tbuckley/cabot-search huggingface dataset:
Comment on ASCO-ESMO Consensus Statement on Quality Cancer Care
Authors: Barry Goldspiel, John Wiernikowski
Journal: Journal of Clinical Oncology (2006)

US Intergroup trial of adjuvant therapy with concurrent chemoradiotherapy and the multiple positive adjuvant chemotherapy trials (in which either a minority of patients or no patients received PORT), chemotherapy (without concurrent radiation) does represent standard adjuvant therapy."We feel it is important to interpret these trials paying careful attention to critical details; only two of the trials included patients whom we would consider candidates (N2) for PORT.The International Adjuvant Lung trial allowed PORT but did not report the results of PORT outcomes. 4 The Adjuvant Navelbine International Trialist Association trial reported PORT outcomes and most interestingly, patients with N2 involvement who received PORT (predetermined by treatment centers), and chemotherapy had a 5-year overall survival of 47% compared with 34% for those who received chemotherapy alone. 5 However, after reviewing our report with the insight gained from both the accompanying Editorial 6 and the respondents' letter, we have identified one particular flaw.All failed to mandate a prospective adjuvant phase III chemoadjuvant radiation therapy trial.This trial needs to be properly designed with appropriate end points (survival and morbidity) and adequate power.Radiotherapy dose and treatment planning techniques must be the current standard with proper centralized quality assurance of the radiation technique utilized.Failure to do so will not only result in more controversy but also fail to improve the standard of care for lung cancer patients following surgery.
Join us at The Lancet Clinic
Authors: Sabine Kleinert, Richard Horton, Elena Becker-Barroso, Niall Boyce, David Collingridge, Justine Davies, Emma Grainger, Peter Hayward, John McConnell, Zoë Mullan, Lan-Lan Smith
Journal: The Lancet Oncology (2015)

On Oct 5, 2015, we launch the first 45 disease-specific pages of a major new online initiative involving all Lancet journals that will bring together an overview Seminar and relevant Reviews, Clinical Series, Commissions, research, Case Reports, and Clinical Pictures. Over the next 18 months or so when The Lancet Clinic is complete, there will be online pages for 135 diseases, which we have identified by a combination of global burden of disease data and clinical practice needs. We hope that The Lancet Clinic will help practising doctors make better informed decisions that ultimately lead to better lives of people worldwide, and help others who want to educate or update themselves keep abreast of the evolving evidence base. Importantly, these pages will be updated at regular intervals. The authors of newly commissioned Seminars have agreed to provide regular summaries of important new evidence for 4 years. Individual clinical editors will pull together newly published material from across the Lancet journals and post links to these on the page regularly. In addition, we are continuing our regular editorial policies of commissioning more specialised Clinical Reviews and Series across The Lancet Group to provide a more focused and in-depth assessment for key diseases. And beyond providing knowledge and information, we want to encourage academic and practising clinicians to use this knowledge for advocacy and change. In 2014, The Lancet published the first Clinical Commission on liver disease in the UK and in February, 2015, we launched our first Clinical Campaign based on this Commission. A Cancer Campaign as a joint effort between The Lancet and The Lancet Oncology followed in April. Clinical Campaigns aim to effect change based on data, knowledge, and expert interpretation in partnership with others. Further Clinical Commissions on asthma, hypertension, dementia, tuberculosis, traumatic brain injury, psychotherapy, chronic obstructive pulmonary disease, and others are underway across all Lancet journals. With these Clinical Commissions and Campaigns, we hope to extend our goal to publish the best science for better lives to being an active partner in using this science for actual change. Commissions and Campaigns will be part of the disease pages to encourage engagement and actions. The Lancet Clinic invites you to be part of this endeavour.
The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease
Authors: Elena Myasoedova, Arun Chandran, Birkan Ilhan, Brittny T Major, C John Michet, Eric L Matteson, Cynthia S Crowson
Journal: Annals of the Rheumatic Diseases (2015)

To examine the role of rheumatoid arthritis (RA) flare, remission and RA severity burden in cardiovascular disease (CVD).In a population-based cohort of patients with RA without CVD (age ≥30 years; 1987 American College of Rheumatology criteria met in 1988-2007), we performed medical record review at each clinical visit to estimate flare/remission status. The previously validated RA medical Records-Based Index of Severity (RARBIS) and Claims-Based Index of RA Severity (CIRAS) were applied. Age- and sex-matched non-RA subjects without CVD comprised the comparison cohort. Cox models were used to assess the association of RA activity/severity with CVD, adjusting for age, sex, calendar year of RA, CVD risk factors and antirheumatic medications.Study included 525 patients with RA and 524 non-RA subjects. There was a significant increase in CVD risk in RA per time spent in each acute flare versus remission (HR 1.07 per 6-week flare, 95% CI 1.01 to 1.15). The CVD risk for patients with RA in remission was similar to the non-RA subjects (HR 0.90, 95% CI 0.51 to 1.59). Increased cumulative moving average of daily RARBIS (HR 1.16, 95% CI 1.03 to 1.30) and CIRAS (HR 1.38, 95% CI 1.12 to 1.70) was associated with CVD. CVD risk was higher in patients with RA who spent more time in medium (HR 1.08, 95% CI 0.98 to 1.20) and high CIRAS tertiles (HR 1.18, 95% CI 1.06 to 1.31) versus lower tertile.Our findings show substantial detrimental role of exposure to RA flare and cumulative burden of RA disease severity in CVD risk in RA, suggesting important cardiovascular benefits associated with tight inflammation control and improved flare management in patients with RA.
A Phylogenetic Analysis of Indel Dynamics in the Cotton Genus
Authors: C. E. Grover, Y. Yu, R. A. Wing, A. H. Paterson, J. F. Wendel
Journal: Molecular Biology and Evolution (2008)

Genome size evolution is a dynamic process involving counterbalancing mechanisms whose actions vary across lineages and over time. Whereas the primary mechanism of expansion, transposable element (TE) amplification, has been widely documented, the evolutionary dynamics of genome contraction have been less thoroughly explored. To evaluate the relative impact and evolutionary stability of the mechanisms that affect genome size, we conducted a phylogenetic analysis of indel rates for 2 genomic regions in 4 Gossypium genomes: the 2 coresident genomes (A(T) and D(T)) of tetraploid cotton and its model diploid progenitors, Gossypium arboreum (A) and Gossypium raimondii (D). We determined the rates of sequence gain or loss along each branch, partitioned by mechanism, and how these changed during species divergence. In general, there has been a propensity toward growth of the diploid genomes and contraction in the polyploid. Most of the size difference between the diploid species occurred prior to polyploid divergence and was largely attributable to TE amplification in the A/A(T) genome. After separating from the true parents of the polyploid genomes, both diploid genomes experienced slower sequence gain than in the ancestor, due to fewer TE insertions in the A genome and a combination of increased deletions and decreased TE insertions in the D genome. Both genomes of the polyploid displayed increased rates of deletion and decreased rates of insertion, leading to a rate of near stasis in D(T) and overall contraction in A(T) resulting in polyploid genome contraction. As expected, TE insertions contributed significantly to the genome size differences; however, intrastrand homologous recombination, although rare, had the most significant impact on the rate of deletion. Small indel data for the diploids suggest the possibility of a bias as the smaller genomes add less or delete more sequence through small indels than do the larger genomes, whereas data for the polyploid suggest increased sequence turnover in general (both as small deletions and small insertions). Illegitimate recombination, although not demonstrated to be a dominant mechanism of genome size change, was biased in the polyploid toward deletions, which may provide a partial explanation of polyploid genomic downsizing.
Fetal lung growth. Influence of pulmonary arterial flow and surgery in sheep.
Authors: L D Wallen, S F Perry, J T Alston, J E Maloney
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Aberrant pulmonary arterial flow has been associated with pulmonary hypoplasia, which is a common cause of death in newborns. The current experiments were designed to confirm whether interruption of postductal main pulmonary artery (MPA) flow causes pulmonary hypoplasia. In addition, the effect of fetal surgery on lung growth was investigated. Fetal sheep, instrumented at 107 to 115 d gestation (MPA ligated [n = 5], sham operated [n = 3], and monitored [no thoracotomy, n = 5]), and unoperated twin fetuses (140-d controls, n = 5) were used for analysis of lung growth at 136 to 140 d gestation. Morphometric measurement of lung tissue volumes and assays of DNA, protein, and saturated phosphatidylcholine (SPC) were used to assess lung growth. MPA ligation significantly decreased lung growth and maturation as indicated by decreased surface area and volumes of fine nonparenchyma, future airspace, and parenchymal tissue, and by decreased lung weights, total DNA, protein, and SPC content. There was a significant increase in the volume percentage of coarse nonparenchyma and a decrease in the volume percentage of future airspace. The pattern of lung growth after MPA ligation suggests that growth of peripheral airspace and parenchymal tissue components does not occur, resulting in a significant decrease in the amount of new tissue formed and delayed tissue maturation. Fetal surgery significantly changed only DNA, protein, and SPC content. Studies of the regulation of lung growth must consider the role of pulmonary arterial flow and the smaller, but significant effects of fetal surgery.
Towards a computational neuroscience of autism-psychosis spectrum disorders
Authors: Tony Vladusich
Journal: Behavioral and Brain Sciences (2008)

Abstract Crespi &amp; Badcock (C&amp;B) hypothesize that psychosis and autism represent opposite poles of human social cognition. I briefly outline how computational models of cognitive brain function may be used as a resource to further develop and experimentally test hypotheses concerning “autism-psychosis spectrum disorders.” 1
Progression-Specific Genes Identified by Expression Profiling of Matched Ductal Carcinomas <i>In situ</i> and Invasive Breast Tumors, Combining Laser Capture Microdissection and Oligonucleotide Microarray Analysis
Authors: Christina S. Schuetz, Michael Bonin, Susan E. Clare, Kay Nieselt, Karl Sotlar, Michael Walter, Tanja Fehm, Erich Solomayer, Olaf Riess, Diethelm Wallwiener, Raffael Kurek, Hans J. Neubauer
Journal: Cancer Research (2006)

Becoming invasive is a crucial step in breast cancer oncogenesis. At this point, a lesion carries the potential for spreading and metastasis--a process, whose molecular characteristics still remain poorly understood. In this article, we describe a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast ductal carcinomas to identify novel molecular markers characterizing the transition from DCIS to IDC. The purpose of this study was to better understand the molecular biology of this transition and to identify candidate genes whose products might serve as prognostic markers and/or as molecular targets for treatment. To obtain cellular-based gene expression profiles from epithelial tumor cells, we combined laser capture microdissection with a T7-based two-round RNA amplification and Affymetrix oligonucleotide microarray analysis. Altogether, a set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC and replicate DCIS/IDC preparations from three of the nine tumors. Cluster analysis on expression data shows the robustness and reproducibility of the techniques we established. Using multiple statistical methods, 546 significantly differentially expressed probe sets were identified. Eighteen candidate genes were evaluated by RT-PCR. Examples of genes already known to be associated with breast cancer invasion are BPAG1, LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C, SART2, and TNFAIP6 was localized to epithelial tumor cells by in situ hybridization and/or immunohistochemistry, confirming the accuracy of laser capture microdissection sampling and microarray analysis.
Transmission of multidrug-resistant tuberculosis in the UK: a cross-sectional molecular and epidemiological study of clustering and contact tracing
Authors: Laura F Anderson, Surinder Tamne, Timothy Brown, John P Watson, Catherine Mullarkey, Dominik Zenner, Ibrahim Abubakar
Journal: The Lancet Infectious Diseases (2014)

Between 2000 and 2012 the number of multidrug-resistant (MDR) tuberculosis cases in the UK increased from 28 per year to 81 per year. We investigated the proportion of MDR tuberculosis cases arising from transmission in the UK and associated risk factors.We identified patients with MDR tuberculosis notified in England, Wales, and Northern Ireland between Jan 1, 2004, and Dec 31, 2007, by linking national laboratory and surveillance data. Data for laboratory isolates, including drug sensitivities and 24-mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing were obtained routinely from the National Tuberculosis Reference laboratories as part of national tuberculosis surveillance. We investigated clusters of cases with indistinguishable MIRU-VNTR profiles to identify epidemiological links. We calculated transmission using the n-1 method and established associated risk factors by logistic regression. We also assessed the likelihood of transmission to additional secondary active tuberculosis cases, identified through conventional contact tracing.204 patients were diagnosed with MDR tuberculosis in the study period; 189 (92·6%) had an MIRU-VNTR profile. We identified 12 clusters containing 40 individuals and 149 unique strains. The proportion of cases attributable to recent transmission, on the basis of molecular data, was 15% (40 cases clustered-12 clusters/189 with a strain type). The proportion of cases attributable to recent transmission (ie, transmission within the UK) after adjustment for epidemiological links was 8·5% (22 cases with epidemiological links-six clusters/189 cases with a strain type). Being UK born (odds ratio 4·81; 95% CI 2·03-11·36, p=0·0005) and illicit drug use (4·75; 1·19-18·96, p=0·026) were significantly associated with clustering. The most common transmission setting was the household but 21 of 22 of epidemiological links were missed by conventional contact tracing. 13 secondary active tuberculosis cases identified by conventional contact tracing were mostly contacts of patients with MDR tuberculosis from countries of high tuberculosis burden. 11 (85%) of 13 shared the same country of birth as the index case, of whom ten did not share a strain type or drug resistance pattern.Transmission of MDR tuberculosis in the UK is low and associated with being UK born or illicit drug use. MIRU-VNTR typing with cluster investigation was more successful at identifying transmission events than conventional contact tracing. Individuals with tuberculosis who have had contact with a known MDR tuberculosis source case from a country of high tuberculosis burden should have drug-sensitivity testing on isolates to ensure appropriate treatment is given.Public Health England.
Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma?
Authors: T. Frauenfelder, M. Tutic, W. Weder, R.P. Götti, R.A. Stahel, B. Seifert, I. Opitz
Journal: European Respiratory Journal (2011)

The purpose of our study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST (response evaluation criteria in solid tumours) criteria. 30 patients with digitally available chest computed tomography (CT) scans before and after three cycles of chemotherapy were included. Three readers independently assessed tumour response using two different methods: 1) the modified RECIST criteria; and 2) the tumour volumetric approach using dedicated software (Myrian; Intrasense, Paris, France). Inter-rater reliability of unidimensional and volumetric measurements was assessed using intraclass correlation. Tumour response classification for modified RECIST was compared to the volumetric approach applying unidimensional RECIST volumetric equivalent criteria. The determination of unidimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general κ 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general κ 0.9) were found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as "stable disease" was higher for the volumetric approach using tumour-equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT using Myrian software is a reliable, reproducible and sensitive method to measure tumour volume and, thus, therapy response after induction chemotherapy.
Accessing Antiretroviral Therapy Following Release From Prison
Authors: Jacques Baillargeon, Thomas P. Giordano, Josiah D. Rich, Z. Helen Wu, Katherine Wells, Bradley H Pollock, David P. Paar
Journal: JAMA (2009)

<h3>Context</h3>Interruption of antiretroviral therapy (ART) during the first weeks after release from prison may increase risk for adverse clinical outcomes, transmission of human immunodeficiency virus (HIV), and drug-resistant HIV reservoirs in the community. The extent to which HIV-infected inmates experience ART interruption following release from prison is unknown.<h3>Objectives</h3>To determine the proportion of inmates who filled an ART prescription within 60 days after release from prison and to examine predictors of this outcome.<h3>Design, Setting, and Participants</h3>Retrospective cohort study of all 2115 HIV-infected inmates released from the Texas Department of Criminal Justice prison system between January 2004 and December 2007 and who were receiving ART before release.<h3>Main Outcome Measure</h3>Proportion of inmates who filled an ART prescription within 10, 30, and 60 days of release from prison.<h3>Results</h3>Among the entire study cohort (N = 2115), an initial prescription for ART was filled by 115 (5.4%) inmates within 10 days of release (95% confidence interval [CI], 4.5%-6.5%), by 375 (17.7%) within 30 days (95% CI, 16.2%-19.4%), and by 634 (30.0%) within 60 days (95% CI, 28.1%-32.0%). In a multivariate analysis of predictors (including sex, age, race/ethnicity, viral load, duration of ART, year of discharge, duration of incarceration, parole, and AIDS Drug Assistance Program application assistance), Hispanic and African American inmates were less likely to fill a prescription within 10 days (adjusted estimated risk ratio [RR], 0.4 [95% CI, 0.2-0.8] and 0.4 [95% CI, 0.3-0.7], respectively) and 30 days (adjusted estimated RR, 0.7 [95% CI, 0.5-0.9] and 0.7 [95% CI, 0.5-0.9]). Inmates with an undetectable viral load were more likely to fill a prescription within 10 days (adjusted estimated RR, 1.8 [95% CI, 1.2-2.7]), 30 days (1.5 [95% CI, 1.2-1.8]), and 60 days (1.3 [95% CI, 1.1-1.5]). Inmates released on parole were more likely to fill a prescription within 30 days (adjusted estimated RR, 1.3 [95% CI, 1.1-1.6]) and 60 days (1.5 [95% CI, 1.4-1.7]). Inmates who received assistance completing a Texas AIDS Drug Assistance Program application were more likely to fill a prescription within 10 days (adjusted estimated RR, 3.1 [95% CI, 2.0-4.9]), 30 days (1.8 [95% CI, 1.4-2.2]), and 60 days (1.3 [95% CI, 1.1-1.4]).<h3>Conclusion</h3>Only a small percentage of Texas prison inmates receiving ART while incarcerated filled an initial ART prescription within 60 days of their release.
Non-redundant properties of IL-1α and IL-1β during acute colon inflammation in mice
Authors: Marina Bersudsky, Lotem Luski, Daniel Fishman, Rosalyn M White, Nadya Ziv-Sokolovskaya, Shahar Dotan, Peleg Rider, Irena Kaplanov, Tegest Aychek, Charles A Dinarello, Ron N Apte, Elena Voronov
Journal: Gut (2013)

<h3>Objective</h3> The differential role of the IL-1 agonists, IL-1α, which is mainly cell-associated versus IL-1β, which is mostly secreted, was studied in colon inflammation. <h3>Design</h3> Dextran sodium sulfate (DSS) colitis was induced in mice globally deficient in either IL-1α or IL-1β, and in wild-type mice, or in mice with conditional deletion of IL-1α in intestinal epithelial cells (IECs). Bone marrow transplantation experiments were performed to assess the role of IL-1α or IL-1β of myeloid versus colon non-hematopoietic cells in inflammation and repair in acute colitis. <h3>Results</h3> IL-1α released from damaged IECs acts as an alarmin by initiating and propagating colon inflammation, as IL-1α deficient mice exhibited mild disease symptoms with improved recovery. IL-1β is involved in repair of IECs and reconstitution of the epithelial barrier during the resolution of colitis; its deficiency correlates with disease exacerbation. Neutralisation of IL-1α in control mice during acute colitis led to alleviation of clinical and histological manifestations, whereas treatment with rIL-1Ra or anti-IL-1β antibodies was not effective. Repair after colitis correlated with accumulation of CD8 and regulatory T cells in damaged crypts. <h3>Conclusions</h3> The role of IL-1α and IL-1β differs in DSS-induced colitis in that IL-1α, mainly of colon epithelial cells is inflammatory, whereas IL-1β, mainly of myeloid cell origin, promotes healing and repair. Given the dissimilar functions of each IL-1 agonistic molecule, an IL-1 receptor blockade would not be as therapeutically effective as specific neutralising of IL-1α, which leaves IL-1β function intact.
Caffeine, maximal power output and fatigue.
Authors: J H Williams, J F Signorile, W S Barnes, T W Henrich
Journal: British Journal of Sports Medicine (1988)

The purpose of this investigation was to determine the effects of caffeine ingestion on maximal power output and fatigue during short term, high intensity exercise. Nine adult males performed 15 s maximal exercise bouts 60 min after ingestion of caffeine (7 mg.kg-1) or placebo. Exercise bouts were carried out on a modified cycle ergometer which allowed power output to be computed for each one-half pedal stroke via microcomputer. Peak power output under caffeine conditions was not significantly different from that obtained following placebo ingestion. Similarly, time to peak power, total work, power fatigue index and power fatigue rate did not differ significantly between caffeine and placebo conditions. These results suggest that caffeine ingestion does not increase one's maximal ability to generate power. Further, caffeine does not alter the rate or magnitude of fatigue during high intensity, dynamic exercise.