tbuckley/cabot-search huggingface dataset:
Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris)
Authors: Marie Pedersen, Bernadette Schoket, Roger W. Godschalk, John Wright, Hans von Stedingk, Margareta Törnqvist, Jordi Sunyer, Jeanette K. Nielsen, Domenico F. Merlo, Michelle A. Mendez, Helle M. Meltzer, Viktória Lukács, Anette Landström, Soterios A. Kyrtopoulos, Katalin Kovács, Lisbeth E. Knudsen, Margaretha Haugen, Laura J. Hardie, Kristine B. Gützkow, Sarah Fleming, Eleni Fthenou, Peter B. Farmer, Aina Espinosa, Leda Chatzi, Gunnar Brunborg, Nigel J. Brady, Maria Botsivali, Khelifa Arab, Lívia Anna, Jan Alexander, Silvia Agramunt, Jos C. Kleinjans, Dan Segerbäck, Manolis Kogevinas
Journal: Environmental Health Perspectives (2013)

Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs.Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy.Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires.Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g)Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.Citation: Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Törnqvist M, Sunyer J, Nielsen JK, Merlo DF, Mendez MA, Meltzer HM, Lukács V, Landström A, Kyrtopoulos SA, Kovács K, Knudsen LE, Haugen M, Hardie LJ, Gützkow KB, Fleming S, Fthenou E, Farmer PB, Espinosa A, Chatzi L, Brunborg G, Brady NJ, Botsivali M, Arab K, Anna L, Alexander J, Agramunt S, Kleinjans JC, Segerbäck D, Kogevinas M. 2013. Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother–child study (NewGeneris). Environ Health Perspect 121:1200–1206; http://dx.doi.org/10.1289/ehp.1206333
PROPEL: A randomized trial of mericitabine plus peginterferon alpha-2a/ribavirin therapy in treatment-naïve HCV genotype 1/4 patients
Authors: Heiner Wedemeyer, Donald Jensen, Robert Herring, Peter Ferenci, Mang-Ming Ma, Stefan Zeuzem, Maribel Rodriguez-Torres, Natalie Bzowej, Paul Pockros, John Vierling, David Ipe, Marie Lou Munson, Ya-Chi Chen, Isabel Najera, James Thommes
Journal: Hepatology (2013)

Mericitabine is a nucleoside analog polymerase inhibitor of hepatitis C virus (HCV). Treatment-naïve HCV genotype 1 or 4 patients were randomized to double-blind treatment with oral mericitabine at a dosage of 500 mg twice-daily (BID) for 12 weeks (A), 1,000 mg BID for 8 (B) or 12 weeks (C and D), or placebo BID for 12 weeks (E). All patients received pegylated interferon alpha-2a (Peg-IFNα-2a; 40 kD)/ribavirin (RBV) at standard doses for 24 or 48 weeks during and after mericitabine/placebo therapy. Patients in arms A-C who maintained a virologic response (VR) (HCV RNA &lt;15 IU/mL) from weeks 4 to 22 stopped all treatment at week 24; all other patients (arms A-E) continued Peg-IFNα-2a/RBV to complete 48 weeks. The primary outcome was sustained VR (SVR) (HCV RNA &lt;15 IU/mL after 24 weeks of untreated follow-up; SVR-24). VR rates were higher in arms A-D than in arm E at weeks 4 and 12 overall, in patients with and without cirrhosis and in patients with CC and non-CC IL28B genotypes. However, the overall SVR-24 rate in arms D (50.6%) and E (placebo, 51.2%) was similar and those in the response-guided therapy arms A, B, and C were lower (48.8%, 42.0%, and 32.9%, respectively). No viral breakthrough or mericitabine-resistance mutations (S282T) were observed during mericitabine therapy. Conclusion : Treatment with mericitabine plus Peg-IFNα-2a/RBV for 8 or 12 weeks provided potent suppression of HCV RNA, was well tolerated, and did not select resistant variants, but did not increase SVR rates, compared to placebo. IFN-free and IFN-containing trials of mericitabine of longer treatment duration are ongoing. (HEPATOLOGY 2013;58:524–537)
Abstract 3487: Synergy with combined inhibition of upstream EGFR-HER2 and downstream RAF-MEK nodes in breast cancer cells with activating RAS and RAF mutations
Authors: Teddy S. Nagaria, Peter A. Greer, Waheed Sangrar
Journal: Cancer Research (2010)

Abstract Targeted therapies have been developed to target a variety of oncogenic proteins implicated in breast cancer. These include epidermal growth factor receptor (EGFR), epidermal growth factor receptor type-2 (HER-2), as well as RAS, RAF and MEK, which together comprise the mitogen activated protein kinase (MAPK) cascade. Herein, we explored the therapeutic efficacy of tyrosine kinase inhibitors of EGFR and HER-2 by testing these inhibitors on a human metastatic breast cancer cell line MDA-MB-231. We also determined whether inhibiting tyrosine kinase receptors correlated with the activity of downstream nodes such as MEK and ERK. We report that EGFR inhibitors potently inhibited the phosphorylation of EGFR, but had no effect on MEK and ERK activity, which were observed to be constitutively active in this cell line. Interestingly, MEK/ERK insensitivity correlated with cytotoxic resistance of MDA-MB-231 cells to EGFR inhibitor treatment. In contrast, targeting both EGFR and HER-2 with a dual EGFR/HER-2 inhibitor Lapatinib resulted in significantly improved cytotoxic effects and a partial reduction in MEK and ERK activity. In comparison to the effects of Lapatinib, targeting RAF with Sorafenib resulted in almost complete abrogation of MEK/ERK signaling activity and enhanced cytotoxicity. Our results are consistent with earlier reports suggesting that MAPK signaling is required for MDA-MB-231 cell survival, consistent with the reported presence of activating RAS and RAF mutations in this cell line. Our data highlight the role of RAS and RAF mutations in the uncoupling of downstream nodes (MEK and ERK) from upstream receptor activation. Lastly, the MEK inhibitor U1026 fully inhibited ERK activity but exhibited poor cytotoxicity. This suggests that MDA-MB-231 cells may circumvent MEK inhibition through upstream survival pathways mediated by activated RAS or RAF. An apparent synergistic cytotoxic effect was noted when combining Sorafenib and U1026. Cytotoxic synergy was also observed when Sorafenib was combined with Lapatinib. These putative synergistic drug combinations show promise in that they could deliver significant cytotoxic effects with reduced doses. We find there is merit in targeting multiple oncogenic nodes concurrently to promote additional therapeutic benefits. This also shows potential use in targeting a broader variety of cancer cells that harbor constitutive MAPK signaling associated with oncogenic RAS or RAF mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3487.
Therapeutic efficacy of combined blockade of CTLA-4 +/- PD-L1 +/- IDO is associated with re-activation of T cells directly within the tumor microenvironment
Authors: Stefani Spranger, Thomas Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts A major subset of human cancers is associated with CD8+ T cell infiltration yet tumor rejection fails due to the dominant effects of multiple immune inhibitory mechanisms. These include expression of the inhibitory receptors CTLA-4 and PD-1 by T cells and expression of the
SANITATION ON THE RIVIERA
Authors: J. Jones
Journal: BMJ (1930)

<h3>Abstract</h3> <h3>Purpose</h3> There is an urgent need to identify new predictive biomarkers for treatment response to both platinum doublet chemotherapy (PD) and immune checkpoint blockade (ICB) with pembrolizumab. Here we evaluated whether treatment outcome could be affected by <i>KRAS</i> mutational status in patients with metastatic (stage IV) non-small cell lung cancer (NSCLC). <h3>Methods</h3> All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage IV NSCLC in the region of West Sweden were included in this multi-center retrospective study. Primary study outcome was overall survival (OS). <h3>Results</h3> Out of 580 stage IV NSCLC patients, 35.5% harbored an activating mutation in the <i>KRAS</i> gene (KRAS<sup>MUT</sup>). Compared to <i>KRAS</i> wild-type (KRAS<sup>WT</sup>), KRAS<sup>MUT</sup> was a negative factor for OS (<i>p</i> = 0.014). On multivariate analysis, KRAS<sup>MUT</sup> persisted as a negative factor for OS (HR 1.288, 95% CI 1.091-1.521, <i>p</i> = 0.003). When treated with first-line platinum doublet (<i>n</i> = 195), KRAS<sup>MUT</sup> is a negative factor for survival (<i>p</i> = 0.018) with median OS 9 months vs KRAS<sup>WT</sup> 11 months. On multivariate analysis, KRAS<sup>MUT</sup> persisted as a negative factor for OS (HR 1.564, 95%CI 1.124-2.177, <i>p</i> = 0.008). KRAS<sup>MUT</sup> patients with high PD-L1 expression (PD-L1<sup>high</sup>) had better OS than PD-L1<sup>high</sup> KRAS<sup>WT</sup> patients (<i>p</i> = 0.036). In response to first-line ICB, KRAS<sup>MUT</sup> patients had a significant (<i>p</i> = 0.006) better outcome than KRAS<sup>WT</sup> with a median OS 23 vs 6 months. On multivariable Cox analysis, KRAS<sup>MUT</sup> status was an independent prognostic factor for better OS (HR 0.349, 95%CI 0.148-0.822, <i>p</i> = 0.016). <h3>Conclusions</h3> <i>KRAS</i> mutations is a positive predictive factor for treatment with pembrolizumab and a negative predictive factor for platinum doublet chemotherapy as well as general OS in stage IV NSCLC.
Ethics Consultation in United States Hospitals: A National Survey
Authors: Ellen Fox, Sarah Myers, Robert A. Pearlman
Journal: The American Journal of Bioethics (2007)

Context: Although ethics consultation is commonplace in United States (U.S.) hospitals, descriptive data about this health service are lacking. Objective: To describe the prevalence, practitioners, and processes of ethics consultation in U.S. hospitals. Design: A 56-item phone or questionnaire survey of the "best informant" within each hospital. Participants: Random sample of 600 U.S. general hospitals, stratified by bed size. Results: The response rate was 87.4%. Ethics consultation services (ECSs) were found in 81% of all general hospitals in the U.S., and in 100% of hospitals with more than 400 beds. The median number of consults performed by ECSs in the year prior to survey was 3. Most individuals performing ethics consultation were physicians (34%), nurses (31%), social workers (11%), or chaplains (10%). Only 41% had formal supervised training in ethics consultation. Consultation practices varied widely both within and between ECSs. For example, 65% of ECSs always made recommendations, whereas 6% never did. These findings highlight a need to clarify standards for ethics consultation practices.
Efficacy of confronting smokers with airflow limitation for smoking cessation
Authors: D. Kotz, G. Wesseling, M. J. H. Huibers, O. C. P. van Schayck
Journal: European Respiratory Journal (2009)

The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease (COPD) increases the rate of smoking cessation. In total, 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and randomly allocated to: confrontational counselling by a nurse with nortriptyline for smoking cessation (experimental group); regular counselling by a nurse with nortriptyline (control group 1); or “care as usual” for smoking cessation by the general practitioner (control group 2). Only the experimental group was confronted with their abnormal spirometry (mean forced expiratory volume in one second (FEV 1 ) post-bronchodilator 80.5% predicted, mean FEV 1 /forced vital capacity post-bronchodilator 62.5%). There was no difference in cotinine-validated prolonged abstinence rate between the experimental group (11.2%) and control group 1 (11.6%) from week 5–52 (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.43–2.18). The abstinence rate was approximately twice as high in the experimental group compared with control group 2 (5.9%), but this difference was not statistically significant (OR 2.02, 95% CI 0.63–6.46). The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry. The high failure rates (≥88%) highlight the need for treating tobacco addiction as a chronic relapsing disorder.
Women's Medical College of Baltimore.
Authors: W. T. Briggs
Journal: JAMA (1892)

<h3>To the Editor of the Journal of the American Medical Association:</h3> In commencing the instruction in Latin of the students of the Woman's Medical College of this city, I gave the following reasons why as medical students they should acquire a knowledge of that language. I am glad to say that all the students of the college except three or four, and they having previously studied it elsewhere, have joined the class. Because though called a "dead" language, and although not now spoken by any nation, it is not really dead, but flourishes with a perennial and ever increasing vigor. Because of its wide and far-reaching influence on the structure and development of the languages of all civilized nations, especially those of Southern Europe. Because the resources of our language do not suffice for the constantly needed new supply of words, for which we are compelled to resort to the
Giving influenza vaccination to all elderly people would raise ethical issues
Authors: D. King, R. Morgan
Journal: BMJ (1997)

Editor–We agree with Carolyn Diguiseppi that evidence exists for giving influenza vaccine to everyone aged over 65.1 Interestingly, medical insurance companies in the United States have shown that it is cost effective to vaccinate people aged over 65 to reduce the burden of morbidity and mortality. This age related targeting of influenza vaccine would certainly make things simpler …
CD4+ T-Lymphocytopenia without HIV Infection -- No Lights, No Camera, Just Facts
Authors: Anthony S. Fauci
Journal: New England Journal of Medicine (1993)

The devastating global impact of the acquired immunodeficiency syndrome (AIDS) has greatly sensitized the public to the threat of new microbes that are capable of wreaking havoc on the world's population. It is not surprising, therefore, that the unanticipated revelation last July at the Ninth International AIDS Conference in Amsterdam of a small number of people with markedly depressed CD4+ T-lymphocyte counts, with or without opportunistic diseases, in the absence of any evidence of human immunodeficiency virus (HIV) infection or other recognizable cause of immunosuppression resulted in extraordinary media attention and hence great public concern. Among the several subsequent meetings . . .
Netherlands aims to tackle health divide
Authors: T. Sheldon
Journal: BMJ (2001)

Better educated and wealthier Dutch people enjoy on average 12 more years of good health and four more years of life than their poorer, less well educated compatriots.

This socioeconomic divide seems to have increased and may widen further as death rates among richer people fall faster than among the poorer sections of society, because of healthier lifestyles and better access to medical care.

These are among the conclusions of a five year investigation into socioeconomic health inequalities, which was commissioned by the Dutch government and charged with making recommendations on reducing the divide. Socioeconomic inequalities remain similar to …
Genetic Linkage in Neurologic Diseases
Authors: Joseph B. Martin
Journal: New England Journal of Medicine (1987)

Until recently, the hope of identifying genes associated with dominant inherited neurologic disorders seemed remote. Now that has changed. The powerful techniques of molecular biology have provided methods for locating, by linkage analysis, the genes responsible for several of these diseases and for using the same techniques for presymptomatic or prenatal diagnosis of carriers of the abnormal genes. DNA polymorphisms were first identified in the β-globin gene family less than 10 years ago.1 During the past four years, restriction-fragment–length polymorphisms (RFLPs) have been found with use of DNA probes that reside near the gene locus implicated in Huntington's disease2 (chromosome . . .
Filters inserted into the vena cava may be useful for some indications
Authors: M. G Cowling
Journal: BMJ (1998)

EDITOR Minerva suggests that a study published in the New England Journal of Medicine on the insertion of a filter into the vena cava to prevent pulmonary embolism casts doubt on the value of this treatment.1 In this study patients with proximal deep vein thrombosis, deemed to be at high risk of pulmonary embolism, were …
How full is the glass?
Authors: Irving Kirsch, Blair T Johnson
Journal: BMJ (2008)

Instead of speculating about our differing methods as the source of our differing conclusions, Turner and Rosenthal instead focused on our adoption of UK’s National Institute for Health and Clinical Excellence (NICE) criteria for clinical significance. NICE adopted Cohen’s definition of a “medium” effect size (0.5) for clinical significance.1 2 Cohen intended that a medium effect size represent an effect of a size likely to …
The Correction of Hyponatremia in Congestive Heart Failure
Authors: E. HUGH LUCKEY, ALBERT L. RUBIN
Journal: Circulation (1960)

Hyponatremia in congestive heart failure occurs principally in the terminal phases of the natural history of heart disease. Fortunately, in some instances it may occur as a transient event in a setting of sudden deterioration in cardiac function. In such instances, it may be reversible. The most important factor in the occurrence of hyponatremia in these patients is an inordinate retention of water. Thus, the hyponatremia is the result of dilution. Correction of hyponatremia requires the elimination of water in excess of sodium. The futility and dangers of the use of hypertonic sodium chloride are emphasized. A method of controlled administration of mercurial diuretics after elevation of the plasma chlorides toward normal with consequent production of acidosis with chloride salts is reviewed. Diuresis following this procedure results in sodium losses in urine that are hypotonic in relation to plasma. The plasma sodium gradually returns to normal, and the patient progressively loses weight.
EXPLORING THE RELATIONSHIP BETWEEN EPICARDIAL AND INTRA-THORACIC ADIPOSE TISSUE AND VASCULAR CALCIFICATIONS IN TYPE 1 DIABETES: EPIDEMIOLOGY OF DIABETES INTERVENTIONS AND COMPLICATIONS
Authors: Panteha Rezaeian, Jye-Yu Backlund, Sirous Darabian, Aryabod Razipour, Patricia Cleary, Matthew Budoff
Journal: Journal of the American College of Cardiology (2014)
The Lumbar Puncture
Authors: Frank Petito, Fred Plum
Journal: New England Journal of Medicine (1974)

A spate of letters on the subject of lumbar puncture (LP)1 2 3 to the Journal during the last year attest that despite 80 years of experience, controversy still surrounds such basics as indications, technic and avoidance of post-LP headache.Indications for the LP are somewhat on the decline as technical neurodiagnostic methods improve. In the diagnosis of suspected intracranial mass lesions minimal-risk studies such as electroencephalography and radioisotopic brain scan, or definitive procedures such as angiography, pneumoencephalography, or computerized axial tomography, have reduced the utility of the LP except to detect a non-neoplastic process. With intracranial mass lesions, it is rare . . .
Viridans Streptococcal Pneumonia
Authors: Harold D. Rose
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Pratter and Irwin (1980;243:2515) recently described two patients with viridans streptococcal pulmonary parenchymal infections. The organism was recovered in pure culture from a percutaneous transtracheal aspirate in both patients and from a percutaneous lung aspirate and the pleural fluid in one patient. Blood cultures were sterile. Although their laboratory did not speciate these organisms, they suggested that viridans streptococci isolated from these sources be speciated in the future. We agree with this approach but would comment on our recent experience in isolating these organisms from transtracheal aspirates. The physician house staff at our hospital are encouraged to perform a percutaneous transtracheal aspiration on patients with a clinical diagnosis of bacterial pneumonia who are either unable to produce a representative sputum specimen or in whom a Gram's stain of a sputum smear is inconclusive. The culture results of all aspirates submitted between Dec 1, 1977, and Feb 29, 1980,
Neonatal imitation and an epigenetic account of mirror neuron development
Authors: Elizabeth A. Simpson, Nathan A. Fox, Antonella Tramacere, Pier F. Ferrari
Journal: Behavioral and Brain Sciences (2014)

Abstract Neonatal imitation should not exclusively be considered at the population-level; instead, we propose that inconsistent findings regarding its occurrence result from important individual differences in imitative responses. We also highlight what we consider to be a false dichotomy of genetic versus learning accounts of the development of mirror neurons, and instead suggest a more parsimonious epigenetic perspective.
Diabetes Insipidus Following Cardiorespiratory Arrest
Authors: Martin Rothschild
Journal: JAMA (1977)

Diabetes insipidus following cardiac arrest and hypoxemic encephalopathy occurred in two patients. In both, severe hypoxemic brain damage was followed within three days by clinical and laboratory features of diabetes insipidus, which were corrected by administration of exogenous vasopressin. Hypothalamic injury resulting in diabetes insipidus should be considered in the differential diagnosis of polyuria and dehydration occurring in critically ill patients who have suffered cardiorespiratory arrest. (<i>JAMA</i>238:620-621, 1977)