bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of salvage therapy using Carfilzomib for relapsed or refractory multiple myeloma patients: a multicentre retrospective observational study
Authors: Muchtar Eli , Gatt Moshe E. , Rouvio Ory , Ganzel Chezi , Chubar Evgeni , Suriu Celia , Tadmor Tamar , Shevetz Olga , Lavi Noa , Shochat Tzippy , Cohen Yael C. , Avivi Irit , Raanani Pia , Magen Hila 
Published: November 2015

SummaryCarfilzomib has been established in previous years as a treatment for patients with relapsed and/or refractory multiple myeloma (RR‐MM). A retrospective multicentre study to evaluate the clinical use of carfilzomib for RR‐MM outside of a clinical trial setting was conducted by our group. One hundred and thirty‐five patients were included. All patients had been previously exposed to bortezomib and 93% had also been treated with lenalidomide. The vast majority of patients received carfilzomib as part of a two‐ or three‐drug combination. The overall response rate was 47·2%. Multivariate analysis revealed bortezomib resistance, lenalidomide resistance and albumin <35 g/l to negatively impact the likelihood of achieving response. The median duration of response was 8·4 months, and was significantly higher in patients receiving three‐drug combination and patients presenting without extramedullary disease. The median progression‐free survival and overall survival for the entire cohort was 4·9 months (95% confidence interval [CI] 3·8–6·4) and 12·2 months (95% CI 9‐not reached), respectively. Toxicity was manageable, although treatment‐related death was seen in 5% of patients. In the setting of progressive multiple myeloma, carfilzomib in a combination regimens yields effective results with a manageable toxicity.
Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high‐risk MDS
Authors: Mawad Raya , Becker Pamela S. , Hendrie Paul , Scott Bart , Wood Brent L. , Dean Carol , Sandhu Vicky , Deeg Hans Joachim , Walter Roland , Wang Lixia , Myint Han , Singer Jack W. , Estey Elihu , Pagel John M. 
Published: November 2015

AbstractTosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high‐risk myelodysplastic syndrome (MDS). Thirty‐four patients ≥60 years old (median age 70 years; range, 60–83) were randomized to receive tosedostat (120 mg on days 1–21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2/d) or decitabine (20 mg/m2/d) every 35 d. Twenty‐nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS‐refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3‐internal tandem duplication mutations. Median follow‐up was 11·2 months (range, 0·5–22·3), and median survival was 11·5 months (95% confidence interval, 5·2–16·7). Twenty‐three patients (67·6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3–4 non‐haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials.
The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab
Authors: Forero‐Castro Maribel , Robledo Cristina , Lumbreras Eva , Benito Rocio , Hernández‐Sánchez Jesús M. , Hernández‐Sánchez María , García Juan L. , Corchete‐Sánchez Luis A. , Tormo Mar , Barba Pere , Menárguez Javier , Ribera Jordi , Grande Carlos , Escoda Lourdes , Olivier Carmen , Carrillo Estrella , García de Coca Alfonso , Ribera Josep‐María , Hernández‐Rivas Jesús M. 
Published: November 2015

SummaryThe introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose‐Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array‐based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next‐generation sequencing (NGS). Ninety‐seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression‐free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array‐CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia
Authors: Irving Julie A. E. 
Published: November 2015

SummaryAcute lymphoblastic leukaemia is the most common childhood cancer and for those children who relapse, prognosis is poor and new therapeutic strategies are needed. Recurrent pathways implicated in relapse include RAS, JAK STAT, cell cycle, epigenetic regulation, B cell development, glucocorticoid response, nucleotide metabolism and DNA repair. Targeting these pathways is a rational therapeutic strategy and may deliver novel, targeted therapies into the clinic. Relapse often stems from a minor clone present at diagnosis and thus analysis of persisting leukaemia during upfront therapy may allow targeted drug intervention to prevent relapse.
A review of chemical reactions of nitrification intermediates and their role in nitrogen cycling and nitrogen trace gas formation in soil
Authors: Heil J. , Vereecken H. , Brüggemann N. 
Published: November 2015

SummarySoil is a major source of nitrogen trace gases (NTGs). Microbial denitrification has long been identified as a source of NTGs under reducing conditions, whereas the production of NTGs during nitrification is far from being completely understood. This review updates information about the role of abiotic processes in the formation of gaseous N products in soil and brings attention to the potential interplay of microbial and chemical soil processes that tend to be neglected in research on NTG emissions. Several reactions that involve the nitrification intermediates, nitrite (NO2−) and hydroxylamine (NH2OH), are known to produce the NTGs nitric oxide (NO) and nitrous oxide (N2O). These abiotic reactions are: the self‐decomposition of NO2−, reactions of NO2− with reduced metal cations, nitrosation of soil organic matter (SOM) by NO2−, the reaction between NO2− and NH2OH, and the oxidation of NH2OH by Fe3+ or MnO2. These reactions can occur over a broad range of soil characteristics, but they are disregarded in most current research on NTG studies in favour of biological processes only. Relatively few studies have tried to quantify the contribution of abiotic processes to total NTG emissions, which results in uncertainty in emission models and mitigation strategies. It is difficult to discriminate between biological and abiotic sources because both processes can proceed at the same time in the same soil layer. The potential of stable isotope techniques to disentangle the different processes in soil and to constrain budgets of atmospheric NTGs better are highlighted. Recent advances in stable isotope technologies, such as infrared real‐time laser spectroscopy, provide considerable potential for both natural abundance and tracer studies in this field.
Causality between abundance and diversity is weak for wintering migratory waterbirds
Authors: Guan Lei , Jia Yifei , Saintilan Neil , Wang Yuyu , Liu Guanhua , Lei Guangchun , Wen Li 
Published: November 2015

Summary

The species–area relationship, which is closely linked with the more general species‐energy theory, is one of the most well‐known patterns in geographical ecology, but the underlying causes remain contentious. The more individuals hypothesis (MIH) articulates a causal path from resource availability to population abundance to species richness. The MIH has been tested with a range of taxa including plants, invertebrates and land birds but never with migratory waterbirds.

Using multiyear simultaneous survey data of wintering waterbirds in 10 lakes at Poyang Lake, China, and remotely sensed habitat condition measurements, we applied structural equation modelling (SEM) to test three causal paths: (A) good habitat conditions (e.g. habitat availability and heterogeneity) attract more species (high richness); (B) habitat conditions promote abundance (more individuals); and (C) habitat conditions promote abundance, which in turn increases richness.

We also modelled responses of species richness and abundance to habitat conditions using generalised additive mixed modelling (GAMM) to assess their co‐variation.

While our analysis confirmed the first two paths, we found no support for the third, which is the central postulate of the MIH. In addition, in agreement with GAMM, SEM indicated that species richness was more closely related to habitat quality than to abundance. Our findings suggest that wintering waterbird species richness and abundance are two intrinsic community indices that covary with environmental variables.
Candidates’ Education and Turnout: Evidence from Italyn Municipal Elections
Authors: Benedetto Marco Alberto De , Paola Maria De 
Published: November 2015

Abstract
We analyze the impact that the educational level of candidates running for the position of mayor has on electoral turnout by using a large dataset for Italyn municipal elections held between 1993 and 2011. We firstly estimate a municipality fixed effects model and show that the median education of candidates standing in an election is positively correlated with turnout. To handle endogeneity issues arising from the unobservable time variant features of electoral races, we build on the literature which shows that politicians’ educational level is positively affected by their wage and apply a Fuzzy Regression Discontinuity Design on the basis of the fact that the wages of mayors in Italy increase non-monotonically at different thresholds. Results show that an exogenous increase in the median educational level of candidates, induced by a higher wage, leads to an increase in turnout of about 1 percentage point.
Genetic association between leg conformation in young pigs and sow longevity
Authors: Le T.H. , Madsen P. , Lundeheim N. , Nilsson K. , Norberg E. 
Published: November 2015

SummaryLongevity is important in pig production with respect to both economic and ethical aspects. Direct selection for longevity might be ineffective because ‘true’ longevity can only be recorded when a sow has been culled or died. Thus, indirect selection for longevity using information from other traits that can be recorded early in life and are genetically correlated with longevity might be an alternative. Leg conformation has been included in many breeding schemes for a number of years. However, proving that leg conformation traits are good early indicators for longevity still remains. Our aim was to study genetic associations between leg conformation traits of young (5 months; 100 kg) Swedish Yorkshire pigs in nucleus herds and longevity traits of sows in nucleus and multiplier herds. Data included 97 533 animals with information on conformation (Movement and Overall score) recorded at performance testing and 26 962 sows with information on longevity. The longevity traits were as follows: stayability from 1st to 2nd parity, lifetime number of litters and lifetime number of born alive piglets. Genetic analyses were performed with both linear models using REML and linear‐threshold models using Bayesian methods. Heritabilities estimated using the Bayesian method were higher than those estimated using REML, ranging from 0.10 to 0.24 and 0.07 to 0.20, respectively. All estimated genetic correlations between conformation and longevity traits were significant and favourable. Heritabilities and genetic correlations between conformation and longevity indicate that selection on leg conformation should improve sow longevity.
Role of habitat heterogeneity and landscape connectivity in shaping gene flow and spatial population structure of a dominant rodent species in a tropical dry forest
Authors: Garrido‐Garduño T. , Téllez‐Valdés O. , Manel S. , Vázquez‐Domínguez E. 
Published: November 2015

AbstractEvaluating how habitat heterogeneity and landscape connectivity influence fine‐scale population processes of gene flow and spatial population structure is key for understanding animal dispersal. Liomys pictus is a heteromyid rodent that inhabits tropical dry deciduous and semideciduous forests, where it is a dominant, abundant species and a key element on the ecosystem as seed disperser. We evaluated how landscape features shaped the genetic structure and gene flow at a fine scale among L. pictus populations in a well‐conserved natural environment. On the basis of L. pictus ecological characteristics (e.g. dominant species, female philopatry), we predicted that forested areas (irrespective of vegetation type) should facilitate dispersal if the forest vegetation acted as a kind of corridor, and that these patterns will be different between sexes. We tested these assumptions (104 individuals, six sampling localities, 14 microsatellite loci) after checking for discrete genetic groups using Bayesian clustering methods, by assessing the effect of landscape variables on patterns of gene flow combining Mantel and partial Mantel tests, least‐cost path and circuit theories. L. pictus differentiated into genetic clusters delimited by clear landscape boundaries. Accordingly, resistance hypotheses results showed that precipitation and stream channels were the main environmental and landscape attributes influencing gene flow. Exchange of a majority of migrants was detected from the center into other sampling localities, indicating higher dispersal throughout deciduous and semideciduous forest corridors, whereas isolation by distance was found only for females. Our approach allowed us to elucidate animal environmental space use, identifying some of the landscape features linked to the species dispersal patterns, which can serve as a basis for the study and comparison with other tropical forests and species. It can also have conservation applications, for instance, preserving the forested corridors we identified as significant for dispersal can likely benefit other codistributed, threatened rodent species.
Survey of outcomes in a faculty development program on simulation pedagogy
Authors: Roh Young Sook , Kim Mi Kang , Tangkawanich Thitiarpha 
Published: November 2015

AbstractAlthough many nursing programs use simulation as a teaching‐learning modality, there are few systematic approaches to help nursing educators learn this pedagogy. This study evaluates the effects of a simulation pedagogy nursing faculty development program on participants' learning perceptions using a retrospective pre‐course and post‐course design. Sixteen Thai participants completed a two‐day nursing faculty development program on simulation pedagogy. Thirteen questionnaires were used in the final analysis. The participants' self‐perceived learning about simulation teaching showed significant post‐course improvement. On a five‐point Likert scale, the composite mean attitude, subjective norm, and perceived behavioral control scores, as well as intention to use a simulator, showed a significant post‐course increase. A faculty development program on simulation pedagogy induced favorable learning and attitudes. Further studies must test how faculty performance affects the cognitive, emotional, and social dimensions of learning in a simulation‐based learning domain.
Structural outcomes in the Cleft Care UK study. Part 2: dento‐facial outcomes
Authors: Al‐Ghatam R. , Jones T. E. M. , Ireland A. J. , Atack N. E. , Chawla O. , Deacon S. , Albery L. , Cobb A. R. M. , Cadogan J. , Leary S. , Waylen A. , Wills A. K. , Richard B. , Bella H. , Ness A. R. , Sandy J. R. 
Published: November 2015

Structured AbstractObjectivesTo compare facial appearance and dento‐alveolar relationship outcomes from the CSAG (1998) and CCUK (2013) studies.Setting and sample populationFive‐year‐olds born with non‐syndromic unilateral cleft lip and palate. Those in the original CSAG were treated in a dispersed model of care with low‐volume operators. Those in CCUK were treated in a more centralized, high‐volume operator model.Materials and methodsWe compared facial appearance using frontal view photographs (252 CCUK, 239 CSAG) and dental relationships using study models (198 CCUK, 223 CSAG). Facial appearance was scored by a panel of six assessors using a standardized and validated outcome tool. Dento‐alveolar relationships were scored by two assessors using the 5‐Year‐Olds’ Index. Ordinal regression was used to compare results between surveys.ResultsExcellent or good facial appearance was seen in 36.2% of CCUK compared with 31.9% in CSAG. In CCUK, 21.6% were rated as having poor or very poor facial appearance compared with 27.6% in CSAG. The percentage rated as having excellent or good dento‐alveolar relationships was 53.0% in CCUK compared with 29.6% in CSAG. In CCUK, 19.2% were rated as having poor or very poor dento‐alveolar relationships compared to 36.3% in CSAG. The odds ratios for improved outcome in CCUK compared to CSAG were 1.43 (95% CI 1.03, 1.97) for facial appearance and 2.29 (95% CI 1.47, 3.55) for dento‐alveolar relationships.ConclusionsFacial and dento‐alveolar outcomes were better in CCUK children compared to those in CSAG.
Functional outcomes in the Cleft Care UK study – Part 3: oral health and audiology
Authors: Smallridge J. , Hall A. J. , Chorbachi R. , Parfect V. , Persson M. , Ireland A. J. , Wills A. K. , Ness A. R. , Sandy J. R. 
Published: November 2015

Structured AbstractObjectivesTo compare oral health and hearing outcomes from the Clinical Standards Advisory Group (CSAG, 1998) and the Cleft Care UK (CCUK, 2013) studies.Setting and sample populationTwo UK‐based cross‐sectional studies of 5‐year‐olds born with non‐syndromic unilateral cleft lip and palate undertaken 15 years apart. CSAG children were treated in a dispersed model of care with low‐volume operators. CCUK children were treated in a centralized, high volume operator system.Materials and methodsOral health data were collected using a standardized proforma. Hearing was assessed using pure tone audiometry and middle ear status by otoscopy and tympanometry. ENT and hearing history were collected from medical notes and parental report.ResultsOral health was assessed in 264 of 268 children (98.5%). The mean dmft was 2.3, 48% were caries free, and 44.7% had untreated caries. There was no evidence this had changed since the CSAG survey. Oral hygiene was generally good, 96% were enrolled with a dentist. Audiology was assessed in 227 of 268 children (84.7%). Forty‐three per cent of children received at least one set of grommets – a 17.6% reduction compared to CSAG. Abnormal middle ear status was apparent in 50.7% of children. There was no change in hearing levels, but more children with hearing loss were managed with hearing aids.ConclusionsOutcomes for dental caries and hearing were no better in CCUK than in CSAG, although there was reduced use of grommets and increased use of hearing aids. The service specifications and recommendations should be scrutinized and implemented.
Cleft Care UK study. Part 5: child psychosocial outcomes and satisfaction with cleft services
Authors: Waylen A. , Ness A. R. , Wills A. K. , Persson M. , Rumsey N. , Sandy J. R. 
Published: November 2015

Structured AbstractObjectivesTo describe the impact of cleft service centralization on parental perceptions of child outcomes and satisfaction with care from the Cleft Care UK (CCUK) study and compare them to the Clinical Standards Advisory Group (CSAG) study that took place 15 years earlier.Setting and Sample PopulationA subgroup of respondents from a UK multicentre cross‐sectional study (CCUK) of 5‐year‐olds born with non‐syndromic unilateral cleft lip and palate.Materials and MethodsData on parents’ perceptions of child self‐confidence and their satisfaction with treatment outcomes and service provision were collected via self‐report questionnaires. Data were compared with findings from the 1998 CSAG study.ResultsFewer parents in the CCUK study perceived their children as having poor self‐confidence than in the 1998 CSAG study (8 and 19%, respectively). At least 81% of parents report satisfaction with the child's facial features after surgery and 98% report being satisfied with the care received. These results are similar to those reported in 1998. There is no evidence of an adverse impact on families’ ability to attend appointments at the cleft clinic following centralization. Levels of reported problems (around 30%) with attendance were similar to those reported by CSAG.ConclusionCentralization of cleft services appears to have improved parental perceptions of some child outcomes but has made little difference to already high levels of parental satisfaction with cleft care services. Centralization is not associated with an increase in the proportion of families who find it difficult to attend appointments.
The SloR metalloregulator is involved in the Streptococcus mutans oxidative stress response
Authors: Crepps S.C. , Fields E.E. , Galan D. , Corbett J.P. , Von Hasseln E.R. , Spatafora G.A. 
Published: November 2015

SummarySloR, a 25‐kDa metalloregulatory protein in Streptococcus mutans modulates the expression of multiple genes, including the sloABC operon that encodes essential Mn2+ transport and genes that promote cariogenesis. In this study, we report on SloC‐ and SloR‐deficient strains of S. mutans (GMS284 and GMS584, respectively) that demonstrate compromised survivorship compared with their UA159 wild‐type progenitor and their complemented strains (GMS285 and GMS585, respectively), when challenged with streptonigrin and/or in growth competition experiments. The results of streptonigrin assays revealed significantly larger zones of inhibition for GMS584 than for either UA159 or GMS585, indicating weakened S. mutans survivorship in the absence of SloR. Competition assays revealed a compromised ability for GMS284 and GMS584 to survive peroxide challenge compared with their SloC‐ and SloR‐proficient counterparts. These findings are consistent with a role for SloC and SloR in S. mutans aerotolerance. We also predicted differential expression of oxidative stress tolerance genes in GMS584 versus UA159 and GMS585 when grown aerobically. The results of quantitative RT‐PCR experiments revealed S. mutans sod, tpx, and sloC expression that was upregulated in GMS584 compared with UA159 and GMS585, indicating that the impact of oxidative stress on S. mutans is more severe in the absence of SloR than in its presence. The results of electrophoretic mobility shift assays indicate that SloR does not bind to the sod or tpx promoter regions directly, implicating intermediaries that may arbitrate the SloR response to oxidative stress.