tbuckley/cabot-search huggingface dataset:
Testing Clonal Relatedness of Tumors Using Array Comparative Genomic Hybridization: A Statistical Challenge
Authors: Irina Ostrovnaya, Colin B. Begg
Journal: Clinical Cancer Research (2010)

In recent years several investigative groups have sought to use array technologies that characterize somatic alterations in tumors, such as array comparative genomic hybridization (ACGH), to classify pairs of tumors from the same patients as either independent primary cancers or metastases. A wide variety of strategies have been proposed. Several groups have endeavored to use hierarchical clustering for this purpose. This technique was popularized in genomics as a means of finding clusters of patients with similar gene expression patterns with a view to finding subcategories of tumors with distinct clinical characteristics. Unfortunately, this method is not well suited to the problem of classifying individual pairs of tumors as either clonal or independent. In this article we show why hierarchical clustering is unsuitable for this purpose, and why this method has the paradoxical property of producing a declining probability that clonal tumor pairs will be correctly identified as more information is accrued (i.e., more patients). We discuss alternative strategies that have been proposed, which are based on more conventional conceptual formulations for statistical testing and diagnosis, and point to the remaining challenges in constructing valid and robust techniques for this problem.
Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
Authors: Sanae Haga, Keita Terui, Hui Qi Zhang, Shin Enosawa, Wataru Ogawa, Hiroshi Inoue, Torayuki Okuyama, Kiyoshi Takeda, Shizuo Akira, Tetsuya Ogino, Kaikobad Irani, Michitaka Ozaki
Journal: Journal of Clinical Investigation (2003)

Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration. In order to investigate the hepatoprotective effects of Stat3, we examined whether Stat3 protects against Fas-mediated liver injury in the mouse. A constitutively activated form of Stat3 (Stat3-C) was adenovirally overexpressed in mouse liver by intravenous injection, and then a nonlethal dose of Fas agonist (Jo2) was injected intraperitoneally into the mouse (0.3 μg/g body wt). Stat3-C dramatically suppressed both apoptosis and necrosis induced by Jo2. In contrast, liver-specific Stat3-knockout mice failed to survive following Jo2 injection. Stat3-C upregulated expression of FLICE inhibitor protein (FLIP), Bcl-XL, and Bcl-2, and accordingly downregulated activities of FLICE and caspase-3 that were redox-independent. Interestingly, Stat3-C also upregulated the redox-associated protein redox factor-1 (Ref-1) and reduced apoptosis in liver following Jo2 injection by suppressing oxidative stress and redox-sensitive caspase-3 activity. These findings indicate that Stat3 activation protects against Fas-mediated liver injury by inhibiting caspase activities in redox-dependent and -independent mechanisms.
Serratia marcescens Infections from Inhalation Therapy Medications: Nosocomial Outbreak
Authors: Charles V. Sanders, James P. Luby, Waldemar G. Johanson, Jack A. Barnett, Jay P. Sanford
Journal: Annals of Internal Medicine (1970)

An outbreak of nosocomial infections caused by non-pigmented Serratia marcescens is described. There were 655 bacterial isolates from 374 patients during a 10-month period; 50.4% of isolates were from sputum, 24.5% from urine, and the remainder from wounds, blood, and miscellaneous sites. Opened bottles of aerosol inhalation therapy medications were implicated. Forty-three percent of a random sample of opened bottles were contaminated with S. marcescens, and viable bacterial counts reached 107 organisms per milliliter. Factors responsible for initiation of the epidemic were defined, control measures were instituted, and the outbreak stopped. This experience emphasizes the problems in recognition of hospital-associated infections. The importance of underlying host determinants in the occurrence of disease from exposure to Gram-negative bacilli is discussed.
Adult onset polymyositis/dermatomyositis: clinical and laboratory features and treatment response in 75 patients.
Authors: E T Koh, A Seow, B Ong, P Ratnagopal, H Tjia, H H Chng
Journal: Annals of the Rheumatic Diseases (1993)

To determine possible similarities and differences in clinical and laboratory features and treatment response between patients in Singapore with polymyositis (PM) and dermatomyositis (DM) and reported series.Case records of adult patients (16 years old and above) referred to the 3 main electromyographic (EMG) laboratories in Singapore between 1 June 1986 and 31 May 1991 were reviewed if the referring diagnosis was myositis or myopathy for investigation. A computer search for adult patients with a diagnosis of PM/DM (ICD codes 710.3, 710.4, 517.8) who attended the main rheumatology and neurology centre during this period was also carried out. The criteria for PM/DM proposed by Bohan and Peter was adopted.The incidence of PM/DM was 7.7 cases per million population per year. There were 35 PM and 40 DM cases with a median age at diagnosis of 50.7 years (SD: 16.7) and significantly more females in the PM group (p < 0.05). At presentation, 86.7% had proximal myopathy, 34.7% had arthralgia/arthritis and 18.7% had cutaneous vasculitis. The creatine kinase level was elevated in 89.3% of patients and positive EMG and muscle biopsy in 79.4% and 76.4% respectively. Systemic lupus erythematosus was the commonest associated connective tissue disease. The percentage of patients with malignancy was higher in DM compared with PM (p < 0.01) and they were significantly older (mean age 61.8 years) (p < 0.001). Patients who achieved remission were significantly younger (mean age 46.4 years, p < 0.05). The overall mortality rate was 26.7% with infection and malignancy as the main causes of death.The results of the study suggest ethnicity does not influence the expression of PM/DM in view of the considerable similarities in frequency and clinical expression of disease in the population studied compared with series from other countries.
SOME NOTES ON THE ABSORPTION OF IRON
Authors: D. G. M. Munro
Journal: BMJ (1911)

JUY 5,1II1 IR NMEDICAL JOURNAL I0above, was begun, and except for the two rises of tempera- *ture occurring with the other symptoms of poisoning, no fevers have occurred, and trypanosomes have not been 'found in the peripheral blood or in animals inoculated with blood and spinal fluid.That is, parasites and fever have been absent for one and a half years.
Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-γ
Authors: Christian Schürch, Carsten Riether, Michael A. Amrein, Adrian F. Ochsenbein
Journal: The Journal of Experimental Medicine (2013)

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia arising from the oncogenic break point cluster region/Abelson murine leukemia viral oncogene homolog 1 translocation in hematopoietic stem cells (HSCs), resulting in a leukemia stem cell (LSC). Curing CML depends on the eradication of LSCs. Unfortunately, LSCs are resistant to current treatment strategies. The host’s immune system is thought to contribute to disease control, and several immunotherapy strategies are under investigation. However, the interaction of the immune system with LSCs is poorly defined. In the present study, we use a murine CML model to show that LSCs express major histocompatibility complex (MHC) and co-stimulatory molecules and are recognized and killed by leukemia-specific CD8+ effector CTLs in vitro. In contrast, therapeutic infusions of effector CTLs into CML mice in vivo failed to eradicate LSCs but, paradoxically, increased LSC numbers. LSC proliferation and differentiation was induced by CTL-secreted IFN-γ. Effector CTLs were only able to eliminate LSCs in a situation with minimal leukemia load where CTL-secreted IFN-γ levels were low. In addition, IFN-γ increased proliferation and colony formation of CD34+ stem/progenitor cells from CML patients in vitro. Our study reveals a novel mechanism by which the immune system contributes to leukemia progression and may be important to improve T cell–based immunotherapy against leukemia.
Ischemic Preconditioning Provides Both Acute and Delayed Protection against Renal Ischemia and Reperfusion Injury in Mice
Authors: Jin Deok Joo, Mihwa Kim, Vivette D. D’Agati, H. Thomas Lee
Journal: Journal of the American Society of Nephrology (2006)

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.
Association of Vitamin D Receptor Genetic Variants with Susceptibility to Asthma and Atopy
Authors: Audrey H. Poon, Catherine Laprise, Mathieu Lemire, Alexandre Montpetit, Donna Sinnett, Erwin Schurr, Thomas J. Hudson
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Genome scans for asthma have identified suggestive or significant linkages on 17 different chromosomes, including chromosome 12, region q13-23, housing the vitamin D receptor (VDR) gene. Through interaction with VDR, 1,25-dihydroxyvitamin D3 mediates numerous biological activities, such as regulation of helper T-cell development and subsequent cytokine secretion profiles. Variants of the VDR have been found to be associated with immune-mediated diseases that are characterized by an imbalance in helper T-cell development, such as Crohn's disease and tuberculosis. The VDR, hence, is a good candidate to be investigated for association with asthma, which is characterized by enhanced helper T-cell type 2 activity. Here, we examined VDR genetic variants in an asthma family-based cohort from Quebec. We report six variants to be strongly associated with asthma and four with atopy (0.0005 < or = p < or = 0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004 < or = p < or = 0.01). The findings have been replicated by another research team in a second but not in a third cohort. These results identify VDR variants as genetic risk factors for asthma/atopy and implicate a non-human leukocyte antigen immunoregulatory molecule in the pathogenesis of asthma and atopy.
Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis
Authors: Martin Adam, Tamara Schikowski, Anne Elie Carsin, Yutong Cai, Benedicte Jacquemin, Margaux Sanchez, Andrea Vierkötter, Alessandro Marcon, Dirk Keidel, Dorothee Sugiri, Zaina Al Kanani, Rachel Nadif, Valérie Siroux, Rebecca Hardy, Diana Kuh, Thierry Rochat, Pierre-Olivier Bridevaux, Marloes Eeftens, Ming-Yi Tsai, Simona Villani, Harish Chandra Phuleria, Matthias Birk, Josef Cyrys, Marta Cirach, Audrey de Nazelle, Mark J. Nieuwenhuijsen, Bertil Forsberg, Kees de Hoogh, Christophe Declerq, Roberto Bono, Pavilio Piccioni, Ulrich Quass, Joachim Heinrich, Deborah Jarvis, Isabelle Pin, Rob Beelen, Gerard Hoek, Bert Brunekreef, Christian Schindler, Jordi Sunyer, Ursula Krämer, Francine Kauffmann, Anna L. Hansell, Nino Künzli, Nicole Probst-Hensch
Journal: European Respiratory Journal (2014)

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO 2 , NO x ) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m −3 increase in NO 2 exposure was associated with lower levels of FEV 1 (−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m −3 in PM 10 , but not other PM metrics (PM 2.5 , coarse fraction of PM, PM absorbance), was associated with a lower level of FEV 1 (−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.
Does bowel cancer screening detect colorectal cancers at an earlier stage?
Authors: P. Patel, T. Pirani, R. Leicester, M. Bouwer, A. Poullis
Journal: Gut (2011)

<h3>Introduction</h3> The NHS bowel cancer screening program (NHS BCSP) currently screens persons between the ages of 60 and 69 for bowel cancer with the aim to detect early cancer and reduce colorectal cancer (CRC) mortality. The inclusion age is currently being extended to 74. The NHS BCSP began in 2006 in England and Nationwide coverage was achieved in 2010. Individuals are invited biennially to provide a stool sample for faecal occult blood test (FOBt) analysis. Bowel cancer usually presents once symptoms occur and as a result at an advanced stage (Duke9s stage at diagnosis A 11% vs C/D 54%1). Pilot studies of the NHS BCSP showed a reduction in the stage of cancer at diagnosis (Duke9s stage at diagnosis (42% stage A, C/D 28.2%2). This abstract examines whether the introduction of the NHS BCSP has a real-life effect on stage of CRC at diagnosis in patients from a large screening centre. <h3>Methods</h3> Data from BCSP patients from January 2007 to December 2009 were obtained from the database at the South West London BCS centre based at St. Georges9. Data on non-BCSP patients from January 2003 to December 2007 was obtained from local cancer network databases. <h3>Results</h3> The table below shows the numbers of cancers and their stage at diagnosis for both patient groups. A higher proportion of Duke9s A CRC are diagnosed in patients through the BCSP (43% vs 13%; p&lt;0.05 c<sup>2</sup> test). 26 cancers in the BCSP were in fact polyp cancers which have been included in the Duke9s A group. <h3>Conclusion</h3> Our results are in keeping with previous pilot data2 and a previously presented abstract3 and show that the BCSP detects CRC at a relatively earlier stage compared to non-BCSP patients. This study needs to be repeated at intervals to see whether this difference changes with further BCSP rounds.
Primary healthcare factors and hospital admission rates for COPD: no association
Authors: Patrick White, Ana Lucia Jamieson
Journal: Thorax (2013)

As the ‘observant researchers’ who questioned the R2 value reported by Calderon-Larranaga et al we were disappointed by the correction in Thorax , 10 July 2013.1 ,2 Our concerns were raised by the high adjusted R2 value of 0.75 in the multivariate linear regression of the association of primary care trust (PCT) factors with PCT hospital admission rates and the high bivariate R2 value attributed to general practitioner (GP) supply.

The authors pointed out to us their misreading of the bivariate ‘GP supply’ R2 of 0.14% which led to the error. We were surprised to read in their correction that the R2 value of 14.4% …
How policy informs the evidence
Authors: G. Davey Smith
Journal: BMJ (2001)

Education and debate p 222 

Who would not want health policy to be based on evidence? “Evidence based medicine” and “evidence based policy” have such reassuring and self evidently desirable qualities that it may seem contrary to question their legitimacy in relation to reducing health inequalities. However, these terms are now so familiar that it is easy to forget the important question about what sort of data provide appropriate evidence for particular types of decisions. The sort of evidence gathered on the benefits of interventions aimed at individuals may not help in guiding policies directed towards reducing health inequalities.

In this week's BMJ readers have the opportunity to assess part of the process leading to the recommendations of the Independent Inquiry into Health Inequalities (the Acheson inquiry),1 established in 1997 to help the government formulate policy to reduce health inequalities. The inquiry established an evaluation group to report on the quality of the evidence it used to reach its conclusions and support its recommendations.2 This group critiqued submissions to the inquiry, and a list of its own remedies for health inequalities—their “10 steps to health equality”—was released before the Acheson inquiry had itself reported (see box on bmj.com).3

The evaluation group appears to have applied evidence based principles to its consideration of ways to reduce inequalities in health. Essentially it wanted evidence from controlled intervention studies, and its main evaluation consisted of …
DXplain. An evolving diagnostic decision-support system
Authors: G. O. Barnett
Journal: JAMA (1987)

DXplain is an evolving computer-based diagnostic decision-support system designed for use by the physician who has no computer expertise. DXplain accepts a list of clinical manifestations and then proposes diagnostic hypotheses. The program explains and justifies its interpretations and provides access to a knowledge base concerning the differential diagnosis of the signs and symptoms. DXplain was developed with the support and cooperation of the American Medical Association. The system is distributed to the medical community through AMA/NET--a nationwide computer communications network sponsored by the American Medical Association--and through the Massachusetts General Hospital Continuing Education Network. A key element in the distribution of DXplain is the planned collaboration with its physician-users whose comments, criticisms, and suggestions will play an important role in modifying and enhancing the knowledge base.
Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study
Authors: Jean-Michel Molina, Chloe Orkin, David M Iser, Francisco-Xavier Zamora, Mark Nelson, Christoph Stephan, Benedetta Massetto, Anuj Gaggar, Liyun Ni, Evguenia Svarovskaia, Diana Brainard, G Mani Subramanian, John G McHutchison, Massimo Puoti, Jürgen K Rockstroh
Journal: The Lancet (2015)
Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial
Authors: D. P Trivedi
Journal: BMJ (2003)

TNFR-associated factors (TRAFs) participate in the signaling of many TNFR family members, including CD40, CD120a (TNFR1), and CD120b (TNFR2). Previously, we found that a dominant-negative TRAF2 molecule inhibits CD40-mediated Ab secretion by the mouse B cell line CH12.LX. However, disruption of the TRAF2 binding site in the cytoplasmic domain of CD40 does not diminish the ability of CD40 to stimulate Ab secretion, nor is this mutation able to circumvent the inhibition of Ab secretion by dominant-negative TRAF2. Here we demonstrate that CD40-induced TNF stimulates IgM production through CD120b and that CD120b signaling is required for optimal CD40-induced IgM secretion. Furthermore, although both CD40 and CD120b can bind TRAF2, TRAF2-dependent CD40 signals cannot substitute for TRAF2-dependent CD120b signals in the activation of IgM secretion. Our results indicate a potentially important role for CD120b in the activation of IgM secretion and that TRAF2 is used by CD40 and CD120b in distinct ways.
The Impact of Sugar Cane–Burning Emissions on the Respiratory System of Children and the Elderly
Authors: José E.D. Cançado, Paulo H.N. Saldiva, Luiz A.A. Pereira, Luciene B.L.S. Lara, Paulo Artaxo, Luiz A. Martinelli, Marcos A. Arbex, Antonella Zanobetti, Alfesio L.F. Braga
Journal: Environmental Health Perspectives (2006)

We analyzed the influence of emissions from burning sugar cane on the respiratory system during almost 1 year in the city of Piracicaba in southeast Brazil. From April 1997 through March 1998, samples of inhalable particles were collected, separated into fine and coarse particulate mode, and analyzed for black carbon and tracer elements. At the same time, we examined daily records of children (<13 years of age) and elderly people (>64 years of age) admitted to the hospital because of respiratory diseases. Generalized linear models were adopted with natural cubic splines to control for season and linear terms to control for weather. Analyses were carried out for the entire period, as well as for burning and nonburning periods. Additional models were built using three factors obtained from factor analysis instead of particles or tracer elements. Increases of 10.2 microg/m3 in particles<or=2.5 microm/m3 aerodynamic diameter (PM2.5) and 42.9 microg/m3 in PM10 were associated with increases of 21.4% [95% confidence interval (CI), 4.3-38.5] and 31.03% (95% CI, 1.25-60.21) in child and elderly respiratory hospital admissions, respectively. When we compared periods, the effects during the burning period were much higher than the effects during nonburning period. Elements generated from sugar cane burning (factor 1) were those most associated with both child and elderly respiratory admissions. Our results show the adverse impact of sugar cane burning emissions on the health of the population, reinforcing the need for public efforts to reduce and eventually eliminate this source of air pollution.