bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microstructure and mineral composition of dystrophic calcification associated with the idiopathic inflammatory myopathies
Authors: Eidelman Naomi , Boyde Alan , Bushby Andrew J , Howell Peter GT , Sun Jirun , Newbury Dale E , Miller Frederick W , Robey Pamela G , Rider Lisa G 
Published: October 2009

Abstract
Introduction
Calcified deposits (CDs) in skin and muscles are common in juvenile dermatomyositis (DM), and less frequent in adult DM. Limited information exists about the microstructure and composition of these deposits, and no information is available on their elemental composition and contents, mineral density (MD) and stiffness. We determined the microstructure, chemical composition, MD and stiffness of CDs obtained from DM patients.

Methods
Surgically-removed calcinosis specimens were analyzed with fourier transform infrared microspectroscopy in reflectance mode (FTIR-RM) to map their spatial distribution and composition, and with scanning electron microscopy/silicon drift detector energy dispersive X-ray spectrometry (SEM/SDD-EDS) to obtain elemental maps. X-ray diffraction (XRD) identified their mineral structure, X-ray micro-computed tomography (μCT) mapped their internal structure and 3D distribution, quantitative backscattered electron (qBSE) imaging assessed their morphology and MD, nanoindentation measured their stiffness, and polarized light microscopy (PLM) evaluated the organic matrix composition.

Results
Some specimens were composed of continuous carbonate apatite containing small amounts of proteins with a mineral to protein ratio much higher than in bone, and other specimens contained scattered agglomerates of various sizes with similar composition (FTIR-RM). Continuous or fragmented mineralization was present across the entire specimens (μCT). The apatite was much more crystallized than bone and dentin, and closer to enamel (XRD) and its calcium/phophorous ratios were close to stoichiometric hydroxyapatite (SEM/SDD-EDS). The deposits also contained magnesium and sodium (SEM/SDD-EDS). The MD (qBSE) was closer to enamel than bone and dentin, as was the stiffness (nanoindentation) in the larger dense patches. Large mineralized areas were typically devoid of collagen; however, collagen was noted in some regions within the mineral or margins (PLM). qBSE, FTIR-RM and SEM/SDD-EDS maps suggest that the mineral is deposited first in a fragmented pattern followed by a wave of mineralization that incorporates these particles. Calcinosis masses with shorter duration appeared to have islands of mineralization, whereas longstanding deposits were solidly mineralized.

Conclusions
The properties of the mineral present in the calcinosis masses are closest to that of enamel, while clearly differing from bone. Calcium and phosphate, normally present in affected tissues, may have precipitated as carbonate apatite due to local loss of mineralization inhibitors.
In Situ Cytotoxic and Memory T Cells Predict Outcome in Patients With Early-Stage Colorectal Cancer
Authors: Pagès Franck , Kirilovsky Amos , Mlecnik Bernhard , Asslaber Martin , Tosolini Marie , Bindea Gabriela , Lagorce Christine , Wind Philippe , Marliot Florence , Bruneval Patrick , Zatloukal Kurt , Trajanoski Zlatko , Berger Anne , Fridman Wolf-Herman , Galon Jérôme 
Published: October 2009

Purpose Many patients who present with early-stage colorectal cancer (International Union Against Cancer TNM stages I and II) are nevertheless at high risk of relapse. We hypothesized that intratumoral immune reaction could influence their prognosis. Patients and Methods The intratumoral immune reaction was investigated in 29 tumors by large-scale real-time polymerase chain reaction. Cytotoxic (CD8) and memory (CD45RO) T cells were quantified by immunohistochemical analyses of tissue microarrays from the center (CT) and the invasive margin (IM) of the 602 tumors from two independent cohorts. The results were correlated with tumor recurrence and patient survival. Results Patients with a strong infiltration of CD45RO+ cells in the tumor exhibited an increased expression of T-helper 1 and cytotoxicity-related genes. Densities of CD45RO+ and CD8+ cells in tumor regions (CT/IM) classified the patients into four distinct prognostic groups based on the presence of high density of each marker in each tumor region. The four groups were associated with dramatic differences in disease-free, disease-specific, and overall survival (all P < .0001). Five years after diagnosis, only 4.8% (95% CI, 0.6% to 8.8%) of patients with high densities of CD8+ plus CD45RO+ cells had tumor recurrence, and 86.2% (CI, 79.4% to 93.6%) survived. In contrast, the tumor recurred in 75% (95% CI, 17% to 92.5%) of patients with low densities of these cells, and only 27.5% (95% CI, 10.5% to 72%) survived (all P < .0001). Multivariate analyses showed that the immune criteria had independent effects on the rates of complete remission and survival. Conclusion The combined analysis of CD8+ plus CD45RO+ cells in specific tumor regions could provide a useful criterion for the prediction of tumor recurrence and survival in patients with early-stage colorectal cancer.
Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Authors: Graeser Monika K. , Engel Christoph , Rhiem Kerstin , Gadzicki Dorothea , Bick Ulrich , Kast Karin , Froster Ursula G. , Schlehe Bettina , Bechtold Astrid , Arnold Norbert , Preisler-Adams Sabine , Nestle-Kraemling Carolin , Zaino Mohammad , Loeffler Markus , Kiechle Marion , Meindl Alfons , Varga Dominic , Schmutzler Rita K. 
Published: October 2009

Purpose To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors. Patients and Methods A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene. Results The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer. Conclusion Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.
Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study
Authors: Mucci Lorelei A. , Powolny Anna , Giovannucci Edward , Liao Zhiming , Kenfield Stacey A. , Shen Rulong , Stampfer Meir J. , Clinton Steven K. 
Published: October 2009

Purpose Tumor growth requires the development of independent vascular networks that are often primitive in morphology and function. We examined whether microvessel morphology contributes to the considerable biologic heterogeneity of prostate cancer. Methods We evaluated microvessel morphology as a predictor of prostate cancer mortality among 572 men in the Health Professionals Follow-Up Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy tumor block sections for endothelial marker CD34 and assessed microvessel density, vessel size (area and diameter), and irregularity of vessel lumen using image analysis. Proportional hazards models were used to assess microvessel density and morphology in relation to lethal prostate cancer. Results Poorly differentiated tumors exhibited greater microvessel density, greater irregularity of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men developed bone metastases or died of cancer. Men with tumors exhibiting the smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI, 1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal disease. Adjusting for Gleason grade and prostate-specific antigen levels did not qualitatively change the results. Microvessel density was not linked to cancer-specific mortality after adjusting for clinical factors. Conclusion Aggressive tumors form vessels that are primitive in morphology and function, with consequences for metastases. Vascular size and irregularity reflect the angiogenic potential of prostate cancer and may serve as biomarkers to predict prostate cancer mortality several years after diagnosis.
Evidence-Based Approach to the Introduction of Positron Emission Tomography in Ontario, Canada
Authors: Evans William K. , Laupacis Andreas , Gulenchyn Karen Y. , Levin Les , Levine Mark 
Published: October 2009

Purpose The uptake of new health care technologies is usually driven by industry promotion, physician interest, patient demand, and institutional ability to acquire the technology. The introduction of positron emission tomography (PET) scanning in the province of Ontario, Canada, followed a different path. Methods The Ontario provincial government, through its Ministry of Health and Long-Term Care, commissioned a systematic review of the literature. When this found only weak evidence that PET has a positive impact on clinical outcomes, the Ministry introduced a provincial PET evaluation program to close the evidence gap. Results This article describes the challenges encountered establishing the PET evaluation program. These included the design and conduct of the initial clinical trials, the establishment of a PET cancer registry, standardizing how PET scans were performed and reported, and gaining acceptance by health professionals for the evaluative program. Conclusion The proliferation of health technologies is a key driver of increasing health care costs. The Ontario approach to the introduction of PET is a model worth consideration by health systems seeking to ensure that they receive value for money based on a strong evidentiary base when introducing new health technologies.
VMP (Bortezomib, Melphalan, and Prednisone) Is Active and Well Tolerated in Newly Diagnosed Patients With Multiple Myeloma With Moderately Impaired Renal Function, and Results in Reversal of Renal Impairment: Cohort Analysis of the Phase III VISTA Study
Authors: Dimopoulos Meletios A. , Richardson Paul G. , Schlag Rudolf , Khuageva Nuriet K. , Shpilberg Ofer , Kastritis Efstathios , Kropff Martin , Petrucci Maria T. , Delforge Michel , Alexeeva Julia , Schots Rik , Masszi Tamás , Mateos Maria-Victoria , Deraedt William , Liu Kevin , Cakana Andrew , van de Velde Helgi , San Miguel Jesús F. 
Published: October 2009

Purpose To assess bortezomib plus melphalan and prednisone (VMP) and melphalan and prednisone (MP) in previously untreated patients with multiple myeloma (MM) with renal impairment enrolled on the phase III VISTA study, and to evaluate renal impairment reversibility. Patients and Methods Patients received nine 6-week cycles of VMP (bortezomib 1.3 mg/m2, melphalan 9 mg/m2, prednisone 60 mg/m2) or MP. Patients with serum creatinine higher than 2 mg/dL were excluded. Results In the VMP/MP arms, 6%/4%, 27%/30%, and 67%/66% of patients had baseline glomerular filtration rate (GFR) of ≤ 30, 31 to 50, and higher than 50 mL/min, respectively. Response rates were higher and time to progression (TTP) and overall survival (OS) longer with VMP versus MP across renal cohorts. Response rates with VMP and TTP in both arms did not appear significantly different between patients with GFR ≤ 50 or higher than 50 mL/min; OS appeared somewhat longer in patients with normal renal function in both arms. Renal impairment reversal (baseline GFR < 50 improving to > 60 mL/min) was seen in 49 (44%) of 111 patients receiving VMP versus 40 (34%) of 116 patients receiving MP. By multivariate analysis, younger age (< 75 years; P = .006) and less severe impairment (GFR ≥ 30 mL/min; P = .027) were associated with higher reversal rates. In addition, treatment with VMP approached significance (P = .07). In both arms, rates of grade 4 and 5 adverse events (AEs) and serious AEs appeared higher in patients with renal impairment; with VMP, rates of discontinuations/bortezomib dose reductions due to AEs did not appear affected. Conclusion VMP is a feasible, active, and well-tolerated treatment option for previously untreated patients with MM with moderate renal impairment, resulting in 44% renal impairment reversal.
Evaluating the Combined Effect of Comorbidity and Prostate-Specific Antigen Kinetics on the Risk of Death in Men After Prostate-Specific Antigen Recurrence
Authors: Wo Jennifer Y. , Chen Ming-Hui , Nguyen Paul L. , Renshaw Andrew A. , Loffredo Marian J. , Kantoff Philip W. , D'Amico Anthony V. 
Published: October 2009

Purpose We examined whether time-dependent continuous prostate-specific antigen (PSA) velocity at recurrence was associated with all cause mortality (ACM) adjusting for comorbidity levels among men treated with definitive radiation therapy (RT) alone with or without androgen suppression therapy (AST) in the setting of a randomized controlled trial. Patients and Methods From 1995 to 2001, 206 men with localized, unfavorable prostate cancer were randomly assigned to receive RT alone or RT and AST combined. Cox multivariate regression analysis was performed to evaluate the relationship between PSA velocity at recurrence and ACM, adjusting for known prostate cancer prognostic factors, including Adult Comorbidity Evaluation 27 comorbidity level. Results With a median follow-up of 8.4 years, 89 biochemical recurrences and 74 ACM deaths occurred. Among all patients, higher PSA velocity was associated with increased ACM (hazard ratio [HR], 1.47; 95% CI, 1.07 to 1.44; P < .001) after adjusting for age, treatment arm, comorbidity score, and salvage AST. For 89 patients with biochemical recurrence, increasing PSA velocity at recurrence (HR, 1.60; 95% CI, 1.23 to 2.09; P ≤ .001) and moderate to severe comorbidity score (HR, 7.94; 95% CI, 1.55 to 40.52; P = .01) were associated with increased ACM. PSA velocity at recurrence was associated with significantly higher risk of ACM among patients with no or minimal comorbidity (P < .001), but not moderate to severe comorbidity (P = .12). Conclusion Rapid PSA velocity at recurrence is significantly associated with an increased risk of ACM among patients with no or minimal comorbidity but not moderate to severe comorbidity. These findings support judicious use of salvage AST, particularly in men with moderate to severe comorbidities, where prospective surveillance protocols are needed.
Quality of Life Supersedes the Classic Prognosticators for Long-Term Survival in Locally Advanced Non–Small-Cell Lung Cancer: An Analysis of RTOG 9801
Authors: Movsas Benjamin , Moughan Jennifer , Sarna Linda , Langer Corey , Werner-Wasik Maria , Nicolaou Nicos , Komaki Ritsuko , Machtay Mitchell , Wasserman Todd , Bruner Deborah Watkins 
Published: October 2009

PurposeTo determine the added value of quality of life (QOL) as a prognostic factor for overall survival (OS) in patients with locally advanced non–small-cell lung cancer (NSCLC) treated on Radiation Therapy Oncology Group RTOG-9801.Patients and MethodsTwo hundred forty-three patients with stage II/IIIAB NSCLC received induction paclitaxel and carboplatin (PC) and then concurrent weekly PC and hyperfractionated radiation (to 69.6 Gy). Patients were randomly assigned to amifostine (AM) or no AM during chemoradiotherapy. The following pretreatment factors were analyzed as prognostic factors for OS: Karnofsky performance status, stage, sex, age, race, marital status, histology, tumor location, hemoglobin, tobacco use, treatment arm (AM v no AM) and QOL scores (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [QLQ-C30] and Lung Cancer 13 [LC-13]). A multivariate (MVA) Cox proportional hazards model was performed using a backwards selection process.ResultsOf the 239 analyzable patients, 91% had a baseline global QOL score. Median follow-up time was 59 months for patients still alive and 17 months for all patients. Median baseline QLQ-C30 global QOL score was 66.7 on both treatment arms. Whether the global QOL score was treated as a dichotomized variable (based on the median score) or a continuous variable, all other variables fell out of the MVA for OS. Patients with a global QOL score less than 66.7 had an approximately 70% higher rate of death than patients with scores ≥ 66.7 (P = .004). A 10-point higher baseline global QOL score corresponded to a decrease in the hazard of death by approximately 10% (P = .004). The other independent QOL predictors for OS were the QLQ-C30 physical functioning (P = .011) and LC-13 dyspnea scores (P = .012).ConclusionIn this analysis, baseline global QOL score replaced known prognostic factors as the sole predictor of long-term OS for patients with locally advanced NSCLC.
Luminescence Properties of Yttrium Borate Samples with the Morphologies Controlled by Solvothermal Method
Authors: Hosokawa Saburo , Inoue Masashi 
Published: October 2009

Abstract
Solvothermal reaction of yttrium chloride hydrate and trimethoxyborane in 1,4-butanediol in the presence of amines at 315 °C directly yielded YBO3 crystals having flower-like morphology (particle size; 3–8 μm). The crystal growth toward the c axis was inhibited by adsorption of amines on the ab plane, and plate-like crystals were formed. The luminescence chromaticity of Y0.9Eu0.1BO3 samples synthesized by solvothermal reaction was different from that prepared by solid-state reaction; samples synthesized by the solvothermal reaction exhibited larger relative intensity ratio of the emission at 580 nm to that at 610 nm than samples prepared by the solid-state reaction.
Flipping DNA to Generate and Regulate Microbial Consortia
Authors: Ramadas Rohini , Thattai Mukund 
Published: October 2009

AbstractCommunities of interdependent microbes, found in diverse natural contexts, have recently attracted the attention of bioengineers. Such consortia have potential applications in biosynthesis, with metabolic tasks distributed over several phenotypes, and in live-cell microbicide therapies where phenotypic diversity might aid in immune evasion. Here we investigate one route to generate synthetic microbial consortia and to regulate their phenotypic diversity, through programmed genetic interconversions. In our theoretical model, genotypes involve ordered combinations of DNA elements representing promoters, protein-coding genes, and transcription terminators; genotypic interconversions are driven by a recombinase enzyme that inverts DNA segments; and selectable phenotypes correspond to distinct patterns of gene expression. We analyze the microbial population as it evolves along a graph whose nodes are distinct genotypes and whose edges are interconversions. We show that the steady-state proportion of each genotype depends on its own growth advantage, as well as on its connectivity to other genotypes. Multiple phenotypes with identical or distinct growth rates can be indefinitely maintained in the population, while their proportion can be regulated by varying the rate of DNA flipping. Recombinase-based synthetic constructs have already been implemented; the graph-theoretic framework developed here will be useful in adapting them to generate microbial consortia.
Evolution at a High Imposed Mutation Rate: Adaptation Obscures the Load in Phage T7
Authors: Springman R , Keller T , Molineux I J , Bull J J 
Published: October 2009

AbstractEvolution at high mutation rates is expected to reduce population fitness deterministically by the accumulation of deleterious mutations. A high enough rate should even cause extinction (lethal mutagenesis), a principle motivating the clinical use of mutagenic drugs to treat viral infections. The impact of a high mutation rate on long-term viral fitness was tested here. A large population of the DNA bacteriophage T7 was grown with a mutagen, producing a genomic rate of 4 nonlethal mutations per generation, two to three orders of magnitude above the baseline rate. Fitness—viral growth rate in the mutagenic environment—was predicted to decline substantially; after 200 generations, fitness had increased, rejecting the model. A high mutation load was nonetheless evident from (i) many low- to moderate-frequency mutations in the population (averaging 245 per genome) and (ii) an 80% drop in average burst size. Twenty-eight mutations reached high frequency and were thus presumably adaptive, clustered mostly in DNA metabolism genes, chiefly DNA polymerase. Yet blocking DNA polymerase evolution failed to yield a fitness decrease after 100 generations. Although mutagenic drugs have caused viral extinction in vitro under some conditions, this study is the first to match theory and fitness evolution at a high mutation rate. Failure of the theory challenges the quantitative basis of lethal mutagenesis and highlights the potential for adaptive evolution at high mutation rates.
Health Literacy and Child Health Outcomes: A Systematic Review of the Literature
Authors: DeWalt Darren A. , Hink Ashley 
Published: October 2009

OBJECTIVES: To review the relationship between parent and child literacy and child health outcomes and interventions designed to improve child health outcomes for children or parents with low literacy skills.METHODS: We searched Medline and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for articles published from 1980 through 2008 and included studies that reported original data, measured literacy and ≥1 health outcome, and assessed the relationship between literacy and health outcomes. Health outcomes included health knowledge, health behaviors, use of health care resources, intermediate markers of disease status, and measures of morbidity. Two abstractors reviewed each study for inclusion. Included studies were abstracted into evidence tables and were assessed by using an 11-item quality scale.RESULTS: We reviewed 4182 new titles and abstracts published since 2003. Fifty-eight articles were retained for full review, and 13 met the inclusion criteria. Eleven articles from the systematic review from 1980 to 2003 met the inclusion criteria, giving us a total of 24 articles. Children with low literacy generally had worse health behaviors. Parents with low literacy had less health knowledge and had behaviors that were less advantageous for their children's health compared with parents with higher literacy. Children whose parents had low literacy often had worse health outcomes, but we found mixed results for the relationship of literacy to the use of health care services. Interventions found that improving written materials can increase health knowledge, and combining good written materials with brief counseling can improve behaviors including adherence. The average quality of the studies was fair to good.CONCLUSIONS: Child and parent literacy seems associated with important health outcomes. Future research can help us understand under what circumstances this relationship is causal, how literacy and health outcomes are related in noncausal pathways, the relative importance of parent and child literacy, and what interventions effectively reduce health literacy–related disparities.