bluuebunny/crossref_metadata_2025_split huggingface dataset:
Women's access to abortion after 20 weeks' gestation for fetal chromosomal abnormalities: Views and experiences of doctors in New South Wales and Queensland
Authors: Black Kirsten I. , Douglas Heather , de Costa Caroline 
Published: April 2015

BackgroundInduced abortions after 20 weeks' gestation comprise around one per cent of all terminations in Australia and mostly occur following the diagnosis of a fetal anomaly. However, these abortions are overly represented in legal cases against doctors and challenging to organise in those states where abortion remains in the criminal code and health department directives impose regulations. This study explores barriers to abortion access after 20 weeks' gestation in the states of Queensland and New South Wales.Materials and MethodsWe approached and sought consent from 22 doctors involved in abortion provision (15 in Queensland and seven in NSW), who responded in depth to a set of clinical scenarios. This study presents participants' responses to three clinical scenarios of women presenting with a fetal chromosomal abnormality after 20 weeks' gestation.ResultsOf the 22 medical practitioners in this study, 18 reported that access to late‐term abortion in their state was restricted. The two key factors perceived to affect the decision to terminate a pregnancy in this context were the legal status of abortion and Department of Health policies mandating that applications for abortion be presented to clinical ethics committees. Practitioners reported that committees were slow to convene and inconsistent in their decisions.ConclusionsEthics committee involvement for late‐term abortions is required by state health policy in NSW and Queensland, where abortion is still a criminal offence. This process is seen by abortion providers to hinder timely access to services and excludes women from the decision‐making process.
Mutual upregulation of endothelin‐1 and IL‐25 in atopic dermatitis
Authors: Aktar M. K. , Kido‐Nakahara M. , Furue M. , Nakahara T. 
Published: April 2015

AbstractBackgroundEndothelin‐1 (ET‐1) has been reported to evoke histamine‐independent pruritus in mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET‐1 in the skin inflammation of AD.MethodsTo examine the role of ET‐1 in AD, we investigated the expression of ET‐1 and IL‐25 in the skin of an AD mouse model and patients with AD and examined the mutual regulatory relationship between ET‐1 and IL‐25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line.ResultsWe immunohistochemically confirmed the upregulation of ET‐1 and IL‐25 expression in the epidermis of both the AD mouse model and patients with AD. In vitro, IL‐25 upregulated ET‐1 mRNA and protein expression in a concentration‐ and time‐dependent fashion in HaCaT cells. This IL‐25‐induced ET‐1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET‐1 also induced IL‐25 upregulation. The enhancing effect of ET‐1 on IL‐25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor.ConclusionThese findings suggest that mutual upregulation of ET‐1 and IL‐25 takes place in the epidermis of AD, which may be a future target for antipruritic agents.
The impact of salt on the late Messinian to recent tectonostratigraphic evolution of the Cyprus subduction zone
Authors: Reiche Sönke , Hübscher Christian , Ehrhardt Axel 
Published: April 2015

AbstractMessinian evaporites of locally more than 3‐km thickness occupy the subduction zone between Cyprus and Eratosthenes Seamount. Based on a dense grid of seismic reflection profiles, we report on compressional salt tectonics and its impact on the Late Miocene to Quaternary structural evolution of the Cyprus subduction zone. Results show that evaporites have experienced significant post‐Messinian shortening along the plate boundary. Shortening has initiated allochthonous salt advance between Cyprus and Eratosthenes Seamount, representing an excellent example of salt which efficiently escapes subduction and accretion. Further east, between Eratosthenes Seamount and the Hecataeus Rise, evaporites were compressionally inflated without having advanced across post‐Messinian strata. Such differences in the magnitude of salt tectonic shortening may reflect a predominately north–south oriented post‐Messinian convergence direction, raising the possibility of a later coupling between the motion of Cyprus and Anatolia than previously thought. Along the area bordered by Cyprus and Eratosthenes Seamount a prominent step in the seafloor represents the northern boundary of a controversially debated semi‐circular depression. Coinciding with the southern edge of the salt sheet, this bathymetric feature is suggested to have formed as a consequence of compressional salt inflation and seamount‐directed salt advance. Topographic lows on top of highly deformed evaporites are locally filled by up to 700 m of late Messinian sediments. The uppermost 200 m of these sediments were drilled in the course of ODP Leg 160 and interpreted to represent Lago Mare‐type deposits (Robertson, Tectonophysics, 1998d, 298, 63‐82). Lago Mare deposits are spatially restricted to the western part of the subduction zone, pinching out towards the east whereas presumably continuing into the Herodotus Basin further west. We suggest a sea level control on late Messinian Lago Mare sedimentation, facilitating sediment delivery into basinal areas whereas inhibiting Lago Mare deposition into the desiccated Levant Basin. Locally, early salt deformation is believed to have provided additional accommodation space for Lago Mare sedimentation, resulting in the presently observed minibasin‐like geometry.
Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy
Authors: Prickett S. R. , Rolland J. M. , O'Hehir R. E. 
Published: April 2015

SummaryAllergen immunotherapy (AIT) has been practised since 1911 and remains the only therapy proven to modify the natural history of allergic diseases. Although efficacious in carefully selected individuals, the currently licensed whole allergen extracts retain the risk of IgE‐mediated adverse events, including anaphylaxis and occasionally death. This together with the need for prolonged treatment regimens results in poor patient adherence. The central role of the T cell in orchestrating the immune response to allergen informs the choice of T cell targeted therapies for down‐regulation of aberrant allergic responses. Carefully mapped short synthetic peptides that contain the dominant T cell epitopes of major allergens and bind to a diverse array of HLA class II alleles, can be delivered intradermally into non‐inflamed skin to induce sustained clinical and immunological tolerance. The short peptides from allergenic proteins are unable to cross‐link IgE and possess minimal inflammatory potential. Systematic progress has been made from in vitro human models of allergen T cell epitope‐based peptide anergy in the early 1990s, through proof‐of‐concept murine allergy models and early human trials with longer peptides, to the current randomized, double‐blind, placebo‐controlled clinical trials with the potential new class of synthetic short immune‐regulatory T cell epitope peptide therapies. Sustained efficacy with few adverse events is being reported for cat, house dust mite and grass pollen allergy after only a short course of treatment. Underlying immunological mechanisms remain to be fully delineated but anergy, deletion, immune deviation and Treg induction all seem contributory to successful outcomes, with changes in IgG4 apparently less important compared to conventional AIT. T cell epitope peptide therapy is promising a safe and effective new class of specific treatment for allergy, enabling wider application even for more severe allergic diseases.
Prophylactic immunization of mice with phospholipase A2‐loaded gas‐filled microbubbles is protective against Th2‐mediated honeybee venom allergy
Authors: Bioley G. , Lassus A. , Terrettaz J. , Tranquart F. , Corthésy B. 
Published: April 2015

SummaryBackgroundPeople suffering from honeybee venom allergy can be treated by venom immunotherapy, which consists in the subcutaneous injection of increasing doses of allergen extracts over a period of 3–5 years. Such a procedure is time‐consuming, and the risks of severe side reactions are important. Approaches based on the use of novel adjuvants to blunt pro‐allergic Th2‐type immune responses represent a sound alternative.ObjectivesIn this study, we evaluated in a mouse model of honeybee venom allergy the protection induced by the prophylactic use of the major allergen phospholipase A2 (PLA2) associated with microbubbles (MB).MethodsAntibody (Ab) and T cell responses, as detected by ELISA and CFSE‐based proliferation assays, were first examined after prophylactic immunization of CBA/J mice with PLA2‐MB, and second after sensitization with native PLA2. Mice were eventually challenged with a lethal dose of PLA2 to assess protection against anaphylaxis.ResultsProphylactic immunization with PLA2‐MB induced PLA2‐specific IgG and IgA Ab, triggered the production of IFN‐γ and IL‐10 and the differentiation of PLA2‐specific Foxp3+ Treg. Immunized/sensitized mice displayed the following: (1) increased titres of potent blocking IgG1, IgG2a and IgG3 Ab, (2) both reduced allergen‐specific T cell proliferation and Th2‐type cytokine production and (3) elevated frequencies of specific Foxp3+ Treg and increased production of TGF‐β, as compared to naïve/sensitized animals. Immunomodulation correlated with reduced signs of anaphylaxis after allergen challenge.Conclusions and Clinical RelevanceOur data demonstrate the ability of PLA2‐MB to prophylactically protect mice against subsequent sensitization and death‐inducing PLA2 challenge for up to 4 months, revealing so far unravelled immunomodulatory properties of MB. These data, combined with the safe use of MB as contrast agents for in situ imaging in humans, render them an immunotherapeutic agent of great interest for further evaluation.
Objective eliciting doses of peanut‐allergic adults and children can be combined for risk assessment purposes
Authors: Klemans R. J. B. , Blom W. M. , van Erp F. C. , Masthoff L. J. N. , Rubingh C. M. , van der Ent C. K. , Bruijnzeel‐Koomen C. A. F. M. , Houben G. F. , Pasmans S. G. M. A. , Meijer Y. , Knulst A. C. 
Published: April 2015

SummaryBackgroundTo improve food labelling strategies, information regarding eliciting doses (EDs) and the effect of patient characteristics on these EDs is necessary.ObjectiveTo establish EDs for objective and subjective symptoms and analyse the effect of sensitization levels and other patient characteristics on threshold distribution curves (TDCs).MethodsThreshold data from 100 adults and 262 children with a positive food challenge were analysed with interval‐censoring survival analysis (ICSA) and fitted to a TDC from which EDs could be extracted. Possible influencing factors were analysed as covariates by ICSA. A hazard ratio (HR) was calculated in case of a significant effect.ResultsTDCs for both objective and subjective symptoms were significantly different between adults and children (P < 0.001). Objective ED05 values, however, were comparable (2.86 mg peanut protein in adults and 6.38 mg in children). Higher levels of sIgE to Ara h 2 and peanut extract were associated with a larger proportion of patient groups reacting to a dose increase with objective symptoms (adults and children) or subjective symptoms (adults, in children a trend). Age had a similar effect in children (HR 1.05 for objective symptoms and 1.09 for subjective symptoms). Gender had no effect on TDCs.Conclusion and Clinical RelevanceSubjective and objective TDCs were different between adults and children, but objective ED05 values were comparable, meaning that threshold data from children and adults can be combined for elaboration of reference doses for risk assessment. Higher sIgE levels to Ara h 2 and peanut extract were associated with a larger proportion of both patient groups to react to a certain dose increase.
Phenotype and molecular characteristics in 45 Chinese children with 5α‐reductase type 2 deficiency from South China
Authors: Cheng Jing , Lin Ruizhu , Zhang Wen , Liu Guochang , Sheng Huiying , Li Xiuzhen , Zhou Zhihong , Mao Xiaojian , Liu Li 
Published: April 2015

SummaryContextAffected by steroid 5α‐reductase type 2 deficiency (5α‐RD2), 46, XY individuals present divergent phenotypes characterized by undervirilization of male external genitalia. To identify the disorder, mutational analysis of 5α‐reductase type 2 gene (SRD5A2) is a reliable approach. The genotype–phenotype relationship has not been elucidated.ObjectiveTo improve the diagnosis and expand the knowledge of the disease, we collected and analysed relevant data of clinical diagnosis, biological investigation and molecular determination in 45 children with the SRD5A2 gene mutations from South China in our centre.Subjects and methodsWe studied a cohort of 45 Chinese children with SRD5A2 gene mutations.ResultsIsolated microphallus (35·6%) and microphallus associated with various degrees of hypospadias (55·6%) were frequent phenotype. Female external genitalia with clitoromegaly (8·9%) were rare. 16 of 18 (88·9%) cases had hCG‐stimulated T/DHT ratio above 10. In 45 patients, we identified 15 different mutations. Five have never been described: p.His90ThrfsX31, p.Gly21Arg, p.Gly149Asp, p.Arg145Leu and p.Gly66Arg. The p.Arg227Gln mutation was detected in 41 (91·1%) patients. The p.Leu89Val polymorphism was found in 38 (84·4%) patients. Homozygous mutations were presented in 16 (35·6%) patients, compound heterozygous mutations in 20 (44·4%) patients, compound heterozygous mutations alone with the p.Leu89Val polymorphism in nine (20·0%) patients. Exons 1 and 4 were most affected, and the number of mutant alleles per exon was 78·1% and 12·2%, respectively.ConclusionsThe study demonstrated a wide spectrum of phenotypes, biological profiles and genotypes in the children with 5α‐RD2 from South China. The heterozygous mutation p.Arg227Gln is presumably a hot spot mutation and suggests a founder effect in the population of South China that may explain a moderate phenotype among our patients. Our report provides new insights into the molecular mechanism of 5α‐RD2 and help to the diagnosis and treatment of this disease.
Epicentral Disruption of Structural Connectivity in Alzheimer's Disease
Authors: Mallio Carlo Augusto , Schmidt Ruben , de Reus Marcel A. , Vernieri Fabrizio , Quintiliani Livia , Curcio Giuseppe , Beomonte Zobel Bruno , Quattrocchi Carlo Cosimo , van den Heuvel Martijn P. 
Published: April 2015

SummaryAimsNeurodegenerative changes observed in Alzheimer's disease (AD) have been suggested to begin at the entorhinal cortex and hippocampus and then to propagate in a stereotypical fashion. Using diffusion‐weighted imaging, we test whether disruption of structural connectivity in AD is centered on these “epicenters of disease”.MethodsFifteen healthy controls, 14 amnestic mild cognitive impairment (aMCI), 13 mild, and 15 moderate patients with AD were enrolled. The percentages of affected connections directly linking to the epicenter (named first ring) and to nodes with topological distance 2 from the epicenter (named second ring) were calculated.ResultsFor the group of aMCI patients, just 5.3% of the first ring (n.s.) and 2.9% of the second ring (n.s.) connections were affected. However, for mild AD there was disruption involving 20% of the first ring (P < 0.0001) and 10.3% of the second ring (P < 0.0001) connections. In the moderate AD group, a stronger effect was observed, with 38.0% of the first ring (P < 0.0001) connections and 17.9% of the second ring (P < 0.0001) connections affected.ConclusionOur results favor an epicentral disruption of structural connectivity in aMCI and AD around entorhinal and hippocampal regions, consistent with the transneuronal spread hypothesis.
Stem cell factor is essential for preserving NOD/SCID reconstitution capacity of ex vivo expanded cord blood CD34+ cells
Authors: Du Zheng , Wang Ziyan , Zhang Weiwei , Cai Haibo , Tan Wen‐Song 
Published: April 2015

AbstractObjectivesStem cell factor (SCF) is essential in the haematopoietic stem cells (HSCs) niche, and is therefore used extensively in haematopoietic stem and progenitor cells (HSPCs) ex vivo expansion. However, in the literature, dose and schedule of SCF feeding varies widely. We previously proposed a novel SCF feeding regimen with proven effectiveness for HSPCs expansion; however, physiological function of expanded cells with this SCF feeding regimen required further research.Materials and methodsCD34+ cells were cultured with or without SCF supplementation in serum‐free medium for 10 days. Expanded cells were transplanted into sublethally irradiated non‐obese diabetic/severe combined immune‐deficient (NOD/SCID) mice. Engraftment and multilineage reconstitution of transplanted cells were determined. Also, clonogenic potential of engrafted cells was analysed.ResultsCells, both cultured with and without SCF supplementation, successfully engrafted and reconstituted blood cell lineages in NOD/SCID mice. However, level of engraftment and multilineage reconstitution reduced when cells were expanded without SCF supplementation. Meanwhile, frequencies of colony‐forming cells (CFCs) amongst bone marrow cells were higher in mice transplanted with CD34+ cells expanded with SCF supplementation.ConclusionsReconstitution capacity reduced when CD34+ cells were expanded without SCF supplementation, though this feeding regimen did not have any effect on cell expansion. This finding suggested that SCF was essential for preserving NOD/SCID reconstitution capacity of ex vivo expanded CD34+ cells.
Species‐specific effects of subdaily temperature fluctuations on consumption, growth and stress responses in two physiologically similar fish species
Authors: Coulter David P. , Sepúlveda Maria S. , Troy Cary D. , Höök Tomas O. 
Published: April 2015

AbstractFluctuations in water temperature can have important physiological consequences for fishes. Effects of daily thermal cycles are well studied and can be beneficial, increasing prey consumption and growth rates when mean and maximum temperatures of the fluctuations are at or below the species’ optimum temperature. While less studied, subdaily temperature fluctuations are also common in many aquatic habitats and can be caused by both natural and anthropogenic processes. We performed laboratory experiments to examine how two fish species (yellow perch, Perca flavescens, and walleye, Sander vitreus) with similar thermal preferences respond to chronic exposure to subdaily temperature variability. We selected temperature treatments that reflected observed thermal variation after examining water temperature data from multiple aquatic systems. We then separately exposed yellow perch and walleye to a stable 23 °C treatment and 12‐h cycles of 23 ± 2 °C or 23 ± 4 °C for 45 days. Adult yellow perch exposed to fluctuations of 23 ± 4 °C over 12 h expressed higher consumption, growth and food conversion efficiency than fish experiencing stable 23 °C. Temperature fluctuations, though, resulted in mortalities and the development of skin ulcers in yellow perch that did not occur under stable temperatures. In contrast, the same 12‐h temperature fluctuations did not result in mortalities or stress responses in juvenile walleye. Moreover, unlike yellow perch, growth rates of walleye were lower under 12‐h temperature fluctuations compared with the stable 23 °C treatment. Our results indicate that species with similar thermal preferences can respond differently to the same subdaily temperature fluctuations.
Long‐term stability of eelgrass fish assemblages in two highly developed coastal estuaries
Authors: Obaza A. , Hoffman R. , Clausing R. 
Published: April 2015

AbstractChanges in fish assemblages were tracked in representative eelgrass (Zostera marina L.) beds within two estuaries on the urbanised coast of southern California, USA, San Diego Bay and Mission Bay, from 1987 to 2010. Assemblages were sampled twice yearly (spring and summer) at day and night using beach seines. Assemblage stability was examined over time along with changes in assemblage structure across time of day and season, including the influence of temporally variable abiotic variables. Only the occasionally occurring fish, those present in <70% of samples, in Mission Bay appeared to be shifting to a new assemblage. Although season and sampling time significantly affected assemblages, correlations with abiotic factors were low. Given the long history of urban development of these estuaries, community shifts may have occurred prior to the onset of sampling, giving the appearance of stability. Alternatively, eelgrass habitat may be providing a refuge from long‐term disturbances.
Delineating closely related species with DNA barcodes for routine biological monitoring
Authors: Carew Melissa E. , Hoffmann Ary A. 
Published: April 2015

Summary

DNA barcoding has proven useful for identifying species, and there is increasing interest in this approach to determine species compositions for routine biological monitoring. Generally, DNA barcodes applied to taxa used for monitoring are clearly linked to species, but where taxa are closely related separation using DNA barcodes can be ambiguous. This raises challenges for monitoring, especially if closely related taxa are not recognised as separate species and these species have different environmental responses.

Here we examine whether separation of closely related taxa with DNA barcodes is supported by other gene sequences and whether morphological and environmental differences occur among related species that cannot be easily separated. We selected six Chironomidae genera where initial neighbour‐joining analysis of DNA barcodes produced monophyletic groups supported by high bootstraps (>95%), but groups were separated by low nucleotide divergence of 3–7%. Taxon separation based on DNA barcodes and mitochondrial cytochrome b (CytB) gene sequences were compared to delineations based on nuclear sequences from the carbomoylphosphate synthase‐like gene region 1 (CAD1) and the zinc metalloproteinase (ZMP) gene.

Species delineations with DNA barcodes were not always the same as those defined with nuclear sequences, morphological variation or differences in pollution and salinity tolerance. Morphological differences and some environmental differences were often in agreement with taxon separation based on nuclear CAD1 (and ZMP) sequences rather than DNA barcodes (and CytB variation).

This study suggests that nuclear sequence data when used in combination with DNA barcodes can help separate closely related taxa into groups useful for routine biological monitoring.