bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST6Gal-I sialyltransferase confers cisplatin resistance in ovarian tumor cells
Authors: Schultz Matthew J , Swindall Amanda F , Wright John W , Sztul Elizabeth S , Landen Charles N , Bellis Susan L 
Published: April 2013

Abstract

Background
Platinum drugs, including cisplatin, are a frontline therapeutic in ovarian cancer treatment and acquired resistance to these agents is a major contributor to ovarian cancer morbidity and mortality. In this study a novel glycosylation-dependent mechanism for cisplatin resistance is described. Specifically, cisplatin-induced cell death is blocked by the activity of the ST6Gal-I sialyltransferase. ST6Gal-I modifies specific receptors by adding a negatively charged sialic acid sugar which influences diverse receptor functions. Overexpression of ST6Gal-I is a hallmark of ovarian and other cancers and its expression has been correlated to metastasis and poor prognosis.

Methods
Tumor cell viability and apoptotic induction were determined in cell lines with ST6Gal-I overexpression and knockdown. In addition, cell populations with acquired resistance to cisplatin were assayed for endogenous ST6Gal-I expression.

Results
We show that forced expression of ST6Gal-I in OV4 ovarian cancer cells that lack endogenous ST6Gal-I causes reduced activation of caspase 3 and increased cell viability following cisplatin treatment. Conversely, forced ST6Gal-I knockdown in Pa-1 cells with high endogenous ST6Gal-I increases cisplatin-induced caspase activation and cell death. A2780 ovarian cancer cells selected for stable cisplatin resistance display upregulated endogenous ST6Gal-I when compared with parental, cisplatin-sensitive, A2780 cells. Similarly, extended low dose cisplatin treatment of a Pa-1 polyclonal ST6Gal-I shRNA knockdown population led to selection for subclones with elevated ST6Gal-I expression.

Conclusions
Receptor sialylation by ST6Gal-I confers a survival advantage for tumor cells in the presence of cisplatin. These collective findings support a role for ST6Gal-I in chemoresistance and highlight ST6Gal-I as a potential therapeutic target for platinum resistant tumors.
Effect of antimicrobial growth promoter administration on the intestinal microbiota of beef cattle
Authors: Reti Kristen L , Thomas Matthew C , Yanke L Jay , Selinger L Brent , Inglis G Douglas 
Published: April 2013

Abstract

Background
Antimicrobial growth promoters (AGPs) are antimicrobial agents administered to livestock in feed for prolonged periods to enhance feed efficiency. Beef cattle are primarily finished in confined feeding operations in Canada and the USA, and the administration of AGPs such as chlortetracycline and sulfamethazine (Aureo S-700 G) is the standard. The impacts of AGPs on the intestinal microbiota of beef cattle are currently uncertain; it is documented that AGPs administered to beef cattle pass through the rumen and enter the intestine. To ascertain the impacts of Aureo S-700 G on the small and large intestinal microbiota of beef cattle (mucosa-associated and within digesta), terminal restriction fragment length polymorphism (T-RFLP) analysis and quantitative PCR (qPCR) for total bacteria were applied. Beef cattle were maintained in an experimental feedlot (five replicate pens per treatment), and AGP treatment cattle were administered Aureo S-700 G in feed, whereas control cattle were administered no antimicrobials. As the intestinal microbiota of beef cattle has not been extensively examined, clone library analysis was applied to ascertain the primary bacterial constituents of the intestinal microbiota.

Results
Comparative T-RFLP and qPCR analysis (n = 122 samples) revealed that bacterial community fingerprints and bacterial load within digesta differed from those associated with mucosa. However, the administration of Aureo S-700 G did not affect bacterial community fingerprints or bacterial load within the small and large intestine relative to control cattle. Analysis of >1500 near full length 16S rDNA clones revealed considerably greater bacterial diversity in the large relative to the small intestine of beef cattle. Mucosa-associated bacterial communities in the jejunum were dominated by Proteobacteria, and differed conspicuously from those in the ileum and large intestine. Although the ileum contained bacterial clones that were common to the jejunum as well as the cecum, Firmicutes clones associated with mucosa dominated in the ileum, cecum, and descending colon. In the descending colon, clone library analysis did not reveal a difference in the richness or diversity of bacterial communities within digesta relative to those associated with mucosa. However, T-RFLP analysis indicated a significant difference in T-RF relative abundance (i.e. difference in relative taxon abundance) between mucosa-associated and digesta communities attributed in part to the differential abundance of Bacteriodes, Alistipes, Oscillibacter, and unclassified Clostridiales.

Conclusions
These data demonstrate that there was no significant difference in the composition of the predominant intestinal bacteria constituents within animals administered Aureo S-700 G and those not administered AGPs after a 28 day withdrawal period.
The impact of clinical versus pathological staging in oral cavity carcinoma–a multi-institutional analysis of survival
Authors: Biron Vincent L , O'Connell Daniel A , Seikaly Hadi 
Published: April 2013

Objectives To evaluate any disparity in clinical versus pathological TNM staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of this on survival. Design Demographic, survival, staging, and pathologic data on all patients undergoing surgical treatment for OCSCC in Alberta between 1998 and 2006 was collected. Clinical and pathological TNM staging data were compared. Patients were stratified as pathologically downstaged, upstaged or unchanged. Setting Tertiary care centers in Alberta, Canada. Main outcome measures Survival differences between groups were analyzed using Kaplan-Meier and Cox regression models. Results Patients with clinically early stage tumors were pathologically upstaged in 21.9% of cases and unchanged in 78.1% of cases. Patients with clinically advanced stage tumors were pathologically downstaged in 7.9% of cases and unchanged in 92.1% of cases. Univariate and multivariate estimates of disease-specific survival showed no statistically significant differences in survival when patients were either upstaged or downstaged. Conclusions Some disparity exists in clinical versus pathological staging in OCSCC, however, this does not have any significant impact on disease specific survival.
Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice
Authors: Laufer Benjamin I. , Mantha Katarzyna , Kleiber Morgan L. , Diehl Eric J. , Addison Sean M. F. , Singh Shiva M. 
Published: April 2013

SummaryFetal alcohol spectrum disorders (FASDs) are characterized by life-long changes in gene expression, neurodevelopment and behavior. What mechanisms initiate and maintain these changes are not known, but current research suggests a role for alcohol-induced epigenetic changes. In this study we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. We found long-lasting alterations in DNA methylation as a result of fetal alcohol exposure, specifically in the imprinted regions of the genome harboring ncRNAs and sequences interacting with regulatory proteins. A large number of major nodes from the identified networks, such as Pten signaling, contained transcriptional repressor CTCF-binding sites in their promoters, illustrating the functional consequences of alcohol-induced changes to DNA methylation. Next, we assessed ncRNA expression using two independent array platforms and quantitative PCR. The results identified 34 genes that are targeted by the deregulated miRNAs. Of these, four (Pten, Nmnat1, Slitrk2 and Otx2) were viewed as being crucial in the context of FASDs given their roles in the brain. Furthermore, ~20% of the altered ncRNAs mapped to three imprinted regions (Snrpn-Ube3a, Dlk1-Dio3 and Sfmbt2) that showed differential methylation and have been previously implicated in neurodevelopmental disorders. The findings of this study help to expand on the mechanisms behind the long-lasting changes in the brain transcriptome of FASD individuals. The observed changes could contribute to the initiation and maintenance of the long-lasting effect of alcohol.
Acute Myocardial Infarct Detection with Dual Energy CT: Correlation with Single Photon Emission Computed Tomography Myocardial Scintigraphy in a Canine Model
Authors: Peng Jin , Zhang Long Jiang , Schoepf U Joseph , Gibbs Kevin P , Ji Heng Shan , Yang Gui Fen , Zhu Hong , Lu Guang Ming 
Published: April 2013

Background Dual-energy CT (DECT) has been used to detect myocardial infarct. However, few comparable studies with histopathological findings as gold standard have been published. Purpose To investigate the accuracy of DECT iodine maps for detecting acute myocardial infarction compared with single photon emission computed tomography (SPECT) in a canine model using histopathological findings as the reference standard. Material and Methods A model of myocardial ischemia was created by ligating the left anterior descending (LAD) coronary artery after thoracotomy in six dogs, while another three dogs undergoing thoracotomy without LAD ligature served as a control group. Contrast-enhanced DECT scans of the heart were performed, followed by resting 99mTc-MIBI SPECT myocardial perfusion imaging in all nine dogs before and 3 h after the procedure. Triphenyltetrazolium chloride (TTC) staining was performed and analyzed. In the short axis of the left ventricle, the wall surface was divided into 17 segments, which were assessed for infarcted myocardium on conventional CT from average-weighted data, DECT myocardial iodine maps, conventional CT plus DECT, SPECT, and histopathology. Inter-observer and inter-modality agreement for conventional CT, DECT myocardial iodine maps, and SPECT were calculated. CT value of infracted and non-infracted areas was measured. Results With the histopathological results as the reference standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0% (30/40), 92.0% (104/113), 76.9% (30/39), 91.2% (104/114), 87.6% (134/153) for conventional CT, 85.0% (34/40), 84.1% (95/113), 65.4% (34/52), 94.1% (95/101), 84.3% (129/153) for DECT myocardial iodine maps; 87.5% (35/40), 92.9% (105/113), 81.4% (35/43), 95.5% (105/110), 91.5% (140/153) for conventional CT plus DECT; 82.5% (33/40), 90.3% (102/113), 75.0% (33/44), and 93.6% (102/109), 88.2% (135/153) for SPECT, respectively. Excellent inter-observer agreement (Kappa value .0.8) and good inter-modality agreement (Kappa value >0.6) for each modality were found. CT values of infarcted myocardium (26±22 HU, 36±33 HU, 34±16 HU) were lower than those of non-infarcted myocardium (115±16 HU, 121±28 HU, 123±11 HU) on images of 140 kVp, 80 kVp, and average-weighted 120 kVp images (all P < 0.05). Conclusion With histopathology as the reference standard, DECT myocardial iodine maps can detect acute myocardial infarction with diagnostic accuracy comparable to resting SPECT myocardial perfusion imaging in a canine model. DECT plus conventional CT had a potential to improve the detection of acute myocardial infarction.
Effects of Magnetically Labeled Exogenous Endothelial Progenitor Cells on Cerebral Blood Perfusion and Microvasculature Alterations after Traumatic Brain Injury in Rat Model
Authors: Chen Xiao , Yin Jun , Wu Xiaoning , Li Ran , Fang Jingqin , Chen Rong , Zhang Bo , Zhang Weiguo 
Published: April 2013

Background Increasing evidence suggests that endothelial progenitor cells (EPCs), a subgroup of bone marrow hematopoietic stromal cells, play a critical role in neovascularization and tissue repair. Purpose To explore the effect of exogenous EPCs on the cerebral blood perfusion and microvessels in the injured region in rat model with traumatic brain injury (TBI). Material and Methods: EPCs were collected from the spleens of healthy Sprague-Dawley rats. Fifty-four Sprague-Dawley rats were randomly divided into six groups. The controlled cortical impact TBI was performed. Spleen-derived exogenous EPCs labeled with superparamagnetic iron oxide (SPIO) (SPIO-EPCs) were transplanted into the blood by tail vein of rats at 6 and 12 h after TBI, respectively. Magnetic resonance imaging (MRI) and computed tomography perfusion imaging were performed at various time points. Microvascular density was determined by immunohistochemistry. Results In SPIO-EPCs group, patchlike hypointensities were detected in the injured region at 24 h after transplantation, and the range of hypointensities tended to expand gradually over time on MRI, which was confirmed by Prussian blue staining. Computed tomography perfusion imaging parameters were gradually developed from hyperperfusion to normal, while, microvascular density was gradually increased during 72 to 168 h after injury. The values of these indices in SPIO-EPCs group were significantly lower than those in SPIO-alone group at the same time point, but no significant differences were found in different time groups. Conclusion The intravenously transplanted EPCs diminish the brain injury through restoring cerebral blood perfusion and increasing the cerebral microvasculature in the injured region in rat model with TBI.
Usefulness of a Guiding Sheath for Fluoroscopic Stent Placement in Patients with Malignant Gastroduodenal Obstruction
Authors: Park Jung-Hoon , Song Ho-Young , Kim Myoung Sun , Chung Rosa , Kim Jin Hyoung , Na Han Kyu , Nam Deok Ho 
Published: April 2013

Background Self-expandable metallic stent placement is widely used to manage malignant gastroduodenal obstructions. However, there are difficulties in negotiating a guidewire (GW) and a stent delivery system (SDS). Purpose To investigate feasibility, usefulness, and safety of a guiding sheath for fluoroscopic stent placement in patients with malignant gastroduodenal obstructions. Material and Methods In July 2001 to August 2011, 726 patients with malignant gastroduodenal obstructions underwent stent placement. Guiding sheath was used in patients in whom a GW could not be passed through the obstruction and a SDS failed to reach the obstruction. Sheath usefulness was evaluated based on the ability of the sheath to successfully assist. The technical success rate and the most frequent reasons for the use of a sheath were evaluated. Results The guiding sheath was needed in 148 of 726 patients (20%). The overall technical success rate was 98% with the guiding sheath. In two of 148 patients, stent placement failed because, the GW could not be passed through the obstruction, in the other, the SDS could not be passed. A minority of patients reported mild discomfort. Patients with pancreatic cancer and duodenal obstruction were significantly more likely to require the use of guiding sheaths (P = 0.002, P < 0.001, respectively). Conclusion Using a guiding sheath for fluoroscopic stent placement appears to be feasible, useful and safe in patients with malignant gastroduodenal obstructions.
Changes in Renal Doppler Ultrasonographic Parameters in Patients Managed with Rigid Ureteroscopy
Authors: Tokgöz Özlem , Tokgöz Hüsnü , Ünal İLker , Voyvoda Nuray , ŞErifo&Gbrave;Lu İSmail 
Published: April 2013

BackgroundThere has been no study evaluating the intrarenal hemodynamic changes after ureteroscopy in the published literature.PurposeTo determine preoperative and postoperative intrarenal vascular parameters such as resistive index (RI), pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV), measure changes on these values (ΔRI, ΔPI, ΔPSV, ΔEDV) after ureteroscopy (URS) and compare the outcomes with the results of normal contralateral kidneys, and finally investigate possible parameters that would affect renal vascular resistance changes.Material and MethodsWe prospectively studied 47 patients who underwent rigid URS. Preoperative grayscale and Doppler ultrasonography (CDUS) measurements were obtained 24 h before URS. Similarly, postoperative CDUS measurements were done 24 h after the operation. The degree of hydronephrosis and location of stones in the obstructed kidneys, diameters of both kidneys, and thickness of renal parenchyma were evaluated with gray-scale US followed by CDUS with calculation of the intrarenal RI, PI, PSV, and EDV values for each kidney.ResultsFor the operated kidneys, statistically significant P values were noticed when RI and PI values were considered (P < 0.001). ΔRI and ΔPI of the operated kidneys were also significantly greater than the values for non-operated kidneys (P < 0.001).However, it was not the case for ΔPSV and ΔEDV values. In Spearman correlation coefficient analysis, ΔRI was found to be correlated with the parameters: “operative time” and “irrigation fluid volume”. No significant relation was documented between ΔRI and the other parameters: age, gender, side of ureteroscopy, stone location, and degree of hydronephrosis.ConclusionSignificant changes in RI and PI values in patients treated with URS reveal that URS can cause a significant increase in renal vascular resistance. With the increase in operative time and irrigation fluid volume used during the operation, RI seems to be significantly increased.
Enhancement Characteristics of Retroperitoneal Lymphomatous LYMPH Nodes
Authors: Hagtvedt Trond , Aaløkken Trond Mogens , Smith Hans-Jørgen , Graff Bjørn Anton , Holte Harald , Kolbenstvedt Alf 
Published: April 2013

Background Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck and the mediastinum showed that the LLN had lower enhancement values than normal lymph nodes. Purpose To elucidate the contrast medium enhancement curves of LLN in the retroperitoneum by comparing the curves of LLN with those of normal lymph nodes, to test whether differences between these curves could be of diagnostic value, and to compare the present enhancement curves of LLN of the retroperitoneum with the curves of LLN of the neck and the mediastinum from previous similar investigations. Material and Methods Twenty-eight consecutive patients with LLN of the retroperitoneum (three with Hodgkin's lymphoma [HL]) and 21 control patients with sarcomas and thus presumably normal retroperitoneal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and the investigation of mediastinal lymph nodes comprised 24 patients with LLN. Results The enhancement curves of the retroperitoneal LLN had significantly lower attenuation than those of the retroperitoneal control nodes. A combination of peak contrast value and time to peak adjusted to total body weight yielded a diagnostic accuracy which at the best showed a sensitivity of 90.5% with a specificity of 82.6%. The LLN of the retroperitoneum had higher attenuation values than corresponding nodes of the mediastinum but no significant difference was found between LLN of the retroperitoneum and LLN of the neck in previous similar investigations. Conclusion The comparison of enhancement curves of retroperitoneal LLN with retroperitoneal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck and of the mediastinum. The best diagnostic accuracy was achieved by combining the parameters peak contrast value and time to peak and adjusting these values to the body weight. Peak enhancement of the retroperitoneal LLN was higher and arrived earlier than that of the mediastinal nodes from the previous investigation.
A practical guide to monitoring for adverse drug reactions during antihypertensive drug therapy
Authors: Mcdowell Sarah E , Thomas Sarah K , Coleman Jamie J , Aronson Jeffrey K , Ferner Robin E 
Published: April 2013

Summary Monitoring of patients taking antihypertensive treatment can identify potential adverse drug reactions (ADRs). However, published guidelines give divergent or incomplete recommendations on monitoring for ADRs. Using a predetermined strategy, we undertook a systematic review to identify hypertension guidelines published from January 2001 to October 2011 with recommendations for monitoring for ADRs. We screened 88 abstracts and 187 web-based guidelines, and identified 19 published guidelines on monitoring the biochemical effects of antihypertensive drug therapy. We then produced a set of practical clinical guidelines, synthesized from those recommendations. Our recommendations are designed to provide efficient monitoring. They reduce the number of tests to a minimum consistent with safe practice and align monitoring schedules, so that creatinine, potassium and sodium concentrations are measured at the same times in all cases. The instructions for biochemical monitoring in current guidelines differ greatly, both in the extent of advice and in the detail provided. The current lack of consistent and workable instructions poses serious difficulties for practitioners. The recommendations distilled from this systematic review should help practitioners when they monitor therapy with antihypertensive drugs.
Enhancing the h index for the objective assessment of healthcare researcher performance and impact
Authors: Patel Vanash M , Ashrafian Hutan , Bornmann Lutz , Mutz RÜDiger , Makanjuola Jonathan , Skapinakis Petros , Darzi Ara , Athanasiou Thanos 
Published: April 2013

Summary Objective To investigate whether the h index (a bibliometric tool which is increasingly used to assess and appraise an individual's research performance) could be improved to better measure the academic performance and citation profile for individual healthcare researchers. Design Cohort study. Setting Faculty of Medicine, Imperial College London, UK. Participants Publication lists from 1 January 2000 until 31 December 2009 for 501 academic healthcare researchers from the Faculty of Medicine. Main outcome measures The h index for each researcher was calculated over a nine-year period. The citation count for each researcher was differentiated into high ( h2 upper), core ( h2 centre) and low ( h2 lower) visibility areas. Segmented regression model (sRM) was used to statistically estimate number of high visibility publications (sRM value). Validity of the h index and other proposed adjuncts were analysed against academic rank and conventional bibliometric indicators. Results Construct validity was demonstrated for h index, h2 upper, h2 centre, h2 lower and sRM value (all P < 0.05). Convergent validity of the h index and sRM value was shown by significant correlations with total number of publications ( r =0.89 and 0.86 respectively, P<0.05) and total number of citations ( r = 0.96 and 0.65, respectively, P<0.05). Significant differences in h index and sRM value existed between non-physician and physician researchers ( P < 0.05). Conclusions This study supports the construct validity of the h index as a measure of healthcare researcher academic rank. It also identifies the assessment value of our developed indices of h2 upper, h2 centre, h2 lower and sRM. These can be applied in combination with the h index to provide additional objective evidence to appraise the performance and impact of an academic healthcare researcher.