tbuckley/cabot-search huggingface dataset:
OT1-01-03: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Multicenter Study Comparing Denosumab with Placebo as Adjuvant Treatment for Women with Early-Stage Breast Cancer Who Are at High Risk of Disease Recurrence (D-CARE).
Authors: PE Goss, CH Barrios, R Bell, D Finkelstein, H Iwata, M Martin, A Braun, C Ke, T Maniar, S Braun, R Dansey, RE Coleman
Journal: Cancer Research (2011)

Abstract Background Bone is a common site of distant recurrence in women with early-stage breast cancer. Cancer cells are thought to stimulate osteoclast-mediated bone resorption, which releases growth factors and cytokines that promote tumor growth. RANK Ligand (RANKL) is the key mediator of osteoclast-induced bone destruction. In preclinical studies, RANKL inhibition reduced the incidence of bone and lung metastases, suppressed tumor progression, and prolonged survival of tumor-bearing mice. Effects were additive with hormonal, chemotherapy, or targeted therapies. Denosumab is a fully human monoclonal antibody against RANKL, approved in the U.S. for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In patients with castrate-resistant prostate cancer, denosumab significantly improved bone metastasis-free survival (BMFS) compared to placebo. The D-CARE trial evaluates BMFS effects of denosumab in women with stage II or III breast cancer. Methods: Women with node-positive or locally advanced (T3 or T4) disease, and known hormone and HER-2 receptor status are eligible. Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination must be planned with curative intent. Women with a prior history of breast cancer (other than ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) or distant metastasis, oral bisphosphonate (BP) use within 1 year or any intravenous BP use are excluded. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 mos, then every 3 mos, for a total of 5 yrs treatment. All patients receive vitamin D (≥ 400 IU) and calcium (≥ 500 mg) supplements. Primary endpoint of this event-driven trial is BMFS. Secondary endpoints include disease-free (DFS) and overall survival. The study is powered for both, BMFS and DFS. Safety, quality of life assessments and biomarkers are additional endpoints. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154 began enrolling patients in June 2010. PG and DF are supported in part by the Avon Foundation, NY. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-01-03.
Murine Cytomegalovirus Infection Increases Aortic Expression of Proatherosclerotic Genes
Authors: Mary Susan Burnett, Sarfraz Durrani, Eugenio Stabile, Motoyasu Saji, Cheol W. Lee, Tim D. Kinnaird, Eric P. Hoffman, Stephen E. Epstein
Journal: Circulation (2004)

The possible etiologic role of infection in cardiovascular disease is still debated. Having previously demonstrated that murine cytomegalovirus (MCMV) infection of apolipoprotein (apo) E-/- mice increases atherosclerotic lesion size, we determined if MCMV infection produces proatherogenic changes in aortic gene expression. Additionally, in cholesterol-fed C57BL/6J mice, we examined the effects of MCMV infection on aortic lesion area.C57BL/6J apoE-/- and wild-type C57BL/6J mice were infected with MCMV. At various time points, aortas were collected and pooled. Total RNA was extracted and hybridized to Affymetrix murine chips or analyzed for specific gene expression using TaqMan reverse transcription-polymerase chain reaction. Data from infected and uninfected mice were compared. A separate group of cholesterol-fed C57BL/6J mice were infected with MCMV, and lesion area in the aortic sinus was assessed using oil red O staining. Acute MCMV infection altered aortic expression of atherogenic genes in young apoE-/- and C57BL/6J mice-specifically, monocyte chemoattractant protein-1, monokine induced by interferon-gamma, and interferon-gamma inducible protein 10. Acute infection in adult 9-month-old apoE-/- mice with well-established lesions increased aortic expression of monocyte chemoattractant protein-1. Atherosclerotic lesion area in cholesterol-fed C57BL/6J mice was increased after infection with MCMV.MCMV infection significantly increases atherosclerotic lesion area and aortic expression of atherogenic genes. These infection-induced effects indicate mechanisms by which cytomegalovirus may contribute to atherosclerotic disease initiation and progression and to the precipitation of clinical events. These results additionally add to data compatible with the concept that infection does play an important role in atherosclerotic disease.
Abstract 1990: Loss of Olfactomedin 4 gene leads to neoplastic progression in the murine prostate.
Authors: Hongzhen Li, Wenli Liu, Jianqiong Zhu, Weiping Chen, Chu-Xia Deng, Griffin P. Rodgers
Journal: Cancer Research (2013)

Abstract The murine olfactomedin 4 gene (Olfm4) encodes an olfactomedin-related glycoprotein whose physiological and pathological functions in the prostate are largely unknown. We have observed that homozygous Olfm4 mutant mice develop prostatic intra epithelial neoplisa (PIN), high grade PIN, adenocarcinoma and metastatic tumor in an age-dependent manner. We also found that increased proliferation of prostate epithelial cells in Olfm4-null mice. In this report, we studied the mechanisms underlying neoplastic progression of Olfm4-deficient mice prostate. We have performed microarray analysis to compare Olfm4 knockout and wild-type mice prostate at 3 and 15 months of ages. A total of 187 genes were found commonly changed in both 3 and 15 months, whereas 894 and 1090 genes were significantly changed in 3 and 15 months respectively. Enrichment Gene Go Diseases analysis showed prostatic neoplasms was at the top of 10 listed diseases. We found that 95 genes for neoplastic procession markers were significantly changed in the prostate of Olfm4-deficient mice. Among the genes, 39 genes were up-regulated and 37 genes were down regulated more than 1.5-fold. The qRT-PCR confirmed consistently higher expression of Ets1, Vav3, Shh, Sdc2, and Mmp19, and down-regulation of the genes Rnasel and Psca in Olfm4 knockout mice compared with Olfm4 wild-type mice. We also confirmed expression of Ets1 and Mmp19 by using western blot and immunohistochemistry analysis. Interestingly, in the GEO prostate cancer database, which compares tumor to normal tissue and metastatic tumor to normal tissue, expression of OLFM4 and RNASEL were down-regulated, in contrast, expression of ETS1 and MMP19 were up-regulated. Therefore, the gene expression profiles in the GEO database confirmed and extended Ets1, Mmp19 and Rnasel in Olfm4 knockout mice. Our finding indicates that loss of OLFM4 leads to progression of prostate cancer. Citation Format: Hongzhen Li, Wenli Liu, Jianqiong Zhu, Weiping Chen, Chu-Xia Deng, Griffin P. Rodgers. Loss of Olfactomedin 4 gene leads to neoplastic progression in the murine prostate. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1990. doi:10.1158/1538-7445.AM2013-1990
Abstract 5027: Identification of novel immune checkpoints as potential targets for cancer immunotherapy
Authors: Galit Rotman, Ofer Levy, Amir Toporik, Gady Cojocaru, Liat Dassa, Ilan Vaknin, Shirley Sameah-Greenwald, Inbal Barbiro, Jinhong Fan, Susan Watson, John Hunter, Eyal Neria, Zurit Levine
Journal: Cancer Research (2014)

Abstract Members of the B7/CD28 family of immune checkpoints, such as CTLA4, PD1 and PDL-1, play critical roles in immune cell regulation and have emerged as promising drug targets for cancer immunotherapy. We hypothesize that additional immune checkpoints play a role as negative immune regulators and thus may serve as targets for therapeutic mAbs. Utilizing Compugen's predictive discovery platform, we identified novel members of this family that may serve as immune checkpoints. The therapeutic relevance of three of these proteins, CGEN-15001T, CGEN-15022, and CGEN-15049, was confirmed following the validation of their immunomodulatory properties and their expression in various cancers. Two of these proteins, CGEN-15001T and CGEN-15022, are the basis of a license and collaboration agreement recently signed with Bayer as targets for cancer immunotherapy. Here we present results obtained for an additional novel immune checkpoint, CGEN-15049. Following its ectopic expression on cancer cell lines, CGEN-15049 inhibits the activity of NK cells and cytotoxic T cells (CTLs). The fusion protein, consisting of the extracellular domain of CGEN-15049 fused to an IgG Fc domain, displays robust inhibition of T cell activation and enhances iTregs differentiation. IHC studies indicate that CGEN-15049 is expressed in tumor cells of numerous types of cancers, as well as in tumor infiltrating immune cells. Based on its immunomodulatory activities on immune cell types with key roles in cancer immune evasion, together with its expression pattern in cancer tissues, CGEN-15049 may serve as mAb target for cancer immunotherapy. Citation Format: Galit Rotman, Ofer Levy, Amir Toporik, Gady Cojocaru, Liat Dassa, Ilan Vaknin, Shirley Sameah-Greenwald, Inbal Barbiro, Jinhong Fan, Susan Watson, John Hunter, Eyal Neria, Zurit Levine. Identification of novel immune checkpoints as potential targets for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5027. doi:10.1158/1538-7445.AM2014-5027
BMA launches pre-election health manifesto
Authors: Lynn Eaton
Journal: BMJ (2005)

As the date of the UK general election grows closer, the BMA has launched its challenge for all the political parties in the United Kingdom, highlighting the issues it feels should be tackled to improve health care.

The five point manifesto for the forthcoming election, widely predicted to be on 5 May, calls for improvements in public health; better choice for patients; limiting the role of the private sector; involving doctors, patients, and the public more in policy initiatives about the NHS; and further investment in the medical profession.

Launching the manifesto, BMA chairman James Johnson said, “The NHS …
Echocardiographic Destruction of Albumin Microbubbles Directs Gene Delivery to the Myocardium
Authors: Ralph V. Shohet, Shuyuan Chen, Yan-Ting Zhou, Zhuowei Wang, Robert S. Meidell, Roger H. Unger, Paul A. Grayburn
Journal: Circulation (2000)

Background —The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hypothesis that albumin-coated microbubbles could be used to effectively deliver an adenoviral transgene to rat myocardium by ultrasound-mediated microbubble destruction. Methods and Results —Recombinant adenovirus containing β-galactosidase and driven by a constitutive promoter was attached to the surface of albumin-coated, perfluoropropane-filled microbubbles. These bubbles were infused into the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contain virus, virus alone, and virus plus ultrasound. One group underwent ultrasound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for β-galactosidase expression. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chloro-3-indolyl-β- d -galactopyranoside substrate, indicating expression of the transgene. None of the control animals showed myocardial expression of the β-galactosidase transgene. By quantitative analysis, β-galactosidase activity was 10-fold higher in the treated group than in controls ( P &lt;0.0001). Conclusions —Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.
Disk Infections and Abdominal Pain
Authors: C. Roger Sullivan, Richard E. Symmonds
Journal: JAMA (1964)

Three patients requiring abdominal exploration because of severe abdominal pain were found to have infection of the intervertebral disk. Clues to diagnosis of intervertebral infection are: backache, which is spasmodic and referred to the lower abdominal quadrants; an elevated erythrocyte sedimentation rate; narrowing of the involved intervertebral disk; erosion of the vertebral end plates; and bridging of the disk space by new bone formation. The presence of leukocytosis and fever is not required for diagnosis. Immobilization of the spinal column is the most effective treatment. Spontaneous fusion of the involved segments of the spinal column is the rule and antibiotics should be used only when the infection has extended from the interspace to surrounding soft tissues.
The Frame of Reference of Three-dimensional Vectorcardiograms Drawn by a Computer-driven Cathode Ray Tube
Authors: L. Brinberg
Journal: Cardiovascular Research (1969)

Journal Article The Frame of Reference of Three-dimensional Vectorcardiograms Drawn by a Computer-driven Cathode Ray Tube Get access Louis Brinberg Louis Brinberg † From the Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, U.S.A. † Present address: 65 East 93rd Street, New York City, 10028, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 2, April 1969, Pages 227–234, https://doi.org/10.1093/cvr/3.2.227 Published: 01 April 1969 Article history Received: 09 July 1968 Published: 01 April 1969
Allopurinol Enhances the Contractile Response to Dobutamine and Exercise in Dogs With Pacing-Induced Heart Failure
Authors: Tomohiko Ukai, Che-Ping Cheng, Hideo Tachibana, Akihiko Igawa, Zhu-Shan Zhang, Heng-Jie Cheng, William C. Little
Journal: Circulation (2001)

Background —Superoxide (O 2 − ) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca 2+ sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF. Methods and Results —We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E ES ) and stroke work–end-diastolic volume relation (M SW ). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant ( P &lt;0.05) increases in E ES (5.0±0.6 versus 3.3±0.6 mm Hg/mL) and M SW . Dobutamine and allopurinol produced greater increases in E ES (5.4±0.6 versus 7.4±0.6 mm Hg/mL) and M SW (60.1±7.4 versus 73.7±4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt max , stroke volume, and M SW were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol. Conclusions —Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise.
Hydralazine induced lupus syndrome with eye disease.
Authors: M Doherty, P J Maddison, R H Grey
Journal: BMJ (1985)

2 observations de vasculite retinienne bilaterale au cours de syndromes de type lupique compliquant le traitement par hydralazine. Dans un ces cas on note aussi une episclerite. Les symptomes disparaissent quelques semaines apres l'arret de l'hydralazine mais les anticorps antinucleaires restent presents
Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: An antiallergic activity☆☆☆★★★
Authors: G CIPRANDI, C PRONZATO, G PASSALACQUA, V RICCA, J GROGEN, G MELA, P VARESE, C BERTOLINI, M BAGNASCO, G CANONICA
Journal: Journal of Allergy and Clinical Immunology (1996)
The role of the Human Performance Laboratory
Authors: H. Thomason
Journal: British Journal of Sports Medicine (1977)

Over the last decade coaches and their charges have become more aware of the facilities that are available in some scientific establishments in this country which seemingly could be useful to them in their efforts to improve performance.The assessment of athletes in Human Performance Laboratories has now become more widespread.However, some physiologists have been guilty of using these athletes as guinea-pigs and providing little information that is of use to them in their quest for performance improvements.
Serum Dioxin Concentrations and Age at Menarche
Authors: Marcella Warner, Steven Samuels, Paolo Mocarelli, Pier Mario Gerthoux, Larry Needham, Donald G. Patterson, Brenda Eskenazi
Journal: Environmental Health Perspectives (2004)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is associated with delays in pubertal development in animal studies. On 10 July 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure experienced by a human population. Twenty years later, we initiated the Seveso Women’s Health Study (SWHS), a retrospective cohort study of female residents of the most contaminated areas, to determine whether the women were at higher risk for reproductive disease. We examined the association of TCDD serum levels, based on measurements in serum collected soon after the explosion, with reported age at menarche among the 282 SWHS women who were premenarcheal at the time of the explosion. We found no change in risk of onset of menarche with a 10-fold increase in TCDD (e.g., 10–100 ppt; hazard ratio = 0.95; 95% confidence interval, 0.83–1.09; p-value for trend = 0.46). When TCDD levels were categorized, there was also no evidence of a dose–response trend (p = 0.65). In summary, we found that individual serum TCDD measurements are not significantly related to age at menarche among women in the SWHS cohort. The women in this study experienced substantial TCDD exposure during the postnatal but prepubertal developmental period. Given that animal evidence suggests in utero exposure has the most significant effect on onset of puberty, continued follow-up of the offspring of the SWHS cohort is important.
REPORT OF COMMITTEE ON VISUAL STANDARDS FOR DRIVERS OF MOTOR VEHICLES
Authors: Conrad Berens
Journal: JAMA (1925)

Acting on the request of the section that the standards submitted last year be modified, your committee has carefully considered the criticisms and suggestions offered and desires to submit the following, hoping it may meet with the section's approval: (<i>b</i>) The applicant has vision of at least 20/50 in one eye and vision of at least 20/100 in the other eye, with or without glasses. Applicants with less vision than 20/100 in the poorer eye may, under certain conditions, be qualified by a special or county board. (See below.) (<i>c</i>) Double vision shall disqualify. <h3>SPECIAL OR COUNTY BOARDS OF PHYSICAL LICENSURE</h3> In each state there shall be a board of physical licensure in each county, or one for several counties, consisting of two general practitioners or surgeons, and one ophthalmologist, which shall meet at stated intervals and have final decision in all cases. These boards so constituted shall be empowered
Precipitation of Congestive Heart Failure: Social and Emotional Factors
Authors: LAWRENCE V. PERLMAN
Journal: Annals of Internal Medicine (1971)

Because of discrepancies in the literature and common lack of knowledge about the role of emotions in the precipitation of congestive heart failure, a group of 105 patients with congestive heart failure and a comparison group of 50 patients were studied. Emotional factors antedated hospitalization in 49% (51 of 105) of the group with congestive failure and 24% (12 of 50) of the other group (P < 0.01). Congestive-failure patients also had difficulty accepting their illness, and overt denial was observed in eight patients as compared to none of the comparison group. Patients' attitudes toward their living arrangements correlated with the presence of a preceding emotional event. When a patient lived with close relatives, emotional events were commoner than when interpersonal relationships were at a formal level (nursing home or domiciliary facility). Patients most satisfied with living conditions had less preceding emotional upsets.
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome
Authors: Catherine Boileau, Dong Chuan Guo, Nadine Hanna, Ellen S. Regalado, Delphine Detaint, Limin Gong, Mathilde Varret, Siddharth K. Prakash, Alexander H. Li, Hyacintha D'Indy, Alan C. Braverman, Bernard Grandchamp, Callie S. Kwartler, Laurent Gouya, Regie Lyn P Santos-Cortez, Marianne Abifadel, Suzanne M. Leal, Christine Muti, Jay Shendure, Marie Sylvie Gross, Mark J. Rieder, Alec Vahanian, Deborah A. Nickerson, Jean Baptiste Michel, Guillaume Jondeau, Dianna M. Milewicz
Journal: Nature Genetics (2012)
135 Staging of hepatic fibrosis by liver elastometry (fibroscan) in recurrent HCV infection in liver transplant recipients
Authors: F. Corradi, F. Piscaglia, R. Tame, A. Colecchia, P. Andreone, A. D Errico-Grigioni, F. Vasuri, A. Venturi, A. Lanzi, P. Boni, L. Bolondi
Journal: Journal of Hepatology (2006)
Antimicrobial efficacy of tobramycin polymeric nanoparticles for Pseudomonas aeruginosa infections in cystic fibrosis: Formulation, characterisation and functionalisation with dornase alfa (DNase)
Authors: Jill Deacon, Sharif M. Abdelghany, Derek J. Quinn, Daniela Schmid, Julianne Megaw, Ryan F. Donnelly, David S. Jones, Adrien Kissenpfennig, J. Stuart Elborn, Brendan F. Gilmore, Clifford C. Taggart, Christopher J. Scott
Journal: Journal of Controlled Release (2014)
Elevated Presence of Dendritic Cell Subsets in Chronic Rhinosinusitis
Authors: Sarah Peterson, Kate Welch, Julie Poposki, Lydia Suh, Roderick Carter, James Norton, Kathryn E. Hulse, Anju Peters, Leslie C. Grammer, Bruce Tan, Rakesh Chandra, David Conley, Robert Kern, Robert P. Schleimer, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2013)
Evaluation of the Obese Patient-Reply
Authors: George A. Bray
Journal: JAMA (1976)

The series in theThe Journalentitled TOWARD OPTIMAL LABORATORY USE was intended to focus on the laboratory as an instrument in the diagnosis of disease and as a tool for following treatment. The algorithm that we constructed had this goal in mind. From the frequency with which hypertension, hyperlipidemia, hyperglycemia, and abnormal thyroid function tests were uncovered when using this algorithm, it should be apparent that these are conditions for which obesity may be a valuable marker. Although the diabetics were known before our screening, there were no clinical criteria suggesting thyroid disease in the two patients with abnormal laboratory values (2/57 = 4%). Many of the measurements suggested in this algorithm are also appropriate for other patients, as Dr Gillette notes, but the frequency of abnormalities might well be different.  Dr Gillette has pointed out the desirability of obtaining additional information about obese patients, and I completely