bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and Clinical Considerations in Concomitant Bone Marrow Involvement by Plasma Cell Myeloma and Chronic Lymphocytic Leukemia/Monoclonal B-Cell Lymphocytosis: A Series of 15 Cases and Review of Literature
Authors: Alley Christopher L. , Wang Endi , Dunphy Cherie H. , Gong Jerald Z. , Lu Chuanyi M. , Boswell Elizabeth L. , Burchette James , Lagoo Anand S. 
Published: April 2013

Context.—Plasma cell myeloma and chronic lymphocytic leukemia are both common hematologic malignancies, sharing many epidemiologic features. Concomitant detection of the 2 conditions poses special diagnostic challenges for the pathologist.
Objective.—To describe the pathologic findings in cases of concomitant bone marrow involvement by myeloma and CD5+ monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome.
Design.—Fifteen cases that met the diagnostic criteria were identified from pathology databases at 4 participating institutions. Morphologic findings were reviewed, additional immunohistochemical stains performed, and flow cytometric, cytogenetic, and relevant laboratory and clinical information was summarized. Previously published cases were searched from electronic databases and cross-references.
Results.—Most patients (13 of 15) were older males. Often (11 of 15) they presented clinically with myeloma, yet had both monotypic plasma cells and B cells in the diagnostic marrow. In 4 patients, myeloma developed 24 months or later after chronic lymphocytic leukemia. In 7 patients, myeloma and CD5+ B cells showed identical immunoglobulin light-chain restriction. Primary differential diagnoses include lymphoplasmacytic lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia with plasmacytoid differentiation. CD56 and/or cyclin D1 expression by plasma cells was helpful for correct diagnosis. Most patients in our cohort and published reports were treated for plasma cell myeloma.
Conclusions.—Concomitant detection of myeloma and chronic lymphocytic leukemia in the bone marrow is a rare event, which must be carefully differentiated from lymphomas with lymphoplasmacytic differentiation for correct treatment.
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.
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.
Synthesis and Labeling of RNA In Vitro
Authors: Huang Chao , Yu Yi‐Tao 
Published: April 2013

AbstractThis 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

AbstractThe 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

AbstractThe 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

AbstractTime‐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

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

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

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

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