bluuebunny/crossref_metadata_2025_split huggingface dataset:
A health website recommendation from Gold Coast general practitioners to their patients
Authors: Usher Wayne 
Published: September 2010

Introduction: To identify health website recommendation trends by Gold Coast (Australia) general practitioners (GPs) to their patients. Method: A mixed method approach to data collection and analysis was employed. Quantitative data were collected using a prepaid postal survey, consisting of 17 questions, mailed to 250 (61 per cent) of 410 GPs on the Gold Coast (Australia). The resulting empirical data and resulting themes were further used to design semi-structured interview questions. A total of 15 (8 male, 7 female) GPs volunteered to be interviewed. Results: Fifty-nine per cent of participating GPs recommend health websites to their patients during consultations. Male GPs (63 per cent), those aged 41–50 years (55 per cent), and those practising for < 10 years (60 per cent) were more inclined to recommend a health website to a patient. From the survey data, eight principle categories presented themselves as to GPs’ recommendation trends, these including; ‘Do not recommend websites’ – (1) Limited time, (2) Prefer to personally discuss, (3) Reliability issues, (4) Biased information – and ‘Do recommend health websites’ – (5) Helps to educate patient, (6) Enhances the doctor–patient relationship, (7) Age-appropriate technology, (8) Treatment orientated. The semi-structured interviews presented a further eight sub-categories and have been identified as: (1) Fewer female GPs than male GPs recommend health websites, (2) Age and years of experience of GPs affect internet prescription trends, (3) Patients more knowledgeable, (4) ‘Sweeteners’ offered by pharmaceutical companies, (5) A high influence by pharmaceutical companies on the WWW/internet, (6) A lack of knowledge pertaining to reliability issues – issues of trust, (7) Limited knowledge pertaining to interactivity and usability components, and (8) A need for further medical education for GPs. Conclusion: More than half of the surveyed GPs actively recommend websites to their patients, with a GP’s sex, age and years of experience influencing his or her recommendation decisions. There are numerous and varied reasons as to why GPs ‘do’ or ‘do not’ recommend health websites to their patients. Web-based continuing medical education courses or programmes in medical schools may help GPs develop the skills necessary for the delivery of effective e-health care.
A mechanistic rationale for combining alemtuzumab and rituximab in the treatment of ALL
Authors: Nijmeijer Bart A. , van Schie Marianke L. J. , Halkes Constantijn J. M. , Griffioen Marieke , Willemze Roelof , Falkenburg J. H. Frederik 
Published: September 2010

Abstract
B-lineage acute lymphoblastic leukemia (ALL) may express CD52 and CD20. Alemtuzumab (ALM) and rituximab (RTX) are therapeutic antibodies directed against CD52 and CD20, respectively, but showed limited activity against ALL in clinical trials. The mechanisms for the impaired responses remained unclear. We studied expression of CD52 and CD20 on ALL cells and found that most cases coexpressed CD52 and CD20. However, distinct CD52-negative (CD52−) subpopulations were detected in most cases as the result of defective glycophosphatidyl-inositol anchoring. Although ALM efficiently eradicated CD52-positive (CD52+) cells in NOD/scid mice engrafted with primary human ALL, CD52− subclones escaped therapy. In the same model, RTX showed limited activity resulting from occurrence of CD20 down-modulation. However, CD52− cells concurrently lacked the glycophosphatidyl-inositol–anchored complement regulators CD55 and CD59 and showed increased susceptibility to RTX-mediated complement-dependent cytotoxicity in vitro. At the same time, ALM was shown to inhibit down-modulation of CD20 in response to RTX by depleting the trogocytic capacity of phagocytic cells. Probably because of these complementary mechanisms, combined administration of ALM and RTX induced complete responses in vivo. Based on these data, we propose a mechanistic rationale for combined application of RTX and ALM in ALL.
Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations
Authors: Pecci Alessandro , Gresele Paolo , Klersy Catherine , Savoia Anna , Noris Patrizia , Fierro Tiziana , Bozzi Valeria , Mezzasoma Anna Maria , Melazzini Federica , Balduini Carlo L. 
Published: September 2010

Abstract
Platelet transfusion is currently the primary medical treatment for reducing thrombocytopenia in patients with inherited thrombocytopenias. To evaluate whether stimulating megakaryopoiesis could increase platelet count in these conditions, we treated patients with a severe thrombocytopenia induced by MYH9 mutations (MYH9-related disease) with a nonpeptide thrombopoietin receptor agonist, eltrombopag. Twelve adult patients with MYH9-RD and platelet counts of less than 50 × 109/L received 50 mg of eltrombopag orally per day for 3 weeks. Patients who achieved a platelet count higher than 150 × 109/L stopped therapy, those with 100 to 150 platelets × 109/L continued treatment at the same eltrombopag dose for 3 additional weeks, while those with less than 100 platelets × 109/L increased the eltrombopag dose to 75 mg for 3 weeks. Major responses (platelet count of at least 100 × 109/L or 3 times the baseline value) were obtained in 8 patients, minor responses (platelet counts at least twice the baseline value) in 3. One patient did not respond. Bleeding tendency disappeared in 8 of 10 patients with bleeding symptoms at baseline. Mild adverse events were reported in 2 patients. The availability of thrombopoietin mimetics opened new prospects in the treatment of inherited thrombocytopenias. This study is registered at www.clinicaltrials.gov as NCT01133860 (European Union Drug Regulating Authorities Clinical Trials number 2008-001903-42).
Obtaining additional information by using exercise testing in the laboratory in the diagnosis of asthma
Authors: Stensrud T. 
Published: September 2010

Educational aimsTo explain how to get more information out of an exercise challenge.To obtain knowledge about different exercise test protocols and ergometers.To obtain knowledge about the importance of assessing different physiological variables during exercise.To obtain knowledge about how different climatic conditions influence exercise-induced bronchoconstriction (EIB) and exercise capacity.SummaryDifferent test protocols are commonly used in the diagnosis of EIB and in the assessment of exercise capacity (). Recently one study has shown the possibility of combining assessment of EIB and into one EIB test protocol, even though the gold standard in assessment of is an incremental protocol. Additional and useful information about asthma can be obtained and differential diagnoses to EIB can be assessed by measuring different physiological variables during the EIB challenge. The following article will focus on the advantages of measuring exercise capacity during an EIB test, after a short discussion of different test protocols and ergometers.
Alternatives to exercise challenge for the objective assessment of exercise-induced bronchospasm: eucapnic voluntary hyperpnoea and the osmotic challenge tests
Authors: Porsbjerg C. , Brannan J.D. 
Published: September 2010

Educational aimsTo describe alternative tests for the assessment of exercise-induced bronchoconstriction and to describe the mechanisms by which bronchoconstriction is caused.To describe how these tests are performed and how to interpret the test results.To choose the most appropriate test for a given clinical problem.SummaryExercise-induced bronchoconstriction (EIB) is caused by evaporative water loss due to conditioning large volumes of air in a short period. This leads to an increase in osmolarity of the airway surface, which provides a favourable environment for release of bronchoconstricting mediators from inflammatory cells in the airways. Thus, stimuli that mimic this water loss or increase the osmolarity of the airway surface may be used as ‘surrogates’ for exercise challenge testing. The most widely used tests are eucapnic voluntary hyperpnoea (EVH) or osmotic challenges (e.g.hyperosmolar saline and mannitol). However, there are some differences in the methodology that need to be considered when using these tests. Importantly, EVH and the osmotic challenge tests overcome some of the practical and safety limitations of performing exercise testing at high intensity. The utility of these alternative tests for assessing EIB is discussed.
Exercise and asthma: β2-agonists and the competitive athlete
Authors: Boulet L-P. , Hancox R.J. , Fitch K.D. 
Published: September 2010

Educational aimsDiscuss the role of inhaled β-agonists in the management of exercise-induced asthma and exercise-induced bronchoconstriction.Review the beneficialversusuntoward effects of inhaled β-agonists on asthma, exercise-induced asthma and exercise-induced bronchoconstriction.Report on current and past usage of these drugs by Olympic athletes.SummaryInhaled β-agonists effectively block exercise-induced asthma/exercise-induced bronchoconstriction (EIA/EIB). They are the treatment of choice for this condition and are used by many elite and Olympic athletes. However, regular or frequent use of inhaled β-agonists leads to an increase in the underlying severity of EIA/EIB and a reduction in their bronchoprotective and bronchodilator effects, which means that they become less effective at preventing and treating EIA/EIB. Emphasis should be placed on preventative measures and anti-inflammatory treatments such as inhaled corticosteroids in order to minimise the need for inhaled β-agonists to prevent EIA/EIB.
The WTX/AMER1 gene family: evolution, signature and function
Authors: Boutet Agnès , Comai Glenda , Schedl Andreas 
Published: September 2010

Abstract

Background

WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/β-catenin signaling in fish and mammals thus linking it to an essential pathway involved in normal development and cancer formation. Interestingly, WTX seems to also localize to an intranuclear component called paraspeckles. In spite of the growing interest of molecular biologists in WTX, little is known about its paralogs and its phylogenetic history.

Results
Using the amino-acid sequence of WTX/AMER1 as a tool for the assignment of orthology and paralogy, we here identify two novel proteins, AMER2 and AMER3, as "WTX" related. This Amer gene family is present in all currently available vertebrate genome sequences, but not invertebrate genomes and is characterized by six conserved blocks of sequences. The phylogenetic analysis suggests that the protoAmer gene originated early in the vertebrate lineage and was then duplicated due to whole genome duplications (WGD) giving rise to the three different Amer genes.

Conclusion
Our study represents the first phylogenetic analysis of Amer genes and reveals a new vertebrate specific gene family that is likely to have played an important role in the evolution of this subphylum. Divergent and conserved molecular functions of Wtx/Amer1, Amer2 and Amer3 are discussed.
Foodborne norovirus outbreak: the role of an asymptomatic food handler
Authors: Barrabeig Irene , Rovira Ariadna , Buesa Javier , Bartolomé Rosa , Pintó Rosa , Prellezo Hortènsia , Domínguez Àngela 
Published: September 2010

Abstract

Background
In July 2005 an outbreak of acute gastroenteritis occurred on a residential summer camp in the province of Barcelona (northeast of Spain). Forty-four people were affected among residents and employees. All of them had in common a meal at lunch time on 13 July (paella, round of beef and fruit). The aim of this study was to investigate a foodborne norovirus outbreak that occurred in the residential summer camp and in which the implication of a food handler was demonstrated by laboratory tests.

Methods
A retrospective cohort study was designed. Personal or telephone interview was carried out to collect demographic, clinical and microbiological data of the exposed people, as well as food consumption in the suspected lunch. Food handlers of the mentioned summer camp were interviewed.
Ten stool samples were requested from symptomatic exposed residents and the three food handlers that prepared the suspected food. Stools were tested for bacteries and noroviruses. Norovirus was detected using RT-PCR and sequence analysis.
Attack rate, relative risks (RR) and its 95% confidence intervals (CI) were calculated to assess the association between food consumption and disease.

Results
The global attack rate of the outbreak was 55%. The main symptoms were abdominal pain (90%), nausea (85%), vomiting (70%) and diarrhoea (42.5%). The disease remitted in 24-48 hours. Norovirus was detected in seven faecal samples, one of them was from an asymptomatic food handler who had not eaten the suspected food (round of beef), but cooked and served the lunch. Analysis of the two suspected foods isolated no pathogenic bacteria and detected no viruses. Molecular analysis showed that the viral strain was the same in ill patients and in the asymptomatic food handler (genotype GII.2 Melksham-like).

Conclusions
In outbreaks of foodborne disease, the search for viruses in affected patients and all food handlers, even in those that are asymptomatic, is essential. Health education of food handlers with respect to hand washing should be promoted.
Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin
Authors: Serra Ryan , Al-saidi Abdel-ghany , Angelov Nikola , Nares Salvador 
Published: September 2010

AbstractBackgroundPhenytoin (PHT) has been reported to induce gingival (gum) overgrowth (GO) in approximately 50% of patients taking this medication. While most studies have focused on the effects of PHT on the fibroblast in the pathophysiology underlying GO, few studies have investigated the potential regulatory role of macrophages in extracellular matrix (ECM) turnover and secretion of proinflammatory mediators. The aim of this study was to evaluate the effects of PHT and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin (HPPH) on LPS-elicited MMP, TIMP, TNF-α and IL-6 levels in macrophages.MethodsHuman primary monocyte-derived macrophages (n= 6 independent donors) were pretreated with 15-50 μg/mL PHT-Na+or 15-50 μg/mL HPPH for 1 hour. Cells were then challenged with 100 ng/ml purified LPS from the periodontal pathogen,Aggregatibacter actinomycetemcomitans. Supernatants were collected after 24 hours and levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, TIMP-2, TIMP-3, TIMP-4, TNF-α and IL-6 determined by multiplex analysis or enzyme-linked immunoadsorbent assay.ResultsA dose-dependent inhibition of MMP-1, MMP-3, MMP-9, TIMP-1 but not MMP-2 was noted in culture supernatants pretreated with PHT or HPPH prior to LPS challenge. MMP-12, TIMP-2, TIMP-3 and TIMP-2 were not detected in culture supernatants. High concentrations of PHT but not HPPH, blunted LPS-induced TNF-α production although neither significantly affected IL-6 levels.ConclusionThe ability of macrophages to mediate turnover of ECM via the production of metalloproteinases is compromised not only by PHT, but its metabolite, HPPH in a dose-dependent fashion. Further, the preferential dysregulation of macrophage-derived TNF-α but not IL-6 in response to bacterial challenge may provide an inflammatory environment facilitating collagen accumulation without the counteracting production of MMPs.
Nitric Oxide is Negatively Correlated to Pain during Acute Inflammation
Authors: Hamza May , Wang Xiao-Min , Wu Tongtong , Brahim Jaime S , Rowan Janet S , Dionne Raymond A 
Published: September 2010

Background:The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.Results:Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100–180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo goup but not in the ketorolac group.Conclusion:We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.
Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain
Authors: Kondo Maho , Shiono Maki , Itoh Genzo , Takei Norio , Matsushima Takahide , Maeda Masahiro , Taru Hidenori , Hata Saori , Yamamoto Tohru , Saito Yuhki , Suzuki Toshiharu 
Published: September 2010

Abstract

Background
X11-family proteins, including X11, X11-like (X11L) and X11-like 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) and regulate APP metabolism. Both X11 and X11L are expressed specifically in brain, while X11L2 is expressed ubiquitously. X11L is predominantly expressed in excitatory neurons, in contrast to X11, which is strongly expressed in inhibitory neurons. In vivo gene-knockout studies targeting X11, X11L, or both, and studies of X11 or X11L transgenic mice have reported that X11-family proteins suppress the amyloidogenic processing of endogenous mouse APP and ectopic human APP with one exception: knockout of X11, X11L or X11L2 has been found to suppress amyloidogenic metabolism in transgenic mice overexpressing the human Swedish mutant APP (APPswe) and the mutant human PS1, which lacks exon 9 (PS1dE9). Therefore, the data on X11-family protein function in transgenic human APP metabolism in vivo are inconsistent.

Results
To confirm the interaction of X11L with human APP ectopically expressed in mouse brain, we examined the amyloidogenic metabolism of human APP in two lines of human APP transgenic mice generated to also lack X11L. In agreement with previous reports from our lab and others, we found that the amyloidogenic metabolism of human APP increased in the absence of X11L.

Conclusion
X11L appears to aid in the suppression of amyloidogenic processing of human APP in brain in vivo, as has been demonstrated by previous studies using several human APP transgenic lines with various genetic backgrounds. X11L appears to regulate human APP in a manner similar to that seen in endogenous mouse APP metabolism.
A rare mitochondrial disorder: Leigh syndrome - a case report
Authors: Shrikhande Dhananjay Y , Kalakoti Piyush , Syed MM Aarif , Ahya Kunal , Singh Gurmeet 
Published: September 2010

AbstractLeigh syndrome is a rare progressive neurodegenerative, mitochondrial disorder of childhood with only a few cases documented from India. The clinical presentation of Leigh syndrome is highly variable. However, in most cases it presents as a progressive neurological disease with motor and intellectual developmental delay and signs and symptoms of brain stem and/or basal ganglia involvement. Raised lactate levels in blood and/or cerebrospinal fluid is noted. It is the neuroimaging, mainly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the diagnosis. Here, we report a case of 7 months old female child presenting to us with status epilepticus, delayed developmental milestones and regression of the achieved milestones suspected to be a case of neurodegenerative disorder, which on MRI was diagnosed as Leigh syndrome.
Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme
Authors: Ovaska Kristian , Laakso Marko , Haapa-Paananen Saija , Louhimo Riku , Chen Ping , Aittomäki Viljami , Valo Erkka , Núñez-Fontarnau Javier , Rantanen Ville , Karinen Sirkku , Nousiainen Kari , Lahesmaa-Korpinen Anna-Maria , Miettinen Minna , Saarinen Lilli , Kohonen Pekka , Wu Jianmin , Westermarck Jukka , Hautaniemi Sampsa 
Published: September 2010

Abstract
Background
Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed.

Methods
We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available.

Results
We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website.

Conclusions
Our results demonstrate that integrated analysis and visualization of multidimensional and heterogeneous data by Anduril enables drawing conclusions on functional consequences of large-scale molecular data. Many of the identified genetic loci and genes having significant survival effect have not been reported earlier in the context of glioblastoma multiforme. Thus, in addition to generally applicable novel methodology, our results provide several glioblastoma multiforme candidate genes for further studies.
Anduril is available at http://csbi.ltdk.helsinki.fi/anduril/
The glioblastoma multiforme analysis results are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/