tbuckley/cabot-search huggingface dataset:
Variation over time and interdependence between disease progression and death among patients with glioblastoma on RTOG 0525
Authors: Meihua Wang, James J. Dignam, Minhee Won, Walter Curran, Minesh Mehta, Mark R. Gilbert
Journal: Neuro-Oncology (2015)

We assessed the longitudinal hazard characteristics for death and progression in patients with glioblastoma, evaluated the impact of prognostic factors and treatment on the hazard within different time intervals to determine if effects are time varying, and quantified the influence of progression on survival.Among patients randomized to Radiation Therapy Oncology Group trial 0525, which compared dose-dense with standard-dose temozolomide, we estimated the hazards of death and treatment failure (death or progression) over time and their interdependence.The peak hazard of death was reached at around 16 months with a slow decline after that; the hazard of progression/death reached a peak at around 6 months and decreased dramatically thereafter. The survival advantages for patients with MGMT gene promoter methylation and recursive partitioning analysis class III were substantial in the first 2 years, but lessened thereafter. The progression-free survival benefit of dose-dense over standard-dose temozolomide occurred in the first 6 months (hazard ratio: 0.70; 95% CI: 0.58-0.86; P < .001), although it diminished thereafter. After adjusting for recursive partitioning analysis class and MGMT methylation status, the hazard ratio of death for patients who had progressed over nonprogressors was 6.59 (95% CI: 5.15-8.43; P < .001).After the peak hazard of death, a consistently high hazard remains, but it is lower than in the peak period. The progression hazard peak is earlier, and then hazard consistently declines. The rate of dying after disease progression is about 6.59 times the rate for nonprogressors, suggesting that progression-free survival may be a relevant clinical endpoint.
Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study
Authors: D. Schadendorf, M.M. Amonkar, M. Milhem, K. Grotzinger, L.V. Demidov, P. Rutkowski, C. Garbe, R. Dummer, J.C. Hassel, P. Wolter, P. Mohr, U. Trefzer, C. Lefeuvre-Plesse, A. Rutten, N. Steven, G. Ullenhag, L. Sherman, F.S. Wu, K. Patel, M. Casey, C. Robert
Journal: Annals of Oncology (2014)
Cell-surface antigens associated with recombinant mink cell focus-inducing murine leukemia viruses.
Authors: M W Cloyd, J W Hartley, W P Rowe
Journal: The Journal of Experimental Medicine (1979)

Distinct type-specific antigens were detected on cells infected with cloned mink cell focus-inducing (MCF) murine leukemia viruses by means of cell surface immunofluorescence absorption assays with rabbit antisera raised against naturally-occurring AKR MCF viruses. The MCF type-specific antibodies were present in high titer and not absorbable by cells infected with ecotropic, xenotropic, or wild mouse amphotropic murine leukemia viruses, or combinations of ecotropic and xenotropic viruses. Three MCF subtype-specific reactions were identified. One subspecificity (operationally designated MCFA-1) defined antigenic determinant(s) distributed among MCF viruses in general. Another (MCFA-2) specified determinant(s) induced by all naturally occurring MCF isolates not of Friend or Moloney origin. A third subspecificity (MCFA-3) was induced by some MCF isolates, and not by others; the presence of this antigen did not correlate with the source of any presently known biological property of the viruses. In addition, type-specific antigenic determinants of ecotropic and xenotropic murine leukemia viruses were expressed on MCF virus-infected cells. The serological profile of MCF viruses thus supports the contention that they are env gene recombinants between ecotropic and xenotropic murine leukemia viruses. However, new, distinct MCF-specific determinants are also generated, and these could be useful markers in studying MCF viruses.
Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells
Authors: Silke Appel, Andreas M. Boehmler, Frank Grünebach, Martin R. Müller, Anette Rupf, Markus M. Weck, Ulrike Hartmann, Volker L. Reichardt, Lothar Kanz, Tim H. Brümmendorf, Peter Brossart
Journal: Blood (2003)
Anthropometric and physiological profiles of sepak takraw players
Authors: M N Jawis, R Singh, H J Singh, M N Yassin
Journal: British Journal of Sports Medicine (2005)

Anthropometric and physiological profiles of national sepak takraw players were determined.Thirty nine players, specialising in the three playing positions (tekong/server, feeder, and killer/spiker) were divided into three age categories of under 15 (U15), under 18 (U18), and under 23 (U23) years of age. Height, weight, percent body fat (%bf), maximum oxygen consumption (Vo(2max)), range of motion (ROM), back and leg strength, and heart rate, for the estimation of oxygen consumption during matches, were recorded. Statistical analysis was performed using one way ANOVA for independent measurements and data are presented as mean+/-standard deviation.The U23 players were significantly taller and heavier with significantly better ROM of the neck, trunk, and ankle joints and back and leg strength than the U15 players. No significant difference was found in %bf between the three age categories. Mean maximum heart rate during exercise was significantly higher in the U15 group when compared to the U18 and U23 groups (p<0.05). Mean Vo2max was similar between the three groups. Estimated oxygen consumption during matches was 69.1%, 68.5%, and 56.4% of Vo2max in the killer, tekong, and the feeder groups, respectively.The mean height, body weight, and cardiopulmonary capacities of the players were within the Malaysian population norms, but were somewhat lower than those of players of other court games from other countries. %bf was also lower in these players. This study provides the much needed anthropometric and physiological data of sepak takraw players for further development of this sport.
Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG
Authors: Jacobus Pfisterer, Marie Plante, Ignace Vergote, Andreas du Bois, Hal Hirte, Angel J. Lacave, Uwe Wagner, Anne Stähle, Gavin Stuart, Rainer Kimmig, Sigrid Olbricht, Tien Le, Janusz Emerich, Walther Kuhn, James Bentley, Christian Jackisch, Hans-Joachim Lück, Justine Rochon, Annamaria Hayden Zimmermann, Elizabeth Eisenhauer
Journal: Journal of Clinical Oncology (2006)

Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients.Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS).Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted.Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.
Electron microscopic observations on the accumulation of large granular lymphocytes (pit cells) and kupffer cells in the liver of rats treated with continuous infusion of interleukin-2
Authors: Luc Bouwens, Andreas Marinelli, Peter J. K. Kuppen, Alex M. M. Eggermont, Cornelis J. H. van de Velde, Eddie Wisse
Journal: Hepatology (1990)

Treatment schedules were investigated for in vivo induction of lymphokine-activated killer cells in the rat liver. Treatment of rats with continuous systemic or regional infusion of recombinant human interleukin-2 with a dose of 4 to 8 x 10(4) U/day during 7 days, resulted in an increase in number of large granular lymphocytes or pit cells in the liver up to 43 times normal. Kupffer cells, nongranular lymphocytes, monocytes and neutrophils also increased in number, but with a maximal fivefold increase this was much less pronounced than for large granular lymphocytes. Kupffer cells showed morphological signs of activation and were frequently seen in mitosis. Frequent mitoses were also observed for large granular lymphocytes, but not for other leukocytes. This indicates that the effect of interleukin-2 treatment on hepatic (sinusoidal) cells was primarily directed to large granular lymphocytes and Kupffer cells. The large granular lymphocyte accumulation occurred mainly intrasinusoidally, but they were also frequently observed in the space of Disse where they are not found in control rats. This may be explained partly by the observed damage or gaps in the endothelial lining. The intrasinusoidal large granular lymphocytes adhered to the endothelium and to Kupffer cells. Higher responses, for all cell types, were found when interleukin-2 was administered regionally, that is, through the hepatic artery rather than through the systemic route (jugular vein), although the differences were not statistically significant. Doses below 4 x 10(4) U/day did not result in significant increases of large granular lymphocytes in the liver.
Solvent Exposure Imparts Similar Selective Pressures across a Range of Yeast Proteins
Authors: G. C. Conant, P. F. Stadler
Journal: Molecular Biology and Evolution (2009)

We study how an amino acid residue's solvent exposure influences its propensity for substitution by analyzing multiple alignments of 61 yeast genes for which the crystal structure is known.We find that the selective constraint on the interior residues is on average 10 times that of residues on the surface.Surprisingly, there is no correlation between the overall selective constraint observed for a protein alignment and the ratio of constraints on interior and surface residues.By modeling the selective constraint on several amino acid properties, we show that although residue volume and hydropathy are strongly conserved across most alignments, there is little variation in interior versus surface conservation for these two properties.By contrast, residue charge (isoelectric point) is less generally conserved when considering the protein as a whole but shows a strong constraint against the introduction of charged residues into the protein interior.
Candidate lesion-based criteria for defining a positive sacroiliac joint MRI in two cohorts of patients with axial spondyloarthritis
Authors: Ulrich Weber, Mikkel Østergaard, Robert G W Lambert, Susanne J Pedersen, Stanley M Chan, Veronika Zubler, Kaspar Rufibach, Zheng Zhao, Walter P Maksymowych
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To determine candidate lesion-based criteria for a positive sacroiliac joint (SIJ) MRI based on bone marrow oedema (BMO) and/or erosion in non-radiographic axial spondyloarthritis (nr-axSpA); to compare the performance of lesion-based criteria with global evaluation by expert readers. <h3>Methods</h3> Two independent cohorts A/B of 69/88 consecutive patients with back pain aged ≤50 years, with median symptom duration 1.3/10.0 years, were referred for suspected SpA (A) or acute anterior uveitis plus back pain (B). Patients were classified according to rheumatologist expert opinion based on clinical examination, pelvic radiography and laboratory values as having nr-axSpA (n=51), ankylosing spondylitis (n=34) or non-specific back pain (n=72). Four blinded readers assessed SIJ MRI, recording the presence/absence of SpA by concomitant global evaluation of T1-weighted spin echo (T1SE) and short τ inversion recovery (STIR) scans and, thereafter, whether BMO and/or erosion were present/absent in each SIJ quadrant of each MRI slice. We derived candidate lesion-based criteria based on the number of SIJ quadrants with BMO and/or erosion and calculated mean sensitivity and specificity for SpA. <h3>Results</h3> For both cohorts A/B, global assessment showed high specificity (0.95/0.83) compared with the Assessment in SpondyloArthritis international Society (ASAS) definition (0.76/0.74). BMO ≥3 (0.89/0.84) or ≥4 (0.92/0.87) showed comparably high specificity to global assessment. Erosion ≥2 and/or BMO ≥3 or ≥4 were associated with comparably high sensitivity to global assessment without affecting specificity. These combined criteria showed both higher sensitivity and specificity than the ASAS definition. <h3>Conclusions</h3> Lesion-based criteria for a positive SIJ MRI based on both BMO and/or erosion performed best for classification of axial SpA, reflecting the contextual information provided by T1SE and STIR sequences.
Risk for ventricular fibrillation in peripartum cardiomyopathy with severely reduced left ventricular function—value of the wearable cardioverter/defibrillator
Authors: David Duncker, Arash Haghikia, Thorben König, Stephan Hohmann, Klaus‐Jürgen Gutleben, Ralf Westenfeld, Hanno Oswald, Helmut Klein, Johann Bauersachs, Denise Hilfiker‐Kleiner, Christian Veltmann
Journal: European Journal of Heart Failure (2014)
<i>Trichophyton</i> species: use of volatile fingerprints for rapid identification and discrimination
Authors: N. Sahgal, B. Monk, M. Wasil, N. Magan
Journal: British Journal of Dermatology (2006)

Journal Article Trichophyton species: use of volatile fingerprints for rapid identification and discrimination Get access N. Sahgal, N. Sahgal Applied Mycology Group, Cranfield Health, Cranfield University, Silsoe, Bedford MK45 4DT, U.K. *Bedford Hospital NHS Trust, South Wing, Britannia Road, Bedford MK42 9DJ, U.K Search for other works by this author on: Oxford Academic Google Scholar B. Monk, B. Monk Applied Mycology Group, Cranfield Health, Cranfield University, Silsoe, Bedford MK45 4DT, U.K. *Bedford Hospital NHS Trust, South Wing, Britannia Road, Bedford MK42 9DJ, U.K Search for other works by this author on: Oxford Academic Google Scholar M. Wasil, M. Wasil Applied Mycology Group, Cranfield Health, Cranfield University, Silsoe, Bedford MK45 4DT, U.K. *Bedford Hospital NHS Trust, South Wing, Britannia Road, Bedford MK42 9DJ, U.K Search for other works by this author on: Oxford Academic Google Scholar N. Magan N. Magan Applied Mycology Group, Cranfield Health, Cranfield University, Silsoe, Bedford MK45 4DT, U.K. *Bedford Hospital NHS Trust, South Wing, Britannia Road, Bedford MK42 9DJ, U.K Naresh Magan. E‐mail: n.magan@cranfield.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 6, 1 December 2006, Pages 1209–1216, https://doi.org/10.1111/j.1365-2133.2006.07549.x Published: 01 December 2006 Article history Accepted: 02 July 2006 Published: 01 December 2006
A Two-Center Randomized Controlled Feasibility Trial of Insulin Pump Therapy in Young Children With Diabetes
Authors: Darrell M. Wilson, Bruce A. Buckingham, Elizabeth L. Kunselman, Mary M. Sullivan, Helen U. Paguntalan, Stephen E. Gitelman
Journal: Diabetes Care (2005)

OBJECTIVE—Our goals were to determine if continuous subcutaneous insulin infusion (CSII), compared with those continuing multiple daily injections (MDIs), can be safely used in young children, if those on CSII will have superior glycemic control, if subjects using CSII will have less hypoglycemia for their level of control, and if families using CSII will report an improved quality of life. RESEARCH DESIGN AND METHODS—We conducted a randomized 1-year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months’ duration. Prospective outcomes included measures of overall glycemic control (HbA1c and continuous glucose monitoring system), the incidence of severe hypoglycemia and diabetic ketoacidosis, the percent of glucose values below 3.9 mmol/l, and the parents’ report of quality of life. RESULTS—The 19 subjects’ ages ranged from 1.7 to 6.1 (mean 3.6) years, duration of diabetes ranged from 0.6 to 2.6 (mean 1.4) years, and baseline HbA1c ranged from 6.7 to 9.6% (mean 7.9%). Seven subjects were male. Nine subjects were randomized to start CSII and 10 to continue on MDI. All baseline characteristics were well balanced. Overall metabolic control, diabetes quality of life, and the incidence of hypoglycemia were similar in the two groups. No subject had diabetic ketoacidosis, while one subject in each group had an episode of severe hypoglycemia. No CSII subject discontinued using the pump during or after the study. CONCLUSIONS—CSII can be a safe and effective method to deliver insulin in young children.
Desensitization of Platelet-Derived Growth Factor Receptor-β by Oxidized Lipids in Vascular Cells and Atherosclerotic Lesions
Authors: Cecile Vindis, Isabelle Escargueil-Blanc, Meyer Elbaz, Bertrand Marcheix, Marie-Helene Grazide, Koji Uchida, Robert Salvayre, Anne Nègre-Salvayre
Journal: Circulation Research (2006)

The platelet-derived growth factor receptor-beta (PDGFRbeta) signaling pathway regulates smooth muscle cell (SMC) migration and proliferation and plays a role in the vascular wall response to injury. Oxidized low-density lipoprotein (oxLDL) in atherosclerotic lesions can activate the PDGFRbeta pathway, but the long-term effects of oxLDL on PDGFRbeta function are not well understood. We found that oxLDL induced a dual effect on PDGFRbeta signaling. Initial activation of the PDGFR was followed by desensitization of the receptor. PDGFRbeta desensitization was not attributable to PDGFRbeta degradation or changes in localization to the caveolae but instead resulted from decreased PDGF binding and inhibition of PDGFRbeta tyrosine kinase activity. This inhibition was associated with formation of (4HNE)- and acrolein-PDGFRbeta adducts and was mimicked by preincubation of cells with 4HNE. These PDGFRbeta adducts were also detected in aortae of apolipoprotein-deficient mice and hypercholesterolemic rabbits and in human carotid plaques. The aldehyde scavengers DNPH and Hydralazine prevented both oxLDL- and 4HNE-induced structural modification and PDGFRbeta signaling dysfunction in cells and in vivo. OxLDL inhibition of PDGF signaling may contribute to defective SMC proliferation and decrease the stability of a vulnerable plaque.
Probiotics to Prevent or Treat Excessive Infant Crying
Authors: Valerie Sung, Sarsha Collett, Tanyth de Gooyer, Harriet Hiscock, Mimi Tang, Melissa Wake
Journal: JAMA Pediatrics (2013)

IMPORTANCE Excessive infant crying is common, distressing, but without proven effective prevention or management options. Probiotics may be a promising solution. OBJECTIVE To examine whether probiotics are effective in the prevention/management of crying ("colic") in infants 3 months or younger. DATA SOURCES A systematic search of MEDLINE, EMBASE, and the Cochrane Library, supplemented by the metaRegister of Controlled Trials. STUDY SELECTION Studies that randomized infants 3 months or younger to oral probiotics vs placebo or no or standard treatment with the outcome of infant crying, measured as the duration or number of episodes of infant crying/distress or diagnosis of "infant colic." Twelve of the 1180 initially identified studies were selected. DATA EXTRACTION AND SYNTHESIS This review/meta-analysis was conducted according to guidelines from the Cochrane Handbook for Systematic Reviews of Interventions, with reporting following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were independently extracted by 3 of us. MAIN OUTCOME(S) AND MEASURE(S) Infant crying, measured as the duration or number of episodes of infant crying/distress, or diagnosis of "infant colic." RESULTS Of the 12 trials (1825 infants) reviewed, 6 suggested probiotics reduced crying, and 6 did not. Three of the 5 management trials concluded probiotics effectively treat colic in breastfed babies; 1 suggested possible effectiveness in formula-fed babies with colic, and 1 suggested ineffectiveness in breastfed babies with colic. Meta-analysis of 3 small trials of breastfed infants with colic found that Lactobacillus reuteri markedly reduced crying time at 21 days (median difference, -65 minutes/d; 95% CI, -86 to -44). However, all trials had potential biases. Meanwhile, of 7 prevention trials, 2 suggested possible benefits. Considerable variability in the study populations, study type, delivery mode/dose of probiotic supplementation, and outcomes precluded meta-analysis. CONCLUSIONS AND RELEVANCE Although L reuteri may be effective as treatment for crying in exclusively breastfed infants with colic, there is still insufficient evidence to support probiotic use to manage colic, especially in formula-fed infants, or to prevent infant crying. Results from larger rigorously designed studies applicable to all crying infants will help draw more definitive conclusions.
Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma
Authors: Jason J. Luke, F. Stephen Hodi
Journal: Clinical Cancer Research (2011)

The U.S. Food and Drug Administration recently approved vemurafenib for the treatment of BRAF valine in exon 15, at codon 600 (V600E) mutant metastatic melanoma. Vemurafenib is a competitive small-molecule serine-threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Compared with dacarbazine chemotherapy, vemurafenib significantly improved the 6-month overall survival of patients from 64% to 84% and exhibited a response rate of approximately 50%. Median progression-free survival was also significantly improved with vemurafenib as compared with dacarbazine (5.3 versus 1.6 months, respectively), and this was consistent among groups analyzed, including age, sex, geography, Eastern Cooperative Oncology Group status, disease stage, and serum lactate dehydrogenase. The success of targeting melanoma genomics has created a paradigm shift for future drug development. Currently, the elucidation of resistant mechanisms to vemurafenib therapy remains an important area of active investigation that will shape rational drug treatments for melanoma. The development of vemurafenib, the role of BRAF targeting, and the changing landscape of treatment for melanoma provide a new foundation for clinical investigation.