bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study
Authors: Downs Jenny , Torode Ian , Wong Kingsley , Ellaway Carolyn , Elliott Elizabeth J , Izatt Maree T , Askin Geoffrey N , Mcphee Bruce I , Cundy Peter , Leonard Helen ,   the Rett syndrome spinal fusion group
Published: December 2015

AimScoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome.MethodData were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population‐based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood.ResultsAfter adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12–0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06–0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16–1.03; p=0.06).InterpretationWith appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.
Prediction of 10‐year vascular risk in patients with diabetes: the AD‐ON risk score
Authors: Woodward M. , Hirakawa Y. , Kengne A.‐P. , Matthews D. R. , Zoungas S. , Patel A. , Poulter N. , Grobbee R. , Cooper M. , Jardine M. , Chalmers J. ,   on behalf of the ADVANCE Collaborative Group
Published: December 2015

AimsTo formulate a combined cardiovascular risk score in diabetes that could be useful both to physicians and healthcare funders.MethodsData were derived from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE‐ON) study, a randomized controlled trial (mean duration 5 years) with a post‐randomization follow‐up (mean 4.9 years), that included 11 140 high‐risk patients with diabetes. The outcome analysed was the occurrence of either fatal or non‐fatal macrovascular or renal disease. A Cox regression model was used to determine weightings in the risk score. The resultant score was recalibrated to each of three major global regions, as covered by the ADVANCE‐ON study.ResultsOver a median of 9.9 years, 1145 patients experienced at least one component of the combined outcome event. The resultant score, the AD‐ON risk score, incorporated 13 demographic or clinical variables. Its discrimination was modest [c‐statistic = 0.668 (95% confidence interval 0.651, 0.685)] but its calibration was excellent (predicted and observed risks coincided well, within disparate global regions). In terms of the integrated discrimination improvement index, its performance was marginally superior, over a 10‐year risk horizon, to existing risk scores in clinical use, from a restricted version of the same data, for macrovascular and renal disease separately.ConclusionsThe AD‐ON risk score has advantages over the existing vascular risk scores in diabetes that used data from the original ADVANCE trial, which treat macrovascular and renal diseases separately. These advantages include its simplicity of use and global application.
A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells
Authors: Saini C. , Petrenko V. , Pulimeno P. , Giovannoni L. , Berney T. , Hebrok M. , Howald C. , Dermitzakis E. T. , Dibner C. 
Published: December 2015

AimTo determine the impact of a functional human islet clock on insulin secretion and gene transcription.MethodsEfficient circadian clock disruption was achieved in human pancreatic islet cells by small interfering RNA‐mediated knockdown of CLOCK. Human islet secretory function was assessed in the presence or absence of a functional circadian clock by stimulated insulin secretion assays, and by continuous around‐the‐clock monitoring of basal insulin secretion. Large‐scale transcription analysis was accomplished by RNA sequencing, followed by quantitative RT‐PCR analysis of selected targets.ResultsCircadian clock disruption resulted in a significant decrease in both acute and chronic glucose‐stimulated insulin secretion. Moreover, basal insulin secretion by human islet cells synchronized in vitro exhibited a circadian pattern, which was perturbed upon clock disruption. RNA sequencing analysis suggested alterations in 352 transcript levels upon circadian clock disruption. Among them, key regulators of the insulin secretion pathway (GNAQ, ATP1A1, ATP5G2, KCNJ11) and transcripts required for granule maturation and release (VAMP3, STX6, SLC30A8) were affected.ConclusionsUsing our newly developed experimental approach for efficient clock disruption in human pancreatic islet cells, we show for the first time that a functional β‐cell clock is required for proper basal and stimulated insulin secretion. Moreover, clock disruption has a profound impact on the human islet transcriptome, in particular, on the genes involved in insulin secretion.
Loss of c‐Kit and bone marrow failure upon conditional removal of the GATA‐2 C‐terminal zinc finger domain in adult mice
Authors: Li Haiyan S. , Jin Jin , Liang Xiaoxuan , Matatall Katie A. , Ma Ying , Zhang Huiyuan , Ullrich Stephen E. , King Katherine Y. , Sun Shao‐Cong , Watowich Stephanie S. 
Published: December 2015

AbstractHeterozygous mutations in the transcriptional regulator GATA‐2 associate with multilineage immunodeficiency, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The majority of these mutations localize in the zinc finger (ZnF) domains, which mediate GATA‐2 DNA binding. Deregulated hematopoiesis with GATA‐2 mutation frequently develops in adulthood, yet GATA‐2 function in the bone marrow remains unresolved. To investigate this, we conditionally deleted the GATA‐2 C‐terminal ZnF (C‐ZnF) coding sequences in adult mice. Upon Gata2 C‐ZnF deletion, we observed rapid peripheral cytopenia, bone marrow failure, and decreased c‐Kit expression on hematopoietic progenitors. Transplant studies indicated GATA‐2 has a cell‐autonomous role in bone marrow hematopoiesis. Moreover, myeloid lineage populations were particularly sensitive to Gata2 hemizygosity, while molecular assays indicated GATA‐2 regulates c‐Kit expression in multilineage progenitor cells. Enforced c‐Kit expression in Gata2 C‐ZnF‐deficient hematopoietic progenitors enhanced myeloid colony activity, suggesting GATA‐2 sustains myelopoiesis via a cell intrinsic role involving maintenance of c‐Kit expression. Our results provide insight into mechanisms regulating hematopoiesis in bone marrow and may contribute to a better understanding of immunodeficiency and bone marrow failure associated with GATA‐2 mutation.
Retinal lesions induce fast intrinsic cortical plasticity in adult mouse visual system
Authors: Smolders Katrien , Vreysen Samme , Laramée Marie‐Eve , Cuyvers Annemie , Hu Tjing‐Tjing , Van Brussel Leen , Eysel Ulf T. , Nys Julie , Arckens Lutgarde 
Published: December 2015

AbstractNeuronal activity plays an important role in the development and structural–functional maintenance of the brain as well as in its life‐long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post‐lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, agranular and granular retrosplenial cortex showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this was faster in higher order visual areas than in V1. The lesion did, however, induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy‐based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 vs. lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region‐ and cell‐type‐specific contributions to functional recovery, up to microcircuit level.
Dopamine increases NMDA‐stimulated calcium flux in striatopallidal neurons through a matrix metalloproteinase‐dependent mechanism
Authors: Li Yan , Partridge John , Berger Carissa , Sepulveda‐Rodriguez Alberto , Vicini Stefano , Conant Katherine 
Published: December 2015

AbstractDopamine (DA) is a potent neuromodulator known to influence glutamatergic transmission in striatal medium spiny neurons (MSNs). It acts on D1‐ and D2‐like DA receptors that are expressed on two distinct subpopulations. MSNs projecting to the substantia nigra express D1 receptors (D1Rs), while those projecting to the lateral globus pallidus express D2 receptors (D2Rs). D1R signalling in particular can increase excitatory transmission through varied protein kinase A‐dependent, cell‐autonomous pathways. Mechanisms by which D1R signalling could increase excitatory transmission in D2R‐bearing MSNs have been relatively less explored. Herein, the possibility is considered that D1R agonists increase levels of soluble factors that subsequently influence N‐methyl‐d‐aspartate (NMDA)‐stimulated calcium flux in D2R neurons. This study focuses on matrix metalloproteinases (MMPs) and MMP‐generated integrin binding ligands, important soluble effectors of glutamatergic transmission that may be elevated in the setting of excess DA. It was observed that DA and a D1R agonist, SKF81297, increase MMP activity in extracts from striatal slices, as determined by cleavage of the substrate β‐dystroglycan. Using mice engineered to express the calcium indicator GCaMP3 in striatopallidal D2R‐bearing neurons, it was also observed that SKF81297 pretreatment of slices (60 min) potentiates NMDA‐stimulated calcium increases in this subpopulation. Effects are diminished by pretreatment with an antagonist of MMP activity or an inhibitor of integrin‐dependent signalling. Together, results suggest that DA signalling can increase excitatory transmission in D2R neurons through an MMP‐dependent mechanism. Future studies may be warranted to determine whether D1R‐stimulated MMP‐dependent processes contribute to behaviours in which increased activity in striatopallidal MSNs plays a role.
Delivery and evaluation of recombinant adeno‐associated viral vectors in the equine distal extremity for the treatment of laminitis
Authors: Mason J. B. , Gurda B. L. , Van Wettere A. , Engiles J. B. , Wilson J. M. , Richardson D. W. 
Published: December 2015

SummaryReasons for performing studyOur long‐term aim is to develop a gene therapy approach for the prevention of laminitis in the contralateral foot of horses with major musculoskeletal injuries and non‐weightbearing lameness.ObjectivesThe goal of this study was to develop a practical method to efficiently deliver therapeutic proteins deep within the equine foot.Study designRandomised in vivo experiment.MethodsWe used recombinant adeno‐associated viral vectors (rAAVs) to deliver marker genes using regional limb perfusion through the palmar digital artery of the horse.ResultsVector serotypes rAAV2/1, 2/8 and 2/9 all successfully transduced equine foot tissues and displayed similar levels and patterns of transduction. The regional distribution of transduction within the foot decreased with decreasing vector dose. The highest transduction values were seen in the sole and coronary regions and the lowest transduction values were detected in the dorsal hoof‐wall region. The use of a surfactant‐enriched vector diluent increased regional distribution of the vector and improved the transduction in the hoof‐wall region. The hoof‐wall region of the foot, which exhibited the lowest levels of transduction using saline as the vector diluent, displayed a dramatic increase in transduction when surfactant was included in the vector diluent (9‐ to 81‐fold increase). In transduced tissues, no significant difference was observed between promoters (chicken β‐actin vs. cytomegalovirus) for gene expression. All horses tested for vector‐neutralising antibodies were positive for serotype‐specific neutralising antibodies to rAAV2/5.ConclusionsThe current experiments demonstrate that transgenes can be successfully delivered to the equine distal extremity using rAAV vectors and that serotypes 2/8, 2/9 and 2/1 can successfully transduce tissues of the equine foot. When the vector was diluted with surfactant‐containing saline, the level of transduction increased dramatically. The increased level of transduction due to the addition of surfactant also improved the distribution pattern of transduction.
Use of taxonomy to delineate spatial extent of atlas data for species distribution models
Authors: Niamir Aidin , Skidmore Andrew K. , Toxopeus Albertus G. , Real Raimundo 
Published: December 2015

AbstractAimThe use of atlas data in combination with a variety of modelling approaches has become a common practice in species distribution studies. The spatial extent over which species distribution models (SDMs) should be fitted (i.e. the spatial extent) is often arbitrary and coincides with the extent of the atlases. In order to develop reliable SDMs using species atlas data, we propose an approach that incorporates the taxonomy of species and therefore delineates the spatial extent for SDMs.LocationMainland Spain.MethodsWe used atlas data to generate taxonomically delineated datasets for 365 terrestrial species. The presence records in the datasets were identical to those in the atlas, while the absence records were delimited to the presence of at least one species in the same family or order. We also generated two randomly delineated datasets that were the same size as the taxonomically delineated datasets. We assessed the predictive performance of the SDMs specifically by studying the model calibration (Miller's statistic) and discrimination capacity (area under the curve of the receiver operating characteristic plot), along with the geographical similarity pattern of the predicted maps.ResultsThe models that were trained using the taxonomically delineated datasets produced significantly improved models in terms of calibration, while their discrimination capacity was no greater than that of the models trained using the atlas dataset. The improvements to the calibration of the taxonomically delineated datasets were significantly greater than those with random absence sets.Main conclusionDelineating the spatial extent using taxonomical information leads to a significant improvement in the model performance of SDMs. This restriction can reduce the effect of environmental events beyond the species history during model parameterization, thus allowing the models obtained to more precisely depict the potential distribution of the species. We therefore recommend considering the delineation of spatial extent using species taxonomy when atlas data are employed in SDMs.
Recovery of renal function after radical nephrectomy and risk factors for postoperative severe renal impairment: A Japanese multicenter longitudinal study
Authors: Kawamura Naoko , Yokoyama Minato , Fujii Yasuhisa , Ishioka Junichiro , Numao Noboru , Matsuoka Yoh , Saito Kazutaka , Arisawa Chizuru , Okuno Tetsuo , Noro Akira , Morimoto Shinji , Kihara Kazunori 
Published: December 2015

ObjectivesTo investigate longitudinal changes in renal function after radical nephrectomy, and to explore risk factors of postoperative severe renal impairment in a Japanese multicenter cohort.MethodsThe present retrospective study included 701 patients who had no metastasis, end‐stage kidney disease or bilateral kidney cancer, who underwent radical nephrectomy and who were followed up for at least 1 year. The longitudinal change in postoperative renal function during a 10‐year follow‐up period was evaluated according to the presence or absence of potential risk factors including greater age, chronic kidney disease, hypertension, diabetes mellitus and cardiovascular disease. A slope of annual change in estimated glomerular filtration rate was analyzed using a linear mixed model. Associations between the potential risk factors and a >50% estimated glomerular filtration rate decrease were evaluated using a multivariate Cox regression model.ResultsOverall, the postoperative estimated glomerular filtration rate recovered over time with a significant positive slope of 0.34 mL/min/1.73 m2/year. Renal function did not tend to recover in patients with chronic kidney disease, hypertension, diabetes mellitus or cardiovascular disease. The multivariate analysis showed that greater age and diabetes mellitus were independent risk factors for severe renal impairment.ConclusionsOverall, patients who had deteriorated renal function immediately after radical nephrectomy recovered over time. However, patients with chronic kidney disease, hypertension, diabetes mellitus and cardiovascular disease did not tend to recover renal function postoperatively. Greater age and diabetes mellitus were independent risk factors for a >50% decrease in estimated glomerular filtration rate.
Fiscal Consolidation Policies in the Context of Italy's Two Recessions
Authors: Figari Francesco , Fiorio Carlo V. 
Published: December 2015

AbstractItaly experienced a double‐dip Great Recession: after the start of the global financial crisis, Italy had a second serious recession in 2011 as a result of the sovereign debt crisis. The reaction of Italian governments was minimal at the beginning but more serious action has been taken to address Italy's fiscal problems since the start of the sovereign debt crisis in 2011. The policies adopted have helped to move the public finances to a more sustainable position, but household real incomes decreased by 13 per cent, with this reduction being quite unevenly felt across the household income distribution. The medium‐term outlook is still uncertain: a great deal depends on the capacity of the Italian economy to reduce the level of public debt and to return to sustained economic growth, which has been very weak for more than a decade.
The Moral Case for Intelligent Speed Adaptation
Authors: Smids Jilles 
Published: December 2015

AbstractSpeeding is a major problem in road safety. Intelligent Speed Adaptation (ISA) is a potential solution, but the moral acceptability of ISA has been called into question both in the popular media and in academic discussions. In this article, a moral case is made for making warning and limiting versions of ISA obligatory in all cars. The practice of car driving involves frequent speeding, which imposes unacceptable risks of harm on other road users. In this article, I argue that ISA can therefore be justified on the basis of the harm it prevents, as is the current criminalisation of speeding. I defend obligatory ISA against three objections. First, ISA is likely to introduce some additional risk for drivers. However, drivers should accept these risks to reduce the risks from driving for other parties to an acceptable level. Second, although limiting ISA reduces drivers' options for moral agency and exercising self‐restraint to some extent, this consequence is defensible. Third, accepting ISA does not commit us to accepting an entire range of other behaviour‐regulating technologies.
The influence of geological movements on the population differentiation of Biston panterinaria (Lepidoptera: Geometridae)
Authors: Cheng Rui , Jiang Nan , Yang Xiushuai , Xue Dayong , Liu Shuxian , Han Hongxiang 
Published: December 2015

AbstractAimEast Asia is known for its exceptionally high levels of biodiversity, which is connected to its high level of species differentiation. Geological movements are the most important factor promoting the species differentiation in East Asia. In this paper, we choose Biston panterinaria, a moth species widely distributed in East Asia, to study the relative contributions of geographical isolation and glaciation cycles to its current genetic constitution.LocationEast Asia.MethodsPhylogenetic analyses were based on three data sets. beast was used to estimate the divergence time and reconstruct the maximum clade credibility tree. Mismatch distribution and Bayesian skyline plots (BSP) were used to infer historical population fluctuations. maxent was used to predict the potential species distributions during two periods: the present day and the Last Glacial Maximum (LGM).ResultsThe phylogenetic tree and the median joining network strongly supported four reciprocally monophyletic lineages: northern, Yunnan‐Tibet, southern and Yunnan‐SE. The estimates of divergence time suggested that three differentiation processes occurred at approximately 1.17, 0.76 and 0.67 Ma. Within the northern and southern lineages, lineage divergence occurred at approximately 0.17 and 0.16 Ma. Mismatch distribution and BSP suggested that the northern and southern lineages experienced one expansion after the LGM, and this result was consistent with the result of the ecological niche model.Main conclusionsOur results suggested that B. panterinaria experienced three fragmentations of wide‐ranging ancestral populations, and that mountain barrier isolation induced by geological movements is the main driver of lineage differentiation. Climatic oscillations during the Pleistocene affected the population differentiation within both the northern and southern lineages. The distribution of the four lineages of B. panterinaria is generally consistent with the zoogeographical regionalization of China. This study provides direct evidence for the importance of mountain barriers in promoting population differentiation.
Long‐term epidemiological survey of Kudoa thyrsites (Myxozoa) in Atlantic salmon (Salmo salar L.) from commercial aquaculture farms
Authors: Marshall W L , Sitjà‐Bobadilla A , Brown H M , MacWilliam T , Richmond Z , Lamson H , Morrison D B , Afonso L O B 
Published: December 2015

AbstractKudoa thyrsites (Myxozoa) encysts within myocytes of a variety of fishes. While infected fish appear unharmed, parasite‐derived enzymes degrade the flesh post‐mortem. In regions of British Columbia (BC), Canada, up to 4–7% of fillets can be affected, thus having economic consequences and impacting the competitiveness of BC's farms. K. thyrsites was monitored in two farms having high (HP) or low (LP) historical infection prevalence. At each farm, 30 fish were sampled monthly for blood and muscle during the first year followed by nine samplings during year two. Prevalence and intensity were measured by PCR and histology of muscle samples. In parallel, fillet tests were used to quantify myoliquefaction. Infections were detected by PCR after 355 and 509 degree days at LP and HP farms, respectively. Prevalence reached 100% at the HP farm by 2265 degree days and declined during the second year, whereas it plateaued near 50% at the LP farm. Infection intensities decreased after 1 year at both farms. Blood was PCR‐positive at both farms between 778 and 1113 degree days and again after 2000 degree days. This is the first monitoring project in a production environment and compares data between farms with different prevalence.