tbuckley/cabot-search huggingface dataset:
Silencing of RON Receptor Signaling Promotes Apoptosis and Gemcitabine Sensitivity in Pancreatic Cancers
Authors: Jocelyn Logan-Collins, Ryan M. Thomas, Peter Yu, Dawn Jaquish, Evangeline Mose, Randall French, William Stuart, Rebecca McClaine, Bruce Aronow, Robert M. Hoffman, Susan E. Waltz, Andrew M. Lowy
Journal: Cancer Research (2010)

The RON receptor tyrosine kinase is overexpressed in premalignant pancreatic intraepithelial neoplasia (PanIN) and in the majority of pancreatic cancers. In pancreatic cells, RON is an important K-Ras effector and RON ligand can enhance migration/invasion and apoptotic resistance. However, the pathobiological significance of RON overexpression in pancreatic cancers has yet to be fully established. In this study, we demonstrate that RON signaling mediates a unique transcriptional program that is conserved between cultured cells derived from murine PanIN or human pancreatic cancer cells grown as subcutaneous tumor xenografts. In both systems, RON signaling regulates expression of genes implicated in cancer-cell survival, including Bcl-2 and the transcription factors signal transducer and activator of transcription 3 (STAT 3) and c-Jun. shRNA-mediated silencing of RON in pancreatic cancer xenografts inhibited their growth, primarily by increasing susceptibility to apoptosis and by sensitizing them to gemcitabine treatment. Escape from RON silencing was associated with re-expression of RON and/or expression of phosphorylated forms of the related c-Met or epidermal growth factor receptors. These findings indicate that RON signaling mediates cell survival and in vivo resistance to gemcitabine in pancreatic cancer, and they reveal mechanisms through which pancreatic cancer cells may circumvent RON-directed therapies.
Childhood Adversities Associated With Risk for Eating Disorders or Weight Problems During Adolescence or Early Adulthood
Authors: Jeffrey G. Johnson, Patricia Cohen, Stephanie Kasen, Judith S. Brook
Journal: American Journal of Psychiatry (2002)

A community-based prospective longitudinal study was conducted to investigate the association between childhood adversities and problems with eating or weight during adolescence and early adulthood.A community-based sample of 782 mothers and their offspring were interviewed during the childhood, adolescence, and early adulthood of the offspring. Childhood maltreatment, eating problems, environmental risk factors, temperament, maladaptive parental behavior, and parental psychopathology were assessed during childhood and adolescence. Eating disorders and problems with eating or weight in the offspring were assessed during adolescence and early adulthood.A wide range of childhood adversities were associated with elevated risk for eating disorders and problems with eating or weight during adolescence and early adulthood after the effects of age, childhood eating problems, difficult childhood temperament, parental psychopathology, and co-occurring childhood adversities were controlled statistically. Numerous unique associations were found between specific childhood adversities and specific types of problems with eating or weight, and different patterns of association were obtained among the male and female subjects. Maladaptive paternal behavior was uniquely associated with risk for eating disorders in offspring after the effects of maladaptive maternal behavior, childhood maltreatment, and other co-occurring childhood adversities were controlled statistically.Childhood adversities may contribute to greater risk for the development of eating disorders and problems with eating and weight that persist into early adulthood. Maladaptive paternal behavior may play a particularly important role in the development of eating disorders in offspring.
Randomized Trial of Continuous Subcutaneous Delivery of Exenatide by ITCA 650 Versus Twice-Daily Exenatide Injections in Metformin-Treated Type 2 Diabetes. Diabetes Care 2013;36:2559–2565
Authors: Robert R. Henry, Julio Rosenstock, Douglas K. Logan, Thomas R. Alessi, Kenneth Luskey, Michelle A. Baron
Journal: Diabetes Care (2013)

In the print version of the article listed above, in Table 2, the units for stage II (12–24 weeks) ITCA 650 20→20 mg, ITCA 650 20→60 mg, and Ex-BID/ITCA 650 …
Appropriate Role for Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Patients With Early-Stage Breast Cancer
Authors: Gary H. Lyman
Journal: Journal of Clinical Oncology (2014)

Few areas of modern medicine have captured the imagination more than the rapid and groundbreaking progress that has been observed in the treatment of patients with early-stage breast cancer (ESBC). It is perhaps because of such dramatic advances that some investigators, not unlike those who take pride in the progress against childhoodleukemia,havebeenaskingwhetherthesameorevenbetter resultscouldbeobtainedwithlessinvasiveapproaches. 1 Inadditionto breast-conserving surgery and the increasing role of more targeted and less toxic treatments, we now have less invasive surgical procedures for both achieving adequate margins and for the assessment of the axillary lymph node status. 2,3
Hidradenitis suppurativa-acne inversa: a relevant dermatosis in paediatric patients
Authors: V. Bettoli, M. Ricci, S. Zauli, A. Virgili
Journal: British Journal of Dermatology (2015)

Journal Article Hidradenitis suppurativa–acne inversa: a relevant dermatosis in paediatric patients Get access V. Bettoli, V. Bettoli Department of Clinical and Experimental Medicine Section of Dermatology University of Ferrara Via Savonarola 9 44100 Ferrara Italy Search for other works by this author on: Oxford Academic Google Scholar M. Ricci, M. Ricci Department of Clinical and Experimental Medicine Section of Dermatology University of Ferrara Via Savonarola 9 44100 Ferrara Italy Search for other works by this author on: Oxford Academic Google Scholar S. Zauli, S. Zauli Department of Clinical and Experimental Medicine Section of Dermatology University of Ferrara Via Savonarola 9 44100 Ferrara Italy Search for other works by this author on: Oxford Academic Google Scholar A. Virgili A. Virgili Department of Clinical and Experimental Medicine Section of Dermatology University of Ferrara Via Savonarola 9 44100 Ferrara Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1328–1330, https://doi.org/10.1111/bjd.13951 Published: 01 November 2015
Evaluating Diagnostic Accuracy in the Face of Multiple Reference Standards
Authors: Christiana A. Naaktgeboren, Joris A.H. de Groot, Maarten van Smeden, Karel G.M. Moons, Johannes B. Reitsma
Journal: Annals of Internal Medicine (2013)

A universal challenge in studies that quantify the accuracy of diagnostic tests is establishing whether each participant has the disease of interest. Ideally, the same preferred reference standard would be used for all participants; however, for practical or ethical reasons, alternative reference standards that are often less accurate are frequently used instead. The use of different reference standards across participants in a single study is known as differential verification. Differential verification can cause severely biased accuracy estimates of the test or model being studied. Many variations of differential verification exist, but not all introduce the same risk of bias. A risk-of-bias assessment requires detailed information about which participants receive which reference standards and an estimate of the accuracy of the alternative reference standard. This article classifies types of differential verification and explores how they can lead to bias. It also provides guidance on how to report results and assess the risk of bias when differential verification occurs and highlights potential ways to correct for the bias.
Efficacy and Safety of Canakinumab in a Large Cohort of Cryopyrin-Associated Periodic Syndrome (CAPS) Patients across All Severity Phenotypes
Authors: R. Cartwright, J. Smith, P. Hawkins, J. Kuemmerle-Deschner, E. Hachulla, I. Kone-Paut, J. Hoyer, P. Quartier, M. Gattorno, A. Widmer, N. Patel, R. Preiss, K. Leslie
Journal: Journal of Allergy and Clinical Immunology (2011)
Barrier recovery rate varies time-dependently in human skin
Authors: M. Denda, T. Tsuchiya
Journal: British Journal of Dermatology (2000)

The recovery in cutaneous barrier functions, assessed in terms of transepidermal water loss, 1 h after tape stripping of volar forearm skin in human volunteers, was investigated at different times over the 24 h day. The barrier recovery rate was significantly lower between 20:00 h and 23:00 h than that at other time points. The skin surface temperature and the basal transepidermal water loss reached their highest values at about 03:00 h (33.6 degrees C and 0.30 mg cm-2 h-1), while the cortisol level in the saliva was highest at 09:00 h (7.8 pmol mL-1). These results suggest significant time-dependent variation in cutaneous barrier repair independent of changes in skin temperature and cortisol level.
Contemporary Medical Options for Treating Patients With Heart Failure
Authors: Marvin A. Konstam, Douglas L. Mann
Journal: Circulation (2002)

study: A 72-year-old woman presented with shortness of breath.Three months earlier, she had begun to notice dyspnea on exertion.This dyspnea progressed to the point that she noted dyspnea at rest in the 24 hours before presentation.She had a history of long-standing mild hypertension, treated with a calcium-channel antagonist, and type 2 diabetes.She denied chest pain, lightheadedness, and abdominal or ankle swelling, although she believed that she had gained between 5 and 10 pounds in recent weeks.On examination, she had a blood pressure of 150/90 mm Hg, a regular pulse at a rate of 90 min Ϫ1 , jugular venous pressure of about 8 cm water, faint bibasilar crackles, a prominent and displaced apical impulse, and a summation gallop, with no murmurs, no organomegaly, or ascites, but with 1ϩ ankle edema.Laboratory findings were notable for a creatinine level of 2.0 mg/dL, a random blood sugar level of 220 mg/dL, and proteinuria (protein:creatinineϭ400 mg/g).Her ECG showed sinus rhythm, left atrial enlargement, left ventricular hypertrophy (LVH), Q waves in the inferior leads, and inferolateral ST-and T-wave changes.The ECG findings were unchanged, except for a heart rate that had increased from a tracing taken 6 months earlier.Her chest x-ray showed a mildly enlarged cardiac silhouette and questionable evidence of pulmonary venous congestion.An echocardiogram showed a moderately dilated left ventricle with increased wall thickness, inferobasilar akinesis, and an ejection fraction estimated between 30% and 35%.
Cancer Risk in the Swiss HIV Cohort Study: Associations With Immunodeficiency, Smoking, and Highly Active Antiretroviral Therapy
Authors: G. M. Clifford, J. Polesel, M. Rickenbach, L. Dal Maso, O. Keiser, A. Kofler, E. Rapiti, F. Levi, G. Jundt, T. Fisch, A. Bordoni, D. De Weck, S. Franceschi
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Persons infected with human immunodeficiency virus (HIV) have an increased risk for several cancers, but the influences of behavioral risk factors, such as smoking and intravenous drug use, and highly active antiretroviral therapy (HAART) on cancer risk are not clear. Methods: Patient records were linked between the Swiss HIV Cohort Study and Swiss cantonal cancer registries. Observed and expected numbers of incident cancers were assessed in 7304 persons infected with HIV followed for 28 836 person-years. Relative risks for cancer compared with those for the general population were determined by estimating cancer registry–, sex-, age-, and period-standardized incidence ratios (SIRs). Results: Highly elevated SIRs were confirmed in persons infected with HIV for Kaposi sarcoma (KS) (SIR = 192, 95% confidence interval [CI] = 170 to 217) and non-Hodgkin lymphoma (SIR = 76.4, 95% CI = 66.5 to 87.4). Statistically significantly elevated SIRs were also observed for anal cancer (SIR = 33.4, 95% CI = 10.5 to 78.6); Hodgkin lymphoma (SIR = 17.3, 95% CI = 10.2 to 27.4); cancers of the cervix (SIR = 8.0, 95% CI = 2.9 to 17.4); liver (SIR = 7.0, 95% CI = 2.2 to 16.5); lip, mouth, and pharynx (SIR = 4.1, 95% CI = 2.1 to 7.4); trachea, lung, and bronchus (SIR = 3.2, 95% CI = 1.7 to 5.4); and skin, nonmelanomatous (SIR = 3.2, 95% CI = 2.2 to 4.5). In HAART users, SIRs for KS (SIR = 25.3, 95% CI = 10.8 to 50.1) and non-Hodgkin lymphoma (SIR = 24.2, 95% CI = 15.0 to 37.1) were lower than those for nonusers (KS SIR = 239, 95% CI = 211 to 270; non-Hodgkin lymphoma SIR = 99.3, 95% CI = 85.8 to 114). Among HAART users, however, the SIR (although not absolute numbers) for Hodgkin lymphoma (SIR = 36.2, 95% CI = 16.4 to 68.9) was comparable to that for KS and non-Hodgkin lymphoma. No clear impact of HAART on SIRs emerged for cervical cancer or non–acquired immunodeficiency syndrome-defining cancers. Cancers of the lung, lip, mouth, or pharynx were not observed among nonsmokers. Conclusion: In persons infected with HIV, HAART use may prevent most excess risk of KS and non-Hodgkin lymphoma, but not that of Hodgkin lymphoma and other non–acquired immunodeficiency syndrome-defining cancers. No cancers of the lip, mouth, pharynx, or lung were observed in nonsmokers.
Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients
Authors: D.C.F. Törnberg, H. Marteus, U. Schedin, K. Alving, J.O.N. Lundberg, E. Weitzberg
Journal: European Respiratory Journal (2002)

Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation. Ten tracheotomized patients and seven healthy subjects were studied. The mean±sem fraction of exhaled NO from the nose, mouth and trachea was 56±8, 14±4 and 6±1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64±14, 11±3 and 4±1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation. There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.
Treatment of Vulvar Intraepithelial Neoplasia with Topical Imiquimod
Authors: Manon van Seters, Marc van Beurden, Fiebo J.W. ten Kate, Ilse Beckmann, Patricia C. Ewing, Marinus J.C. Eijkemans, Marjolein J. Kagie, Chris J.M. Meijer, Neil K. Aaronson, Alex KleinJan, Claudia Heijmans-Antonissen, Freek J. Zijlstra, Matthé P.M. Burger, Theo J.M. Helmerhorst
Journal: New England Journal of Medicine (2008)

Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immune-response modulator, for the treatment of this condition.Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome was a reduction of more than 25% in lesion size at 20 weeks. Secondary outcomes were histologic regression, clearance of human papillomavirus (HPV) from the lesion, changes in immune cells in the epidermis and dermis of the vulva, relief of symptoms, improvement of quality of life, and durability of response. Reduction in lesion size was classified as complete response (elimination), strong partial response (76 to 99% reduction), weak partial response (26 to 75% reduction), or no response (< or =25% reduction). The follow-up period was 12 months.Lesion size was reduced by more than 25% at 20 weeks in 21 of the 26 patients (81%) treated with imiquimod and in none of those treated with placebo (P<0.001). Histologic regression was significantly greater in the imiquimod group than in the placebo group (P<0.001). At baseline, 50 patients (96%) tested positive for HPV DNA. HPV cleared from the lesion in 15 patients in the imiquimod group (58%), as compared with 2 in the placebo group (8%) (P<0.001). The number of immune epidermal cells increased significantly and the number of immune dermal cells decreased significantly with imiquimod as compared with placebo. Imiquimod reduced pruritus and pain at 20 weeks (P=0.008 and P=0.004, respectively) and at 12 months (P=0.04 and P=0.02, respectively). The lesion progressed to invasion (to a depth of <1 mm) in 3 of 49 patients (6%) followed for 12 months (2 in the placebo group and 1 in the imiquimod group). Nine patients, all treated with imiquimod, had a complete response at 20 weeks and remained free from disease at 12 months.Imiquimod is effective in the treatment of vulvar intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN11290871 [controlled-trials.com].).
Mechanisms of virus induced exacerbations of asthma
Authors: J. M. Corne, S. T. Holgate
Journal: Thorax (1997)

airways morphology, though work in this area is agonist sulfonterol against ovalbumin induced Centre Block, limited by the few obvious examples of naturally contraction is reduced. 26 The nature of this Southampton Generaloccurring URT viral infections in animals.Two effect has been examined further. 27 Mice in-Hospital, Tremona Road, of the early studies described changes due to fected with influenza A that developed in-Southampton SO16 respiratory syncytial virus infection in the fections confined to the URT were compared 6YD, UK ferret 16 and a poorly adapted strain of influenza with those that developed infections of both J M Corne S T Holgate in the mouse, 17 both of which gave rise to a cold the upper and lower respiratory tracts.Only in those animals with lower respiratory tract like illness without an associated pneumonia.
Relationship Between Adherence to Evidence-Based Pharmacotherapy and Long-term Mortality After Acute Myocardial Infarction
Authors: Jeppe N. Rasmussen, Alice Chong, David A. Alter
Journal: JAMA (2007)

The extent to which drug adherence may affect survival remains unclear, in part because mortality differences may be attributable to "healthy adherer" behavioral attributes more so than to pharmacological benefits.To explore the relationship between drug adherence and mortality in survivors of acute myocardial infarction (AMI).Population-based, observational, longitudinal study of 31 455 elderly AMI survivors between 1999 and 2003 in Ontario. All patients filled a prescription for statins, beta-blockers, or calcium channel blockers, with the latter drug considered a control given the absence of clinical trial-proven survival benefits.Patient adherence was subdivided a priori into 3 categories--high (proportion of days covered, > or =80%), intermediate (proportion of days covered, 40%-79%), and low (proportion of days covered, <40%)--and compared with long-term mortality (median of 2.4 years of follow-up) using multivariable survival models (and propensity analyses) adjusted for sociodemographic factors, illness severity, comorbidities, and concomitant use of evidence-based therapies.Among statin users, compared with their high-adherence counterparts, the risk of mortality was greatest for low adherers (deaths in 261/1071 (24%) vs 2310/14,345 (16%); adjusted hazard ratio, 1.25; 95% confidence interval, 1.09-1.42; P = .001) and was intermediary for intermediate adherers (deaths in 472/2407 (20%); adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .03). A similar but less pronounced dose-response-type adherence-mortality association was observed for beta-blockers. Mortality was not associated with adherence to calcium channel blockers. Moreover, sensitivity analyses demonstrated no relationships between drug adherence and cancer-related admissions, outcomes for which biological plausibility do not exist.The long-term survival advantages associated with improved drug adherence after AMI appear to be class-specific, suggesting that adherence outcome benefits are mediated by drug effects and do not merely reflect an epiphenomenon of "healthy adherer" behavioral attributes.
Adrenalectomy permits a late, local TNF‐α release in LPS‐challenged rat airways
Authors: A. Miller-Larsson, A. Runström, R Brattsand
Journal: European Respiratory Journal (1999)

The normal rise of circulating endogenous glucocorticosteroids (GCS), in response to immunological stimuli, can be impaired in patients with inflammatory diseases. The aim of this study was to investigate whether abolition of the endogenous GCS response promotes local production of the pro-inflammatory cytokine, tumour necrosis factor (TNF)-alpha, in challenged airways and affects the cellular response in rats. In adrenalectomized or sham operated rats, the trachea and main bronchi were lavaged at various times after intratracheal instillation of low dose lipopolysaccharide (LPS). TNF-alpha in lavage fluid and plasma corticosterone were measured, and cells were differentiated. In adrenalectomized rats, LPS-induced in the airways a biphasic TNF-alpha release peaking at 2 and 6 h, whereas in sham operated rats the second peak was absent; probably inhibited by the strong rise of plasma corticosterone. The second peak was abolished in adrenalectomized rats by pretreatment with exogenous GCS. The LPS-induced neutrophil influx and a decrease in mononuclear cells were prolonged in adrenalectomized rats. In conclusion, abolition of the endogenous glucocorticosteroid response promotes the late release of tumour necrosis factor-alpha in the airways and prolongs the cellular response. This suggests that a normal rise of endogenous glucocorticosteroid after an immunological trigger contributes to a dampening of the late inflammatory activity.
RNA Interference in Biology and Medicine
Authors: Ollivier Milhavet, Devin S. Gary, Mark P. Mattson
Journal: Pharmacological Reviews (2003)

First discovered in plants the nematode <i>Caenorhabditis elegans</i>, the production of small interfering RNAs (siRNAs) that bind to and induce the degradation of specific endogenous mRNAs is now recognized as a mechanism that is widely employed by eukaryotic cells to inhibit protein production at a post-transcriptional level. The endogenous siRNAs are typically 19- to 23-base double-stranded RNA oligonucleotides, produced from much larger RNAs that upon binding to target mRNAs recruit RNases to a protein complexthat degrades the targeted mRNA. Methods for expressing siRNAs in cells in culture and in vivo using viral vectors, and for transfecting cells with synthetic siRNAs, have been developed and are being used to establish the functions of specific proteins in various cell types and organisms. RNA interference methods provide several major advantages over prior methods (antisense DNA or antibody-based techniques) for suppressing gene expression. Recent preclinical studies suggest that RNA interference technology holds promise for the treatment of various diseases. Pharmacologists have long dreamed of the ability to selectively antagonize or eliminate the function of individual proteins—RNAi technology may eventually make that dream a reality.