bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rituximab‐PECC induction followed by 90Y‐ibritumomab tiuxetan consolidation in relapsed or refractory DLBCL patients who are ineligible for or have failed ASCT: results from a phase II HOVON study
Authors: Lugtenburg Pieternella J. , Zijlstra Josee M. , Doorduijn Jeanette K. , Böhmer Lara H. , Hoogendoorn Mels , Berenschot Henriette W. , Beeker Aart , van der Burg‐de Graauw Nicole C. , Schouten Harry C. , Bilgin Yavuz M. , Kersten Marie‐Jose , Koene Harry R. , Herbers Alexandra H. E. , de Jong Daphne , Hijmering Nathalie , Lam King H. , Chiţu Dana , Brouwer Rolf E. , van Imhoff Gustaaf W. ,   the Dutch HOVON group
Published: July 2019

SummaryPatients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R‐PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio‐immunotherapy consolidation with 90Y‐ibritumomab tiuxetan in responsive patients. Primary endpoints were failure‐free survival (FFS) and incidence of grade ≥3 adverse events from start of 90Y‐ibritumomab tiuxetan. The overall response rate after R‐PECC was 50%. Twenty‐nine of 31 responsive patients proceeded to 90Y‐ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90Y‐ibritumomab tiuxetan. One‐year FFS and overall survival (OS) from start of 90Y‐ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33–68%) and 62% (95% CI, 42–77%), respectively. One‐year FFS and OS from start of R‐PECC was 28% (95% CI, 17–39%) and 49% (95% CI, 36–61%), respectively. Toxicities of R‐PECC and 90Y‐ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R‐PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90Y‐ibritumomab tiuxetan resulted in long‐term response durations in approximately one third of the patients that received it.
Leydig cell failure with testicular radiation doses <20Gy: The clinical effects of total body irradiation conditioned haematopoietic stem cell transplantation for childhood leukaemia during long‐term follow‐up
Authors: Taneja Surina , Rao Anupama , Nussey Stephen , Leiper Alison 
Published: July 2019

AbstractObjectiveTestosterone replacement is generally considered likely to be required only at testicular radiation doses in excess of 20Gy. Long‐term data are not available for patients receiving 9‐14.4Gy as part of Total Body Irradiation in childhood.DesignRetrospective cohort study. Data collection: notes review, laboratory results, prescription of testosterone.PatientsForty‐two of 96 boys who received Total Body Irradiation (9‐14.4Gy) and Haematopoietic Stem Cell Transplantation for childhood leukaemia at Great Ormond Street Hospital between 1981‐2011 and survived >5 years.MeasurementsThe serum concentrations of testosterone and gonadotrophins and the prescription of testosterone were recorded.ResultsOf the 42 boys included, 37 (88%) entered puberty spontaneously and 5 required induction. Median length of follow‐up was 19.4 years (range 5‐33.1). At last follow‐up, 23 of the 37 (62%) with spontaneous puberty were receiving testosterone replacement and 4 of the 5 (80%) with induced puberty.ConclusionThis study with the benefit of long follow‐up indicates that Leydig cell failure occurs with radiation doses <20Gy. It may occur many years after irradiation and mandates long‐term screening for hypogonadism.
An Ontological Framework for Supporting the Design and Evaluation of Visual Analytics Systems
Authors: Chen Min , Ebert David S. 
Published: July 2019

AbstractDesigning, evaluating, and improving visual analytics (VA) systems is a primary area of activities in our discipline. In this paper, we present an ontological framework for recording and categorizing technical shortcomings to be addressed in a VA workflow, reasoning about the causes of such problems, identifying technical solutions, and anticipating secondary effects of the solutions. The methodology is built on the theoretical premise that designing a VA workflow is an optimization of the cost‐benefit ratio of the processes in the workflow. It makes uses three fundamental measures to group and connect “symptoms”, “causes”, “remedies”, and “side‐effects”, and guide the search for potential solutions to the problems. In terms of requirement analysis and system design, the proposed methodology can enable system designers to explore the decision space in a structured manner. In terms of evaluation, the proposed methodology is time‐efficient and complementary to various forms of empirical studies, such as user surveys, controlled experiments, observational studies, focus group discussions, and so on. In general, it reduces the amount of trial‐and‐error in the lifecycle of VA system development.
netflower: Dynamic Network Visualization for Data Journalists
Authors: Stoiber C. , Rind A. , Grassinger F. , Gutounig R. , Goldgruber E. , Sedlmair M. , Emrich Š. , Aigner W. 
Published: July 2019

AbstractJournalists need visual interfaces that cater to the exploratory nature of their investigative activities. In this paper, we report on a four‐year design study with data journalists. The main result is netflower, a visual exploration tool that supports journalists in investigating quantitative flows in dynamic network data for story‐finding. The visual metaphor is based on Sankey diagrams and has been extended to make it capable of processing large amounts of input data as well as network change over time. We followed a structured, iterative design process including requirement analysis and multiple design and prototyping iterations in close cooperation with journalists. To validate our concept and prototype, a workshop series and two diary studies were conducted with journalists. Our findings indicate that the prototype can be picked up quickly by journalists and valuable insights can be achieved in a few hours. The prototype can be accessed at: http://netflower.fhstp.ac.at/
Aetiology and disease severity are among the determinants of quality of life in bronchiectasis
Authors: Terpstra Lotte C. , Biesenbeek Sonja , Altenburg Josje , Boersma Wim G. 
Published: July 2019

AbstractIntroductionQuality of life (QoL) is known to be impaired in patients with bronchiectasis, which is generally attributed to exacerbations and chronic pulmonary symptoms. The aim of this study was to determine if aetiology and disease severity are associated with QoL in bronchiectasis.MethodsWe conducted a retrospective analysis of clinical stable patients with bronchiectasis. Diagnostic workup into the aetiology of bronchiectasis was conducted according to the current guidelines. QoL was measured by QoL‐B questionnaire (QoL‐B), data on sputum microbiology, pulmonary function tests and the disease severity were obtained.ResultsThe aetiology of bronchiectasis was investigated in the total of 200 patients. The most commonly identified aetiologies were post‐infective (39.5%) and idiopathic (12.5%). Patients with chronic obstructive pulmonary disease (COPD)‐related bronchiectasis showed a significant lower QoL (P < .05) as compared to the other aetiologies. In the total population, an increasing disease severity as measured by FACED, E‐FACED and the bronchiectasis severity index was correlated with a lower QoL.ConclusionsOur results showed that QoL in bronchiectasis is related both to aetiology, with worse QoL in COPD‐related bronchiectasis, and to disease severity, which suggests more attention in advance for these specific patient groups with bronchiectasis.
Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family
Authors: Wu Dawen , Zhong Zhanghua , Chen Yunfei , Ding Haibo , Yang Minxia , Lian Ningfang , Huang Zhigui , Zhang Qiaoxian , Zhao Jianming , Deng Chaosheng 
Published: July 2019

AbstractObjectiveThe aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) in protein C (PROC) and protein S (PROS1) genes with deep venous thrombosis (DVT) in a thrombophilia family. MethodsDNA were extracted from blood of participants. Five PROC SNPs and 11 PROS1 SNPs were selected from the Hapmap and 1000 Genomes databases. The minor allele frequencies (MAFs) of SNPs in the thrombophilia family (Group I) and healthy controls (Group II) were detected. SNPs were analysed by Chi‐square, logistic regression and linkage disequilibrium patterns.ResultsMAFs for all 16 SNPs were greater than 0.05. Chi‐square analysis showed significant differences between Group I and Group II in the frequency of mutant alleles of rs1799808, rs5936, rs6123, rs12634349, rs6441600 and rs13062355 SNPs (P < .05). Logistic regression analysis found that mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT in this family (OR > 1, L95 > 1). Linkage disequilibrium was found among 15 of the PROC and PROS SNPs.ConclusionsSingle nucleotide polymorphisms (SNPs) of PROC and PROS1 may be closely associated with DVT in this thrombophilia family. Mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT, whereas mutant alleles of rs1799810, rs6123 and rs12634349 may protect individuals from DVT. With the exception of rs9681204, there was linkage disequilibrium between PROC and PROS1 SNPs. We found that 12 haplotypes were in linkage disequilibrium, but linkage disequilibrium was strong in only eight of these (frequency >5%).
Beyond isolation by distance: What best explains functional connectivity among populations of three sympatric plant species in an ancient terrestrial island system?
Authors: Nevill Paul Gerard , Robinson Todd P. , Di Virgilio Giovanni , Wardell‐Johnson Grant 
Published: July 2019

AbstractAimUnderstanding how landscape features affect gene flow is critical to connectivity conservation and restoration management. Here, we examined the relationship between functional connectivity (gene flow) and structural connectivity (area and spatial configuration of habitats) in three co‐occurring short‐range plant taxa in an ancient terrestrial island system.LocationLow‐altitude mountain range south‐western Australia.MethodsWe analysed spatial patterns of genetic differentiation at nuclear microsatellite loci using Bayesian clustering. Circuit theory modelling was used to generate all possible pathways that connect populations as resistance distance matrices based on two surfaces for each taxon. The first surface assumes a flat terrain and tests whether genetic similarity declines only with distance—isolation by distance (IBD). The second surface is habitat suitability based on species distribution modelling (SDM), which tests whether genetic similarity is a function of connected and suitable habitat. Multiple matrix regression with randomization was used to test the significance of the resistance distance matrices at predicting two metrics of genetic differentiation (FST and DEST). Variance explained was partitioned using redundancy analysis.ResultsGenetic structure for the insect‐pollinated taxa—Acacia adinophylla—and Tetratheca aphylla subsp. aphylla was at similar spatial scales. Unexpectedly, a higher level of genetic structure was found in the wind‐pollinated Lepidosperma bungalbin. IBD best explained the gene flow of A. adinophylla (R2 = 0.41–0.43) with partial support provided by habitat suitability (R2 = 0.04–0.07). In contrast, connectivity by habitat suitability was highest for T. aphylla subsp. aphylla (R2 = 0.56–0.59). Drivers of L. bungalbin connectivity were inconsistent between the two measures of genetic differentiation.Main conclusionsGene flow is facilitated by different factors for the three taxa. Habitat fragmentation would most strongly impede gene flow for T. aphylla subsp. aphylla. Geographical distance cannot be assumed as the sole or best determinant of gene flow among populations, nor can findings be generalized to coexisting taxa.
Clinical outcomes according to the modified endoscopic criteria for neoadjuvant chemotherapy in resectable esophageal squamous cell carcinoma
Authors: Kadota Tomohiro , Abe Seiichiro , Yoda Yusuke , Yoshinaga Shigetaka , Oda Ichiro , Kojima Takashi , Kato Ken , Daiko Hiroyuki , Yano Tomonori 
Published: July 2019

ObjectivesNeoadjuvant chemotherapy (nCT) followed by surgery is one of the standard treatments for resectable esophageal squamous cell carcinoma (ESCC). According to the Response Evaluation Criteria in Solid Tumors, endoscopic evaluation of a primary lesion is not recommended during nCT because of reduced objectivity. This study aimed to develop and validate endoscopic evaluation criteria for nCT.MethodsThis study retrospectively investigated patients with T2/3 ESCC who underwent nCT followed by radical esophagectomy across two institutions (test and validation sets). We retrospectively estimated the therapeutic effect by classifying patients according to degree of tumor shrinkage (evaluated with endoscopy) as follows: marked reduction (MR), half reduction (HR), insufficient reduction (IR), and progressive disease (PD). Three endoscopists evaluated patients in the test set. Another three endoscopists evaluated patients in the validation set. We analyzed recurrence‐free survival (RFS) 3 years after surgery.ResultsOf 129 patients in the test set, 44 had MR, 35 had HR, 44 had IR, and six had PD. The 3‐year RFS rates were 55% (overall), 79% (MR), 54% (HR), 35% (IR), and 33% (PD). Of 91 patients in the validation set, 22 had MR, 49 had HR, 18 had IR, and two had PD. The 3‐year RFS rates were 54% (overall), 77% (MR), 55% (HR), 22% (IR), and 50% (PD).ConclusionsOur endoscopic criteria for nCT predicted prognosis; however, future studies are needed to further investigate our criteria before general application in the clinical setting.
Parent and adolescent communication with healthcare professionals about Type 1 diabetes management at adolescents’ outpatient clinic appointments
Authors: Rawdon C. , Gallagher P. , Glacken M. , Swallow V. , Lambert V. 
Published: July 2019

AbstractAimThis study aimed to identify the ways in which adolescents living with Type 1 diabetes and their parents communicate about Type 1 diabetes management with healthcare professionals in a clinical setting.MethodsTwenty‐nine adolescents (aged 11–17 years) and their parents were purposively recruited from two outpatient clinics for non‐participant observations. Outpatient clinic appointments, which consisted of multiple consultations with healthcare professionals, were observed and audio‐recorded. Outpatient clinic appointments were categorized based on the nature and extent of communication by the adolescent and their parent(s) in relation to Type 1 diabetes management activities.ResultsData from 29 outpatient clinic appointments, consisting of a total of 68 observed consultations, were analysed and a continuum consisting of three patterns of communication was identified (parent‐led, collaborative and adolescent‐led). Healthcare professionals should attend to the nature and extent of communication by adolescents and their parents in relation to Type 1 diabetes management activities because parent and adolescent engagement in communication during clinic appointments may also reflect their degree of involvement in daily Type 1 diabetes management.ConclusionsThis continuum provides a framework for healthcare professionals to use to identify communication patterns in consultations which in turn may allow healthcare professionals to encourage more effective communication about Type 1 diabetes management from adolescents and their parents in clinic consultations. This may have a positive impact on the sharing of Type 1 diabetes management responsibilities and adolescents’ developing self‐management skills as roles change during this developmental period.
Working with Insulin, Carbohydrates, Ketones and Exercise to Manage Diabetes (WICKED): evaluation of a self‐management course for young people with Type 1 diabetes
Authors: Johnson B. , Norman P. , Sanders T. , Elliott J. , Whitehead V. , Campbell F. , Hammond P. , Ajjan R. , Heller S. 
Published: July 2019

AbstractAimsTo evaluate a 5‐day self‐management education course for young people with Type 1 diabetes and assess its effects on knowledge, self‐efficacy, beliefs, distress, self‐management behaviours and HbA1c.MethodsThis is an evaluation of a structured education course. Young people (aged 16–24 years) with Type 1 diabetes were recruited from three diabetes centres. In the first centre, participants completed self‐report measures of knowledge, self‐efficacy, positive and negative outcome expectancies, and hypoglycaemic worries at baseline (n=47) and the end of the course (n=42). In two additional centres, participants completed these and other measures assessing self‐management behaviours, cognitive adaptation to diabetes and diabetes distress at baseline (n=32), the end of the course (n=27) and 3‐month follow‐up (n = 27). HbA1c levels were recorded at baseline (n=79), 6 months (n=77) and 12 months (n=65).ResultsThere were statistically significant increases in self‐report knowledge, self‐efficacy, positive outcome expectancies and self‐management behaviours, and a statistically significant decrease in negative outcome expectances, between baseline and the end of the course. There were also statistically significant increases in self‐report knowledge, self‐efficacy, self‐management behaviours and cognitive adaptation to diabetes between baseline and 3‐month follow‐up. Compared with baseline, HbA1c levels decreased by a mean (sd) of 5.44 (19.93) mmol/mol (0.48%) at 6 months (P=0.019), and by 5.98 (23.32) mmol/mol (0.54%) at 12 months (P =0.043).DiscussionThe results indicate the potential benefits of a self‐management course designed to address the developmental needs and challenges faced by young people with Type 1 diabetes. Further studies with larger numbers and appropriate controls are required to confirm these initial findings.
Allopatric populations of the invasive larch casebearer differ in cold tolerance and phenology
Authors: Ward Samuel F. , Eidson Erika L. , Kees Aubree M. , Venette Robert C. , Aukema Brian H. 
Published: July 2019

1. Traits of non‐native insect herbivores may vary spatially due to local genetic differences, rapid post‐introduction evolution, and/or novel host plant associations.2. Populations of larch casebearer,Coleophora laricellaHübner, originally from Europe have likely been isolated for > 60 years in North America on eastern larch,Larix laricina(Du Roi) K. Koch, and western larch,Larix occidentalisNutt.3. This study investigated cold tolerance and phenology of larvae collected from eastern larch in Minnesota, and western larch in Oregon, Idaho, and Montana, U.S.A.4. Mean supercooling points of larvae from Minnesota were up to 10 °C lower than supercooling points of larvae from Oregon, Idaho, and Montana.5. At ambient environmental conditions in spring, overwintering larvae from Minnesota required a mean (± SE) of 172 ± 19 degree‐days above 5 °C to break winter quiescence and actively wander, significantly more than required by larvae from Oregon (66 ± 4), Idaho (64 ± 1), and Montana (60 ± 2).6. Across all assays and despite substantial latitudinal and elevational variation among western larch sites, no significant differences in any traits were detected among larvae collected from western larch.7. Spatial variation in cold tolerance and phenological traits of larch casebearer may be attributable to insect genetic differences and/or host plant effects, but exact mechanisms remain unknown. Differences in thermal biology between regions may result in disparate effects of climate change on insect populations and should be accounted for when forecasting insect dynamics across large spatial scales.
Teacher competence frameworks in Hungary: A case study on the continuum of teacher learning
Authors: Symeonidis Vasileios 
Published: July 2019

AbstractThe aim of this article is to examine the development and implementation of teacher competence frameworks in Hungary. Supported by European structural funds, Hungary introduced a teacher competence framework for initial teacher education in 2006 and another for the career promotion and appraisal of teachers in 2013. Employing the process tracing method, the article follows the evolution of teacher competence frameworks over time, based on a document analysis and expert interviews with policy officials and teacher educators. Findings show that the Hungarian teacher competence frameworks evolved as an outcome of a broader Europeanisation process in teacher education, on the one hand, and of internal political priorities, on the other. Strong political commitment was often linked to weak implementation capacities, so that dissatisfaction was created on the side of teachers. Depending on the way local actors use these frameworks, some perceive it as a way of limiting teacher autonomy, whilst others feel it promotes teacher professionalism.
Stress‐induced and ATF7‐dependent epigenetic change influences cellular senescence
Authors: Maekawa Toshio , Liu Binbin , Liu Yang , Yoshida Keisuke , Muratani Masafumi , Chatton Bruno , Ishii Shunsuke 
Published: July 2019

AbstractCellular senescence plays an important role in aging and is induced by cyclin‐dependent kinase (Cdk) inhibitors that accumulate following stresses during aging. However, the underlying mechanism remains elusive. Herein, we demonstrate that activating transcription factor 7 (ATF7), the stress‐responsive recruiter of histone H3K9 di‐ and trimethyltransferases, functions in the accumulation of Cdk inhibitors. Atf7‐deficient (Atf7‒/‒) mice have a shorter lifespan than wild‐type (WT) mice. Levels of p16Ink4a Cdk inhibitor mRNA increased with age more rapidly in Atf7‒/‒ mice than in WT animals. ATF7 binds to the p16Ink4a gene promoter and was released with age. Consistently, histone H3K9me2 levels on the p16Ink4a gene promoter were lower in Atf7‒/‒ mice than in WT animals. Similar results were obtained when Atf7‒/‒ and WT mouse embryonic fibroblasts (MEFs) were cultured under 20% oxygen conditions, which induces cellular senescence via oxidative stress. Phosphorylation of ATF7 by p38 was also increased with the passage of MEFs, consistent with previous observations that ATF7 phosphorylation by p38 induces its release from chromatin. These results indicate that stress‐induced and ATF7‐dependent epigenetic changes on p16Ink4a genes play an important role in cellular senescence.