bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of panobinostat with ponatinib synergistically overcomes imatinib‐resistant CML cells
Authors: Matsuda Yasufumi , Yamauchi Takahiro , Hosono Naoko , Uzui Kanako , Negoro Eiju , Morinaga Koji , Nishi Rie , Yoshida Akira , Kimura Shinya , Maekawa Taira , Ueda Takanori 
Published: May 2016

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR‐ABL gene amplification or mutation. We investigated the cytotoxicity of a pan‐ABL tyrosine kinase inhibitor, ponatinib, and a pan‐histone deacetylase inhibitor, panobinostat, against IM‐resistant CML cells in vitro. Two different IM‐resistant cell lines, K562/IM‐R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3. K562/IM‐R1 overexpressed BCR‐ABL due to gene amplification. Ba/F3/T315I was transfected with a BCR‐ABL gene encoding T315I‐mutated BCR‐ABL. Ponatinib inhibited the growth of both K562/IM‐R1 and Ba/F3/T315I as potently as it inhibited their parental cells with an IC50 of 2–30 nM. Panobinostat also similarly inhibited the growth of all of the cell lines with an IC50 of 40–51 nM. This was accompanied by reduced histone deacetylase activity, induced histone H3 acetylation, and an increased protein level of heat shock protein 70, which suggested disruption of heat shock protein 90 chaperone function for BCR‐ABL and its degradation. Importantly, the combination of ponatinib with panobinostat showed synergistic growth inhibition and induced a higher level of apoptosis than the sum of the apoptosis induced by each agent alone in all of the cell lines. Ponatinib inhibited phosphorylation not only of BCR‐ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM‐R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM‐resistant CML cells including those with T315I‐mutated BCR‐ABL.
The amount of care delivered: challenges of indices in oral health studies
Authors: van Dommelen Paula , Schuller Annemarie A. 
Published: May 2016

AbstractObjectivesUntreated dental caries is the most prevalent medical condition worldwide, with considerable variations in prevalence between regions and countries. The care index (CI) and the restorative index (RI) are generally used to make comparisons between and within countries of levels of care delivered. However, several methodological challenges can be identified that limit the interpretation and comparison of these indices. The objective of this manuscript was to evaluate these challenges and to provide solutions.MethodsFive challenges were identified: (i) the comparability of CI and RI, (ii) the use of multiple definitions of CI and RI, (iii) CI and RI measured for surfaces or teeth, (iv) the skewness of F/D(M)F (restored teeth or surfaces as a fraction of the total number of decayed, (missing), and filled teeth or surfaces), and (v) the relationship between CI, RI and D(M)F. Time‐series data were obtained – for people aged 25–44 years with low socioeconomic status – from four cross‐sectional studies performed in 1995, 2002, 2007 and 2013 in the Netherlands, and those data were subjected to descriptive analyses.ResultsThe analyses showed that the choice of index and definition had a major impact on the results, which varied in terms of absolute size and trends. Moreover, CI and RI are expressed as mean scores, but the distributions of F/DMF and F/DF were highly skewed. CI and RI may therefore mask groups of individuals who still need care. The proportion of individuals receiving most restorative care was much higher in the group with low levels of caries than in the groups with more caries. This implies that, when the need for care decreases over time, the restorative care indices can be expected to increase, even though there may be no improvement in the amount of care delivered.ConclusionsWe argue that epidemiological studies of oral health in the future should clarify the definitions used to describe the care delivered and investigate subgroups of F/DMF or F/DF in categories based on the extent of caries. These figures could be used to monitor changes in treatment provision and to highlight inequalities in the provision of care.
Early Recanalization Postintravenous Thrombolysis in Ischemic Stroke with Large Vessel Occlusion: A Digital Subtraction Angiography Study
Authors: Mao Yi‐Ting , Mitchell Peter , Churilov Leonid , Dowling Richard , Dong Qiang , Yan Bernard 
Published: May 2016

SummaryAimsWe aimed to evaluate early recanalization postintravenous (i.v.) tissue plasminogen activator (t‐PA) by digital subtraction angiography (DSA) in acute ischemic stroke (AIS) with large vessel occlusion (LVO).MethodsWe performed baseline CT angiography to identify LVO in AIS. Recanalization pre‐ and post‐intra‐arterial therapy (IAT) was categorized to none, partial, and global recanalization (GR). Modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome.ResultsAmong 1610 patients with AIS, 286 received IV t‐PA. Of these, 55 patients with LVO were included. The median time from IV t‐PA to DSA was 120 min (interquartile range, 79–152). Recanalization post‐IV t‐PA was observed in seven patients (12.7%). By occlusion sites, the recanalization rates were as follows: extracranial internal carotid artery 2 of 14 (14.3%); intracranial internal carotid artery 3 of 24 (12.5%); M1 of middle cerebral artery 3 of 39 (7.7%); M2 of middle cerebral artery 1 of 40 (2.5%); vertebral artery 0 of 4; and basilar artery 0 of 7. GR post‐IAT was associated with favorable outcomes (odds ratio: 8.6; 95% confidence interval, 1.5–48.0; P = 0.014).ConclusionEarly recanalization assessed by DSA post‐IV t‐PA is rarely observed in acute ischemic stroke patients with LVO.
Weigh Forward: a clinical audit of weight management in Australian general practice
Authors: Hemmes R. A. , Adam N. , Dixon J. B. 
Published: May 2016

SummaryWeigh Forward was a prospective clinical audit, aimed to assess the use and efficacy of 12‐week weight management program in general practice. Twenty‐eight practitioners participated in the audit, with a total of 258 patients observed. Of these, 147 (57%) were retained to 24 weeks. Practices were asked to implement a structured 12‐week weight loss program, and encouraged to utilize relevant weight management guidelines as necessary. Patients were followed up regularly, and comprehensively assessed at baseline, 12 and 24 weeks. Evaluations were made of patient weight loss, practitioner willingness to utilize available weight loss interventions, practitioner set weight loss goals and the appropriateness of such goals. Overall, the 57% of completing patients lost an average of 6.1% ± 0.5% body weight, with 27.2% losing ≥10% body weight. Practitioners were hesitant to intensify treatment, and those with comorbidities were less likely (odds ratio 1.8; 95% CI 1.4–2.4) to receive intensified treatment than those without. Practitioners also tended to set high weight loss goals, with a mean goal of 17.3% body‐weight loss. The clinically significant mean weight loss demonstrates that practitioners are able to generate meaningful weight loss in primary care settings, however, could benefit from increased use of available interventions.
Lymph node size is not a reliable criterion for predicting nodal metastasis in rectal neuroendocrine tumours
Authors: Kim B. C. , Kim Y. E. , Chang H. J. , Lee S. H. , Youk E. G. , Lee D.‐S. , Lee J. B. , Lee E.‐J. , Kim M. J. , Sohn D. K. , Oh J. H. 
Published: May 2016

AbstractAimThe study was designed to assess the correlation between lymph node (LN) size and LN metastasis in patients with rectal neuroendocrine tumours (NETs).MethodForty patients who underwent curative resection with lymphadenectomy for a rectal NET between January 2007 and December 2012 were included. The short and long diameters of entire nodes were microscopically measured using a slide gauge.ResultsIn all, 1052 LNs were collected from the 40 patients, with 49 (4.7%) showing evidence of metastasis. Metastasis‐positive LNs had significantly greater long and short diameters (P < 0.001) than metastasis‐negative LNs. Of the 49 metastatic LNs, 29 (59.2%) were ≤ 5 mm in largest diameter. In five patients, the largest metastatic LN was only 2–3 mm in diameter. In clinically node‐negative (cN0) patients, 18 (51.4%) patients had metastatic LNs (pN1).ConclusionThe size of LNs containing metastasis varied widely, with some being very small. LN size alone is therefore not a sufficient predictor of tumour metastasis in rectal NETs. Radical surgery with lymphadenectomy should be considered for patients with rectal NETs with high risk factors for LN metastasis, even those without LN enlargement.
Drivers of Extinction Risk in Terrestrial Vertebrates
Authors: Ducatez Simon , Shine Richard 
Published: May 2016

AbstractRising rates of extinction create an urgent need to identify the mechanisms and drivers of endangerment. One critical question is whether major phylogenetic lineages are equally at risk to the same threats. We used the IUCN Red List classification to explore the effect of four major threatening processes (habitat alteration, invasive species, climate change and overexploitation) on 7,441 species in four terrestrial vertebrate classes. As expected, species rated as vulnerable to a higher number of threats were also at greater risk of extinction. However, this pattern differed strongly among classes. Notably, invasive species and climate change were strongly associated with increased risk of extinction in birds but not mammals. These large‐scale differences might be artifacts of differing methodologies used by class specialists to classify species vulnerability; or might reflect biological differences. That ambiguity needs to be resolved, because it has strong implications for the assessment and amelioration of threatening processes.
Characterizing social–ecological units to inform biodiversity conservation in cultural landscapes
Authors: Hanspach Jan , Loos Jacqueline , Dorresteijn Ine , Abson David J. , Fischer Joern 
Published: May 2016

AbstractAimCultural landscapes and their biodiversity are threatened by land use changes and the abandonment of traditional farming techniques. Conceptualizing cultural landscapes as social–ecological systems can be useful to develop strategies for biodiversity conservation. First, this study aimed to develop a typology of social–ecological units based on land use patterns. Second, we sought to relate this typology to biophysical and socio‐demographic drivers as well as to biodiversity outcomes.LocationSouthern Transylvania (Romania).MethodsWe developed a typology of villages in Southern Transylvania based on land use data. We collected species richness data for plants, butterflies and birds, modelled local richness data for each village and related these values to the village typology. Also, we related village typology to biophysical and socio‐demographic variables.ResultsWe identified four types of villages that showed distinct species richness patterns. Bird richness was highest in forest‐dominated and mixed‐land use villages; plant richness was highest in pasture‐dominated villages; and butterfly richness was high in arable‐dominated, mixed‐land use and pasture‐dominated villages. The four types of villages had distinct topographic characteristics and also differed in terms of ethnic composition, migration patterns and geographic location. Drawing on a combined understanding of social–ecological variables, different conservation actions could be prioritized for each of the four village types.Main conclusionsApplying social–ecological approaches has the potential to inform biodiversity conservation in cultural landscapes. Social–ecological typologies can improve our understanding of complex systems and provide useful input for the development of effective strategies for biodiversity conservation.
Novel outcome measures for Charcot−Marie−Tooth disease: validation and reliability of the 6‐min walk test and StepWatch™ Activity Monitor and identification of the walking features related to higher quality of life
Authors: Padua L. , Pazzaglia C. , Pareyson D. , Schenone A. , Aiello A. , Fabrizi G. M. , Cavallaro T. , Santoro L. , Manganelli F. , Gemignani F. , Vitetta F. , Quattrone A. , Mazzeo A. , Russo M. , Vita G. ,   the CMT‐TRIAAL Group
Published: May 2016

Background and purposeCharcot−Marie−Tooth (CMT) disease is the most common inherited neuropathy, but therapeutic options have been limited to symptom management. Past pharmacological trials have failed, possibly due to insensitive outcome measures (OMs). The aim of the current study was to evaluate the validity and reliability of the 6‐min walk test (6MWT) and StepWatch™ Activity Monitoring (SAM) with other previously validated OMs in CMT disease.MethodsA prospective multicenter study was performed, consecutively enrolling 168 CMT patients (104 with CMT1A, 27 with CMT1B, 37 with X‐linked CMT) from Italian centers specializing in CMT care.ResultsStatistical analysis showed that the 6MWT was highly related with all previously used OMs. Some, but not all, SAM parameters were related to commonly used OMs but may provide more information about quality of life.ConclusionsThe current study demonstrated the validity and reliability of the 6MWT and SAM as OMs for CMT. Moreover, SAM provides data that correlate better with quality of life measures, making it useful in future rehabilitation trials.
Biochar alters the soil microbiome and soil function: results of next‐generation amplicon sequencing across Europe
Authors: Jenkins Joseph R. , Viger Maud , Arnold Elizabeth C. , Harris Zoe M. , Ventura Maurizio , Miglietta Franco , Girardin Cyril , Edwards Richard J. , Rumpel Cornelia , Fornasier Flavio , Zavalloni Costanza , Tonon Giustino , Alberti Giorgio , Taylor Gail 
Published: May 2016

AbstractWide‐scale application of biochar to soil has been suggested as a mechanism to offset increases inCO2emissions through the long‐term sequestration of a carbon rich and inert substance to the soil, but the implications of this for soil diversity and function remain to be determined. Biochar is capable of inducing changes in soil bacterial communities, but the exact impacts of its application are poorly understood. Using three European sites [UK SRC, short rotation coppice, French grassland (FR) and ItalianSRF, short rotation forestry (IT)] treated with identical biochar applications, we undertook 16S andITSampliconDNAsequencing. In addition, we carried out assessments of community change over time and N and P mobilization in theUK. Significant changes in bacterial and community structure occurred due to treatment, although the nature of the changes varied by site.STAMPdifferential abundance analysis showed enrichment ofGemmatimonadeteandAcidobacteriainUKbiochar plots 1 year after application, whilst control plots exhibited enrichedGemmataceae, IsosphaeraceaeandKoribacteraceae. Increased mobility of ammonium and phosphates was also detected after 1 year, coupled with a shift from acid to alkaline phosphomonoesterase activity, which may suggest an ecological and functional shift towards a more copiotrophic ecology. Italy also exhibited enrichments, in both theProteobacteria(driven by an increase in the orderRhizobiales) and theGemmatimonadetes. No significant change in the abundance of individual taxa was noted inFR, although a small significant change in unweightedUNIFRACoccurred, indicating variation in the identities of taxa present due to treatment. Fungalβdiversity was affected by treatment inITandFR, but was unaffected inUKsamples. The effects of time and site were greater than that of biochar application inUKsamples. Overall, this report gives a tantalizing view of the soil microbiome at several sites across Europe and suggests that although application of biochar has significant effects on microbial communities, these may be small compared with the highly variable soil microbiome that is found in different soils and changes with time.
Social Interaction Promotes Risk Taking in a Stag Hunt Game
Authors: Bolton Gary E. , Feldhaus Christoph , Ockenfels Axel 
Published: May 2016

Abstract
We demonstrate that people are more willing to take risks in a stag hunt game when the agent of uncertainty is another person, thereby promoting cooperation. Recent social cognition research suggests an explanation for this pattern, which is based on the idea that games that align interests between subjects activate a trust mindset.
Providing patient information and education in practice: the role of the health librarian
Authors: Truccolo Ivana 
Published: May 2016

AbstractIn this article, guest writer Ivana Truccolo presents an overview of her work at the Scientific and Patient Library of a Cancer Comprehensive Centre in Italy coordinating the patient education process. She discusses the historical evolution of the concept of patient education and how this has run alongside the role of the health librarian in the provision of consumer health information. Details are provided about various patient education programmes in place at the Centre. In particular, various activities are discussed including patient education classes, the development of patient education handouts and a narrative medicine programme which includes a literary competition. The article concludes with a specific outline of the role the health librarian can play in the provision of consumer health information and patient education.H.S.
A global survey of HIV‐positive people's attitudes towards cure research
Authors: Simmons R , Kall M , Collins S , Cairns G , Taylor S , Nelson M , Fidler S , Porter K , Fox J ,   the Collaborative HIV Eradication of viral Reservoirs (CHERUB) Survey collaboration
Published: May 2016

ObjectivesInvolvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research.MethodsPLHIV were recruited in June−November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks.ResultsA total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty‐one per cent were aged 25–44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2–17 years]. Eighty‐eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV‐negative (69%). Ninety‐five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201–350 cells/μL vs. ≥ 350 cells/μL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11–4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45–64 years were less likely to accept risks [OR 0.58 (95% CI 0.37–0.90) and OR 0.18 (95% CI 0.07–0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%).ConclusionsCure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.
Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study
Authors: Li D.‐G. , Du H.‐Y. , Gerhard S. , Imke M. , Liu W. 
Published: May 2016

AbstractBackgroundPhenoxyethanol is a widely used preservative in personal care products. Transient receptor potential vanilloid 1 (TRPV1) on cell membrane is activated by TRPV1 agonist capsaicin resulting in an opening of the channel for calcium influx, which is linked with neurosensory sensations characterized by itching, burning and stinging of skin. Whether uncomfortable skin sensations caused by phenoxyethanol claimed by people having sensitive skin are also due to activation of TRPV1 has not been reported in the literature.ObjectiveThe aim of this study was to evaluate whether the TRPV1 is involved in the induction of itching and burning sensation by phenoxyethanol.Methods and materialsThe effect of phenoxyethanol on TRPV1 was assessed in vitro on HaCaT cells. The activation of TRPV1 and its inhibition by a TRPV1 antagonist were evaluated by cellular calcium influx. TRPV1 protein expression was also investigated by Western blot. In vivo in a split‐face study, phenoxyethanol formulated at 1% was compared to a formulation additionally containing a TRPV1 antagonist. By applying the formulations to the nasolabial fold, the scores of phenoxyethanol‐induced sensations were compared to those of the TRPV1 antagonist.ResultsIn vitro phenoxyethanol induced calcium influx in HaCaT cells in a dose‐dependent manner after 20 min. This effect was abolished by a solution containing the TRPV1 antagonist trans‐tert‐butyl cyclohexanol (ID1609). Phenoxyethanol had no effect on the expression of TRPV1, whereas capsaicin caused a significant downregulation of this receptor in the same experiment. In vivo 1% phenoxyethanol induced a skin burning and itching sensation in a cohort of 60 of 243 Chinese female subjects being sensitive to phenoxyethanol discomfort. The uncomfortable skin sensations were significantly inhibited by ID1609.ConclusionsDifferent to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our experiments demonstrated that phenoxyethanol induces skin misperception and uncomfortable skin sensations like itching and burning comparable to capsaicin via activating TRPV1. The stimulation was inhibited by blocking TRPV1 with ID1609. The present data strengthened hitherto studies that TRPV1 plays a critical role in sensitive skin.