tbuckley/cabot-search huggingface dataset:
Live Vaccine Against Measles, Mumps, and Rubella and the Risk of Hospital Admissions for Nontargeted Infections
Authors: Signe Sørup, Christine S. Benn, Anja Poulsen, Tyra G. Krause, Peter Aaby, Henrik Ravn
Journal: JAMA (2014)

In low-income countries, live measles vaccine reduces mortality from causes other than measles infection. Such nonspecific effects of vaccines might also be important for the health of children in high-income settings.To examine whether the live vaccine against measles, mumps, and rubella (MMR) is associated with lower rates of hospital admissions for infections among children in Denmark.Population-based cohort study of Danish children born 1997-2006 and followed up from ages 11 months to 2 years (last follow-up, August 31, 2008). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months.Incidence rate ratios (IRRs) of hospital admissions for any infection, comparing receipt of MMR vs DTaP-IPV-Hib as the most recent vaccine. Risks, risk difference, and number needed to vaccinate were calculated for receiving MMR on time.The study included 495,987 children contributing with 56,889 hospital admissions for any type of infection during 509,427 person-years (rate, 11.2 per 100 person-years). For the 456,043 children who followed the recommended schedule and received MMR after the third dose of DTaP-IPV-Hib, MMR (rate, 8.9 per 100 person-years) vs the third dose of DTaP-IPV-Hib (rate, 12.4 per 100 person-years) as the most recent vaccine was associated with an adjusted IRR of 0.86 (95% CI, 0.84-0.88) for any admission for infection. There were 19,219 children immunized out of sequence. The adjusted IRR was 0.87 (95% CI, 0.80-0.95) for those receiving MMR (rate, 9.9 per 100 person-years) after the second dose of DTaP-IPV-Hib (rate, 15.1 per 100 person-years). However, in the 1981 children who subsequently received the third dose of DTaP-IPV-Hib (rate, 12.8 per 100 person-years) after MMR, the IRR for hospital admissions for infection was significantly greater (adjusted IRR, 1.62 [95% CI, 1.28-2.05]). The risk of admission for an infection between ages 16 months and 24 months was 4.6% (95% CI, 4.5%-4.7%) for receiving MMR on time and 5.1% (95% CI, 5.0%-5.2%) for not receiving MMR on time. The risk difference was 0.5 percentage point (95% CI, 0.4-0.6), and the number needed to vaccinate with MMR before age 16 months to prevent 1 admission for any infection was 201 (95% CI, 159-272).In a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections. These findings require replication in other high-income populations.
Double-blind placebo-controlled trial of etanercept in the prevention of work disability in ankylosing spondylitis: Table 1
Authors: Nick Barkham, Laura C Coates, Helen Keen, Elizabeth Hensor, Alexander Fraser, Anthony Redmond, Lorna Cawkwell, Paul Emery
Journal: Annals of the Rheumatic Diseases (2010)

Objectives Etanercept has been shown to be rapidly effective in suppressing disease activity in ankylosing spondylitis (AS). The aim of this study was to determine whether etanercept improves work instability as measured by the Ankylosing Spondylitis Work Instability Scale (AS-WIS). Method Forty patients with active AS who were in work but were work unstable were recruited. Patients were randomised to receive 25 mg etanercept or placebo twice weekly for 12 weeks. The primary outcome was change in AS-WIS at week 12. The AS-WIS is a patient-derived outcome measure which allows stratification of the risk of job loss. Secondary outcomes included clinical outcomes and gait parameters. Results The mean improvement in AS-WIS score at week 12 was 2.75 in the etanercept group and 0.68 in the placebo group (p=0.125). The risk of job loss decreased for 11 (55%) of the etanercept group compared with 7 (35%) in the placebo group. Conversely, the risk of job loss increased in 3 (15%) of the placebo group compared with 1 (5%) in the etanercept group. There was no statistically significant difference between treatment groups in change in WIS categories (Mann–Whitney U test=0.153, p=0.160). Significant improvement with etanercept was seen at week 12 in clinical outcomes and gait parameters. Etanercept was well tolerated, with no dropouts due to adverse events. Conclusion This small study confirms the efficacy of etanercept on clinical outcome measures in patients with AS and suggests an effect on work instability which needs to be replicated in a larger controlled study.
Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study
Authors: M. Wadbo, C-G. Löfdahl, K. Larsson, B.E. Skoogh, G. Tornling, E. Arweström, T. Bengtsson, K. Ström
Journal: European Respiratory Journal (2002)

The aim of this study was to compare the effects of formoterol, ipratropium bromide and a placebo on walking distance, lung function, symptoms and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) patients. A total of 183 patients (mean age 64 yrs, 86 female) with moderate-to-severe nonreversible COPD participated in this randomised, double-blind, parallel-group study. After a 2-week placebo run-in, patients were randomised to formoterol Turbuhaler® 18 μg b.i.d. (delivered dose), ipratropium bromide 80 μg t.i.d. via a pressurised metered dose inhaler, or placebo for 12 weeks. Inhaled short-acting β 2 -agonists were allowed as relief medication and inhaled glucocorticosteroids were allowed at a constant dose. The primary variable was walking distance in the shuttle walking test (SWT). Baseline mean SWT distance was 325 m, mean forced expiratory volume in one second (FEV 1 ) was 40% predicted. Clinically significant improvements in SWT (&gt;30 m) were seen in 41, 38 and 30% of formoterol, ipratropium and placebo patients, respectively (not significant). Mean increases from run-in were 19, 17 and 5 m in the formoterol, ipratropium and placebo groups, respectively. Both active treatments significantly improved FEV 1 , forced vital capacity, peak expiratory flow and daytime dyspnoea score compared with placebo. Formoterol reduced relief medication use compared with placebo. Neither active treatment improved QoL. Formoterol and ipratropium improved airway function and symptoms, without significant improvements in the shuttle walking test.
Informed Cytology for Triaging HPV-Positive Women: Substudy Nested in the NTCC Randomized Controlled Trial
Authors: Christine Bergeron, Paolo Giorgi-Rossi, Frederic Cas, Maria Luisa Schiboni, Bruno Ghiringhello, Paolo Dalla Palma, Daria Minucci, Stefano Rosso, Manuel Zorzi, Carlo Naldoni, Nereo Segnan, Massimo Confortini, Guglielmo Ronco
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Human papillomavirus (HPV)–based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status.
Drugs and the Youthful Police Informer
Authors: WERNER I. HALPERN, ADELLE GORDON
Journal: American Journal of Psychiatry (1971)

The authors describe the problems of adolescents who gave false information to police about drug abuse in their communities. Such patients were invariably lonely and isolated from their families and peers; their informing gained them immediate response and approval from adults. Environmental change, while it may alleviate their problems, is difficult to achieve. Early detection can prevent later difficulties.
Effects of Intravenous Glucose Load on Insulin Secretion in Patients With Ketosis-Prone Diabetes During Near-Normoglycemia Remission
Authors: Aidar R. Gosmanov, Dawn Smiley, Gonzalo Robalino, Joselita M. Siqueira, Limin Peng, Abbas E. Kitabchi, Guillermo E. Umpierrez
Journal: Diabetes Care (2010)

OBJECTIVE Most patients with ketosis-prone type 2 diabetes (KPD) discontinue insulin therapy and remain in near-normoglycemic remission. The aim of this study was to determine the effect of glucotoxicity on β-cell function during remission in obese patients with KPD. RESEARCH DESIGN AND METHODS Age- and BMI-matched obese African Americans with a history of KPD (n = 8), severe hyperglycemia but without ketosis (ketosis-resistant type 2 diabetes, n = 7), and obese control subjects (n = 13) underwent intravenous infusion of 10% dextrose at a rate of 200 mg per m2/min for 20 h. β-Cell function was assessed by changes in insulin and C-peptide concentrations during dextrose infusion and by changes in acute insulin response (AIR) and first-phase insulin release (FPIR) to arginine stimulation before and after dextrose infusion. RESULTS The mean ± SD time to discontinue insulin therapy was 7.1 ± 1.7 weeks in KPD and 9.6 ± 2.3 weeks in ketosis-resistant type 2 diabetes (NS). During a 20-h dextrose infusion, changes in insulin, C-peptide, and the C-peptide–to–glucose ratio were similar among diabetic and control groups. During dextrose infusion, subjects with ketosis-resistant type 2 diabetes had greater areas under the curve for blood glucose than subjects with KPD and control subjects (P &amp;lt; 0.05). The AIR and FPIR to arginine stimulation as well as glucose potentiation to arginine assessed before and after dextrose infusion were not different among the study groups. CONCLUSIONS Near-normoglycemia remission in obese African American patients with KPD and ketosis-resistant type 2 diabetes is associated with a remarkable recovery in basal and stimulated insulin secretion. At near-normoglycemia remission, patients with KPD displayed a pattern of insulin secretion similar to that of patients with ketosis-resistant type 2 diabetes and obese nondiabetic subjects.
PATHOGENESIS OF THYMIC CHANGES IN NZB MICE WITH HEMOLYTIC ANEMIA
Authors: Richard Siegler
Journal: The Journal of Experimental Medicine (1965)

Lymphoid follicles evolve in the perivascular connective tissue of many organs, including the thymuses, in NZB/Bl mice with hemolytic anemia. In previously published studies, these thymic follicles have been held to be causal in the autoimmune genesis of the hemolytic anemia. The present study contradicts this interpretation by demonstrating: (a) lymphoid follicles develop in the perivascular connective tissue of many organs in NZB mice, and are not restricted to the thymuses; and (b) thymic lymphoid follicles develop in aged Swiss mice without hemolytic anemia. Contrary to previous reports, the thymuses of NZB mice contain normal numbers of Hassall's corpuscles, which develop from preexisting thymic epithelial cells, and not from blood vessels.
Purinergic Inhibition of ENaC Produces Aldosterone Escape
Authors: James D. Stockand, Elena Mironova, Vladislav Bugaj, Timo Rieg, Paul A. Insel, Volker Vallon, Janos Peti-Peterdi, Oleh Pochynyuk
Journal: Journal of the American Society of Nephrology (2010)

The mechanisms underlying “aldosterone escape,” which refers to the excretion of sodium (Na+) during high Na+ intake despite inappropriately increased levels of mineralocorticoids, are incompletely understood. Because local purinergic tone in the aldosterone-sensitive distal nephron downregulates epithelial Na+ channel (ENaC) activity, we tested whether this mechanism mediates aldosterone escape. Here, urinary ATP concentration increased with dietary Na+ intake in mice. Physiologic concentrations of ATP decreased ENaC activity in a dosage-dependent manner. P2Y2−/− mice, which lack the purinergic receptor, had significantly less increased Na+ excretion than wild-type mice in response to high-Na+ intake. Exogenous deoxycorticosterone acetate and deletion of the P2Y2 receptor each modestly increased the resistance of ENaC to changes in Na+ intake; together, they markedly increased resistance. Under the latter condition, ENaC could not respond to changes in Na+ intake. In contrast, as a result of aldosterone escape, wild-type mice had increased Na+ excretion in response to high-Na+ intake regardless of the presence of high deoxycorticosterone acetate. These data suggest that control of ENaC by purinergic signaling is necessary for aldosterone escape.
Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial
Authors: Athanassios Argiris, Musie Ghebremichael, Jill Gilbert, Ju-Whei Lee, Kamakshi Sachidanandam, Jill M. Kolesar, Barbara Burtness, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2013)

We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN).Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing.Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response.The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.
Targeting tumor-associated macrophages as a novel strategy against breast cancer
Authors: Y. Luo
Journal: Journal of Clinical Investigation (2006)

Tumor-associated macrophages (TAMs) are associated with tumor progression and metastasis. Here, we demonstrate for the first time that legumain, a member of the asparaginyl endopeptidase family functioning as a stress protein, overexpressed by TAMs, provides an ideal target molecule. In fact, a legumain-based DNA vaccine served as a tool to prove this point, as it induced a robust CD8+ T cell response against TAMs, which dramatically reduced their density in tumor tissues and resulted in a marked decrease in proangiogenic factors released by TAMs such as TGF-beta, TNF-alpha, MMP-9, and VEGF. This, in turn, led to a suppression of both tumor angiogenesis and tumor growth and metastasis. Importantly, the success of this strategy was demonstrated in murine models of metastatic breast, colon, and non-small cell lung cancers, where 75% of vaccinated mice survived lethal tumor cell challenges and 62% were completely free of metastases. In conclusion, decreasing the number of TAMs in the tumor stroma effectively altered the tumor microenvironment involved in tumor angiogenesis and progression to markedly suppress tumor growth and metastasis. Gaining better insights into the mechanisms required for an effective intervention in tumor growth and metastasis may ultimately lead to new therapeutic targets and better anticancer strategies.
Prospective Application of Pre-Defined Intravascular Ultrasound Criteria for Assessment of Intermediate Left Main Coronary Artery Lesions
Authors: Jose M. de la Torre Hernandez, Felipe Hernández Hernandez, Fernando Alfonso, Jose R. Rumoroso, Ramon Lopez-Palop, Mario Sadaba, Pilar Carrillo, Juan Rondan, Iñigo Lozano, Juan M. Ruiz Nodar, Jose A. Baz, Eduard Fernandez Nofrerias, Fernando Pajin, Tamara Garcia Camarero, Hipolito Gutierrez
Journal: Journal of the American College of Cardiology (2011)
Abstract 965: Identification of KJ-Pyr-9 as a potent MYC inhibitor
Authors: Jonathan R. Hart, Klaus Bister, Kim D. Janda, Peter K. Vogt
Journal: Cancer Research (2015)

Abstract We have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. KJ-Pyr-9 functions as an inhibitor of MYC in biochemical assays, in cells and in xenograft experiments. In vitro, KJ-Pyr-9 binds to MYC as well as MYC-MAX dimers and can disrupt binding of MYC-MAX dimers with E-box DNA. In cells, MYC-MAX dimerization can be disrupted in cells as demonstrated by protein fragment complementation assays. KJ-PYR-9 disrupts the transcriptional targets of MYC. The P493-6 cell line has tetracycline regulatable MYC expression. For this cell line, the transcriptional targets of MYC can be readily observed upon the addition of 0.1 ug/mL doxycycline. Both doxycycline and KJ-PYR-9 negatively regulate MYC transcriptional signatures as determined by GSEA. The growth of a variety of different MYC-dependent cell lines are inhibited, including MYC translocated Burkitt's lymphoma cell lines expressing high levels of MYC as well as solid tumor cell lines expressing moderate amounts of MYC. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells. Citation Format: Jonathan R. Hart, Klaus Bister, Kim D. Janda, Peter K. Vogt. Identification of KJ-Pyr-9 as a potent MYC inhibitor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 965. doi:10.1158/1538-7445.AM2015-965
Cyclooxygenase-2 Is Expressed in Neuroblastoma, and Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Tumor Growth <b> <i>In vivo</i> </b>
Authors: John I. Johnsen, Magnus Lindskog, Frida Ponthan, Ingvild Pettersen, Lotta Elfman, Abiel Orrego, Baldur Sveinbjörnsson, Per Kogner
Journal: Cancer Research (2004)

Abstract Neuroblastoma is the single most common and deadly tumor of childhood and is often associated with therapy resistance. Cyclooxygenases (COXs) catalyze the conversion of arachidonic acid to prostaglandins. COX-2 is up-regulated in several adult epithelial cancers and is linked to proliferation and resistance to apoptosis. We detected COX-2 expression in neuroblastoma primary tumors and cell lines but not in normal adrenal medullas from children. Treatment of neuroblastoma cells with nonsteroidal anti-inflammatory drugs, inhibitors of COX, induced caspase-dependent apoptosis via the intrinsic mitochondrial pathway. Treatment of established neuroblastoma xenografts in nude rats with the dual COX-1/COX-2 inhibitor diclofenac or the COX-2–specific inhibitor celecoxib significantly inhibited tumor growth in vivo (P &amp;lt; 0.001). In vitro, arachidonic acid and diclofenac synergistically induced neuroblastoma cell death. This effect was further pronounced when lipooxygenases were simultaneously inhibited. Proton magnetic resonance spectroscopy (1H MRS) of neuroblastoma cells treated with COX inhibitors demonstrated accumulation of polyunsaturated fatty acids and depletion of choline compounds. Thus, 1H MRS, which can be performed with clinical magnetic resonance scanners, is likely to provide pharmacodynamic markers of neuroblastoma response to COX inhibition. Taken together, these data suggest the use of nonsteroidal anti-inflammatory drugs as a novel adjuvant therapy for children with neuroblastoma.
Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling
Authors: Dan Levy, Alex J Kuo, Yanqi Chang, Uwe Schaefer, Christopher Kitson, Peggie Cheung, Alexsandra Espejo, Barry M Zee, Chih Long Liu, Stephanie Tangsombatvisit, Ruth I Tennen, Andrew Y Kuo, Song Tanjing, Regina Cheung, Katrin F Chua, Paul J Utz, Xiaobing Shi, Rab K Prinjha, Kevin Lee, Benjamin A Garcia, Mark T Bedford, Alexander Tarakhovsky, Xiaodong Cheng, Or Gozani
Journal: Nature Immunology (2010)
Factors Related to Underuse of Surveillance Mammography Among Breast Cancer Survivors
Authors: Nancy L. Keating, Mary Beth Landrum, Edward Guadagnoli, Eric P. Winer, John Z. Ayanian
Journal: Journal of Clinical Oncology (2005)

Purpose Many older breast cancer survivors do not undergo annual mammography despite guideline recommendations. We identified factors associated with underuse of surveillance mammography and examined whether variation was explained by differences in follow-up care. Patients and Methods We used Surveillance, Epidemiology, and End Results-Medicare data to identify a population-based sample of 44,511 women fee-for-service Medicare enrollees aged ≥ 65 years who were diagnosed with stage I or II breast cancer in 1992 to 1999 who underwent primary surgical therapy. We assessed factors associated with mammography during months 7 to 18, 19 to 30, and 31 to 42 after breast cancer diagnosis using repeated-measures logistic regression; and we examined whether follow-up care with providers of various specialties explained variation in mammography use. Results Only three quarters of women (77.6%) underwent mammography during months 7 to 18 after diagnosis, and only 56.7% had mammography yearly over 3 years. In multivariable analyses, women who were older, black, unmarried, and living in certain regions were less likely than other women to undergo surveillance mammography (all P &lt; .05). Patients with more visits and patients who continued to see a medical oncologist, radiation oncologist, or surgeon were most likely to have mammograms (P &lt; .001); however, adjusting for visits with providers did not explain the lower mammography rates based on age, race, marital status, and geographic region. Conclusion Many elderly breast cancer survivors do not undergo annual surveillance mammography, particularly women who are older, black, and unmarried, and this underuse was not explained by access to follow-up care. New strategies are needed to increase use of surveillance mammography and decrease variations based on nonclinical factors that are likely unrelated to appropriateness of medical care.