bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adeno-associated viral vectors engineered for macrolide-adjustable transgene expression In mammalian cells and mice
Authors: Fluri David A , Baba Marie Daoud-El , Fussenegger Martin 
Published: November 2007

Abstract

Background
Adjustable gene expression is crucial in a number of applications such as de- or transdifferentiation of cell phenotypes, tissue engineering, various production processes as well as gene-therapy initiatives. Viral vectors, based on the Adeno-Associated Virus (AAV) type 2, have emerged as one of the most promising types of vectors for therapeutic applications due to excellent transduction efficiencies of a broad variety of dividing and mitotically inert cell types and due to their unique safety features.

Results
We designed recombinant adeno-associated virus (rAAV) vectors for the regulated expression of transgenes in different configurations. We integrated the macrolide-responsive E.REX systems (EON and EOFF) into rAAV backbones and investigated the delivery and expression of intracellular as well as secreted transgenes for binary set-ups and for self- and auto-regulated one-vector configurations. Extensive quantitative analysis of an array of vectors revealed a high level of adjustability as well as tight transgene regulation with low levels of leaky expression, both crucial for therapeutical applications. We tested the performance of the different vectors in selected biotechnologically and therapeutically relevant cell types (CHO-K1, HT-1080, NHDF, MCF-7). Moreover, we investigated key characteristics of the systems, such as reversibility and adjustability to the regulating agent, to determine promising candidates for in vivo studies. To validate the functionality of delivery and regulation we performed in vivo studies by injecting particles, coding for compact self-regulated expression units, into mice and adjusting transgene expression.

Conclusion
Capitalizing on established safety features and a track record of high transduction efficiencies of mammalian cells, adeno- associated virus type 2 were successfully engineered to provide new powerful tools for macrolide-adjustable transgene expression in mammalian cells as well as in mice.
Effectiveness and costs of implementation strategies to reduce acid suppressive drug prescriptions: a systematic review
Authors: Smeets Hugo M , Hoes Arno W , de Wit Niek J 
Published: November 2007

Abstract
Background
Evaluation of evidence for the effectiveness of implementation strategies aimed at reducing prescriptions for the use of acid suppressive drugs (ASD).

Methods
A systematic review of intervention studies with a design according to research quality criteria and outcomes related to the effect of reduction of ASD medication retrieved from Medline, Embase and the Cochrane Library. Outcome measures were the strategy of intervention, quality of methodology and results of treatment to differences of ASD prescriptions and costs.

Results
The intervention varied from a single passive method to multiple active interactions with GPs. Reports of study quality had shortcomings on subjects of data-analysis. Not all outcomes were calculated but if so rction of prescriptions varied from 8% up to 40% and the cost effectiveness was in some cases negative and in others positive. Few studies demonstrated good effects from the interventions to reduce ASD.

Conclusion
Poor quality of some studies is limiting the evidence for effective interventions. Also it is difficult to compare cost-effectiveness between studies. However, RCT studies demonstrate that active interventions are required to reduce ASD volume. Larger multi-intervention studies are necessary to evaluate the most successful intervention instruments.
Older adults' perspectives on key domains of childhood social and economic experiences and opportunities: a first step to creating a multidimensional measure
Authors: Yen Irene H , Stewart Anita L , Scherzer Teresa , Pérez-Stable Eliseo J 
Published: November 2007

Abstract
Objectives
Although research has found that childhood socioeconomic status (SES) is associated with physical and mental health in mid- and later life, most of these studies used conventional, single dimension SES measures for the childhood period such as household income or educational attainment of parents. Life course and health disparities research would benefit from identification and measurement of a variety of childhood social and economic experiences and opportunities that might affect health in later life.

Design
This study utilized qualitative research methods to identify key dimensions of childhood experiences related to SES. We conducted in-depth interviews with 25 adults age 55 to 80 years from diverse economic and ethnic backgrounds. Topics included home, neighborhood, school, and work experiences during early childhood and adolescence. Interviews were audio-taped and transcripts were coded to identify thematic domains.

Results
We identified eight thematic domains, many of which had clear subdomains: home and family circumstances, neighborhood, work and money, potential for advancement through schooling, school quality and content, discrimination, influence and support of adults, and leisure activities. These domains highlight individual characteristics and experiences and also economic and educational opportunities.

Conclusion
These domains of childhood social and economic circumstances add breadth and depth to conventional conceptualization of childhood SES. When the domains are translated into a measurement tool, it will allow for the possibility of classifying people along multiple dimensions, such as from a low economic circumstance with high levels of adult support.
Calibrating E-values for MS2 database search methods
Authors: Alves Gelio , Ogurtsov Aleksey Y , Wu Wells W , Wang Guanghui , Shen Rong-Fong , Yu Yi-Kuo 
Published: November 2007

Abstract

Background
The key to mass-spectrometry-based proteomics is peptide identification, which relies on software analysis of tandem mass spectra. Although each search engine has its strength, combining the strengths of various search engines is not yet realizable largely due to the lack of a unified statistical framework that is applicable to any method.

Results
We have developed a universal scheme for statistical calibration of peptide identifications. The protocol can be used for both de novo approaches as well as database search methods. We demonstrate the protocol using only the database search methods. Among seven methods -SEQUEST (v27 rev12), ProbID (v1.0), InsPecT (v20060505), Mascot (v2.1), X!Tandem (v1.0), OMSSA (v2.0) and RAId_DbS – calibrated, except for X!Tandem and RAId_DbS most methods require a rescaling according to the database size searched. We demonstrate that our calibration protocol indeed produces unified statistics both in terms of average number of false positives and in terms of the probability for a peptide hit to be a true positive. Although both the protocols for calibration and the statistics thus calibrated are universal, the calibration formulas obtained from one laboratory with data collected using either centroid or profile format may not be directly usable by the other laboratories. Thus each laboratory is encouraged to calibrate the search methods it intends to use. We also address the importance of using spectrum-specific statistics and possible improvement on the current calibration protocol. The spectra used for statistical (E-value) calibration are freely available upon request.

Open peer review
Reviewed by Dongxiao Zhu (nominated by Arcady Mushegian), Alexey Nesvizhskii (nominated by King Jordan) and Vineet Bafna. For the full reviews, please go to the Reviewers' comments section.
A procephalic territory in Drosophila exhibiting similarities and dissimilarities compared to the vertebrate midbrain/hindbrain boundary region
Authors: Urbach Rolf 
Published: November 2007

Abstract
Background
In vertebrates, the primordium of the brain is subdivided by the expression of Otx genes (forebrain/anterior midbrain), Hox genes (posterior hindbrain), and the genes Pax2, Pax5 and Pax8 (intervening region). The latter includes the midbrain/hindbrain boundary (MHB), which acts as a key organizer during brain patterning. Recent studies in Drosophila revealed that orthologous sets of genes are expressed in a similar tripartite pattern in the late embryonic brain, which suggested correspondence between the Drosophila deutocerebral/tritocerebral boundary region and the vertebrate MHB. To gain more insight into the evolution of brain regions, and particularly the MHB, I examined the expression of a comprehensive array of MHB-specific gene orthologs in the procephalic neuroectoderm and in individually identified neuroblasts during early embryonic stages 8-11, at which the segmental organization of the brain is most clearly displayed.

Results and conclusion
I show that the early embryonic brain exhibits an anterior Otx/otd domain and a posterior Hox1/lab domain, but that Pax2/5/8 orthologs are not expressed in the neuroectoderm and neuroblasts of the intervening territory. Furthermore, the expression domains of Otx/otd and Gbx/unpg exhibit a small common interface within the anterior deutocerebrum. In contrast to vertebrates, Fgf8-related genes are not expressed posterior to the otd/unpg interface. However, at the otd/unpg interface the early expression of other MHB-specific genes (including btd, wg, en), and of dorsoventral patterning genes, closely resembles the situation at the vertebrate MHB. Altogether, these results suggest the existence of an ancestral territory within the primordium of the deutocerebrum and adjacent protocerebrum, which might be the evolutionary equivalent of the region of the vertebrate MHB. However, lack of expression of Pax2/5/8 and Fgf8-related genes, and significant differences in the expression onset of other key regulators at the otd/unpg interface, imply that genetic interactions crucial for the vertebrate organizer activity are absent in the early embryonic brain of Drosophila.
Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans
Authors: Bauer Huang Sarah L , Saheki Yasunori , VanHoven Miri K , Torayama Ichiro , Ishihara Takeshi , Katsura Isao , van der Linden Alexander , Sengupta Piali , Bargmann Cornelia I 
Published: November 2007

Abstract
Background
The left and right AWC olfactory neurons in Caenorhabditis elegans differ in their functions and in their expression of chemosensory receptor genes; in each animal, one AWC randomly takes on one identity, designated AWCOFF, and the contralateral AWC becomes AWCON. Signaling between AWC neurons induces left-right asymmetry through a gap junction network and a claudin-related protein, which inhibit a calcium-regulated MAP kinase pathway in the neuron that becomes AWCON.

Results
We show here that the asymmetry gene olrn-1 acts downstream of the gap junction and claudin genes to inhibit the calcium-MAP kinase pathway in AWCON. OLRN-1, a protein with potential membrane-association domains, is related to the Drosophila Raw protein, a negative regulator of JNK mitogen-activated protein (MAP) kinase signaling. olrn-1 opposes the action of two voltage-activated calcium channel homologs, unc-2 (CaV2) and egl-19 (CaV1), which act together to stimulate the calcium/calmodulin-dependent kinase CaMKII and the MAP kinase pathway. Calcium channel activity is essential in AWCOFF, and the two AWC neurons coordinate left-right asymmetry using signals from the calcium channels and signals from olrn-1.

Conclusion
olrn-1 and voltage-activated calcium channels are mediators and targets of AWC signaling that act at the transition between a multicellular signaling network and cell-autonomous execution of the decision. We suggest that the asymmetry decision in AWC results from the intercellular coupling of voltage-regulated channels, whose cross-regulation generates distinct calcium signals in the left and right AWC neurons. The interpretation of these signals by the kinase cascade initiates the sustained difference between the two cells.
The determinants of gene order conservation in yeasts
Authors: Poyatos Juan F , Hurst Laurence D 
Published: November 2007

Abstract
Background
Why do some groups of physically linked genes stay linked over long evolutionary periods? Although several factors are associated with the formation of gene clusters in eukaryotic genomes, the particular contribution of each feature to clustering maintenance remains unclear.

Results
We quantify the strength of the proposed factors in a yeast lineage. First we identify the magnitude of each variable to determine linkage conservation by using several comparator species at different distances to Saccharomyces cerevisiae. For adjacent gene pairs, in line with null simulations, intergenic distance acts as the strongest covariate. Which of the other covariates appear important depends on the comparator, although high co-expression is related to synteny conservation commonly, especially in the more distant comparisons, these being expected to reveal strong but relatively rare selection. We also analyze those pairs that are immediate neighbors through all the lineages considered. Current intergene distance is again the best predictor, followed by the local density of essential genes and co-regulation, with co-expression and recombination rate being the weakest predictors. The genome duplication seen in yeast leaves some mark on linkage conservation, as adjacent pairs resolved as single copy in all post-whole genome duplication species are more often found as adjacent in pre-duplication species.

Conclusion
Current intergene distance is consistently the strongest predictor of synteny conservation as expected under a simple null model. Other variables are of lesser importance and their relevance depends both on the species comparison in question and the fate of the duplicates following genome duplication.
IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis
Authors: Antonopoulos Christos , Cumberbatch Marie , Mee John B , Dearman Rebecca J , Wei Xiao-Qing , Liew Foo Y , Kimber Ian , Groves Richard W 
Published: November 2007

AbstractLangerhans cells (LC) migrate rapidly from epidermis to lymph node following epicutaneous application of antigen. In this study, we have explored the role of IL-18, a cytokine with structural similarities to IL-1β, in murine LC migration and contact hypersensitivity (CHS), which to oxazolone (OX) and 2-4,dinitrofluorobenzene (DNFB) was suppressed significantly in IL-18 knockout (IL-18−/−) mice and could be rescued by local intradermal administration of IL-18 prior to sensitization, suggesting that the defect in these mice was in the afferent phase of CHS. To determine the effect of IL-18 on LC migration, mice were treated topically with OX or DNFB, and remaining LC numbers were assessed. A significant decline in remaining epidermal LC occurred in wild-type (WT) mice but did not occur in IL-18−/− mice. Sodium lauryl sulfate, a nonantigenic LC migratory stimulus, induced equivalent LC migration in IL-18−/− and WT mice. In IL-18−/− mice, IL-1β and TNF-α were equally able to mobilize LC from epidermis, indicating that migration in response to these cytokines is not dependent on IL-18 and suggesting that IL-18 acts upstream of these cytokines in the initiation of antigen-induced LC migration. Moreover, IL-1β but not IL-18 was able to rescue the defective CHS response observed in caspase-1−/− mice, which have no functional IL-1β or IL-18. These data indicate that IL-18 is a key proximal mediator of LC migration and CHS, acting upstream of IL-1β and TNF-α, and may play a central role in regulation of cutaneous immune responses.
Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1
Authors: Björkman Lena , Karlsson Jennie , Karlsson Anna , Rabiet Marie-Josèphe , Boulay Francois , Fu Huamei , Bylund Johan , Dahlgren Claes 
Published: November 2007

AbstractSerum amyloid A (SAA) is one of the acute-phase reactants, a group of plasma proteins that increases immensely in concentration during microbial infections and inflammatory conditions, and a close relationship between SAA levels and disease activity in rheumatoid arthritis (RA) has been observed. RA is an inflammatory disease, where neutrophils play important roles, and SAA is thought to participate in the inflammatory reaction by being a neutrophil chemoattractant and inducer of proinflammatory cytokines. The biological effects of SAA are reportedly mediated mainly through formyl peptide receptor like-1 (FPRL1), a G protein-coupled receptor (GPCR) belonging to the formyl peptide receptor family. Here, we confirmed the affinity of SAA for FPRL1 by showing that stably transfected HL-60 cells expressing FPRL1 were activated by SAA and that the response was inhibited by the use of the FPRL1-specific antagonist WRWWWW (WRW4). We also show that SAA activates the neutrophil NADPH-oxidase and that a reserve pool of receptors is present in storage organelles mobilized by priming agents such as TNF-α and LPS from Gram-negative bacteria. The induced activity was inhibited by pertussis toxin, indicating the involvement of a GPCR. However, based on FPRL1-specific desensitization and use of FPRL1 antagonist WRW4, we found the SAA-mediated effects in neutrophils to be independent of FPRL1. Based on these findings, we conclude that SAA signaling in neutrophils is mediated through a GPCR, distinct from FPRL1. Future identification and characterization of the SAA receptor could lead to development of novel, therapeutic targets for treatment of RA.
Computed Tomography Scans Do Not Improve the Predictive Power of 1996 National Cancer Institute–Sponsored Working Group Chronic Lymphocytic Leukemia Response Criteria
Authors: Blum Kristie A. , Young Donn , Broering Sarah , Lucas Margaret S. , Fischer Beth , Lin Thomas S. , Grever Michael R. , Byrd John C. 
Published: November 2007

Purpose National Cancer Institute–sponsored Working Group (NCI-WG) response criteria for chronic lymphocytic leukemia (CLL) rely on physical examination, blood, and bone marrow evaluations. The widespread use of computed tomography (CT) scans has prompted many to advocate for the incorporation of this test into CLL response criteria. Patients and Methods In a retrospective review of 82 CLL patients treated at the Ohio State University (Columbus, OH), we compared CT assessed response using non-Hodgkin's lymphoma (NHL) response definitions with NCI-WG response. Results Responses by NCI-WG criteria included five complete responses (CRs), 32 partial responses (PRs), 21 patients with stable disease (SD), 17 patients with progressive disease (PD), and seven patients not assessable (NA). Responses by NHL-CT criteria included three CRs, 12 unconfirmed CRs (CRus), 16 PRs, 26 with SD, four with PD, and 21 NA. Using NCI-WG criteria, progression-free survival (PFS) was 27.3 months for CR and 11.4 months for PR. With NHL-CT criteria, PFS was 18.4 months for CR, 11.7 months for CRu, and 14.5 months for PR. In multivariate analysis, both NCI-WG and NHL-CT response correlated with PFS (P = .009 and .001, respectively). Conclusion Current NCI-WG CLL response criteria are a significant predictor of PFS in previously treated CLL patients, with no additional benefit from the inclusion of CT scans. Although retrospective, these results highlight the importance of prospective validation of CT scans before routine inclusion in CLL response criteria.
Major Congenital Anomalies Place Extremely Low Birth Weight Infants at Higher Risk for Poor Growth and Developmental Outcomes
Authors: Walden Rachel V. , Taylor Sarah C. , Hansen Nellie I. , Poole W. Kenneth , Stoll Barbara J. , Abuelo Dianne , Vohr Betty R. ,   for the National Institute of Child Health and Human Development Neonatal Research Network
Published: November 2007

BACKGROUND. Studies of growth and neurodevelopmental impairment in extremely low birth weight infants often exclude infants with major congenital anomalies; thus, there are few outcome data available on these infants.OBJECTIVES. The purpose of this work was to compare growth and neurodevelopmental outcomes of extremely low birth weight infants with major anomalies to extremely low birth weight infants without these findings. It was hypothesized that infants with severe anomalies would have worse growth, neurodevelopmental, and survival outcomes.METHODS. A retrospective cohort analysis was performed on 5920 extremely low birth weight infants surviving beyond 12 hours of life at 19 neonatal network centers between 1998 and 2001. Infants with significant anomalies were more likely to die before 18 to 22 months' corrected age. A total of 3705 children underwent neurodevelopmental and anthropometric evaluation at 18 to 22 months' corrected age. Statistical significance for unadjusted comparisons was determined by Wilcoxon tests for continuous variables and χ2 or Fisher's exact tests for categorical variables. Regression models were used to compare the outcomes after adjusting for potential confounders.RESULTS. Children with major congenital anomalies were more likely to have Bayley Mental Development Index scores of ≤70, Psychomotor Development Index scores of ≤70, neurodevelopmental impairment, moderate-to-severe cerebral palsy, length in the ≤10th percentile, head circumference in the ≤10th percentile, more rehospitalizations, and higher rates of early intervention use at 18 to 22 months' corrected age.CONCLUSIONS. At 18 to 22 months' corrected age, extremely low birth weight infants born with major anomalies have nearly twice the risk for neurodevelopmental impairment, increased risk of poor growth, and &gt;3 times greater risk of rehospitalization when compared with extremely low birth weight infants without major anomalies. This information may be valuable for counseling parents regarding the outcomes of these infants and for the facilitation of appropriate support and intervention services.
Endoscopos stent vagy sebészi bypass? A pancreastumor esetében alkalmazható palliatív módszerek összehasonlítása klinikai vizsgálatok bizonyítékai alapjánr
Authors: Olgyai Gábor , Oláh Attila 
Published: November 2007

Absztrakt
A szerzők a rendelkezésre álló legfrissebb evidence based adatok alapján tekintik át az irresecabilis pancreastumorok kapcsán alkalmazható palliatív módszerek két alternatívájának, a hagyományos sebészi bypassműtéteknek és az endoscopos stentimplantatióknak az eredményeit. A meta-analízisek elemzése alapján biliaris plasztikstentek alkalmazása csak rövid, 6 hónapot meg nem haladó várható túlélés esetén javasolható. Ennél hosszabb életkilátás esetén az öntáguló fémstent a költséghatékonyabb. Ez utóbbi módszer a hagyományos sebészi bypassműtéttel minden szempontból egyenrangú. Feltétlenül a sebészi módszernek van azonban prioritása minden esetben, ahol az irresecabilitas a korrekt staginget követően is kétséges, vagy ahol egyidejűleg gyomorürülési zavar is fennáll.
A duodenalis stentek alkalmazása nem javasolható rutinszerűen. A magas késői szövődmények aránya (stentmigratio, perforatio, obstructio) miatt csak szelektált esetekben, előrehaladott stádiumban, vagy fokozott műtéti kockázat mellett érdemes megkísérelni a módszert.