tbuckley/cabot-search huggingface dataset:
Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial
Authors: C. Weinstein, K. Jordan, S.A. Green, E. Camacho, S. Khanani, E. Beckford-Brathwaite, W. Vallejos, L.W. Liang, S.J. Noga, B.L. Rapoport
Journal: Annals of Oncology (2015)

BackgroundTo establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC.Patients and methodsIn this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25–120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0–120 and 0–24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points.ResultsThe fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated.ConclusionSingle-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population.ClinicalTrials.govNCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).
Abstract P234: Cardiovascular Risk Prediction With Minimal Physiologic Variables
Authors: Monika M Safford, Lisandro Colantonio, Joshua Richman
Journal: Circulation (2015)

Introduction: Cardiovascular risk prediction relies on physiologic parameters, limiting the utility of tools such as the Pooled Cohort Risk Equation (PCRE) for self-administration outside clinical contexts. Tools that can be widely administered in places such as stores or pharmacies that offer blood pressure (BP) assessment could increase detection of high risk individuals and motivate care seeking. We developed a risk prediction approach that relies only on BP and otherwise self-reported variables and compared it with the PCRE. Methods: We identified 16,833 in the REasons for Geographic AND Racial Differences in Stroke (REGARDS) study without coronary heart disease (CHD) and &lt;80 years of age at baseline. CHD and stroke were expert adjudicated. Data included variables required to calculate the PCRE, as well as variables for the BP-self-report models (sociodemographics, medical history, and items assessed by validated questionnaires [e.g., Short Form-12]). We developed two predictive models for the composite endpoint of incident CHD or stroke using 1) survival trees (Tree) and 2) generalized additive models (GAM). For 5 iterations the cohort was randomly partitioned into equal training and testing subsets. Tree models and GAM were fit using the training subset and predicted risks calculated for the testing subset using the PCRE, Tree and GAM methods. C-statistics were calculated overall and stratified by age dichotomized at 65 for each model. Results: For the overall cohort, the mean C-statistics over the 5 iterations were PCRE: 0.69 (Range 0.65-0.74); GAM BP-self-report: 0.70 (0.67-0.72); Tree BP-self-report: 0.59 (0.55-0.66). For participants aged over 65 years the GAM had the highest mean of 0.64 vs. 0.58 (PCRE) and 0.54 (Tree). See Figure. Conclusion: A predictive statistical model using only self-reported data and systolic BP can have similar predictive performance to the PCRE, with potential marginal improvement noted for subjects over age 65 years.
Endothelial progenitor cells as markers of severity in hypertrophic cardiomyopathy
Authors: Athanasia Kalyva, Maria E. Marketou, Fragiskos I. Parthenakis, Charalampos Pontikoglou, Joanna E. Kontaraki, Spyros Maragkoudakis, Stylianos Petousis, Gregory Chlouverakis, Helen A. Papadaki, Panos E. Vardas
Journal: European Journal of Heart Failure (2015)
Elevated Serum Folic Acid Concentrations Were Associated with Higher mRNA Expression of DHFR Gene in Patients with Hereditary Spherocytosis
Authors: Clovis Paniz, Maylla Rodrigues Lucena, Juliano Felix Bertinato, Patricia Mendonça da Silva Amorim, Guilherme Wataru Gomes, Maria Stella Figueiredo, Ralph Green, Rodolfo Cancado, Claudia R Bonini Domingos, Vera Bláia-D'Avila, Marcelo Cliquet, Elvira Maria Guerra-Shinohara
Journal: Blood (2014)
Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008‐2011)
Authors: Yong‐ho Lee, Seung Up Kim, Kijun Song, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Byung‐Wan Lee, Eun Seok Kang, Bong‐Soo Cha, Kwang‐Hyub Han
Journal: Hepatology (2015)

Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the Korean National Health and Nutrition Examination Surveys 2008‐2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB‐4, and Forns index. Significant liver fibrosis was defined as FIB‐4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass [kg]/body mass index (kg/m 2 ]) was calculated using dual‐energy X‐ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P &lt; 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76‐2.68 depending on the subgroup, all P &lt; 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52‐0.67, all P &lt; 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB‐4 and Forns index) produced similar results. Conclusion: Sarcopenia is associated with significant liver fibrosis in subjects with NAFLD, and the association is independent of obesity and insulin resistance. (H epatology 2016;63:776–786)
<i>Citius, Altius, Fortius</i>: beneficial effects of resistance training for young athletes: Narrative review
Authors: Avery D Faigenbaum, Rhodri S Lloyd, James MacDonald, Gregory D Myer
Journal: British Journal of Sports Medicine (2015)

The motto of the Olympic Games is Citius, Altius, Fortius which is Latin for ‘Faster, Higher, Stronger’. It is a clarion call to all competitors, including the youngest, to engage in training strategies that prepare athletes to be the best in the world. Existing research indicates that various forms of resistance training can elicit performance improvements in young athletes. Stronger young athletes will be better prepared to learn complex movements, master sport tactics, and sustain the demands of training and competition. An integrative training programme grounded in resistance training and motor skill development can optimise a young athlete's potential to maximise their athletic and sporting performance, while reducing the risk of a sports-related injury. Resistance training may be especially important for modern-day young athletes who are more likely to specialise in one sport at an early age at the expense of enhancing general physical fitness and learning diversified sport skills. Structured interventions that include qualified instruction; targeted movement practice; and strength and conditioning activities that are developmentally appropriate, progressive and technique driven are needed to attain a level of athleticism that is consistent with the Olympic motto.
The role of NF- B activation in the pathogenesis of acute pancreatitis
Authors: Z Rakonczay, P Hegyi, T Takacs, J McCarroll, A K Saluja
Journal: Gut (2007)

Acute pancreatitis is an inflammatory disease of the pancreas which, in its most severe form, is associated with multi-organ failure and death. Recently, signalling molecules and pathways which are responsible for the initiation and progression of this disease have been under intense scrutiny. One important signalling molecule, nuclear factor κB (NF-κB), has been shown to play a critical role in the development of acute pancreatitis. NF-κB is a nuclear transcription factor responsible for regulating the transcription of a wide variety of genes involved in immunity and inflammation. Many of these genes have been implicated as central players in the development and progression of acute pancreatitis. This review discusses recent advances in the investigation of pancreatic and extrapancreatic (lungs, liver, monocytes and macrophages, and endothelial cells) NF-κB activation as it relates to acute pancreatitis.
Austin Powers bites back: a cross sectional comparison of US and English national oral health surveys
Authors: Carol C Guarnizo-Herreño, Georgios Tsakos, Aubrey Sheiham, Michael G Marmot, Ichiro Kawachi, Richard G Watt
Journal: BMJ (2015)

<b>Objective</b>&nbsp;To compare oral health in the US and England and to assess levels of educational and income related oral health inequalities between both countries. <b>Design</b>&nbsp;Cross sectional analysis of US and English national surveys. <b>Setting</b>&nbsp;Non-institutionalised adults living in their own homes. <b>Participants</b>&nbsp;Oral health measures and socioeconomic indicators were assessed in nationally representative samples: the Adult Dental Health Survey 2009 for England, and the US National Health and Nutrition Examination Survey 2005-08. Adults aged ≥25 years were included in analyses with samples of 8719 (England) and 9786 (US) for analyses by education, and 7184 (England) and 9094 (US) for analyses by income. <b>Main outcome measures</b>&nbsp;Number of missing teeth, self rated oral health, and oral impacts on daily life were outcomes. Educational attainment and household income were used as socioeconomic indicators. Age standardised estimates of oral health were compared between countries and across educational and income groups. Regression models were fitted, and relative and absolute inequalities were measured using the relative index of inequality (RII) and the slope index of inequality (SII). <b>Results</b>&nbsp;The mean number of missing teeth was significantly higher in the US (7.31 (standard error 0.15)) than in England (6.97 (0.09)), while oral impacts were higher in England. There was evidence of significant social gradients in oral health in both countries, although differences in oral health by socioeconomic position varied according to the oral health measure used. Consistently higher RII and SII values were found in the US than in England, particularly for self rated oral health. RII estimates for self rated oral health by education were 3.67 (95% confidence interval 3.23 to 4.17) in the US and 1.83 (1.59 to 2.11) in England. In turn, SII values were 42.55 (38.14 to 46.96) in the US and 18.43 (14.01 to 22.85) in England. <b>Conclusions</b>&nbsp;The oral health of US citizens is not better than the English, and there are consistently wider educational and income oral health inequalities in the US compared with England.
Phase I dose-escalation and pharmacokinetic study of amrubicin in patients with recurrent advanced lung cancer
Authors: I. Okamoto, A. Hamada, Y. Matsunaga, J.-I. Sasaki, S. Fujii, H. Uramoto, H. Yamagata, I. Mori, H. Kishi, H. Semba
Journal: Journal of Clinical Oncology (2005)

2068 Background: Amrubicin (AMR) is a totally synthetic 9-amino-anthracycline and potent topoisomerase II inhibitor. AMR is converted enzymatically to the C-13 hydroxymetabolite amrubicinol (AMR-OH), an active metabolite which demonstrates 10 to 100 times more cytotoxic than AMR. The objectives of this study were to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of AMR and AMR-OH when administered intravenously on days 1–3 to previously treated patients with recurrent advanced lung cancers. Method: Dose escalation was initiated at 30 mg/m2. For PK analysis, plasma sampling was performed during the first cycle of treatment and both AMR and AMR-OH concentrations were assayed using a validated high-performance liquid chromatographic assay. Results: In total, fifteen pts (12 men, 3 wemen, median: 64y, non-small cell lung cancer (NSCLC): 7, small cell lung cancer (SCLC):8) were enrolled. All patients received prior platinum-based chemotherapy. Six pts were entered to dose level 1 (30 mg/m2), 6 in dose level 2 (35 mg/m2) and 3 in dose level 3 (40 mg/m2). A total of 40 cycles of chemotherapy was administered. The most frequent toxicities were neutropenia. As a non-hematological toxicity, grade 3 pneumonitis occurred in one pt at dose level 2. Since all the three pts treated at dose level 3 experienced dose-limiting toxicities (neutropenia, febrile neutropenia, and arrhythmia), this dose level (40 mg/m2) was determined to be MTD. Partial response was seen in 1/15 pts, stable disease in 10/15 pts. Dose dependent PKs of AMR and AMR-OH were observed and interindividual variability in the enzymatic conversion of AMR to AMR-OH was quite small. Conclusion: The recommended dose of AMR in patients with recurrent lung cancer is 35 mg/m2 once a day from day 1 to day 3. The activity of this agent is being evaluated in phase II studies in previously treated patients with NSCLC and SCLC. No significant financial relationships to disclose.
In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons
Authors: Philipp Mächler, Matthias T. Wyss, Maha Elsayed, Jillian Stobart, Robin Gutierrez, Alexandra von Faber-Castell, Vincens Kaelin, Marc Zuend, Alejandro San Martín, Ignacio Romero-Gómez, Felipe Baeza-Lehnert, Sylvain Lengacher, Bernard L. Schneider, Patrick Aebischer, Pierre J. Magistretti, L. Felipe Barros, Bruno Weber
Journal: Cell Metabolism (2015)
Abstract P1-09-21: Metabolic syndrome is prevalent in women with newly diagnosed breast cancer
Authors: Louise C Wong, Carolyn Behrendt, Robin Smith, Joanne E Mortimer
Journal: Cancer Research (2015)

Abstract Purpose: We estimate the prevalence of metabolic syndrome (MetSyn) among women with newly diagnosed breast cancer and explore potential risk factors. Methods: From January 2012 to May 2014, women with newly diagnosed localized breast cancer were enrolled into a longitudinal survivorship study. At baseline, results of physical exam, use of concomitant medications, serum lipid profile and vitamin D were obtained from the medical record, while quality of life variables were measured via questionnaires in English. MetSyn was defined as at least 3 of 5 criteria: central obesity (BMI &amp;gt;30 or waist &amp;gt;=88 cm); triglycerides &amp;gt;=150 mg/dL; HDL cholesterol &amp;lt;50 mg/dL or cholesterol-lowering treatment; systolic &amp;gt;=130 or diastolic &amp;gt;=85 mm Hg blood pressure or treatment for hypertension; fasting glucose &amp;gt;=100mg/dL or diagnosis of Type 2 diabetes. Risk factors for MetSyn (age, education, serum vitamin D, self-reported energy in past month) were evaluated using multivariate logistic regression. Results: Subjects (n=154) were age 52.0 +10.1 years. Prevalence of MetSyn at baseline was 46.1(+4.0)%; for another 1.9(+1.1)% (n=3), MetSyn status was indeterminate due to lack of data on HDL and triglycerides. Among subjects with MetSyn (n=71), most had been diagnosed with hypertension (81.7%) and diabetes (61.4%). Without MetSyn (n=80), the latter conditions were much less prevalent (31.3% and 22.5%, respectively, both p&amp;lt;0.0001). Adjusted for race and year of accrual, the likelihood of MetSyn at baseline was higher per year of age (Odds Ratio (O.R.) 1.05, 95% CI 1.01-1.10, p=0.015), lower per increasing educational attainment (from less than high school to high school/some college, to bachelor’s, to graduate degree: O.R. 0.58, 0.36-0.93, p=0.024), and higher per increasing "time in past month with a lot of energy" (from little/no time to most of the time, to all of the time: O.R. 2.30, 1.11-4.75, p=0.025). An inverse association with serum Vit D (p=0.14) did not reach statistical significance. Conclusions: Metabolic syndrome is present in nearly half of women newly diagnosed with breast cancer and is associated with age, less education, and more energy in past month. Citation Format: Louise C Wong, Carolyn Behrendt, Robin Smith, Joanne E Mortimer. Metabolic syndrome is prevalent in women with newly diagnosed breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-21.
Cellular Cytotoxicity and Serum Inhibition in Normal Mice Following Transfer of Syngeneic Tumor-Sensitized Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Bernard Fisher, M.D., Norman Wolmark, M.D., Elizabeth A. Saffer, B.A.
Journal: JNCI Journal of the National Cancer Institute (1980)

Investigations were performed to elucidate changes in normal syngeneic recipients after they received tumor-sensitized cells. Transfer of regional or nonregional lymph node cells or spleen cells from tumor-bearing inbred C3HeB/FeJ mice to normal syngeneic recipients caused the recipients to produced bone marrow, which mediated in vitro cytolysis of immunizing tumor target cells. This finding was not entirely limited to transfer of lymphoid cells. The transfer of myeloid cells, granulocytes, and cultured macrophages from tumor-bearing mice also produced cytotoxic cells. The extent of cytotoxicity following cell transfer was related to the duration of tumor growth in cell donors, to the degree of cytotoxicity, and to the number of cells transferred. Both the iv and ip routes were equally effective. Treatment of cells before transfer with trypsin or pronase, mitomycin C, or sublethal irradiation failed to prevent development of cytotoxicity in cells of the recipient, whereas freeze-thawing abolished this event. Serum from the cell recipient could inhibit the cytotoxicity demonstrated by lymphoid cells derived from the recipient or from a tumor-bearing animal. The findings indicate that "information" transferred to normal animals not previously exposed to a tumor results in production of tumor-specific cytotoxic cells in these animals.
“Bendopnea” or “Kamptopnea?”
Authors: Rodney H. Falk
Journal: JACC Heart Failure (2014)

Thibodeau et al. [(1)][1] are to be congratulated on their detailed hemodynamic study of the effects of bending on intracardiac pressures. They demonstrate that dyspnea with bending is associated with a significant positional elevation of right- and left-sided filling pressures. The phenomenon was
Role of MYCN on ERAP1 and ERAP2 expression in neuroblastoma
Authors: Sonia Albini, Matteo Forloni, Loredana Cifaldi, Maria Zaira Limongi, Patrizio Giacomini, Doriana Fruci
Journal: Cancer Research (2008)

164  In this study we have investigated the molecular mechanism involved in the expression of two major components of the antigen processing machinery by MYCN in the most aggressive forms of neuroblastoma.  Neuroblastoma (NB) is the most common neuroectodermal cancer of childhood. The most aggressive forms are immunologically characterized by a severe reduction in major histocompatibility complex (MHC) class I molecules associated with amplification of the MYCN oncogene. The MHC class I presented on the cell surface plays an important role in the killer T lymphocyte-mediated immune response. We have recently shown that human cell lines from various tumours show de-regulated expression of two ER aminopeptidases, ERAP1 and ERAP2, that are closely involved in the generation of HLA class I binding peptides. HLA class I expression in such cell lines correlates significantly with ERAP1 expression. Here, in order to explore the possibility that the enhanced expression of MYCN oncogene may affect expression of ERAP1 and ERAP2, twelve NB cell lines were analysed for expression of MYCN, ERAP1, ERAP2 and HLA class I molecules. All NB cell lines expressing moderate to high levels of MYCN expression were low in HLA class I, ERAP1 and ERAP2 expression. Conversely, all NB cell lines low in MYCN expression were high in ERAP1 and/or HLA class I and ERAP2 expression. In the MYCN amplified NB cell lines, the expression of ERAP1, ERAP2 and HLA class I could be restored by IFN-γ, suggesting that these defects are non-structural in nature, but rather reflect abnormalities in regulatory mechanisms involved in the expression of these molecules.  MYCN contributes to oncogenesis by activating and repressing a large repertoire of genes. Because the repressor function of N-Myc has been found critical for cell transformation, to verify whether MYCN affects the expression of ERAP1 and ERAP2, we studied a NB cell line transfected with a MYCN vector regulated by tetracycline. Our data indicate that MYCN regulates the expression of these molecules.  MYCN performs its repressive function by interfering with positive transcription factors. To identify the transcription factor(s) involved in the ERAPs expression, several potential candidates were overexpressed in MYCN amplified (SH-EP21N) and not amplified (SH-EP) cell lines and ERAP1 and ERAP2 were analysed. Overexpression of two transcription factors enhanced expression of ERAP1 and ERAP2 in not amplified MYCN SH-EP cell line, but not in MYCN amplified SH-EP21N cell line. These data suggest that MYCN interaction with these transcription factors reduces their transcriptional activity.  We show that NB is characterized by complicated mechanisms correlated to antigen processing components deficiency through MYCN overexpression. Such mechanisms play an important role in immune evasion of neuroblastoma tumor.
The psychiatrist's view Preventing violent crime is not a medical role
Authors: G. Adshead
Journal: BMJ (1995)

The maintenance of civil order is a political issue, which may not be improved by becoming “medicalised.” Not only does this let central government off the hook it may also marginalise the problem. It is already too easy for the Home Office and the Department of Health to bounce the needs of crime victims between them. Doctors do not necessarily have any training or expertise in social policy matters, and, more importantly, no public mandate to take them over.

Being involved in crime prevention can backfire on health carers. If health carers have some role in crime prevention, should they …