tbuckley/cabot-search huggingface dataset:
Lessons from Controversy: Ovarian Cancer Screening and Serum Proteomics
Authors: D. F. Ransohoff
Journal: JNCI Journal of the National Cancer Institute (2005)

In 2002 a study reported that a blood test, based on pattern-recognition proteomics mass spectroscopy analysis of serum, was nearly 100% sensitive and specific to detect ovarian cancer. Plans to introduce a commercial screening test by early 2004 were delayed amid concerns about whether the approach was reproducible and reliable. In this issue of JNCI, two commentaries discuss whether the initial results are reproducible and whether bias may account for results. This essay describes how threats to validity from chance and bias may cause erroneous results and inflated expectations in the kind of observational research being conducted in several "-omics" fields to assess molecular markers for diagnosis and prognosis of cancer. To address such threats and to realize the potential of new -omics technology will require application of appropriate rules of evidence in the design, conduct, and interpretation of clinical research about molecular markers.
18F9 (4-(3,6-bis (ethoxycarbonyl)-4,5,6,7-tetrahydrothieno (2,3-c) pyridin-2-ylamino)-4-oxobutanoic acid) enhances insulin-mediated glucose uptake in vitro and exhibits antidiabetic activity in vivo in db/db mice
Authors: Rathinasabapathy Anandharajan, Sufyan G. Sayyed, Lalit S. Doshi, Pooja Dixit, Prakash G. Chandak, Amol V. Dixit, Manoja K. Brahma, Nitin J. Deshmukh, Ravindra Gupte, Anagha Damre, Jaspreet Suthar, Muralidhara Padigaru, Somesh D. Sharma, Kumar V.S. Nemmani
Journal: Metabolism (2009)
Use and Outcomes of Peritoneal Dialysis among Aboriginal People in Canada
Authors: Marcello Tonelli, Brenda Hemmelgarn, Braden Manns, Sara Davison, Clara Bohm, Sita Gourishankar, George Pylypchuk, Karen Yeates, John S. Gill
Journal: Journal of the American Society of Nephrology (2004)

There has been a dramatic increase in the incidence of ESRD among Aboriginal people in North America. Although peritoneal dialysis (PD) seems to be the dialysis modality of choice for this often rural-dwelling population, few data exist to confirm this. This study was conducted to evaluate rates of PD use, technique failure, and mortality among incident Aboriginal dialysis patients. Adults of white or Aboriginal race who initiated dialysis in three Canadian provinces between January 1, 1990, and December 31, 2000, were included and followed until December 31, 2001. Logistic regression and Cox proportional hazards models were used to examine adjusted associations between Aboriginal race and PD use, technique failure, and mortality. Among the 3823 patients of white (n = 3138; 82.1%) or Aboriginal (n = 685; 17.9%) race, 835 (21.8%) initiated dialysis on PD. After adjustment for age and comorbidity and comparison with white patients, Aboriginal patients were significantly less likely to initiate therapy on PD compared with white patients (odds ratio, 0.51; 95% confidence interval, 0.40 to 0.65), with a nonsignificant trend toward a higher risk for technique failure (hazards ratio, 1.46; 95% confidence interval, 0.95 to 2.23). Adjusted survival among Aboriginal PD patients seemed similar to both white PD patients and Aboriginal patients who were treated with hemodialysis. In summary, among people who were treated with dialysis in Canada, PD was used less frequently in Aboriginal patients than in those of white race. Although Aboriginal patients who initiate dialysis on PD seemed more likely to experience technique failure, their adjusted risk for death was similar to that of white patients. Future studies should address barriers to the initiation and maintenance of PD in the Aboriginal population, especially those who reside in rural locations.
Institute of Medicine Outlines Priorities for Comparative Effectiveness Research
Authors: Bridget M. Kuehn
Journal: JAMA (2009)

fetal acid-base status; there isnotyet evidence to classify them as either normal or abnormal. Maconesnotedthis3-tierclassification systemisbasedonexpertopinion,notrigorousscientificevidence.“Despitethefact that it is used in 85% of births, there has been no new research in the last decade on fetal heart monitoring, so our document calls for more research,” he said. Such research appears long overdue. Macones and colleagues wrote that there are no randomized controlled trials comparing the benefits of electronic fetal monitoring with other forms of observation during labor and that benefits attributed to the technique are based on studies comparing it with intermittent fetal heart rate auscultation. Such studies indicate that electronicmonitoring,when compared with auscultation, reduces the risk of neonatal seizures. However, electronic fetal monitoring also increased the overall cesarean delivery rate as well as the risk of use of both vacuum and forceps operative techniques during a vaginal delivery, without reducing perinatal mortality or the risk of cerebral palsy. In addition, the false-positive rate of electronic monitoring for predicting cerebral palsy is greater than 99%, the guideline authors said. As for interpreting fetal heart rate tracings, Macones said work is needed to decrease variability and increase accuracy. The ACOG’s revision cited 1 study in which 4 obstetricians independently examined 50 tracings and reached similar interpretations in only 22% of the cases; 2 months later, in a review of the same 50 tracings, the obstetricians’ second interpretation differed from their initial evaluation in 21% of the tracings (Nielsen PV et al. Acta Obstet Gynecol Scand. 1987;66[5]:421-424). Thesamestudy foundthat reinterpretation of fetal heart rate tracings is subject to bias based on outcomes. The researchers foundthatareviewerwasmore likelytofindevidenceoffetalhypoxiaand tocriticizeanobstetrician’smanagement of the labor and delivery if the outcome for the fetuswaspoor insteadofgood.
GDNF Acts through PEA3 to Regulate Cell Body Positioning and Muscle Innervation of Specific Motor Neuron Pools
Authors: Georg Haase, Eric Dessaud, Alain Garcès, Béatrice de Bovis, Marie-Christine Birling, Pierre Filippi, Henning Schmalbruch, Silvia Arber, Odile deLapeyrière
Journal: Neuron (2002)
Simvastatin Reduces Neointimal Thickening in Low-Density Lipoprotein Receptor–Deficient Mice After Experimental Angioplasty Without Changing Plasma Lipids
Authors: Zhiping Chen, Tatsuya Fukutomi, Alexandre C. Zago, Raila Ehlers, Patricia A. Detmers, Samuel D. Wright, Campbell Rogers, Daniel I. Simon
Journal: Circulation (2002)

Background — Statins exert antiinflammatory and antiproliferative actions independent of cholesterol lowering. To determine whether these actions might affect neointimal formation, we investigated the effect of simvastatin on the response to experimental angioplasty in LDL receptor–deficient (LDLR −/− ) mice, a model of hypercholesterolemia in which changes in plasma lipids are not observed in response to simvastatin. Methods and Results — Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDLR −/− mice treated with low-dose (2 mg/kg) or high-dose (20 mg/kg) simvastatin or vehicle subcutaneously 72 hours before and then daily after injury. After 7 and 28 days, intimal and medial sizes were measured and the intima to media area ratio (I:M) was calculated. Total plasma cholesterol and triglyceride levels were similar in simvastatin- and vehicle-treated mice. Intimal thickening and I:M were reduced significantly by low- and high-dose simvastatin compared with vehicle alone. Simvastatin treatment was associated with reduced cellular proliferation (BrdU), leukocyte accumulation (CD45), and platelet-derived growth factor–induced phosphorylation of the survival factor Akt and increased apoptosis after injury. Conclusions — Simvastatin modulates vascular repair after injury in the absence of lipid-lowering effects. Although the mechanisms are not yet established, additional research may lead to new understanding of the actions of statins and novel therapeutic interventions for preventing restenosis.
Potentiation of Inflammatory CXCL8 Signalling Sustains Cell Survival in PTEN-deficient Prostate Carcinoma
Authors: Pamela J. Maxwell, Jonathan Coulter, Steven M. Walker, Melanie McKechnie, Jessica Neisen, Nuala McCabe, Richard D. Kennedy, Manuel Salto-Tellez, Chris Albanese, David J.J. Waugh
Journal: European Urology (2012)
Identifying Individuals with a Reduced GFR Using Ambulatory Laboratory Database Surveillance
Authors: Amit X. Garg, Muhammad Mamdani, David N. Juurlink, Carl van Walraven
Journal: Journal of the American Society of Nephrology (2005)

The use of outpatient laboratory databases to identify people with a low GFR may be part of an effective strategy to increase their use of treatments to prevent kidney failure. All renal function data from 17 independent outpatient laboratories in Eastern Ontario were combined to determine the proportion of adults with at least one serum creatinine measurement during a 1-yr period. The detection rates of low GFR were measured using different algorithms, and what proportion of identified low GFR was transient was considered. Canadian census data were used to calculate rates and proportions. Renal function testing was common. Of the 1,090,000 adult residents, 32% of the entire population and 63% of seniors had at least one serum creatinine measured during the study year. Sixteen percent of the population (49% of those with tests performed) had at least one GFR <80 ml/min per 1.73 m2, 5% (16%) had at least one GFR <60 ml/min per 1.73 m2, and 0.6% (1.7%) had at least one GFR <30 ml/min per 1.73 m2. Low GFR were usually not transient: 68% of individuals with subsequent testing at least 30 d later had a similar or worse GFR. Ambulatory laboratory database case finding, particularly in older patients, seems to be a promising method for easily identifying large segments of the population with persistent reductions in GFR. Whether such identification leads to improved health outcomes warrants further study.
Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.
Authors: R De Caterina, P Libby, H B Peng, V J Thannickal, T B Rajavashisth, M A Gimbrone, W S Shin, J K Liao
Journal: Journal of Clinical Investigation (1995)

To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.
Development of a standardized low‐dose double‐blind placebo‐controlled challenge vehicle for the EuroPrevall project
Authors: S. A. Cochrane, L. J. Salt, E. Wantling, A. Rogers, J. Coutts, B. K. Ballmer‐Weber, P. Fritsche, M. Fernández‐Rivas, I. Reig, A. Knulst, T.‐M. Le, R. Asero, K. Beyer, M. Golding, R. Crevel, E. N. Clare Mills, A. R. Mackie
Journal: Allergy (2011)

To cite this article: Cochrane SA, Salt LJ, Wantling E, Rogers A, Coutts J, Ballmer‐Weber BK, Fritsche P, Fernández‐Rivas M, Reig I, Knulst A, Le T‐M, Asero R, Beyer K, Golding M, Crevel R, Clare Mills EN, Mackie AR. Development of a standardized low‐dose double‐blind placebo‐controlled challenge vehicle for the EuroPrevall Project. Allergy 2012; 67 : 107–113. Abstract Background: Double‐blind placebo‐controlled food challenge (DBPCFC) is the gold standard for diagnosing food allergy. Standardized materials and protocols are essential for comparing DBPCFC results for multicentre studies such as EuroPrevall. This required the development and piloting of a standardized vehicle and low‐dose protocol for confirming food allergy and determination of minimum eliciting doses (MEDs). Methods: A low‐dose DBPCFC protocol was developed, with eight titrated protein doses from 3 μg to 1 g. This was delivered using a simple, microbiologically stable food base incorporating allergenic food ingredients manufactured at three sites and centrally distributed to clinical centres. Allergen blinding was assessed by a professional sensory testing panel using a triangle test. Homogeneity and allergen content were confirmed by ELISA and clinical efficacy was assessed in a pilot study, using celeriac and hazelnut as exemplars. Results: Celeriac and hazelnut ingredients were sufficiently blinded in the dessert. The dessert meals were successfully piloted with hazelnut in allergy clinics in Spain, the Netherlands and Italy and with celeriac and hazelnut in Zurich. The challenges elicited a range of subjective and objective reactions ranging in severity from mild itching of the oral mucosa to bronchospasm. Conclusions: A standardized challenge vehicle proven to sufficiently blind processed, powdered hazelnut and celeriac ingredients and that can be reproducibly manufactured has been developed. This pilot study shows that the vehicle is promising for the confirmation of food allergy and determination of MEDs in adults and children with body weight &gt;28.8 kg (approximately 7–11 years old).
Epiphora and Canalicular Stenosis Associated With Adjuvant Docetaxel in Early Breast Cancer: Is Excessive Tearing Clinically Important?
Authors: Bita Esmaeli, Vicente Valero
Journal: Journal of Clinical Oncology (2013)

Docetaxel, as a single agent or in combination, is widely used in the palliative treatment of many common solid tumors, including breast, lung, and prostate cancers.Docetaxel is also used in many of the adjuvant regimens in early breast cancer, including the docetaxel, carboplatin, and trastuzumab regimen, the docetaxel and cyclophosphamide combination, and those with or without an anthracycline or trastuzumab (docetaxel/doxorubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide followed by docetaxel, doxorubicin/cyclophosphamide followed by docetaxel, and doxorubicin/cyclophosphamide followed by docetaxel plus trastuzumab).Adjuvant-based docetaxel may lead to well-known acute and chronic adverse events including neutropenic fever or infection, stomatitis, hypersensitive reaction, rash, fluid retention, peripheral neuropathy, and fatigue.The safety profile of docetaxel is schedule and dose dependent.Excessive tearing (epiphora) is a common adverse event reported in patients who receive docetaxel for metastatic disease. 1-10However, there is little published information about ocular toxicity, including epiphora, in the adjuvant setting.Two large docetaxel-based adjuvant phase III studies briefly reported docetaxel-related ocular toxicity.In the Breast Cancer International Research Group (BCIRG) trial 001, lacrimal disorder was reported in 11.3% versus 7.1% of patients who received TAC versus those who received fluorouracil/doxorubicin/ cyclophosphamide, respectively. 11In the Eastern Cooperative Oncology Group study 1199, grade 3 and 4 lacrimation was reported in 5% of patients who received weekly adjuvant docetaxel versus less than 1% of patients who received adjuvant paclitaxel once per week, paclitaxel once every 3 weeks, or docetaxel once every 3 weeks. 12Other ocular symptoms such as conjunctivitis were also reported in less than 1% in patients in this trial, including those who received docetaxel once per week. 12n the article that accompanies this editorial, Chan et al 13 studied the prevalence of epiphora, canalicular stenosis, and nasolacrimal duct obstruction in patients with early-stage breast carcinoma who received adjuvant docetaxel-based combination chemotherapy.This is a large prospective report evaluating ocular toxicity in patients with early breast cancer receiving adjuvant therapy, although several previous studies have reported the association between docetaxel and epiphora and its anatomic correlates, canalic-
Postural Hypotension: Causes, Clinical Features, Investigation, and Management
Authors: Christopher J. Mathias, DPhil, DSc, FRCP, Jeffery R. Kimber, BSc, MB, BS, MRCP
Journal: Annual Review of Medicine (1999)

Postural hypotension may result from various neurogenic and non-neurogenic causes. It may be a key feature of certain disorders, such as the primary chronic autonomic failure syndromes; it can complicate a variety of diseases, such as diabetes mellitus; and its prevalence increases with advancing age. When symptomatic, it may result in loss of consciousness and thus cause injury. Postural hypotension can be suspected from the patient's history and is readily documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. Treatment of the causative disorder is often curative when there are non-neurogenic causes. A combination of nonpharmacological and pharmacological measures is needed in the management of neurogenic postural hypotension.
Radiosensitization of Squamous Cell Carcinoma by the Alkylphospholipid Perifosine in Cell Culture and Xenografts
Authors: Stefan R. Vink, Saskia Lagerwerf, Elly Mesman, Jan H.M. Schellens, Adrian C. Begg, Wim J. van Blitterswijk, Marcel Verheij
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Combined modality treatment has improved outcome in various solid tumors. Besides classic anticancer drugs, a new generation of biological response modifiers has emerged that increases the efficacy of radiation. Here, we have investigated whether perifosine, an orally applicable, membrane-targeted alkylphospholipid, enhances the antitumor effect of radiation in vitro and in vivo. Experimental Design: Several long-term and short-term in vitro assays (clonogenic survival, sulforhodamine B cytotoxicity, apoptosis, and cell cycle analysis) were used to assess the cytotoxic effect of perifosine in combination with radiation. In vivo, the response of human KB squamous cell carcinoma xenografts was measured after treatment with perifosine, irradiation, and the combination. Radiolabeled perifosine was used to determine drug disposition in tumor and normal tissues. At various intervals after treatment, tumor specimens were collected to document histopathologic changes. Results: In vitro, perifosine reduced clonogenic survival, enhanced apoptosis, and increased cell cycle arrest after radiation. In vivo, radiation and perifosine alone induced a dose-dependent tumor growth delay. When combining multiple perifosine administrations with single or split doses of radiation, complete and sustained tumor regression was observed. Histopathologic analysis of tumor specimens revealed a prominent apoptotic response after combined treatment with radiation and perifosine. Radiation-enhanced tumor response was observed at clinically relevant plasma perifosine concentrations and accumulating drug disposition of &amp;gt;100 μg/g in tumor tissue. Conclusions: Perifosine enhances radiation-induced cytotoxicity, as evidenced by reduced clonogenic survival and increased apoptosis induction in vitro and by complete tumor regression in vivo. These data provide strong support for further development of this combination in clinical studies.
Ablation of junctin or triadin is associated with increased cardiac injury following ischaemia/reperfusion
Authors: Wen-Feng Cai, Tracy Pritchard, Stela Florea, Chi-Kueng Lam, Peidong Han, Xiaoyang Zhou, Qunying Yuan, Stephan E. Lehnart, Paul D. Allen, Evangelia G. Kranias
Journal: Cardiovascular Research (2012)

Junctin and triadin are calsequestrin-binding proteins that regulate sarcoplasmic reticulum (SR) Ca2+ release by interacting with the ryanodine receptor. The levels of these proteins are significantly down-regulated in failing human hearts. However, the significance of such decreases is currently unknown. Here, we addressed the functional role of these accessory proteins in the heart's responses to ischaemia/reperfusion (I/R) injury. Isolated mouse hearts were subjected to global I/R, and contractile parameters were assessed in wild-type (WT), junctin-knockout (JKO), and triadin-knockout (TKO) hearts. Both JKO and TKO were associated with significantly depressed post-I/R contractile recovery. However, ablation of triadin resulted in the most severe post-I/R phenotype. The additional contractile impairment of TKO hearts was not related to a mitochondrial death pathway, but attributed to endoplasmic reticulum (ER) stress-mediated apoptosis. Activation of the X-box-binding protein-1 and transcriptional up-regulation of C/EBP-homologous protein (CHOP) provided a molecular mechanism of caspase-12-dependent apoptosis in myocytes. In addition, elevation of cytosolic Ca2+ during reperfusion was associated with the activation of calpain proteases and troponin I breakdown. Accordingly, treatment with the calpain inhibitor MDL-28170 significantly ameliorated post-I/R impairment of contractile recovery in intact hearts. These findings indicate that deficiency of either junctin or triadin impairs the contractile recovery in post-ischaemic hearts, which appears to be primarily attributed to increased ER stress and activation of calpain.