bluuebunny/crossref_metadata_2025 huggingface dataset:
Ductal Carcinoma In Situ of the Breast: Current Concepts and Future Directions
Authors: Siziopikou Kalliopi P.
Published: April 2013

Context.—In situ carcinomas of the breast constitute 15% to 30% of all newly diagnosed breast cancer cases; 80% of these in situ lesions belong to the ductal carcinoma in situ (DCIS) category. Similar to invasive breast carcinomas, DCIS is not a single disease but rather many distinct diseases with different histopathologic and molecular characteristics, a propensity to progress to invasive disease, and differential response to treatment.

Objective.—To review the classic pathologic parameters of clinical significance and the differential diagnosis of the DCIS lesions, present our new understanding of the importance of biomarkers, and discuss innovative approaches for targeted therapy in DCIS.

Data Sources.—Extensive review of the relevant peer-reviewed literature.

Conclusions.—In DCIS, improved understanding of the underlying biologic pathways of tumor progression is expected to lead to more accurate classification and innovative targeted treatment approaches for the management of these lesions.
Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine
Authors: Goyal Rajen , Gersbach Elizabeth , Yang Ximing J. , Rohan Stephen M.
Published: April 2013

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies.

Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management.

Data Sources.—Published literature and personal experience.

Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.
Understanding Sources of Bias in Diagnostic Accuracy Studies
Authors: Schmidt Robert L. , Factor Rachel E.
Published: April 2013

Context.—Accuracy is an important feature of any diagnostic test. There has been an increasing awareness of deficiencies in study design that can create bias in estimates of test accuracy. Many pathologists are unaware of these sources of bias.

Objective.—To explain the causes and increase awareness of several common types of bias that result from deficiencies in the design of diagnostic accuracy studies.

Data Sources.—We cite examples from the literature and provide calculations to illustrate the impact of study design features on estimates of diagnostic accuracy. In a companion article by Schmidt et al in this issue, we use these principles to evaluate diagnostic studies associated with a specific diagnostic test for risk of bias and reporting quality.

Conclusions.—There are several sources of bias that are unique to diagnostic accuracy studies. Because pathologists are both consumers and producers of such studies, it is important that they be aware of the risk of bias.
Quality Appraisal of Diagnostic Accuracy Studies in Fine-Needle Aspiration Cytology: A Survey of Risk of Bias and Comparability
Authors: Schmidt Robert L. , Factor Rachel E. , Witt Benjamin L. , Layfield Lester J.
Published: April 2013

Context.—The quality of diagnostic accuracy studies is determined by 2 key factors: risk of bias and comparability. Bias can distort accuracy estimates and poor reporting impairs comparability. While diagnostic accuracy studies for fine-needle aspiration cytology (FNAC) are frequently published, the methodologic issues associated with this body of literature have never been reviewed.

Objective.—To assess the quality of design and reporting of diagnostic test accuracy studies in FNAC.

Data Sources.—Diagnostic accuracy studies were identified by a Medline (US National Library of Medicine) search. Sixty-four FNAC diagnostic test accuracy studies were randomly selected for structured review with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) survey. Studies were divided between 2 time periods: 2000-2001 and 2009-2011.

Conclusions.—Diagnostic test accuracy studies of FNAC suffer from numerous deficiencies in study design, which negatively affect the reliability of accuracy estimates.
Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine
Authors: Raparia Kirtee , Villa Celina , DeCamp Malcolm M. , Patel Jyoti D. , Mehta Minesh P.
Published: April 2013

Context.—Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the so-called driver mutations, which may serve as “druggable” therapeutic targets. Thus, development of personalized approaches for the treatment of non–small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors.

Objective.—To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC.

Data Sources.—Peer-reviewed published literature and personal experience.

Conclusions.—There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.
Socio-Economic Analysis of Soyabeanutilization in Akure South Local Government Area, Ondo State
Authors: J.A. Folayan  , J.O. Bifarin
Published: April 2013

This study was carried out for the purpose of analyzing the socio-economic of soyabean inAkure South Local Government Area of Ondo state with the objective of examining the socio-economic characteristics of the respondents Data were collected from one hundred (100) respondents drawn from five communities using well structured questionnaire. The data were analyzed using frequency distribution, percentages and regression model while gross margin was used to determined the profitability of the utilization operators. The outcome of the study revealed that 76% of the respondents involved in utilization were females, about 82% of the respondents were married and 87% were educated. All 100% of the respondent reported that utilization increase their annual incomes. The gross margin result revealed that N11, 877 accrued to a respondent per month in the study area. The outcome of regression analysis revealed that the level of education, occupation, family size, experience and annual income had positive correlation with quantity of utilization whereas, the negative correlation in the storage, inadequate finance, lack of producing farmers, inadequate enlightenment campaign programme by extension workers were emphasized as the problems confronting the utilization in the area. It is recommended that the government should put in place adequate and efficient credit facility to enhance operational activities, provide regular and continuous enlightenment campaign programme by extension workers to the respondents and assist in the regular provision of adequate storage facilities and power supply for preservation of the products.
Japanese Character Input: Its State and Problems
Authors: Morita Ichiko
Published: April 2013

Computer processing of information is highly advanced in japan, and it continues to be researched and improved by the cooperative efforts of the government, private corporations, and individual scientists, who are among the best in the world. This paper introduces various approaches to the computer input of information currently developed in japan, and discusses the possibility of their applications to the processing of East Asian-vernacular language materials in large research libraries in this country.
Cost Analysis of an Automated and Manual Cataloging and Book Processing System
Authors: Druschel Joselyn
Published: April 2013

A comparative cost analysis of an automated network system (WLN) and a local manual system of cataloging and book processing at Washington State University Libraries indicates that the automated system is about 20 percent less costly than the manual system. A per-unit cost approach was used in calculating the monthly cost of each system based on the average number of items processed per month under the automated system. The process and the results of the analysis are presented in a series of charts which detail the tasks, items processed, unit and total monthly costs of both the manual and automated systems. The higher costs of the manual system were essentially staff costs.
How Long the Wait until We Can Call It Television
Authors: Borrell Jerry
Published: April 2013

How Long the Wait until We Can Call It Television
Data Processing Library: A Very Special Library
Authors: Cook Sherry
Published: April 2013

Data Processing Library: A Very Special Library
An Automated Music Programmer (MUSPROG)
Authors: Harrison David F. , Herber Randolph J.
Published: April 2013

A system to compile programs of recorded music for broadast by the University of Iowa's radio stations. The system also provides a permanent catalog of all recorded music holdings and an accurate inventory control. The program, which operates on an IBM 360/65, is available in FORTRAN IV, COBOL and PL/1, with assembly language subroutines and external maintenance programs.
File Organization of Library Records
Authors: Warheit I. A.
Published: April 2013

Library records and their utilization are described and the various types of file organization available are examined. The serial file with a series of inverted indexes is preferred to the simple serial file or a threaded list file. It is shown how various records should be stored, according to their utilization, in the available storage devices in order to achieve optimum cost-performance.
A Fast Algorithm for Automatic Classification
Authors: Dattola R. T.
Published: April 2013

An economical classification process of order n of log n (for n elements), which does not employ n-square procedures. Conversion proofs are given and possible information retrieval applications are discussed.
Information Retrieval Using a Middleware Approach
Authors: Boberić Krstićev Danijela
Published: April 2013

This paper explores the use of a mediator/wrapper approach to enable the search of an existing library management system using different information retrieval protocols. It proposes an architecture for a software component that will act as an intermediary between the library system and search services. It provides an overview of different approaches to add Z39.50 and Search/Retrieval via URL (SRU) functionality using a middleware approach that is implemented on the BISIS library management system. That wrapper performs transformation of Contextual Query Language (CQL) into Lucene query language. The primary aim of this software component is to enable search and retrieval of bibliographic records using the SRU and Z39.50 protocols, but the proposed architecture of the software components is also suitable for inclusion of the existing library management system into a library portal. The software component provides a single interface to server-side protocols for search and retrieval of records. Additional protocols could be used. This paper provides practical demonstration of interest to developers of library management systems and those who are trying to use open-source solutions to make their local catalog accessible to other systems.
Modeling a Library Web Site Redesign Process: Developing a User-Centered Web Site Through Usability Testing
Authors: Becker Danielle A. , Yannotta Lauren
Published: April 2013

This article presents a model for creating a strong, user-centered web presence by pairing usability testing and the design process. Four rounds of usability testing were conducted throughout the process of building a new academic library web site. Participants were asked to perform tasks using a talk-aloud protocol. Tasks were based on guiding principles of web usability that served as a framework for the new site. Results from this study show that testing throughout the design process is an effective way to build a web site that not only reflects user needs and preferences, but can be easily changed as new resources and technologies emerge.
Editorial Board Thoughts: Libraries as Makerspace?
Authors: Colegrove Patrick "Tod"
Published: April 2013

Editorial Board Thoughts: Libraries as Makerspace?
Editor's Comments
Authors: Gerrity Robert
Published: April 2013

Editor's Comments
Synthesis and Labeling of RNA In Vitro
Authors: Huang Chao , Yu Yi‐Tao
Published: April 2013

This unit discusses several methods for generating large amounts of uniformly labeled, end‐labeled, and site‐specifically labeled RNAs in vitro. The methods involve a number of experimental procedures, including RNA transcription, 5′ dephosphorylation and rephosphorylation, 3′ terminal nucleotide addition (via ligation), site‐specific RNase H cleavage directed by 2′‐O‐methyl RNA‐DNA chimeras, and 2‐piece splint ligation. The applications of these RNA radiolabeling approaches are also discussed. Curr. Protoc. Mol. Biol. 102:4.15.1–4.15.14. © 2013 by John Wiley & Sons, Inc.
Flow Cytometric Analysis of Cell Division by Dilution of CFSE and Related Dyes
Authors: Lyons A. Bruce , Blake Stephen J. , Doherty Kathleen V.
Published: April 2013

The technique described in this unit uses the intracellular fluorescent label carboxyfluorescein diacetate succinimidyl ester (CFSE) to track proliferating cells. Covalently bound CFSE is divided equally between daughter cells, allowing discrimination of successive rounds of cell division. The technique is applicable to in vitro cell division, as well as to in vivo division of adoptively transferred cells and can resolve eight or more successive generations. CFSE is long lived, permitting analysis for several months after cell transfer, and has the same spectral characteristics as fluorescein, so monoclonal antibodies conjugated to phycoerythrin or other compatible fluorochromes may be used to immunophenotype the dividing cells. In addition, information is given on a second‐generation dye, Cell Trace Violet (CTV), excited by 405‐nm blue laser light. CTV is chemically related to CFSE, but allows the 488‐nm line of the Argon laser to be used for other probes. Curr. Protoc. Cytom. 64:9.11.1‐9.11.12. © 2013 by John Wiley & Sons, Inc.
Flow Cytometry of the Side Population (SP)
Authors: Petriz Jordi
Published: April 2013

The side population (SP) has become an important hallmark for the definition of the stem‐cell compartment, especially for the detection of stem cells and for their physical isolation by fluorescence‐activated cell sorting (FACS). SP cells are CD34−and were discovered using ultraviolet excitation based on the efflux of Hoechst 33342 (Ho342). Although the method works as originally described, the protocol is difficult for most investigators to perform: first, because the ability to discriminate SP cells is based on the differential retention of Ho342 during a functional assay; second, because of the difficulties in setting the right experimental and acquisition conditions; and third, because analysis of the acquired data requires extensive expertise in flow cytometry to accurately detect the SP events. More recently, a new assay based on the efflux of Vybrant DyeCycle Violet stain (DCV) has been documented to discriminate SP cells. This unit contains many helpful pointers to aid the user in obtaining the best possible results with these assays.Curr. Protoc. Cytom. 64:9.23.1‐9.23.20. © 2013 by John Wiley & Sons, Inc.
Time‐Lapse Microscopy Approaches to Track Cell Cycle and Lineage Progression at the Single‐Cell Level
Authors: Errington Rachel J. , Chappell Sally C. , Khan Imtiaz A. , Marquez Nuria , Wiltshire Marie , Griesdoorn Victoria D. , Smith Paul J.
Published: April 2013

Time‐lapse microscopy can be described as the repeated collection of an image (in n‐dimensions; x, y, z, λ) or field of view from a microscope at discrete time intervals. The duration of the time interval defines the temporal resolution, which in turn characterizes the type of event detected. This unit describes the implementation of time‐lapse microscopy to link initial cell cycle position during acute exposures to anti‐cancer agents with anti‐proliferative consequences for individual cells. The approach incorporates fundamental concepts arising from the ability to capture simple video sequences of cells from which it is possible to extract kinetic descriptors that reflect the interplay of mitosis and cell death in the growth of an unsynchronized tumor population. Utilizing a multi‐well format enables the user to screen different drug derivatives, multiple dose ranges, or cell cultures with unique genetic backgrounds. The objective of this unit is to present the basic methodology for capturing time‐lapse sequences and touch upon subsequent mining of the data for deriving event curves and possible cell lineage maps. Curr. Protoc. Cytom. 64:12.4.1‐12.4.13. © 2013 by John Wiley & Sons, Inc.
Meta‐Analysis of Healing and Prevention of Digital Ulcers in Systemic Sclerosis
Authors: Tingey Theresa , Shu Jenny , Smuczek Joseph , Pope Janet
Published: April 2013

Objective

To assess the efficacy of therapies in healing and preventing digital ulcers (DUs) in systemic sclerosis (SSc; scleroderma).

Methods

Medline and EMBASE databases, and American College of Rheumatology and European League Against Rheumatism abstracts, were searched. Randomized controlled trials (RCTs) with outcomes investigating healing or prevention of DUs in SSc and comparing a pharmacologic therapy with placebo or an active agent were included. The pooled risk ratios (RRs) using the fixed‐effects model were calculated and heterogeneity was tested using the I2 statistic.

Results

Sixty studies were found; 19 were not randomized, and 10 did not give DU quantitative data or no comparison of a different drug, leaving 31 RCTs with a total of 1,989 patients. Quality was 3 of 5 or less for 11 trials. DUs were not the primary outcome in many RCTs. Phosphodiesterase type 5 (PDE‐5) inhibitors were significant for DU healing (RR 3.28 [95% confidence interval (95% CI) 1.32, 8.13], P = 0.01). Two large bosentan trials were significant for mean number of new DUs (standardized mean difference [SMD] −0.34 [95% CI −0.57, −0.11], P = 0.004). Oral prostacyclins were not statistically different from placebo, but intravenous (IV) iloprost prevented new DUs (SMD 0.77 [95% CI −1.46, −0.08], P = 0.03). Single trials for atorvastatin and vitamin E were positive in the prevention and healing of DU, respectively. There were many negative trials: antiplatelet therapy, oral N‐acetylcysteine, heparin, dimethyl sulfoxide, ketanserin, prazosin, prostaglandin E1, cyclofenil, quinapril, and topical nitroglycerin formulation.

Conclusion

Small sample sizes, few comparative trials, and heterogeneity limits the conclusions. The results suggest a role for PDE‐5 inhibitors in the healing of DUs; bosentan and IV iloprost may prevent new DUs.
Safety and Immunogenicity of Yellow Fever 17D Vaccine in Adults Receiving Systemic Corticosteroid Therapy: An Observational Cohort Study
Authors: Kernéis Solen , Launay Odile , Ancelle Thierry , Iordache Laura , Naneix‐Laroche Véronique , Méchaï Frédéric , Fehr Thierry , Leroy Jean‐Philippe , Issartel Bertrand , Dunand Jean , van der Vliet Diane , Wyplosz Benjamin , Consigny Paul‐Henri , Hanslik Thomas
Published: April 2013

Objective

To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy.

Methods

All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self‐administered standardized questionnaire within 10 days after immunization. YF‐specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids.

Results

Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1–60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1–67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5–20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4–45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination.

Conclusion

After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large‐scale studies are needed to confirm these results.
Impact of Etanercept on Work and Activity Impairment in Employed Moderate to Severe Rheumatoid Arthritis Patients in the United States
Authors: Hone Devon , Cheng Annie , Watson Crystal , Huang Baisong , Bitman Bojena , Huang Xing‐Yue , Gandra Shravanthi R.
Published: April 2013

Objective

To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA).

Methods

This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test.

Results

RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12‐month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233–22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001).

Conclusion

In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment.
Tanezumab Reduces Osteoarthritic Hip Pain: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase III Trial
Authors: Brown Mark T. , Murphy Frederick T. , Radin David M. , Davignon Isabelle , Smith Michael D. , West Christine R.
Published: April 2013

Objective

To compare the efficacy of tanezumab versus placebo for reducing pain and improving physical function in patients with osteoarthritis (OA) of the hip.

Methods

This was a 32‐week, randomized, double‐blind, placebo‐controlled, phase III trial. Patients with baseline Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively, and patient's global assessment of OA as “fair,” “poor,” or “very poor” were treated at baseline and weeks 8 and 16. Coprimary efficacy end points were change from baseline to week 16 in WOMAC Pain and Physical Function subscales and patient's global assessment, analyzed using analysis of covariance. Adverse events (AEs) were monitored throughout.

Results

Patients (n = 621) were randomized 1:1:1:1 to treatment with intravenous tanezumab 2.5 mg, 5 mg, or 10 mg or placebo. Each tanezumab group showed significant improvement for the 3 coprimary end points versus placebo (P ≤ 0.001 for all). AE incidence ranged from 55% to 58% across tanezumab groups versus 44% for placebo. Safety findings were similar to those previously reported. The tanezumab OA clinical program was temporarily placed on hold because of AEs leading to joint replacement. Total joint replacements were reported in 8 patients: 1 in the 10 mg, 2 in the 5 mg, 2 in the 2.5 mg, and 3 in the placebo group. A total of 9 joints were replaced (8 hips [7 index joints] and 1 shoulder).

Conclusion

Our findings indicate that tanezumab provides superior pain relief and improvement in physical function and patient's global assessment versus placebo in patients with painful hip OA, and is generally well tolerated.
Identification of Soluble 14‐3‐3∊ as a Novel Subchondral Bone Mediator Involved in Cartilage Degradation in Osteoarthritis
Authors: Priam Sabrina , Bougault Carole , Houard Xavier , Gosset Marjolaine , Salvat Colette , Berenbaum Francis , Jacques Claire
Published: April 2013

Objective

Mechanical stress plays an important role in cartilage degradation and subchondral bone remodeling in osteoarthritis (OA). The remodeling of the subchondral bone could initiate cartilage loss in OA through the interplay of bone and cartilage. The aim of this study was to identify soluble mediators released by loaded osteoblasts/osteocytes that could induce the release of catabolic factors by chondrocytes.

Methods

Murine osteoblasts/osteocytes were subjected to cyclic compression, and then conditioned medium from either compressed (CCM) or uncompressed (UCM) cells was used to stimulate mouse chondrocytes. Chondrocyte expression of matrix metalloproteinase 3 (MMP‐3), MMP‐13, type II collagen, and aggrecan was assessed by reverse transcription–polymerase chain reaction, Western blotting, and enzyme‐linked immunosorbent assay. Soluble mediators released by compressed osteoblasts/osteocytes were identified using iTRAQ (isobaric tags for relative and absolute quantification), a differential secretome analysis. Subchondral bone and cartilage samples were isolated from OA patients, and culture medium conditioned with OA subchondral bone or cartilage was used to stimulate human chondrocytes.

Results

Stimulation of mouse chondrocytes with CCM strongly induced the messenger RNA (mRNA) expression and protein release of MMP‐3 and MMP‐13 and inhibited the mRNA expression of type II collagen and aggrecan. Differential secretome analysis revealed that 10 proteins were up‐regulated in compressed osteoblasts/osteocytes. Among them, soluble 14‐3‐3∊ (s14‐3‐3∊) dose‐dependently induced the release of catabolic factors by chondrocytes, mimicking the effects of cell compression. Addition of a 14‐3‐3∊ blocking antibody greatly attenuated the CCM‐mediated induction of MMP‐3 and MMP‐13 expression. Furthermore, in human OA subchondral bone, s14‐3‐3∊ was strongly released, and in cultures of human OA chondrocytes, s14‐3‐3∊ stimulated MMP‐3 expression.

Conclusion

The results of this study identify s14‐3‐3∊ as a novel soluble mediator critical in the communication between subchondral bone and cartilage in OA. Thus, s14‐3‐3∊ may be a potential target for future therapeutic or prognostic applications in OA.
Overexpression of Sirtuin 6 Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen‐Induced Arthritis
Authors: Lee Hwa‐Suk , Ka Sun‐O , Lee Sang‐Myeong , Lee Sang‐Il , Park Jin‐Woo , Park Byung‐Hyun
Published: April 2013

Objective

Sirtuin 6 (SIRT‐6) is an NAD+‐dependent deacetylase and mono‐ADP‐ribosyltransferase. It is known to interfere with the NF‐κB signaling pathway and thereby has an antiinflammatory function. Due to the central role of NF‐κB in rheumatoid arthritis (RA) development, we undertook this study to test our hypothesis that SIRT‐6 could have antiarthritic effects.

Methods

An adenovirus containing SIRT‐6 complementary DNA (Ad‐SIRT6) was used to deliver SIRT‐6 to human RA fibroblast‐like synoviocytes in vitro as well as to mice with collagen‐induced arthritis (CIA) in vivo via bilateral intraarticular injections into the ankle joints.

Results

In vitro experiments demonstrated that SIRT‐6 overexpression suppressed NF‐κB target gene expression induced by tumor necrosis factor α. SIRT‐6 overexpression inhibited osteoclast differentiation induced by macrophage colony‐stimulating factor and RANKL in bone marrow–derived macrophages. Mice with CIA had an increased incidence of disease and developed arthritis in the hind paws. In contrast, mice injected with Ad‐SIRT6 showed attenuated severity of arthritis based on clinical scores, hind paw thickness, and radiographic and pathologic findings. Moreover, the injection of Ad‐SIRT6 down‐regulated local and systemic levels of proinflammatory cytokines. After induction of CIA, mice injected with Ad‐SIRT6 showed significantly decreased arthritis severity, from the onset of clinical signs to the end of the study.

Conclusion

These results suggest that blocking the NF‐κB pathway by SIRT‐6 in rheumatoid joints reduces both the inflammatory response and tissue destruction. Therefore, the development of an immunoregulatory strategy based on SIRT‐6 may have therapeutic potential for the treatment of RA.
Work and personal e‐mail use by university employees: PIM practices across domain boundaries
Authors: Capra Robert , Khanova Julia , Ramdeen Sarah
Published: April 2013

In this article, we present findings from a survey of nearly 600 university employees' e‐mail use. The study provides a detailed comparison of use patterns between work and personal e‐mail accounts. Our results suggest that users engage in more “keeping” behaviors with work e‐mail than with personal e‐mail—respondents reported more frequent use of keeping actions and larger inbox sizes for their work accounts. However, we found correlations between individual respondents' e‐mail behaviors in the two contexts, indicating that personal preferences can play a role. We also report results pointing to e‐mail as an important boundary management artifact. We show evidence that the use of multiple e‐mail accounts may be a work‐personal boundary placement strategy, but also observe that a fair amount of boundary permeation occurs through e‐mail. To our knowledge, this study is one of the first to compare e‐mail use in both work and personal contexts across the same sample. Our findings extend prior research on personal information management regarding e‐mail use, and help inform the role of e‐mail in managing work‐personal boundaries. The results have implications for the design of e‐mail systems, organizational e‐mail policies, user training, and understanding the impacts of technology on daily life.
A Less Conservative Stability Condition of Time‐Delay Systems with Polytopic Uncertainty
Authors: Wu Ai‐Guo , Lin Qingqiang , Fu Yan‐Ming , Duan Guang‐Ren
Published: April 2013

This paper considers the problem of stability analysis of time‐delay systems with time‐varying delay. By introducing a small scalar, the products between system matrices and Lyapunov matrices are decoupled with the help of the introduced additional matrices. Therefore, when the time‐delay systems with polytopic uncertainties are investigated, the vertex‐dependent Lyapunov function can be allowed, and thus the conservativeness can be reduced. Numerical examples are given to verify the effectiveness of the proposed results.
Improving of red colorants production by a new Penicillium purpurogenum strain in submerged culture and the effect of different parameters in their stability
Authors: Santos‐Ebinuma Valéria Carvalho , Roberto Inês Conceição , Simas Teixeira Maria Francisca , Pessoa Adalberto
Published: April 2013

There is a worldwide interest in the development of processes for colorants production from natural sources such as microorganism. The aim of this study was to optimize red colorants production by Penicillium purpurogenum DPUA 1275 and to evaluate the effect of pH, temperature, salts and polymers on the stability of these colorants. Under optimized conditions, a 78% increase in red colorants production was achieved. The best pH and temperature conditions were obtained at pH 8.0 and 70°C, respectively. In the presence of salts NaCl and Na2SO4, both at concentrations of 0.1 and 0.5 M in Mcllvaine buffer (pH 8.0), the red colorants showed good stability. In the presence of both polymers polyethylene glycol and sodium polyacrylate, the red colorants kept their color intensity. Thus, this study presents characteristics of red colorants produced by P. purpurogenum that can be applied in different industries after toxicological examination. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:778–785, 2013
Experimental and theoretical investigation of multistage extraction of 1,3‐propanediol using the extraction system phosphate/1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate/water
Authors: Müller Anja , Lutze Philip , Górak Andrzej
Published: April 2013

The separation of 1,3‐propanediol from fermentation broth is a challenging and energy‐demanding step using conventional unit operations. One alternative process is the use of an aqueous two‐phase system incorporating ionic liquids to use synergy effects of both technologies. Within this manuscript, the technical feasibility of the extraction of 1,3‐propanediol using the aqueous two‐phase system phosphate (salt)/1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate (ionic liquid)/water in a continuously operated process in pilot‐scale is presented. The extraction was performed in a multistage mixer–settler unit and successfully modeled with an equilibrium‐stage model and correlations to describe the liquid–liquid equilibrium of the salt/ionic liquid/water two‐phase system. The developed and validated model was used for a further investigation of the influence of different process parameters in the determined operating window. Theses parameters include the number of stages, the phase ratio, the pH, and the mass fraction of the involved components. The results prove that the phosphate and 1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate mass fraction, the phase ratio, and the number of stages have a considerable influence on the recovery of 1,3‐propanediol, whereas the pH value has only a smaller impact. Those results can be used for optimization of the system as well as for targeting future research within this area. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:933–942, 2013
Interaction between abscisic acid and nitric oxide in PB90‐induced catharanthine biosynthesis of catharanthus roseus cell suspension cultures
Authors: Chen Qian , Chen Zunwei , Lu Li , Jin Haihong , Sun Lina , Yu Qin , Xu Hongke , Yang Fengxia , Fu Mengna , Li Shengchao , Wang Huizhong , Xu Maojun
Published: April 2013

Elicitations are considered to be an important strategy to improve production of secondary metabolites of plant cell cultures. However, mechanisms responsible for the elicitor‐induced production of secondary metabolites of plant cells have not yet been fully elucidated. Here, we report that treatment of Catharanthus roseus cell suspension cultures with PB90, a protein elicitor from Phytophthora boehmeriae, induced rapid increases of abscisic acid (ABA) and nitric oxide (NO), subsequently followed by the enhancement of catharanthine production and up‐regulation of Str and Tdc, two important genes in catharanthine biosynthesis. PB90‐induced catharanthine production and the gene expression were suppressed by the ABA inhibitor and NO scavenger respectively, showing that ABA and NO are essential for the elicitor‐induced catharanthine biosynthesis. The relationship between ABA and NO in mediating catharanthine biosynthesis was further investigated. Treatment of the cells with ABA triggered NO accumulation and induced catharanthine production and up‐regulation of Str and Tdc. ABA‐induced catharanthine production and gene expressions were suppressed by the NO scavenger. Conversely, exogenous application of NO did not stimulate ABA generation and treatment with ABA inhibitor did not suppress NO‐induced catharanthine production and gene expressions. Together, the results showed that both NO and ABA were involved in PB90‐induced catharanthine biosynthesis of C. roseus cells. Furthermore, our data demonstrated that ABA acted upstream of NO in the signaling cascade leading to PB90‐induced catharanthine biosynthesis of C. roseus cells. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:994–1001, 2013
Improvement of mammalian cell culture performance through surfactant enabled concentrated feed media
Authors: Hossler Patrick , McDermott Sean , Racicot Christopher , Fann John C. H.
Published: April 2013

The design of basal and feed media in mammalian cell culture is paramount towards ensuring acceptable upstream process performance in various operation modes, especially fed‐batch culture. Mammalian cell culture media designs have evolved from the classical formulations designed by Eagle and Ham, to today's formulations designed from continuous improvement and statistical frameworks. Feed media is especially important for ensuring robust cell growth, productivity, and ensuring the product quality of recombinant therapeutics are within acceptable ranges. Numerous studies have highlighted the benefit of various media designs, supplements, and feed addition strategies towards the resulting cell culture process. In this work we highlight the use of a top‐down level approach towards feed media design enabled by the use of select surfactants for the targeted enrichment of a chemically defined feed media. The use of the enriched media was able to improve product titers at g/L levels, without adversely impacting the growth of multiple Chinese Hamster Ovary cell lines or the product quality of multiple recombinant antibodies. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1023–1033, 2013
Redefining the coccygeal plexus
Authors: Woon Jason T.K. , Stringer* Mark D.
Published: April 2013

The coccygeal plexus is variably described in anatomy texts and has rarely been studied despite the idiopathic nature of coccydynia in up to one‐third of affected patients. The plexus was therefore investigated using a combination of microdissection and histology. The distal sacrum and coccyx in continuity with ischiococcygeus were removed en bloc from 16 embalmed cadavers (mean age 78 ± 10 years, 7 females) with no local disease. Ten specimens underwent microdissection of the coccygeal plexus and the remaining six were examined histologically after staining with hematoxylin and eosin and S100 immunohistochemistry to demonstrate nerve fibers. The coccygeal plexus is formed within ischiococcygeus from the ventral rami of S4, S5, and Co1 with a contribution (gray rami communicantes) from the sacral sympathetic trunk. It gives rise to anococcygeal nerves which pierce ischiococcygeus and the sacrospinous ligament to supply the subcutaneous tissue on the dorsal aspect of the coccyx. Some branches from the plexus pass medially anterior to the coccyx. The coccycgeal plexus is formed within ischiococcygeus rather than on its pelvic surface and appears to supply skin in the anococcygeal region. It probably also contributes to the innervation of ischiococcygeus, the sacrospinous ligament, coccygeal ligaments, and periosteum. It deserves to be considered as a potential pain generator that may be implicated in some patients with coccydynia. Clin. Anat. 27:254–260, 2014. © 2013 Wiley Periodicals, Inc.
Long‐term outcomes of complete versus incomplete revascularization after drug‐eluting stent implantation in patients with multivessel coronary disease
Authors: Gao Zhan , Xu Bo , Yang Yue‐jin , Yuan Jin‐qing , Chen Jue , Chen Ji‐lin , Qiao Shu‐bin , Wu Yong‐jian , Yan Hong‐bin , Gao Run‐lin
Published: April 2013

Background

A limited number of studies on the impact of complete revascularization (CR) vs. incomplete revascularization (IR) on long‐term outcomes in patients with multivessel coronary disease (MVD) in current percutaneous coronary intervention (PCI) practice have yielded inconsistent results.

Methods

Between April 2004 and November 2010, 7,376 consecutive patients with MVD underwent PCI at the Fuwai Hospital in Beijing, China. Patients who underwent prior CABG and those who had an acute myocardial infarction (MI) within 24 hr before revascularization or presented with cardiogenic shock were excluded. Angiographic CR was defined as successful angioplasty of all diseased lesions in the major epicardial coronary vessels and their first degree side branches (diameter ≥2.5 mm), and proximal CR was defined as successful angioplasty of all diseased proximal arteries.

Results

Among 7,065 patients with MVD undergoing PCI treatment, angiographic CR was performed in 1,188 patients (16.8%), and proximal CR in 2,053 patients (29.1%). The study found that either angiographic or proximal IR were associated with significantly higher estimated 3‐year rate of cardiac death (2.55% vs. 1.13%, log‐rank P = 0.016; and 2.70% vs. 1.43%, log‐rank P = 0.024, respectively). After adjustment for differences in baseline characteristics between IR and CR patients, angiographic IR was associated with a significantly higher rate of cardiac death (adjusted hazards ratio [HR]: 2.56, 95% confidence interval [CI]: 1.03–6.41) while proximal IR was associated with a numerically higher rate of cardiac death (adjusted HR: 1.72, 95% CI: 0.93–3.17). For the subgroup of ≥2‐vessel IR with total occlusion, either angiographic or proximal IR patients had significantly higher rate of cardiac death (adjusted HR: 4.25, 95% CI: 1.50–12.09; and adjusted HR: 3.02, 95% CI: 1.40–6.52, respectively).

Conclusion

Compared with IR, patients with CR had better clinical outcomes, supporting CR as first choice for patients with MVD. © 2013 Wiley Periodicals, Inc.
Percutaneous closure of tricuspid paravalvular leak
Authors: Turner Mariel E. , Lai Wyman W. , Vincent Julie A.
Published: April 2013

While transcatheter closure of mitral and aortic paravalvular leaks has been well‐described, there are no prior reports of such procedures for prosthetic tricuspid valves. We describe our experience with percutaneous closure of a tricuspid paravalvular leak in a 34‐year‐old patient with a history of tricuspid atresia. He had previously undergone repair with placement of a right atrium‐to‐right ventricle conduit and most recently, placement of a bio‐prosthetic tricuspid valve. He subsequently developed significant tricuspid paravalvular leak with symptoms of severe right heart failure. His clinical status was improved following successful transcatheter closure of the defect. © 2013 Wiley Periodicals, Inc.
Transcatheter closure of perimembranous ventricular septal defect using amplatzer ductal occluder
Authors: Lee Sang Mi , Song Jin Young , Choi Jae Young , Lee Sang Yoon , Paik Jae Sook , Chang So Ick , Shim Woo Seop , Kim Seong Ho
Published: April 2013

Objective

To show that transcatheter closure of perimembranous ventricular septal defect (PMVSD) with the Amplatzer ductal occluder (ADO, AGA Medical Corp, Plymouth, Minnesota) is a safe and effective treatment option.

Background

Transcatheter closure of PMVSD is a challenging procedure. Recently, the Amplatzer PMVSD occluder (APMVSDO, AGA Medical Corp, Plymouth, Minnesota) has been shown to be effective in closing hemodynamically significant PMVSDs. However, the high incidence of complete atrioventricular block (CAVB) after device occlusion of a PMVSD has been a hot issue as well.

Methods

Among several devices used in closing PMVSD percutaneously, we prefer the ADO because of the anatomic resemblance between PMVSD with aneurysm and patent ductus arteriosus, and it has no right ventricular disc which may contribute to the occurrence of CAVB.

Results

Between August 2009 and May 2012, 21 patients (5 males and 16 females) underwent percutaneous PMVSD closure using ADO. The patients' ages ranged from 3 to 42 years (median: 7 years), and their weights ranged from 18 kg to 60 kg (median: 27 kg). All patients showed echocardiographic signs of left ventricular volume overload and trivial to small mitral regurgitation (Qp/Qs = 1.7 ± 0.4). The mean defect size of the right ventricular side was 4.3 ± 1.0 mm. Devices 2 mm larger than the measured narrowest VSD diameter were selected in most patients. The ADOs were successfully implanted in all patients without any significant complications except one transient CAVB, one case of delivery wire fracture, and one case of surgery due to significant residual leak. Small residual shunts were observed immediately after the device implantation, but they disappeared during follow‐up for 18 of 20 patients. The mean follow‐up period was 20 ± 9 months, and CAVB or aortic regurgitation was not observed in all patients.

Conclusion

Transcatheter closure of PMVSD with the ADO is a safe and promising treatment option, but long‐term follow‐up in a large number of patients would be warranted. © 2013 Wiley Periodicals, Inc.