tbuckley/cabot-search huggingface dataset:
ADAPTcycle: Adjuvant dynamic marker-adjusted personalized therapy comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2- early breast cancer.
Authors: Nadia Harbeck, Oleg Gluz, Matthias Christgen, Monika Graeser, Felix Hilpert, Katja Krauss, Hans Heinrich Kreipe, Ulrike Nitz, Ronald E. Kates, Timo Schinkoethe, Rachel Wuerstlein, Sherko Kuemmel
Journal: Journal of Clinical Oncology (2019)

TPS596 Background: WSG (West German Study Group)-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, controlled (neo)adjuvant, non-blinded, randomized phase III trial (EudraCT 2018-003749-40). It investigates whether HR+/HER2- intermediate-risk patients (pts) (about 20 % of HR+/HER2- early breast cancer, EBC) identified during screening (OncotypeDX and 3-week endocrine therapy (ET)) derive additional benefit from 2-years of the CDK4/6 inhibitor ribociclib plus ET compared to chemotherapy (CT) (followed by adjuvant ET). Co-primary endpoints are disease-free and distant disease-free survival. Methods: Starting Q1 2019 (enrollment 36 months, 80 sites), 5600 pts will be screened and 1670 randomized in a 3:2 ratio (1002 to ribociclib + ET; 668 to standard CT followed by ET). Pre-/postmenopausal pts with histologically confirmed invasive HR+/HER2- EBC at clinically enhanced risk (cT2-4 or Ki67 &gt; 20 % or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: Recurrence Score (RS) ≤ 25 and poor endocrine response or RS &gt; 25 and good endocrine response in p/cN0-1 pts or RS ≤ 25 with good endocrine response in c/pN2-3 pts. Endocrine responsiveness is determined by Ki67 response (drop to ≤ 10 %) after 3-week ET. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment can be given in the neoadjuvant or adjuvant setting. 5-year follow-up consists of standard adjuvant ET. Patient reported outcomes (ePROs) are collected using CANKADO; ECG monitoring is performed using a novel CANKADO-based methodology. For translational analyses, tumor tissue will be collected at baseline (prior to ET), after 3-weeks ET (+/- 1w). Additional samples are required if residual tumor is diagnosed in case of neoadjuvant treatment and at time of recurrence. Exploratory tissue biomarker research will be conducted to assess alterations of molecular markers (e. g., ESR1, PIK3CA, CCND1, CDKN2A, RB1). Circulating DNA and tumor cells from blood samples will be used to assess mutations, gene expression, etc. Clinical trial information: 2018-003749-40.
The public's view of the future of Medicare
Authors: R. J. Blendon
Journal: JAMA (1995)

AS WE REACHED the 30th anniversary of the enactment of Medicare, widespread national debate about the future of the program continues. The controversy involves strong disagreements over Medicare's short-term future as well as the shape the program should take in the next century. Health policy experts, national politicians, and opinion leaders have written and spoken extensively on this topic. But less attention has been paid to the views of the average citizen on the future of Medicare. This article seeks to fill that void. We attempt to answer three basic questions. First, how much do Americans know about Medicare and its problems? Second, what do they want to do about the program in the short term, particularly with regard to avoiding bankruptcy of the Medicare Hospital Trust Fund and achieving savings to help balance the federal budget? Last, what is the public's vision of the Medicare program in the next
The Precautionary Principle in Environmental Science
Authors: David Kriebel, Joel Tickner, Paul Epstein, John Lemons, Richard Levins, Edward L. Loechler, Margaret Quinn, Ruthann Rudel, Ted Schettler, Michael Stoto
Journal: Environmental Health Perspectives (2001)

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.
Ozone and Semen Quality
Authors: Jens Peter Bonde
Journal: Environmental Health Perspectives (2007)

Risk of Lymphohematopoietic Malignancies in Uranium MinersR ˇer ˇicha et al. (2006) analyzed data from Czech uranium miners with respect to incidence of malignancies of the lymphohematopoietic system.Their results, however, do not correspond with those of two recent studies on German uranium miners (Kreuzer et al. 2004; Möhner et al. 2006).R ˇer ˇicha et al. ( 2006) used a casecohort design, in which the subcohort was stratified by attained age and duration of employment.Stratification by age is a standard approach in case-cohort studies to optimize data ascertainment in the subcohort.However, stratification by duration of employment is problematic, because in occupational epidemiology it should be assumed that the duration of employment is highly correlated with cumulative exposure.Therefore, this kind of stratification contradicts the general demand for a random selection of controls with respect to exposure under study.Comparing the ratios of sampling fractions (< 12 months vs. ≥ 12 months duration of employment) between age groups results in a heterogeneous picture (Table 1).It is not uncommon in occupational cohort studies to include only subjects with a duration of employment of at least a certain number of months into the cohort.An analysis of only those miners with an employment duration of at least 12 months would be in line not only with the standard methodology but also with earlier published results of the authors (R ˇer ˇicha et al. 1998).Hence, the authors should have at least explained their reasoning for including the remaining miners in a second set of strata.In addition, they should have presented separate results for both duration strata to validate the result of the combined analysis.Given the above-mentioned assumption concerning the relationship between duration of employment and cumulative exposure, I calculated crude incidence rate ratios using data from Table 1 of R ˇer ˇicha et al. (2006).The age-specific odds ratios cover a wide range (0.29-7.16), and a corresponding test yields only borderline homogeneity.Consequently, completeness of matching with the cancer registry needs to be discussed.According to the study design, the time period between last exposure and begin of follow-up can span up to 27 years; therefore, the healthy-worker survivor effect could be an important issue in this study (R ˇer ˇicha et al. 2006).In light of the discussion on the magnitude of the latency period for leukemia, more detailed results would be useful to get an impression on, for example, the effect of the year of last exposure.
Phase II Trial of Docetaxel and Cisplatin Combination Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
Authors: Bonnie S. Glisson, Barbara A. Murphy, Gary Frenette, Fadlo R. Khuri, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the antitumor activity and toxicity of docetaxel plus cisplatin chemotherapy in patients with recurrent or incurable squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with recurrent or incurable SCCHN were eligible if they were chemotherapy naive or if they had received one prior regimen as neoadjuvant or concurrent treatment with radiation. Patients who had received chemotherapy for recurrence or prior taxanes were ineligible. Patients received docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 on day 1; cycles were repeated every 21 days. RESULTS: Toxic effects and length of survival were assessable in 36 patients and tumor response was assessable in 32, for whom the overall response rate was 40% (13 of 32) (6% complete response and 34% partial response). Median time to response was 5 weeks, and median duration was 4.9 months. In the intent to treat population (n = 36), median time to disease progression was 4 months. Median survival (n = 36) was 9.6 months, and the 12-month survival rate was 27%. Grade 4 neutropenia was observed in 71% of patients. Two patients (6%) experienced serious fever during grade 4 neutropenia (without documented infection) that required intravenous antibiotics, and an additional four patients had grade 3 infection. Other severe (grades 3 and 4) toxic effects were asthenia (25%), nausea (11%), fever (8%), vomiting (8%), severe hypersensitivity reactions (8%), and diarrhea (8%). Severe stomatitis (grade 3) occurred in only one patient. CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable safety profile for palliation of recurrent SCCHN. Relative to the standard regimen of cisplatin/fluorouracil, this regimen may offer higher tumor response and survival rates with short outpatient administration and a lower incidence of severe mucosal toxicity.
Renovascular Hypertension.
Authors: Albert N. Brest
Journal: JAMA (1963)

This monograph offers a penetrating analysis of the renal functional characteristics of renal artery occlusive disease. After presenting a thorough discussion of the characteristic functional defect in renovascular hypertension, the author describes and analyzes (in individual chapter form) a number of studies on several related subjects in the renovascular hypertensive field: (1) ureteral catheterization studies on patients with bilateral renal artery stenosis; (2) functional changes in the nonoccluded kidney after nephrectomy for unilateral renal artery occlusive disease; (3) collateral circulation to the ischemic kidney; (4) renal vein extraction ratios of p-aminohippurate in patients with renal artery occlusive disease; (5) observations on the relationship between changes in the volume of glomerular filtrate and reabsorption of water and sodium in the human nephron; and (6) the relationship of the macula densa in transferring tubular changes in sodium concentration to the juxtaglomerular cells. The book is of particular interest to the renologist, urologist
At McDonald's, 'the customers rule'
Journal: JAMA (1990)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 168: Stress Dependent MicroRNA Mediate Crosstalk Between DNA Repair ′ Senescence &amp; Angiogenic Signaling
Authors: Cristina Espinosa-Diez, RaeAnna Wilson, Namita Chaterjee, Clay Hudson, Rebbeca Ruhl, Erin Helms, Sudarshan Anand
Journal: Circulation Research (2017)

The endothelium is highly exposed to a myriad of stressors that can lead to endothelial dysfunction if persistent. One of the hallmarks of endothelial stress is increased DNA damage. MRN complex plays a vital role in DNA double strand break repair and replication. Nevertheless, its role in cardiovascular impair has not been studied in depth. Our results show that a cohort of microRNAs, upregulated under genotoxic and oxidative stress conditions, target MRN complex inducing senescent phenotype in endothelial cells. These microRNAs are rapidly transcribed in response to different types of stress, however the transcription factors that induce the expression of these miRs in response to DNA damage in endothelial cells is not known. We have profiled a subset of active transcription factors as c-Myc, Nrf2 and Nrf1 that robustly induce these miRs. Furthermore, our gain and loss-of-function studies indicate that these miRs, miR-99b and miR-494, affect telomerase activity, enable the activation of p21 and Rb pathways and regulate angiogenic sprouting. Ectopic expression of the miR mimics inhibits angiogenesis in vivo suggesting that targeting the MRN complex could be a viable anti-angiogenic strategy. Finally, our studies suggest a crosstalk between VEGF signaling and DNA Damage. Genetic and pharmacological disruption of VEGFR-2 signaling and the MRN complex reveal a surprising co-dependency of these pathways in regulating EC senescence and proliferation. Using a pathway focused gene expression array we find that disruption of the MRN complex leads to a robust transcription of CD44, a known driver of senescence as well as a negative regulator of VEGF signaling. Our work identifies a putative miR-facilitated mechanism by which endothelial cells can be insulated against VEGF signaling to facilitate the onset of senescence. We propose that stress response drives specific microRNA expression perturbing canonical VEGF signaling, proliferation and senescence by thresholding DNA damage repair in the vasculature.
Effect of Age on Immune Function in Terms of Chemically Induced Cancers
Authors: Michael Bennett
Journal: Environmental Health Perspectives (1979)

Neonatal, fetal, and very old animals are particularly sensitive to chemical carcinogenesis. Reasons for this increased sensitivity could be due to increased susceptibility of "target" organs or cells, peculiar hormonal levels at these age groups, relatively deficient immune functions, or combinations of these and/or other factors. During the late fetal and first three weeks of neonatal life, the immune system is rapidly maturing, is relatively incompetent, and its diverse components are developing at different rates. For example, thymus-dependent (T) alloreactive cells capable of proliferating in mixed lymphocyte reactions (T helper cells) develop by 7 days of age, but precursors of T killer cells are not competent until approximately 14 days of age. Bursa equivalent-dependent (B) cells capable of generating antibody responses are present in fetal liver but are extremely sensitive to tolerance induction until 10-14 days of age when IgD cell surface receptors are detectable. Marrow-dependent (M) cells responsible for regulation of suppressor cells and for natural cytotoxicity to transformed tumor cells do not mature until 3 weeks of age. In very old animals, the thymus is atrophic and cell-mediated immunity is moderately suppressed. Natural cytotoxicity against tumor cells is less than normal but antibody formation (B cell function) is adequate. Gonadotrophic hormones of the pituitary or placenta are high during pregnancy, the early neonatal period, after the menopause, and in a large fraction of men over 60 years of age. These and other hormones are immunosuppressive and could theoretically facilitate carcinogenesis. The particular immune cell type, if any, responsible for resistance to chemically induced tumors has not been determined. One can only state that susceptibility to chemical carcinogenesis is associated with a relative dysfunction of the immune system and that age is an important factor.
Degradation and intracellular accumulation of a residualizing hyaluronan derivative by liver endothelial cells
Authors: C McGary
Journal: Hepatology (1993)

The release and intracellular accumulation of 125I-hyaluronan degradation products was studied in cultured liver endothelial cells with hyaluronan oligosaccharides (relative molecular mass = approximately 44,000) uniquely modified and radiolabeled at the terminal reducing sugar. Two methods were combined to measure 125I-hyaluronan degradation by liver endothelial cells. (a) Cetylpyridinium chloride precipitation of hyaluronan oligosaccharides was used as a rapid, convenient assay to monitor the appearance of hyaluronan degradation products. Hyaluronan oligosaccharides less than 54 to 60 monosaccharides in length were not precipitated with cetylpyridinium chloride and thus were assessed as degraded. (b) Gel filtration chromatography was used to estimate the size range of oligosaccharides produced by liver endothelial cells. After internalization of 125I-hyaluronan, liver endothelial cells released radioactive degradation products into the culture media after a lag period of 2.5 to 3.0 hr. The intracellular accumulation of degraded 125I-hyaluronan was linear for at least 2 hr even though no degradation products were released. The long lag before release of degraded 125I-hyaluronan is likely caused by the modified chemical structure at the reducing end of the hyaluronan derivative; the derivative acts like a residualizing label. After this lag the release of degraded 125I-hyaluronan proceeded linearly for up to 12 hr. The extracellular 125I-hyaluronan degradation products eluted with a distribution coefficient of 1.3 on a gel filtration column. The major intracellular 125I-labeled degradation product showed the same retardation (distribution coefficient = 1.3). This retention may be caused by the hydrophobic aromatic and alkyl modifications to the former reducing sugar, also characteristics of a residualizing label. In addition, at least two larger minor intermediates were observed intracellularly. The rate of intracellular 125I-hyaluronan degradation was dependent on hyaluronan concentration and reached a maximal rate (159 molecules/cell/sec) at 2 × 10−7 mol/L. This was about half the maximal rate of endocytosis (285 molecules/cell/sec) at a hyaluronan concentration of 1.3 × 10−7 mol/L. The apparent ligand concentration that gives half-maximal responses for endocytosis and intracellular degradation was 0.6 × 10−7 and 1.0 × 10−7 mol/L, respectively. (HEPATOLOGY 1993;18:1465–1476.)
Dysphagia caused by migrated mesh after paraesophageal hernia repair
Authors: Q. Arroyo, F. Argüelles-Arias, M. Jimenez-Saenz, J. Herrerias-Gutierrez, F. Pellicer Bautista
Journal: Endoscopy (2011)

Correction to: Dysphagia caused by migrated mesh after paraesophageal hernia repairEndoscopy 2011; 43(S 02): E257-E258DOI: 10.1055/s-0030-1256520
Hematology of Infancy and Childhood
Authors: Ruth Andrea Seeler
Journal: JAMA (1975)

A new classic is off the press! A logical integration of the basic sciences and clinical medicine is now handily available in one volume. The book makes no attempt to be encyclopedic and excludes the details of laboratory methodology and the bulk of morphology. What it does is integrate a combination of biochemistry, physiology, and pathology texts into exciting prose explaining the how and why of pediatric hematological disorders. The presentation is clear and logical, with a fine balance between the clinical aspects of diagnosis and management on the one hand and overview and specifics on the other. Over one half of the 900 pages is devoted to the erythrocyte and its problems. Although less voluminous in paging, the sections devoted to white blood cells, platelets, coagulation, and the hematological malignancies are comprehensive and complete. I was particularly pleased by the chapters dealing with the theory and practice of component
ORTHOPEDIC SURGERY
Journal: JAMA (1970)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sedation
Authors: G. Carrasco, R. Molina, J. Costa, J. M. Soler, J. Paniagua, L. I. Cabré, E. Gravino, D. Leone, C. Caruso, G. Scioli, R. Tufano, J. Marti-Flich, B. Palmier, P. Arvers, J. Picard, G. Marggraf, J. Friedrich, V. Schumann, H. Lux, N. Doetsch, Mustafa Gönüllü, Leman Akbaş, Simay Serin, Yusuf Sarioĝlu, Tijen Kaya, J. A. Sanchez-Izquierdo Riera, E. Alted López, M. A. Gómez Aguinaga, S. Bermejo Aznarez, M. J. Jiménez Martín, A. Montera Castillo, P. Kessler, S. Probst, C. Müller, V. Lischke, W. Seiz, U. Schwulera
Journal: Intensive Care Medicine (1992)
1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults
Journal: JAMA (1993)

CDC has revised the classification system for HIV infection to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions. This classification system replaces the system published by CDC in 1986 (1) and is primarily intended for use in public health practice. Consistent with the 1993 revised classification system, CDC has also expanded the AIDS surveillance case definition to include all HIV-infected persons who have < 200 CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte percentage of total lymphocytes of < 14. This expansion includes the addition of three clinical conditions--pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer--and retains the 23 clinical conditions in the AIDS surveillance case definition published in 1987 (2); it is to be used by all states for AIDS case reporting effective January 1, 1993.