bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of five frozen human-pooled serum samples assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference procedure in a traceability investigation of γ-glutamyltransferase catalytic concentration measurements in China
Authors: Xia Changyu , Tong Qing , Wang Qingtao , Tang Zhuling , Qi Lili , Chi Shan , Zhang Man , Wang Xuejing , Li Haixia , Xu Guobin 
Published: April 2010

Background The in vitro directive of the European Union requires traceability to the international recommended reference procedures. The application of the reference procedures is necessary in order to evaluate the accuracy of γ-glutamyltransferase (GGT) assays of routine measurement systems in China. Methods Five frozen patient-pooled serum samples were assigned values by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference procedure in order to evaluate the traceability of the results of GGT catalytic activity from six homogeneous systems. One of the serum samples was used to calibrate seven non-homogeneous systems. Results All of the homogeneous systems, except the Dade system (Dade Bering Inc, IL, USA), achieved traceability within the measurement range. The Roche and Hitachi systems were better than the other systems. After calibration, the variance of the non-homogeneous systems decreased dramatically from between 14.50% and 25.23% to between 1.25% and 3.09% and the bias decreased from between −11.4% and −4.1% to between 0.5% and 3.5%. Conclusion Manufacturers in China should ensure that their calibration systems correspond to the IFCC reference procedures. Fresh frozen pooled patient serum assigned by reference laboratories can be used to calibrate non-homogeneous systems in order to achieve traceability.
A simple liquid chromatography linked to tandem mass spectrometry method for measurement of serum cholinesterase activity using succinylcholine as substrate
Authors: Spencer Jennifer D , Rushton David , Allen Keith R 
Published: April 2010

BackgroundIndividuals who are unable to metabolize the short-acting muscle relaxant succinylcholine due to abnormal cholinesterase activity are currently investigated via spectrophotometry using artificial substrates and enzyme inhibitors. Methods have been described using succinylcholine as substrate but with measurement of the product choline. However, choline may be released from other endogenous substrates within the serum. Direct measurement of the in vitro metabolism of succinylcholine as substrate may provide a better indication of the in vivo situation with regard to cholinesterase status.MethodsThe rate of in vitro metabolism of succinylcholine by cholinesterase was measured using liquid chromatography linked to tandem mass spectrometry (LC-MS/MS). A comparison was made using serum samples in which cholinesterase activity had been measured using propionylthiocholine as substrate and phenotyped by enzyme inhibitor studies.ResultsA good correlation ( r = 0.9, P < 0.0001) was found between cholinesterase activity measured by LC-MS/MS using succinylcholine as substrate compared with propionylthiocholine as substrate measured spectrophotometrically. All serum samples with a cholinesterase activity of <1 IU/L, as measured using succinylcholine as substrate, were considered to be at increased risk of succinylcholine sensitivity. These latter results correlated well to the atypical phenotypes.ConclusionsA simple and fast LC-MS/MS technique for the measurement of cholinesterase activity using succinylcholine as substrate has been described. This method clearly identifies patients at risk of prolonged apnoea following succinylcholine administration and compares favourably with existing spectrophotometric methods using artificial substrates.
Reflex and reflective testing: efficiency and effectiveness of adding on laboratory tests
Authors: Srivastava Rajeev , Bartlett William A , Kennedy Ian M , Hiney Allan , Fletcher Colin , Murphy Michael J 
Published: April 2010

Background Laboratory investigations may be added to existing requests either automatically on the basis of algorithms (reflex testing) or by laboratory professionals (reflective testing). The clinical utility of reflex and reflective testing is not fully established. We studied efficiency (number of tests that needs to be added to make a diagnosis) and effectiveness (number of diagnoses) of reflex and reflective testing in selected biochemical scenarios. Methods Using fixed rules, we prospectively measured efficiency and effectiveness of reflex and reflective testing in the following scenarios (reflex initiators in parentheses): (1) hypovitaminosis D (hypocalcaemia plus elevated alkaline phosphatase activity); (2) hypomagnesaemia (hypokalaemia or hypocalcaemia); (3) hypothyroidism (high thyroid-stimulating hormone [TSH]); (4) hyperthyroidism (low TSH); (5) haemochromatosis (reflex or reflective addition of iron studies, followed by reflective addition of genetic studies). Separately, using a different data-set, we examined the impact of varying TSH thresholds on outcomes in the biochemical diagnosis of hyper- and hypothyroidism. Results In patients aged over 55 y, 25-hydroxy-vitamin D <50 nmol/L could be predicted with ≥90% certainty when albumin-adjusted calcium was ≤2.1 mmol/L plus alkaline phosphatase >150 U/L. Higher numbers of tests were needed to make a diagnosis in other scenarios. In general, more diagnoses were made by reflex testing. Outside the euthyroid TSH range, efficiency of diagnosis of hyper- and hypothyroidism became asymptotic, while effectiveness declined. Conclusions Near-maximal efficiency of reflex testing can be achieved, depending on the reflex and diagnostic thresholds applied. Reflective and reflex testing are complementary activities, the clinical utility of which depends on the initiators used.
Lipid-Rich Variant of Appendiceal Well-Differentiated Endocrine Tumor (Carcinoid)
Authors: La Rosa Stefano , Finzi Giovanna , Puppa Giacomo , Capella Carlo 
Published: April 2010

Abstract
Well-differentiated endocrine tumors (WDETs) of the appendix show characteristic morphologic features, including proliferation of cells with finely granulated eosinophilic cytoplasm. However, clear cell WDETs, which can present a diagnostic challenge, have been occasionally described, but it is unknown whether they represent a morphologic variant with distinct clinicopathologic features. Moreover, the clear cell appearance of the cytoplasm has never been explained. We studied 13 appendiceal WDETs composed of clear cells, which showed an immunophenotype identical to that of conventional appendiceal WDETs. Ultrastructural examination demonstrated abundant lipid accumulation. Patient survival was excellent and equal to that of conventional appendiceal WDETs. These neoplasms, which represent a lipid-rich variant of appendiceal WDETs, do not have different relevant clinical implications compared with conventional WDETs, but it is important to know of their existence for the differential diagnosis with more aggressive neoplasms, including goblet cell carcinoids and appendiceal metastases from clear cell carcinomas.
A Novel Flow Cytometric Antibody Panel for Distinguishing Burkitt Lymphoma From CD10+ Diffuse Large B-Cell Lymphoma
Authors: Schniederjan Stephanie D. , Li Shiyong , Saxe Debra F. , Lechowicz Mary J. , Lee Kathryn L. , Terry Paul D. , Mann Karen P. 
Published: April 2010

Abstract
Rapid and accurate differential diagnosis between Burkitt lymphoma (BL) and CD10+ diffuse large B-cell lymphoma (DLBCL) is imperative because their treatment differs. Recent studies have characterized several antigens differentially expressed in these 2 types of lymphoma. Our goal was to determine whether use of these markers would aid in the differential diagnosis of BL vs CD10+ DLBCL by flow cytometric immunophenotyping (FCI). Twenty-three cases of CD10+ B-cell lymphomas with available cryopreserved samples were identified (13 BL and 10 CD10+ DLBCL). Multiparameter FCI was performed using the following antibodies: CD18, CD20, CD43, CD44, and CD54 and isotype controls. Expression of CD44 and CD54 was detected at a significantly lower level in BL compared with CD10+ DLBCL (P = .001 and P = .01, respectively). There was not a significant difference in expression of CD18 and CD43. Our data show that expression of CD44 and CD54 differs significantly between BL and CD10+ DLBCL.
Genetic health messages in the mass media: Do the general public perceive non‐personalized genetic health message as personally relevant?
Authors: Smerecnik Chris M. R. , Mesters Ilse , Candel Math J. J. M. , de Vries Hein , de Vries Nanne K. 
Published: April 2010

Objectives. Although health messages communicating the role of genetics in health and disease development are increasingly prevalent in our society, no research has examined whether the general public perceives such messages as believable or personally relevant. We examined whether the general public accepted genetic health messages and viewed them personally relevant in promoting their preventive behaviour.Design. Experimental pre‐test–post‐test measurement design was employed to contrast the information acceptance and perceived personal relevance of the genetic health message with a general health message.Methods. We presented a randomly selected group of Dutch participants (N=1,319) with either a health message about the genetic risk factors for salt sensitivity or with a general health message about salt sensitivity without reference to genetic risk factors. Risk perception and intention to restrict salt intake was assessed before and after participants read the messages while information acceptance and perceived personal relevance was only assessed post‐test.Results. Although we observed no effects of health message type on information processing, previously aware participants perceived the genetic health message as less personally relevant compared to the general health message. This difference in personal relevance resulted in lower estimates of susceptibility and a lower intention to engage in preventive behaviour among previously unaware participants.Conclusions. Genetic health messages in the mass media may not be effective in promoting (intentions to engage in) preventive behaviour due to their low perceived personal relevance by the public. Hence, identifying strategies to increase personal relevance for genetic education is needed.
Early Hepatic Insulin Resistance Precedes the Onset of Diabetes in Obese C57BLKS-db/db Mice
Authors: Davis Richard C. , Castellani Lawrence W. , Hosseini Maryam , Ben-Zeev Osnat , Mao Hui Z. , Weinstein Michael M. , Jung Dae Young , Jun John Y. , Kim Jason K. , Lusis Aldons J. , Péterfy Miklós 
Published: April 2010

OBJECTIVE
To identify metabolic derangements contributing to diabetes susceptibility in the leptin receptor–deficient obese C57BLKS/J-db/db (BKS-db) mouse strain.

RESEARCH DESIGN AND METHODS
Young BKS-db mice were used to identify metabolic pathways contributing to the development of diabetes. Using the diabetes-resistant B6-db strain as a comparison, in vivo and in vitro approaches were applied to identify metabolic and molecular differences between the two strains.

RESULTS
Despite higher plasma insulin levels, BKS-db mice exhibit lower lipogenic gene expression, rate of lipogenesis, hepatic triglyceride and glycogen content, and impaired insulin suppression of gluconeogenic genes. Hepatic insulin receptor substrate (IRS)-1 and IRS-2 expression and insulin-stimulated Akt-phosphorylation are decreased in BKS-db primary hepatocytes. Hyperinsulinemic-euglycemic clamp studies indicate that in contrast to hepatic insulin resistance, skeletal muscle is more insulin sensitive in BKS-db than in B6-db mice. We also demonstrate that elevated plasma triglyceride levels in BKS-db mice are associated with reduced triglyceride clearance due to lower lipase activities.

CONCLUSIONS
Our study demonstrates the presence of metabolic derangements in BKS-db before the onset of β-cell failure and identifies early hepatic insulin resistance as a component of the BKS-db phenotype. We propose that defects in hepatic insulin signaling contribute to the development of diabetes in the BKS-db mouse strain.
Lipoprotein Subfraction Cholesterol Distribution Is Proatherogenic in Women With Type 1 Diabetes and Insulin Resistance
Authors: Maahs David M. , Hokanson John E. , Wang Hong , Kinney Gregory L. , Snell-Bergeon Janet K. , East Ashley , Bergman Bryan C. , Schauer Irene E. , Rewers Marian , Eckel Robert H. 
Published: April 2010

OBJECTIVEIndividuals with type 1 diabetes have a less atherogenic fasting lipid profile than those without diabetes but paradoxically have increased rates of cardiovascular disease (CVD). We investigated differences in lipoprotein subfraction cholesterol distribution and insulin resistance between subjects with and without type 1 diabetes to better understand the etiology of increased CVD risk.RESEARCH DESIGN AND METHODSFast protein liquid chromatography was used to fractionate lipoprotein cholesterol distribution in a substudy of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (n = 82, age 46 ± 8 years, 52% female, 49% with type 1 diabetes for 23 ± 8 years). Insulin resistance was assessed by a hyperinsulinemic-euglycemic clamp.RESULTSAmong men, those with type 1 diabetes had less VLDL and more HDL cholesterol than control subjects (P &lt; 0.05), but among women, those with diabetes had a shift in cholesterol to denser LDL, despite more statin use. Among control subjects, men had more cholesterol distributed as VLDL and LDL but less as HDL than women; however, among those with type 1 diabetes, there was no sex difference. Within sex and diabetes strata, a more atherogenic cholesterol distribution by insulin resistance was seen in men with and without diabetes, but only in women with type 1 diabetes.CONCLUSIONSThe expected sex-based less atherogenic lipoprotein cholesterol distribution was not seen in women with type 1 diabetes. Moreover, insulin resistance was associated with a more atherogenic lipoprotein cholesterol distribution in all men and in women with type 1 diabetes. This lipoprotein cholesterol distribution may contribute to sex-based differences in CVD in type 1 diabetes.
Role of KLF15 in Regulation of Hepatic Gluconeogenesis and Metformin Action
Authors: Takashima Mototsugu , Ogawa Wataru , Hayashi Kumiko , Inoue Hiroshi , Kinoshita Shinichi , Okamoto Yasuo , Sakaue Hiroshi , Wataoka Yu , Emi Aki , Senga Yoko , Matsuki Yasushi , Watanabe Eijiro , Hiramatsu Ryuji , Kasuga Masato 
Published: April 2010

OBJECTIVE
An increase in the rate of gluconeogenesis is largely responsible for the hyperglycemia in individuals with type 2 diabetes, with the antidiabetes action of metformin being thought to be achieved at least in part through suppression of gluconeogenesis.

RESEARCH DESIGN AND METHODS
We investigated whether the transcription factor KLF15 has a role in the regulation of gluconeogenesis and whether KLF15 participates in the antidiabetes effect of metformin.

RESULTS
Here we show that KLF15 regulates the expression of genes for gluconeogenic or amino acid–degrading enzymes in coordination with the transcriptional coactivator peroxisome proliferator–activated receptor γ coactivator 1α. Liver-specific ablation of KLF15 in diabetic mice resulted in downregulation of the expression of genes for gluconeogenic or amino acid catabolic enzymes and in amelioration of hyperglycemia. Exposure of cultured hepatocytes to metformin reduced the abundance of KLF15 through acceleration of its degradation and downregulation of its mRNA. Metformin suppressed the expression of genes for gluconeogenic or amino acid–degrading enzymes in cultured hepatocytes, and these effects of metformin were attenuated by restoration of KLF15 expression. Administration of metformin to mice inhibited both the expression of KLF15 and glucose production in the liver, the latter effect also being attenuated by restoration of hepatic KLF15 expression.

CONCLUSIONS
KLF15 plays an important role in regulation of the expression of genes for gluconeogenic and amino acid–degrading enzymes and that the inhibitory effect of metformin on gluconeogenesis is mediated at least in part by downregulation of KLF15 and consequent attenuation of the expression of such genes.
E-Cadherin Expression Is Regulated by miR-192/215 by a Mechanism That Is Independent of the Profibrotic Effects of Transforming Growth Factor-β
Authors: Wang Bo , Herman-Edelstein Michal , Koh Philip , Burns Wendy , Jandeleit-Dahm Karin , Watson Anna , Saleem Moin , Goodall Gregory J. , Twigg Stephen M. , Cooper Mark E. , Kantharidis Phillip 
Published: April 2010

OBJECTIVE
Increased deposition of extracellular matrix (ECM) within the kidney is driven by profibrotic mediators including transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF). We investigated whether some of their effects may be mediated through changes in expression of certain microRNAs (miRNAs).

RESEARCH DESIGN AND METHODS
Proximal tubular cells, primary rat mesangial cells, and human podocytes were analyzed for changes in the expression of key genes, ECM proteins, and miRNA after exposure to TGF-β (1–10 ng/μl). Tubular cells were also infected with CTGF-adenovirus. Kidneys from diabetic apoE mice were also analyzed for changes in gene expression and miRNA levels.

RESULTS
TGF-β treatment was associated with morphologic and phenotypic changes typical of epithelial-mesenchymal transition (EMT) including increased fibrogenesis in all renal cell types and decreased E-cadherin expression in tubular cells. TGF-β treatment also modulated the expression of certain miRNAs, including decreased expression of miR-192/215 in tubular cells, mesangial cells, which are also decreased in diabetic kidney. Ectopic expression of miR-192/215 increased E-cadherin levels via repressed translation of ZEB2 mRNA, in the presence and absence of TGF-β, as demonstrated by a ZEB2 3′-untranslated region luciferase reporter assay. However, ectopic expression of miR-192/215 did not affect the expression of matrix proteins or their induction by TGF-β. In contrast, CTGF increased miR-192/215 levels, causing a decrease in ZEB2, and consequently increased E-cadherin mRNA.

CONCLUSIONS
These data demonstrate the linking role of miRNA-192/215 and ZEB2 in TGF-β/CTGF–mediated changes in E-cadherin expression. These changes appear to occur independently of augmentation of matrix protein synthesis, suggesting that a multistep EMT program is not necessary for fibrogenesis to occur.
Evaluation of topical application of 10% imidacloprid–1% moxidectin to prevent Bartonella henselae transmission from cat fleas
Authors: Bradbury Christina A. , Lappin Michael R. 
Published: April 2010

Abstract
Objective—To determine whether monthly topical administration of a combination of 10% imidacloprid and 1% moxidectin would lessen flea (Ctenocephalides felis) transmission of Bartonella henselae among cats.
Design—Controlled trial.
Animals—18 specific pathogen–free cats housed in 3 groups of 6.
Procedures—3 enclosures were separated by mesh to allow fleas to pass among groups yet prevent cats from contacting one another. One group was inoculated IV with B henselae, and after infection was confirmed, the cats were housed in the middle enclosure. This infected group was flanked by a group that was treated topically with 10% imidacloprid–1% moxidectin monthly for 3 months and by an untreated group. On days 0, 15, 28, and 42, 100 fleas/cat were placed on each of the 6 cats in the B henselae–infected group. Blood samples were collected from all cats weekly for detection of Bartonella spp via PCR assay, bacterial culture, and serologic assay.
Results—B henselae infection was confirmed in the cats infected IV and in all untreated cats after flea exposure; none of the cats treated with the imidacloprid-moxidectin combination became infected.
Conclusions and Clinical Relevance—In this setting, monthly topical administration of 10% imidacloprid–1% moxidectin reduced flea infestation, compared with infestation in untreated cats, and thus prevented flea transmission of B henselae to treated cats. Regular monthly use of this flea control product in cats may lessen the likelihood of humans acquiring B henselae infection.
Comparison of urine dipstick, sulfosalicylic acid, urine protein-to-creatinine ratio, and species-specific ELISA methods for detection of albumin in urine samples of cats and dogs
Authors: Lyon Shane D. , Sanderson Michael W. , Vaden Shelly L. , Lappin Michael R. , Jensen Wayne A. , Grauer Gregory F. 
Published: April 2010

Abstract
Objective—To evaluate the use of dipstick, sulfosalicylic acid (SSA), and urine protein-tocreatinine ratio (UP:C) methods for use in detection of canine and feline albuminuria.
Design—Evaluation study.
Sample Population—599 canine and 347 feline urine samples.
Procedures—Urine was analyzed by use of dipstick, SSA, and UP:C methods; results were compared with those for a species-specific ELISA to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive and negative likelihood ratios.
Results—Positive results for dipstick and SSA tests (trace reaction or greater) in canine urine had moderate specificity (dipstick, 81.2%; SSA, 73.3%) and poor PPV (dipstick, 34.0%; SSA, 41.8%). Values improved when stronger positive results (≥ 2+) for the dipstick and SSA tests were compared with ELISA results (specificity, 98.9% and 99.0% for the urine dipstick and SSA tests, respectively; PPV, 90.7% and 90.2% for the dipstick and SSA tests, respectively). Data obtained for cats revealed poor specificity (dipstick, 11.0%; SSA, 25.4%) and PPV (dipstick, 55.6%; SSA, 46.9%). Values improved slightly when stronger positive test results (≥ 2+) were used (specificity, 80.0% and 94.2% for the dipstick and SSA tests, respectively; PPV, 63.5% and 65.2% for the dipstick and SSA tests, respectively). The UP:C had high specificity for albuminuria in dogs and cats (99.7% and 99.2%, respectively) but low sensitivity (28.7% and 2.0%, respectively).
Conclusions and Clinical Relevance—Caution should be used when interpreting a positive test result of a dipstick or SSA test for canine or feline albuminuria.
Severity of patellar luxation and frequency of concomitant cranial cruciate ligament rupture in dogs: 162 cases (2004–2007)
Authors: Campbell Courtney A. , Horstman Christopher L. , Mason David R. , Evans Richard B. 
Published: April 2010

Abstract
Objective—To evaluate severity of medial patellar luxation (MPL) and frequency of concomitant cranial cruciate ligament rupture (CCLR) in dogs.
Design—Retrospective case series.
Animals—162 dogs (266 stifle joints).
Procedures—Medical records of 162 small-breed dogs with MPL were reviewed. Signalment, body weight, luxation grade, bilateral or unilateral MPL, CCLR, and difference in luxation grades between stifle joints were evaluated. Association between severity of MPL and CCLR was investigated.
Results—58 dogs had unilateral MPL, and 104 dogs had bilateral MPL. Dogs ranged from 8.4 months to 16.7 years of age (mean, 5.7 years), and mean body weight was 5.45 kg (12 lb). Forty-one percent of all dogs had concomitant CCLR. Mean age for dogs with MPL alone was 3.0 years, which differed significantly from mean age of dogs with MPL and concomitant CCLR (7.8 years). Dogs with grade IV MPL were significantly more likely to have concomitant CCLR than were dogs with any other grade of MPL. In dogs with bilateral MPL and unilateral CCLR, there was a significantly higher grade of luxation in the stifle joint with CCLR.
Conclusions and Clinical Relevance—Small-breed dogs with MPL and concomitant CCLR were older than were dogs with only MPL. Dogs with grade IV MPL were more likely to have CCLR than were dogs with other grades of MPL. Most dogs with concomitant CCLR had a higher MPL grade in the affected stifle joint than in the intact joint. These findings should be beneficial in client education and clinical diagnosis.