coiro Mario , Doyle James A. , Hilton Jason 
Published: January 2019

SummaryThe timing of the origin of angiosperms is a hotly debated topic in plant evolution. Molecular dating analyses that consistently retrieve pre‐Cretaceous ages for crown‐group angiosperms have eroded confidence in the fossil record, which indicates a radiation and possibly also origin in the Early Cretaceous. Here, we evaluate paleobotanical evidence on the age of the angiosperms, showing how fossils provide crucial data for clarifying the situation. Pollen floras document a Northern Gondwanan appearance of monosulcate angiosperms in the Valanginian and subsequent poleward spread of monosulcates and tricolpate eudicots, accelerating in the Albian. The sequence of pollen types agrees with molecular phylogenetic inferences on the course of pollen evolution, but it conflicts strongly with Triassic and early Jurassic molecular ages, and the discrepancy is difficult to explain by geographic or taphonomic biases. Critical scrutiny shows that supposed pre‐Cretaceous angiosperms either represent other plant groups or lack features that might confidently assign them to the angiosperms. However, the record may allow the Late Jurassic existence of ecologically restricted angiosperms, like those seen in the basalANITAgrade. Finally, we examine recently recognized biases in molecular dating and argue that a thoughtful integration of fossil and molecular evidence could help resolve these conflicts.