tbuckley/cabot-search huggingface dataset:
Abstract P245: Dry Air Triggers Paroxysmal Atrial Fibrillation in Patients with Implantable Cardioverter Defibrillators
Authors: Jennifer Nguyen, Mark S Link, Heike Luttmann-Gibson, Francine Laden, Joel Schwartz, Benjamin Wessler, Murray A Mittleman, Diane R Gold, Douglas W Dockery
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) is responsible for substantial morbidity and mortality, yet little is known about the environmental factors that may trigger AF episodes. Weather has been proposed as a potential precipitant of paroxysmal AF. Hypothesis: We assessed the hypothesis that changes in outdoor ambient temperature and outdoor absolute humidity may trigger paroxysmal AF in the following 24 hours. Methods: Patients with dual chamber implantable cardioverter defibrillators (ICDs) living in eastern Massachusetts were enrolled between September 2006 and March 2010 from the Tufts Medical Center Cardiac Arrhythmia Clinic (Boston, Massachusetts) and followed prospectively for episodes of paroxysmal AF lasting at least 30 seconds. Arrhythmias documented by the ICD were reviewed and interpreted by an electrophysiologist masked to exposure. The date and time of AF episodes were linked to hourly weather data measured at Boston Logan International Airport. We examined the hypothesis using a time-stratified case-crossover analysis matched on calendar month, day of week and time of day and adjusted for air pollution and barometric pressure. To reduce the possibility of over-representation of clustered events and to reflect the averaging time of the exposure, incident AF episodes were included in the analysis if at least 24 hours had passed since the previous AF episode. Results: Of 200 patients enrolled, 49 experienced at least one AF episode (n = 328 episodes). After excluding events with missing exposure or covariate information, analyses were confined to 230 AF episodes among 47 patients. The 47 patients with paroxysmal AF were followed for an average of 1.9 years, and 32 (68%) were male, 45 (96%) were Caucasian, the mean age was 67 years, 24 (51%) had a history of prior AF episodes, 27 (57%) had a pre-implantation ejection fraction &lt; 35%, and 29 (62%) received the ICD for primary prophylaxis. Outdoor temperature in the previous 24 hours was not associated with AF (odds ratio (OR) = 1.13; 95% confidence interval (CI): 0.89, 1.43, p = 0.32, per interquartile range (IQR) decrease of 6.3°C). Lower absolute humidity in the previous 24 hours was associated with a higher risk of AF onset (OR = 1.33; 95% CI: 1.02, 1.74, p = 0.04, per IQR decrease of 3.5 g/m 3 ); this risk increased slightly for the previous 3 hours (OR = 1.39; 95% CI: 1.06, 1.82, p = 0.02, per IQR decrease of 3.7 g/m 3 ). Conclusions: In conclusion, drier air was associated with a transiently higher risk of paroxysmal AF in the following 24 hours among patients with dual chamber ICDs.
Incidence of Secondary Malignancies Following Allogeneic Hematopoietic Cell Transplantation: A Single Center Experience
Authors: Fotios V. Michelis, Rouslan Kotchetkov, Rebecca M. Grunwald, Aamir Azeem, Jieun Uhm, Naheed Alam, Laura McGillis, Anna Lambie, David Loach, Vikas Gupta, John Kuruvilla, Jeffrey H. Lipton, Dennis D. Kim, Matthew D. Seftel, Hans A. Messner
Journal: Blood (2014)
Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study
Authors: Eric Pujade-Lauraine, Frédéric Selle, Béatrice Weber, Isabelle-Laure Ray-Coquard, Ignace Vergote, Jozef Sufliarsky, Josep Maria Del Campo, Alain Lortholary, Anne Lesoin, Philippe Follana, Gilles Freyer, Beatriz Pardo, Laura Vidal, Bengt Tholander, Laurence Gladieff, Mouna Sassi, Pilar Garin-Chesa, Serge Nazabadioko, Kristell Marzin, Korinna Pilz, Florence Joly
Journal: Journal of Clinical Oncology (2016)

Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator’s choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Authors: Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula McGovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T. Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A’Hern, Amanda Swain, Lakshmi P. Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J. Lord, Alan Ashworth, Mark A. Rubin, Karen E. Knudsen, Felix Y. Feng, Arul M. Chinnaiyan, Emma Hall, Johann S. de Bono
Journal: New England Journal of Medicine (2015)

Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.
Abstract 13923: LDL-Cholesterol Lowering Increased Mortality in Mice with Inherited Cardiomyopathy
Authors: Joseph C Godoy, Anna Schwarz, Jan M Schilling, Elizabeth K Asfaw, Erika A Alvarez, Nancy D Dalton, Ingrid R Niesman, Hemal H Patel, Alice E Zemljic-Harpf
Journal: Circulation (2012)

Treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) lowers low-density lipoprotein cholesterol (LDL-C) for prevention of cardiovascular disease. It has been shown th...
Abstract 15997: First Report of a Dose Dependent Effect of Statin Therapy on Urinary 11-dehydrothromboxane Br2 rLevels: A New Marker for Personalizing Statin Therapy
Authors: Anand Singla, Kevin Bliden, Udaya Tantry, Ali Tabrizchi, Gordon Ens, Kirk Guyer, Mark Antonino, Paul A Gurbel
Journal: Circulation (2012)

BACKGROUND: Aspirin (ASA) and statins are primary treatment strategies for patients with cardiovascular disease. It has been proposed that urinary 11-dehydrothromboxane B2 (11-DTxB2) is a marker of...
Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data
Authors: Candyce H. Kroenke, Jessica Chubak, Lisa Johnson, Adrienne Castillo, Erin Weltzien, Bette J. Caan
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification.
Hepatic Arterial Chemotherapy: Still on Trial
Authors: D.J. Kerr, R.J. Midgley C. S. McArdle
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.8.1806 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10764447 Hepatic Arterial Chemotherapy: Still on Trial D.J. KerrxD.J. KerrSearch for articles by this author , R.J. Midgley C. S. McArdlexR.J. Midgley C. S. McArdleSearch for articles by this author Show More University of Birmingham Cancer Research Campaign Institute for Cancer Studies BirminghamUnited Kingdom https://doi.org/10.1200/JCO.2000.18.8.1806 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
<i>In vivo</i>cardiac reprogramming using an optimal single polycistronic construct: Figure 1
Authors: Hong Ma, Li Wang, Chaoying Yin, Jiandong Liu, Li Qian
Journal: Cardiovascular Research (2015)

Direct cardiac reprogramming holds great promise for cardiac regeneration and disease modelling.1–15 We recently reported that stoichiometry of Gata4 (G), Mef2c (M), and Tbx5 (T) influences the efficiency and quality of induced cardiomyocyte (iCM) reprogramming.16 We generated a full set of polycistronic vectors to manipulate the relative levels of G, M, and T protein expression. Among the six combinations, MGT that expresses a relative high expression of M and low expressions of G and T resulted in the most efficient in vitro iCM reprogramming.16 Here, we performed genetic lineage tracing in a murine myocardial infarction (MI) model to determine whether MGT could improve in vivo iCM reprogramming efficiency and result in a further improvement in ventricular contractile function compared with the traditional separate G, M, and T (G/M/T) delivery.

We took advantage of the unique feature that retrovirus infects only dividing cells to deliver MGT, G/M/T, or dsRed into actively dividing cardiac fibroblasts, but not CMs, in MI hearts.3 We prepared retrovirus encoding the single-triplet MGT as well as G/M/T and dsRed control viruses. These viruses were subjected to ultracentrifugation and were concentrated at 1 × 1010 p.f.a./mL. According to the previously established protocol,3 8–12 week old male mice were treated with 10 μL of ultra-high-titre retrovirus (∼1010 p.f.a./mL) by injection into the myocardial wall immediately following coronary artery ligation.

To determine whether MGT enhances reprogramming of non-myocytes into iCMs in vivo , we performed genetic lineage tracing experiments using Periostin-Cre; R26R-lacZ mice3 to quantify the number of iCMs that had a fibroblast origin. Consistent with previous reports,3 we did not detect any β-galactosidase activity in the CMs of control …
Cord blood monocyte–derived inflammatory cytokines suppress IL-2 and induce nonclassic “T<sub>H</sub>2-type” immunity associated with development of food allergy
Authors: Yuxia Zhang, Fiona Collier, Gaetano Naselli, Richard Saffery, Mimi LK. Tang, Katrina J. Allen, Anne-Louise Ponsonby, Leonard C. Harrison, Peter Vuillermin
Journal: Science Translational Medicine (2016)

Infants who develop food allergy display hyperresponsive innate immunity at birth that promotes nonclassical T H 2 differentiation.
Phylogenetic test of the molecular clock and linearized trees.
Authors: N Takezaki, A Rzhetsky, M Nei
Journal: Molecular Biology and Evolution (1995)

To estimate approximate divergence times of species or species groups with molecular data, we have developed a method of constructing a linearized tree under the assumption of a molecular clock. We present two tests of the molecular clock for a given topology: two-cluster test and branch-length test. The two-cluster test examines the hypothesis of the molecular clock for the two lineages created by an interior node of the tree, whereas the branch-length test examines the deviation of the branch length between the tree root and a tip from the average length. Sequences evolving excessively fast or slow at a high significance level may be eliminated. A linearized tree will then be constructed for a given topology for the remaining sequences under the assumption of rate constancy. We have used these methods to analyze hominoid mitochondrial DNA and drosophilid Adh gene sequences.
Stool consistency as a major confounding factor affecting microbiota composition: an ignored variable?
Authors: Jack A Gilbert, John Alverdy
Journal: Gut (2015)

In this age of the microbiome, the one request most oft heard is ‘so what is the biomarker for this disease?’ In a world of ‘one-size-fits-all’ solutions, and a one pathogen-one disease framework of investigation, most doctors, clinical healthcare professionals, and healthcare industrialists just want the punchline—what is the bacterium that is causing that disease? The problem with this approach is that it remains a challenge to fully understand whether a given microbiome has any causative influence on a given condition, or whether identified associations have any relevance outside of a given case study. Unlike monomicrobial diseases where Koch's postulates can be applied, the interaction between the microbial ecology of the body, and health and disease is extremely complex, leading to fuzzy concepts of organismal ratios and phylogenetic groups of organisms being associated with a specific condition. In their recent paper, Vandeputte et al 1 seek to determine whether gut-transit time has an influence on microbial community profiles in stool, and by what mechanism this occurs, as well as considering whether this influence could have an impact on clinical studies.

Clinicians and microbiome researchers continue to struggle with the delicate balance that exists between elucidating the pathogenesis of a disease and defining the role of a particular organism, or group of organisms in this process. This can be a slippery slope; on the one hand, we want a microbiome-based diagnosis and a discriminative biomarker. …
Prognostic significance of sex in childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study.
Authors: J J Shuster, P Wacker, J Pullen, J Humbert, V J Land, D H Mahoney, S Lauer, A T Look, M J Borowitz, A J Carroll, B Camitta
Journal: Journal of Clinical Oncology (1998)

In childhood B-precursor acute lymphoblastic leukemia (ALL), possible interactions among sex, time, and widely used prognostic factors (age, WBC count, and DNA index) were investigated for the first 5 years after diagnosis.All eligible patients aged 1 to less than 22 years, registered between February 1986 and September 1994 in two B-precursor ALL studies from the Pediatric Oncology Group (POG), were included in the analysis. Cutpoints for age (3.0, 5.0, and 10.0 years), WBC count (10, 50, and 100 x 10(9)/L), and DNA index (DI; 1.16) were defined. Four time periods after diagnosis (years 1, 2, 3, and 4 and 5 combined) were selected for the study of prognostic significance over time. The cut-off date for analysis was April 1996.A total of 3,717 children (2,010 boys and 1,707 girls) were included in the outcome analysis. No major differences between the sexes were observed in age, duration of symptoms before registration, WBC count, hemoglobin level, platelet count, ploidy, presence of CNS disease at diagnosis, or induction failure rate. Event-free survival (EFS) differences between sexes became significantly different from 2 years following diagnosis. At 5 years, in all subsets analyzed, boys fared worse than girls, although not all differences were statistically significant. Major sex differences in EFS were observed in older children (10 to 22 years), in patients with intermediate WBC counts (10 to 50 x 10(9)/ L), and in children who fit both of these subgroups, in whom the 2-year EFS was almost 20% higher in girls than in boys, reaching a 38% difference at 5 years.This study shows an outcome interaction among sex, time, and commonly used prognostic variables. The important sex difference observed at 2 and 5 years suggests that more intensive consolidation and/or maintenance therapy in some boys with B-precursor ALL should be investigated.
Miliary mesothelioma: A consequence of trimodality therapy?
Authors: Lesek Purek, Sophie Laroumagne, Hervé Dutau, Philippe Astoul
Journal: European Respiratory Journal (2011)

Background:  Malignant pleural mesothelioma (MPM) is a rare cancer. Trimodality therapy (TMT) for resectable MPM, combining Cisplatin-based chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant high-dose radiotherapy, is one of the therapeutic strategies with prolonged survival in selective cases. From two recent clinical cases showing dissemination of the disease after multimodal approach, the authors perform a review of the literature trying to find a link between metastatic evolution and aggressive therapeutic strategy.   Case reports:  Two patients presenting with chest pain and pleural effusion had MPM considered, after careful preoperative work–up including negative cerebral magnetic resonance imaging (MRI), positron emission tomography (PET) and negative mediastinoscopy, at a resectable stage. Both patients underwent TMT receiving 3 cycles of chemotherapy followed by EPP and post-operative high-dose radiotherapy. Recurrence of disease occurred 32 and 36 months respectively after the end of TMT with the pattern of miliary spread in the contralateral pulmonary parenchyma and with mediastinal lymph node involvement histologically confirmed by biopsies taken under endoscopic procedure.   Discussion:  The progression of MPM is usually recurrent and localized on the ipsilateral hemithorax and metastasis are usually rare. Few papers show a miliary metastatic pattern and the question should be if invasive and aggressive approach increases this risk and this spectacular progression of a so-called “local disease”.  In our opinion true distant metastatic recurrences will become an important problem in future and a new therapeutic/strategic approach is necessary to maximize distant metastatis control rates.
Applying for flexible training
Authors: J. Sayer
Journal: BMJ (1995)

EDITOR,--One of the drawbacks of the present flexible training scheme is that the system for applying is not rapid enough.1 For those whose partners are on short term contracts, such as junior doctors, the delays inherent in the scheme belie its flexibility.

I applied in August 1993 for a place on the scheme as a part time senior registrar in gastroenterology. I was interviewed and …
Autologous Hematopoietic Stem Cell Transplantation in Refractory Systemic Vasculitis Involving Central Nervous System.
Authors: Yu Oyama, Richard K. Burt, Ann E. Traynor, Laisvyde Statkute, Kathleen A. Quigley, Kimberly Yaung, Mary Brush, Walter G. Barr
Journal: Blood (2004)
The grumbling appendix.
Journal: BMJ (1979)

recently reported by Goldstone.Of the 34 patients operated on, 13 had myeloid metaplasia, four leukaemia, two lymphoma, two cysts, one Gaucher's disease, and in nine the splenomegaly was said to be "non-specific."Both symptoms and the haematological abnormalities were improved in 31 cases (90%).In patients with leukaemias and lymphomas removal of large spleens is said to reduce the toxic effects of subsequent radiotherapy and to minimise its effects on the lung and kidney.4-6There is some controversy, however, on whether splenectomy does increase patients' tolerance to chemo- therapy.In children there is a well-recognised increased susceptibility to infection after splenectomy,10 11 and many believe that antibiotics should be given for two years postoperatively.Even in adults there may be a considerable morbidity associated with splenectomy, and mortality rates as high as 150/ have been reported in some series.Thrombocytosis may be a problem in the first few weeks after operation.Both morbidity and mortality seem to correlate with the size of the spleen, so that once symptoms develop operation should be advocated early rather than late.
Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group.
Authors: J A Levi, D Thomson, V Harvey, G Gill, D Raghavan, M Tattersall, R Snyder, I Burns, T Sandeman, M Byrne
Journal: Journal of Clinical Oncology (1990)

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.