tbuckley/cabot-search huggingface dataset:
Medicare, Medicaid, and Mental Health Care
Authors: Thomas R. Blair, Randall T. Espinoza
Journal: JAMA (2015)

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Abstract 777: Efficacy of nab-paclitaxel on 5-fluorouracil (5-FU) resistant human gastric cancer cell lines
Authors: Mamoru Nukatsuka, Takashi Kobunai, Kazuaki Matsuoka, Teiji Takechi
Journal: Cancer Research (2014)

Abstract Purpose: 5-Fluorouracil (5-FU)-based combination chemotherapy is widely used for the treatment of advanced gastric cancer in Japan. Thus, the development of effective chemotherapy for 5-FU-resistant gastric cancer after 5-FU-based chemotherapy is important. Nab-paclitaxel is an albumin-bound, 130-nm particle form of paclitaxel that exhibits a higher activity and lower toxicity than solvent-based paclitaxel. In the present study, the activity of nab-paclitaxel alone or in combination with 5-FU was evaluated in four 5-FU resistant cell lines. Method: 5-FU-resistant human gastric cancer cell lines were established from parent cells (MKN-45, MKN-74, NCI-N87, and KATO-III) by continuous exposure to escalating concentrations of 5-FU over a one-year period. The sensitivities of these cell lines to chemotherapeutic agents (5-FU and nab-paclitaxel) were evaluated using the WST-8 colorimetric assay. To evaluate the effects of the combination of 5-FU and nab-paclitaxel, the combination index (CI) value was calculated using CalcuSyn 2.0 (Biosoft, Cambridge, UK). The gene expressions of secreted protein acidic and rich in cysteine (SPARC) in the parent and 5-FU-resistant cell lines were evaluated using a Whole Human Genome 44K oligo DNA microarray (Agilent Technologies, Santa Clara, CA). Results: The IC50 value of 5-FU ranged from 2.35 to 36.7 μM, and its ratio (resistant cell lines/parent cell lines) ranged from 2.6 to 15.6. The IC50 value of nab-paclitaxel ranged from 4.45 to 54.5 nM, and its ratio ranged from 1.0 to 1.2. Therefore, the 5-FU-resistant cell lines used in this study showed no signs of cross-resistance to nab-paclitaxel. The calculated CI value treated with 5-FU and nab-paclitaxel was approximately 1; therefore, nab-paclitaxel additively inhibited the cell growth when administered in combination with 5-FU. Interestingly, the combination of 5-FU and nab-paclitaxel had an additive cytotoxic activity in the 5-FU-resistant human gastric cell lines in vitro. The relative expression of SPARC mRNA in the resistant cell lines to that in the parent ones ranged from 0.86 to 1.47, and SPARC expression might be weakly correlated with the acquisition of 5-FU resistance. Conclusion: Nab-paclitaxel might be a promising agent for the treatment of 5-FU-resistant human gastric cancer when used alone or in combination with 5-FU. These results suggest that nab-paclitaxel might be a promising chemotherapy for gastric cancer patients who relapse after undergoing 5-FU-based chemotherapy. Citation Format: Mamoru Nukatsuka, Takashi Kobunai, Kazuaki Matsuoka, Teiji Takechi. Efficacy of nab-paclitaxel on 5-fluorouracil (5-FU) resistant human gastric cancer cell lines. [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 777. doi:10.1158/1538-7445.AM2014-777
Allogeneic Bone Marrow Transplantation for Therapy-Related Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Long-Term Study of 70 Patients—Report of the French Society of Bone Marrow Transplantation
Authors: I. Yakoub-Agha, P. de La Salmonière, P. Ribaud, L. Sutton, E. Wattel, M. Kuentz, J.P. Jouet, G. Marit, N. Milpied, E. Deconinck, N. Gratecos, M. Leporrier, I. Chabbert, D. Caillot, G. Damaj, C. Dauriac, F. Dreyfus, S. François, L. Molina, M.L. Tanguy, S. Chevret, E. Gluckman
Journal: Journal of Clinical Oncology (2000)

To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT).From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease.With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome.BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.
Histologic Features and Observational Variation in Cerebellar Gliomas in Children2
Authors: F. H. Gilles, K. Winston, A. Fulchiero, A. Leviton
Journal: JNCI Journal of the National Cancer Institute (1977)

Variation existed in the recognition of histologic features commonly used in the evaluation of cerebellar gliomas of childhood. Some histologic features (e.g., perivascular pseudorosettes, leptomeningeal deposits, and calcification) were more reliably observed than were others (e.g., Rosenthal fibers, cell density, and hypervascularity). Knowledge of which features tend to have greater observational variation may lead to improved definitions, less reliance on these features in clinical decisions, further studies of the potential sources of the variation, and guidelines for minimizing observational variation.
A Simple Method to Improve the Reliability of Tree Reconstructions
Authors: M Schoniger, A von Haeseler
Journal: Molecular Biology and Evolution (1993)

The efficiencies of distance-matrix methods for correct tree reconstruction under a variety of substitution rates, transition-transversion biases, and different model trees were studied.If substitution rates are high and the ratio of transitions and transversions is large, even a Kimura two-parameter correction fails very often to reconstruct the model tree.We show that a combination of combinatorial weighting by Williams and Fitch and the Jukes-Cantor correction significantly increases the efficiency of tree-reconstruction methods, for a large fraction of evolutionary parameters.We explain why this approach is superior to any other weighting/correction scheme tested, as long as sequences are sufficiently long or substitution rates are sufficiently large.An approximate threshold for switching to a different weighting scheme is given.1.
Comparing a combination of validated questionnaires with Level III portable monitor in the diagnosis and severity of sleep apnea
Authors: Margarida Aguiar, Liliana Campos, Carina Santos, Silvia Rodrigues, Susana Simões, Sofia Furtado
Journal: European Respiratory Journal (2014)

Questionnaires have been validated as screening tool in adult populations at risk for obstructive sleep apnea (OSA). Portable monitors (PM) have gained acceptance for the confirmation of OSA in patients (pts) with a high pretest probability of the disorder. We evaluated the diagnostic utility of validated questionnaires and a Level III PM in the diagnosis and severity of OSA.  The aim was to evaluate if pts with a high pretest probability of OSA according to pre-determined questionnaires would have high prevalence and severity of OSA. Consecutive pts referred to the sleep clinic completed 3 questionnaires (Standford Sleepiness Scale (SSS), Berlin Questionnaire (BQ) and STOP-Bang) and were then submitted to a Level III PM test.  In 2013, 353 pts were evaluated at our sleep clinic, 64% males. All were submitted to Level III testing and presented the following severity of obstructive apnea (IAH 5 mild, IAH>15 moderate, IAH>30 severe); negative 25%, mild 26%, moderate 17% and severe 32%. In the SSS, 12 pts (4%) scored more than 3. Eight patients (66,7%) scored positive (IAH > 5). Three had severe, 4 moderate and 1 mild results in the poligraphy. One hundred and twenty six pts (35,7%) scored positive in all three categories of BQ. 99(79%) scored positive (IAH > 5). 29% mild, 17% moderate and 33% severe. In the Stop-Bang, out of a total of 219 answers, 103 pts (47%) scored more than 4. Out of these 103 pts, 89% scored positive (IAH>5); 27% mild, 20% moderate and 43% severe.  None of the questionnaires evaluated were able to predict the severity of OSA, however, STOP-Bang, when positive, was highly suggestive of the presence of OSA.
Malignant Biliary Tract Obstruction: Evaluation and Therapy
Authors: David Chu, Douglas G. Adler
Journal: Journal of the National Comprehensive Cancer Network (2010)

Malignant biliary tract obstruction is a common clinical entity. Patients with tumors causing biliary tract obstruction are often asymptomatic until disease is significantly advanced. Symptoms of obstructive jaundice can significantly impair quality-of-life unless intervention to decompress the biliary tract, either curative or palliative, is performed. This article reviews the evaluation and management of patients with malignant biliary tract obstruction, including the available imaging and treatment modalities (endoscopic, percutaneous, and surgical approach) for relieving malignant biliary tract obstruction.
Abstract 5622: Effectiveness of Hybrid Therapy With Warfarin and Statins to Reduce the Incidence of Ischemic Stroke in High-risk Patients With Atrial Fibrillation
Authors: Yoshiyuki Hama, Marehiko Ueda, Hiroyuki Takano, Yasunori Hiranuma, Yasuhiko Hori, Akira Miyazaki, Masato Yamanouchi, Junji Kanda, Yoichi Kuwabara, Issei Komuro
Journal: Circulation (2009)

Background HMG-CoA reductase inhibitor statins have been recently used to prevent ischemic stroke in patients with coronary artery disease. However, whether or not such statins truly reduce the risk of ischemic stroke in patients with atrial fibrillation (AF) remains to be clearly elucidated. Methods We performed a retrospective cohort study at 4 Japanese centers. The study sample consisted of a cohort of 1152 patients (mean age, 67±10 years; men, 64 %; 513 paroxysmal AF) who had documented AF on electrocardiograms before August 2002 and who also visited our hospitals after September 2002. The statin group consisted of 179 patients (16%). A cox proportional hazards analysis was performed to control for baseline differences. We assessed the incidence of ischemic stroke. Results During a follow-up of 61±23 months, 151 patients experienced ischemic stroke. Since the statin group had more risk factors for stroke, such as a history of congestive heart failure, hypertension and diabetes mellitus, than the non-statin group, the statin group had a higher CHADS2 score (congestive heart failure, hypertension, age, diabetes, stroke [doubled]) than the non-statin group (statin group 1.93±1.15 vs. non-statin group 1.42±1.19, p&lt;0.001). The incidence of ischemic stroke was similar in both groups (statin group 12.0% vs. non-statin group, 17.5%, P = 0.08). For patients with a CHADS2 score ranging from 2– 6 with concomitant warfarin use, however, ischemic stroke was significantly less frequent in the statin group (statin group 11.7% vs. non-statin group, 26.0%, P = 0.045) although the incidence of major bleeding was similar in both groups (statin group 14.4% vs. non-statin group, 21.1%, P = 0.508). After adjustment for differences in baseline clinical variables, statin use was significantly associated with the incidence of ischemic stroke (hazard ratio[HR], 0.43; 95% confidence interval[CI], 0.23 to 0.83; P = 0.012), Conclusions In comparison to warfarin alone, the hybrid therapy with warfarin and statin was therefore suggested to be more effective in high-risk patients with atrial fibrillation.
A new paradigm for tumor immune escape: β-catenin-driven immune exclusion
Authors: Stefani Spranger, Thomas F. Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Increasing evidence is emerging that immunotherapeutic interventions, including checkpoint blockade, are predominantly effective in patients with a pre-existing T cell-inflamed tumor microenvironment. Understanding the mechanisms leading to a non-T cell-inflamed microenvironment are crucial for the development of novel treatment modalities to expand the fraction of patients benefiting from immunotherapy. Based on the hypothesis that one source of inter-patient heterogeneity would lie at differential activation of specific oncogene pathways within the tumor cells themselves, our group recently observed that tumor-cell intrinsic activation of the WNT/β-catenin pathway correlates with absence of T cells from the microenvironment in metastatic melanoma. Genetically-engineered mouse models confirmed a causal relationship, via a mechanism of failed Batf3-lineage dendritic cell recruitment. Hence, tumor cell-intrinsic activation of β-catenin is the first oncogenic pathway demonstrated to exclude the anti-tumor immune response, revealing a potential therapeutic target for improving immunotherapy responsiveness.
Survival of the fittest: retrospective cohort study of the longevity of Olympic medallists in the modern era
Authors: Philip M Clarke, Simon J Walter, Andrew Hayen, William J Mallon, Jeroen Heijmans, David M Studdert
Journal: British Journal of Sports Medicine (2015)

Objective To determine whether Olympic medallists live longer than the general population. Design Retrospective cohort study, with passive follow-up and conditional survival analysis to account for unidentified loss to follow-up. Setting and participants 15 174 Olympic athletes from nine country groups (United States, Germany, Nordic countries, Russia, United Kingdom, France, Italy, Canada, and Australia and New Zealand) who won medals in the Olympic Games held in 1896–2010. Medallists were compared with matched cohorts in the general population (by country, age, sex, and year of birth). Main outcome measures Relative conditional survival. Results More medallists than matched controls in the general population were alive 30 years after winning (relative conditional survival 1.08,95% confidence interval 1.07 to1.10). Medallists lived an average of2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11,1.09 to 1.13) than that of medallists in power sports (1.05,1.01 to 1.08). Conclusions Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory.
Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.
Authors: L Jaakkimainen, P J Goodwin, J Pater, P Warde, N Murray, E Rapp
Journal: Journal of Clinical Oncology (1990)

An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.
Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling
Authors: Milena Monteiro-Sepulveda, Sothea Touch, Carla Mendes-Sá, Sébastien André, Christine Poitou, Omran Allatif, Aurélie Cotillard, Hélène Fohrer-Ting, Edwige-Ludiwyne Hubert, Romain Remark, Laurent Genser, Joan Tordjman, Kevin Garbin, Céline Osinski, Catherine Sautès-Fridman, Armelle Leturque, Karine Clément, Edith Brot-Laroche
Journal: Cell Metabolism (2015)

In obesity, insulin resistance is linked to inflammation in several tissues. Although the gut is a very large lymphoid tissue, inflammation in the absorptive small intestine, the jejunum, where insulin regulates lipid and sugar absorption is unknown. We analyzed jejunal samples of 185 obese subjects stratified in three metabolic groups: without comorbidity, suffering from obesity-related comorbidity, and diabetic, versus 33 lean controls. Obesity increased both mucosa surface due to lower cell apoptosis and innate and adaptive immune cell populations. The preferential CD8αβ T cell location in epithelium over lamina propria appears a hallmark of obesity. Cytokine secretion by T cells from obese, but not lean, subjects blunted insulin signaling in enterocytes relevant to apical GLUT2 mislocation. Statistical links between T cell densities and BMI, NAFLD, or lipid metabolism suggest tissue crosstalk. Obesity triggers T-cell-mediated inflammation and enterocyte insulin resistance in the jejunum with potential broader systemic implications.
Tachykinin 1 receptor antagonist FK888 suppresses angiotensin converting enzyme inhibitors (ACEIs)-induced tracheal inflammation, an experimental study
Authors: Esraa Ashry, Yaser Gad, Magda Yosry, Amani Osama, Afaf Abdelwareth
Journal: European Respiratory Journal (2013)

Introduction  Several mechanisms have been proposed to explain angiotensin converting enzyme (ACE) inhibitor-induced cough, but the exact mechanism is not known. ACEIs has been shown to induce the production of PGE2 and NO, which have been implicated as a mediator of inflammation in experimental models.  Aim of the work  To study the effect of acute and chronic treatment with ACE inhibitors (perindopril and fosinopril) each alone and in combination with tachykinin 1 antagonist FK888 on tracheal Nitrate/Nitrite (N/N) and PGE2 levels  Material and Methods  About 60 rats of adult rats, of both sexes, weighing 120-150 gm were used in the study. Four groups in acute treatment, four groups in chronic treatment and two control groups (6 rats in each group).  The control group was injected with carboxymethyle cellulose.the treated groups were injected with perindopril or fosinopril either alone or in combination with FK888,three hours later in acute inflammation groups and 21 days later in chronic treatment groups, rats were sacrificed and their tracheae were extracted, homogenized and the supernates were used for of total nitrite/nitrate and PGE2 assay.  Results  Both acute and chronic treatment with perindopril and fosinopril had insignificant increase in tracheal N/N and PGE2 levels (P   Conclusion  The study proved that treatment with the studied ACEIs increased tracheal N/N and PGE2 levels, however, if these mechanisms contribute to ACEIs induced cough or not requires further studies.
Concordance between the new questionnaires to evaluate asthma control
Authors: Estefania Luque, Patricia Guerrero, Ana Gόmez-Bastero, Concepciόn Romero, Layla Mechbal, Teodoro Montemayor
Journal: European Respiratory Journal (2011)

Objectives:  Regarding asthma, the main objective is to control the disease symptoms. Both Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) are one of the most used tools to evaluate asthma control in medical practice. Two studies have been recently published where new cut-off points for ACT (> 21, 19-20 and   1) are established. This leaded us to evaluate the concordance between both test in our patients.   Methods:  We have included 179 asthmatic patients chosen from our medical practice, who performed both questionnaires and were classified in different categories of asthma control, and we analyzed the concordance of the results.   Results:  The average age of our patients was 45±11 years and the FEV1 measured was 2.65±0.95 litres (82±22%).  The classification of our patients, according to the questionnaires is shown in Table 1.  By comparing the results of both questionnaires, we find a very good correlation (correlation coefficient 0.75) and a poor concordance (kappa 0.556), although statistically significant (p    Conclusions:  As we cannot find a good concordance between both questionnaires is not possible to exchange them or their cut-off points, so it would be convenient to carry out prospective multicentre studies using both questionnaires and GINA/GEMA criteria.