tbuckley/cabot-search huggingface dataset:
Industry Relationships Among Academic Institutional Review Board Members
Authors: Eric G. Campbell, Christine Vogeli, Sowmya R. Rao, Melissa Abraham, Roz Pierson, Sandra Applebaum
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> For the past decade, more attention and concern has been directed toward financial relationships between the life science industry and physicians. Relationships between industry and institutional review board (IRB) members represent an important subclass that has the potential to broadly influence decisions regarding medical research. <h3>Objectives</h3> To study the nature, extent, and perceived consequences of industry relationships among IRB members in academic health centers and to compare our results with findings from 2005. <h3>Design, Setting, and Participants</h3> A survey mailed to IRB members from the 115 most research-intensive medical schools and teaching hospitals in the United States from January 16 through May 16, 2014. The survey included questions identical to those used in 2005. Data analysis was conducted from June through October 2014. <h3>Main Outcomes and Measures</h3> The frequency of industry relationships among IRB members and the perceived effect of those relationships on IRB-related activities. <h3>Results</h3> We found no significant change in the percentage of IRB members with an industry relationship from 2005 through 2014 (2005: 37.2%; 95% CI, 32.7%-42.0%; 2014: 32.1%; 95% CI, 28.0%-36.4%;<i>P</i> = .09). However, since 2005, the percentage of members who felt another member did not properly disclose a financial relationship decreased from 10.8% (95% CI, 8.0%-14.4%) to 6.7% (95% CI, 4.7%-9.4%) (<i>P</i> = .04), as did the percentage who felt pressure from their institution or department to approve a protocol (2005: 18.6%; 95% CI, 15.0%-22.9%; 2014: 10.0%; 95% CI, 7.6%-13.0%;<i>P</i> &lt; .001). The percentage of members with a conflict of interest who voted on protocols with which they have a conflict has not changed, although the percentage who said they always disclose relationships increased significantly from 54.9% in 2005 (95% CI, 42.2%-66.9%) to 80.0% in 2014 (95% CI, 65.3%-89.4%) (<i>P</i> = .01). We also found evidence of anti-industry bias in the presentation of protocols to the IRB. <h3>Conclusions and Relevance</h3> The results show significant positive progress in the reporting and management of conflicts of interest among IRB members in academic health centers since 2005 after adjusting for other factors. Additional attention should be focused on deterring IRB members from inappropriately voting on or presenting protocols in a biased manner.
Comparison of a Needle-Type and a Microdialysis Continuous Glucose Monitor in Type 1 Diabetic Patients
Authors: Iris M. Wentholt, Marit A. Vollebregt, Augustus A. Hart, Joost B. Hoekstra, J. Hans DeVries
Journal: Diabetes Care (2005)

OBJECTIVE—We examined the reliability of two continuous glucose sensors in type 1 diabetic patients at night and during rapid glucose excursions and verified the hypothesized nocturnal hypoglycemic drift of the needle-type sensor (CGMSgold) and delay of the microdialysis sensor (GlucoDay). RESEARCH DESIGN AND METHODS—Blood was sampled overnight twice per hour in 13 patients. Rapid-acting insulin was given subcutaneously 30 min after breakfast. Sampling once per minute started 45 min after breakfast and 75 min after insulin injection for 30 min, with the aim of determining peak and nadir glucose values. Mean absolute differences (MADs) between sensor and blood glucose values were calculated. Sensor curves were modeled for all patients using linear regression. Horizontal and vertical shifts of sensor curves from the blood glucose curves were assessed. A vertical shift indicates sensor drift and a horizontal shift sensor delay. RESULTS—Drift was minimal in the needle-type and microdialysis sensors (−0.02 and −0.04 mmol/l). Mean ± SD delay was 7.1 ± 5.5 min for the microdialysis sensor (P &amp;lt; 0.001). MAD was 15.0% for the needle-type sensor and 13.6% for the microdialysis sensor (P = 0.013). After correction for the 7-min delay, the microdialysis MAD improved to 11.7% (P &amp;lt; 0.0001). CONCLUSIONS—The microdialysis sensor was more accurate than the needle-type sensor, with or without correction for a 7-min delay. In contrast to the previous version, the current needle-type sensor did not exhibit nocturnal hypoglycemic drift. Continuous subcutaneous glucose sensors are valuable adjunctive tools for glucose trend analyses. However, considering the large MADs, individual sensor values should be interpreted with caution.
Towards universal access to HIV prevention, treatment, care, and support: the role of tuberculosis/HIV collaboration
Authors: Alasdair Reid, Fabio Scano, Haileyesus Getahun, Brian Williams, Christopher Dye, Paul Nunn, Kevin M De Cock, Catherine Hankins, Bess Miller, Kenneth G Castro, Mario C Raviglione
Journal: The Lancet Infectious Diseases (2006)
Downregulation of MicroRNA miR-520h by E1A Contributes to Anticancer Activity
Authors: Jen-Liang Su, Poshen B. Chen, Ya-Huey Chen, Shang-Chih Chen, Yi-Wen Chang, Yi-Hua Jan, Xiaoyun Cheng, Michael Hsiao, Mien-Chie Hung
Journal: Cancer Research (2010)

The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A-->miRNA-520h-->PP2A/C-->IkappaB kinase-->NF-kappaB-->Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression.
Integrated coronary revascularization—minimally invasive coronary bypass combined with angioplasty: initial experience in 25 patients
Authors: H.A. Cohen, M. Zenati, B. Griffith, A.J.Conrad Smith, J.S. Lee, S. Chough, M. Izzo, Z. Jafar, M. Feldman, P.J. Counihan, A.M. Feldman
Journal: Journal of the American College of Cardiology (1998)
TISSUE INTERACTION IN THE DEVELOPMENT OF THYMUS LYMPHOCYTES
Authors: J. J. T. Owen, M. A. Ritter
Journal: The Journal of Experimental Medicine (1969)

Thymic rudiments from chick and mouse embryos have been cultured in diffusion chambers on the chick chorioallantois. In this situation their supply of blood-borne stem cells is cut off. Although rudiments from older embryos become fully lymphoid under these circumstances, primordia from early embryos fail to develop any lymphoid cells. Early chick rudiments will however develop completely if they are grafted directly to the chorioallantois where they receive a vascular supply. It is concluded that stem cells first enter the chick thymic anlage at between 6 and 7 days' incubation and the mouse thymic rudiment between 10 and 11 days' gestation. During the following few days of development there is a rapid inflow of stem cells to the rudiments. Since it is likely that stem cells, once they have entered the thymic primordium, are capable of only limited proliferation, it must be concluded that an inflow of stem cells continues once full lymphopoiesis has begun, although perhaps at a reduced rate. Finally, the importance of the interaction between stem cell and organ rudiment to normal thymic development is discussed in relation to the pathogenesis of thymic anomalies.
Activation of Tumor-Specific Splice Variant Rac1b by Dishevelled Promotes Canonical Wnt Signaling and Decreased Adhesion of Colorectal Cancer Cells
Authors: Susmita Esufali, George S. Charames, Vaijayanti V. Pethe, Pinella Buongiorno, Bharati Bapat
Journal: Cancer Research (2007)

Abstract Rac1b is a tumor-specific splice variant of the Rac1 GTPase that displays limited functional similarities to Rac1. We have shown previously a novel cross-talk between Rac1 and β-catenin, which induces canonical Wnt pathway activation in colorectal cancer cells. This prompted us to investigate if Rac1b, frequently overexpressed in colon tumors, contributes to Wnt pathway dysregulation. We show that Rac1b overexpression stimulates Tcf-mediated gene transcription, whereas depletion of Rac1b results in decreased expression of the Wnt target gene cyclin D1. Reconstitution experiments revealed an important difference between Rac1 and Rac1b such that Rac1b was capable of functionally interacting with Dishevelled-3 (Dvl-3) but not β-catenin to mediate synergistic induction of Wnt target genes. In agreement, Dvl-3 but not β-catenin caused increased activation of Rac1b levels, which may explain the functional cooperativity displayed in transcription assays. Furthermore, we show that Rac1b negatively regulates E-cadherin expression and results in decreased adhesion of colorectal cancer cells. RNA interference–mediated suppression of Rac1b resulted in reduced expression of Slug, a specific transcriptional repressor of E-cadherin, and a concomitant increase in E-cadherin transcript levels was observed. Intriguingly, mutation of the polybasic region of Rac1b resulted in complete loss of Rac1b stimulatory effects on transcription and suppressive effects on adhesion, indicating the importance of nuclear and membrane localization of Rac1b. Our results suggest that Rac1b overexpression may facilitate tumor progression by enhancing Dvl-3–mediated Wnt pathway signaling and induction of Wnt target genes specifically involved in decreasing the adhesive properties of colorectal cancer cells. [Cancer Res 2007;67(6):2469–79]
Genetic subtraction profiling identifies genes essential for Arabidopsis reproduction and reveals interaction between the female gametophyte and the maternal sporophyte
Authors: Amal J Johnston, Patrick Meier, Jacqueline Gheyselinck, Samuel EJ Wuest, Michael Federer, Edith Schlagenhauf, Jörg D Becker, Ueli Grossniklaus
Journal: Genome biology (2007)

The embryo sac contains the haploid maternal cell types necessary for double fertilization and subsequent seed development in plants. Large-scale identification of genes expressed in the embryo sac remains cumbersome because of its inherent microscopic and inaccessible nature. We used genetic subtraction and comparative profiling by microarray between the Arabidopsis thaliana wild-type and a sporophytic mutant lacking an embryo sac in order to identify embryo sac expressed genes in this model organism. The influences of the embryo sac on the surrounding sporophytic tissues were previously thought to be negligible or nonexistent; we investigated the extent of these interactions by transcriptome analysis. We identified 1,260 genes as embryo sac expressed by analyzing both our dataset and a recently reported dataset, obtained by a similar approach, using three statistical procedures. Spatial expression of nine genes (for instance a central cell expressed trithorax-like gene, an egg cell expressed gene encoding a kinase, and a synergid expressed gene encoding a permease) validated our approach. We analyzed mutants in five of the newly identified genes that exhibited developmental anomalies during reproductive development. A total of 527 genes were identified for their expression in ovules of mutants lacking an embryo sac, at levels that were twofold higher than in the wild type. Identification of embryo sac expressed genes establishes a basis for the functional dissection of embryo sac development and function. Sporophytic gain of expression in mutants lacking an embryo sac suggests that a substantial portion of the sporophytic transcriptome involved in carpel and ovule development is, unexpectedly, under the indirect influence of the embryo sac.
Pegylated Liposomal Doxorubicin Plus Docetaxel Significantly Improves Time to Progression Without Additive Cardiotoxicity Compared With Docetaxel Monotherapy in Patients With Advanced Breast Cancer Previously Treated With Neoadjuvant-Adjuvant Anthracycline Therapy: Results From a Randomized Phase III Study
Authors: Joseph A. Sparano, Anatoly N. Makhson, Vladimir F. Semiglazov, Sergei A. Tjulandin, Olga I. Balashova, Igor N. Bondarenko, Natalia V. Bogdanova, George M. Manikhas, Gennadiy P. Oliynychenko, Valery A. Chatikhine, Sen H. Zhuang, Liang Xiu, Zhilong Yuan, Wayne R. Rackoff
Journal: Journal of Clinical Oncology (2009)

To determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy.This international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m(2) (n = 373) or PLD 30 mg/m(2) followed by docetaxel 60 mg/m(2) every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety.Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively.The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.
Stage-Stratified Approach to AIDS-Related Kaposi's Sarcoma: Implications for Resource-Limited Environments
Authors: Susan E. Krown, Margaret Z. Borok, Thomas B. Campbell, Corey Casper, Dirk P. Dittmer, Mina C. Hosseinipour, Ronald T. Mitsuyasu, Anisa Mosam, Jackson Orem, Warren T. Phipps
Journal: Journal of Clinical Oncology (2014)

In an accompanying editorial, Krell and Stebbing 2 recommended that the same stage-stratified approach, yielding good outcomeswhenappliedasa(nonrandomized)strategyatasinglesiteina high-resource setting, be adopted globally, and that if cost and chemotherapy-related infrastructural barriers could be overcome, pegylated liposomal doxorubicin should be made available for all patients with advanced-stage KS in sub-Saharan Africa (SSA), where the world’s burden of HIV-associated KS is concentrated. As investigatorsinvolvedinstudyingHIV-associatedKSinSSA,webelievethat morecomplexissuesmustberigorouslyaddressedbeforerecommendations for optimal treatment in this setting can be made. The editorial 2 does not consider significant differences between patientsinresource-richandresource-limitedsettingsthatmayinflu
Preferential light absorption in atheromas in vitro. Implications for laser angioplasty.
Authors: M R Prince, T F Deutsch, M M Mathews-Roth, R Margolis, J A Parrish, A R Oseroff
Journal: Journal of Clinical Investigation (1986)

Laser angioplasty, the in situ ablation of arterial obstructions with laser radiation, has been demonstrated in animal models and early clinical trials. A problem with this technique, however, is the possibility of thermal damage to adjacent or underlying normal tissues that also absorb the radiation. Using a spectrophotometer with an integrating sphere and a specially constructed tunable-dye laser-based spectrophotometer, we evaluated the transmittance and remittance of human cadaveric atheromas and adjacent normal aorta from 250 to 1,300 nm to identify wavebands where there is preferential light absorption by atheromas. Data were analyzed by both the Kubelka-Munk formalism and a Beer's law model. Both methods indicate that atheromas absorb more than normal aorta between 420 and 530 nm. At 470 nm the average Kubelka-Munk absorption coefficient of atheromas from 10 cadavers was 54 +/- 9 cm-1 compared with 26 +/- 6 cm-1 for normal aortic specimens from seven cadavers. Yellow chromophores responsible for the atheroma absorbance were extractable with xylenes. Thin-layer chromatography and absorption spectra identified the extracted chromophores as predominantly consisting of a mix of carotenoids, which are known constituents of atheromatous lesions. Preferential absorption of blue light by carotenoids in atheromas may permit selective ablation of atheromatous obstructions with appropriate pulses of laser radiation.
A High Serum Matrix Metalloproteinase-2 Level Is Associated with an Adverse Prognosis in Node-Positive Breast Carcinoma
Authors: Sirpa Leppä, Tiina Saarto, Leena Vehmanen, Carl Blomqvist, Inkeri Elomaa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to determine whether serum matrix metalloproteinase (MMP) -2 and MMP-9 levels could predict overall and disease-free survival in primary node-positive breast cancer. Experimental Design: MMP-2 and MMP-9 levels were quantitatively measured in serum after surgery from 133 patients with primary node-positive breast cancer using enzyme-linked immunoassays. All of the patients received adjuvant therapy, postmenopausal endocrine treatment (tamoxifen or toremifen for 3 years) and premenopausal six cycles of CMF chemotherapy. The follow-up time for all of the patients was 5 years. Results: Overall survival (OS) and disease-free survival (DFS) rates were better among patients with low MMP-2 levels than in patients with high levels (OS, 91% versus 75%, P = 0.020; DFS, 82% versus 58%, P = 0.005). The appearance of bone and visceral metastases was also significantly lower in patients with low serum MMP-2 levels (bone metastases, 10% versus 23%, P = 0.050; visceral metastases, 12% versus 34%, P = 0.018). The prognostic value of MMP-2 levels was most pronounced among a subgroup of estrogen receptor-positive patients (OS, 96% versus 78%, P = 0.052; DFS, 85% versus 58%, P = 0.014), whereas no significant difference was found among estrogen receptor-negative patients (OS, 73% versus 69%, P = 0.25; DFS, 73% versus 63%, P = 0.32). In multivariate analysis, MMP-2 level together with nodal status (NS), progesterone receptor (PgR), and tumor size (T) remained independent predictors for DFS (NS, P = 0.002; PgR, P = 0.004; T, P = 0.023; MMP2, P = 0.039) and OS (NS, P = 0.0002; PgR, P = 0.004; T, P = 0.004; MMP2, P = 0.032). MMP-9 levels did not correlate with survival. Conclusions: The results suggest that serum postoperative MMP-2 level is a predictor of DFS and OS, and could help to stratify breast cancer patients with primary node-positive disease into low- and high-risk groups.
Risk of Second Cancer in Patients With Hairy Cell Leukemia: Long-Term Follow-Up
Authors: Massimo Federico, Pier Luigi Zinzani, Antonio Frassoldati, Marco Vinceti, Alessia Modè, Luciana Annino, Teodoro Chisesi, Guido Pagnucco, Rosangela Invernizzi, Mauro Spriano, Luigi Resegotti, Maurizio Bendandi, Eugenio E. Damasio
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The purpose of the present study was to assess the risk of second cancers in patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: We investigated the incidence of additional cancers in those patients registered in the nationwide registry of the Italian Cooperative Group for the Study of HCL, asking the cooperating centers for additional information on initial and subsequent therapies and on time and type of second malignancies, if they developed. Here we report the final results of this survey, consisting of 54 cases of second malignancies (excluding nine cases of epithelial skin cancer) which developed in 54 patients of 1,022 with adequate follow-up. RESULTS: The cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively. The incidence of second malignancies was not significantly higher than the expected rate (standardized incidence ratio [SIR], 1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of non-Hodgkin’s lymphoma in the entire cohort was 5.3 (95% CI, 1.9 to 11.5). Second malignancies occurred in eight (4.7%) of 386 patients who never received interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line therapy. These differences were not statistically significant. Analysis of the separate calendar periods did not reveal any particular trends with respect to variations in SIR. CONCLUSION: The present study does not support the suspicion that patients with HCL are at increased risk of additional second malignancies, although the incidence of lymphoid neoplasms was significantly higher than expected. In addition, our data indicate that IFN therapy did not exert an oncogenic effect in such patients.
The Role of Pediatricians in Increasing Physical Activity in Youth
Authors: Kathleen F. Janz, Katrina L. Butner, Russell R. Pate
Journal: JAMA Pediatrics (2013)

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