bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical presentation and molecular basis of congenital antithrombin deficiency in children: a cohort study
Authors: Kumar Riten , Chan Anthony K. C. , Dawson Jennifer E. , Forman‐Kay Julie D. , Kahr Walter H. A. , Williams Suzan 
Published: March 2014

SummaryIn this study we report the largest descriptive cohort of congenital antithrombin (AT) deficiency in children, its clinical presentation, molecular basis and genotype‐phenotype correlation. Paediatric patients diagnosed with AT deficiency at two tertiary care children's hospitals over a 10‐year period were retrospectively reviewed. SERPINC1 gene sequencing was offered to subjects who did not already have the test performed. Molecular modelling and stability simulations were performed for the novel mutations identified. Twenty‐nine subjects from 18 pedigrees were identified. Mean age (± standard deviation) at diagnosis and mean duration of follow‐up were 8·4 (± 6·6) years and 6·6 (± 5·7) years respectively. Most recent mean AT activity and AT antigen levels (n = 20) were 0·53 (± 0·09) iu/ml and 0·60 (± 0·17) iu/ml respectively. Ten subjects were diagnosed secondary to low AT activity measured following venous thrombo‐embolism (VTE). All 10 subjects had additional risk factors at the time of VTE. None of the 19 subjects diagnosed with AT deficiency in the setting of positive family history have had VTE with 7·4 (± 5·8) years follow‐up. Mutation analysis has been completed on 19 subjects from 16 pedigrees. Nine unique mutations, including 4 novel mutations were identified.
SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study
Authors: Nordström Lena , Sernbo Sandra , Eden Patrik , Grønbæk Kirsten , Kolstad Arne , Räty Riikka , Karjalainen Marja‐Liisa , Geisler Christian , Ralfkiær Elisabeth , Sundström Christer , Laurell Anna , Delabie Jan , Ehinger Mats , Jerkeman Mats , Ek Sara 
Published: March 2014

SummaryMantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the NordicMCL2/3 protocols. In 2008, aMCLinternational prognostic index (MIPI) was created to enable stratification of the clinical diverseMCLpatients into three risk groups. So far, use of theMIPIin clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment‐related morbidity, additional parameters need to be evaluated to enable risk‐adapted treatment selection. We have investigated the individual prognostic role of theMIPIand molecular markers includingSOX11,TP53 (p53),MKI67 (Ki‐67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining theMIPIwith information on molecular markers.SOX11 was shown to significantly add prognostic information to theMIPI, but in multivariate analysisTP53 was the only significant independent molecular marker. Based on these findings, we propose thatTP53 andSOX11 should routinely be assessed and that a combinedTP53/MIPIscore may be used to guide treatment decisions.
Mitochondrial pharmacology: energy, injury and beyond
Authors: Davidson S M , Lopaschuk G D , Spedding M , Beart P M 
Published: March 2014

While the mitochondrion has long fascinated biologists and the sheer diversity of druggable targets has made it attractive for potential drug development, there has been little success translatable to the clinic. Given the diversity of inborn errors of metabolism and mitochondrial diseases, mitochondrially mediated oxidative stress (myopathies, reperfusion injury, Parkinson's disease, ageing) and the consequences of disturbed energetics (circulatory shock, diabetes, cancer), the potential for meaningful gain with novel drugs targeting mitochondrial mechanisms is huge both in terms of patient quality of life and health care costs. In this themed issue of the British Journal of Pharmacology, we highlight the key directions of the contemporary advances in the field of mitochondrial biology, emerging drug targets and new molecules which are close to clinical application. Authors' contributions are diverse both in terms of species and organs in which the mitochondrially related studies are performed, and from the perspectives of mechanisms under study. Defined roles of mitochondria in disease are updated and previously unknown contributions to disease are described in terms of the interface between basic science and pathological relevance.Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Evaluating Children's Conservation Biology Learning at the Zoo
Authors: JENSEN ERIC 
Published: March 2014

AbstractMillions of children visit zoos every year with parents or schools to encounter wildlife firsthand. Public conservation education is a requirement for membership in professional zoo associations. However, in recent years zoos have been criticized for failing to educate the public on conservation issues and related biological concepts, such as animal adaptation to habitats. I used matched pre‐ and postvisit mixed methods questionnaires to investigate the educational value of zoo visits for children aged 7–15 years. The questionnaires gathered qualitative data from these individuals, including zoo‐related thoughts and an annotated drawing of a habitat. A content analysis of these qualitative data produced the quantitative data reported in this article. I evaluated the relative learning outcomes of educator‐guided and unguided zoo visits at London Zoo, both in terms of learning about conservation biology (measured by annotated drawings) and changing attitudes toward wildlife conservation (measured using thought‐listing data). Forty‐one percent of educator‐guided visits and 34% of unguided visits resulted in conservation biology‐related learning. Negative changes in children's understanding of animals and their habitats were more prevalent in unguided zoo visits. Overall, my results show the potential educational value of visiting zoos for children. However, they also suggest that zoos’ standard unguided interpretive materials are insufficient for achieving the best outcomes for visiting children. These results support a theoretical model of conservation biology learning that frames conservation educators as toolmakers who develop conceptual resources to enhance children's understanding of science.Evaluación del Aprendizaje de Biología de la Conservación por Niños en el Zoológico Jensen
Estimating How Many Undescribed Species Have Gone Extinct
Authors: TEDESCO P. A. , BIGORNE R. , BOGAN A. E. , GIAM X. , JÉZÉQUEL C. , HUGUENY B. 
Published: March 2014

AbstractBecause both descriptions of species and modern human‐driven extinctions started around the same time (i.e., eighteenth century), a logical expectation is that a large proportion of species may have gone extinct without ever having been recorded. Despite this evident and widely recognized assumption, the loss of undescribed species has never been estimated. We quantified this loss for several taxonomic groups and regions for which undescribed species extinctions are likely to have occurred. Across a wide range of taxonomic groups, we applied known extinction rates computed from recorded species losses to assumed exponential decay in the proportion of species remaining undiscovered. Because all previous modeling attempts to project total species richness implicitly assumed that undescribed species extinctions could be neglected, we also evaluated the effect of neglecting them. Finally, because we assumed constant description and extinction probabilities, we applied our model to simulated data that did not conform to this assumption. Actual species losses were severely underestimated by considering only known species extinctions. According to our estimates, the proportion of undiscovered extinct species over all extinctions ranged from 0.15 to 0.59, depending on the taxonomic group and the region considered. This means that recent extinctions may be up to twice as large as the number recorded. When species differed in their extinction or description probabilities, our model underestimated extinctions of undescribed species by up to 20%.Estimación de Cuántas Especies sin Describir Se Han Extinguido
Testing Focus Groups as a Tool for Connecting Indigenous and Local Knowledge on Abundance of Natural resources with Science‐Based Land Management Systems
Authors: Danielsen Finn , Jensen Per M. , Burgess Neil D. , Coronado Indiana , Holt Sune , Poulsen Michael K. , Rueda Ricardo M. , Skielboe Thomas , Enghoff Martin , Hemmingsen Louise H. , Sørensen Marten , Pirhofer‐Walzl Karin 
Published: March 2014

AbstractOne of the clearly stated intentions of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is to bring both “western scientific” and “indigenous and local” knowledge systems within synthetic global, regional, and thematic assessments. A major challenge will be how to use, and quality‐assure, information derived from different knowledge systems. We test how indigenous and local knowledge on natural resources in Miskito and Mayangna communities in Nicaragua, validated through focus groups with community members, compares with information collected on line transects by trained scientists. Both provide comparable data on natural resource abundance, but focus groups are eight times cheaper. Such approaches could increase the amount and geographical scope of information available for assessments at all levels, while simultaneously empowering indigenous and local communities who generally have limited engagement in such processes.
Space matters when defining effective management for invasive plants
Authors: Meier Eliane S. , Dullinger Stefan , Zimmermann Niklaus E. , Baumgartner Daniel , Gattringer Andreas , Hülber Karl 
Published: March 2014

AbstractAimInvasive alien species are a threat to biodiversity and can harm resident plants, animals, humans and infrastructure. To reduce deleterious effects, effective management planning for invasive plants is required. Currently, the effectiveness of management is primarily optimized locally through eradication of individual populations. By contrast, spatial prioritization of control activities at the landscape level has received less attention, despite its potential to improve management planning in complex landscapes, especially under budget constraints.LocationNorth‐eastern Switzerland, Europe.MethodsWe used a dynamic simulation model to evaluate the effectiveness of spatially designed management planning for controlling the expansion of three invasive alien plants (IAPs;Heracleum mantegazzianum, Impatiens glanduliferaandReynoutria japonica) across a heterogeneous landscape in North‐eastern Switzerland. The model predicted the spread ofIAPs from their current distribution under constraints of 361 control options differing in local intensity, frequency, duration, area and spatial prioritization of eradication measures.ResultsOur results demonstrate thatIAP‐control actions under a restricted budget are more effective if control actions are spatially prioritized. Most effective spatial treatments generally prioritized small populations in the case of the annual species and large populations in the case of the perennial species. Further, applying intensive control at early stages generally increased effectiveness of control.Main conclusionsForIAP‐management planning, our findings suggest that control should be applied early whenIAPs start spreading, to maximize success or minimize costs. Further, spatial prioritization schemes are particularly useful under limited financial means forIAP‐management. Finally, our modelling approach may serve as a proof of concept to evaluate the effectiveness of control actions of variousIAPs in complex landscapes.
Modified bowel preparation regimen for use in second‐generation colon capsule endoscopy in patients with ulcerative colitis
Authors: Usui Shingo , Hosoe Naoki , Matsuoka Katsuyoshi , Kobayashi Taku , Nakano Masaru , Naganuma Makoto , Ishibashi Yuka , Kimura Kayoko , Yoneno Kazuaki , Kashiwagi Kazuhiro , Hisamatsu Tadakazu , Inoue Nagamu , Serizawa Hiroshi , Hibi Toshifumi , Ogata Haruhiko , Kanai Takanori 
Published: March 2014

Background and AimWe have reported that second‐generation colon capsule endoscopy (CCE‐2) might be feasible for assessing the severity of mucosal inflammation in ulcerative colitis (UC). However, because of the low rate (69%) of complete evaluation of the colon and owing to inadequate cleansing. We believe that the method of bowel preparation could be improved by reducing volume. In the present study, we attempted to improve the colon‐cleansing regimen in order to optimize the usefulness of CCE‐2 in the management of UC patients.MethodsTwenty patients with histologically confirmed UC were enrolled. Patients took a maximum 2.2 L lavage solution (polyethylene glycol solution and magnesium citrate) in two or three divided doses. To assess the effectiveness of the modified bowel preparation regimen, we evaluated the rate of total colonobservation, the effectiveness of bowel cleansing, andinterobserver agreement in assessing UC disease activity. We used a four‐point grading scale (poor, fair, good, and excellent) for evaluating the quality of bowel cleansing. Matts' endoscopic score was used to evaluate disease activity.ResultsThe rate of total colon observation was 85%, and 15 patients (75%) excreted the CCE‐2 within 8 h. The proportion of excellent plus good cleansing was approximately 60%. There was a substantial interobserver agreement (κ = 0.777) in assessment of overall cleansing, which was still substantial at the fair cleansing level (κ = 0.700).ConclusionUsing CCE‐2, the modified bowel preparation regimen, with reduced volume has the potential to succeed in the evaluation of mucosal severity in UC.
Have infant gross motor abilities changed in 20 years? A re‐evaluation of the Alberta Infant Motor Scale normative values
Authors: Darrah Johanna , Bartlett Doreen , Maguire Thomas O , Avison William R , Lacaze‐Masmonteil Thierry 
Published: March 2014

AimTo compare the original normative data of the Alberta Infant Motor Scale (AIMS) (n=2202) collected 20 years ago with a contemporary sample of Canadian infants.MethodThis was a cross‐sectional cohort study of 650 Canadian infants (338 males, 312 females; mean age 30.9wks [SD 15.5], range 2wks–18mo) assessed once on the AIMS. Assessments were stratified by age, and infants proportionally represented the ethnic diversity of Canada. Logistic regression was used to place AIMS items on an age scale representing the age at which 50% of the infants passed an item on the contemporary data set and the original data set. Forty‐three items met the criterion for stable regression results in both data sets.ResultsThe correlation coefficient between the age locations of items on the original and contemporary data sets was 0.99. The mean age difference between item locations was 0.7 weeks. Age values from the original data set when converted to the contemporary scale differed by less than 1 week.InterpretationThe sequence and age at emergence of AIMS items has remained similar over 20 years and current normative values remain valid. Concern that the ‘back to sleep’ campaign has influenced the age at emergence of gross motor abilities is not supported.
Glucose‐6‐phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose
Authors: Phillpotts Simon , Tash Elliot , Sen Sambit 
Published: March 2014

AbstractGlucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol‐induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy.
Neurofilament heavy chain as a marker of neuroaxonal pathology and prognosis in acute encephalitis
Authors: Sellner J. , Davies N. W. , Howard R. S. , Petzold A. 
Published: March 2014

Background and purposeThe neurological outcome of acute encephalitis can be devastating and early prognosis remains difficult. Biomarkers that quantify the extent of early brain injury are needed to improve the prognostic accuracy and aid patient management. Our objective was to assess whether cerebrospinal fluid (CSF) protein biomarkers of neuroaxonal and glial cell injury are elevated in distinct forms of acute encephalitis and predictive of poor outcome.MethodsThis was a prospective study of patients presenting with acute encephalitis to three teaching hospitals in London, UK. Levels of neurofilament heavy chain (NfH, SMI35) and S100B were quantified in CSF using enzyme‐linked immunosorbent assay. The outcome was assessed by the Glasgow Outcome Scale (GOS).ResultsFifty‐six patients with acute encephalitis were recruited and classified into the following diagnostic categories: infectious (n = 20), inflammatory (n = 14) and unknown etiology (n = 22). Pathological levels of NfH and S100B were observed in 24/56 (43%) and 54/56 (96%), respectively. Patients with infectious encephalitis had significantly higher NfH levels compared with the other two groups (P < 0.05). A poor outcome (GOS < 5) was associated with significantly higher CSF NfH levels within samples taken 2 weeks after symptom onset.ConclusionsThis study suggests that longitudinal CSF NfH levels are of superior prognostic value compared with CSF S100B levels. Prolonged release of NfH, a marker of neuroaxonal damage, was associated with poor outcome. Potentially there is a window of opportunity for future neuroprotective treatment strategies in encephalitis.
Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis, myelitis, vasculitis or intracranial hypertension
Authors: Bremell D. , Dotevall L. 
Published: March 2014

Background and purposeThe treatment recommendation for Lyme neuroborreliosis with central nervous system (CNS) symptoms is intravenous ceftriaxone, according to current American and European guidelines. For Lyme neuroborreliosis with peripheral nervous system (PNS) symptoms, treatment with intravenous ceftriaxone and oral doxycycline is considered equally effective. The purpose of this study was to evaluate the efficacy of oral doxycycline in the treatment of Lyme neuroborreliosis with CNS symptoms.MethodsPatients with Lyme neuroborreliosis who had undergone cerebrospinal fluid (CSF) sampling before and after treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, during the period 1990–2012, were included in this retrospective study. The CSF mononuclear cell count was used as a surrogate marker of treatment outcome. Comparisons of CSF mononuclear cell counts were made between patients with CNS symptoms and patients with PNS symptoms before and after treatment with oral doxycycline.ResultsTwenty‐six patients classified as having CNS symptoms and 115 patients classified as having PNS symptoms were included. The decline in CSF mononuclear cell counts did not differ significantly between the two groups of patients. All patients with CNS disease showed a marked clinical improvement after treatment, even though 62% had remaining symptoms at the end of follow‐up.ConclusionTreatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with Lyme neuroborreliosis with PNS symptoms. The results indicate that oral doxycycline is an effective treatment for Lyme neuroborreliosis irrespective of the severity of symptoms.
Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy
Authors: Cargnin S. , Viana M. , Ghiotto N. , Bianchi M. , Sances G. , Tassorelli C. , Nappi G. , Canonico P. L. , Genazzani A. A. , Terrazzino S. 
Published: March 2014

Background and purposeIt is currently unknown if common genetic variants influence the prognosis of patients with medication overuse headache (MOH). Here the role of two common single nucleotide polymorphisms in the COMT gene (rs4680 and rs6269), as well as the STin2 variable number tandem repeat (VNTR) polymorphism in the SLC6A4 gene, were evaluated as predictors for long‐term outcomes of MOH patients after withdrawal therapy.MethodsGenotyping was conducted by polymerase chain reaction (PCR), PCR restriction fragment length polymorphism analysis or real‐time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. Gene variants association was evaluated by logistic regression analysis adjusted for clinical confounding factors, and the threshold of statistical significance for multiple testing was set at P < 0.012.ResultsSixty‐five MOH patients with unsuccessful detoxification and 83 MOH patients with effective drug withdrawal therapy were available for the analysis. rs4680G allele carriers or the COMT rs6269G‐rs4680G haplotype were found to be associated with a lower risk of relapse within the first year after successful detoxification therapy, in comparison with homozygous rs4680A allele carriers [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05–0.61, P = 0.007] or with the COMT rs6269A‐rs4680A haplotype (OR 0.19, 95% CI 0.06–0.54, P = 0.003), respectively. In addition, carriers of the STin2 VNTR short allele were found at higher odds for the composite poor outcome including unsuccessful withdrawal therapy and relapse within 12 months of follow‐up after successful detoxification (OR 2.81, 95%CI 1.26–6.25, P = 0.009).ConclusionsOur results indicate that genotyping for COMT rs4680 and SLC6A4 STin2 VNTR could be useful for the identification of MOH patients at higher risk of poor prognosis after drug withdrawal.
Melanoma never says die
Authors: Haass Nikolas K. , Schumacher Udo 
Published: March 2014

AbstractDrug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Targeting apoptosis regulators is thus considered a promising approach to sensitizing melanoma to therapy. In the previous issue of Experimental Dermatology, Plötz and Eberle discuss the role that apoptosis plays in melanoma progression and drug resistance and the utility of apoptosis‐inducing BH3‐mimetics as targeted therapy. There are a number of compounds in clinical development and the field seems close to translating recent findings into benefits for patients with melanoma. Thus, this viewpoint is timely and achieves a valuable summary of the current state of apoptosis‐inducing therapy of melanoma.
Face‐to‐face with anti‐inflammatory therapy for rosacea
Authors: Salzer Suzanna , Ruzicka Thomas , Schauber Jürgen 
Published: March 2014

AbstractIn the past, our understanding of rosacea has been inadequate and limited to descriptions of factors that exacerbate and improve the disease. While the pathophysiology of rosacea is complex and multifactorial, cathelicidin peptides have emerged as key players in the pathogenesis of this common dermatological disorder. This article correlates recent findings in abnormal cathelicidin production and proteolytic processing in rosacea with therapeutic actions of current treatment options and, in this way, highlights potential points of intervention for the development of efficient therapeutic alternatives.