tbuckley/cabot-search huggingface dataset:
Induction of remission in active anti-neutrophil cytoplasmic antibody-associated vasculitis with mycophenolate mofetil in patients who cannot be treated with cyclophosphamide
Authors: P. M Stassen, J. W. Cohen Tervaert, C. A Stegeman
Journal: Annals of the Rheumatic Diseases (2006)

Active anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is commonly treated with cyclophosphamide, a drug with serious side effects, and with corticosteroids.
The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro
Authors: C Feldman, R Read, A Rutman, PK Jeffery, A Brain, V Lund, TJ Mitchell, PW Andrew, GJ Boulnois, HC Todd, al. et
Journal: European Respiratory Journal (1992)

The interaction of Streptococcus pneumoniae with human ciliated upper respiratory mucosa was studied in an agar-embedded organ culture of nasal turbinate tissue, which only exposed the intact epithelial surface and its secretion. The ciliary beat frequency, measured along the edge of the organ culture, was slowed by 13% in the presence of S. pneumoniae after 16 h (p less than 0.05) compared with the control, and by 24% after 24 h (p less than 0.01). Light microscopy showed bacteria in a thickened gelatinous layer, which obscured the surface of the organ culture. Transmission and scanning electron microscopy confirmed the association of bacteria with the gelatinous layer above an epithelial surface which showed only minor changes compared to uninfected control organ cultures. Contact between bacteria and normal or damaged epithelial cells was not seen. S. pneumoniae in organ culture developed projections from their surface, which were not present after broth culture. S. pneumoniae interactions with epithelial-derived secretions, the formation of a thickened gelatinous layer, and the effects of bacterial toxins on ciliary motility, may be important during colonization of the respiratory tract.
Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection
Authors: Karin Nielsen-Saines, D. Heather Watts, Valdilea G. Veloso, Yvonne J. Bryson, Esau C. Joao, Jose Henrique Pilotto, Glenda Gray, Gerhard Theron, Breno Santos, Rosana Fonseca, Regis Kreitchmann, Jorge Pinto, Marisa M. Mussi-Pinhata, Mariana Ceriotto, Daisy Machado, James Bethel, Marisa G. Morgado, Ruth Dickover, Margaret Camarca, Mark Mirochnick, George Siberry, Beatriz Grinsztejn, Ronaldo I. Moreira, Francisco I. Bastos, Jiahong Xu, Jack Moye, Lynne M. Mofenson
Journal: New England Journal of Medicine (2012)

The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.
Metabolic Adaptation During a Sequence of No-Flow and Low-Flow Ischemia
Authors: R. Ferrari, A. Cargnoni, P. Bernocchi, E. Pasini, S. Curello, C. Ceconi, T.J.C. Ruigrok
Journal: Circulation (1996)

Background Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hypoperfusion. Methods and Results We investigated, in isolated rabbit heart, whether a brief episode of global ischemia followed by hypoperfusion maintains viability. Four groups were studied: group 1, 300 minutes of aerobia; group 2, 240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hypoperfusion (90% coronary flow reduction), and 60 minutes of reperfusion; and group 4, 240 minutes of hypoperfusion followed by reperfusion. In group 3, viability was maintained. Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2±0.01 to 6.1±0.8), creatine phosphate (CP), and ATP (from 54.5±5.0 and 25.0±1.9 to 5.0±1.1 and 15.3±2.5 μmol/g dry wt, P &lt;.01). Subsequent hypoperfusion failed to restore contraction and pH but improved CP (from 5.0±1.1 to 20.1±3.4, P &lt;.01). Reperfusion restored pH, developed pressure (to 92.3%), and NAD/NADH and caused a washout of lactate and creatine phosphokinase with no alterations of mitochondrial function or oxidative stress. In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2±0.7, diastolic pressure increased to 34±5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred. Reperfusion partially restored cardiac metabolism and function (47%). Conclusions A brief episode of total ischemia without intermittent reperfusion maintains viability despite prolonged hypoperfusion. This could be mediated by metabolic adaptation, preconditioning, or both.
CpG Island Methylator Phenotype and Childhood Leukemia
Authors: Norman J. Lacayo, Jorge F. DiMartino, Michael C. Wei, Gary V. Dahl
Journal: Clinical Cancer Research (2006)

In this issue, Roman-Gomez et al. ([1][1]) report on the correlation of a positive CpG island methylator phenotype (CIMP) status, defined by aberrant hypermethylation of four genes ( DKK3, sFRP2, PTEN , and P73 ) with outcome in children with acute lymphoblastic leukemia (ALL) who harbor the TEL-
Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy
Authors: V. Beral, G. Reeves, D. Bull, J. Green
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundAlthough breast cancer risk is greater in users of estrogen–progestin than estrogen-only formulations of menopausal hormonal therapy, reports on their effects have been somewhat inconsistent. We investigated whether the timing of these therapies affected breast cancer incidence.
Autocrine vascular endothelial growth factor signaling promotes cell proliferation and modulates sorafenib treatment efficacy in hepatocellular carcinoma
Authors: Sui Peng, Ye Wang, Hong Peng, Dong Chen, Shunli Shen, Baogang Peng, Minhu Chen, Riccardo Lencioni, Ming Kuang
Journal: Hepatology (2014)

Tumor cells express vascular endothelial growth factor (VEGF) that can activate VEGF receptors (VEGFRs) on or within tumor cells to promote growth in an angiogenesis-independent fashion; however, this autocrine VEGF pathway has not been reported in hepatocellular carcinoma (HCC). Sorafenib, an angiogenic inhibitor, is the only drug approved for use in advanced HCC patients. Yet the treatment efficacy is diverse and the mechanism behind it remains undetermined. Our aims were to study the molecular mechanisms underlying autocrine VEGF signaling in HCC cells and evaluate the critical role of autocrine VEGF signaling on sorafenib treatment efficacy. By immunohistochemistry, we found robust nuclear and cytoplasmic staining for active, phosphorylated VEGF receptor 1 (pVEGFR1) and phosphorylated VEGF receptor 2 (pVEGFR2), and by western blotting we found that membrane VEGFR1 and VEGFR2 increased in HCC tissues. We showed that autocrine VEGF promoted phosphorylation of VEGFR1 and VEGFR2 and internalization of pVEGFR2 in HCC cells, which was both pro-proliferative through a protein lipase C-extracellular kinase pathway and self-sustaining through increasing VEGF, VEGFR1, and VEGFR2 mRNA expressions. In high VEGFR1/2-expressing HepG2 cells, sorafenib treatment inhibited cell proliferation, reduced VEGFR2 mRNA expression in vitro, and delayed xenograft tumor growth in vivo . These results were not found in low VEGFR1/2-expressing Hep3B cells. In an advanced HCC population on sorafenib treatment for postoperative recurrence, we found that the absence of VEGFR1 or VEGFR2 expression in resected tumor tissues before sorafenib treatment was associated with poorer overall survival. Conclusion : Autocrine VEGF signaling directly promotes HCC cell proliferation and affects the sorafenib treatment outcome in vitro and in vivo , which may enable better stratification for clinical treatment decisions. (Hepatology 2014;60:1264–1277)
Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction
Authors: Marc P. Bonaca, Deepak L. Bhatt, Marc Cohen, Philippe Gabriel Steg, Robert F. Storey, Eva C. Jensen, Giulia Magnani, Sameer Bansilal, M. Polly Fish, Kyungah Im, Olof Bengtsson, Ton Oude Ophuis, Andrzej Budaj, Pierre Theroux, Mikhail Ruda, Christian Hamm, Shinya Goto, Jindrich Spinar, José Carlos Nicolau, Robert G. Kiss, Sabina A. Murphy, Stephen D. Wiviott, Peter Held, Eugene Braunwald, Marc S. Sabatine
Journal: New England Journal of Medicine (2015)

The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding.The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively.In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).
How to read a paper: Statistics for the non-statistician. I: Different types of data need different statistical tests
Authors: T. Greenhalgh
Journal: BMJ (1997)

As medicine leans increasingly on mathematics no clinician can afford to leave the statistical aspects of a paper to the “experts.” If you are numerate, try the “Basic Statistics for Clinicians” series in the Canadian Medical Association Journal 1 2 3 4 or a more mainstream statistical textbook.5 If, on the other hand, you find statistics impossibly difficult, this article and the next in this series give a checklist of preliminary questions to help you appraise the statistical validity of a paper.

### Have they determined whether their groups are comparable, and, if necessary, adjusted for baseline differences?

Most comparative clinical trials include either a table or a paragraph in the text showing the baseline characteristics of the groups being studied. Such a table should show that the intervention and control groups are similar in terms of age and sex distribution and key prognostic variables (such as the average size of a cancerous lump). Important differences in these characteristics, even if due to chance, can pose a challenge to your interpretation of results. In this situation, adjustments can be made to allow for these differences and hence strengthen the argument.6

#### Summary points

In assessing the choice of statistical tests in a paper, first consider whether groups were analysed for their comparability at baseline

Does the test chosen reflect the type of data analysed (parametric or non-parametric, paired or unpaired)?

Has a two tailed test been performed whenever the effect of an intervention could conceivably be a negative one?

Have the data been analysed according to the original study protocol?

If obscure tests have been used, do the authors justify their choice and provide a reference?

### What sort of data have they got, and have they used appropriate statistical tests?

Numbers are often used to label the properties of things. We can assign a number to represent our height, weight, and so on. For properties like these, the measurements can be treated as actual numbers. We can, for example, calculate the …
Treatment with Sunitinib Enabled Complete Resection of Massive Lymphadenopathy not Previously Amenable to Excision in a Patient with Renal Cell Carcinoma
Authors: Jean-Jacques Patard, Rodolphe Thuret, Avakian Raffi, Brigitte Laguerre, Karim Bensalah, Stéphane Culine
Journal: European Urology (2008)
Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: L. Stenholm, J. Stoehlmacher-Williams, S.E. Al-Batran, N. Heussen, S. Akin, C. Pauligk, S. Lehmann, T. Senff, R.D. Hofheinz, G. Ehninger, M. Kramer, E. Goekkurt
Journal: Annals of Oncology (2013)
The National Football Head and Neck Injury Registry
Authors: Joseph S. Torg
Journal: JAMA (1985)

Data on cervical spine injuries resulting from participation in football have been compiled by a national registry. Analysis of epidemiologic data and cinematographic documentation clearly demonstrated that the majority of cervical fractures and dislocations were due to axial loading. On the basis of this observation, rule changes banning both deliberate "spearing" and the use of the top of the helmet as the initial point of contact in making a tackle were implemented at the high school and college level. Subsequently, a marked decrease in cervical spine injury rates has occurred. The occurrence of permanent cervical quadriplegia decreased from 34 in 1976 to five in the 1984 season. It is suggested that axial loading of the cervical spine is also responsible for the catastrophic injuries in diving, rugby, ice hockey, and gymnastics. Implementation of appropriate changes in playing techniques and/or equipment modifications could possibly reduce the incidence of cervical spine injuries in these activities.
GENETIC CONTROL OF THE ANTIBODY RESPONSE
Authors: Hugh O. McDevitt, Michael Sela
Journal: The Journal of Experimental Medicine (1967)

CBA and C57 mice were tested for their ability to make an immune response to a related series of branched, multichain synthetic polypeptide antigens in which the antigenic determinants on the amino termini of the branched side chains were systematically varied. Neither strain responded to the polyglutamic acid determinant. Both strains responded well and equally to the poly(phenylalanine, glutamic acid) determinants. CBA mice responded poorly, and C57 mice responded well to two different antigens bearing poly(tyrosine, glutamic acid) determinants. CBA mice responded well, and CS7 mice responded poorly to two different antigens bearing poly(histidine, glutamic acid) determinants. The genetic control of the immune response to (H,G)-A--L appears to be dominant and polygenic, as it has been shown to be for (T,G)-A--L. The related antigens used in this study show extensive cross-reactions with antisera against other members of the related series.
S100A8/A9 Proteins Mediate Neutrophilic Inflammation and Lung Pathology during Tuberculosis
Authors: Radha Gopal, Leticia Monin, Diana Torres, Samantha Slight, Smriti Mehra, Kyle C. McKenna, Beth A. Fallert Junecko, Todd A. Reinhart, Jay Kolls, Renata Báez-Saldaña, Alfredo Cruz-Lagunas, Tatiana S. Rodríguez-Reyna, Nathella Pavan Kumar, Phillipe Tessier, Johannes Roth, Moisés Selman, Enrique Becerril-Villanueva, Javier Baquera-Heredia, Bridgette Cumming, Victoria O. Kasprowicz, Adrie J. C. Steyn, Subash Babu, Deepak Kaushal, Joaquín Zúñiga, Thomas Vogl, Javier Rangel-Moreno, Shabaana A. Khader
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: A hallmark of pulmonary tuberculosis (TB) is the formation of granulomas. However, the immune factors that drive the formation of a protective granuloma during latent TB, and the factors that drive the formation of inflammatory granulomas during active TB, are not well defined.Objectives: The objective of this study was to identify the underlying immune mechanisms involved in formation of inflammatory granulomas seen during active TB.Methods: The immune mediators involved in inflammatory granuloma formation during TB were assessed using human samples and experimental models of Mycobacterium tuberculosis infection, using molecular and immunologic techniques.Measurements and Main Results: We demonstrate that in human patients with active TB and in nonhuman primate models of M. tuberculosis infection, neutrophils producing S100 proteins are dominant within the inflammatory lung granulomas seen during active TB. Using the mouse model of TB, we demonstrate that the exacerbated lung inflammation seen as a result of neutrophilic accumulation is dependent on S100A8/A9 proteins. S100A8/A9 proteins promote neutrophil accumulation by inducing production of proinflammatory chemokines and cytokines, and influencing leukocyte trafficking. Importantly, serum levels of S100A8/A9 proteins along with neutrophil-associated chemokines, such as keratinocyte chemoattractant, can be used as potential surrogate biomarkers to assess lung inflammation and disease severity in human TB.Conclusions: Our results thus show a major pathologic role for S100A8/A9 proteins in mediating neutrophil accumulation and inflammation associated with TB. Thus, targeting specific molecules, such as S100A8/A9 proteins, has the potential to decrease lung tissue damage without impacting protective immunity against TB.
Roller Disco Neuropathy
Authors: L. Dana Dewitt
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The current craze of disco roller skating has produced a new entrapment syndrome. A 16-year-old female disco roller skater had complaints of numbness along the medial and dorsal aspect of her right foot. Symptoms began after a night of disco roller skating when she noted a throbbing, aching sensation on the dorsum and medial surface of her foot. The next morning she experienced numbness over the same area that persisted for three months while she continued to roller disco. Her examination showed an area of substantially decreased pinprick and light touch on the dorsum and medial surface of the right foot, most dense from the arch to the middle of the top of the foot, involving the great toe, and, to a lesser extent, extending laterally involving the dorsal surface of the second, third, and fourth toes. Findings for the remainder of the neurological examination, including electromyogram
Minority Adult Survivors of Childhood Cancer: A Comparison of Long-Term Outcomes, Health Care Utilization, and Health-Related Behaviors From the Childhood Cancer Survivor Study
Authors: Sharon M. Castellino, Jacqueline Casillas, Melissa M. Hudson, Ann C. Mertens, John Whitton, Sandra L. Brooks, Lonnie K. Zeltzer, Arthur Ablin, Robert Castleberry, Wendy Hobbie, Sue Kaste, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2005)

To determine the influence of race/ethnicity on outcomes in the Childhood Cancer Survivor Study (CCSS).
New penalties proposed for Dutch doctors who flout euthanasia law
Authors: Tony Sheldon
Journal: BMJ (2004)

Doctors could face a wider range of penalties in future for breaking the Netherlands' legal guidelines on euthanasia and assisted suicide, as part of a package of government measures designed to tighten its policy on “life-ending treatment.”

The government is worried that although research indicates doctors carry out about 3500 cases of euthanasia a year they only report about half that number to the authorities.

At the moment the public prosecution service makes a distinction between cases where doctors disregard “procedural” guidelines, such as failing to consult an independent second doctor, and cases where doctors ignore more weighty “material” guidelines, such as the need for a voluntary and well considered …
Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
Authors: Paul Little, Beth Stuart, Michael Moore, Samuel Coenen, Christopher C Butler, Maciek Godycki-Cwirko, Artur Mierzecki, Slawomir Chlabicz, Antoni Torres, Jordi Almirall, Mel Davies, Tom Schaberg, Sigvard Mölstad, Francesco Blasi, An De Sutter, Janko Kersnik, Helena Hupkova, Pia Touboul, Kerenza Hood, Mark Mullee, Gilly O'Reilly, Curt Brugman, Herman Goossens, Theo Verheij
Journal: The Lancet Infectious Diseases (2012)

Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older.Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N).1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595).When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.