bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra‐ and Interindividual Variation in Urine Osmolality and Urine Specific Gravity in Healthy Pet Dogs of Various Ages
Authors: van Vonderen Ilse K. , Kooistra Hans S. , Rijnberk Ad 
Published: March 2010

Urine specific gravity (Usg) and urine osmolality (Uosm) are used routinely to assess renal concentrating ability, but limited data on these variables are available for healthy dogs. Consequently, we studied the intra‐ and interindividual variations in Usg and Uosm in healthy dogs as well as the influence of age and gender on these variables.Dogs were selected for health and anestrus in female dogs through the use of a detailed questionnaire. Eighty‐nine owners collected morning and evening urine samples from their dogs on 2 consecutive days. In 8 dogs in which the Uosm of different samples varied more than 50%, owners collected urine for 24 hours at 2‐hour intervals during the day and at 4‐hour intervals at night. The possible effect of changes in adrenocortical function with age was assessed by measurements of urinary corticoid/creatinine (C/C) ratios.Among all samples, Uosm ranged from 161 to 2,830 mOsm/kg and Usg from 1.006 to > 1.050. In the morning, Uosm (1,541 ± 527 mOsm/kg, range 273–2,620 mOsm/kg) and Usg (1.035 ± 0.010, range 1.009‐ > 1.050) were higher than in the evening (Uosm 1,400 ± 586 mOsm/kg, range 161–2,830 mOsm/kg; Usg 1.031 ± 0.012, range 1.006‐ > 1.050). The interindividual coefficient of variation in Uosm was 34.2% for morning urine samples and 41.9% for evening samples. In 8 dogs with large differences in urine concentration, there were 2– to 3‐fold increases or decreases in Uosm during the day, and the intraindividual coefficient of variation was 33.0%. There was no relation between gender and urine concentration. Urine concentration in both the morning and evening samples decreased with age. Urinary corticoid/creatinine ratios did not change with age.It can be concluded that Uosm and Usg vary widely among healthy dogs. Urine concentration is generally lower in the evening than in the morning and is not related to gender. Urine concentration decreases with age, and this cannot be ascribed to an associated increase in endogenous corticoids.In some dogs, Uosm varies widely during the day, with an intraindividual coefficient of variation approaching the interindividual coefficient of variation. This may be regarded as a biologic variation but also could represent an early undi‐agnosed clinical abnormality.
Effect of Weight Gain and Subsequent Weight Loss on Glucose Tolerance and Insulin Response in Healthy Cats
Authors: Biourge Vincent , Nelson Richard W. , Feldman Edward C. , Willits Neil H. , Morris James G. , Rogers Quinton R. 
Published: March 2010

The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre‐study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat.Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P> .05) increased after weight gain, as compared with baseline. At the end of weight loss, cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P> .05) increase in mean serum glucose concentration and t1/2, and a significant (P> .05) decrease in mean serum insulin concentration and the glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulino‐genic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P> .05), compared with measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P> .05) in measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the number and size of lipid vacuoles in hepatocytes had decreased, and results of IVGTT were similar to those obtained at baseline.These findings confirmed the reversibility of obesity‐induced insulin resistance in cats, and documented initial deterioration in glucose tolerance and insulin response to glucose infusion when weight loss was caused by severe restriction of caloric intake.
Polyuria and Polydipsia and Disturbed Vasopressin Release in 2 Dogs With Secondary Polycythemia
Authors: van Vonderen Ilse K. , Meyer Hein P. , Kraus Johannes S. , Kooistra Hans S. 
Published: March 2010

In dogs, secondary polycythemia (SP) may be associated with polyuria and polydipsia (PU/PD). The pathogenesis of this PU/PD has not yet been explained. We hypothesized that hyperviscosity and increased blood volume in SP might affect vasopressin (VP) release, resulting in PU/PD. This hypothesis was tested in 2 dogs with SP caused by renal neo‐plasia and PU/PD. Osmoregulation of VP release was studied by a modified water deprivation test and by investigating the VP response to hypertonic saline infusion.Water deprivation test results were consistent with an inability to produce concentrated urine despite increasing plasma osmolality. During hypertonic saline infusion, the osmotic threshold of VP release was markedly increased in both dogs, resulting in a delayed VP response to increasing plasma osmolality. The sensitivity of VP release was low normal in both dogs. We conclude that blood hyperviscosity and increased blood volume led to impaired VP release and polyuria.
Radiopaque Markers to Evaluate Gastric Emptying and Small Intestinal Transit Time in Healthy Cats
Authors: Chandler Marjorie L. , Guilford Grant , Lawoko Charles R.O. 
Published: March 2010

Determinations of gastric emptying time (GET) and small intestinal transit time (SITT) are useful in detecting gastrointestinal motility disorders and partial obstructions of the pylorus or small intestine. Barium‐impregnated, polyethylene radiopaque spheres with diameters of 1.5 mm and 5.0 mm have been developed for quantitative assessment of gastrointestinal transit.The purpose of this study was to evaluate GET and SITT using these radiopaque spheres in 10 healthy cats. The cats were randomly assigned to 1 of 3 treatment groups: fasted, fed, and fed plus sedation (acetylpromazine maleate 0.10 mg/kg subcutaneously). A repeated measures study design was used.The mean GETs of 50%, 75%, and 90% of the 1.5‐mm and the 5‐mm spheres in the unfed cats were 0.36, 0.58, and 0.74 hours, and 0.41, 0.68, and 1.02 hours, respectively. These values were significantly (P ±.05) more rapid than the GETs of 50%, 75%, and 90% of the 1.5‐mm and 5‐mm spheres of either the sedated fed cats (4.39, 5.68, 6.65 and 5.15, 5.99, 6.91 hours) or the unsedated fed cats (6.43, 8.12, 9.06 and 7.49, 8.49, 9.22 hours).The mean GETs of 50% and 75% of the 1.5‐mm and 5‐mm and of 90% of the 1.5‐mm spheres were significantly (P±.05) more rapid in sedated than in unsedated fed cats. The GET of 50% of the 1.5‐mm spheres was significantly more rapid (P±.05) than that of the 5‐mm spheres in the fed cats. The mean SITTs, which ranged from 2.25 to 3.05 hours, were not significantly different (P> .05) among the treatment groups or between the 1.5‐mm and 5‐mm spheres.The GET of spheres given to fasted cats is significantly more rapid than that of fed cats. Subcutaneous injection of acetylpromazine speeds GET in fed cats. The SITT of small and large spheres was not influenced by feeding or by acetyl‐promazine injection.
Retrospective Analysis of the Clinical Utility of Ambulatory Electrocardiographic (Holter) Recordings in Syncopal Dogs: 44 Cases (1991–1995)
Authors: Miller Rita H. , Lehmkuhl Linda B. , Bonagura John D. , Beall Melissa J. 
Published: March 2010

The objective of this study was to evaluate retrospectively the clinical utility of ambulatory (Holter) electrocardiographic monitoring in syncopal dogs and to compare the Holter recording with the clinic electrocardiogram (ECG) in these animals. Fifty Holter reports and 44 medical records from 44 dogs were evaluated. A syncopcal episode occurred during monitoring in 24% of the recordings. No obvious relationship was found between the frequency of syncope occurring before Holter recording and the likelihood of a dog having an episode during recording. Holter recordings were helpful in establishing a diagnosis 42% of the time, but no relationship was detected between the frequency of episodes occurring before Holter recording and the likelihood of a diagnostically useful Holter. An arrhythmia was ruled out as the cause of syncope in 12% of the recordings and was implicated as the cause of syncope in 30% of recordings. Of these, 20% were ventricular tachyarrhythmias and 10% were bradyarrhythmias including pacemaker failure. Ambulatory electrocardiographic recordings led to a therapeutic change in 38% of cases.A comparison of the Holter recordings and clinic ECGs documented the expected increased sensitivity for Holter detection of arrhythmias. The average clinic ECG heart rate consistently exceeded the average Holter heart rate with a mean difference between the average heart rates recorded by the two techniques of 31 bpm (range — 8–87 bpm).
The algebra of cell-zeta values
Authors: Brown Francis , Carr Sarah , Schneps Leila 
Published: March 2010

AbstractIn this paper, we introduce cell-forms on 𝔐0,n, which are top-dimensional differential forms diverging along the boundary of exactly one cell (connected component) of the real moduli space 𝔐0,n(ℝ). We show that the cell-forms generate the top-dimensional cohomology group of 𝔐0,n, so that there is a natural duality between cells and cell-forms. In the heart of the paper, we determine an explicit basis for the subspace of differential forms which converge along a given cellX. The elements of this basis are called insertion forms; their integrals overXare real numbers, called cell-zeta values, which generate a ℚ-algebra called the cell-zeta algebra. By a result of F. Brown, the cell-zeta algebra is equal to the algebra of multizeta values. The cell-zeta values satisfy a family of simple quadratic relations coming from the geometry of moduli spaces, which leads to a natural definition of a formal version of the cell-zeta algebra, conjecturally isomorphic to the formal multizeta algebra defined by the much-studied double shuffle relations.
LEARNING DECISION TREES WITH LOG CONDITIONAL LIKELIHOOD
Authors: LIANG HAN , YAN YUHONG , ZHANG HARRY 
Published: March 2010

In machine learning and data mining, traditional learning models aim for high classification accuracy. However, accurate class probability prediction is more desirable than classification accuracy in many practical applications, such as medical diagnosis. Although it is known that decision trees can be adapted to be class probability estimators in a variety of approaches, and the resulting models are uniformly called Probability Estimation Trees (PETs), the performances of these PETs in class probability estimation, have not yet been investigated. We begin our research by empirically studying PETs in terms of class probability estimation, measured by Log Conditional Likelihood (LCL). We also compare a PET called C4.4 with other representative models, including Naïve Bayes, Naïve Bayes Tree, Bayesian Network, KNN and SVM, in LCL. From our experiments, we draw several valuable conclusions. First, among various tree-based models, C4.4 is the best in yielding precise class probability prediction measured by LCL. We provide an explanation for this and reveal the nature of LCL. Second, compared with non tree-based models, C4.4 also performs best. Finally, LCL does not dominate another well-established relevant metric — AUC, which suggests that different decision-tree learning models should be used for different objectives. Our experiments are conducted on the basis of 36 UCI sample sets. We run all the models within a machine learning platform — Weka. We also explore an approach to improve the class probability estimation of Naïve Bayes Tree. We propose a greedy and recursive learning algorithm, where at each step, LCL is used as the scoring function to expand the decision tree. The algorithm uses Naïve Bayes created at leaves to estimate class probabilities of test samples. The whole tree encodes the posterior class probability in its structure. One benefit of improving class probability estimation is that both classification accuracy and AUC can be possibly scaled up. We call the new model LCL Tree (LCLT). Our experiments on 33 UCI sample sets show that LCLT outperforms all state-of-the-art learning models, such as Naïve Bayes Tree, significantly in accurate class probability prediction measured by LCL, as well as in classification accuracy and AUC.
Blockade of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase and Murine Double Minute Synergistically Induces Apoptosis in Acute Myeloid Leukemia via BH3-Only Proteins Puma and Bim
Authors: Zhang Weiguo , Konopleva Marina , Burks Jared K. , Dywer Karen C. , Schober Wendy D. , Yang Jer-Yen , McQueen Teresa J. , Hung Mien-Chie , Andreeff Michael 
Published: March 2010

Abstract
Molecular aberrations of the Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK and/or Murine double minute (MDM2)/p53 signaling pathways have been reported in 80% and 50% of primary acute myeloid leukemia (AML) samples and confer poor outcome. In this study, antileukemic effects of combined MEK inhibition by AZD6244 and nongenotoxic p53 activation by MDM2 antagonist Nutlin-3a were investigated. Simultaneous blockade of MEK and MDM2 signaling by AZD6244 and Nutlin-3a triggered synergistic proapoptotic responses in AML cell lines [combination index (CI) = 0.06 ± 0.03 and 0.43 ± 0.03 in OCI/AML3 and MOLM13 cells, respectively] and in primary AML cells (CI = 0.52 ± 0.01). Mechanistically, the combination upregulated levels of BH3-only proteins Puma and Bim, in part via transcriptional upregulation of the FOXO3a transcription factor. Suppression of Puma and Bim by short interfering RNA rescued OCI/AML3 cells from AZD/Nutlin-induced apoptosis. These results strongly indicate the therapeutic potential of combined MEK/MDM2 blockade in AML and implicate Puma and Bim as major regulators of AML cell survival. Cancer Res; 70(6); 2424–34
Transcriptional Pathway Signatures Predict MEK Addiction and Response to Selumetinib (AZD6244)
Authors: Dry Jonathan R. , Pavey Sandra , Pratilas Christine A. , Harbron Chris , Runswick Sarah , Hodgson Darren , Chresta Christine , McCormack Rose , Byrne Natalie , Cockerill Mark , Graham Alexander , Beran Garry , Cassidy Andrew , Haggerty Carolyn , Brown Helen , Ellison Gillian , Dering Judy , Taylor Barry S. , Stark Mitchell , Bonazzi Vanessa , Ravishankar Sugandha , Packer Leisl , Xing Feng , Solit David B. , Finn Richard S. , Rosen Neal , Hayward Nicholas K. , French Tim , Smith Paul D. 
Published: March 2010

Abstract
Selumetinib (AZD6244, ARRY-142886) is a selective, non–ATP-competitive inhibitor of mitogen-activated protein/extracellular signal–regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR–based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies. Cancer Res; 70(6); 2264–73
BRD7, a Subunit of SWI/SNF Complexes, Binds Directly to BRCA1 and Regulates BRCA1-Dependent Transcription
Authors: Harte Mary T. , O'Brien Garrett J. , Ryan Niamh M. , Gorski Julia J. , Savage Kienan I. , Crawford Nyree T. , Mullan Paul B. , Harkin D. Paul 
Published: March 2010

Abstract
We carried out a yeast two-hybrid screen using a BRCA1 bait composed of amino acids 1 to 1142 and identified BRD7 as a novel binding partner of BRCA1. This interaction was confirmed by coimmunoprecipitation of endogenous BRCA1 and BRD7 in T47D and HEK-293 cells. BRD7 is a bromodomain containing protein, which is a subunit of PBAF-specific Swi/Snf chromatin remodeling complexes. To determine the functional consequences of the BRCA1-BRD7 interaction, we investigated the role of BRD7 in BRCA1-dependent transcription using microarray-based expression profiling. We found that a variety of targets were coordinately regulated by BRCA1 and BRD7, such as estrogen receptor α (ERα). Depletion of BRD7 or BRCA1 in either T47D or MCF7 cells resulted in loss of expression of ERα at both the mRNA and protein level, and this loss of ERα was reflected in resistance to the antiestrogen drug fulvestrant. We show that BRD7 is present, along with BRCA1 and Oct-1, on the ESR1 promoter (the gene which encodes ERα). Depletion of BRD7 prevented the recruitment of BRCA1 and Oct-1 to the ESR1 promoter; however, it had no effect on the recruitment of the other Swi/Snf subunits BRG1, BAF155, and BAF57 or on RNA polymerase II recruitment. These results support a model whereby the regulation of ERα transcription by BRD7 is mediated by its recruitment of BRCA1 and Oct-1 to the ESR1 promoter. Cancer Res; 70(6); 2538–47
Oncolytic Viral Therapy for Prostate Cancer: Efficacy of Reovirus as a Biological Therapeutic
Authors: Thirukkumaran Chandini M. , Nodwell Michael J. , Hirasawa Kensuke , Shi Zhong-Qiao , Diaz Roman , Luider Joanne , Johnston Randal N. , Forsyth Peter A. , Magliocco Anthony M. , Lee Patrick , Nishikawa Sandra , Donnelly Bryan , Coffey Matt , Trpkov Kiril , Fonseca Kevin , Spurrell Jason , Morris Don G. 
Published: March 2010

Abstract
Reovirus is a nonattenuated double-stranded RNA virus that exploits aberrant signaling pathways allowing selective cytotoxicity against multiple cancer histologies. The use of reovirus as a potential treatment modality for prostate cancer has not previously been described, and in this study evidence of in vitro and in vivo activity against prostate cancer was seen both in preclinical models and in six patients. The human prostate carcinoma cell lines PC-3, LN-CaP, and DU-145 exposed to replication-competent reovirus showed evidence of infection as illustrated by viral protein synthesis, cytopathic effect, and release of viral progeny. This oncolytic effect was found to be manifested through apoptosis, as DNA fragmentation, Apo 2.7 expression, Annexin V binding, and poly(ADP-ribose) polymerase cleavage were observed in live reovirus-infected cells, but not in uninfected or dead virus–treated cells. In vivo, hind flank severe combined immunodeficient/nonobese diabetic murine xenograft showed reduction in tumor size when treated with even a single intratumoral injection of reovirus. Finally, intralesional reovirus injections into a cohort of six patients with clinically organ-confined prostate cancer resulted in minimal side effects and evidence of antitumor activity. Histologic analysis after prostatectomy found a significant CD8 T-cell infiltration within the reovirus-injected areas as well as evidence of increased caspase-3 activity. These findings suggest that reovirus therapy may provide a promising novel treatment for prostate cancer and also imply a possible role for viral immune targeting of tumor. Cancer Res; 70(6); 2435–44
Novel STAT3 Phosphorylation Inhibitors Exhibit Potent Growth-Suppressive Activity in Pancreatic and Breast Cancer Cells
Authors: Lin Li , Hutzen Brian , Zuo Mingxin , Ball Sarah , Deangelis Stephanie , Foust Elizabeth , Pandit Bulbul , Ihnat Michael A. , Shenoy Satyendra S. , Kulp Samuel , Li Pui-Kai , Li Chenglong , Fuchs James , Lin Jiayuh 
Published: March 2010

Abstract
The constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in most types of human cancer where it plays important roles in survival, drug resistance, angiogenesis, and other functions. Targeting constitutive STAT3 signaling is thus an attractive therapeutic approach for these cancers. We have recently developed novel small-molecule STAT3 inhibitors, known as FLLL31 and FLLL32, which are derived from curcumin (the primary bioactive compound of turmeric). These compounds are designed to bind selectively to Janus kinase 2 and the STAT3 Src homology-2 domain, which serve crucial roles in STAT3 dimerization and signal transduction. Here we show that FLLL31 and FLLL32 are effective inhibitors of STAT3 phosphorylation, DNA-binding activity, and transactivation in vitro, leading to the impediment of multiple oncogenic processes and the induction of apoptosis in pancreatic and breast cancer cell lines. FLLL31 and FLLL32 also inhibit colony formation in soft agar and cell invasion and exhibit synergy with the anticancer drug doxorubicin against breast cancer cells. In addition, we show that FLLL32 can inhibit the induction of STAT3 phosphorylation by IFNα and interleukin-6 in breast cancer cells. We also show that administration of FLLL32 can inhibit tumor growth and vascularity in chicken embryo xenografts as well as substantially reduce tumor volumes in mouse xenografts. Our findings highlight the potential of these new compounds and their efficacy in targeting pancreatic and breast cancers that exhibit constitutive STAT3 signaling. Cancer Res; 70(6); 2445–54