tbuckley/cabot-search huggingface dataset:
It's Now or Never: Fertility-Related Knowledge, Decision-Making Preferences, and Treatment Intentions in Young Women With Breast Cancer—An Australian Fertility Decision Aid Collaborative Group Study
Authors: Michelle Peate, Bettina Meiser, Michael Friedlander, Helen Zorbas, Susan Rovelli, Ursula Sansom-Daly, Jennifer Sangster, Dusan Hadzi-Pavlovic, Martha Hickey
Journal: Journal of Clinical Oncology (2011)

For many young women with early breast cancer, fertility is a priority. Interventions to retain fertility options generally need to be accessed before chemotherapy, but many women do not receive information regarding these options in a timely fashion. Knowledge about fertility and decisional conflict has not previously been measured in young patients with breast cancer considering future pregnancies.One hundred eleven young women with early breast cancer who had not yet completed their families were recruited around the time of diagnosis. Knowledge regarding fertility-related information, decisional conflict, and preferences regarding fertility information and decision making was measured.From a potential fertility-related knowledge score of 10, the mean was 5.2 (standard deviation = 2.3; range, 0 to 10). Decreased knowledge was associated with increased decisional conflict about pursuing fertility preserving interventions (odds ratio [OR] = 0.57; 95% CI, 0.44 to 0.73; P < .001). Thirty-one percent of women reported that they would consider undertaking in vitro fertilization (IVF) as a method to conserve their fertility, whereas 38% were uncertain. Consideration of IVF was not related to whether subjects were in a committed relationship (OR = 1.20; P = .716) or a definite desire for more children (OR = 1.54; P = .513).Around diagnosis, many young patients with breast cancer have low levels of knowledge about fertility issues. Further, low knowledge is associated with increased decisional conflict, which is likely to undermine the quality of decision making. These findings suggest that targeted and timely fertility information may reduce decisional conflict and increase informed choice. Neither relationship status nor firm plans regarding future children reliably predict desire to pursue fertility preservation.
Diminished Alveolar Microvascular Reserves in Type 2 Diabetes Reflect Systemic Microangiopathy
Authors: William W. Chance, Chanhaeng Rhee, Cuneyt Yilmaz, D. Merrill Dane, M. Lourdes Pruneda, Philip Raskin, Connie C.W. Hsia
Journal: Diabetes Care (2008)

Alveolar microvascular function is moderately impaired in type 1 diabetes, as manifested by restriction of lung volume and diffusing capacity (DL(CO)). We examined whether similar impairment develops in type 2 diabetes and defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy.A cross-sectional study was conducted at a university-affiliated diabetes treatment center and outpatient diabetes clinic, involving 69 nonsmoking type 2 diabetic patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q), DL(CO), membrane diffusing capacity (measured from nitric oxide uptake [DL(NO)]), and pulmonary capillary blood volume (V(C)) were determined at rest and exercise for comparison with those in 45 healthy nonsmokers as well as with normal reference values.In type 2 diabetic patients, peak levels of oxygen uptake, Q and DL(CO), DL(NO), and V(C) at exercise were 10-25% lower compared with those in control subjects. In nonobese patients (BMI <30 kg/m(2)), reductions in DL(CO), DL(NO), and V(C) were fully explained by the lower lung volume and peak Q, but these factors did not fully explain the impairment in obese patients (BMI >30 kg/m(2)). The slope of the increase in V(C) with respect to Q was reduced approximately 20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to A1C level, retinopathy, neuropathy, and microalbuminuria in a sex-specific manner.Alveolar microvascular reserves are reduced in type 2 diabetes, reflecting restriction of lung volume, alveolar perfusion, and capillary recruitment. This reduction correlates with glycemic control and extrapulmonary microangiopathy and is aggravated by obesity.
Caveolin-1 (<i>CAV1</i>) Is a Target of EWS/FLI-1 and a Key Determinant of the Oncogenic Phenotype and Tumorigenicity of Ewing's Sarcoma Cells
Authors: Oscar M. Tirado, Silvia Mateo-Lozano, Joaquín Villar, Luis E. Dettin, Anna Llort, Soledad Gallego, Jozef Ban, Heinrich Kovar, Vicente Notario
Journal: Cancer Research (2006)

Abstract Tumors of the Ewing's sarcoma family (ESFT), such as Ewing's sarcoma (EWS) and primitive neuroectodermal tumors (PNET), are highly aggressive malignancies predominantly affecting children and young adults. ESFT express chimeric transcription factors encoded by hybrid genes fusing the EWS gene with several ETS genes, most commonly FLI-1. EWS/FLI-1 proteins are responsible for the malignant phenotype of ESFT, but only few of their transcriptional targets are known. Using antisense and short hairpin RNA–mediated gene expression knockdown, array analyses, chromatin immunoprecipitation methods, and reexpression studies, we show that caveolin-1 (CAV1) is a new direct target of EWS/FLI-1 that is overexpressed in ESFT cell lines and tumor specimens and is necessary for ESFT tumorigenesis. CAV1 knockdown led to up-regulation of Snail and the concomitant loss of E-cadherin expression. Consistently, loss of CAV1 expression inhibited the anchorage-independent growth of EWS cells and markedly reduced the growth of EWS cell–derived tumors in nude mice xenografts, indicating that CAV1 promotes the malignant phenotype in EWS carcinogenesis. Reexpression of CAV1 or E-cadherin in CAV1 knockdown EWS cells rescued the oncogenic phenotype of the original EWS cells, showing that the CAV1/Snail/E-cadherin pathway plays a central role in the expression of the oncogenic transformation functions of EWS/FLI-1. Overall, these data identify CAV1 as a key determinant of the tumorigenicity of ESFT and imply that targeting CAV1 may allow the development of new molecular therapeutic strategies for ESFT patients. (Cancer Res 2006; 66(20): 9937-47)
Procalcitonin Kinetics as a Prognostic Marker of Ventilator-associated Pneumonia
Authors: Charles-Edouard Luyt, Valérie Guérin, Alain Combes, Jean-Louis Trouillet, Said Ben Ayed, Maguy Bernard, Claude Gibert, Jean Chastre
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We investigated the value of procalcitonin kinetics as a prognostic marker during ventilator-associated pneumonia (VAP). This prospective, observational study was conducted in a medical intensive care unit in a university hospital. All consecutive patients with microbiologically proven VAP who survived 3 days after its diagnosis were included and grouped according to clinical outcome: favorable or unfavorable, defined as death, VAP recurrence, or extrapulmonary infection requiring antibiotics before Day 28. Serum procalcitonin levels were measured on Days 1, 3, and 7 for all patients. Among the 63 patients included, 38 had unfavorable outcomes. On Day 1, they were more critically ill than patients with a favorable outcome. Serum procalcitonin levels decreased during the clinical course of VAP but were significantly higher from Day 1 to Day 7 in patients with unfavorable outcomes. Multivariate analyses retained serum procalcitonin levels on Days 1, 3, and 7 as strong predictors of unfavorable outcome. Based on these data, procalcitonin could be a prognostic marker of outcome during VAP.
A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease
Authors: Diego J. Laderach, Lucas D. Gentilini, Laura Giribaldi, Victor Cardenas Delgado, Lorena Nugnes, Diego O. Croci, Nader Al Nakouzi, Paula Sacca, Gabriel Casas, Osvaldo Mazza, Margaret A. Shipp, Elba Vazquez, Anne Chauchereau, Jeffery L. Kutok, Scott J. Rodig, María T. Elola, Daniel Compagno, Gabriel A. Rabinovich
Journal: Cancer Research (2012)

Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the "galectin signature" of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated "galectin-specific signature" that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease.
Comparison of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep in patients with chronic obstructive lung disease.
Authors: E Daskalopoulou, D Patakas, V Tsara, F Zoglopitis, E Maniki
Journal: Thorax (1990)

The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.
Adverse respiratory outcomes associated with occupational exposures at a soy processing plant
Authors: K. J. Cummings, D. M. Gaughan, G. J. Kullman, D. H. Beezhold, B. J. Green, F. M. Blachere, T. Bledsoe, K. Kreiss, J. Cox-Ganser
Journal: European Respiratory Journal (2010)

This study aimed to characterise the relationship between adverse health outcomes and occupational risk factors among workers at a soy processing plant. A questionnaire, spirometry, methacholine challenge, immune testing and air sampling for dust and soy were offered. Prevalence ratios (PRs) of respiratory problems from comparisons with the US adult population were calculated. Soy-specific immunoglobulin (Ig)G and IgE among participants and healthcare worker controls were compared. Associations between health outcomes and potential explanatory variables were examined using logistic regression. 147 (52%) out of 281 employees, including 66 (70%) out of 94 production workers, participated. PRs were significantly elevated for wheeze, sinusitis, ever-asthma and current asthma. Participants had significantly higher mean concentrations of soy-specific IgG (97.9 mg·L<sup>−1</sup><i>versus</i> 1.5 mg·L<sup>−1</sup>) and prevalence of soy-specific IgE (21% <i>versus</i> 4%) than controls. Participants with soy-specific IgE had three-fold greater odds of current asthma or asthma-like symptoms, and six-fold greater odds of work-related asthma-like symptoms; the latter additionally was associated with production work and higher peak dust exposures. Airways obstruction was associated with higher peak dust. Work-related sinusitis, nasal allergies and rash were associated with reported workplace mould exposure. Asthma and symptoms of asthma, but not other respiratory problems, were associated with immune reactivity to soy.
Detection of human cytomegalovirus (HCMV) pp67-mRIMA and pp65 antigenemia in relation to development of clinical HCMV disease in renal transplant recipients
Authors: I. Brook, M. Degré, K.I. Kristiansen, H. Rollag, E. Holter, K.P. Nordal
Journal: Clinical Microbiology and Infection (2001)
The Implications of Regional Variations in Medicare Spending. Part 1: The Content, Quality, and Accessibility of Care
Authors: Elliott S. Fisher, David E. Wennberg, Thrse A. Stukel, Daniel J. Gottlieb, F. L. Lucas, Étoile L. Pinder
Journal: Annals of Internal Medicine (2003)

Background: The health implications of regional differences in Medicare spending are unknown. Objective: To determine whether regions with higher Medicare spending provide better care. Design: Cohort study. Setting: National study of Medicare beneficiaries. Patients: Patients hospitalized between 1993 and 1995 for hip fracture (n = 614 503), colorectal cancer (n = 195 429), or acute myocardial infarction (n = 159 393) and a representative sample (n = 18 190) drawn from the Medicare Current Beneficiary Survey (19921995). Exposure Measurement: End-of-life spending reflects the component of regional variation in Medicare spending that is unrelated to regional differences in illness. Each cohort member's exposure to different levels of spending was therefore defined by the level of end-of-life spending in his or her hospital referral region of residence (n = 306). Outcome Measurements: Content of care (for example, frequency and type of services received), quality of care (for example, use of aspirin after acute myocardial infarction, influenza immunization), and access to care (for example, having a usual source of care). Results: Average baseline health status of cohort members was similar across regions of differing spending levels, but patients in higher-spending regions received approximately 60% more care. The increased utilization was explained by more frequent physician visits, especially in the inpatient setting (rate ratios in the highest vs. the lowest quintile of hospital referral regions were 2.13 [95% CI, 2.12 to 2.14] for inpatient visits and 2.36 [CI, 2.33 to 2.39] for new inpatient consultations), more frequent tests and minor (but not major) procedures, and increased use of specialists and hospitals (rate ratio in the highest vs. the lowest quintile was 1.52 [CI, 1.50 to 1.54] for inpatient days and 1.55 [CI, 1.50 to 1.60] for intensive care unit days). Quality of care in higher-spending regions was no better on most measures and was worse for several preventive care measures. Access to care in higher-spending regions was also no better or worse. Conclusions: Regional differences in Medicare spending are largely explained by the more inpatient-based and specialist-oriented pattern of practice observed in high-spending regions. Neither quality of care nor access to care appear to be better for Medicare enrollees in higher-spending regions.
A Majority of Breast Cancer Specimens with 1-9 % ER Positivity Behave Like Hormone Receptor Negative Tumors
Authors: K. Desai, N. Dendukuri, S. Manjunath, M. Correa, B.S. Srinath, K.S. Gopinath, T.S. Sridhar, A. Mehta, D.C. Doval, J.S. Prabhu
Journal: Annals of Oncology (2013)
Acute Aortic Syndromes
Authors: Thomas T. Tsai, Christoph A. Nienaber, Kim A. Eagle
Journal: Circulation (2005)

physician to King George II, first described on necropsy an acute aortic dissection.Over the course of more than 200 years, we have developed a growing awareness and understanding of acute and chronic aortic syndromes.Recent advances in imaging and therapeutic techniques have further emphasized the importance of early diagnosis of acute aortic syndromes, which continues to be crucial to survival.However, we continue to be uncomfortable in the diagnosis and management of this highly lethal disorder.In the present report, we review the etiology, pathophysiology, clinical presentation, outcomes, and therapeutic approaches to acute aortic syndromes.In each section, we summarize the most clinically relevant issues as "take home points" (THPs) to affirm their importance in the diagnosis and management of this disorder.
Hypoxia-Dependent Modification of Collagen Networks Promotes Sarcoma Metastasis
Authors: T.S. Karin Eisinger-Mathason, Minsi Zhang, Qiong Qiu, Nicolas Skuli, Michael S. Nakazawa, Tatiana Karakasheva, Vera Mucaj, Jessica E.S. Shay, Lars Stangenberg, Navid Sadri, Ellen Puré, Sam S. Yoon, David G. Kirsch, M. Celeste Simon
Journal: Cancer Discovery (2013)

Intratumoral hypoxia and expression of hypoxia-inducible factor-1α (HIF-1α) correlate with metastasis and poor survival in patients with sarcoma. We show here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF-1α enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF-1α or PLOD2 expression disrupts collagen modification, cell migration, and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSL-Kras(G12D/+); Trp53(fl/fl) murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF-1α-deficient tumors, and analysis of human sarcomas reveals elevated HIF1A and PLOD2 expression in metastatic primary lesions. Pharmacologic inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF-1α controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination.Undifferentiated pleomorphic sarcoma (UPS) is a commonly diagnosed and particularly aggressive sarcoma subtype in adults, which frequently and fatally metastasizes to the lung. Here, we show the potential use of a novel therapeutic target for the treatment of metastatic UPS, specifi cally the collagen-modifying enzyme PLOD2.
Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production
Authors: Daisuke Hata, Yuko Kawakami, Naoki Inagaki, Chris S. Lantz, Toshio Kitamura, Wasif N. Khan, Mari Maeda-Yamamoto, Toru Miura, Wei Han, Stephen E. Hartman, Libo Yao, Hiroichi Nagai, Anne E. Goldfeld, Frederick W. Alt, Stephen J. Galli, Owen N. Witte, Toshiaki Kawakami
Journal: The Journal of Experimental Medicine (1998)

We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells.
Efficacy of Nonoxynol 9 Contraceptive Sponge Use in Preventing Heterosexual Acquisition of HIV in Nairobi Prostitutes
Authors: Joan Kreiss
Journal: JAMA (1992)

<h3>Objective.</h3> —To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV). <h3>Design.</h3> —Prospective, randomized placebo-controlled trial. <h3>Setting.</h3> —Research clinic for prostitutes in Nairobi, Kenya. <h3>Patients and Interventions.</h3> —One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively. <h3>Main Outcome Measure.</h3> —HIV seroconversion. <h3>Results.</h3> —Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3;<i>P</i>&lt;.0001) and vulvitis (RR, 3.3;<i>P</i>&lt;.0001) and a reduced risk of gonococcal cervicitis (RR, 0.4;<i>P</i>&lt;.0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8). <h3>Conclusions.</h3> —Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women. (<i>JAMA</i>. 1992;268:477-482)
Selective serotonin reuptake inhibitors
Authors: John R Geddes, Andrea Cipriani
Journal: BMJ (2004)

The increasing use of antidepressants—particularly the selective serotonin reuptake inhibitors (SSRIs)—might be grounds for optimism because it might indicate that one of the great health problems of our age is increasingly being recognised and treated. Instead SSRIs have become embroiled in controversy over both their effectiveness and safety. As well as the doubts about efficacy, the media have fuelled concern that SSRIs may cause serious adverse effects, ranging from worsening depression to suicide. The scientific evidence shows that the media has blown the risk of suicide out of proportion.