bluuebunny/crossref_metadata_2025 huggingface dataset:
Making journals accessible front
&
back: examining open journal systems at CSU Northridge
Authors: Borchard Laurie , Biondo Michael , Kutay Stephen , Morck David , Weiss Andrew Philip
Published: January 2015

Purpose

– This study aims to examine Public Knowledge Project (PKP) Open Journal Systems (OJS) for its overall web accessibility and compliance with the Federal Electronic and Information Technology Accessibility and Compliance Act, also known as Section 508.

Design/methodology/approach

– Twenty-one individual web pages in the CSUN test instance of PKP’s OJS version 2.4.0 used in three back-end journal development user roles were examined using three web-accessibility tools (WAVE, Fangs, Functional Accessibility Evaluator). Errors in accessibility were then logged and mapped to specific Web Content Accessibility Guidelines (WCAG) criteria.

Findings

– In all, 202 accessibility errors were reported across the 21 OJS pages selected for testing. Because of this, the OJS cannot be efficiently utilized by assistive technologies and therefore does not pass the minimal level of acceptability as described in the WCAG 2.0. However, the authors found that the types of errors reported in this study could be simply and effectively remedied.

Research limitations/implications

– Further studies will need to corroborate, on a larger scale, the problems of accessibility found in the specific pages. Only three user roles were examined; other roles will need to be analyzed for their own problems with accessibility. Finally, although specific errors were noted, most can be easily fixed.

Practical implications

– There is an important need for accessible software design. In the case of CSUN, one of the campus partners will be better served by improving the web accessibility of the authors’ online open access journals.

Originality/value

– Although many studies and analyses of Section 508 compliance of front-facing web resources have been conducted, very few appear to address the back-end of such tools. This is the first to examine what problems in accessibility journal users with disabilities might encounter as OJS system administrators, journal managers or journal editors.
E-ViVa, the national Hellenic fulltext database on Librarianship and Information Science
Authors: Tsimpoglou Filippos , V. Koukounidou Vasiliki , K. Sakka Eleni
Published: January 2015

Purpose

– The purpose of this paper is to present E-ViVa (Ellinike Vivliothikonomike Vase), the national Hellenic fulltext database on Librarianship and Information Science, developed by the Library of the University of Cyprus. The objectives of E-ViVa are to identify, locate, gather, organize, index, digitize, preserve and promote the results of the research conducted in Greece and Cyprus in the scientific fields of Archival, Library and Information Sciences.

Design/methodology/approach

– The paper provides data concerning the volume, the coverage, the inclusion criteria, the content, the format and the platform of the database, as well as the steps that have been followed for the development. The legal framework related with the copyright issues that are raised are also discussed.

Findings

– A comparison is attempted between the coverage of E-ViVa and the relative records included in five subject-related databases: eLIS, LISA, LISTA, ISI-SSCI and SCOPUS. Finally the future plans for the project are presented.

Research limitations/implications

– Future plans concerning E-ViVa are based on the completeness of the database, the linguistic exploitation of the terms used through time and check of Lotka's law application concerning authors.

Practical implications

– As the vast majority of the records and fulltext are not provided by any other organized database, E-ViVa emerges as a “must search first” for any future author of scientific paper concerning the situation on librarianship research in Greece and Cyprus. The case of E-ViVa and the methodology that was followed can be used as a pattern for developing national databases on LIS or other fields.

Social implications

– E-ViVa is offered as an open access database with fulltext.

Originality/value

– E-ViVa is the only fulltext database on Librarianship and Information Science, which concentrates the related publications produced in or related to Greece and Cyprus.
Factors affecting the satisfaction of an online community for archive management in Taiwan
Authors: HSU Fang-Ming , Chen Tser-Yieth , Fan Chiu-Tsu , Lin Chun-Min , Chiu Chu-Mei
Published: January 2015

Purpose

– The purpose of this paper is to investigate the relationship between the richness of information and the satisfaction of participants in an online community regarding archive management in Taiwan.

Design/methodology/approach

– An investigation was deployed to attendants in 20 training courses created by the National Archives Administration (NAA) in Taiwan for records staff on the topic of digital preservation. The responses were collected from respondents who were participating in an online community for archive management. Through structural equation modeling method, this study examined the effects of channel richness, information transparency and accessibility of archive to brand image and trust and then continued to the satisfaction of professional participants to archive management in an online community.

Findings

– Appropriate disclosure of information regarding archiving can effectively improve the satisfaction of participants in the online community to archive. Channel richness of communication, information transparency and accessibility of archive significantly affect the brand image of archive and the trust of participants to archivists and finally affect the satisfaction of participants in the online community towards archive management.

Practical implications

– The larger the amount of information exchanged, the more the trust among participants and the better brand image of the archives. The more trust and brand image exists among participants, the more satisfaction they will obtain from archive management.

Originality/value

– The results can provide a strategic direction for managers of the national archive and the online community in government agencies to allocate resources for enhancing the information richness and the image of archive as well as achieving the satisfaction of participants in the professional community.
Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71‐associated meningoencephalitis
Authors: Li Huajun , Li Shuxian , Zheng Jianfeng , Cai Chunyan , Ye Bin , Yang Jun , Chen Zhimin
Published: January 2015

Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α and IFN‐γ, in cerebrospinal fluid (CSF) from patients with EV71‐related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL‐6 and IFN‐γ concentrations were significantly higher in patients with EV71‐related ME than in those with FC. Additionally, both CSF IL‐6 and IFN‐γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL‐6 and IFN‐γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL‐6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71‐related ME from FC. In conclusion, IL‐6 and IFN‐γ may be associated with EV71‐induced neuropathology.
Spatially non‐local model of inelastic deformations: applications for rock failure problem
Authors: Dorovsky V. , Romensky Е. , Sinev А.
Published: January 2015

A spatially non‐local model for inelastic deformation of solids is proposed and studied. The non‐locality of deformation is taken into account by the additional parameter of state beyond the classical parameters such as stress and strain tensors. This additional parameter is the curvature tensor expressed in terms of the metric strain tensor, and it is called the failure parameter. In the case of small deformation, it is equivalent to the Saint‐Venant incompatibility tensor. Thermodynamic properties of the model are studied, and governing differential equations for spatially non‐local model are formulated, which are composed by the elasticity equations and parabolic equation for the failure parameter. The model can be applied to the study of the rock failure problem, and as an example, the one‐dimensional problem for the deformation of half‐plane loaded by the normal surface stress is studied. Stationary and non‐stationary formulations of the problem are considered, and qualitative agreement with available experimental data is observed.
Variation in neighbourhood context shapes frugivore‐mediated facilitation and competition among co‐dispersed plant species
Authors: Albrecht Jörg , Bohle Victoria , Berens Dana G. , Jaroszewicz Bogdan , Selva Nuria , Farwig Nina
Published: January 2015

Co‐occurring and simultaneously fruiting plant species may either compete for dispersal by shared frugivores or enhance each other's dispersal through joint attraction of frugivores. While competitive plant–plant interactions are expected to cause the evolutionary divergence of fruit phenologies, facilitative interactions are assumed to promote their convergence. To which extent competitive and facilitative interactions among plant species with similar phenological niches are controlled by spatial variation in their local abundance and co‐occurrence is poorly understood.

Here, we test the hypotheses that when a plant species fruits in high densities, large phenological overlap with other plant species causes competition for seed dispersers owing to frugivore satiation. Conversely, we expect large phenological overlap to enhance the dispersal of a plant species fruiting in low densities through attraction of frugivores by other species in its local neighbourhood.

We test these predictions on plant–frugivore networks based on seed removal from 15 woody, fleshy‐fruited plant species by 30 avian and 4 mammalian frugivore species across 13 study sites in Białowieża Forest, Poland.

A null model indicated that fruit phenologies of the regional plant assemblage were more differentiated than expected by chance. In the local networks, the tendency of plants to share frugivores increased with phenological overlap. High phenological overlap reduced the seed removal rates, interaction strength (proportion of interactions) and the number of partners of plant species fruiting in high densities. Conversely, plant species fruiting in low densities mainly profited from high phenological overlap with other species. Importantly, the sharing of mutualistic partners among co‐fruiting plant species was also reflected in their co‐occurrence.

Synthesis. Our study highlights that, in spite of the overall signal of competition, frugivore‐mediated interactions among cofruiting plant species may consistently promote the establishment and persistence of rare species through facilitation. In addition, our results suggest that, among other factors, indirect coupling of species through shared mutualistic partners might be an important determinant of plant community assembly. The coupling through shared mutualists may cause the formation of associations among co‐dispersed plant species and might contribute to the coexistence of species in plant–animal mutualistic communities.
Eliciting web site preferences of people with learning disabilities
Authors: Williams Peter
Published: January 2015

The Internet can be an excellent tool to help people with learning disabilities access relevant and appropriately written information. However, little work has been undertaken to ascertain web design or content preferences for this cohort. This paper examines methods to address this issue. Twenty five participants were presented with three web sites dealing with employment information. They were asked to browse each and carry out a series of set‐tasks. Interviews and a rating scale ascertained preferences. The problem of acquiescence bias, the tendency for people to automatically agree with those in perceived positions of authority, was minimised by the avoidance of ‘polar interrogatives’ (questions requiring a ‘yes/no’ or similarly polarised answer).

Participants liked the use of pictures, especially when they featured other young people with learning disabilities. Abstract content related to money or benefits often went unnoticed. Audio was appreciated where offered, although not extensively used. Preferences regarding text size and menu position were also established. Results are compared to other relevant literature and recommendations formulated to help web developers and information providers. The methodological issues inherent in this study were the use of the rating system, and the interview technique. The former was adapted following early findings that the neutral position, on a three point scale, was confusing. Using four points avoided this problem and produced more varied results. Avoiding polar interrogatives greatly helped in minimising ‘acquiescence bias’. The study concludes that it is possible to elicit considerable information from people who find it difficult to articulate their views.
Outpatient Clinic for Health Education: Contribution to Self‐Management and Self‐Care for People With Heart Failure
Authors: de Souza Carneiro Camila , Dias de Oliveira Ana Paula , de Lima Lopes Juliana , Bachion Maria Márcia , Herdman T. Heather , Moorhead Sue A. , Bottura Leite de Barros Alba Lúcia
Published: January 2015

Objective

To report the experience of an outpatient nursing education clinic caring for people with chronic heart failure.

Experience Report

In this service, qualified “listening,” recreational educational actions about the disease and its treatment are conducted, based on the interventions from the Nursing Interventions Classification (NIC), as well as the evaluation of self‐care behaviors with the outcomes from the Nursing Outcomes Classification (NOC). This article describes the practice of health education activities and the use of NANDA‐I‐NIC‐NOC in a nursing clinic.

Conclusion

The outpatient clinic supports client learning about the treatment of disease and stimulates self‐control of health behaviors.

Implications for Nursing Practice

This experience report will guide nurses in the establishment of outpatient nursing education clinics for different populations of patients with chronic health conditions.

Objetivo

Relatar a experiência de um ambulatório de educação em saúde para pessoas com insuficiência cardíaca crônica.

Relato De Experiência

Neste serviço são realizadas a “escuta” qualificada e ações educativas sobre a doença e o tratamento, baseadas nas intervenções da Classificação de Intervenções de Enfermagem (NIC), bem como a avaliação dos comportamentos de autocuidado dos resultados da Classificação dos Resultados de Enfermagem (NOC). Este artigo descreve a atividade de educação em saúde e o uso da NANDA‐I‐NIC‐NOC na prática clínica.

Conclusão

O ambulatório apoia o aprendizado do paciente sobre o tratamento da doença e estimula o autocontrole de comportamentos de saúde.

Implicações Para A PrÁtica

Este relato de experiência guiará os enfermeiros no estabelecimento de um ambulatório de educação de enfermagem para diferentes populações de pacientes com doenças crônicas.
CEO inside debt and investment‐cash flow sensitivity
Authors: Han Jianlei , Pan Zheyao
Published: January 2015

This paper provides a new explanation for investment‐cash flow sensitivity from the perspective of CEO inside debt holdings. We examine the effect of CEO pensions and deferred compensation (inside debt) on investment‐cash flow sensitivity for a sample of U.S. manufacturing firms from 2006 to 2012. We find that the firms with higher relative CEO leverage ratios (CEO's debt/equity ratio scaled by the firm's debt/equity ratio) generate higher investment‐cash flow sensitivity. Moreover, one standard deviation increase in the logarithm of the relative CEO leverage ratio enlarges investment‐cash flow sensitivity by 50 per cent. This positive relationship still holds even after we take account of endogeneity and financial constraints.
Adenosine 2A receptors modulate reward behaviours for methamphetamine
Authors: Chesworth Rose , Brown Robyn M. , Kim Jee Hyun , Ledent Catherine , Lawrence Andrew J.
Published: January 2015

Addiction to methamphetamine (METH) is a global health problem for which there are no approved pharmacotherapies. The adenosine 2A (A2A) receptor presents a potential therapeutic target for METH abuse due to its modulatory effects on striatal dopamine and glutamate transmission. Notably, A2A receptor signalling has been implicated in the rewarding effects of alcohol, cocaine and opiates; yet, the role of this receptor in METH consumption and seeking is essentially unknown. Therefore, the current study used A2A knockout (KO) mice to assess the role of A2A in behaviours relevant to METH addiction. METH conditioned place preference was absent in A2A KO mice compared with wild‐type (WT) littermates. Repeated METH treatment produced locomotor sensitization in both genotypes; however, sensitization was attenuated in A2A KO mice in a dose‐related manner. METH intravenous self‐administration was intact in A2A KO mice over a range of doses and schedules of reinforcement. However, the motivation to self‐administer was reduced in A2A KO mice. Regression analysis further supported the observation that the motivation to self‐administer METH was reduced in A2A KO mice even when self‐administration was similar to WT mice. Sucrose self‐administration was also reduced in A2A KO mice but only at higher schedules of reinforcement. Collectively, these data suggest that A2A signalling is critically required to integrate rewarding and motivational properties of both METH and natural rewards.
Addressing Population‐Specific Multiple Testing Burdens in Genetic Association Studies
Authors: Sobota Rafal S. , Shriner Daniel , Kodaman Nuri , Goodloe Robert , Zheng Wei , Gao Yu‐Tang , Edwards Todd L. , Amos Christopher I. , Williams Scott M.
Published: January 2015

The number of effectively independent tests performed in genome‐wide association studies (GWAS) varies by population, making a universal P‐value threshold inappropriate. We estimated the number of independent SNPs in Phase 3 HapMap samples by: (1) the LD‐pruning function in PLINK, and (2) an autocorrelation‐based approach. Autocorrelation was also used to estimate the number of independent SNPs in whole genome sequences from 1000 Genomes. Both approaches yielded consistent estimates of numbers of independent SNPs, which were used to calculate new population‐specific thresholds for genome‐wide significance. African populations had the most stringent thresholds (1.49 × 10−7 for YRI at r2 = 0.3), East Asian populations the least (3.75 × 10−7 for JPT at r2 = 0.3). We also assessed how using population‐specific significance thresholds compared to using a single multiple testing threshold at the conventional 5 × 10−8 cutoff. Applied to a previously published GWAS of melanoma in Caucasians, our approach identified two additional genes, both previously associated with the phenotype. In a Chinese breast cancer GWAS, our approach identified 48 additional genes, 19 of which were in or near genes previously associated with the phenotype. We conclude that the conventional genome‐wide significance threshold generates an excess of Type 2 errors, particularly in GWAS performed on more recently founded populations.
De Novo Mutations in the BMPR2 Gene in Patients with Heritable Pulmonary Arterial Hypertension
Authors: Momose Yuichi , Aimi Yuki , Hirayama Tomomi , Kataoka Masaharu , Ono Masae , Yoshino Hideaki , Satoh Toru , Gamou Shinobu
Published: January 2015

A substantial proportion of patients with pulmonary arterial hypertension (PAH) have mutations in the Bone Morphogenetic Protein Receptor type‐2 (BMPR2) gene. PAH due to BMPR2 mutations is inherited as an autosomal dominant trait with several unique features, including a wide variety of mutations, reduced penetrance, a skewed gender ratio, variable expressivity and genetic anticipation. To address the genetic background of these unique features of BMPR2 mutation, we conducted a systematic analysis of 15 PAH families with BMPR2 mutation. The exonic protein coding sequence of BMPR2 was amplified by polymerase chain reaction and the products were sequenced directly to detect point mutations in BMPR2. Parental identification was carried out to confirm the parental relationship using multiplex 15 loci analysis. Combining mutation detection in family members with parental identification, we described three cases of de novo mutation in the BMPR2 gene by different modes in a PAH family. These de novo mutations may account for the wide variety of mutations in BMPR2. Taken together with the juvenile onset of the disease, there is possibly some balance of de novo mutations and untransmittable mutations which keeps the frequency of PAH low in the general population.
Impression management motive and voice: Moderating effects of self‐monitoring, self‐efficacy, and voice instrumentality
Authors: Choi Byoung Kwon , Moon Hyoung Koo , Chun Jae Uk
Published: January 2015

The purpose of this study is to examine how employees’ impression management motive influences their voice by considering dispositional and situational variables. Drawing on the theory of self‐motive, we hypothesized that voice would be more positively related to impression management motive than prosocial motive. In addition, based on the interactional approach of motive and trait and trait activation theory, we hypothesized that the relationship between impression management motive and voice would be moderated by self‐monitoring, self‐efficacy, and voice instrumentality. Using a sample of 307 supervisor–subordinate dyads from South Korea, we found that, although prosocial motive had a positive influence on voice, impression management motive had a stronger influence on voice than prosocial motive. We also found that the positive influence of impression management motive on voice was stronger for employees with high levels of self‐monitoring, self‐efficacy, and voice instrumentality. This study helps verify the boundary conditions as to when impression management motive is strongly related to voice. In addition, this study will provide theoretical clues for resolving the inconsistent findings on the relationship between impression management motive and voice.
A randomized phase I clinical study of cis‐urocanic acid eye drops in healthy adult subjects
Authors: Jauhonen Hanna‐Mari , Kari Eeva , Pylkkänen Liisa , Poutanen Jutta , Laihia Jarmo , Kaarniranta Kai , Leino Lasse
Published: January 2015

Purpose

To evaluate safety, ocular tolerability and pharmacokinetics of 0.5% and 2.5% cis‐urocanic acid (cis‐UCA) eye drops.

Methods

In this phase I, double‐blinded, placebo‐controlled trial, 37 healthy volunteers were randomized to three treatment arms: 0.5% cis‐UCA (12 subjects), 2.5% cis‐UCA (12 subjects) and placebo eye drops (13 subjects). In the first part, the subjects were dosed topically on a randomized eye with one drop three times at 7 ± 1 hr intervals during 1 day. In the second part, the subjects self‐administered three daily drops at 7 ± 1 hr intervals on both eyes for 14 days. Physical examination of the eyes was performed seven times during the study. Tolerability of cis‐UCA was assessed by ocular comfort rating questionnaire. Pharmacokinetic blood and urine samples were analysed under good laboratory practice (GLP).

Results

All subjects completed both parts of the study. There were no significant adverse events (AEs). The most common treatment‐related ocular AE was eye irritation (62.2% of subjects). Cis‐UCA concentrations in plasma remained below the limit of quantification (0.195 μg/ml) in all but two subjects. The fraction of the administered drug excreted into urine over the total collection period ranged from 3.2% to 61.6% of the last dose and from 1.1% to 20.5% of the daily dose.

Conclusions

Topical ocular administration of cis‐UCA solution is safe and apart from mild‐ and short‐lasting eye irritation after administration well tolerated in healthy adult subjects. Topical ocular dosing leads to transient systemic exposure to cis‐UCA that does not cause systemic AEs.
Intra‐ and intermale variability of mature sperm traits analysed in two brackish water populations of the pipefish Syngnathus abaster (Syngnathidae)
Authors: Piras Francesca , Biagi Francesca , Floris Antonello , Farina Vittorio , Zedda Marco , Franzoi Piero , Carcupino Marcella
Published: January 2015

Sperm cells are highly diversified in animals, and considerable research effort has focused on variation in sperm morphology among species. Surprisingly, little is known about intraspecific variation in sperm morphology. We analysed within‐ and between‐male variation in mature sperm traits in two brackish water populations of the pipefish Syngnathus abaster. Four morphometric parameters, such as the width and length of the head (including nucleus, and midpiece), length of flagellum and total sperm length were taken into account. The differences in all morphometric parameters analysed between populations were not statistically significant. Moreover, the multidimensional scaling analysis shows that (i) the two populations seem to be indistinguishable based on their spermatozoa and (ii) there is not polymorphism, being sperm not distinguishable into discrete classes both within a single male and between males of each populations. The latter datum does not seem to support the presence of polymorphic sperm in syngnathids. Both populations, however, exhibit a high variation in all sperm traits, both among individual sperm within an ejaculate and among males within each population. The relationship between sperm traits variability and the low selection pressure determined by the absence of postcopulatory sexual selection (i.e. absence of sperm competition) is discussed.
Physiologically based pharmacokinetic model for 6‐mercpatopurine: exploring the role of genetic polymorphism in TPMT enzyme activity
Authors: Ogungbenro Kayode , Aarons Leon ,   the CRESim & Epi‐CRESim Project Groups
Published: January 2015

Aims

To extend the physiologically based pharmacokinetic (PBPK) model developed for 6‐mercaptopurine to account for intracellular metabolism and to explore the role of genetic polymorphism in the TPMT enzyme on the pharmacokinetics of 6‐mercaptopurine.

Methods

The developed PBPK model was extended for 6‐mercaptopurine to account for intracellular metabolism and genetic polymorphism in TPMT activity. System and drug specific parameters were obtained from the literature or estimated using plasma or intracellular red blood cell concentrations of 6‐mercaptopurine and its metabolites. Age‐dependent changes in parameters were implemented for scaling, and variability was also introduced for simulation. The model was validated using published data.

Results

The model was extended successfully. Parameter estimation and model predictions were satisfactory. Prediction of intracellular red blood cell concentrations of 6‐thioguanine nucleotide for different TPMT phenotypes (in a clinical study that compared conventional and individualized dosing) showed results that were consistent with observed values and reported incidence of haematopoietic toxicity. Following conventional dosing, the predicted mean concentrations for homozygous and heterozygous variants, respectively, were about 10 times and two times the levels for wild‐type. However, following individualized dosing, the mean concentration was around the same level for the three phenotypes despite different doses.

Conclusions

The developed PBPK model has been extended for 6‐mercaptopurine and can be used to predict plasma 6‐mercaptopurine and tissue concentration of 6‐mercaptopurine, 6‐thioguanine nucleotide and 6‐methylmercaptopurine ribonucleotide in adults and children. Predictions of reported data from clinical studies showed satisfactory results. The model may help to improve 6‐mercaptopurine dosing, achieve better clinical outcome and reduce toxicity.
Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be effective treatment for transfusional iron overload
Authors: Aygun Banu , Mortier Nicole A. , Kesler Karen , Lockhart Alexandre , Schultz William H. , Cohen Alan R. , Alvarez Ofelia , Rogers Zora R. , Kwiatkowski Janet L. , Miller Scott T. , Sylvestre Pamela , Iyer Rathi , Lane Peter A. , Ware Russell E. ,   the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) Trial Investigators
Published: January 2015

Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (−8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well‐tolerated, with net iron removal in most children who completed 30 months of protocol‐directed treatment.
RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv(16) subtype
Authors: Estécio Marcos R. H. , Maddipoti Sirisha , Bueso‐Ramos Carlos , DiNardo Courtney D. , Yang Hui , Wei Yue , Kondo Kimie , Fang Zhihong , Stevenson William , Chang Kun‐Sang , Pierce Sherry A. , Bohannan Zachary , Borthakur Gautam , Kantarjian Hagop , Garcia‐Manero Guillermo
Published: January 2015

Correlative and functional studies support the involvement of the RUNX gene family in haematological malignancies. To elucidate the role of epigenetics in RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23 leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1 and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly variable among patient samples, with clear association to cytogenetic status. High frequency of RUNX3 hypermethylation (85% of the 20 studied cases) was found in AML patients with inv(16)(p13.1q22) compared to other AML subtypes (31% of the other 49 cases). RUNX3 hypermethylation was also frequent in ALL (100% of the six cases) but low in MDS (21%). In support of a functional role, hypermethylation of RUNX3 was correlated with low levels of protein, and treatment of cell lines with the DNA demethylating agent, decitabine, resulted in mRNA re‐expression. Furthermore, relapse‐free survival of non‐inv(16)(p13.1q22) AML patients without RUNX3 methylation was significantly better (P = 0·016) than that of methylated cases. These results suggest that RUNX3 silencing is an important event in inv(16)(p13.1q22) leukaemias.
Clinical outcomes of a novel therapeutic vaccine with Tax peptide‐pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study
Authors: Suehiro Youko , Hasegawa Atsuhiko , Iino Tadafumi , Sasada Amane , Watanabe Nobukazu , Matsuoka Masao , Takamori Ayako , Tanosaki Ryuji , Utsunomiya Atae , Choi Ilseung , Fukuda Tetsuya , Miura Osamu , Takaishi Shigeo , Teshima Takanori , Akashi Koichi , Kannagi Mari , Uike Naokuni , Okamura Jun
Published: January 2015

Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type‐I (HTLV‐I)‐infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV‐I Tax‐specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti‐ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate‐ to high‐risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax‐specific CTL responses were observed with peaks at 16–20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide‐pulsed DC vaccine is a safe and promising immunotherapy for ATL.
Expression of BAF57 in ovarian cancer cells and drug sensitivity
Authors: Yamaguchi Takahiro , Kurita Tomoko , Nishio Kazuto , Tsukada Junichi , Hachisuga Toru , Morimoto Yasuo , Iwai Yoshiko , Izumi Hiroto
Published: January 2015

The SMARCE1 (SWI / SNF‐related, matrix‐associated, and actin‐dependent regulator of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we reported that BAF57 is a predictive marker of endometrial carcinoma. In this study, we investigated BAF57 expression in ovarian cancer cell lines and their sensitivities to cisplatin, doxorubicin, paclitaxel, and 5‐fluorouracil. BAF57 expression was strongly correlated with sensitivities to cisplatin, doxorubicin, and 5‐fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was also correlated with BAF57 expression, but without significance. In A2780 ovarian cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest at G1 phase and the sensitivities to these anticancer agents. cDNA microarray analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were positively regulated by BAF57, including ATP‐binding cassette, sub‐family G (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer cells by Western blot analysis, and that ABCG2 gene expression might be regulated transcriptionally. These results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy.
Clinical significance of estrogen receptor β in breast and prostate cancer from biological aspects
Authors: Omoto Yoko , Iwase Hirotaka
Published: January 2015

Breast and prostate cancers are among the most common of all cancers. They are referred to as hormone‐dependent cancers, because estrogen and androgen are involved in their development and growth. The effects of these hormones are mediated by their respective receptors, estrogen receptor (ER) α and androgen receptor. Around 18 years ago, a second ER, ERβ, which has a very similar structure to ERα, was discovered. Its function has been investigated using a variety of methods and biological systems, leading to our present understanding that ERβ can interact with or inhibit ERα and androgen receptor function directly and/or indirectly, suppress cell growth, and influence responsiveness to endocrine therapy. In order to apply the “inhibition of cell growth” function to cancer treatment, several specific ERβ agonists have been synthesized and are being tested for effectiveness in cancer treatment. We need to keep our eyes on ERβ.
Recent advances in myelodysplastic syndromes: Molecular pathogenesis and its implications for targeted therapies
Authors: Harada Hironori , Harada Yuka
Published: January 2015

Myelodysplastic syndromes (MDS) are defined as stem cell disorders caused by various gene abnormalities. Recent analysis using next‐generation sequencing has provided great advances in identifying relationships between gene mutations and clinical phenotypes of MDS. Gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins and components of the cohesion complex participate in the pathogenesis and progression of MDS. Mutations in RNA splicing and DNA methylation occur early and are considered “founding mutations”, whereas others that occur later are regarded as “subclonal mutations”. RUNX1 mutations are more likely to subclonal; however, they apparently play a pivotal role in familial MDS. These genetic findings may lead to future therapies for MDS.
Enriching the isotopic toolbox for migratory connectivity analysis: a new approach for migratory species breeding in remote or unexplored areas
Authors: Pekarsky Sasha , Angert Alon , Haese Barbara , Werner Martin , Hobson Keith A. , Nathan Ran
Published: January 2015

Aim

We examined three potential enhancements of the stable isotope technique for elucidating migratory connectivity in birds inhabiting poorly studied areas, illustrated for Eurasian cranes (Grus grus) that overwinter in and migrate through Israel. First, we examined the use of oxygen stable isotopes (δ18O), seldom applied for this purpose. Second, we examined the relationship between ambient water δ18O and hydrogen stable isotope (δ2H) values derived from various models, to determine the geographical origins of migrants. Third, we introduced the use of probabilistic distribution modelling to refine the assignment to origin of migrants lacking detailed distribution maps.

Location

Feather samples were collected in the Hula Valley (northern Israel) and across the species breeding range in north Eurasia.

Methods

We analysed δ18O and δ2H in primary and secondary flight feathers using standard mass spectrometry. The maximum entropy (maxent) model was used to map the probability surface of potential breeding areas, as a Bayesian prior for assigning Hula Valley cranes to potential breeding grounds.

Results

We found that δ18O was suitable and informative. The soil water isoscape performed better for δ18O while precipitation isoscape was preferable for δ2H. The maxent‐based probability surface largely refined assignments. Overall, most (>85%) cranes were assigned to the area west of the Ural Mountains, but for two individuals, most of the assigned area (>90%) was farther east, suggesting, for the first time, that Eurasian cranes may undertake the North Asia–Middle East (and perhaps Africa) migration flyway.

Main conclusions

Our results call for broader use of δ18O in migratory connectivity studies and for application of probabilistic distribution modelling. We also encourage investigation of factors determining δ18O and δ2H integration into animal tissues. The proposed framework may help improve our understanding of migratory connectivity of species inhabiting previously unexplored areas and thus contribute to the development of efficient conservation plans.
Endoscopic ultrasonography using new functions for pancreatobiliary diseases: Current status and future perspectives
Authors: Katanuma Akio , Isayama Hiroyuki , Bapaye Amol
Published: January 2015

A new endoscopic ultrasound processor (EU‐ME2 Premier Plus) has recently been developed. It improves fundamental imaging and enables three new functions; namely, tissue harmonic echo (THE), elastography, and contrast harmonic endoscopic ultrasonography (CH‐EUS). However, many aspects regarding the usefulness of these three functions in the diagnosis of pancreatobiliary diseases remain unknown. In connection with and prior to the convening of Endoscopy Forum Japan 2014, endoscopic ultrasonography using EU‐ME2 Premier Plus was carried out for pancreatic, bile duct, and gallbladder cases at 12 participating institutions (Japan [n = 10]; other Asian countries [n = 2]). A questionnaire survey was conducted regarding the usefulness of EU‐ME2 Premier Plus for each EUS case. In addition, participants’ views were surveyed by asking them to vote as to whether or not the three functions of EU‐ME2 Premier Plus were useful for several items under pancreatic, bile duct, and gallbladder indications. According to the participants’ views, THE (particularly THE‐P mode) is essential for the diagnosis of cystic lesions. Many participants viewed elastography as useful in only extremely limited cases. Although CH‐EUS was not considered useful for all cases, its indications covered a broad range. Additional studies are warranted to clarify the functions of EU‐ME2 Premier Plus in more detail.
Spectral Doppler Interrogation of the Pulmonary Veins in Atrial Septal Defect
Authors: Fadel Bahaa M. , Mohty Dania , Aldawood Wafa , Dahdouh Ziad , Di Salvo Giovanni
Published: January 2015

The various components of the pulmonary venous (PV) flow are linked to physiological and pathological changes that predominantly occur in the left heart. Thus, spectral Doppler interrogation of the PVs provides hemodynamic insight mainly into left‐sided cardiac function. An exception to the dependence of PV flow on left heart events occurs in the setting of an atrial septal defect (ASD). The latter causes a portion of the PV blood flow, intended to cross the mitral valve, to be channeled into the more compliant right heart. This phenomenon makes the PV flow more dependent on the left‐to‐right interatrial shunt. The identification on the PV Doppler of a pattern that suggests uncoupling with left heart hemodynamics should raise the suspicion of an underlying ASD.
Echo Doppler Estimation of Pulmonary Capillary Wedge Pressure in Patients with Severe Aortic Stenosis
Authors: Biner Simon , Topilsky Yan , Banai Shmuel , Steinvil Arie , Arbel Yaron , Siegel Robert James , Beigel Roy , Keren Gad , Finkelstein Ariel
Published: January 2015

Background

Transcatheter aortic valve replacement (TAVR) has become a treatment option for patients with severe aortic stenosis (AS) and high surgical risk. Assessment of symptoms in these patients is challenging because of advanced age, comorbidities, and limited physical activity. Noninvasive quantification of pulmonary capillary wedge pressure (PCWP) in candidates for TAVR may be helpful for risk stratification. The objective of the study was to create a model for estimation of PCWP by echo Doppler in patients with severe AS.

Methods and Results

Data from 80 patients with severe AS referred for TAVR were used to develop an echo Doppler model for predicting PCWP. Its performance was evaluated in the test cohort of 33 patients who had invasive and noninvasive evaluation. No single echo Doppler parameter estimated PCWP accurately. In the retrospective analysis, the multilinear regression provided an accurate estimate of PCWP (r2 = 0.74). The model included, in order of importance (all P < 0.05), the ratio of early transmitral velocity (E) to annular velocity (E’), the left ventricular ejection fraction, and the velocity time integral of tricuspid regurgitation signal. In the prospective cohort of patients with severe AS, the model demonstrated good predictive ability of PCWP (r = 0.77, P < 0.01).

Conclusion

In patients with severe AS, noninvasive estimation of PCWP is possible by integration of two‐dimensional, spectral, and tissue Doppler variables.
Long‐range seasonal migration in insects: mechanisms, evolutionary drivers and ecological consequences
Authors: Chapman Jason W. , Reynolds Don R. , Wilson Kenneth
Published: January 2015

Myriad tiny insect species take to the air to engage in windborne migration, but entomology also has its ‘charismatic megafauna’ of butterflies, large moths, dragonflies and locusts. The spectacular migrations of large day‐flying insects have long fascinated humankind, and since the advent of radar entomology much has been revealed about high‐altitude night‐time insect migrations. Over the last decade, there have been significant advances in insect migration research, which we review here. In particular, we highlight: (1) notable improvements in our understanding of lepidopteran navigation strategies, including the hitherto unsuspected capabilities of high‐altitude migrants to select favourable winds and orientate adaptively, (2) progress in unravelling the neuronal mechanisms underlying sun compass orientation and in identifying the genetic complex underpinning key traits associated with migration behaviour and performance in the monarch butterfly, and (3) improvements in our knowledge of the multifaceted interactions between disease agents and insect migrants, in terms of direct effects on migration success and pathogen spread, and indirect effects on the evolution of migratory systems. We conclude by highlighting the progress that can be made through inter‐phyla comparisons, and identify future research areas that will enhance our understanding of insect migration strategies within an eco‐evolutionary perspective.
Predicting changes in the distribution and abundance of species under environmental change
Authors: Ehrlén Johan , Morris William F.
Published: January 2015

Environmental changes are expected to alter both the distribution and the abundance of organisms. A disproportionate amount of past work has focused on distribution only, either documenting historical range shifts or predicting future occurrence patterns. However, simultaneous predictions of abundance and distribution across landscapes would be far more useful. To critically assess which approaches represent advances towards the goal of joint predictions of abundance and distribution, we review recent work on changing distributions and on effects of environmental drivers on single populations. Several methods have been used to predict changing distributions. Some of these can be easily modified to also predict abundance, but others cannot. In parallel, demographers have developed a much better understanding of how changing abiotic and biotic drivers will influence growth rate and abundance in single populations. However, this demographic work has rarely taken a landscape perspective and has largely ignored the effects of intraspecific density. We advocate a synthetic approach in which population models accounting for both density dependence and effects of environmental drivers are used to make integrated predictions of equilibrium abundance and distribution across entire landscapes. Such predictions would constitute an important step forward in assessing the ecological consequences of environmental changes.
Study on the accumulative fatigue damage rules under multiaxial two‐stage step spectra constructed by loadings with similar lives
Authors: Xia T. X. , Yao W. X. , Ji Y. F. , Wang C. J.
Published: January 2015

In this paper, the influence on the multiaxial fatigue damage accumulation caused by loading path variation was studied. For 2024‐T4 aluminium alloy, the damage evolution during the entire life was first observed. On the basis of the observation, the stage I of fatigue damage evolution was further divided into two sub‐stages, and the dominant stress parameters of these two sub‐stages were proposed. Taking the dominant stress parameters into account, a phased accumulative fatigue damage model was proposed. Then, 12 multiaxial two‐stage step spectra constructed by loadings with approximately identical fatigue lives were carried out on 2024‐T4 aluminium alloy. The accumulative fatigue damage was calculated by the proposed model, and another five commonly used models and the calculated results were compared. According to the comparison, the newly proposed model had the most accurate results with the smallest scatter.