bluuebunny/crossref_metadata_2025_split huggingface dataset:
Appraisal of immunoglobulin free light chain as a marker of response
Authors: Dispenzieri Angela , Zhang Lijun , Katzmann Jerry A. , Snyder Melissa , Blood Emily , DeGoey Roberta , Henderson Kimberly , Kyle Robert A. , Oken Martin M. , Bradwell Arthur R. , Greipp Philip R. 
Published: March 2008

AbstractThe immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis. We used the data and stored samples from a mature Eastern Cooperative Oncology Group clinical trial (E9486) to assess serum levels of FLC at baseline and after 2 months of alkylator-based therapy. For serial determinations, the absolute level of involved serum FLC or the difference of the involved and uninvolved FLC is preferred over the ratio of involved to uninvolved FLC. FLC response after 2 months of therapy was superior to early M-protein measurement to predict overall response. The ideal cut-point for FLC change appears to be between 40% and 50% reduction. The correlation between serial measurements of serum FLC and urine M-protein is inadequate to abolish the serial 24-hour urine protein. Although baseline values of FLC are prognostic in newly diagnosed myeloma patients, serial measurements do not appear to have added value in patients who have M-proteins measurable by electrophoresis.
Addition of the microchromosome GGA25 to the chicken genome sequence assembly through radiation hybrid and genetic mapping
Authors: Douaud Marine , Fève Katia , Gerus Marie , Fillon Valérie , Bardes Suzanne , Gourichon David , Dawson Deborah A , Hanotte Olivier , Burke Terry , Vignoles Florence , Morisson Mireille , Tixier-Boichard Michèle , Vignal Alain , Pitel Frédérique 
Published: March 2008

Abstract

Background
The publication of the first draft chicken sequence assembly became available in 2004 and was updated in 2006. However, this does not constitute a definitive and complete sequence of the chicken genome, since the microchromosomes are notably under-represented. In an effort to develop maps for the microchromosomes absent from the chicken genome assembly, we developed radiation hybrid (RH) and genetic maps with markers isolated from sequence currently assigned to "chromosome Unknown" (chrUn). The chrUn is composed of sequence contigs not assigned to named chromosomes. To identify and map sequence belonging to the microchromosomes we used a comparative mapping strategy, and we focused on the small linkage group E26C13.

Results
In total, 139 markers were analysed with the chickRH6 panel, of which 120 were effectively assigned to the E26C13 linkage group, the remainder mapping elsewhere in the genome. The final RH map is composed of 22 framework markers extending over a 245.6 cR distance. A corresponding genetic map was developed, whose length is 103 cM in the East Lansing reference population. The E26C13 group was assigned to GGA25 (Gallus gallus chromosome 25) by FISH (fluorescence in situ hybridisation) mapping.

Conclusion
The high-resolution RH framework map obtained here covers the entire chicken chromosome 25 and reveals the existence of a high number of intrachromosomal rearrangements when compared to the human genome. The strategy used here for the characterization of GGA25 could be used to improve knowledge on the other uncharacterized small, yet gene-rich microchromosomes.
Microsatellite data suggest significant population structure and differentiation within the malaria vector Anopheles darlingi in Central and South America
Authors: Mirabello Lisa , Vineis Joseph H , Yanoviak Stephen P , Scarpassa Vera M , Póvoa Marinete M , Padilla Norma , Achee Nicole L , Conn Jan E 
Published: March 2008

Abstract

Background

Anopheles darlingi is the most important malaria vector in the Neotropics. An understanding of A. darlingi's population structure and contemporary gene flow patterns is necessary if vector populations are to be successfully controlled. We assessed population genetic structure and levels of differentiation based on 1,376 samples from 31 localities throughout the Peruvian and Brazilian Amazon and Central America using 5–8 microsatellite loci.

Results
We found high levels of polymorphism for all of the Amazonian populations (mean R
S = 7.62, mean H
O = 0.742), and low levels for the Belize and Guatemalan populations (mean R
S = 4.3, mean H
O = 0.457). The Bayesian clustering analysis revealed five population clusters: northeastern Amazonian Brazil, southeastern and central Amazonian Brazil, western and central Amazonian Brazil, Peruvian Amazon, and the Central American populations. Within Central America there was low non-significant differentiation, except for between the populations separated by the Maya Mountains. Within Amazonia there was a moderate level of significant differentiation attributed to isolation by distance. Within Peru there was no significant population structure and low differentiation, and some evidence of a population expansion. The pairwise estimates of genetic differentiation between Central America and Amazonian populations were all very high and highly significant (F
ST = 0.1859 – 0.3901, P < 0.05). Both the D
A and F
ST distance-based trees illustrated the main division to be between Central America and Amazonia.

Conclusion
We detected a large amount of population structure in Amazonia, with three population clusters within Brazil and one including the Peru populations. The considerable differences in N
e among the populations may have contributed to the observed genetic differentiation. All of the data suggest that the primary division within A. darlingi corresponds to two white gene genotypes between Amazonia (genotype 1) and Central America, parts of Colombia and Venezuela (genotype 2), and are in agreement with previously published mitochondrial COI gene sequences interpreted as incipient species. Overall, it appears that two main factors have contributed to the genetic differentiation between the population clusters: physical distance between the populations and the differences in effective population sizes among the subpopulations.
Transduction of E2F-1 TAT fusion proteins represses expression of hTERT in primary ductal breast carcinoma cell lines
Authors: Elliott Kimberly A , Rickords Lee F , Labrum J Marcelete 
Published: March 2008

Abstract

Background
Telomerase expression is detectable in 81–95% of breast carcinomas and may serve as a therapeutic target. The objective of this study was to investigate repression of telomerase activity in primary ductal breast cancer cells through transcriptional regulation of the catalytic subunit hTERT. We hypothesized that inhibition of telomerase expression could be achieved via Tat mediated protein transduction of the repressor protein E2F-1.

Methods
Protein purification techniques were refined to yield biologically active Tat fusion proteins (TFPs) capable of transducing the breast cancer cell lines HCC1937 and HCC1599. Cell lines were treated with wildtype E2F-1 (E2F-1/TatHA), mutant E2F-1 (E132/TatHA) and a control Tat peptide (TatHA) for 24 hours. Total RNA was isolated from treated cells, reverse transcribed and fold changes in gene expression for hTERT determined via real-time RT-qPCR.

Results
Significant repression of the catalytic subunit of telomerase (hTERT) was present in both HCC1937 and HCC1599 cells following treatment with E2F-1/TatHA. In HCC1937 cells, hTERT was repressed 3.5-fold by E2F-1/TatHA in comparison to E132/TatHA (p < 0.0012) and the TatHA peptide controls (p < 0.0024). In HCC1599 cells, hTERT was also repressed with E2F-1/TatHA treatment by 4.0-fold when compared to the E132/TatHA control (p < 0.0001). A slightly lower hTERT repression of 3.3-fold was observed with E2F-1/TatHA in the HCC1599 cells when compared to the TatHA control (p < 0.0001).

Conclusion
These results suggest that transduction of E2F-1/TatHA fusion proteins in vitro is an effective repressor of hTERT expression in the primary ductal breast cancer cell lines HCC1937 and HCC1599.
The Quality Improvement Demonstration Study: An example of evidence-based policy-making in practice
Authors: Shimkhada Riti , Peabody John W , Quimbo Stella A , Solon Orville 
Published: March 2008

Abstract

Background
Randomized trials have long been the gold-standard for evaluating clinical practice. There is growing recognition that rigorous studies are similarly needed to assess the effects of policy. However, these studies are rarely conducted. We report on the Quality Improvement Demonstration Study (QIDS), an example of a large randomized policy experiment, introduced and conducted in a scientific manner to evaluate the impact of large-scale governmental policy interventions.

Methods
In 1999 the Philippine government proposed sweeping reforms in the National Health Sector Reform Agenda. We recognized the unique opportunity to conduct a social experiment. Our ongoing goal has been to generate results that inform health policy. Early on we concentrated on developing a multi-institutional collaborative effort. The QIDS team then developed hypotheses that specifically evaluated the impact of two policy reforms on both the delivery of care and long-term health status in children. We formed an experimental design by randomizing matched blocks of three communities into one of the two policy interventions plus a control group. Based on the reform agenda, one arm of the experiment provided expanded insurance coverage for children; the other introduced performance-based payments to hospitals and physicians. Data were collected in household, hospital-based patient exit, and facility surveys, as well as clinical vignettes, which were used to assess physician practice. Delivery of services and health status were evaluated at baseline and after the interventions were put in place using difference-in-difference estimation.

Results
We found and addressed numerous challenges conducting this study, namely: formalizing the experimental design using the existing health infrastructure; securing funding to do research coincident with the policy reforms; recognizing biases and designing the study to account for these; putting in place a broad data collection effort to account for unanticipated findings; introducing sustainable policy interventions based on the reform agenda; and providing results in real-time to policy makers through a combination of venues.

Conclusion
QIDS demonstrates that a large, prospective, randomized controlled policy experiment can be successfully implemented at a national level as part of sectoral reform. While we believe policy experiments should be used to generate evidence-based health policy, to do this requires opportunity and trust, strong collaborative relationships, and timing. This study nurtures the growing attitude that translation of scientific findings from the bedside to the community can be done successfully and that we should raise the bar on project evaluation and the policy-making process.
A transient benign lymph node-based proliferation of T-cells simulating non-Hodgkin lymphoma in a patient with psoriasis treated with tumor necrosis factor alpha and CD11a antagonists
Authors: Hurley M Yadira , George Mary Noel , Leonardi Craig L , Frater John L 
Published: March 2008

Abstract

Background
Therapeutic biologic agents are uncommonly associated with lymphoma.

Case presentation
We report a patient with psoriasis treated with the biologic agents efalizumab (Raptiva®) and etanercept (Enbrel®), who developed painless lymphadenopathy with peripheral lymphocytosis during treatment, simulating a non-Hodgkin lymphoma clinically and pathologically. Lymphocytosis and lymphadenopathy spontaneously remitted following cessation of etanercept therapy and have not recurred.

Conclusion
Distinction between clinically benign lymphoid proliferations related to antipsoriasis therapy and malignant lymphoma avoids the unnecessary use of anti-lymphoma chemotherapy.
Long term survival after coronary endarterectomy in patients undergoing combined coronary and valvular surgery – a fifteen year experience
Authors: Kumar Sanjay , Agarwala Sandeep , Talbot Charlie , Nair R. Unnikrishnan 
Published: March 2008

Abstract

Background
Coronary Endarterectomy (CE) in patients undergoing coronary artery bypass graft (CABG) surgery has been shown to be beneficial in those with diffuse coronary artery disease. There are no published data on its role and benefit in patients undergoing more complex operations. We present our experience with CE in patients undergoing valve surgery with concomitant CABG.

Materials and methods
Between 1989 and 2003, 237 patients underwent CABG with valve surgery under a single surgeon at our institution. Of these, 41 patients needed CE. Data was retrospectively obtained from hospital records and database. Further follow-up was obtained by telephone interview. All variables were analyzed by univariate analysis for significant factors relating to hospital mortality. Morbidity and long term survival was also studied. There were 29 males and 12 females with a mean age of 67.4 ± 8.1 and body mass index of 26.3 ± 3.3. Their mean euroscore was 7.6 ± 3.2 and the log euro score was 12.2 ± 16.1.

Results
Thirty-two patients were discharged from the intensive therapy unit within 48 hours after surgery. Average hospital stay was 12.7 ± 10.43 days. Thirty day mortality was 9.8%. Six late deaths occurred during the 14 year follow up. Ten year survival was 57.2% (95% CL 37.8%–86.6%). Three of the survivors had Class II symptoms, with one requiring nitrates. None required further percutaneous or surgical intervention. We compared the result with the available mortality figure from the SCTS database.

Conclusion
Compared to the SCTS database for these patients, we have observed that CE does not increase the mortality in combined procedures. By accomplishing revascularization in areas deemed ungraftable, we have shown an added survival benefit in this group of patients.
Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8+ T cell immunity
Authors: Huang Xiao-Li , Fan Zheng , Borowski LuAnn , Rinaldo Charles R 
Published: March 2008

AbstractMaturation of dendritic cells (DC) to enhance their capacity to activate T cell immunity to HIV-1 is a key step in immunotherapy of HIV-1 infection with DC. We compared maturation of DC derived from HIV-1-uninfected subjects and infected subjects on antiretroviral therapy (ART) or ART naïve by CD40 ligand (CD40L) and combinations of TLR3 ligand polyinosinic:polycytidylic acid [poly(I:C)] and inflammatory cytokines IFN-γ, IFN-α, IL-1β, and TNF-α. The greatest levels of virus-specific IFN-γ production by CD8+ T cells were stimulated by DC treated with CD40L, followed by DC treated with the poly(I:C)-cytokine combination. The highest levels of IL-12p70 were produced by DC treated with CD40L + IFN-γ, followed by CD40L and the poly(I:C)-cytokine combination. Neutralization of IL-12p70 indicated that it was only partially involved in direct enhancement of antiviral CD8+ T cell activity. DC stimulation of antiviral CD8+ T cell reactivity was enhanced by activated CD4+ T cells at low concentrations but was suppressed at higher CD4+ T cell concentrations. Maturation of DC with CD40L obviated the need for CD4+ T cell help and overcame this suppressive activity. Finally, we showed that DC from HIV-1-infected subjects on ART, which were treated with the poly(I:C)-cytokine combination, retained the capacity to produce IL-12p70 and activate anti-HIV-1 CD8+ T cell responses after restimulation with CD40L, with or without IFN-γ. Thus, DC from HIV-1-infected subjects can be engineered with CD40L or a poly(I:C)-cytokine combination for enhancing CD8+ T cell responses to HIV-1, which has potential applications in HIV-1 immunotherapy.
Free Triiodothyronine Has a Distinct Circadian Rhythm That Is Delayed but Parallels Thyrotropin Levels
Authors: Russell W. , Harrison R. F. , Smith N. , Darzy K. , Shalet S. , Weetman A. P. , Ross R. J. 
Published: March 2008

AbstractContext: TSH is known to have a circadian rhythm, but the relationship between this and any rhythm in T4 and T3 has not been clearly demonstrated.Objective: With a view to optimizing thyroid hormone replacement therapy, we have used modern assays for free T4 (FT4) and free T3 (FT3) to investigate circadian rhythmicity.Setting: The study was performed at a university hospital.Design and Subjects: This was a cross-sectional study in 33 healthy individuals with 24-h blood sampling (TSH in 33 and FT4 and FT3 in 29 individuals) and cosinor analysis.Results: Of the individuals, 100% showed a sinusoidal signal in TSH, for FT4 76%, and for FT3 86% (P &lt; 0.05). For FT4 and FT3, the amplitude was low. For TSH the acrophase occurred at a clock time of 0240 h, and for FT3 approximately 90 minutes later at 0404 h. The group cosinor model predicts that TSH hormone levels remain above the mesor between 2020 and 0820 h, and for FT3 from 2200–1000 h. Cross correlation of FT3 with TSH showed that the peak correlation occurred with a delay of 0.5–2.5 h. When time-adjusted profiles of TSH and FT3 were compared, there was a strong correlation between FT3 and TSH levels (ρ = 0.80; P &lt; 0.0001). In contrast, cross correlation revealed no temporal relationship between FT4 and TSH.Conclusions: FT3 shows a circadian rhythm with a periodicity that lags behind TSH, suggesting that the periodic rhythm of FT3 is due to the proportion of T3 derived from the thyroid. Optimizing thyroid hormone replacement may need to take these rhythms into account.
Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?
Authors: Machens Andreas , Hauptmann Steffen , Dralle Henning 
Published: March 2008

Abstract
Context: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer.
Objective: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer.
Design: This was a retrospective study.
Setting: The investigation took place at a tertiary referral center.
Patients: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer.
Main Outcome Measure: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases.
Results: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41–54 vs. 4–27%; P = 0.001) and number (means of 3.0–10.8 vs. 0–1.1 positive nodes, P &lt; 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14–27 vs. 0–7%; P = 0.027), distant metastasis (9–23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40–55 vs. 53–82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels.
Conclusions: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.
A Maximal-Space Algorithm for the Container Loading Problem
Authors: Parreño F. , Alvarez-Valdes R. , Tamarit J. M. , Oliveira J. F. 
Published: March 2008

In this paper, a greedy randomized adaptive search procedure (GRASP) for the container loading problem is presented. This approach is based on a constructive block heuristic that builds upon the concept of maximal space, a nondisjoint representation of the free space in a container. This new algorithm is extensively tested over the complete set of Bischoff and Ratcliff problems [Bischoff, E. E., M. S. W. Ratcliff. 1995. Issues in the development of approaches to container loading. Omega 23 377–390], ranging from weakly heterogeneous to strongly heterogeneous cargo, and outperforms all the known nonparallel approaches that, partially or completely, have used this set of test problems. When comparing against parallel algorithms, it is better on average but not for every class of problem. In terms of efficiency, this approach runs in much less computing time than that required by parallel methods. Thorough computational experiments concerning the evaluation of the impact of algorithm design choices and internal parameters on the overall efficiency of this new approach are also presented.
Efficacy of Add-On Topiramate Therapy in Psychiatric Patients with Weight Gain
Authors: Cates Marshall E , Feldman Jacqueline M , Boggs Angela A , Woolley Thomas W , Whaley Nanci P 
Published: March 2008

BACKGROUND: Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain. OBJECTIVE: To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting. METHODS: A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002–2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI). RESULTS: Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1–4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45–1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy. CONCLUSIONS: Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.