bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of hollow-fiber membrane oxygenators with different perfusion modes during normothermic and hypothermic CPB in a simulated neonatal model
Authors: Ündar Akif , Ji Bingyang , Lukic Branka , Zapanta Conrad M , Kunselman Allen R , Reibson John D , Khalapyan Tigran , Baer Larry , Weiss William J , Rosenberg Gerson , Myers John L 
Published: January 2007

Purpose: The objectives of this investigation were (1) to compare two hollow-fiber membrane oxygenators (Capiox Baby RX versus Lilliput 1-D901) in terms of pressure drops and surplus hemodynamic energy (SHE) during normothermic and hypothermic cardiopulmonary bypass (CPB) in a simulated neonatal model; and (2) to evaluate pulsatile and non-pulsatile perfusion modes for each oxygenator in terms of SHE levels. Methods: In a simulated patient, CPB was initiated at a constant pump flow rate of 500 mL/min. The circuit was primed with fresh bovine blood. After 5 min of normothermic CPB, the pseudo-patient was cooled down to 25°C for 10 min followed by 30 min of hypothermic CPB. The pseudo-patient then underwent 10 min of rewarming and 5 min of normothermic CPB. At each experimental site (pre- and post-oxygenator and pre-aortic cannula), SHE was calculated using the following formula {SHE (ergs/cm3) = 1332 [((ffpdt)/(ffdt))-mean arterial pressure]} (f = pump flow and p = pressure). A linear mixed-effects model that accounts for the correlation among repeated measurements was fit to the data to assess differences in SHE between oxygenators, pumps, and sites. Tukey’s multiple comparison procedure was used to adjust p-values for post-hoc pairwise comparisons. Results: The pressure drops in the Capiox group compared to the Lilliput group were significantly lower during hypothermic non-pulsatile (21.3∓0.5 versus 50.7∓0.9 mmHg, p B < 0.001) and pulsatile (22∓0.0 versus 53.3∓0.5 mmHg, p < 0.001) perfusion, respectively. Surplus hemodynamic energy levels were significantly higher in the pulsatile group compared to the non-pulsatile group, with Capiox (1655∓92 versus 10 008∓1370 ergs/cm3, p < 0.001) or Lilliput (1506∓112 versus 7531∓483 ergs/cm3, p < 0.001) oxygenators. During normothermic CPB, both oxygenators had patterns similar to those observed under hypothermic conditions. Conclusions: The Capiox oxygenator had a significantly lower pressure drop in both pulsatile and non-pulsatile perfusion modes. For each oxygenator, the SHE levels were significantly higher in the pulsatile mode.
Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients
Authors: Braun Jan-Peter , Jakob Stephan M , Volk Thomas , Doepfmer Ulrich R , Moshirzadeh Maryam , Stegmann Shirin , Dohmen Pascal M , Spies Claudia 
Published: January 2007

Objective: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). Methods: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-ΔΔG(v-a)) and hepato-venous and arterial (-ΔΔG(hv-a)) compartments were calculated. Measurements and results: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p =0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p =0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p =0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p =0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p =0.001, 0.033, respectively). Conclusion: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.
Discoid Meniscus
Authors: Atay Ozgur Ahmet , Pekmezci Murat , Doral Mahmut Nedim , Sargon Mustafa Fevzi , Ayvaz Mehmet , Johnson Darren L. 
Published: January 2007

Background The ultrastructure of the normal menisci has been thoroughly investigated and found to correlate with meniscal tears. Although discoid menisci are accepted to have the same composition as their normal counterparts, to our knowledge, no study in the literature has investigated this issue. Purpose To investigate the ultrastructure of the discoid menisci and compare it with nondiscoid menisci. Study Design Descriptive laboratory study. Methods Meniscal biopsies were taken from 12 patients who were operated for meniscus tear and diagnosed with discoid meniscus and from 6 patients who were operated for meniscal tear and did not have a diagnosis of discoid meniscus. The samples were examined with transmission electron microscopy. Results The study group demonstrated a decrease in the number of collagen fibers compared with the control group. Also, the homogeneous course of the collagen fibers observed in the control group was replaced by a heterogeneous course in the study group. Conclusion The ultrastructure of the discoid meniscus is different from the normal menisci. Clinical Relevance This difference may contribute to the vulnerability of the discoid meniscus to tears.
Excessive Apoptosis in Patellar Tendinopathy in Athletes
Authors: Lian Øystein , Scott Alex , Engebretsen Lars , Bahr Roald , Duronio Vincent , Khan Karim 
Published: January 2007

Background The pathogenesis of tendon overuse injuries is poorly understood. The histopathology underlying tendinopathy at various anatomical locations is similar and may reflect a common pathologic process. Hypothesis Apoptosis contributes to the pathophysiology in patellar tendinopathy. Study Design Case control study; Level of evidence, 3. Methods We compared biopsy specimens from the patellar tendon in patients with patellar tendinopathy diagnosed clinically and with typical magnetic resonance image findings with biopsy specimens from a control group without any previous or current knee complaints to suggest patellar tendinopathy. The presence of apoptosis was examined with immunohistochemical methods using a polyclonal antibody recognizing active caspase-3, confirmed by labeling DNA strand breaks (F7-26 antibody) and nuclear morphology (fragmentation and condensation). Results The number of apoptotic cells per unit area (4.5 mm2) was 0.91 ± 0.81 (SD) in tendinopathic samples and 0.21 ± 0.21 in controls (P = .026). Although the tendinopathic samples displayed increased cellularity (average 162.5 nuclei/mm 2 vs 98.9 nuclei/mm2), the apoptotic index was higher (0.42% vs 0.17%, P = .014). Conclusion Increased apoptotic cell death is a feature of patellar tendinosis. The role of apoptosis within the broader framework and time course of tendon overuse injury remains to be established.
Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis
Authors: Corral Javier , Hernandez-Espinosa David , Soria Jose Manual , Gonzalez-Conejero Rocio , Ordonez Adriana , Gonzalez-Porras Jose Ramon , Perez-Ceballos Elena , Lecumberri Ramon , Sanchez Ignacio , Roldan Vanessa , Mateo Jose , Minano Antonia , Gonzalez Marcos , Alberca Ignacio , Fontcuberta Jordi , Vicente Vicente 
Published: January 2007

AbstractThe antithrombin A384S mutation has a relatively high frequency in the British population but has not been identified in other populations. This variant has been associated with cases of thrombotic disease, but its clinical relevance in venous thrombosis remained unclear. We have conducted a secondary analysis of the prevalence of the mutation in a large case-control study, including 1018 consecutive Spanish patients with venous thromboembolism. In addition, we evaluated its functional consequences in 20 carriers (4 homozygous). This mutation, even in the homozygous state, did not affect anti-Xa activity or antigen levels, and it only slightly impaired anti-IIa activity. Thus, routine clinical methods cannot detect this anomaly, and, accordingly, this alteration could have been underestimated. We identified this mutation in 0.2% of Spanish controls. Among patients, this variant represented the first cause of antithrombin anomalies. Indeed, 1.7% patients carried the A384S mutation, but 0.6% had any other antithrombin deficiency. The mutated allele was associated with an increased risk of venous thrombosis with an adjusted OR of 9.75 (95% CI, 2.2-42.5). This is the first study supporting that antithrombin A384S mutation is a prevalent genetic risk factor for venous thrombosis and is the most frequent cause of antithrombin deficiency in white populations.
Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia
Authors: Fazi Francesco , Zardo Giuseppe , Gelmetti Vania , Travaglini Lorena , Ciolfi Alberto , Di Croce Luciano , Rosa Alessandro , Bozzoni Irene , Grignani Francesco , Lo-Coco Francesco , Pelicci Pier Giuseppe , Nervi Clara 
Published: January 2007

Abstract
Alteration of lineage-specific transcriptional programs for hematopoiesis causes differentiation block and promotes leukemia development. Here, we show that AML1/ETO, the most common translocation fusion product in acute myeloid leukemia (AML), counteracts the activity of retinoic acid (RA), a transcriptional regulator of myelopoiesis. AML1/ETO participates in a protein complex with the RA receptor alpha (RARα) at RA regulatory regions on RARβ2, which is a key RA target gene mediating RA activity/resistance in cells. At these sites, AML1/ETO recruits histone deacetylase, DNA methyltransferase, and DNA-methyl-CpG binding activities that promote a repressed chromatin conformation. The link among AML1/ETO, heterochromatic RARβ2 repression, RA resistance, and myeloid differentiation block is indicated by the ability of either siRNA-AML1/ETO or the DNA methylation inhibitor 5-azacytidine to revert these epigenetic alterations and to restore RA differentiation response in AML1/ETO blasts. Finally, RARβ2 is commonly silenced by hypermethylation in primary AML blasts but not in normal hematopoietic precursors, thus suggesting a role for the epigenetic repression of the RA signaling pathway in myeloid leukemogenesis.
Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance
Authors: Terol Javier , Conesa Ana , Colmenero Jose M , Cercos Manuel , Tadeo Francisco , Agustí Javier , Alós Enriqueta , Andres Fernando , Soler Guillermo , Brumos Javier , Iglesias Domingo J , Götz Stefan , Legaz Francisco , Argout Xavier , Courtois Brigitte , Ollitrault Patrick , Dossat Carole , Wincker Patrick , Morillon Raphael , Talon Manuel 
Published: January 2007

Abstract

Background
Improvement of Citrus, the most economically important fruit crop in the world, is extremely slow and inherently costly because of the long-term nature of tree breeding and an unusual combination of reproductive characteristics. Aside from disease resistance, major commercial traits in Citrus are improved fruit quality, higher yield and tolerance to environmental stresses, especially salinity.

Results
A normalized full length and 9 standard cDNA libraries were generated, representing particular treatments and tissues from selected varieties (Citrus clementina and C. sinensis) and rootstocks (C. reshni, and C. sinenis × Poncirus trifoliata) differing in fruit quality, resistance to abscission, and tolerance to salinity. The goal of this work was to provide a large expressed sequence tag (EST) collection enriched with transcripts related to these well appreciated agronomical traits. Towards this end, more than 54000 ESTs derived from these libraries were analyzed and annotated. Assembly of 52626 useful sequences generated 15664 putative transcription units distributed in 7120 contigs, and 8544 singletons. BLAST annotation produced significant hits for more than 80% of the hypothetical transcription units and suggested that 647 of these might be Citrus specific unigenes. The unigene set, composed of ~13000 putative different transcripts, including more than 5000 novel Citrus genes, was assigned with putative functions based on similarity, GO annotations and protein domains

Conclusion
Comparative genomics with Arabidopsis revealed the presence of putative conserved orthologs and single copy genes in Citrus and also the occurrence of both gene duplication events and increased number of genes for specific pathways. In addition, phylogenetic analysis performed on the ammonium transporter family and glycosyl transferase family 20 suggested the existence of Citrus paralogs. Analysis of the Citrus gene space showed that the most important metabolic pathways known to affect fruit quality were represented in the unigene set. Overall, the similarity analyses indicated that the sequences of the genes belonging to these varieties and rootstocks were essentially identical, suggesting that the differential behaviour of these species cannot be attributed to major sequence divergences. This Citrus EST assembly contributes both crucial information to discover genes of agronomical interest and tools for genetic and genomic analyses, such as the development of new markers and microarrays.
An improved genetic system for detection and analysis of protein nuclear import signals
Authors: Marshall Kris S , Zhang Zhiying , Curran Jennifer , Derbyshire Stephanie , Mymryk Joe S 
Published: January 2007

Abstract

Background
Nuclear import of proteins is typically mediated by their physical interaction with soluble cytosolic receptor proteins via a nuclear localization signal (NLS). A simple genetic assay to detect active NLSs based on their function in the yeast Saccharomyces cerevisiae has been previously described. In that system, a chimera consisting of a modified bacterial LexA DNA binding domain and the transcriptional activation domain of the yeast Gal4 protein is fused to a candidate NLS. A functional NLS will redirect the chimeric fusion to the yeast cell nucleus and activate transcription of a reporter gene.

Results
We have reengineered this nuclear import system to expand its utility and tested it using known NLS sequences from adenovirus E1A. Firstly, the vector has been reconstructed to reduce the level of chimera expression. Secondly, an irrelevant "stuffer" sequence from the E. coli maltose binding protein was used to increase the size of the chimera above the passive diffusion limit of the nuclear pore complex. The improved vector also contains an expanded multiple cloning site and a hemagglutinin epitope tag to allow confirmation of expression.

Conclusion
The alterations in expression level and composition of the fusions used in this nuclear import system greatly reduce background activity in β-galactosidase assays, improving sensitivity and allowing more quantitative analysis of NLS bearing sequences.
Kv1.1 null mice have enlarged hippocampus and ventral cortex
Authors: Persson Ann-Sophie , Westman Eric , Wang Fu-Hua , Khan Firoj Hossain , Spenger Christian , Lavebratt Catharina 
Published: January 2007

Abstract

Background
Mutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy. Mice that express a malfunctional, truncated Kv1.1 (BALB/cByJ-Kv1.1

mceph/mceph
) show a markedly enlarged hippocampus and ventral cortex in adulthood.

Results
To determine if mice lacking Kv1.1 also develop a brain enlargement similar to mceph/mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was then studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1

mceph/mceph
, BALB/cByJ-Kv1.1

mceph/+, BALB.C3HeB -Kv1.1
-/+ and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex.

Conclusion
Total absence of Kv1.1 can induce excessive overgrowth of hippocampus and ventral cortex in mice with a BALB/cByJ background, while mice with one wild type Kv1.1 allele develop normal-sized brains.
FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders
Authors: Chiappetta Gennaro , Ferraro Angelo , Botti Gerardo , Monaco Mario , Pasquinelli Rosa , Vuttariello Emilia , Arnaldi Liliane , Di Bonito Maurizio , D'Aiuto Giuseppe , Pierantoni Giovanna Maria , Fusco Alfredo 
Published: January 2007

Abstract

Background
Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases.

Methods
We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis.

Results
FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples.

Conclusion
The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders.
Benchmarks in Clinical Productivity: A National Comprehensive Cancer Network Survey
Authors: Stewart F. Marc , Wasserman Robert L. , Bloomfield Clara D. , Petersdorf Stephen , Witherspoon Robert P. , Appelbaum Frederick R. , Ziskind Andrew , McKenna Brian , Dodson Jennifer M. , Weeks Jane , Vaughan William P. , Storer Barry , Perkel Sara , Waldinger Marcy 
Published: January 2007

Purpose Oncologists in academic cancer centers usually generate professional fees that are insufficient to cover salaries and other expenses, despite significant clinical activity; therefore, supplemental funding is frequently required in order to support competitive levels of physician compensation. Relative value units (RVUs) allow comparisons of productivity across institutions and practice locations and provide a reasonable point of reference on which funding decisions can be based. Methods We reviewed the clinical productivity and other characteristics of oncology physicians practicing in 13 major academic cancer institutions with membership or shared membership in the National Comprehensive Cancer Network (NCCN). The objectives of this study were to develop tools that would lead to better-informed decision making regarding practice management and physician deployment in comprehensive cancer centers and to determine benchmarks of productivity using RVUs accrued by physicians at each institution. Three hundred fifty-three individual physician practices across the 13 NCCN institutions in the survey provided data describing adult hematology/medical oncology and bone marrow/stem-cell transplantation programs. Data from the member institutions participating in the survey included all American Medical Association Current Procedural Terminology (CPT®) codes generated (billed) by each physician during each organization's fiscal year 2003 as a measure of actual clinical productivity. Physician characteristic data included specialty, clinical full-time equivalent (CFTE) status, faculty rank, faculty track, number of years of experience, and total salary by funding source. The average adult hematologist/medical oncologist in our sample would produce 3,745 RVUs if he/she worked full-time as a clinician (100% CFTE), compared with 4,506 RVUs for a 100% CFTE transplant oncologist. Results and Conclusion Our results suggest specific clinical productivity targets for academic oncologists and provide a methodology for analyzing potential factors associated with clinical productivity and developing clinical productivity targets specific for physicians with a mix of research, administrative, teaching, and clinical salary support.
The Effect of Pharmacotherapy Audit Meetings on Early New Drug Prescribing by General Practitioners
Authors: Florentinus Stefan R , Hulten Rolf van , Kloth Marjolein EM , Heerdink Eibert R , Griens AMG Fabiënne , Leufkens Hubert GM , Groenewegen Peter P 
Published: January 2007

Background: New drugs are cornerstones of clinical practice. However, when included in practice in an erratic fashion, there is valid concern about uncertain risk–benefit for patients and increased healthcare expenditures. In several countries, general practitioners (GPs) and pharmacists work closely together to ensure proper use of new drugs in clinical practice. Objective: To estimate the effect of pharmacotherapy audit meetings (PTAMs) between GPs and community pharmacists on prescribing of newly marketed drugs by GPs. Methods: We conducted an observational study of new drug prescribing in a cohort of 103 GPs, working in 59 practices, from 1999 until 2003. The main outcome measures were the decisions to start therapy with a new drug or with an existing older drug from the same therapeutic category within the first 6 months after market introduction. Multilevel modeling was used for analyses. Results: Overall, in 6.1% of the decisions to start drug therapy, GPs chose the drug that was most recently introduced into the market. The GPs attending lowquality PTAMs made 1861 decisions to start therapy; in 112 (6.0%) of those decisions, a new drug was preferred over an older alternative. GPs participating in high-quality PTAMs preferred a new drug in only 3.4% of the 3138 decisions made. Compared with GPs participating in PTAMs on the highest quality level (level 4), GPS attending level 1 or level 2 PTAMs were more than twice as likely to start therapy with new drugs than with older drugs (OR 2.24; 95% CI 1.04 to 4.81 vs OR 2.31; 95% CI 1.30 to 4.09, respectively). Conclusions: PTAMs may be an effective way to control early prescribing of new drugs in general practice. For PTAMs to be effective, it is vital that GPs and pharmacists set common goals on how to optimize pharmacotherapy. This concordance should be reflected in PTAMs that result in concrete decisions with auditing of GP prescribing behavior. Pharmacists should play an active role in organizing PTAMs to increase their influence on drug prescribing.