tbuckley/cabot-search huggingface dataset:
Testing Molecular Therapies in Hepatocellular Carcinoma: The Need for Randomized Phase II Trials
Authors: Josep M. Llovet, Jordi Bruix
Journal: Journal of Clinical Oncology (2009)

Josep M. Llovet, Mount Sinai Liver Cancer Program, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY; Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Hospital Clinic; and Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Catalonia, Spain Jordi Bruix, Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Hospital Clinic, Barcelona, Catalonia, Spain
AUGUSTUS at EGASP: using EST, protein and genomic alignments for improved gene prediction in the human genome.
Authors: Mario Stanke, Ana Tzvetkova, Burkhard Morgenstern
Journal: Genome biology (2006)

Abstract Background A large number of gene prediction programs for the human genome exist. These annotation tools use a variety of methods and data sources. In the recent ENCODE genome annotation assessment project (EGASP), some of the most commonly used and recently developed gene-prediction programs were systematically evaluated and compared on test data from the human genome. AUGUSTUS was among the tools that were tested in this project. Results AUGUSTUS can be used as an ab initio program, that is, as a program that uses only one single genomic sequence as input information. In addition, it is able to combine information from the genomic sequence under study with external hints from various sources of information. For EGASP, we used genomic sequence alignments as well as alignments to expressed sequence tags (ESTs) and protein sequences as additional sources of information. Within the category of ab initio programs AUGUSTUS predicted significantly more genes correctly than any other ab initio program. At the same time it predicted the smallest number of false positive genes and the smallest number of false positive exons among all ab initio programs. The accuracy of AUGUSTUS could be further improved when additional extrinsic data, such as alignments to EST, protein and/or genomic sequences, was taken into account. Conclusion AUGUSTUS turned out to be the most accurate ab initio gene finder among the tested tools. Moreover it is very flexible because it can take information from several sources simultaneously into consideration.
Short cigarette smoke exposure facilitates sensitisation and asthma development in mice
Authors: Ellen A. Lanckacker, Kurt G. Tournoy, Hamida Hammad, Gabriele Holtappels, Bart N. Lambrecht, Guy F. Joos, Tania Maes
Journal: European Respiratory Journal (2012)

Epidemiological studies indicate that cigarette smoke exposure is a risk factor for increased sensitisation and asthma development. The aim of this study was to examine the impact of cigarette smoke on sensitisation and allergic airway inflammation in response to a low dose of house dust mite (HDM), and to obtain potential mechanistic insights. Mice were exposed to low doses of HDM extract combined with air or cigarette smoke exposure, either during allergen sensitisation or during the development of allergic airway disease. Mice concomitantly exposed to low-dose HDM, combined with cigarette smoke for 3 weeks, demonstrated an asthmatic phenotype with significantly increased airway eosinophilia, goblet cell metaplasia, airway hyperresponsiveness and a rise in HDM-specific serum immunoglobulin G1, compared to sole HDM or cigarette smoke exposure. In addition, short cigarette smoke inhalation, during the initial contact with HDM allergens, was sufficient to facilitate sensitisation and development of a complete asthmatic phenotype after rechallenge with HDM. Mechanistically, short cigarette smoke exposure amplified dendritic cell-mediated transport of fluorescein isothiocyanate-labelled HDM allergens to the intrathoracic lymph nodes and generated a local T-helper cell type 2 response. Short cigarette smoke exposure is sufficient to facilitate allergic sensitisation and the development of low-dose HDM-induced allergic asthma, possibly by affecting dendritic cell function.
Lysophosphatidic Acid Induction of Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer Cells
Authors: Y.-L. Hu, M.-K. Tee, E. J. Goetzl, N. Auersperg, G. B. Mills, N. Ferrara, R. B. Jaffe
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Lysophosphatidic acid (LPA) stimulates ovarian tumor growth at concentrations present in ascitic fluid. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and plays a pivotal role in the formation of ovarian cancer-associated ascites. We examined whether LPA promotes ovarian tumor growth by increasing angiogenesis via VEGF. Methods: VEGF expression was examined in a simian virus 40 T-antigen-immortalized ovarian surface epithelial cell line (IOSE-29) and in ovarian cancer cell lines (OVCAR-3, SKOV-3, and CAOV-3) treated with LPA. VEGF promoter activity was measured in OVCAR-3 cells after transfection or cotransfection with c-Fos and c-Jun, components of AP1 transcription factor, potential binding sites for which are present in the VEGF promoter. The expression of the LPA receptors Edg2 and Edg4 was also assessed. All statistical tests were two-sided. Results: LPA treatment increased steady-state VEGF messenger RNA (mRNA) levels in OVCAR-3 cells in a timeand dose-dependent fashion and stimulated VEGF promoter activity without prolonging mRNA half-life in these cells, but LPA had little effect on IOSE-29 cells. Forced overexpression of c-Jun and c-Fos in OVCAR-3 cells stimulated VEGF promoter activity fourfold. LPA also elevated VEGF protein levels by 1.5-fold in SKOV-3 cells (P = .0148), 1.9-fold in CAOV-3 cells (P<.001), and threefold in OVCAR-3 cells (P<.0001). Both Edg2 and Edg4 were detected in ovarian cancer cells; however, only Edg2 was present in normal ovarian surface epithelial cells and IOSE-29 cells. Conclusions: LPA stimulates ovarian tumor growth, at least in part, via induction of VEGF expression through transcriptional activation. However, this LPA response is not evident in normal ovarian surface epithelial cells. Our data suggest that Edg4, but not Edg2, plays a role in LPA stimulation of ovarian tumor growth.
Cap polyposis: an inflammatory disorder or a spectrum of mucosal prolapse syndrome?
Authors: T Konishi, T Watanabe, Y Takei, T Kojima, H Nagawa
Journal: Gut (2005)

We read with great interest the letter by Maunoury and colleagues ( Gut 2005; 54 :313–14). They reported on a case of cap polyposis unresponsive to infliximab, in contrast with the successful report by Bookman and colleagues.1 Maunoury et al stated that the success with infliximab reported by Bookman et al might have been due to spontaneous regression of cap polyposis. Maunoury et al speculated that a role for tumour necrosis factor α (TNF-α) in the pathogenesis of this rare disorder was unacceptable and other mechanism, such as abnormal colonic motility, may be important.

The pathogenesis of cap polyposis …
Osteopontin as a Potential Diagnostic Biomarker for Ovarian Cancer
Authors: Jae-Hoon Kim
Journal: JAMA (2002)

Development of new biomarkers for ovarian cancer is needed for early detection and disease monitoring. Analyses involving complementary DNA (cDNA) microarray data can be used to identify up-regulated genes in cancer cells, whose products may then be further validated as potential biomarkers.To describe validation studies of an up-regulated gene known as osteopontin, previously identified using a cDNA microarray system.Experimental and cross-sectional studies were conducted involving ovarian cancer and healthy human ovarian surface epithelial cell lines and cultures, archival paraffin-embedded ovarian tissue collected between June 1992 and June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated for a pelvic mass between June 1992 and June 2001 in gynecologic oncology services at 2 US academic institutions. Plasma samples from 107 women selected from an epidemiologic study of ovarian cancer initiated between May 1992 and March 1997 were used as healthy controls.Relative messenger RNA expression in cancer cells and fresh ovarian tissue, measured by real-time polymerase chain reaction as 2(-DeltaDeltaCT)(a quantitative value representing the amount of osteopontin expression); osteopontin production, localized and scored in ovarian healthy and tumor tissue with immunohistochemical studies; and amount of osteopontin in patient vs control plasma, measured using an enzyme-linked immunoassay.The geometric mean for 2(-DeltaDeltaCT)for osteopontin expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared with 270.4 in 14 ovarian cancer cell lines (P =.03). The geometric mean 2(-DeltaDeltaCT)for osteopontin expression in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with 164.0 in 27 microdissected ovarian tumor tissue samples (P =.06). Immunolocalization of osteopontin showed that tissue samples from 61 patients with invasive ovarian cancer and 29 patients with borderline ovarian tumors expressed higher levels of osteopontin than tissue samples from 6 patients with benign tumors and samples of healthy ovarian epithelium from 3 patients (P =.03). Osteopontin levels in plasma were significantly higher (P<.001) in 51 patients with epithelial ovarian cancer (486.5 ng/mL) compared with those of 107 healthy controls (147.1 ng/mL), 46 patients with benign ovarian disease (254.4 ng/mL), and 47 patients with other gynecologic cancers (260.9 ng/mL).Our findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile.
Genomic diversity of the human intestinal parasite Entamoeba histolytica
Authors: Gareth D Weedall, C Graham Clark, Pia Koldkjaer, Suzanne Kay, Iris Bruchhaus, Egbert Tannich, Steve Paterson, Neil Hall
Journal: Genome biology (2012)

Entamoeba histolytica is a significant cause of disease worldwide. However, little is known about the genetic diversity of the parasite. We re-sequenced the genomes of ten laboratory cultured lines of the eukaryotic pathogen Entamoeba histolytica in order to develop a picture of genetic diversity across the genome. The extreme nucleotide composition bias and repetitiveness of the E. histolytica genome provide a challenge for short-read mapping, yet we were able to define putative single nucleotide polymorphisms in a large portion of the genome. The results suggest a rather low level of single nucleotide diversity, although genes and gene families with putative roles in virulence are among the more polymorphic genes. We did observe large differences in coverage depth among genes, indicating differences in gene copy number between genomes. We found evidence indicating that recombination has occurred in the history of the sequenced genomes, suggesting that E. histolytica may reproduce sexually. E. histolytica displays a relatively low level of nucleotide diversity across its genome. However, large differences in gene family content and gene copy number are seen among the sequenced genomes. The pattern of polymorphism indicates that E. histolytica reproduces sexually, or has done so in the past, which has previously been suggested but not proven.
Lack of Association Between Early Exposure to Cow's Milk Protein and β-Cell Autoimmunity
Authors: Jill M. Norris
Journal: JAMA (1996)

To examine whether infant dietary exposure to cow's milk is associated with beta-cell autoimmunity (BCA), an early predictor of insulin-dependent diabetes mellitus (IDDM).Denver, Colo.Cross-sectional with retrospective analysis.Between January 1994 and December 1995, 253 children from 171 families of persons with IDDM were screened for BCA. All children were between the ages of 9 months and 7 years.BCA was defined as elevated levels of insulin autoantibody, glutamic acid decarboxylase autoantibody, or insulinoma-associated islet tyrosine phosphatases autoantibody (IA-2) above the 99th percentile of 198 normal subjects.Eighteen cases of BCA were detected; 153 unrelated autoantibody-negative children were selected from the cohort as controls. There were no differences in the proportion of cases and controls who were exposed to cow's milk or foods containing cow's milk or to cereal, fruit and vegetable, or meat protein by 3 months or by 6 months of age. Children with BCA were breast-fed for a slightly longer duration than controls (median duration 10 vs 8 months, P=.07).These data suggest that early exposure to cow's milk or other dietary protein is not associated with BCA. This calls into question the importance of cow's milk avoidance as a preventive measure for IDDM.
Left ventricular adaptation to sustained pressure overload in the conscious dog.
Authors: B Crozatier, D Caillet, O Bical
Journal: Circulation Research (1984)

The early adaptation to aortic stenosis was studied in eight conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular minor equator, left ventricular major axis, and ventricular wall thickness. Data were compared during control, acute inflation of a supravalvular aortic cuff occluder and 24 hours after aortic stenosis with and without beta-blockade. Acute aortic stenosis increased peak systolic pressure and end-systolic pressure with a decrease of percent systolic shortening of minor diameter (% delta L). Twenty-four hours after aortic constriction for heart rates, end-diastolic dimensions, and systolic pressures similar to those measured during acute aortic stenosis, % delta L was significantly increased, compared with acute aortic constriction, and was close to control values. End-systolic diameter was not significantly different from control during sustained pressure overload, although end-systolic stress was increased by 26.7 +/- 6.1% (P less than 0.01 with control), representing a leftward shift of the end-systolic stress-diameter relation. Similar results were obtained under beta-blockade. We conclude that there is, in this model of moderate pressure overload, a nonsympathetic increased inotropic state very early after aortic constriction.
Ventricular Geometry, Strain, and Rotational Mechanics in Pulmonary Hypertension
Authors: Sarinya Puwanant, Margaret Park, Zoran B. Popović, W. H. Wilson Tang, Samar Farha, Deepa George, Jacqueline Sharp, Jirapa Puntawangkoon, James E. Loyd, Serpil C. Erzurum, James D. Thomas
Journal: Circulation (2010)

We tested the hypothesis that right ventricular (RV) pressure overload affects RV function and further influences left ventricular (LV) geometry, which adversely affects LV twist mechanics and segmental function.Echocardiographic images were prospectively acquired in 44 patients (age, 46+/-12 years; 82% women) with evidence of pulmonary hypertension (estimated pulmonary artery systolic pressure, 71+/-23 mm Hg) and in 44 age- and gender-matched healthy subjects. Patients with intrinsic LV diseases were excluded. RV lateral wall longitudinal strain (LS) and interventricular septal (IVS) LS were reduced in the pulmonary hypertension group compared with control subjects (-15.9+/-7.6% versus -25.5+/-6.1%, P<0.001; and -17.3+/-4.4% versus -20.2+/-3.9%, P=0.002, respectively), whereas LV lateral wall LS was preserved. RV lateral wall LS and IVS LS, but not LV lateral wall LS, correlated with pulmonary artery systolic pressure (r=0.56, P<0.01; r=0.32, P<0.01) and LV eccentricity index (r=0.57, P<0.01; r=0.57, P<0.01). IVS and LV lateral wall circumferential strain (CS) were both reduced in the pulmonary hypertension group. Although IVS CS and LV lateral wall CS correlated with pulmonary artery systolic pressure and LV eccentricity index, after adjustment of CS for LV eccentricity index, differences between groups persisted for IVS CS (P<0.01) but not LV lateral wall CS (P=0.09). LV torsion was decreased in patients with pulmonary hypertension compared with control subjects (9.6+/-4.9 degrees versus 14.7+/-4.9 degrees , P<0.001). LV torsion inversely correlated with pulmonary artery systolic pressure (r=-0.39, P<0.01) and LV eccentricity index (r=-0.3, P<0.01). LV untwisting rates were similar in both groups (P=0.7).Chronic RV pressure overload directly affects RV longitudinal systolic deformation. RV pressure overload further influences IVS and LV geometry, which impairs LV torsion and segmental LS and CS, more for the IVS than for the free wall of the LV.
Cisplatin- Versus Carboplatin-Based Chemotherapy in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: An Individual Patient Data Meta-analysis
Authors: A. Ardizzoni, L. Boni, M. Tiseo, F. V. Fossella, J. H. Schiller, M. Paesmans, D. Radosavljevic, A. Paccagnella, P. Zatloukal, P. Mazzanti, D. Bisset, R. Rosell
Journal: JNCI Journal of the National Cancer Institute (2007)

Because the efficacy of carboplatin and cisplatin in the treatment of advanced non–small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test ( Q test) was used to test for heterogeneity among trials, and the I 2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P <.001). Carboplatin treatment was associated with a non–statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
Predictors of failure of non-invasive ventilation in patients with respiratory failure; a prospective study
Authors: Sanjay Sobti, Ravi Shekhar Jha, Eema Chaudhary
Journal: European Respiratory Journal (2012)

Introduction  In patients with respiratory failure, randomized studies have shown noninvasive ventilation (NIV) to be associated with lower rates of intubation. In these patients, predictors of NIV failure are not well characterized. We conducted this study to investigate variables predictive of NIV failure in patients with respiratory failure.  Materials And Methods  This prospective study was conducted at a tertiary care hospital in India. Fifty patients were included in the study, and were then followed up to discharge/expiry.  Result  Patients matched on baseline characteristics. Most of the patients (68%) did not have any pre-existing lung disease while 8 out of 50 (16%) had COPD. 4 patients (8%) had bronchial asthma, 2 patients had malignancy and 2 patients(4%) had history of previous Tuberculosis. In associated co-morbidities, 17 patients(34%) had Diabetes and 24 patients(48%) had hypertension.  Oxygen saturation (SaO2) was noted at the time of presentation and was correlated with mortality. Patients with SaO2 less than 75 % were noted to have highest mortality(66%) among all the groups. Similarly data based on pH was noted and it was found that maximum patients (100%) requiring intubation were in the group of pH   60 mm/Hg. Highest mortality was observed in Asthma group(50%), followed by those with Malignancy(40%).  Conclusion  With prudent case selection, NIV is successful in more than 60% of cases. Failure of NIV may be related to the primary diagnosis. Association of co-morbidities as independent predictor of NIV failure needs further study.
Colour Guide to Sports Medicine.
Authors: S. TILL
Journal: Annals of the Rheumatic Diseases (1997)

Colour Guide to Sports Medicine. By E Sherry. (Pp 122; £9.50). Edinburgh: Churchill Livingstone, 1997. ISBN 0443054827.

The increasing recognition of sports medicine as a discipline within mainstream medicine is likely to herald an increasing number of new publications. It was with great interest that I opened the first page of this colour guide. The authors have set out to produce a well illustrated, practical pocket reference book that covers the essentials of sports medicine.

The contents are well laid out and divided into sections that briefly introduce general areas of interest, for example, sports science and sport …