bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetical and Comparative Genomics of Brassica under Altered Ca Supply Identifies Arabidopsis Ca-Transporter Orthologs
Authors: Graham Neil S. , Hammond John P. , Lysenko Artem , Mayes Sean , Ó Lochlainn Seosamh , Blasco Bego , Bowen Helen C. , Rawlings Chris J. , Rios Juan J. , Welham Susan , Carion Pierre W.C. , Dupuy Lionel X. , King Graham J. , White Philip J. , Broadley Martin R. 
Published: August 2014

Abstract
Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca2+ transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans- eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca2+ transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization.
Crystal structure of 2,5-bis(4-methylpyridin-2-yl)pyrazine chloroform disolvate
Authors: Schmitt Laurette , Stoeckli-Evans Helen 
Published: August 2014

The heterocyclic molecule in the title solvate, C16H14N4·2CHCl3, possesses inversion symmetry, with the inversion centre situated at the centre of the pyrazine ring. The outer pyridine rings are inclined to the central pyrazine ring by 4.89 (9)°. The compound crystallized as a chloroform disolvate with the solvent molecules linked to the title molecule by C—H...N hydrogen bonds. In the crystal, molecules are further linked by π–π interactions involving the pyrazine and pyridine rings of neighbouring molecules [inter-centroid distance = 3.5629 (12) Å; symmetry code:x,y + 1,z + 1].
Reproductive ‘Surrogacy’ and Parental Licensing
Authors: Overall Christine 
Published: August 2014

AbstractA serious moral weakness of reproductive ‘surrogacy’ is that it can be harmful to the children who are created. This article presents a proposal for mitigating this weakness. Currently, the practice of commercial ‘surrogacy’ operates only in the interests of the adults involved (the gestator and the commissioning individuals who employ her), not in the interests of the child who is created. Whether ‘surrogacy’ is seen as the purchase of a baby, the purchase of parental rights, or the purchase of reproductive labor, all three views share the same significant flaws. They endorse the transfer, for a fee, of the infant from the woman who gestated it to those who commissioned it, but without justifying such a transfer; they fail to demonstrate that the commissioners have any entitlement to the infant, or, for that matter, suitability to be the infant's parents; and they fail to take any notice of the infant's needs, interests, and wellbeing. A mere genetic connection is not enough to establish that the commissioners are entitled to receive the baby or that they are competent to raise it. Their good intentions, however caring, are not enough. Therefore, just as in the practice of adoption, there should be a formal institutionalized system for screening and licensing the prospective social parents, which would make the infant's needs, interests, and wellbeing paramount. I reply to several potential objections to this proposal, including the objection that genetic parents who raise their own child are not screened and licensed.
Developing Clinical Research Relationship: Views from Within
Authors: Zvonareva Olga , Akrong Lloyd 
Published: August 2014

AbstractThe nature of the relationship between clinical investigator and research participant continues to be contested. The related discussions have largely focused on the doctor‐researcher dichotomy thought to permeate the work of a clinical investigator with research participants, whom in turn occupy two corresponding roles: patient and subject. This paper contributes to current debates on the topic by providing a voice to research participants, whose perspectives have been largely invisible. It draws on 42 in‐depth interviews conducted in Ghana and South Africa with respondents at different stages of involvement in clinical research, ranging from no experience in clinical research to enrollment in several clinical trials. The perspectives of all respondents were largely congruent and rooted in the common view that clinical research contributed to the improvement of local health. They went beyond the researcher/participant versus doctor/patient dichotomy, long established in research ethics, and preferred to view participants and investigators as partners working together to find ways to address local health needs. The conceptualization of investigator‐participant relations as a partnership reinforced expectations of care, transparency and accountability, which were viewed as necessary expressions of mutuality and respect within equal collaborations. It is important to engage with these views in order to avoid antagonizing societal expectations and to build up long‐term public trust, crucial for the continuous operation of clinical research.
Health‐related quality of life in preschool children with Type 1 diabetes
Authors: Sundberg F. , Sand P. , Forsander G. 
Published: August 2014

AbstractAimsTo describe health‐related quality of life in children aged < 7 years with Type 1 diabetes mellitus compared with healthy children of the same age, and to investigate how health‐related quality of life was correlated with aspects of insulin treatment and glycaemic control.MethodsThe participants in this study were 24 children with diabetes (12 girls, mean age 4.5 years) and 27 healthy children (14 girls, mean age 4.6 years). All participants completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the participants with diabetes also completed the Pediatric Quality of Life Inventory 3.0 Type 1 Diabetes Module Scales. HbA1c levels were measured in children with diabetes and the plasma glucose meter memories were uploaded.ResultsChildren aged <7 years with diabetes had lower parent‐rated generic health‐related quality of life compared with healthy children (score: 80 vs 91; P = 0.003). The difference was largest in children aged < 5 years (score: 79 vs 93; P = 0.004). Among the parents of children with Type 1 diabetes, 22% rated their child's generic health‐related quality of life to be at a level of concern (– 1 sd of a general population). Of the children with Type 1 diabetes aged between 5 and 7 years, 40% rated their own generic health‐related quality of life at the same level of concern.ConclusionThis study shows a significantly lower level of generic health‐related quality of life in very young children with diabetes in comparison with healthy children. We suggest screening for health‐related quality of life in children of all ages with Type 1 diabetes mellitus.
Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?
Authors: Mattioli Francesca , Puntoni Matteo , Marini Valeria , Fucile Carmen , Milano Giulia , Robbiano Luigi , Perrotta Silverio , Pinto Valeria , Martelli Antonietta , Forni Gian Luca 
Published: August 2014

AbstractObjectivesBioavailability of deferasirox (DFX) is significantly affected by the timing of administration relative to times and to composition of meals. Its elimination half‐life is also highly variable – in some patients as a result of gene polymorphisms. Understanding whether deferasirox plasma levels are related to specific characteristics of patients could help physicians to devise a drug regimen tailored the individual patient.MethodsWe analyzed deferasirox plasma concentrations (CDFX) in 80 patients with transfusion‐dependent anemias, such as thalassemia, by a high performance liquid chromatography (HPLC) assay. We used a multivariate linear regression model to find significant associations between CDFX and clinical/demographical characteristics of patients. All patients were genotyped for UGT1A1.ResultsFifty‐six patients were female, 24 were male, the great majority (88%) affected by β‐thalassemia, and 15 were children and adolescents. No statistical correlation was detectable between CDFX and DFX dose (P = 0.6). Age, time from last drug intake to blood sampling, and ferritin levels in the 6 months before study initiation were significantly and inversely associated with CDFX in univariate analysis. In the multivariate analysis, the only two factors independently and inversely associated with CDFX levels were time from last drug intake to blood sampling and ferritin levels (P = 0.006). A significant inverse correlation (P = 0.03) was observed between CDFX and UGT1A1*28 gene polymorphism, but only in patients with levels of lean body mass (LBM) below the median (P for interaction = 0.05).ConclusionsThe results could indicate that a higher plasma DFX concentration could be associated with greater chelation efficacy. As a correlation between dose and CDFX was not demonstrated, it seems useful to monitor the concentrations to optimize and determine the most appropriate dose for each patient. Interesting results emerged from the analysis of genetic and physical characteristics of patients: LBM was a borderline significant effect modifier of the relationship between UGT1A1 polymorphisms and CDFX. Individual patient‐tailored dosing of DFX should help to improve iron chelation efficacy and to reduce dose‐dependent drug toxicity.
Primary antifungal prophylaxis with micafungin in patients with haematological malignancies: real‐life data from a retrospective single‐centre observational study
Authors: Nachbaur David , Angelova Olga , Orth‐Höller Dorothea , Ditlbacher Adelheid , Lackner Michaela , Auberger Jutta , Lass‐Flörl Cornelia 
Published: August 2014

AbstractMould‐active antifungal prophylaxis is increasingly used in patients at risk for invasive fungal disease. Between June 2011 and June 2012, one hundred patients with various haematological malignancies at risk for invasive fungal disease received primary antifungal prophylaxis with intravenous micafungin at a daily dosage of 50 mg during neutropenia. The median number of days on micafungin prophylaxis was 14 (range, 6–48 d). The incidence of proven and probable breakthrough invasive fungal diseases (bIFDs) was 6% and 3%, respectively. There were two bloodstream infections caused by yeasts or yeast‐like fungi (Candida krusei, Trichosporon asahii) in two patients during the neutropenic phase after allogeneic haematopoietic stem cell transplantation. Four proven bIFDs caused by non‐Aspergillus moulds and three cases of probable pulmonary bIFDs were documented during the neutropenic phase after induction/consolidation chemotherapy for acute leukaemia. Colonisation with Candida spp. was documented in 51% of the patients with none of the isolates being in vitro micafungin resistant. Compared to a historical control, receiving primary prophylaxis with posaconazole micafungin is at least as effective in preventing IFD. In both cohorts, bIFDs were exclusively caused by emerging pathogens with a highly preserved in vitro sensitivity to amphotericin B.
Characterisation of patient encounters in community pharmacies (with special focus on self-medication)
Authors: De Bolle Leen , Mehuys Els , Christiaens Thierry , Van Tongelen Inge , Remon Jean-Paul , Boussery Koen 
Published: August 2014

Abstract

Objectives
To characterise patient encounters during routine drug dispensing in community pharmacies.

Methods
Cross-sectional survey in community pharmacies (Belgium).

Key findings
Fifty-four per cent of all encounters (N = 1650) concerned patients carrying a prescription, of which 39% were prescriptions for new medication and 61% were repeat prescriptions. In 62% of all encounters, patients asked for non-prescribed medication. Almost one-third of self-medication requests related to special patient populations (mainly children and elderly).

Conclusions
Many encounters related to self-medication, and a substantial number of these self-medication requests concerned vulnerable patient populations.
Can frailty predict complicated care needs and length of stay?
Authors: Rose M. , Pan H. , Levinson M. R. , Staples M. 
Published: August 2014

AbstractThe Reported Edmonton Frail Scale was used to describe the prevalence of frailty in an acute general medical unit. The relationship between frailty, discharge destination, mortality and length of hospital stay was explored. We found that age was associated with frailty, and frailty correlated to an increasing length of hospital stay. Significantly, frailty was associated with complexity in discharge, and this process created a longer length of hospital stay.
Anti‐mouse CD52 monoclonal antibody ameliorates intestinal epithelial barrier function in interleukin‐10 knockout mice with spontaneous chronic colitis
Authors: Wang Honggang , Dong Jianning , Shi Peiliang , Liu Jianhui , Zuo Lugen , Li Yi , Gong Jianfeng , Gu Lili , Zhao Jie , Zhang Liang , Zhang Wei , Zhu Weiming , Li Ning , Li Jieshou 
Published: August 2014

SummaryIntestinal inflammation causes tight junction changes and death of epithelial cells, and plays an important role in the development of Crohn's disease (CD). CD52 monoclonal antibody (CD52 mAb) directly targets the cell surface CD52 and is effective in depleting mature lymphocytes by cytolytic effects in vivo, leading to long‐lasting changes in adaptive immunity. The aim of this study was to investigate the therapeutic effect of CD52 mAb on epithelial barrier function in animal models of IBD. Interleukin‐10 knockout mice (IL‐10−/−) of 16 weeks with established colitis were treated with CD52 mAb once a week for 2 weeks. Severity of colitis, CD4+ lymphocytes and cytokines in the lamina propria, epithelial expression of tight junction proteins, morphology of tight junctions, tumour necrosis factor‐α (TNF‐α)/TNF receptor 2 (TNFR2) mRNA expression, myosin light chain kinase (MLCK) expression and activity, as well as epithelial apoptosis in proximal colon were measured at the end of the experiment. CD52 mAb treatment effectively attenuated colitis associated with decreased lamina propria CD4+ lymphocytes and interferon‐γ/IL‐17 responses in colonic mucosa in IL‐10−/− mice. After CD52 mAb treatment, attenuation of colonic permeability, increased epithelial expression and correct localization of tight junction proteins (occludin and zona occludens protein‐1), as well as ameliorated tight junction morphology were observed in IL‐10−/− mice. CD52 mAb treatment also effectively suppressed the epithelial apoptosis, mucosa TNF‐α mRNA expression, epithelial expression of long MLCK, TNFR2 and phosphorylation of MLC. Our results indicated that anti‐CD52 therapy may inhibit TNF‐α/TNFR2‐mediated epithelial apoptosis and MLCK‐dependent tight junction permeability by depleting activated T cells in the gut mucosa.
Assessing the impact of patient self‐selection on the costs to treat latent tuberculosis infection (LTBI) with isoniazid and transitional rifampin
Authors: Fluegge Kyle R. 
Published: August 2014

AbstractRationale, aims and objectivesThis article examines costs to treat latent tuberculosis infection (LTBI) in an urban clinic population and highlights the potential effectiveness of an alternative transitional treatment regimen.MethodsPatients who experienced side effects on the gold standard of 9 months of isoniazid (9INH) were either continued on isoniazid or transitioned to 4 months of rifampin (4RIF). I use multilevel Tobit models with selection to analyse whether transitioning to 4RIF is less costly than remaining on 9INH among patients experiencing side effects.ResultsResults reveal that self‐selection is present in this clinic data. Using an ordered probit parametric selection rule to account for selection, I find transitioning patients to 4RIF costs significantly less than continuing on 9INH. This result is especially sensitive to selection: not controlling for selection demonstrates that patients transitioning to 4RIF actually cost significantly more to treat. Post hoc analysis revealed that switching to 4RIF significantly reduced the dropout probability among these patients.ConclusionFuture work should more carefully assess the clinical attributes, including effectiveness, of treatment with 9INH and transitional 4RIF as alternative treatment for LTBI.
An investigation into the Professional Quality of Life of dietitians working in acute care caseloads: are we doing enough to look after our own?
Authors: Osland E. J. 
Published: August 2014

AbstractBackgroundThe development of compassion fatigue (CF) has been described across a variety of acute care caseloads in some health professions. The present study was undertaken to determine whether dietitians working in these caseloads also experience CF.MethodsA voluntary, anonymous survey incorporating the Professional Quality of Life tool was developed in an online format, and was e‐mailed to dietitians working in public acute care settings.ResultsEighty‐seven completed surveys were returned. Average rates of compassion satisfaction (CS) and burnout and low rates of secondary traumatic stress (STS) were reported. Dietitians in high‐risk workloads reported higher levels of STS than those with low‐risk workloads (χ2 = 5.4, P = 0.02). Differences in STS were found between those practising in paediatric compared to adult caseloads (χ2 = 16.6, P < 0.01). Dietitians in smaller facilities reported higher STS (χ2 = 10.6, P < 0.01) and lower CS (P = 0.05) than larger facilities. Working for >5 years as a dietitian was associated with higher rates of STS and burnout than in those working for <5 years (χ2 = 7.9, P = 0.05 and χ2 = 3.8, P = 0.05, respectively). Those who perceived greater levels of support reported lower rates of burnout (rs = −0.41, P < 0.01) and higher rates of CS (rs = 0.39, P < 0.01) than those not feeling supported. All dietitians reported undertaking self‐care practices; however, up to 24% reported practices that may represent maladaptive coping methods.ConclusionsAlthough the present study suggests dietitians experience a good professional quality of life, vulnerable areas were identified, suggesting the need for additional support in some areas of dietetic practice.
APRI and FIB‐4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS)
Authors: Teshale E. , Lu M. , Rupp L. B. , Holmberg S. D. , Moorman A. C. , Spradling P. , Vijayadeva V. , Boscarino J. A. , Schmidt M. A. , Gordon S. C. ,   the CHeCS Investigators
Published: August 2014

SummaryWe aim to determine the predictive ability of APRI, FIB‐4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2–F4) from none to minimal fibrosis (F0–F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0–4 equivalent fibrosis stage. Mean APRI and FIB‐4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut‐offs, the AUROCs in distinguishing F2–F4 from F0 to F1 were 0.81 (0.76–0.87) for APRI, 0.81 (0.75–0.86) for FIB‐4 and 0.56 (0.49–0.64) for AST/ALT ratio. APRI and FIB‐4 distinguished F2–F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis.
Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses
Authors: Knych H. K. , Steinmetz S. J. , McKemie D. S. 
Published: August 2014

The anti‐anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA‐containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC‐MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half‐life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative‐like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent.
The genomics of adaptation, divergence and speciation: a congealing theory
Authors: Tittes Silas , Kane Nolan C. 
Published: August 2014

In this issue, Flaxman et al. () report the results of sophisticated whole‐genome simulations of speciation with gene flow, enhancing our understanding of the process by building on previous single‐locus, multilocus and analytical works. Their findings provide us with new insights about how genomes can diverge and the importance of statistical and chromosomal linkage in facilitating reproductive isolation. The authors characterize the conditions under which, even with high gene flow and weak divergent selection, reproductive isolation between populations can occur due to the emergent stochastic process of genomewide congealing, where numerous statistically or physically linked loci of small effect allow selection to limit effective migration rates. The initial congealing event can occur within a broad range conditions, and once initiated, the self‐reinforcing process leads to rapid divergence and ultimately two reproductively isolated populations. Flaxman et al.'s () work is a valuable contribution to our understanding of speciation with gene flow and in making a more predictive field of evolutionary genomics and speciation.
Standing and flowing: the complex origins of adaptive variation
Authors: Welch John J. , Jiggins Chris D. 
Published: August 2014

A population faced with a new selection pressure can only adapt if appropriate genetic variation is available. This genetic variation might come from new mutations or from gene exchange with other populations or species, or it might already segregate in the population as standing genetic variation (which might itself have arisen from either mutation or gene flow). Understanding the relative importance of these sources of adaptive variation is a fundamental issue in evolutionary genetics (Orr & Betancourt ; Barrett & Schluter ; Gladyshev et al. ) and has practical implications for conservation, plant and animal breeding, biological control and infectious disease prevention (e.g. Robertson ; Soulé & Wilcox ; Prentis et al. ; Pennings ). In this issue of Molecular Ecology, Roesti et al. () make an important contribution to this longstanding debate.