bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis
Authors: Gupta Vikas , Richards Sue , Rowe Jacob 
Published: November 2012

Abstract
Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard postremission strategies for adult acute lymphoblastic leukemia in first complete remission, but the optimal strategy remains controversial. There are no randomized trials of allogeneic HCT. In the present study, updated individual patient data were collected and analyzed from studies with information on availability of matched sibling donor (used to mimic randomization) and from randomized trials of autograft versus chemotherapy. Data from 13 studies including 2962 patients, excluding Philadelphia chromosome–positive patients, showed a survival benefit for having a matched sibling donor for patients < 35 years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those ≥ 35 years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03) because of the higher absolute risk of nonrelapse mortality for older patients. No differences were seen by risk group. There was a trend toward inferior survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P = .06). No beneficial effect of autografting was seen compared with chemotherapy in this analysis. We conclude that matched sibling donor myeloablative HCT improves survival only for younger patients, with an absolute benefit of approximately 10% at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality associated with allogeneic HCT may change the relative effects of these treatments in the future.
Proteomic characterization of the Rph15 barley resistance gene-mediated defence responses to leaf rust
Authors: Bernardo Letizia , Prinsi Bhakti , Negri Alfredo Simone , Cattivelli Luigi , Espen Luca , Valè Giampiero 
Published: November 2012

Abstract

Background
Leaf rust, caused by the biotrophic fungal pathogen Puccinia hordei, is one of the most important foliar disease of barley (Hordeum vulgare) and represents a serious threat in many production regions of the world. The leaf rust resistance gene Rph15 is of outstanding interest for resistance breeding because it confers resistance to over 350 Puccinia hordei isolates collected from around the world. Molecular and biochemical mechanisms responsible for the Rph15 effectiveness are currently not investigated. The aim of the present work was to study the Rph15-based defence responses using a proteomic approach.

Results
Protein pattern changes in response to the leaf rust pathogen infection were investigated in two barley near isogenic lines (NILs), Bowman (leaf rust susceptible) and Bowman-Rph15 (leaf rust resistant), differing for the introgression of the leaf rust resistance gene Rph15. Two infection time points, 24 hours and four days post inoculation (dpi), were analysed. No statistically significant differences were identified at the early time point, while at 4 dpi eighteen protein spots were significantly up or down regulated with a fold-change equal or higher than two in response to pathogen infection. Almost all the pathogen-responsive proteins were identified in the Bowman-Rph15 resistant NIL. Protein spots were characterized by LC-MS/MS analysis and found to be involved in photosynthesis and energy metabolism, carbohydrate metabolism, protein degradation and defence. Proteomic data were complemented by transcriptional analysis of the respective genes. The identified proteins can be related to modulation of the photosynthetic apparatus components, re-direction of the metabolism to sustain defence responses and deployment of defence proteins.

Conclusions
The identification of leaf rust infection-modulated defence responses restricted to the resistant NIL support the hypothesis that basal defence responses of Bowman, but not the Rph15 resistance gene-based ones, are suppressed or delayed by pathogen effectors to levels below the detection power of the adopted proteomic approach. Additionally, Rph15-mediated resistance processes identified mainly resides on a modulation of primary metabolism, affecting photosyntesis and carbohydrate pool.
Synergies between RNA degradation and trans-translation in Streptococcus pneumoniae: cross regulation and co-transcription of RNase R and SmpB
Authors: Moreira Ricardo N , Domingues Susana , Viegas Sandra C , Amblar Mónica , Arraiano Cecília M 
Published: November 2012

AbstractBackgroundRibonuclease R (RNase R) is an exoribonuclease that recognizes and degrades a wide range of RNA molecules. It is a stress-induced protein shown to be important for the establishment of virulence in several pathogenic bacteria. RNase R has also been implicated in thetrans-translation process. Transfer-messenger RNA (tmRNA/SsrA RNA) and SmpB are the main effectors oftrans-translation, an RNA and protein quality control system that resolves challenges associated with stalled ribosomes on non-stop mRNAs.Trans-translation has also been associated with deficiencies in stress-response mechanisms and pathogenicity.ResultsIn this work we study the expression of RNase R in the human pathogenStreptococcus pneumoniaeand analyse the interplay of this enzyme with the main components of thetrans-translation machinery (SmpB and tmRNA/SsrA). We show that RNase R is induced after a 37°C to 15°C temperature downshift and that its levels are dependent on SmpB. On the other hand, our results revealed a strong accumulation of thesmpBtranscript in the absence of RNase R at 15°C. Transcriptional analysis of theS. pneumoniae rnrgene demonstrated that it is co-transcribed with the flanking genes,secGandsmpB. Transcription of these genes is driven from a promoter upstream ofsecGand the transcript is processed to yield mature independent mRNAs. This genetic organization seems to be a common feature of Gram positive bacteria, and the biological significance of this gene cluster is further discussed.ConclusionsThis study unravels an additional contribution of RNase R to thetrans-translation system by demonstrating thatsmpBis regulated by this exoribonuclease. RNase R in turn, is shown to be under the control of SmpB. These proteins are therefore mutually dependent and cross-regulated. The data presented here shed light on the interactions between RNase R,trans-translation and cold-shock response in an important human pathogen.
The Plant Short-Chain Dehydrogenase (SDR) superfamily: genome-wide inventory and diversification patterns
Authors: Moummou Hanane , Kallberg Yvonne , Tonfack Libert Brice , Persson Bengt , van der Rest Benoît 
Published: November 2012

Abstract

Background
Short-chain dehydrogenases/reductases (SDRs) form one of the largest and oldest NAD(P)(H) dependent oxidoreductase families. Despite a conserved ‘Rossmann-fold’ structure, members of the SDR superfamily exhibit low sequence similarities, which constituted a bottleneck in terms of identification. Recent classification methods, relying on hidden-Markov models (HMMs), improved identification and enabled the construction of a nomenclature. However, functional annotations of plant SDRs remain scarce.

Results
Wide-scale analyses were performed on ten plant genomes. The combination of hidden Markov model (HMM) based analyses and similarity searches led to the construction of an exhaustive inventory of plant SDR. With 68 to 315 members found in each analysed genome, the inventory confirmed the over-representation of SDRs in plants compared to animals, fungi and prokaryotes. The plant SDRs were first classified into three major types — ‘classical’, ‘extended’ and ‘divergent’ — but a minority (10% of the predicted SDRs) could not be classified into these general types (‘unknown’ or ‘atypical’ types). In a second step, we could categorize the vast majority of land plant SDRs into a set of 49 families. Out of these 49 families, 35 appeared early during evolution since they are commonly found through all the Green Lineage. Yet, some SDR families — tropinone reductase-like proteins (SDR65C), ‘ABA2-like’-NAD dehydrogenase (SDR110C), ‘salutaridine/menthone-reductase-like’ proteins (SDR114C), ‘dihydroflavonol 4-reductase’-like proteins (SDR108E) and ‘isoflavone-reductase-like’ (SDR460A) proteins — have undergone significant functional diversification within vascular plants since they diverged from Bryophytes. Interestingly, these diversified families are either involved in the secondary metabolism routes (terpenoids, alkaloids, phenolics) or participate in developmental processes (hormone biosynthesis or catabolism, flower development), in opposition to SDR families involved in primary metabolism which are poorly diversified.

Conclusion
The application of HMMs to plant genomes enabled us to identify 49 families that encompass all Angiosperms (‘higher plants’) SDRs, each family being sufficiently conserved to enable simpler analyses based only on overall sequence similarity. The multiplicity of SDRs in plant kingdom is mainly explained by the diversification of large families involved in different secondary metabolism pathways, suggesting that the chemical diversification that accompanied the emergence of vascular plants acted as a driving force for SDR evolution.
A questionnaire-based survey to assess patient satisfaction, ease-of-learning, ease-of-use, injection site pain and overall patient satisfaction of the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen compared with other systems of gonadotrophin administration
Authors: Utsunomiya Takafumi , Tanaka Atsushi , Tatsumi Kenichi , Ezcurra Diego 
Published: November 2012

Abstract

Background
Gonadotrophins are used routinely for follicular stimulation during ovarian induction and assisted reproduction techniques. Developments in recombinant follicle-stimulating hormone preparations and their injection devices have improved patient quality of life by enabling patients to self-administer treatment at home. The objective of this study was to investigate patient experiences of learning to use and overall satisfaction with the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen.

Methods
This questionnaire-based survey study was conducted in 23 fertility centres in Japan over a period of 14 months. Patients who were receiving fertility treatment with the follitropin-alpha (FbM) prefilled pen were asked to complete a questionnaire to assess their satisfaction, ease of learning and use, and injection site pain following treatment.

Results
A total of 663 women participated in the study. The majority of patients found the instructions for administering follitropin-alpha with the prefilled pen easy to understand (83.0%; n = 546/658) and patients found that a hands-on demonstration by a nurse or doctor was the most useful tool for learning to use the follitropin-alpha (FbM) prefilled pen (80.0%; n = 497/621). Forty-eight percent (n = 318) of patients in the study had previous experience with different types of fertility medications and the majority of these patients found the follitropin-alpha (FbM) prefilled pen easier to use (75.1%; n = 232/309) and less painful (89.0%; n = 347/390) than their previous medication. The majority (80.2%; n = 521/650) of patients reported overall satisfaction with the follitropin-alpha (FbM) prefilled pen.

Conclusions
The follitropin-alpha (FbM) prefilled pen is an easy-to-use injection device according to this questionnaire-based survey. Patients who had experience of different types of fertility medication preferred the follitropin-alpha (FbM) prefilled pen to other injection devices.
Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants
Authors: Alkhafaji Ali A , Trinquart Ludovic , Baron Gabriel , Desvarieux Moïse , Ravaud Philippe 
Published: November 2012

AbstractBackground"Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society.MethodsTo assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people).ResultsIn the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency,P= 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram.ConclusionsThe clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms.
The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records
Authors: Piscitelli Prisco , Barba Maddalena , Crespi Massimo , Di Maio Massimo , Santoriello Antonio , D’Aiuto Massiliamo , Fucito Alfredo , Losco Arturo , Pentimalli Francesca , Maranta Pasquale , Chitano Giovanna , Argentiero Alberto , Neglia Cosimo , Distante Alessandro , Di Tanna Gian luca , Brandi Maria Luisa , Mazza Alfredo , Marino Ignazio R , Giordano Antonio 
Published: November 2012

Abstract

Background
Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy.

Methods
We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented.

Results
The overall number of mastectomies decreased, with an AAPC of −2.1% (−2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (−3.0%, -3.4 -3.6 and −3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5–4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6).

Conclusions
In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.
The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies
Authors: Kim Jieun E , Dager Stephen R , Lyoo In Kyoon 
Published: November 2012

AbstractAlthough the neurobiological mechanisms underlying panic disorder (PD) are not yet clearly understood, increasing amount of evidence from animal and human studies suggests that the amygdala, which plays a pivotal role in neural network of fear and anxiety, has an important role in the pathogenesis of PD. This article aims to (1) review the findings of structural, chemical, and functional neuroimaging studies on PD, (2) relate the amygdala to panic attacks and PD development, (3) discuss the possible causes of amygdalar abnormalities in PD, (4) and suggest directions for future research.
Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner
Authors: Huisman Marc C , van Golen Larissa W , Hoetjes Nikie J , Greuter Henri N , Schober Patrick , Ijzerman Richard G , Diamant Michaela , Lammertsma Adriaan A 
Published: November 2012

Abstract

Background
Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMRglu is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated.

Methods
Thirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods.

Results
After quality control, 9 CMRglu and 11 CBF scans were available for analysis. Average GM CMRglu values were 0.33 ± 0.04 μmol/cm3 per minute, and average CBF values were 0.43 ± 0.09 mL/cm3 per minute. Good correlation between NLR and parametric CMRglu measurements was obtained as well as between NLR and parametric CBF values. For CMRglu Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates.

Conclusion
Nonlinear regression analysis, allowing for the derivation of regional CBF and CMRglu values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMRglu measurements do not require invasive arterial sampling to define the input function.

Trial registration
ClinicalTrials.gov NCT00626080
Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study
Authors: Agudo Antonio , Bonet Catalina , Travier Noémie , González Carlos A. , Vineis Paolo , Bueno-de-Mesquita H. Bas , Trichopoulos Dimitrios , Boffetta Paolo , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Kaaks Rudolf , Lukanova Annekatrin , Schütze Madlen , Boeing Heiner , Tjonneland Anne , Halkjaer Jytte , Overvad Kim , Dahm Christina C. , Quirós J. Ramon , Sánchez María-José , Larrañaga Nerea , Navarro Carmen , Ardanaz Eva , Khaw Kay-Tee , Wareham Nicholas J. , Key Timothy J. , Allen Naomi E. , Trichopoulou Antonia , Lagiou Pagona , Palli Domenico , Sieri Sabina , Tumino Rosario , Panico Salvatore , Boshuizen Hendriek , Büchner Frederike L. , Peeters Petra H.M. , Borgquist Signe , Almquist Martin , Hallmans Göran , Johansson Ingegerd , Gram Inger T. , Lund Eiliv , Weiderpass Elisabete , Romieu Isabelle , Riboli Elio 
Published: November 2012

Purpose Our aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). Methods The study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AFp), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country. Results The proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AFp were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. Conclusion Using data on cancer incidence for 2008 and our AFp estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark).