tbuckley/cabot-search huggingface dataset:
Randomized, phase II study of bevacizumab with mFOLFOX6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: Resectability and safety in OLIVIA.
Authors: Thomas Gruenberger, John A. Bridgewater, Ian Chau, Pilar Garcia Alfonso, Michel Rivoire, Susan Lasserre, Daniel Waterkamp, Rene Adam
Journal: Journal of Clinical Oncology (2013)

3619^ Background: Patients (pts) with unresectable colorectal cancer liver-only metastases (CLMs) may become resectable after downsizing by chemotherapy (CT) and biologic therapy. Although biologics are thought to improve overall response rate (ORR), the optimal combination of a biologic and CT for resectability remains uncertain. Methods: This open-label, multinational study randomized pts with unresectable CLMs to bevacizumab (BEV) plus mFOLFOX6 or FOLFOXIRI q2w. Resectability was assessed by interdisciplinary review. Unresectability was defined as ≥1 of the following: no possibility of upfront R0/R1 resection of all hepatic lesions, &lt;30% estimated residual liver after resection, or disease in contact with major vessels of the remnant liver. The primary end point was overall resection rate (R0/R1/R2). Results: From 10/2008 to 12/2011, 80 pts were randomized to mFOLFOX6-BEV (n=39) or FOLFOXIRI-BEV (n=41). Pt characteristics were male (46% vs 71%), aged ≥60 y (36% vs 63%), ECOG PS of 1 (23% vs 37%), and ≥5 target CLMs (49% vs 49%) in the mFOLFOX6-BEV and FOLFOXIRI-BEV arms, respectively. Resection rate, ORR, and progression-free survival (PFS) data are shown (Table). Grade ≥3 adverse events (AEs) occurred in 84% and 95% of pts receiving mFOLFOX6-BEV and FOLFOXIRI-BEV, respectively, and included neutropenia (35% vs 48%; febrile, 8% vs 13%) and diarrhea (14% vs 28%). Conclusions: The results suggest that FOLFOXIRI-BEV improves resection rates, ORR, and long-term outcomes vs mFOLFOX6-BEV in pts with initially unresectable CLMs. CT- and BEV-related AEs occurred with the expected incidence and were manageable. FOLFOXIRI-BEV should be evaluated further as an effective regimen to downsize CLMs. Clinical trial information: NCT00778102. [Table: see text]
BCR-ABL1-like Acute Lymphoblastic Leukemia Is Associated with IKZF1 and JAK2 Alterations and inferior Outcome in Adults
Authors: Tobias Herold, Stephanie Schneider, Klaus H Metzeler, Martin Neumann, Luise Hartmann, Nikola P Konstandin, Philipp A Greif, Kathrin Bräundl, Bianka Ksienzyk, Natalia Huk, Irene Schneider, Evelyn Zellmeier, Vindi Jurinovic, Ulrich Mansmann, Wolfgang Hiddemann, Stefan K Bohlander, Karsten Spiekermann, Dieter Hoelzer, Claudia D Baldus, Martin Dreyling, Nicola Gökbuget
Journal: Blood (2014)
Molecular RB1 gene detection of minimal residual disease in metastatic retinoblastoma
Authors: Helen S. L. Chan, Diane Rushlow, John Doyle, James Williams, Esteban M. Abella, Elise Héon, Brenda L. Gallie
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Purpose: Cure of metastatic retinoblastoma (RB) depends on chemotherapy with or without radiation to first reduce the systemic and central nervous system tumor load, followed by marrow-ablative chemotherapy and marrow rescue with stem cell transplant. We propose that the search for RB1 mutant alleles may be useful for assessing the completeness of the remission at the molecular level. This also allows monitoring for the absence of contaminating tumor cells in the stem cells harvested prior to transplant. Method: We developed a highly sensitive allele-specific PCR assay, to detect RB1 mutant alleles in the tumor cells, which are not present in the normal cells, in two children with metastatic but non-germline RB. Child A, age 2.6 years, had tumor infiltrating the orbit and extending intracranially with tumor cells in the cerebrospinal fluid (CSF), 1.6 years after enucleation of one eye for unilateral RB. Child B, age 2.5 years, had tumor infiltrating soft tissues and bone at the base of the skull with bone marrow involvement, 0.5 years after enucleation of one eye for unilateral RB. Results: RB1 mutations of both recurrent tumors were first identified by sequence analysis. The tumor of Child A was homozygous for R251X, and the tumor of Child B was homozygous for R358X. The allele-specific PCR assay was then used to detect the tumor RB1 mutant alleles. Both children had no tumor RB1 mutant alleles detectable in the normal cells in their peripheral blood. In Child A, the assay resolution was adequate to detect the R251X mutation at as low as 1:12,800 dilution, but serial CSF samples during and after chemotherapy showed no detectable R251X mutant. In Child B, the R358X mutation could be detectable at the 1:500 dilution level in the initial bone marrow sample, but serial bone marrow samples during and after chemotherapy showed no detectable R358X mutant. The peripheral blood stem cells harvested from both children also did not show their specific RB1 mutant alleles. Absence of RB1 mutant signals in post-chemotherapy CSF or bone marrow samples and the harvested stem cells supported the suitability of both children proceeding to consolidation with autologous stem cell transplant aimed at curing their metastatic RB. Conclusion: Molecular assaying for the tumor-specific RB1 mutations is complementary to conventional cytological and immunohistochemical evaluations of RB involvement of the CSF and bone marrow. This novel diagnostic tool is very sensitive for assessing minimal residual disease, detecting extraocular RB tumor cells in numbers much lower than possible by conventional methods. Molecular management holds particular promise for evaluating the efficacy of systemic treatment strategies for metastatic RB.
Abstract 2566: Intravascular Ultrasound Guidance may Modify Neointimal Coverage Following Sirolimus-Eluting Stent Implantation
Authors: Fusako Sera, Masaaki Uematsu, Jun-ichi Kotani, Masaki Awata, Takakazu Morozumi, Tetsuya Watanabe, Toshinari Onishi, Osamu Iida, Hitoshi Minamiguchi, Kenji Kawamoto, Masamichi Yano, Kuniyasu Ikeoka, Shin Okamoto, Nobuaki Tanaka, Haruyo Yasui, Takayuki Ishihara, Tomoharu Dohi, Shinsuke Nanto, Seiki Nagata
Journal: Circulation (2008)

Background: Although sirolimus-eluting stent (SES) has significantly reduced in-stent restenosis, insufficient neointimal coverage may result in adverse outcomes. Intravascular ultrasound (IVUS) guided percutaneous coronary intervention improves the patency of bare-metal stents at follow-up. IVUS guidance at the time of SES implantation may also optimize neointimal coverage following stenting. Methods: We evaluated 55 SES implanted lesions using both angioscopy and IVUS at follow-up (12±7 months). The lesions were divided into two groups: IVUS guided implantation (group I, n=40); angiography alone (group A, n=15). Neointimal coverage was classified into 4 grades by angioscopy: no coverage ( G0 ); struts bulged into the lumen, but were covered and still translucently visible ( G1 ); struts were visible, but not clear ( G2 ); and struts were embedded and invisible ( G3 ). Minimal stent area (MSA), external elastic membrane (EEM), lumen cross-sectional area (CSA) and plaque burden were measured by IVUS at follow up. Both proximal and distal references were used. Stent expansion was assessed by stent expansion index (SEI) = MSA/reference EEM CSA. Results: Lesion and procedural characteristics were similar between the groups both at stent implantation and at follow-up. Although the post-procedural quantitative angiographic data were not different between the groups, distribution of the angioscopic grades of neointimal coverage at follow-up were significantly different (group A = 1.0±0.5 grades versus group I = 1.5±0.6 grades, p=0.01). IVUS measurements at follow up showed larger plaque burden at the proximal reference sites (54±12% versus 46±9%, p=0.02) and smaller SEI (0.35±0.09 versus 0.46±0.10, p=0.001) in group A than in group I. Conclusions: IVUS guidance at the time of SES implantation may modify angioscopic grades of the neointimal coverage, possibly optimizing neointimal coverage and preventing thrombosis.
Stretch-Sensitive KCNQ1Mutation
Authors: Robyn Otway, Jamie I. Vandenberg, Guanglan Guo, Anthony Varghese, M. Leticia Castro, Jian Liu, JingTing Zhao, Jane A. Bursill, Ken R. Wyse, Haley Crotty, Olivia Baddeley, Bruce Walker, Dennis Kuchar, Charles Thorburn, Diane Fatkin
Journal: Journal of the American College of Cardiology (2007)
WITHDRAWN: Carnosic acid protects photoreceptor against degeneration in Pde6 mice through activating Nrf2 pathway
Authors: Kai Kang, Matthew J. Tarchick, Minzhong Yu
Journal: Acta Pharmaceutica Sinica B (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Abstract 4370: Ultrasound Balloon Catheter for Mitral Annulus Shrinkage in a Canine Model: Percutaneous Treatment for Mitral Regurgitation
Authors: Atsushi Ikeda, Hiroshi Nakagawa, Jan V Pitha, Eugene Jung, Yong Zou, Tushar Sharma, Ralph Lazzara, Raoul Bonan, Warren M Jackman
Journal: Circulation (2009)

Background: The purpose of this study was to determine whether circumferential endocardial ultrasound (US) energy applications around the mitral annulus (MA) can produce heat-induced shrinkage of M...
Shared Genetic Risk for Sclerosis of Valves and Vessels
Authors: Gerald W. Dorn
Journal: New England Journal of Medicine (2013)

Leonardo da Vinci was the first person to describe the relationship between aortic-valve structure and blood flow. Rejecting Galen's notions of diastolic suction, da Vinci recognized that the heart was a muscular pump. As a hydraulic engineer, he carefully defined the structures of all four heart valves1 and investigated the effects of various valve anatomies on blood flow. Da Vinci created lost-wax plaster casts of left ventricles and aortas of large animals; by blowing molten glass into these molds, he created accurate model aortas. Da Vinci mated these water-filled glass aortas to bulls' hearts and observed normal aortic-valve motion in . . .
Outbreak of 2009 pandemic influenza A (H1N1) at a school - Hawaii, May 2009.
Authors: S. Y. Park, M. N. Nakata, J. L. Elm, M. R. Ching-Lee, R. Rajan, C. A. Giles, H. Hua, R. Kanenaka, M. A. Ando, J. E. Sasaki, C. Le, A. Manuzak, M. Wong, C. A. Whelan, R. Ueki, R. Sciulli, G. Kunimoto, R. Lee, R. Gose, T. Chen, M. V. Sreenivasan
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
CCR6 is a receptor for CCL18 expressed on human lung fibroblasts from IPF lungs
Authors: Gernot Zissel, Kerstin Höhne, Annett Kilic, Corinna Maier, Till Ploenes, Antje Prasse, Martin Trepel, Hermann Eibel, Joachim Müller-Quernheim
Journal: European Respiratory Journal (2011)

Background:  CCL18 is a chemokine released by alternatively activated macrophages binding to a yet unknown receptor. CCL18 induces collagen synthesis by fibroblasts thus indicating that the putative CCL18 receptor is expressed by human lung fibroblasts.   Methods:  To identify the receptor we screened a phage display library; the expression of the receptor was confirmed using conventional antibodies. FGF2 Release was measured by ELISA and expression of collagen and α-smooth muscle actin was estimated by quantitative PCR.   Results:  Phage-display experiments pointed to the CC-chemokine receptor 6 (CCR6) as CCL18-receptor. Staining lung tissue indicated CCR6 expression by AEC-II and fibroblasts in IPF lungs but not in tumour-free areas of resected lungs from SqC-patients. CCR6 was expressed by lung fibroblast lines derived from IPF lungs but was almost absent in lines from healthy areas of lung tissue from squamous carcinoma (SqC) patients. Spontaneous release of fibroblast growth factor 2 (FGF2) was very low in SqC-fibroblasts (71±25pg/ml) but significantly increased in IPF-fibroblasts (603±463pg/ml). Stimulation of fibroblasts with CCL18 induced a non-significant increase in FGF2 release in SqC-fibroblast lines (143±77pg/ml) but led to a significant increase in IPF lines (1194±601pg/ml) which was blocked by an anti-CCR6 antibody in IPF-fibroblast lines (783±632pg/ml) but not in SqC-lines (112±66pg/ml). Likewise, CCL18 induced an up-regulation of collagen I (coll-1) and αSMA expression. Again, induction of coll-I and αSMA expression was blocked by an anti-CCR6 antibody.   Conclusion:  Our data indicate that stimulatory effects of CCL18 on human lung fibroblasts are mediated via CCR6 (patent pending).
Abstract 3612: Lipoprotein(a), Factor V Leiden Mutation and the Risk of Future Venous Thromboembolism in Women
Authors: Jacqueline S Danik, Robert J Glynn, Julie E Buring, Paul M Ridker
Journal: Circulation (2007)

Background: Venous thromboembolism (VTE) results from interactions of many risk factors, both genetic and environmental. Factor V Leiden (FVL) is a prevalent genetic risk factor for VTE. Lp(a), a h...
Using Supervised Principal Components Analysis to Assess Multiple Pollutant Effects
Authors: Steven Roberts, Michael A. Martin
Journal: Environmental Health Perspectives (2006)

Many investigations of the adverse health effects of multiple air pollutants analyze the time series involved by simultaneously entering the multiple pollutants into a Poisson log-linear model. This method can yield unstable parameter estimates when the pollutants involved suffer high intercorrelation; therefore, traditional approaches to dealing with multicollinearity, such as principal component analysis (PCA), have been promoted in this context.A characteristic of PCA is that its construction does not consider the relationship between the covariates and the adverse health outcomes. A refined version of PCA, supervised principal components analysis (SPCA), is proposed that specifically addresses this issue.Models controlling for longterm trends and weather effects were used in conjunction with each SPCA and PCA to estimate the association between multiple air pollutants and mortality for U.S. cities. The methods were compared further via a simulation study.Simulation studies demonstrated that SPCA, unlike PCA, was successful in identifying the correct subset of multiple pollutants associated with mortality. Because of this property, SPCA and PCA returned different estimates for the relationship between air pollution and mortality.Although a number of methods for assessing the effects of multiple pollutants have been proposed, such methods can falter in the presence of high correlation among pollutants. Both PCA and SPCA address this issue. By allowing the exclusion of pollutants that are not associated with the adverse health outcomes from the mixture of pollutants selected, SPCA offers a critical improvement over PCA.
Impact Of Prognostically Detrimental Mutations (ASXL1, EZH2, SRSF2, IDH1/2) On Outcomes In Patients With Myelofibrosis Treated With Ruxolitinib In COMFORT-II
Authors: Paola Guglielmelli, Flavia Biamonte, Lisa Pieri, Giada Rotunno, Chiara Paoli, Rajmonda Fjerza, Enrico Tagliafico, Rossella Manfredini, Valentina Artusi, Elena Tenedini, Lucia Artuso, Isabella Bernardis, Viktoriya Stalbovskaya, Matthew Squires, Claire N Harrison, Alessandro M Vannucchi
Journal: Blood (2013)
P0926 : Representation of human non-alcoholic fatty liver disease in murine models
Authors: A. Teufel, T. Itzel, W. Erhardt, M. Brosch, X.Y. Wang, Y.O. Kim, W. von Schönfels, A. Herrmann, S. Brückner, F. Stickel, T. Chavakis, C. Hellerbrand, T. Becker, S. Schreiber, C. Schafmayer, D. Schuppan, J. Hampe
Journal: Journal of Hepatology (2015)
Abstract 3437: Integrin-linked-kinase Binding Proteins Are Essential Components Of The Cardiac Mechanical Strech Sensor
Authors: Andreas Hartkopf, Inken Huttner, Tillman Dahme, Benjamin Meder, Britta Vogel, Alexander Hess, Hugo A Katus, Wolfgang Rottbauer
Journal: Circulation (2008)

The cardiac strech sensor enables the heart to adapt its force of contraction to continually changing demands. We recently identified in the zebrafish mutant main squeeze (msq) Integrin-Linked-Kinase (ILK) as a component of this strech sensor. Mutations in zebrafish ilk lead to down-regulation of stretch responsive cardiac genes and cause progressive heart failure. Antisense-mediated abrogation of zebrafish β-parvin, which forms complexes with ILK, phenocopies ilk mutant zebrafish. We here describe two novel ILK-binding-proteins, acting in concert with ILK to control cardiac contractility. In a yeast-to-hybrid-screen with a cardiac specific library we identified two ILK-binding proteins (ILK-bp-1 and ILK-bp-2). Just as we have recently shown for ILK, ILK-bp-1/2 are highly expressed in the zebrafish heart and localize at the sarcomeric Z-disc. To reveal the in vivo function of ILK-bp-1/2 we performed knock-down studies on zebrafish with antisense oligonucleotide injection. Similar to the phenotype of ILK-deficient zebrafish, the knock down of ILK-bp-1/2 leads to loss of cardiac contractility and, as shown by in-situ-hybridisation, to down-regulation of the stretch responsive gene anf. We analysed the ILK-bp-1/2 morphant hearts structurally and ultra-structurally. Just as we have recently shown for ilk deficient hearts, we found that their morphogenesis and myofibrillogenesis are normal, indicating that knock-down of ILK-binding-proteins does not induce a structural but rather a functional heart defect. Taken together, these results indicate, that next to β-parvin other ILK-binding proteins play important roles in the control of heart contractility. ILK and ILK-bp-1/2 act in concert to enable the heart to adapt itself to continually changing demands.
Abstract 475: Relationship Between Oxidized Phospholipid Content On Apolipoprotein B-100 Particles, Statin Therapy and Atheroma Volume: Observations From The REVERSAL Study
Authors: Seung-Hyuk Choi, Andrew Chae, Elizabeth R Miller, Fady Ntanios, Anthony N DeMaria, Steven E Nissen, Joseph L Witztum, Sotirios Tsimikas
Journal: Circulation (2007)

Background: Increased levels of oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB) are associated with angiographically defined coronary artery disease, progression of carotid atherosclerosis and predict new cardiovascular events. Interestingly, OxPL/apoB levels increase in response to low-fat diets or therapy with different statins. Furthermore, during dietary-induced atherosclerosis regression in animals, increases in plasma OxPL/apoB levels are associated with reduced OxPL content in atheromatous plaques, suggesting a flux of OxPL from the vessel wall to the lumen. Methods: In a subgroup of 220 patients from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we measured several biomarkers of oxidized LDL (OxLDL), including OxPL/apoB and IgG and IgM apoB-100 immune complexes (apoB-IC) and OxLDL autoantibodies, at baseline and after 18 months of treatment with atorvastatin (AT) 80mg/d or pravastatin (PR) 40mg/d. Measures of total atheroma volume (TAV) and vessel remodeling with intravascular ultrasound (IVUS) were analyzed. Results: Compared to baseline values, OxPL/apoB levels increased 58.5% (P&lt;0.0001) in response to AT and 32.7% (P&lt;0.0001) in response to PR. In contrast, IG apoB-IC, IgM apoB-IC and IgM OxLDL autoantibodies were significantly reduced by both AT and PR (p-value: range 0.04 – 0.0001). However, no differences in OxLDL biomarkers were noted between the AT and PR groups. In the entire group, there were no correlations between TAV and vessel remodeling with any OxLDL biomarkers at baseline or 18 months. Conclusion: Statin therapy results in significant increases in OxPL/apoB and decreases in immune complexes and OxLDL autoantibodies. However, these measures do not correlate with atheroma volume or vessel wall remodeling measured by IVUS. Whether statin-induced changes in plaque characteristics, such as the lipid core, correlate with plasma OxLDL biomarkers remains to be determined.
Does the BMJ attempt independent ascertainment?
Authors: L. Whitaker
Journal: BMJ (1996)

time, which contrasts with a finding of an earlier study by them of similar duration, which indicated that the slope of the fall in glomerular filtration flattens if antihypertensive treatment is continued for a long time.'Because of possible hidden biases in observational studies it is premature to recommend special treatment for patients with diabetic nephropathy who are homozygous for the deletion polymorphism until prospective randomised studies have been carried out.
Abstract 2232: Survival Is Decreased If Ambulance Dispatchers Do Not Recognize Out-of-Hospital Cardiac Arrest
Authors: Jocelyn Berdowski, Fred Beekhuis, Rudolph W Koster
Journal: Circulation (2007)

Introduction Exact content of 112 emergency calls for suspected cardiac arrest (CA) are rarely analyzed. The purpose of this study was to investigate if not recognizing a CA by emergency medical dispatchers influences survival rates. Methods This was a prospective, observational study. During 8 months, all digitalized voice recordings of consecutive 112 high priority emergency calls were collected from the Amsterdam dispatch center and audited for CA recognition, time to recognition of CA and telephone CPR. Also, description of breathing and consciousness that the caller uses to describe a CA were scored. Actual presence of CA during call was assessed from the ambulance crew report. Calls were placed by laypersons on site, not involving trauma. Exclusion criteria were calls by a professional, by the victim or when victim was known to be conscious. Time recordings of call, dispatching and arrival were generated automatically. Survival after 3 months was taken as the primary endpoint. Results Results are shown in table 1 . In 8 months, out of 11.329 calls, 285 involved patients in CA. Of these, 203 were recognized during the call; the remaining 82 cases (29%) were only diagnosed on site. Recognizing CA resulted in faster dispatch and earlier arrival on scene. When not recognizing CA, the dispatchers did not ask the caller about respiration in over 50% of the calls. Not recognizing the CA was associated with no telephone CPR, and significantly lower three-month survival. Conclusion If the dispatcher did not recognize the CA, no CPR instruction is given. The ambulance is dispatched less rapidly and arrives a median of 2 minutes later at the scene. Both factors may contribute to the lower survival rates. Consequent interrogating the caller about the patientâ™s consciousness and respiration could improve CA recognition. In conclusion, not only early call, but also early recognition of a CA by dispatcher contributes to the survival after CA. Table 1: A comparison between calls where the dispatcher did and did not recognize CA
Obstructive Sleep Apnea and the Risk of Sudden Cardiac Death
Authors: Apoor S. Gami, Eric J. Olson, Win K. Shen, R. Scott Wright, Karla V. Ballman, Dave O. Hodge, Regina M. Herges, Daniel E. Howard, Virend K. Somers
Journal: Journal of the American College of Cardiology (2013)
Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil
Authors: Kuldev Singh, Kala Mehta, Naazli M Shaikh, James C Tsai, Marlene R Moster, Donald L Budenz, David S Greenfield, Philip P Chen, John S Cohen, George S Baerveldt, Saad Shaikh
Journal: Ophthalmology (2000)