bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype
Authors: Cheang Maggie C.U. , Voduc David , Bajdik Chris , Leung Samuel , McKinney Steven , Chia Stephen K. , Perou Charles M. , Nielsen Torsten O. 
Published: March 2008

Abstract
Purpose: Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors.
Experimental Design: Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels.
Results: Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome.
Conclusions: The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.
Transcription Factor Signal Transducer and Activator of Transcription 5 Promotes Growth of Human Prostate Cancer Cells In vivo
Authors: Dagvadorj Ayush , Kirken Robert A. , Leiby Benjamin , Karras James , Nevalainen Marja T. 
Published: March 2008

Abstract
Purpose: Signal transducer and activator of transcription 5a/b (Stat5a/b) is the key mediator of prolactin effects in prostate cancer cells via activation of Janus-activated kinase 2. Prolactin is a locally produced growth factor in human prostate cancer. Prolactin protein expression and constitutive activation of Stat5a/b are associated with high histologic grade of clinical prostate cancer. Moreover, activation of Stat5a/b in primary prostate cancer predicts early disease recurrence. Here, we inhibited Stat5a/b by several different methodologic approaches. Our goal was to establish a proof of principle that Stat5a/b is critical for prostate cancer cell viability in vitro and for prostate tumor growth in vivo.
Experimental Design: We inhibited Stat5a/b protein expression by antisense oligonucleotides or RNA interference and transcriptional activity of Stat5a/b by adenoviral expression of a dominant-negative mutant of Stat5a/b in prostate cancer cells in culture. Moreover, Stat5a/b activity was suppressed in human prostate cancer xenograft tumors in nude mice. Stat5a/b regulation of Bcl-XL and cyclin D1 protein levels was shown by antisense suppression of Stat5a/b protein expression followed by Western blotting.
Results and Conclusions: We show here that inhibition of Stat5a/b by antisense oligonucleotides, RNA interference, or adenoviral expression of dominant-negative Stat5a/b effectively kills prostate cancer cells. Moreover, we show that Stat5a/b is critical for human prostate cancer xenograft growth in nude mice. The effects of Stat5a/b on the viability of prostate cancer cells involve Stat5a/b regulation of Bcl-XL and cyclin D1 protein levels but not the expression or activation of Stat3. This work establishes Stat5a/b as a therapeutic target protein for prostate cancer. Pharmacologic inhibition of Stat5a/b in prostate cancer can be achieved by small-molecule inhibitors of transactivation, dimerization, or DNA binding of Stat5a/b.
Evaluation of Colon Cancer–Specific Antigen 2 as a Potential Serum Marker for Colorectal Cancer
Authors: Leman Eddy S. , Schoen Robert E. , Magheli Ahmed , Sokoll Lori J. , Chan Daniel W. , Getzenberg Robert H. 
Published: March 2008

Abstract
Purpose: A blood test to detect colon cancer at a preventable stage would represent a major advancement. We have previously identified colon cancer–specific markers using focused proteomics analysis of nuclear structural proteins. Two of these markers, colon cancer–specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is a distinct novel colon cancer marker identified using focused proteomics.
Experimental Design: Using an indirect ELISA on serum samples obtained from two institutions, we evaluated CCSA-2 as a serum-based colon cancer marker. A total of 111 serum samples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study.
Results: Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 μg/mL has overall specificity of 78.4% [95% confidence interval (95% CI), 67.3-87.1%] and sensitivity of 97.3% (95% CI, 85.8-99.5%) in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90 (95% CI, 0.83-0.95).
Conclusion: Our initial study shows that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity.
The “Book of Will” of Petrus Woskan (1680-1751): Some Insights into the Global Commercial Network of the Armenians in the Indian Ocean
Authors: Bhattacharya Bhaswati 
Published: March 2008

AbstractThis paper argues that “insider” material, preserved by the Armenians in the archives of the cathedral in New Julfa presents, by virtue of its logic, a one-sided, consensual picture. “Outsider” material contests this view and highlights the underlying conflicts of interest that even existed among the core members of the network. The picture that emerges from this study points to a more dynamic, complex structure in which the multiple interests of individual members of family firms, kin, and community members in different capacities were grafted into one. Loopholes in the system were visible as early as the 1720s, long before the center at New Julfa collapsed. Les archives arméniennes ont été conservées dans la cathédrale de la Nouvelle Julfa. Ces sources “internes” présentent, selon nous, une image partiale de consensus. L'examen minutieux des sources “externes” par contre fait ressortir des conflits d'intérêts même entre les grands négociants du réseau arménien. Ces documents-là attestent des structures complexes plus dynamiques. Dans ce cadre s'inscrivaient les multiples intérêts des membres individuels de la firma familiale, des parents, et des membres de la communauté. Et les faiblesses du système sont déjà perceptibles dans les années vingt du XVIIème siècle, bien avant l'effondrement de son centre à la Nouvelle Julfa.
Teaching Concepts Versus Facts in Developmental Biology
Authors: Wood William B. 
Published: March 2008

Note from the Editor Points of View (POV) address issues faced by many people within the life science education community. CBE—Life Sciences Education (CBE-LSE) publishes the POV Feature to present two or more opinions published side-by-side on a common topic. We consider POVs to be “Op-Ed” pieces designed to stimulate thought and dialogue on significant educational issues. They are not meant to be exhaustive treatments of a subject. In this issue, we ask the question, “What are key concepts in developmental biology?” We present three POVs. The first is by CBE-LSE Editor-in-Chief, William Wood, and it is in part based on his experience teaching developmental biology to undergraduates at the University of Colorado, Boulder, including his collaborative experiments in the classroom with Jennifer Knight, the first results of which have been published in CBE-LSE ( Knight and Wood, 2005 ). The second, a partially tongue-in-cheek list of key concepts to convey to students about embryonic development, is by Scott Gilbert (Swarthmore College), author of the leading textbook worldwide for teaching developmental biology, Developmental Biology, 8th ed. (Sinauer Associates, Inc.). The third is by Jeff Hardin (University of Wisconsin–Madison), who has produced Web-based educational materials for teaching developmental biology that are used nationally and internationally for conveying dynamic events during early development (see the WWW feature in this issue by Stark for more details), and who deals with the vexing problem of trying to convey the essential four-dimensional nature of embryonic development to introductory students.
Online extraction of 5-hydroxyindole acetic acid from urine for analysis by liquid chromatography–tandem mass spectrometry
Authors: Perry Heather , Keevil Brian 
Published: March 2008

Background Urinary 5-hydroxyindole acetic acid (5-HIAA) is a useful marker for the turnover of tryptophan metabolites in the diagnosis and monitoring of carcinoid tumours and the carcinoid syndrome. We have developed a simple and cost-effective assay for urinary 5-HIAA using liquid chromatography–tandem mass spectrometry (LC–MS/MS) incorporating an online sample clean-up process to replace a liquid chromatography electrochemical (LC-EC) technique. Methods Acidified urine was serially diluted in ammonium acetate buffer followed by ammonium acetate buffer enriched with 5-hydroxyindole-3-acetic-2,2-D2 acid internal standard. A 2.1 × 10 mm C18 column was used for primary online clean-up and eluted with 100% methanolic mobile phase onto a second dC18 Atlantis 2.1 × 20 mm column. Analytes were detected by mass spectrometry using transitions 192.1 > 146.3 and 194.1 > 148.0 for 5-HIAA and deuterated analyte, respectively. Results Run time was 3 min with 5-HIAA eluting at 1.37 min. The inter and intra-assay imprecision and accuracies of the three levels of inhouse quality control (QC) (30, 300 and 600 μmol/L) were acceptable with coefficient of variations (CVs) and deviation from target values <12% ( n = 15). The average recovery of 5-HIAA spiked into urine was 93.7% with no ion suppression observed. The limit of detection was 2.8 and lower limit of quantification 4.0 μmol/L. Passing–Bablok regression of LC-EC with LC–MS/MS results showed good agreement between the methods, the relationship described as LC–MS/MS = 1.01(LC–EC)–1.22. No systematic or proportional biases were observed over the working range of the method. The assay was linear to at least 2000 μmol/L. Conclusions We have developed a robust method offering a more than six-fold improvement in linearity compared to the existing LC–EC method.
High-resolution melting analysis for detection of familial ligand-defective apolipoprotein B-100 mutations
Authors: Liyanage Khemanganee E , Hooper Amanda J , Defesche Joep C , Burnett John R , van Bockxmeer Frank M 
Published: March 2008

Background Familial ligand-defective apolipoprotein B-100 (FDB) is characterized by elevated plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B, normal triglyceride and HDL-cholesterol levels, the presence of tendon xanthomas, and premature coronary artery disease. FDB cannot be clinically distinguished from heterozygous LDL-receptor-defective familial hypercholesterolaemia (FH) without genetic testing. Methods Amplicons in exon 26 and exon 29 of the APOB gene were screened for established genetic variants including mutations and polymorphisms using high-resolution melting analysis. Six novel variants associated with FDB in hypercholesterolaemic Dutch patients (S3476L, S3488G, Y3533C, T3540M, I4350T, G4368D) were also studied. Results All positive controls, a total of 10 mutations in exon 26 and four mutations in exon 29, were readily detectable by melting curve analysis. In addition, a patient previously not known to be heterozygous for the H3543Y mutation was identified in a screen of hypercholesterolaemic subjects. The method was validated by comparison of high-resolution melting analysis with DNA sequence data in a ‘blinded’ manner in 35 consecutive patients attending a lipid disorders clinic. These patients were classified as ‘definite FH’ by the Dutch Lipid Clinic Network criteria. Five patients were found to be heterozygous for the R3500Q and one for H3543Y. Conclusions We have established a novel, robust method of FDB mutation detection using high-resolution melting analysis in conjunction with DNA sequencing. Compared with existing methods it is not only more cost-effective, but is also capable of detecting new sequence changes and will have importance in cascade screening of affected subjects.
Adolescents' reasons for using a microbicide-like product over time
Authors: Short Mary B , Succop Paul A , Rupp Richard , Rosenthal Susan L 
Published: March 2008

Summary This study examined the reasons that adolescent girls used a product over time. Adolescent girls ( n = 208; 14–21 years) participated in a six-month study in which they completed three face-to-face interviews and 24-weekly phone call interviews. Participants were given microbicide-like products (vaginal lubricants) and encouraged to use them with condoms when they had intercourse. Most of the reasons for use were endorsed by most of the adolescent girls, at some time during the study. Over time, the adolescents were significantly more likely to report the following reasons for use: did not think the product would leak out ( z = 2.49; P < 0.01), the product felt comfortable ( z = 2.41; P < 0.02) and the product was not messy to use ( z = 3.11; P < 0.01). Although it appears that adolescents are interested in microbicides, they may worry about certain characteristics of the product. It will be important to develop anticipatory guidance that focuses on the experience of using the product, making sure adolescent girls continue to use over time.
Transmission of HIV-1 infection due to a fist fight
Authors: Emerson C R , Quah S P 
Published: March 2008

Summary We report a case of HIV-1 infection transmission caused by a fist fight between brothers. A 30-year-old Caucasian UK resident man developed ‘flu-like illness with symptoms of lethargy and weakness. Persistent lymphadenopathy six months later lead to HIV antibody testing, which was positive. Of note, his 37-year-old brother, who was HIV antibody-positive since August 2000, was taking HAART (combivir and nevaripine) with CD4 350 × 106/L (16%) with viral load 4800 copies/mL (log 2.58). A bloody fight had occurred between them four weeks prior to onset of symptoms. Phylogenetic analysis was undertaken. Analysis of the pol gene region indicated that samples from both brothers belonged to the subtype C clade of HIV-1, and that the sequences were closely related to one another. Exposure risk data are extremely useful in helping counsel patients prior to HIV-testing but, as this case illustrates, does not cover all situations.
An audit of completeness of HIV clinical histories: before and after introduction of an HIV proforma
Authors: Natha M , Sheehy C , Pollard M , Pakianathan M , Prime K 
Published: March 2008

Summary The completeness of a ‘first consultation’ human immunodeficiency virus (HIV) clinical history before and after the introduction of an HIV proforma was audited by a retrospective case notes review. Twenty key variables considered essential to every history were assessed. There was a significant improvement in the documentation of 14 of the 18 items for men and 14 of the 20 items for women post-proforma with no deterioration in documentation of any of the variables. Our study supports the introduction of a structured ‘first consultation’ notes proforma for use during consultations with both newly diagnosed HIV-positive patients and those transferring their care from other centres.
Evolutionäre Algorithmen zur Echtzeitoptimierung von Produktionsplänen für Chargenprozesse (Evolutionary Algorithms for the Online Optimization of Batch Production Schedules)
Authors: Sand Guido , Till Jochen , Tometzki Thomas , Urselmann Maren , Emmerich Michael , Engell Sebastian 
Published: March 2008

Die Echtzeitoptimierung von Produktionsplänen für Chargenprozesse ist gekennzeichnet durch kritische Antwortzeiten und unsichere Daten. Unsicherheitsbehaftete Entscheidungsprozesse auf gleitenden Zeithorizonten können durch Modelle mit gemischt-ganzzahliger Kompensation abgebildet werden. Der Beitrag vergleicht zwei hybridisierte evolutionäre Algorithmen für eine Fallstudie aus dieser Problemklasse.
The real-time optimization of batch production schedules is characterized by critical response times and uncertain data. Decision processes under uncertainty on moving horizons can be represented by models with mixed-integer compensation. This contribution compares two hybridized evolutionary algorithms for a case study which belongs to this class of problems.
Qualitätsbasierte Schnittplanoptimierung in der Papierindustrie (Quality-based Retrimming in the Paper Industry)
Authors: Harjunkoski Iiro 
Published: March 2008

Eine neue Strategie zur Schnittplanoptimierung wird diskutiert. Bisherige mathematische Modelle können Qualitätsaspekte nicht genau genug berücksichtigen und müssen deshalb ergänzt werden. Die neuen Algorithmen und Modelle verbinden die Planungs- mit den Qualitätskontrollsystemen und ermöglichen dadurch einen Qualitätsgewinn, der Energie und Rohstoffe spart und gleichzeitig auch die Lieferungsqualität verbessert und den Lieferumfang erhöht.
A new strategy to the trim-loss problem will be presented. The previous approaches are not able to handle quality aspects exactly. The paper presents a novel mathematical model and algorithm that enables the integration of planning and quality control system data. This allows to optimize the trim-loss problem with respect to quality, which results in improved quality, energy and raw material savings, as well as more precise and complete customer deliveries.
Patient Outcomes Following Subepithelial Connective Tissue Graft and Free Gingival Graft Procedures
Authors: Wessel Jeffrey R. , Tatakis Dimitris N. 
Published: March 2008

Background: Subepithelial connective tissue grafts (CTGs) and free gingival grafts (FGGs) are common periodontal procedures with similar indications; however, they may differ regarding patient outcomes. Reports on postoperative periodontal patient outcomes are limited. The aim of this observational trial was to compare patient‐based outcomes for CTGs and FGGs.Methods: Patients who received CTG or FGG completed postoperative questionnaires at 3 days and 3 weeks to assess pain, number of analgesic pills taken, and number of days pills were taken. Postoperative pain was assessed using a visual analog scale (VAS).Results: Twenty‐three subjects (12 CTGs and 11 FGGs) completed the study. Differences between CTG and FGG groups in VAS pain scores at 3 days did not reach statistical significance. The proportion of subjects reporting pain in the palate at 3 days was significantly greater for FGG (P <0.05). There were no significant intergroup differences at 3 weeks. For the FGG group, 3‐week VAS pain scores were less than the 3‐day ones (P <0.01). For the entire study population, the number of days analgesic pills were taken, total number of analgesic pills taken, and number of pills taken from day 3 to the end of the study correlated with the 3‐week pain scores.Conclusions: FGG is associated with a greater incidence of donor site pain compared to CTG at the early postoperative period. Longer‐term pain after soft tissue grafting is associated with greater analgesic usage. There is an opportunity to improve the postoperative protocols of soft tissue grafting, particularly for FGG.
The prevalence of Parkinson’s disease among Vilnius inhabitants
Authors: Valeikiene Vaineta , Ceremnych Jelena , Mieliauskaite Diana , Alekna Vidmantas 
Published: March 2008

AbstractIn a hospital-based study we investigated the prevalence of Parkinson’s disease among inhabitants of the Vilnius city, the capital of Lithuania. The study group was selected from patients who were diagnosed with Parkinson’s disease during the time frame of 1978-2005. Patients’ time of diagnosis were based on the data of dispensary cards, registration journals and/or other documentation. A questionnaire and Mini Mental State Examination provided data for analysis on the conditions of the patients. The prevalence of Parkinson’s disease in Vilnius is 1.32/1000 inhabitants and is higher in men than in women (p < 0.05). The age of Parkinson’s disease onset in men and women is the same (63.77 ± 0.70 years). The rigidity-tremor form of Parkinson’s disease is the most frequent (76.8% of all cases). The PD prevalence rate in Vilnius inhabitants are close to the mean levels observed in studies made in Finland, Austria, Germany. The prevailing form of Parkinson’s disease is rigidity-tremor.
High intracellular Zn2+ ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
Authors: Wong Pooi-Fong , Abubakar Sazaly 
Published: March 2008

AbstractMalignant prostate tissues have markedly reduced zinc (Zn2+) contents in comparison to non-malignant tissues. In this study, we restored a high intracellular Zn2+ level to LNCaP prostate cancer cells by culturing the cells in a growth medium supplemented with a supraphysiological concentration of Zn2+ (10 μg/ml) over 5 weeks. The intracellular Zn2+ level increased in the Zn2+-treated cells, and there was a marked increase in the presence of zincosomes, a Zn2+-specific intracellular organelle. The proliferation rate of the Zn2+-treated cells was markedly reduced. There was also a significant increase (36.6% ± 6.4%) in the total tyrosine phosphorylated proteins. Vaccinia H1-related (VHR) phosphatase, zeta chain-associated protein-70 (ZAP-70) kinase and phosphorylated extracellular signal-regulated protein kinase 1 and 2 (p-ERK 1 and 2) were also present in higher abundance. Treatment with TPEN, which chelates Zn2+, reduced the abundance of VHR phosphatase and ZAP-70 kinase, but increased the abundance of p-ERK 1. However, the TPEN treatment restored the Zn2+-treated LNCaP cell proliferation to a rate comparable to that of the non Zn2+-treated cells. These results highlight the importance of a high intracellular Zn2+ content and the VHR/ZAP-70-associated pathways in the modulation of LNCaP prostate cancer cell growth.