bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homoplasy in genome-wide analysis of rare amino acid replacements: the molecular-evolutionary basis for Vavilov's law of homologous series
Authors: Rogozin Igor B , Thomson Karen , Csürös Miklós , Carmel Liran , Koonin Eugene V 
Published: March 2008

Abstract

Background
Rare genomic changes (RGCs) that are thought to comprise derived shared characters of individual clades are becoming an increasingly important class of markers in genome-wide phylogenetic studies. Recently, we proposed a new type of RGCs designated RGC_CAMs (after Conserved Amino acids-Multiple substitutions) that were inferred using genome-wide identification of amino acid replacements that were: i) located in unambiguously aligned regions of orthologous genes, ii) shared by two or more taxa in positions that contain a different, conserved amino acid in a much broader range of taxa, and iii) require two or three nucleotide substitutions. When applied to animal phylogeny, the RGC_CAM approach supported the coelomate clade that unites deuterostomes with arthropods as opposed to the ecdysozoan (molting animals) clade. However, a non-negligible level of homoplasy was detected.

Results
We provide a direct estimate of the level of homoplasy caused by parallel changes and reversals among the RGC_CAMs using 462 alignments of orthologous genes from 19 eukaryotic species. It is shown that the impact of parallel changes and reversals on the results of phylogenetic inference using RGC_CAMs cannot explain the observed support for the Coelomata clade. In contrast, the evidence in support of the Ecdysozoa clade, in large part, can be attributed to parallel changes. It is demonstrated that parallel changes are significantly more common in internal branches of different subtrees that are separated from the respective common ancestor by relatively short times than in terminal branches separated by longer time intervals. A similar but much weaker trend was detected for reversals. The observed evolutionary trend of parallel changes is explained in terms of the covarion model of molecular evolution. As the overlap between the covarion sets in orthologous genes from different lineages decreases with time after divergence, the likelihood of parallel changes decreases as well.

Conclusion
The level of homoplasy observed here appears to be low enough to justify the utility of RGC_CAMs and other types of RGCs for resolution of hard problems in phylogeny. Parallel changes, one of the major classes of events leading to homoplasy, occur much more often in relatively recently diverged lineages than in those separated from their last common ancestor by longer time intervals of time. This pattern seems to provide the molecular-evolutionary underpinning of Vavilov's law of homologous series and is readily interpreted within the framework of the covarion model of molecular evolution.

Reviewers
This article was reviewed by Alex Kondrashov, Nicolas Galtier, and Maximilian Telford and Robert Lanfear (nominated by Laurence Hurst).
Double rupture of interventricular septum and free wall of the left ventricle, as a mechanical complication of acute myocardial infarction: a case report
Authors: Rentoukas Elias I , Lazaros George A , Kaoukis Andreas P , Matsakas Evangellos P 
Published: March 2008

Abstract

Introduction
Cardiac ruptures following acute myocardial infarction include rupture of the left ventricle free-wall, ventricular septal defects, and papillary muscle rupture. Double myocardial rupture is a rare complication of acute myocardial infarction (0.3 %) and the report of such cases is exclusively limited to a small series of autopsy studies.

Case presentation
In this report we present the unusual case of a 70-year-old woman with acute anteroseptal myocardial infarction, which was complicated by a combined rupture of the interventricular septum near the apex, and the free wall of the left ventricle with concomitant formation of a pseudoaneurysm. The double myocardial rupture was accidentally discovered 10 days later with echocardiography, when the patient, complaining only of mild exertional dyspnea, was hospitalized for a scheduled coronary angiography. The patient underwent successful surgical correction of the double myocardial rupture along with by-pass grafting.

Conclusion
This report highlights the importance of comprehensive noninvasive predischarge diagnostic evaluation of all postinfarct patients, since serious and potentially life-threatening complications might have not been suspected on clinical grounds.
Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity
Authors: Shpacovitch V , Feld M , Hollenberg M D , Luger T A , Steinhoff M 
Published: March 2008

AbstractSerine proteases are well known as enzymes involved in digestion of dietary proteins, blood coagulation, and homeostasis. Only recent groundbreaking studies revealed a novel role of serine proteases as signaling molecules acting via protease-activated receptors (PARs). Important effects of PAR activation on leukocyte motility, cytokine production, adhesion molecule expression, and a variety of other physiological or pathophysiological functions have been described in vitro and in vivo. The crucial role of PAR activation during disease progression was revealed in animal models of different gastrointestinal pathologies, neuroinflammatory and neurodegenerative processes, skin, joint and airway inflammation, or allergic responses. This review focuses on the findings related to the impact of PAR deficiency in animal models of inflammatory and allergic diseases. Additionally, we observe the role of PAR activation in the regulation of functional responses of innate and adaptive immune cells in vitro. Understanding the mechanisms by which PARs exert the effects of serine proteases on immune cells may lead to new therapeutic strategies in inflammation, immune defense, and allergy.
Psychological and Clinical Factors Implicated in Decision Making About a Trial of Low-Dose Tamoxifen in Hormone Replacement Therapy Users
Authors: Rondanina Gabriella , Puntoni Matteo , Severi Gianluca , Varricchio Clara , Zunino Anna , Feroce Irene , Bonanni Bernardo , Decensi Andrea 
Published: March 2008

Purpose To assess the sociodemographic, health-related, and psychological factors that influence the decision of women on hormone replacement therapy (HRT) to participate in a phase III trial of low-dose tamoxifen. Patients and Methods Clinical and psychological factors were assessed in 265 women who accepted and 192 women who refused to participate in a proposed trial. Health-related and sociodemographic factors included age, Gail risk, body mass index, education, current HRT use, regular mammographic screening, smoking habit, physical activity, alcohol use, concern about adverse effects, and physician recommendation. Psychological factors included breast cancer–related worry, absolute and comparative cancer risk perception, anxiety, and depression. Results The most frequent reasons for entry were willingness to participate in a research program (60%), the need/desire to receive frequent medical care (58%), and the desire to contribute to medical knowledge (44%); whereas reasons for refusal included fear of medication abuse (33%), concern about adverse effects (31%), and physician advice against enrollment (24%). In a logistic model, after adjusting for current HRT use, the trial participation was directly associated with satisfaction with clearly explained study objectives (odds ratio [OR] = 9.33; 95% CI, 4.04 to 21.55) and inversely associated with high breast cancer worry (OR = 0.15; 95% CI, 0.03 to 0.77) and age ≥ 60 years (OR = 0.40; 95% CI, 0.22 to 0.73). Conclusion Participation in a chemoprevention trial among HRT users is associated with a younger age, no breast cancer worry, and satisfaction with health care providers, suggesting a condition of psychological well-being as a promoting factor and emphasizing the importance of thorough counseling at study presentation.
Irinotecan/Fluorouracil Combination in First-Line Therapy of Older and Younger Patients With Metastatic Colorectal Cancer: Combined Analysis of 2,691 Patients in Randomized Controlled Trials
Authors: Folprecht Gunnar , Seymour Matthew T. , Saltz Leonard , Douillard Jean-Yves , Hecker Hartmut , Stephens Richard J. , Maughan Timothy S. , Van Cutsem Eric , Rougier Philippe , Mitry Emmanuel , Schubert Ute , Köhne Claus-Henning 
Published: March 2008

Purpose Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC). Patients and Methods Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age ≥ 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients. Results Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and ≥ 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable. Conclusion Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
Analysis of Primary CD30+ Cutaneous Lymphoproliferative Disease and Survival From the Surveillance, Epidemiology, and End Results Database
Authors: Yu James B. , Blitzblau Rachel C. , Decker Roy H. , Housman Douglas M. , Wilson Lynn D. 
Published: March 2008

Purpose Primary CD30+ cutaneous lymphoproliferative disease (PCLPD) is a spectrum of indolent cutaneous T-cell lymphomas. The primary intention of the analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database was to report epidemiologic information and overall survival of patients with PCLPD. Methods We investigated the SEER database from 1973 to 2004 and performed univariable and multivariable survival analysis. Results A total of 268 cases of PCLPD were recorded from 1973 to 2004. Median age at diagnosis was 61 years (range, 5 to 98 years). Among cases, 58% were male, and 42% female. Race distribution was 87% white, 7% black, and 4% Asian/Pacific Islander. A total of 157 patients had primary, localized PCLPD. For the total population (N = 268), overall survival at 3 years was 81% (95% CI, 74% to 87%). Population-matched relative survival at 3 years was 87% (SE, 3.6%). Disease-specific survival at 5 years was 92% (95% CI, 86% to 95%). Head and neck skin site predicted for inferior overall survival in patients with primary, localized PCLPD on univariable analysis (hazard ratio [HR] = 4.4; P = .008; 95% CI, 1.5 to 13.2), and was suggestive of decreased overall survival on multivariate analysis (HR = 3.0; P = .06; 95% CI, 0.95 to 9.7). Conclusion Localized PCLPDs are rare diseases with an excellent overall survival and occur more frequently in whites and in men. Head and neck skin primary site may be associated with poorer survival. Conclusions regarding subsets demonstrating association with survival should be taken with caution, given the small number of deaths analyzed.
Phase I Study of Recombinant Interleukin-21 in Patients With Metastatic Melanoma and Renal Cell Carcinoma
Authors: Thompson John A. , Curti Brendan D. , Redman Bruce G. , Bhatia Shailender , Weber Jeffrey S. , Agarwala Sanjiv S. , Sievers Eric L. , Hughes Steven D. , DeVries Todd A. , Hausman Diana F. 
Published: March 2008

PurposeA phase I study of patients with metastatic malignant melanoma (MM) and renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of recombinant human interleukin-21 (rIL-21).Patients and MethodsPatients who had one or fewer prior systemic treatments for metastatic MM or RCC were treated with rIL-21 administered for two 5-day cycles on days 1 through 5 and 15 through 19 of a treatment course; rIL-21 was administered by rapid intravenous infusion in an outpatient setting. Cohorts of patients received doses ranging from 3 to 100 μg/kg/dose, and an expanded cohort was treated at the MTD. Patients with stable disease (SD) or better could receive additional treatment cycles.ResultsForty-three patients were treated (24 MM; 19 RCC), including 28 in the expanded cohort. Dose-limiting toxicities consisted primarily of transient grade 3 laboratory abnormalities. The MTD was estimated to be 30 μg/kg. The most common adverse events included flu-like symptoms, pruritus, and rash. Twelve patients received up to five additional two-cycle courses of treatment without cumulative toxicity, except for one patient with reversible grade 4 hepatotoxicity. Serum concentrations of rIL-21 increased in a dose-proportional manner. Dose-dependent increases in soluble CD25 reflected lymphocyte activation. Antitumor activity was observed in both MM (one complete response and 11 SD) and RCC (four partial responses, 13 SD).ConclusionOutpatient therapy with rIL-21 at 30 μg/kg was well tolerated, had dose-dependent pharmacokinetics and pharmacodynamics, and was associated with antitumor activity in patients with MM and RCC.
Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
Authors: Burstein Harold J. , Elias Anthony D. , Rugo Hope S. , Cobleigh Melody A. , Wolff Antonio C. , Eisenberg Peter D. , Lehman Mary , Adams Bonne J. , Bello Carlo L. , DePrimo Samuel E. , Baum Charles M. , Miller Kathy D. 
Published: March 2008

Purpose Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). Patients and Methods Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. Results Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. Conclusion Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.
Nano-Scale Hydroxyapatite Coating on Macroscopic Silica Fiber Using Carbon Nanofibers as Templates
Authors: Wu Qiang , Ogihara Hitoshi , Uchida Hisaichiro , Sadakane Masahiro , Nodasaka Yoshinobu , Ueda Wataru 
Published: March 2008

Abstract
Starting from Ca(NO3)2–H3PO4–methanol precursor mixtures and using carbon nanofibers (CNFs) as templates, we have successfully coated nano-scale hydroxyapatite (HAp) layers on macroscopic silica fiber (diameter ca. 5 μm) surfaces. Under controlled experimental conditions, CNFs can be formed on silica fiber with variable yield, layer thickness, and diameters, and thus can be further used as different templates for HAp coating. XRD, FE-SEM, and cross-sectional TEM experimental results provided clear evidence that CNFs can act as effective templates for uniform nano-scale HAp coating on silica fiber. It turned out that heat-treatment at 923 K for 5 h is sufficient for complete removal of the CNFs templates and crystallization of the resulting nano-scale HAp. It was shown that the resulting HAp layer thickness was ca. 2–4 μm, the average crystallite size was ca. 20–40 nm, and the specific surface area was ca. 50–65 m2 g−1. In addition, it was clearly demonstrated that the average layer thickness and amount of HAp was controlled by the layer thickness of CNFs. Therefore, the coating mode of HAp could be reliably controlled through the selection of different kinds of CNFs templates.
The Role of Adsorption Species in the Formation of Ag Nanostructures by a Microwave-Polyol Route
Authors: Tsuji Masaharu , Matsumoto Kisei , Jiang Peng , Matsuo Ryoichi , Hikino Sachie , Tang Xin-Ling , Kamarudin Khairul Sozana Nor 
Published: March 2008

Abstract
The role of adsorption species in reaction solutions has been studied in microwave-polyol synthesis of silver (Ag) nanostructures. When Ag+ ions from AgNO3 were reduced in ethylene glycol by the addition of H2[PtCl6] and poly(vinylpyrrolidone) (PVP), a mixture of one-dimensional (1-D) nanorods and nanowires and 3-D spherical, cubic, and triangular-bipyramidal nanoparticles was obtained within three minutes. It has been previously believed that PVP acts as a surfactant and its selective adsorption on {100} facets results in pentagonal 1-D nanorods or nanowires and cubic and triangular-bipyramidal nanocrystals. We found here that these Ag products could also be formed without the addition of PVP in the presence of Cl− ions, though their yields were lower than those in the presence of PVP by a factor of ≈300. These results indicate that Cl− anions can also act as adsorption species to assist the formation of these Ag nanostructures. It is concluded that the difference in the adsorption ability of different species in solution on Ag nanostructures determines final shapes, sizes, and yields of formed Ag nanostructures.
An Unusual Iodinated 5′-Deoxyxylofuranosyl Nucleoside from an Okinawan Ascidian, Diplosoma sp.
Authors: Margiastuti Pulpi , Ogi Takayuki , Teruya Toshiaki , Taira Junsei , Suenaga Kiyotake , Ueda Katsuhiro 
Published: March 2008

Abstract
An unusual nucleoside, 4-amino-7-(5′-deoxy-β-d-xylofuranosyl)-5-iodopyrrolo[2,3-d]pyrimidine (1), was isolated from an ascidian, Diplosoma sp., and its structure was successfully determined by spectroscopic and chemical analysis. The known didemnenones 2–5 were also isolated. Compound 1 was found to inhibit the division of fertilized sea urchin eggs.
Convenient Synthesis of Angular Triquinane from 4-Alkenylfulvene via Thermal Cycloaddition Followed by Skeletal Rearrangement of the Resulting [4 + 2] Adduct
Authors: Inagaki Sho , Imura Keisuke , Morita Toshio , Yoshimi Yasuharu , Hatanaka Minoru , Kawano Tomikazu 
Published: March 2008

Abstract
Alkenylfulvene prepared by the annulation of allylidenetriphenylphosphorane with 1,4-ynedione proceeded thermal cycloaddition in a highly regio- and stereoselective manner to give [4 + 2] adduct which was then converted into triquinane derivative by the treatment with LHMDS-t-BuOK after hydrolysis of the enol ether group.
Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer
Authors: Powles Trevor J , Howell Anthony , Evans D Gareth , Mccloskey Eugene V , Ashley Sue , Greenhalgh Rosemary , Affen Jenny , Flook Lesley Ann , Tidy Alwynne 
Published: March 2008

Objective To assess the safety and tolerability of a standardized 40 mg red clover isoflavone dietary supplement (Promensil®, Novogen) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women. Study design Healthy women aged 35–70 years (n = 401) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a randomized, double-blind, placebo-controlled pilot trial. Participants were assessed clinically and blood samples taken for biochemical analysis every six months. In addition, study participants underwent mammography, bone density and transvaginal ultrasound (postmenopausal women only) once per year. Results No significant differences in breast density, endometrial thickness, serum cholesterol, follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo. In postmenopausal women, some significant differences in bone marker levels were seen between active and placebo groups, at six months and at 12 months. The adverse event profile was similar across all red clover isoflavone and placebo groups. Conclusion This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women. Supplements containing red clover isoflavones did not adversely affect breast density, skeletal strength or cardiovascular status. In postmenopausal women, endometrial status was not adversely affected. The adverse event profile was similar between red clover isoflavones, and placebo and endocrine status did not differ.
Calcium Channel TRPV6 Is Involved in Murine Maternal–Fetal Calcium Transport
Authors: Suzuki Yoshiro , Kovacs Christopher S , Takanaga Hitomi , Peng Ji-Bin , Landowski Christopher P , Hediger Matthias A 
Published: March 2008

Abstract
Maternal–fetal calcium (Ca2+) transport is crucial for fetal Ca2+ homeostasis and bone mineralization. In this study, the physiological significance of the transient receptor potential, vanilloid 6 (TRPV6) Ca2+ channel in maternal–fetal Ca2+ transport was investigated using Trpv6 knockout mice. The Ca2+ concentration in fetal blood and amniotic fluid was significantly lower in Trpv6 knockout fetuses than in wildtypes. The transport activity of radioactive Ca2+ (45Ca) from mother to fetuses was 40% lower in Trpv6 knockout fetuses than in wildtypes. The ash weight was also lower in Trpv6 knockout fetuses compared with wildtype fetuses. TRPV6 mRNA and protein were mainly localized in intraplacental yolk sac and the visceral layer of extraplacental yolk sac, which are thought to be the places for maternal–fetal Ca2+ transport in mice. These expression sites were co-localized with calbindin D9K in the yolk sac. In wildtype mice, placental TRPV6 mRNA increased 14-fold during the last 4 days of gestation, which coincides with fetal bone mineralization. These results provide the first in vivo evidence that TRPV6 is involved in maternal–fetal Ca2+ transport. We propose that TRPV6 functions as a Ca2+ entry pathway, which is critical for fetal Ca2+ homeostasis.