bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumourigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems
Authors: Nelson Scott A. , Li Zhouyu , Newton Ian P. , Fraser David , Milne Rachel E. , Martin David , Schiffmann David , Yang Xuesong , Dormann Dirk , Weijer Cornelis J. , Appleton Paul L. , Näthke Inke S. 
Published: April 2012

SummaryNonsense mutations that result in expression of truncated, N-terminal fragments of the APC tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumourigenesis by eliminating β-catenin binding sites from APC, which leads to upregulation of β-catenin to result in induction of oncogenes such as MYC. Here we show that in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution, three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of wild type and APC heterozygous tissue from APCMin/+ mice demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, cells expressing N-APC fail to migrate normally; amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but failed to perform directional chemotaxis; multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+intestines are overpopulated with cells suggesting that a lack of migration may cause cell accumulation in a pre-cancerous state.
Endovenous laser ablation for major varicose tributaries
Authors: Myers K A , Clough A , Tilli H 
Published: April 2012

Objective The purpose was to determine whether endovenous laser ablation (EVLA) could be used to treat major varicose tributaries as well as saphenous veins. Methods From 173 major venous systems in 95 patients treated by EVLA over a 12-month period, 108 had major varicose tributaries, of which 78 (70%) were treated by attempted EVLA of the saphenous veins and associated tributaries. Results Treatment was successful in 71 venous segments (83%). The lengths of saphenous veins treated were 3–46 (median 18) cm. and the lengths of tributaries treated were 3–38 (median 14) cm. The diameters of treated saphenous veins were 4–10 (median 6) mm, and the estimated mean diameters of treated tributaries were 3–8 (median 5) mm, as measured prior to operation with the patient in 45° reverse Trendelenburg on a tilt table. There were no early or delayed complications. Conclusions Major varicose tributaries as well as the saphenous veins can be treated by EVLA in approximately two-thirds of cases, with success in the majority selected and with no significant complications.
Bilateral Sudden Sensorineural Hearing Loss and Chronic Venous Cerebrospinal Insufficiency: A Case Report
Authors: Alpini D , Bavera P M , Di Berardino F , Barozzi S , Cesarani A 
Published: April 2012

Objectives: We report a case of bilateral sudden sensorineural hearing loss (SSHL) in a patient suffering from chronic venous cerebrospinal insufficiency (CCSVI). Methods: Audiometric testing confirmed bilateral sensorineural hearing loss with hypoexcitability to caloric stimulation on the left side and echo-colour Doppler examination showed abnormal cerebral venous deficiency. Results: The patient's condition improved after 15 days following medical treatment. Conclusions: CCSVI may explain the anatomical background which provides a predisposing factor for SSHL although further studies are needed to verify whether this observation is casual or coincidental.
Mobile Laboratory Unit: a disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
Authors: Leon-Justel Antonio , Noval-Padillo Jose Angel , Polonio Franciso , Gomez-Cia Tomas , Hinojosa Rafael , Porras Manuel , De-Blas Jose M. , Solomon Cristina , Guerrero Juan M. 
Published: April 2012

AbstractThe management of surgical bleeding during a face transplant in a patient diagnosed with bilateral neurofibromatosis is quite complex. With the actual methods and technology for hemostasis management, it may not always be possible to give the clinician the support needed to manage operative associated bleeding. Bedside hemostasis monitors are needed urgently to assist clinicians in making the correct diagnosis in a timely manner.Our Mobile Laboratory Unit is a disruptive solution for hemostasis management during major surgery as it allows real-time monitoring, the predominant mechanism of bleeding and goal-direct coagulation therapy. The unit is an autonomous mobile platform that can be moved immediately to anywhere its service is needed and offers a complete flexible laboratory test which includes biochemistry, hematology and coagulation studies as standard equipment.In our case the test performed by the unit allowed us to identify the reason for our patient’s bleeding at the bedside. Severely decreased clot firmness of the fibrin-based clot and a less impaired firmness of the whole blood clot, suggested an acceptable contribution of platelets to the clot quality, but decreased polymerization of fibrinogen into fibrin.In our opinion new insights into the pathophysiology of coagulopathy, the availability of technology such as our Mobile Laboratory Unit, and awareness of side effects of intravenous fluids should encourage the idea that perhaps it is time to change hemostasis management in operation-related bleeding.
Blood presence of circulating oncofetal fibronectin mRNA, by RT-PCR, does not represent a useful specific marker for the management and follow-up of thyroid cancer patients
Authors: Vendittelli Francesca , Raffaelli Marco , Fadda Guido , Carelli-Alinovi Cristiana , Paolillo Carmela , Bellantone Rocco , Zuppi Cecilia , Capoluongo Ettore 
Published: April 2012

AbstractRecent studies strongly suggest the use of oncofetal fibronectin (onfFN) mRNA in diagnostic follow-up and staging due to its very high specificity for thyroid cancers. Since the use of this marker has not been well established yet, particularly in the monitoring of minimal residual disease, we have tried to verify the diagnostic power of onfFN and its usefulness as a prognostic molecular marker. For this reason, we evaluated (by RT-PCR) the presence of onfFN mRNAs, not only in blood samples and thyroid tissues (both normal and neoplastic), but also in different biological fluids (such as KMolecular investigations, such as RT-PCR protocol, and sequencing of onfFN cDNAs evaluation of the above-mentioned samples were performed.The onfFN transcript was largely expressed in all benign and malignant thyroid tissues [differentiated thyroid carcinomas (DTCs)] tested as well as in a large number of biological fluids; in particular, 100% urine samples were positive for onfFN transcript as compared to the thyroglobulin (Tg) mRNA (75%), while saliva was always positive for onfFN and never for Tg. These findings indicate that onfFN cannot be considered a marker specific for thyroid cancer presence. Finally, Tg results were positive in a large part of the samples, but not always in concomitance with onfFN.We underline how the complexity of onfFN transcripts could affect the RT-PCR procedure. In addition, the presence of onfFN transcripts in several normal and cancer tissues, along with non-thyroid biological fluids or cells, does not allow the use of this marker for cancer monitoring.
Quantification of human serum insulin concentrations in clinical pharmacokinetic or bioequivalence studies: what defines the “best method”?
Authors: Cassidy James P. , Luzio Stephen D. , Marino Mark T. , Baughman Robert A. 
Published: April 2012

AbstractHistorically, quantitative clinical diagnostic assays (QCDAs) have not been accepted for use in pharmacokinetic or bioequivalence studies because they do not fully comply with the US Food and Drug Administration (FDA) Guidance for Industry: Bioanalytical Method Validation (e.g., full calibration curve not generated with each analytical run). Samples from a bioequivalence study were analysed for insulin and C-peptide concentrations with QCDAs and guidance-conforming radioimmunoassays (RIAs) and the results compared across and within assays.Serum samples (n=1913) from study MKC-TI-142 were analysed first using the Roche E170 electrochemiluminescence immunoassay (ECLIA) for insulin concentration and the Immulite 2000 chemiluminescence immunoassay (CLIA) for C-peptide, and then using the corresponding Millipore RIAs.The insulin assays were highly correlated: rThe science indicates that the QCDAs are appropriate for the quantification of serum insulin (ECLIA) and C-peptide (CLIA) concentrations in human pharmacokinetic and bioequivalence studies even though the calibration curve is not generated in each analytical run.
A comprehensive review of upper reference limits reported for (high-)sensitivity cardiac troponin assays: the challenges that lie ahead
Authors: Cardinaels Eline P.M. , Mingels Alma M.A. , Jacobs Leo H.J. , Meex Steven J.R. , Bekers Otto , van Dieijen-Visser Marja P. 
Published: April 2012

AbstractCardiac troponins (cTn) are the preferred markers for the diagnosis of acute myocardial infarction (AMI). The guidelines recommend the use of the 99th percentile upper reference concentration of a healthy population as the diagnostic cut-off for AMI. However, a broad range of upper reference limits is still employed, complicating the diagnosis of AMI. This overview is meant to assist laboratory specialists to define an appropriate cut-off value for the diagnosis of AMI. Therefore, we provide an overview of the analytical performance and upper reference limits of seven (high-)sensitivity cTn assays: Roche high-sensitivity cTnT and ADVIA Centaur, Stratus CS, Dimension Vista, Vitros ECi, Access and Architect cTnI assays. It is shown that none of the reference populations completely met the guidelines, including those in package inserts. Forty percent of the studies collected less than the advised minimum of 300 subjects. Many studies (50%) did not report their inclusion criteria, while lower 99th percentile limits were observed when more stringent selection criteria were applied. Higher troponin cut-offs were found in men and elderly subjects, suggesting sex- and age-specific cut-offs would be considered. Therefore, there is still need for a large, rigorously screened reference population to more accurately establish cTn upper reference limits.
The performance of high sensitivity troponin for the diagnosis of acute myocardial infarction is underestimated
Authors: Aldous Sally J. , Florkowski Chris M. , Crozier Ian G. , Than Martin P. 
Published: April 2012

AbstractMany papers evaluating high sensitivity troponin assays make the diagnosis of myocardial infarction based on conventional troponin assays in clinical use at the time of recruitment. Such analyses often do not show superiority of high sensitivity assays compared with contemporary assays meeting precision guidelines.Three hundred and twenty-two patients presenting to the emergency department between November 2006 and April 2007 for evaluation for acute coronary syndrome had serial (0 h and >6 h) bloods taken to compare troponin assays (Roche hsTnT, Abbott TnI, Roche TnT and Vitros TnI). The diagnosis of myocardial infarction was made using each troponin assay separately with which that same assay was analysed for diagnostic performance.The rate of myocardial infarction would be 38.9% using serial hsTnT, 31.3% using serial Abbott TnI, 27.1% using serial TnT and 26.4% using serial Vitros TnI. The baseline sensitivities (0 h) are 89.9% (85.2–93.3) for hsTnT, 77.9% (71.0–87.5) for Abbott TnI, 73.0% (65.6–78.7) for TnT and 86.8% (74.6–94.4%) for Vitros TnI. The specificities (peak 0 h and >6 h samples) are 93.1% (91.2–93.1) for hsTnT, 88.3% (86.5–88.3) for Abbott TnI, 92.2% (90.5–92.2) for TnT and 90.6% (70.1–90.6) for Vitros TnI.hsTnT has superior sensitivity for myocardial infarction than even assays at or near guideline precision requirements (Abbott and Vitros TnI). The specificity of hsTnT assay is not as poor as previous analyses suggest.
Measurement of high-molecular-weight adiponectin is not useful in assessing coronary stenosis
Authors: Imatoh Takuya , Miyazaki Motonobu , Kadowaki Ken , Tanihara Shinichi , Akashi Chinami , Une Hiroshi 
Published: April 2012

AbstractIn many studies, high-molecular-weight (HMW) adiponectin has been considered the active form of adiponectin. However, whether HMW adiponectin is a good surrogate marker for coronary artery disease still needs to be elucidated.We conducted a hospital-based cross-sectional study to examine the relationship between total, HMW or non-HMW adiponectin concentrations and coronary stenosis in 83 male patients and 138 male controls.Patients with coronary stenosis had significantly lower total adiponectin concentrations compared with controls. Non-HMW adiponectin concentrations in cases were significantly lower than the controls. However, there were no significant differences between cases and controls in HMW adiponectin concentrations. From the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for total and non-HMW adiponectin was significantly larger than that for HMW adiponectin concentrations. Of the three models, that for non-HMW adiponectin showed the largest AUC (total adiponectin 0.74, HMW adiponectin 0.54, and non-HMW adiponectin 0.79).Despite associations between total adiponectin levels and coronary stenosis, our data go against any apparent association between HMW adiponectin concentrations and coronary stenosis.
Detection of α-globin gene deletion and duplication using quantitative multiplex PCR of short fluorescent fragments
Authors: Mo Zong-Ping , Yu Chang-Shun , Li Ya-Juan , Cao Wei-xi , Zeng Zheng-Yu , Zhan Yi-Xin , Mo Gui-ling , Hu Chaohui , Feng Wenli 
Published: April 2012

AbstractThe aim of this study was to establish a sensitive method that can detect the presence of not only the common but also the unusual or unknown α-globin gene deletions for screening of α-thalassemia. We used quantitative multiplex PCR of short fluorescent fragments (QMPSF) for the α-globin genes (We set up and validated HBA-QMPSF using 50 negative and 100 positive controls of deletional α-thalassemia. To evaluate its ability to detect the presence of the common and unusual or unknown α-globin gene deletions, 579 unrelated samples were simultaneously analyzed using this assay and multiplex Gap polymerase chain reaction (Gap-PCR). The inconsistent results were further confirmed by multiplex ligation-dependent probe amplification (MLPA).HBA-QMPSF was capable of detecting α-globin gene deletions with an acceptable variability as shown by mean values (SD) of allele dosage for the heterozygous deleted control obtained from intra- and inter-experimental replicates [0.63 (0.01) and 0.61 (0.03)]. In 572 out of the 579 unrelated subjects, HBA-QMPSF and multiplex Gap-PCR gave consistent results. In seven cases which were finally proved to be composed of one rare deletion --HBA-QMPSF is able to detect the presence of the common and unusual or unknown α-thalassemia deletions and duplications. It can be used as an initial screening test for α-thalassemia caused by
A sensitive quantitative test strip based point-of-care albuminuria screening assay
Authors: Decavele An-Sofie C. , Fiers Tom , Penders Joris , Delanghe Joris R. 
Published: April 2012

AbstractChronic kidney disease is a major health problem and the global guidelines require screening of albuminuria. Therefore, affordable and sensitive albuminuria screening tests are needed. We explored the potential of urine strips, generally reported in the ordinal scale, measured on an automatic strip reader for reporting quantitative and sensitive albumin results.We compared reflectance data of Combur-TestImprecision of the reflectance signal of the Cobas U411 was measured with commercial control material (Bio-Rad). Inter-run coefficients of variations (CVs) for reflectance for levels 1 and 2 were 1.7%/4.9%, respectively, and intra-run CVs were 1.8%/4.2%, respectively. Good agreement was obtained between the albumin concentration of the BNII and the protein strip reflectance data (n=389): Y (10000/protein reflectance, 1/%)=160+0.132·X (albuminuria BNII, mg/L)–0.0000111·XThe present study demonstrates that reflectance data generated by a test strip reader allows for quantitative analysis of albumin. Although the lower limit of the microalbumin range (30 mg/L) cannot be achieved with the dye-binding method, the results are satisfactory for screening purposes.
The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer
Authors: White Nicole M.A. , Youssef Youssef M. , Fendler Annika , Stephan Carsten , Jung Klaus , Yousef George M. 
Published: April 2012

AbstractKallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications.
Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance
Authors: Avgeris Margaritis , Mavridis Konstantinos , Scorilas Andreas 
Published: April 2012

Abstract
Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2–15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identification as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.
Long-Term Renal and Cardiovascular Outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants by Baseline Estimated GFR
Authors: Rahman Mahboob , Ford Charles E. , Cutler Jeffrey A. , Davis Barry R. , Piller Linda B. , Whelton Paul K. , Wright Jackson T. , Barzilay Joshua I. , Brown Clinton D. , Colon Pedro J. , Fine Lawrence J. , Grimm Richard H. , Gupta Alok K. , Baimbridge Charles , Haywood L. Julian , Henriquez Mario A. , Ilamaythi Ekambaram , Oparil Suzanne , Preston Richard 
Published: April 2012

Summary

Background and objectives
CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.

Design, setting, participants, & measurements
This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4–8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m2) as follows: normal/increased (≥90; n=8027), mild reduction (60–89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.

Results
After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.

Conclusions
CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.
Nietzsche on Agency and Self-Ignorance
Authors: Paul Katsafanas 
Published: April 2012

Abstract
Nietzsche frequently claims that agents are in some sense ignorant of their own actions. But what exactly does Nietzsche mean by this claim, and how would the truth of this claim affect philosophical models of agency? I argue that Nietzsche intends to draw attention to the fact that there are influences on reflective episodes of choice that have three features. First, these influences are pervasive, occurring in every episode of choice. Second, these influences are normatively significant, in that their presence typically affects the outcome of deliberation. Third, these influences are difficult to detect, in that one needs to acquire a great deal of self-knowledge in order to begin to counteract their effects. I briefly sketch the way in which these claims follow from Nietzsche's philosophical psychology.