tbuckley/cabot-search huggingface dataset:
Prognosis of Patients With Breast Cancer: Causes of Death and Effects of Time Since Diagnosis, Age, and Tumor Characteristics
Authors: Edoardo Colzani, Annelie Liljegren, Anna L.V. Johansson, Jan Adolfsson, Henrik Hellborg, Per F.L. Hall, Kamila Czene
Journal: Journal of Clinical Oncology (2011)

The proportion of women living with a diagnosis of breast cancer in developed countries is increasing. Because breast cancer-specific deaths decrease with time since diagnosis, it is important to assess the burden of other causes of death in women diagnosed with breast cancer.Different causes of death within 10 years from diagnosis were assessed in 12,850 women younger than 75 years of age with stage 1 to 3 breast cancer diagnosed in Stockholm and Gotland regions 1990 to 2006. Flexible parametric survival models were used to estimate hazard ratios over time since diagnosis by tumor characteristics and age at diagnosis.The proportion of deaths attributed to breast cancer ranged from 95.0% among women younger than age 45 years at diagnosis to 44.5% among women age 65 to 74 years. The proportions of circulatory system-specific deaths and deaths resulting from other causes increased with older age at diagnosis. Patients with one to three positive lymph nodes were more likely to die as a result of breast cancer during the first 10 years of follow-up compared with women without positive lymph nodes. Women with estrogen receptor (ER) -positive tumors had the same risk of dying as a result of breast cancer 5 years after diagnosis compared with women with ER-negative tumors.Lymph node negativity is an important long-term predictor of more favorable prognosis. The nature of the relationship between ER status and risk of dying as a result of breast cancer after 5 years of follow-up requires further investigation. Circulatory system diseases are an important cause of death, especially in women diagnosed with breast cancer at an older age.
Phenotypic analysis of murine long-term hemopoietic reconstituting cells quantitated competitively in vivo and comparison with more advanced colony-forming progeny.
Authors: M Trevisan, N N Iscove
Journal: The Journal of Experimental Medicine (1995)

Early hemopoietic precursors have been extensively studied using short-term assays based on colony formation or in vivo reconstitution that do not run beyond a few weeks. However, little information is available on the phenotype of the stem cells that are detectable in 6-12-mo transplantation assays, and their relationship to cells detected in short-term assays is not known. In this study, we investigated the phenotype and separability by cell sorting of a spectrum of hemopoietic precursor cells in normal adult mouse marrow, including cells quantitated in a 1 yr competitive transplantation assay in vivo as well as in short-term colony assays in vitro and in vivo. Two principal findings emerged. The first was that cells detected in a variety of short-term assays--CFU-S12 (spleen colony-forming cells), CFCmulti (multilineage colony-forming cells), pre-CFCmulti (precursors of CFCmulti), CFC-E/Mg (erythroid/megakaryocyte CFC) and CFC-G/M (granulocyte/macrophage CFC)--were phenotypically similar and could not be separated from one another using a panel of markers useful in segregating them from more differentiated cells, including buoyant density, sedimentation velocity, adhesiveness to plastic, light scatter, high rhodamine-123 retention, and expression of surface wheat-germ agglutinin (WGA)-binding carbohydrate, H-2K, CD45, AA4.1, heat stable antigen (HSA), CD71, and Ly6A/Sca-1 antigens. Long-term reconstituting (LTR) cells quantitated in vivo differed little from the other precursors in expression of many of the above markers. However, they differed somewhat in lower sedimentation velocity and lower expression of WGA-binding surface carbohydrate, and most strikingly in their conditional adhesiveness to plastic, very low retention of Rh123 and high level expression of Ly6A/Sca-1, to a degree that would permit the quantitative separation of the two precursor classes from each other. The results provide a comprehensive characterization of LTR cells measured to 12 mo in vivo and a direct and quantitative analysis of their separation from cells detected in colony assays.
Computational Prediction of Rice (<i>Oryza Sativa</i>) miRNA Targets
Authors: Sunil Archak, J. Nagaraju
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract Bioinformatic approaches have complemented experimental efforts to inventorize plant miRNA targets. We carried out global computational analysis of rice (Oryza sativa) transcriptome to generate a comprehensive list of putative miRNA targets. Our predictions (684 unique transcripts) showed that rice miRNAs mediate regulation of diverse functions including transcription (41%), catalysis (28%), binding (18%), and transporter activity (11%). Among the predicted targets, 61.7% hits were in coding regions and nearly 72% targets had a solitary miRNA hit. The study predicted more than 70 novel targets of 34 miRNAs putatively regulating functions like stress-response, catalysis, and binding. It was observed that more than half (55%) of the targets were conserved between O. sativa indica and O. sativa japonica. Members of 31 miRNA families were found to possess conserved targets between rice and at least one of other grass family members. About 44% of the unique targets were common between two dissimilar miRNA prediction algorithms. Such an extent of cross-species conservation and algorithmic consensus confers confidence in the list of rice miRNA targets predicted in this study.
Urine IL-18 Is an Early Diagnostic Marker for Acute Kidney Injury and Predicts Mortality in the Intensive Care Unit
Authors: Chirag R. Parikh, Edward Abraham, Marek Ancukiewicz, Charles L. Edelstein
Journal: Journal of the American Society of Nephrology (2005)

Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-18 is increased in human AKI. Thus, whether urine IL-18 is an early diagnostic marker of AKI was investigated. A nested case-control study was performed within the Acute Respiratory Distress Syndrome (ARDS) Network trial. AKI was defined as an increase in serum creatinine by at least 50% within the first 6 d of ARDS study enrollment. A total of 400 urine specimens that were collected on study days 0, 1, and 3 of the ARDS trial were available from 52 case patients and 86 control patients. The data were analyzed in a cross-sectional manner and according to the time before development of AKI. The median urine IL-18 levels were significantly different at 24 and 48 h before AKI in case patients as compared with control patients. On multivariable analysis, urine IL-18 values predicted development of AKI 24 and 48 h later after adjustment for demographics, sepsis, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score, serum creatinine, and urine output. Urine IL-18 levels of >100 pg/ml are associated with increased odds of AKI of 6.5 (95% confidence interval 2.1 to 20.4) in the next 24 h. On diagnostic performance testing, urine IL-18 demonstrates an area under the receiver operating characteristic curve of 73% to predict AKI in the next 24 h. The urine IL-18 values were also significantly different between survivors and nonsurvivors (P < 0.05), and on multivariable analysis, the urine IL-18 value on day 0 is an independent predictor of mortality. Urinary IL-18 levels can be used for the early diagnosis of AKI. Urine IL-18 levels also predict the mortality of patients who have ARDS and are in the intensive care unit.
Natural History and Management of Aortocoronary Saphenous Vein Graft Aneurysms
Authors: F. Daniel Ramirez, Benjamin Hibbert, Trevor Simard, Ali Pourdjabbar, Kumanan R. Wilson, Rebecca Hibbert, Mustapha Kazmi, Steven Hawken, Marc Ruel, Marino Labinaz, Edward R. O'Brien
Journal: Circulation (2012)

D espite ongoing advances in percutaneous revasculariza- tion, coronary artery bypass grafting (CABG) continues to be performed in a large number of patients, with Ͼ400 000 operations reported in 2007 in the United States alone. 1 Although arterial conduits are generally preferred, saphenous vein grafts (SVGs) continue to be used regularly.First described by Riahi and colleagues 2 in 1975, aneurysmal dilatation of aortocoronary SVGs remains a rare yet widely reported phenomenon.Indeed, subsequent literature on the topic consists almost exclusively of case reports and small case series.Thus, the precise incidence of aortocoronary SVG aneurysms (SVGAs) remains difficult to ascertain, although in 1 case series, an incidence of 0.07% was estimated from a review of Ͼ5500 grafts at a single institution. 3However, this likely underestimates the true number because SVGAs often remain clinically silent and no guidelines exist to screen for their development.Given the infrequent identification of SVGAs, our current understanding of the epidemiology and pathogenesis of these aneurysms remains limited.Aneurysms are generally defined as a focal dilatation of vessels Ͼ1.5 times the proximal reference diameter; however, aneurysmal dilatation of aortocoronary SVGs has led to "giant" aneurysm formation, with reports of cases exceeding 10 cm. 4 -6 SVGAs are often incidentally identified on imaging, but cases of rupture, 7 fistula formation with neighboring anatomy, 8 and hemodynamic compromise resulting from compression of adjacent cardiac and vascular structures have been reported. 9To date, 2 reviews have been published that briefly summarize 108 cases of SVGAs. 10,11Traditionally, their management has been surgical-generally resection of the aneurysm with or without bypass of the affected territory.However, with refinement of percutaneous techniques, including the use of Amplatzer devices, covered stents, and arterial coiling, the management options for affected patients From the Divisions of Cardiology (
TUMOR NECROSIS FACTOR RECEPTOR AND Fas SIGNALING MECHANISMS
Authors: D. Wallach, E. E. Varfolomeev, N. L. Malinin, Yuri V. Goltsev, A. V. Kovalenko, M. P. Boldin
Journal: Annual Review of Immunology (1999)

▪ Abstract Four members of the tumor necrosis factor (TNF) ligand family, TNF-α, LT-α, LT-β, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor (CD120b), the lymphotoxin beta receptor (LTβR), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune response functions. Of these, the most thoroughly studied are cell death induction and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signaling by the TNF system and CD95. The downstream signaling molecules identified so far—caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-κB activation cascade—mediate the effects of other inducers as well. However, the molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
PGD in female carriers of balanced Robertsonian and reciprocal translocations by first polar body analysis
Authors: M. Durban
Journal: Human Reproduction Update (2001)

Preimplantation genetic diagnosis (PGD) using the first polar body (1PB) is a modality of PGD that can be used when the woman is the carrier of a genetic disease or of a balanced chromosomal reorganization. PGD using 1PB biopsy in carriers of balanced chromosome reorganizations has not become generalized. Here, we describe our experience based on the analysis of unfertilized or fresh, non-inseminated control oocytes, by fixing separately the 1PB and the corresponding oocyte, and on the study of six clinical cases of PGD using 1PB biopsy (four Robertsonian translocations and two reciprocal translocations). In fresh oocytes, the chromosome morphology of the 1PB was well preserved, and the results were always concordant for each oocyte–1PB pair. This indicates that the 1PB can be reliably used for the diagnosis of chromosome reorganizations. In these studies the technical problems encountered when performing PGD using 1PB biopsies for chromosome studies are also addressed. Three different strategies of 1PB biopsy (laser beam, partial zona dissection and acid Tyrode's) and two different protocols (intracytoplasmic sperm injection before or after 1PB biopsy) and their effect on the percentage of oocytes diagnosed and the fertilization rate, are discussed. In reciprocal translocation cases, published in the literature or studied by us, in which at least nine oocytes had been diagnosed, a correlation has been found between the frequency of non-disjunction observed and the theoretical recombination rate. To date, PGD by 1PB analysis alone or combined with blastomere biopsies in female carriers of chromosomal rearrangements has been used in 18 cases, with a further six cases reported here. A total of 325 cumulus–oocyte complexes have been obtained, of which 294 were biopsied and 224 were diagnosed. A total of 52 embryos was transferred, 19 of which implanted and 17 produced full-term pregnancies.
Functional Health Status Levels of Primary Care Patients
Authors: Eugene Nelson
Journal: JAMA (1983)

A cross-sectional study was conducted on functional status of adults visiting primary care practices. Limitations in physical and mental function were assessed independently in 28 practices by patients (N=1,227) and physicians (N=47) using a simple global index of disability. Results indicated 12% of patients rated their physical limitations as major and 8% rated major emotional limitations during the past month. Comparable assessments by physicians were 5% and 4%, respectively. Differences between patients and physicians were statistically significant and are demonstrated to be clinically relevant. Patients' functional limitations were associated with increased utilization of ambulatory care, older age, lower level of education, unemployment, and a primary diagnosis of a chronic condition. We conclude that functional status can be routinely recorded in medical practice to help describe severity, predict utilization, and improve the physician-patient relationship. (<i>JAMA</i>1983;249:3331-3338)
Abrogation of Signal Transducer and Activator of Transcription 3 Reactivation after Src Kinase Inhibition Results in Synergistic Antitumor Effects
Authors: Faye M. Johnson, Babita Saigal, Hai Tran, Nicholas J. Donato
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The Src family of kinases (SFKs) regulate multiple signal transduction cascades and influence proliferation, motility, survival, and angiogenesis. Dasatinib inhibits SFKs, which leads to cytotoxicity, cell cycle arrest, apoptosis, and decreased invasion of cancer cells. Signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor that regulates survival and proliferation. Dasatinib results in rapid and durable inhibition of c-Src, whereas STAT3 undergoes only transient inactivation. We hypothesized that the reactivation of STAT3 after dasatinib treatment represents the engagement of a compensatory signal for cell survival that blocks the antitumor effects of SFK inhibition. Experimental Design: The effects of upstream inhibitors on STAT3 activation were assessed with western blotting and a quantitative bioplex phosphoprotein assay. We used the 3–(4,5-dimethylthiazol–2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine the cytotoxicity and propidium iodine/annexin V staining with flourescence-activated cell sorting (FACS) analysis to evaluate cell cycle change and apoptosis. The combination index was calculated by the Chou-Talalay equation. Cytokines were quantitated using a multiplexed, particle-based FACS analysis. Results: C-Src and several downstream molecules were rapidly and durably inhibited by dasatinib. However, STAT3 was reactivated by 24 h. The addition of JAK inhibitors during dasatinib incubation resulted in sustained inhibition of STAT3, although JAK activation by dasatinib was not shown. Combined SFK and JAK inhibition resulted in synergistic cytotoxicity due to increased apoptosis. Conclusions: The reactivation of STAT3 during dasatinib treatment is caused by the engagement of a compensatory pathway that suppresses the antitumor effects of SFK inhibition and allows cancer cell survival. Abrogation of this pathway resulted in synergistic cytotoxicity. Given that STAT3 reactivation occurred in 14 of 15 solid tumor cell lines, dasatinib combined with Janus-activated kinase inhibitors may have widespread application in cancer treatment.
TCT-844 Clinical Outcome Of Patients With Low-Flow, Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Implantation
Authors: Jury Schewel, Dimitry Schewel, Christian Frerker, Thomas Thielsen, Felix Meinke, Felix Kreidel, Karl-Heinz Kuck, Ulrich Schäfer
Journal: Journal of the American College of Cardiology (2012)
Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation
Authors: Pierre Jaïs, Bruno Cauchemez, Laurent Macle, Emile Daoud, Paul Khairy, Rajesh Subbiah, Mélèze Hocini, Fabrice Extramiana, Fréderic Sacher, Pierre Bordachar, George Klein, Rukshen Weerasooriya, Jacques Clémenty, Michel Haïssaguerre
Journal: Circulation (2008)

The mainstay of treatment for atrial fibrillation (AF) remains pharmacological; however, catheter ablation has increasingly been used over the last decade. The relative merits of each strategy have not been extensively studied.We conducted a randomized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug. The primary end point was absence of recurrent AF between months 3 and 12, absence of recurrent AF after up to 3 ablation procedures, or changes in antiarrhythmic drugs during the first 3 months. Ablation consisted of pulmonary vein isolation in all cases, whereas additional extrapulmonary vein lesions were at the discretion of the physician. Crossover was permitted at 3 months in case of failure. Echocardiographic data, symptom score, exercise capacity, quality of life, and AF burden were evaluated at 3, 6, and 12 months by the supervising committee. Of 149 eligible patients, 112 (18 women [16%]; age, 51.1+/-11.1 years) were enrolled and randomized to ablation (n=53) or "new" antiarrhythmic drugs alone or in combination (n=59). Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 (63%) and 5 patients (9%), respectively (P=0.0001). At the 1-year follow-up, 13 of 55 patients (23%) and 46 of 52 patients (89%) had no recurrence of AF in the antiarrhythmic drug and ablation groups, respectively (P<0.0001). Symptom score, exercise capacity, and quality of life were significantly higher in the ablation group.This randomized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms, exercise capacity, and quality of life.
Nutritional status of COPD patients with complete respiratory failure on long term home oxygen therapy
Authors: Dominika Posluszna, Emilia Swietlik, Anna Doboszynska, Kinga Kuczynska, Katarzyna Rzeszutek, Lucyna Dymek, Andrzej Dymek
Journal: European Respiratory Journal (2012)

Objectives:

This study aimed in assessing nutritional status in patients with the advanced COPD, treated with long term home oxygen therapy.

Material and methods:

A group of 49 patients with COPD, mean age 67 year, were included into the study. 43 patients smoked cigarettes in the past (91.5%).

Body composition evaluation with bioelectrical impedance analysis (BIA) were performed in all patients. Body Mass Index (BMI) and Fat-Free Mass Index (FFMI) were calculated. FEV1 and FVC were measured. Life quality was assessed with St. George Respiratory Questionnaire (SGRQ).

Results:

17.7% of patients were diagnosed as underweight, in 22.3% the body weight was normal, 61,9% of patients were overweight or obese.

FEV1 value was the lowest in underweighed patients, and the highest in overweighed and obese patients. Strongly positive correlation between FEV1 and FFMI: r=0.45; p<0.01, was also noted.

Statistically significant differences between SGRQ total score and frequency of the undertaken physical activity were seen. In patients, who performed moderate exercises, e.g. walking once a week only, lower life quality was statistically significant (SGRQ Total Score=77.6) in comparison with the patients, who performed physical exercise thrice a week at least (SGRQ Total Score= 67.7) at p<0.04.

Conclusions:

1. Normal body weight was noted in 22.3% of patients with advanced COPD. Overweight and obesity are seen statistically significantly more often than underweight.

2. Respiratory system function are worse in patients diagnosed with malnutrition than that in patients that are overweight and obese.

3. Quality of life in patients more physically active is better than ones with lower physical activity.
Cycloxygenase-2 Inhibition Augments the Efficacy of a Cancer Vaccine
Authors: Andrew R. Haas, Jing Sun, Anil Vachani, Africa F. Wallace, Michael Silverberg, Veena Kapoor, Steven M. Albelda
Journal: Clinical Cancer Research (2006)

Abstract Tumor-derived cyclooxygenase-2 (COX-2) and its product, prostaglandin E2, exert strong immunoinhibitory effects that block dendritic cell function and CD4+ and CD8+ T-cell proliferation and function. We have shown previously that the addition of an oral COX-2 inhibitor to immunogene therapy using IFN-β markedly augmented therapeutic efficacy in murine tumor models. In this study, we hypothesized that COX-2 inhibition might also augment an antitumor vaccination strategy. Mice bearing tumors derived from TC1 cells, a tumor line that expresses the human papillomavirus (HPV) E7 protein, were thus vaccinated with an adenoviral vector expressing HPV E7 protein (Ad.E7). This vaccine approach effectively generated E7-specific CD8+ cells and slowed the growth of small tumors but had little effect on large tumors. However, feeding mice with the COX-2 inhibitor, rofecoxib, restored the effectiveness of the vaccine against large tumors and prolonged survival. This effect was accompanied by a larger percentage of E7-specific CD8+ cells in the regional draining lymph nodes and a markedly increased number of tumor-infiltrating E7-specific CD8+ cells (as determined by flow cytometry) and total CD8+ T cells (as determined by immunohistochemical staining). Increased immunocyte trafficking was likely mediated by the generation of a Th1-type tumor microenvironment because COX-2 inhibition increased expression levels of mRNA for IFN-γ, interleukin-12, IP-10, and MIG while lowering the expression of vascular endothelial growth factor within tumors. This study shows that the effectiveness of a cancer vaccine can be significantly improved by adding COX-2 inhibition.
768 EFFECTIVENESS OF TENOFOVIR FOR CHRONIC HEPATITIS B IN FIELD PRACTICE – 2 YEAR INTERIM RESULTS FROM THE PROSPECTIVE GERMAN MULTICENTER NON-INTERVENTIONAL STUDY (GEMINIS)
Authors: J. Petersen, R. Heyne, S. Mauss, J. Schlaak, W. Schiffelholz, C. Eisenbach, H. Hartmann, M. Wiese, K. Boeker, H.-F. Loehr, C. John, M. Leuschner, C. Trautwein, G. Felten, A. Trein, W. Krause, S. Ruppert, T. Warger, D. Hüppe
Journal: Journal of Hepatology (2013)