bluuebunny/crossref_metadata_2025_split huggingface dataset:
BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.
Authors: Niesvizky Ruben , Jayabalan David S. , Christos Paul J. , Furst Jessica R. , Naib Tara , Ely Scott , Jalbrzikowski Jessica , Pearse Roger N. , Zafar Faiza , Pekle Karen , LaRow April , Lent Richard , Mark Tomer , Cho Hearn J. , Shore Tsiporah , Tepler Jeffrey , Harpel John , Schuster Michael W. , Mathew Susan , Leonard John P. , Mazumdar Madhu , Chen-Kiang Selina , Coleman Morton 
Published: November 2007

AbstractThis trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.
Transgenic blockade of interleukin 6 transsignaling abrogates inflammation
Authors: Rabe Björn , Chalaris Athena , May Ulrike , Waetzig Georg H. , Seegert Dirk , Williams Anwen S. , Jones Simon A. , Rose-John Stefan , Scheller Jürgen 
Published: November 2007

AbstractThe immunoregulatory cytokine interleukin6 (IL6) acts in a pro- and anti-inflammatory fashion. Synthesized by myeloid cells, fibroblasts and endothelial cells, IL6 on target cells, binds to the IL6 receptor (IL6R) and signals via complex formation with the ubiquitously expressed gp130 receptor. Paradoxically, most cells that respond to IL6 during inflammatory states do not express the IL6R and are themselves not directly responsive to the cytokine. A naturally occurring soluble form of the IL6R renders all cells responsive to IL6. This alternative signaling process is called IL6 transsignaling. Here we developed a transgenic strategy based on the overexpression of the soluble form of gp130, which specifically blocks all IL6 responses mediated by the soluble IL6R but does not affect IL6 responses via the membrane bound IL6R. In these mice, inflammatory processes are blocked as in IL6−/− mice, strongly arguing for a major role of the soluble IL6R during inflammation in vivo.
Interleukin-18 production and pulmonary function in COPD
Authors: Imaoka H. , Hoshino T. , Takei S. , Kinoshita T. , Okamoto M. , Kawayama T. , Kato S. , Iwasaki H. , Watanabe K. , Aizawa H. 
Published: November 2007

Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD.Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n = 16), smokers (n = 27) and nonsmokers (n = 23). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I–IV COPD (n = 62), smokers (n = 34) and nonsmokers (n = 47).Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ T-cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-γ were not significantly increased in any of the three groups.In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.
Inferring genome-scale rearrangement phylogeny and ancestral gene order: a Drosophilacase study
Authors: Bhutkar Arjun , Gelbart William M , Smith Temple F 
Published: November 2007

AbstractA simple, fast, and biologically inspired computational approach for inferring genome-scale rearrangement phylogeny and ancestral gene order has been developed. This has been applied to eight Drosophila genomes. Existing techniques are either limited to a few hundred markers or a small number of taxa. This analysis uses over 14,000 genomic loci and employs discrete elements consisting of pairs of homologous genetic elements. The results provide insight into evolutionary chromosomal dynamics and synteny analysis, and inform speciation studies.
FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection
Authors: Ndhlovu Lishomwa C , Loo Christopher P , Spotts Gerald , Nixon Douglas F , Hecht Frederick M 
Published: November 2007

AbstractDuring the course of HIV-1 infection, the status of immune activation has been determined to be a powerful indicator of disease progression. The immune system has adopted self-regulatory mechanisms to counterbalance undesirable immune responses. CD25+CD4+ T regulatory (Treg) cells that express the transcription regulator, forkhead box P3 (FOXP3), play an important role in this immunosuppression. Using a combination of Treg cell discriminatory markers (FOXP3, CD25, CD127), we predicted that an expansion of Treg cell subsets would negatively correlate with immune activation during the early stages of HIV-1 infection. We report that FOXP3+CD127lo expressing CD4+ T cells increases in primary HIV-1 infection over time. Furthermore, the FOXP3+CD127lo CD4+ T cells may, in fact, reduce the levels of T cell activation following primary infection. It is interesting that the positive correlation between FOXP3+CD127lo CD4+ and CD25+CD127lo CD4+ T cells noted in HIV-uninfected persons is not only lost but may also be reversed in early, chronic HIV-1 infection. Unlike FOXP3+CD127lo CD4+, the level of FOXP3+CD25+CD127lo CD4+ T cells did not correlate with T cell activation, suggesting that these cells were not effective in reducing T cell activation. These observations suggest that different Treg populations may have different effects on reducing immune activation in HIV-1 infection and that the FOXP3+CD127lo CD4+ T cell population may be particularly important in limiting immune activation.
Detection of immune danger signals by NALP3
Authors: Martinon Fabio 
Published: November 2007

AbstractThe innate immune system in animals has been forged to detect microbes, coordinate symbiotic responses, and mount immune defenses against pathogens. Recently, innate immunity was shown to detect signals released by damaged cells or tissues such as uric acid or ATP. These danger signals were proposed to be important in promoting and regulating inflammation upon trauma or pathogen insults. The physiological relevance of these signals in the immune response and their mechanisms of action are still unclear. Recent findings suggest that some danger signals activate the NALP3 inflammasome, an innate immune complex that controls inflammatory caspases and IL-1 activation.
Numerical Computation of Subsonic Oscillatory Airforce Coefficients for Wing-Winglet Configurations
Authors: Cheung C.W. 
Published: November 2007

This paper presents the theoretical development and numerical results of a lifting-surface theory for calculating oscillating airforce coefficients for wing-winglet configurations and it follows the author's previous paper on the extension of Davies' T-tail theory for cruciform-tail configurations. The wing-winglet configurations are assumed to vibrate in a simple harmonic motion of infinitesimal amplitude in a subsonic airstream such that linearised aerodynamic theory is applicable for the analysis of the motion. The modes of displacement of the wing-winglet configuration may be either symmetric or antisysmmetric with respect to the centre-line of the configuration in the direction of the flow. A computer program has been developed for the evaluation of oscillatory airforce coefficients for wing-winglet configurations. Aerodynamic stiffness and damping matrices which are normally used for aeroelastic calculations have been obtained for a typical transport aircraft wing-winglet configuration at two winglet dihedral angles and comparisons have been made against those calculated by an alternative doublet-lattice method. The comparisons have been shown to be satisfactory.
Analytical Validation of Serum Proteomic Profiling for Diagnosis of Prostate Cancer: Sources of Sample Bias
Authors: McLerran Dale , Grizzle William E , Feng Ziding , Bigbee William L , Banez Lionel L , Cazares Lisa H , Chan Daniel W , Diaz Jose , Izbicka Elzbieta , Kagan Jacob , Malehorn David E , Malik Gunjan , Oelschlager Denise , Partin Alan , Randolph Timothy , Rosenzweig Nicole , Srivastava Shiv , Srivastava Sudhir , Thompson Ian M , Thornquist Mark , Troyer Dean , Yasui Yutaka , Zhang Zhen , Zhu Liu , Semmes O John 
Published: November 2007

Abstract
Background: This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1.
Methods: We derived the decision algorithm used in this study from the analysis of serum samples from patients with prostate cancer (n = 181) and benign prostatic hyperplasia (BPH) (n = 143) and normal controls (n = 220). We also derived a validation test set from a separate, geographically diverse set of serum samples from 42 prostate cancer patients and 42 controls without prostate cancer. Aliquots were subjected to randomization and blinded analysis, and data from each laboratory site were subjected to the decision algorithm and decoded.
Results: Using the data collected from the validation test set, the decision algorithm was unsuccessful in separating cancer from controls with any predictive utility. Analysis of the experimental data revealed potential sources of bias.
Conclusion: The ability of the decision algorithm to successfully differentiate between prostate cancer, BPH, and control samples using data derived from serum protein profiling was compromised by bias.
Excretion of Methamphetamine and Amphetamine in Human Sweat Following Controlled Oral Methamphetamine Administration
Authors: Barnes Allan J , Smith Michael L , Kacinko Sherri L , Schwilke Eugene W , Cone Edward J , Moolchan Eric T , Huestis Marilyn A 
Published: November 2007

Abstract
Background: Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is important for interpreting sweat and hair testing results in judicial, workplace, and drug treatment settings.
Methods: Participants (n = 8) received 4 10-mg (low) oral doses of sustained-release S-(+)-MAMP HCl (d-MAMP HCl) within 1 week in a double-blind, institutional review board–approved study. Five participants also received 4 20-mg (high) doses 3 weeks later. PharmChek sweat patches (n = 682) were worn for periods of 2 h to 1 week during and up to 3 weeks after dosing. The mass of MAMP and AMP in each patch was measured by GC-MS, with a limit of quantification of 2.5 ng/patch.
Results: MAMP was measurable in sweat within 2 h of dosing. After low and high doses, 92.9% and 62.5% of weekly sweat patches were positive, with a median (range) MAMP of 63.0 (16.8–175) and 307 (199–607) ng MAMP/patch, respectively; AMP values were 15.5 (6.5–40.5) and 53.8 (34.0–83.4) ng AMP/patch. Patches applied 2 weeks after the drug administration week had no measurable MAMP following the low doses, and only 1 positive result following the high doses. Using criteria proposed by the Substance Abuse Mental Health Services Administration, 85.7% (low) and 62.5% (high) weekly sweat patches from the dosing week were positive for MAMP, and all patches applied after the dosing week were negative.
Conclusions: These data characterize the excretion of MAMP and AMP after controlled MAMP administration and provide a framework for interpretation of MAMP sweat test results in clinical and forensic settings.
Reactivity of Urinary Albumin (Microalbumin) Assays with Fragmented or Modified Albumin
Authors: Sviridov Denis , Drake Steven K , Hortin Glen L 
Published: November 2007

AbstractBackground: Controversy exists regarding occurrence and measurement of structural variants of albumin in urine. In this study, we examined cross-reactivity of in vitro modified albumins in assays for urine albumin (microalbumin).Methods: We analyzed albumin modified by reagents, trypsin, or physical treatments or differing in primary sequence (animal albumins) with an immunoturbidimetric assay (Beckman LX20) using goat antiserum and a competitive immunoassay (Siemens Immulite) using a monoclonal antibody. We assessed occurrence of albumin fragments in urine by use of Western blotting of 24 specimens.Results: Chemical modification, modest sequence substitution (gorilla albumin), or cleavage of albumin by cyanogen bromide (CNBr) had little effect on reactivity in the LX20 assay. Albumin extensively cleaved with trypsin retained partial reactivity. The Immulite assay generally was affected more severely by albumin modifications and sequence changes. Western blots of fresh urine specimens or specimens stored at −80 °C showed little albumin fragmentation, but some specimens stored for 3 years at −20 °C had extensively fragmented albumin that was detected by the LX20 but not the Immulite assay.Conclusions: Nearly equivalent reactivity of intact albumin and CNBr fragments in the immunoturbidimetric assay indicates reactivity of antibodies with multiple epitopes throughout albumin. Therefore, it is difficult to abolish reactivity of albumin in this type of urine albumin assay. Differential sensitivity of 2 assays to albumin modification identifies a potential source of assay nonequivalence in measuring urinary albumin, particularly for specimens stored at −20 °C.
Association of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation/Variant/Haplotype and Tumor Necrosis Factor (TNF) Promoter Polymorphism in Hyperlipidemic Pancreatitis
Authors: Chang Yu-Ting , Chang Ming-Chu , Su Ta-Chen , Liang Po-Chin , Su Yi-Ning , Kuo Chun-Hung , Wei Shu-Chen , Wong Jau-Min 
Published: November 2007

AbstractBackground: The mechanism by which hypertriglyceridemia (HTG) leads to pancreatitis is not clear. We sought to determine whether the genes involved in pancreatic ductal or acinar cell injury, including the cationic trypsinogen gene [protease, serine, 1 (trypsin 1) (PRSS1)], the pancreatic secretory trypsin inhibitor gene [serine peptidase inhibitor, Kazal type 1 (SPINK1)], the cystic fibrosis transmembrane conductance regulator gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette subfamily C, member 7) (CFTR)], and inflammation genes such as tumor necrosis factor [tumor necrosis factor, TNF superfamily, member 2 (TNF)] are associated with hyperlipidemic pancreatitis (HLP) in patients with HTG.Methods: We performed genetic analysis of 126 HTG patients in Taiwan (46 with HLP and 80 without HLP). The entire coding and intronic regions of the PRSS1, SPINK1, and CFTR genes were identified by heteroduplex analysis techniques and were confirmed by sequencing analysis. The presence of 125G/C, 1001 + 11C&gt;T, 1540A&gt;G (Met470Val), 2694T&gt;G, and 4521G&gt;A in CFTR, the presence of 272C&gt;T in SPINK1, and TNF promoter polymorphisms (nucleotide positions 1031, 863, 857, 308, and 308) were measured by direct sequencing.Results: Of the 126 HTG patients, 13 (10.3%) carried a CFTR mutation. No PRSS1 or SPINK1 mutations were detected in our patients or in HTG controls. The CFTR gene mutation rates in HTG with and without HLP were 26.1% (12 of 46) and 1.3% (1 of 80), respectively (P &lt;0.0001). The CFTR gene mutations were all Ile556Val. A multivariate analysis of HTG patients indicated that triglycerides, CFTR 470Val, and TNF promoter 863A were independent risk markers for HLP.Conclusions: This genetic study is the first one to address the association of HLP with the CFTR mutation/variant/haplotype and TNF promoter polymorphism in a Chinese HTG population. The results suggest that the occurrence of HLP is multifactorial and polygenic.
Quadruplex Genotyping of F5, F2, and MTHFR Variants in a Single Closed Tube by High-Resolution Amplicon Melting
Authors: Seipp Michael T , Pattison David , Durtschi Jacob D , Jama Mohamed , Voelkerding Karl V , Wittwer Carl T 
Published: November 2007

AbstractBackground: Multiplexed amplicon melting is a closed-tube method for genotyping that does not require probes, real-time analysis, asymmetric PCR, or allele-specific PCR; however, correct differentiation of homozygous mutant and wild-type samples by melting temperature (Tm) analysis requires high-resolution melting analysis and controlled reaction conditions.Methods: We designed 4 amplicons bracketing the F5 [coagulation factor V (proaccelerin, labile factor)] 1691G&gt;A, MTHFR (NADPH) 1298A&gt;C, MTHFR 677C&gt;T, and F2 [coagulation factor II (thrombin)] 20210G&gt;A gene variants to melt at different temperatures by varying amplicon length and adding GC- or AT-rich 5′ tails to selected primers. We used rapid-cycle PCRs with cycles of 19–23 s in the presence of a saturating DNA dye and temperature-correction controls and then conducted a high-resolution melting analysis. Heterozygotes were identified at each locus by curve shape, and homozygous genotypes were assigned by Tm. We blinded samples previously genotyped by other methods before analysis with the multiplex melting assay (n = 110).Results: All samples were correctly genotyped with the exception of 7 MTHFR 1298 samples with atypical melting profiles that could not be assigned. Sequencing revealed that these 5 heterozygotes and 2 homozygotes contained the unexpected sequence variant MTHFR 1317T&gt;C. The use of temperature-correction controls decreased the Tm SD within homozygotes by a mean of 38%.Conclusion: Rapid-cycle PCR with high-resolution melting analysis allows simple and accurate multiplex genotyping to at least a factor of 4.
Accuracy in the Diagnostic Prediction of Acute Appendicitis Based on the Bayesian Network Model
Authors: Sakai S. , Kobayashi K. , Nakamura J. , Toyabe S. , Akazawa K. 
Published: November 2007

Summary

Objectives
: The diagnosis of acute appendicitis is difficult, and a diagnostic error will often lead to either a perforation or the removal of a normal appendix. In this study, we constructed a Bayesian network model for the diagnosis of acute appendicitis and compared the diagnostic accuracy with other diagnostic models, such as the naive Bayes model, an artificial neural network model, and a logistic regression model.

Methods
: The data from 169 patients, who suffered from acute abdominal pain and who were suspected of having an acute appendicitis, were analyzed in this study. Nine variables were used for the evaluation of the accuracy of the four models for the diagnosis of an acute appendicitis. The naive Bayes model, the Bayesian network model, an artificial neural network model, and a logistic regression model were used i this study for the diagnosis of acute appendicitis. These four models were validated by using the “632 + bootstrap method” for resampling. The levels of accuracy of the four models for diagnosis were compared by the error rates and by the areas under the receiver operating characteristic curves.

Results
: Through the course of illness, 50.9% (86 of 169) of the patients were diagnosed as having an acute appendicitis. The error rate was the lowest in the Bayesian network model, as compared with the other diagnostic models. The area under the receiver operating characteristic curve analysis also showed that the Bayesian network model provided the most reliable results.

Conclusion
: The Bayesian network model provided the most accurate results in comparison to other models for the diagnosis of acute appendicitis.
The Development of the Asymmetric Nozaki–Hiyama–Kishi Reaction
Authors: Hargaden Gráinne C. , Guiry Patrick J. 
Published: November 2007

AbstractThis review collates the literature to date on the development of the Nozaki–Hiyama–Kishi (NHK) reaction into an important chromium‐mediated, carbon‐carbon bond forming process. The initial research employed stoichiometric quantities of chromium and this was exploited in the key steps of a range of total syntheses. Thereafter, the NHK reaction was further developed with the discovery of the catalytic variant. The focus of recent investigations is on the application of this reaction in asymmetric synthesis. The asymmetric NHK typically employed a range of salen‐ and oxazoline‐derived chiral ligands and tethered bis(8‐quinolinato)‐chromium complexes. To date, good to high enantioselectivities have been obtained in a variety of NHK‐type processes, including allylation, crotylation, methallylation, allenylation, propargylation and vinylation of a range of aldehydes, with limited examples employing ketones as substrates. Selected examples of the asymmetric NHK in total synthesis will also be described.
Aktivierung von Wasserstoff durch ungesättigte gemischte Metallcluster und ‐komplexe
Authors: Adams Richard D. , Captain Burjor 
Published: November 2007

AbstractAls Folge des ständig steigenden Energiekonsums besteht ein wiederauflebendes Interesse an der Chemie des Wasserstoffs. Jüngste Studien haben elektronisch ungesättigte mehrkernige Metallkomplexe mit sperrigen Liganden hervorgebracht, die eine Vielzahl von Reaktionen mit Wasserstoff eingehen, so auch die einfache Addition und Eliminierung unter milden Bedingungen. Materialien, die große Wasserstoffmengen reversibel absorbieren, sind für die Wasserstoffspeicherung und die katalytische Hydrierung äußerst interessant. Dieser Kurzaufsatz fasst neuere Untersuchungen zu Reaktionen von Wasserstoff mit ungesättigten gemischten Metallclustern und ‐komplexen mit Platinzentren und sperrigen Phosphanliganden zusammen. Einige verwandte Studien zur Kooperativität in Dimetallkomplexen und zur Synthese von Trimetallnanopartikeln auf mesoporösen Trägern als hoch aktive und selektive Hydrierungskatalysatoren werden ebenfalls diskutiert.
Upper bound for ruin probabilities under optimal investment and proportional reinsurance
Authors: Liang Zhibin , Guo Junyi 
Published: November 2007

AbstractIn this paper, we consider the optimal investment and reinsurance from an insurer's point of view to maximize the adjustment coefficient. We obtain the explicit expressions for the optimal results in the diffusion approximation (D‐A) case as well as in the jump‐diffusion (J‐D) case. Furthermore, we derive a sharper bound on the ruin probability, from which we conclude that the case with investment is always better than the case without investment. Some numerical examples are presented to show that the ruin probability in the D‐A case sometimes underestimates the ruin probability in the J‐D case. Copyright © 2007 John Wiley & Sons, Ltd.