tbuckley/cabot-search huggingface dataset:
Multicenter phase II study of temozolomide therapy for brain metastases in patients with malignant melanoma, breast cancer, or non-small cell lung cancer: Final results
Authors: M. Danova, E. Bajetta, L. Crinò, S. Del Prete, S. Cascinu, S. Salvagni, S. Siena
Journal: Journal of Clinical Oncology (2008)

2032 Background: The incidence of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer (BC), or malignant melanoma (MM), has increased in recent years thus representing a major factor in reducing survival because of limited therapeutic options. This phase II study investigated the clinical activity of a dose-dense regimen of temozolomide (TMZ) in patients with BM from advanced NSCLC, BC, and MM. The alternating weekly regimen was chosen based on evidences suggesting that this regimen may overcome resistance to alkylating agents. Methods: This was an open-label, 2-step trial that enrolled patients with measurable BM that had not been previously irradiated. Patients were stratified by primary tumor type (NSCLC, BC, or MM) and were treated with oral TMZ 150 mg/m2/day on days 1–7 and 15–21 every 28 days for up to 15 months or until disease progression. The length of each cycle was increased to 35 days by protocol amendment. The primary endpoint was best response (CR, PR, or stable disease) in the brain as measured with MRI. Secondary endpoints were added by protocol amendment and included progression-free survival (PFS), brain PFS, and overall survival (OS). Results: Between Dec 2000 and Oct 2005, a total of 162 patients were enrolled, and 157 were evaluable for efficacy and safety (NSCLC: n=53; BC: n=51; MM: n=53). Partial response or stable disease was achieved in 14 (26.4%) patients with NSCLC (95 CI: 15.3%, 40.3%), 10 (19.6%) patients with BC (95 CI: 9.8%, 33.1%), and 17 (32.1%) patients with MM (95 CI: 19.9%, 46.3%). Median PFS and median PFS in the brain were 2 months (0.9 - 3.0 and 1.0 - not reached, respectively), regardless of primary tumor type, with the exception of patients with MM treated on the 35-day cycle, in whom median PFS was only 39 days (95% CI: 26, 72 days). Median OS has not been reached. The most frequent adverse events were hematologic toxicity, mainly lymphopenia and thrombocytopenia (more common in NSCLC), nausea and vomiting (more common in MM), and headache (more common in BC). Conclusions: This dose-dense regimen of TMZ is able to achieve responses in patients with BM from NSCLC, BC, or MM with an acceptable safety profile. No significant financial relationships to disclose.
Analysing indicators of performance, satisfaction, or safety using empirical logit transformation
Authors: Sarah Stevens, Jose M Valderas, Tim Doran, Rafael Perera, Evangelos Kontopantelis
Journal: BMJ (2016)

Performance, satisfaction, and safety indicators are commonly measured on a percentage scale. Such indicators are often subject to ceiling or floor effects and performance may be inherently non-linear. For example, improving from 85% to 95% might be more difficult and need more effort than improving from 55% to 65%. As such, analysis of these indicators is not always straightforward and standard linear analysis could be problematic. We present the most common approach to dealing with this problem: a logit transformation of the score, following which standard linear analysis can be conducted on the transformed score. We also demonstrate how estimates can be back-transformed to percentages for easier communication of findings. In this paper, we discuss the benefits of this method, use algebra to describe the relevant steps in the transformation process, provide guidance on interpretation, and provide a tool for analysis.
Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank
Authors: Jessica Tyrrell, Samuel E Jones, Robin Beaumont, Christina M Astley, Rebecca Lovell, Hanieh Yaghootkar, Marcus Tuke, Katherine S Ruth, Rachel M Freathy, Joel N Hirschhorn, Andrew R Wood, Anna Murray, Michael N Weedon, Timothy M Frayling
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. <b>Design</b>&nbsp;Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. <b>Setting</b>&nbsp;UK Biobank. <b>Participants</b>&nbsp;119 669 men and women of British ancestry, aged between 37 and 73 years. <b>Main outcome measures</b>&nbsp;Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. <b>Results</b>&nbsp;In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10<sup>−3</sup>) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10<sup>−15</sup>) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10<sup>−7</sup>), and a £1130 (£680 to £1580) higher annual household income (P=4×10<sup>−8</sup>). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m<sup>2</sup>) caused a £2940 (£1680 to £4200; P=1×10<sup>−5</sup>) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. <b>Conclusions</b>&nbsp;These data support evidence that height and BMI play an important partial role in determining several aspects of a person’s socioeconomic status, especially women’s BMI for income and deprivation and men’s height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.
Antigenically Distinct Forms of Mammary Tumor Virus in Blood and Mammary Tissues of Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. Nandi, Sandra Haslam, Charles D. Aldrich
Journal: JNCI Journal of the National Cancer Institute (1971)

To compare mammary tumor virus (MTV) activity associated with red blood cells (R-MTV) and mammary tissues (M-MTV) of BALB/-cfC3H mice, the neutralizing effects of mouse and rabbit antisera to M-MTV on viral preparations from both sources were studied. The antisera used could neutralize the biologic activity of MTV present in mammary tissue extracts, but not the activity in hemolyzed red blood cells.
Comparative Biochemistry of Three Transplantable Mammary Tumors as Influenced by Steroid Therapy&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: Russell Hilf, Minnie M. Johnson, Charles Breuer, James J. Freeman, Aleck Borman
Journal: JNCI Journal of the National Cancer Institute (1963)

The effect of steroid administration on certain biochemical components of 3 transplantable mammary tumors in the Fischer rat was investigated. As the dose of diethylstilbestrol was increased in animals bearing the responsive R3230-S tumor, the nitrogen content, the ribonucleic acid/deoxyribonucleic acid (RNA/DNA) ratios, RNA, and acid and alkaline phosphatase activities increased significantly. In animals bearing the less responsive R3230 tumor, diethylstilbestrol treatment slightly increased the RNA/DNA ratios and caused a dose-response increase in acid phosphatase activity. None of these endpoints were changed by estrogen treatment in the unresponsive HMC tumor. Treatment with testosterone propionate slightly increased RNA/DNA ratios in the R3230-S and R3230 tumors. Both acid and alkaline phosphatase activity rose in the R3230-S tumor and the acid phosphatase activity increased in the R3230 tumor. There was no change in the HMC tumor-bearing animals. Although certain alterations of adenosinetriphosphatase and 5′-nucleotidase activities were observed, these changes did not follow any definite pattern, or response to dose. The intracellular distribution of these enzymes was similar in the 3 tumors, but the 5′-nucleotidase activity of the HMC tumor was 5 to 10 times higher than that of the other tumors. A screening protocol, based on steroid-induced alterations of the RNA/DNA ratio in the R3230-S tumor, was adopted and preliminary results of the effect of several steroid and carcinolytic agents are reported.
Bleeding in Patients with Atrial Fibrillation Treated with Non Vitamin K Antagonist Oral Anticoagulants: A Population-Based Study
Authors: Martin H. Ellis, Tsipora Neumann, Jeffrey S Ginsberg, John W Eikelboom, Haim Bitterman, Ariel Hammerman, Erez Battat, Sari Greenberg, Jack Hirsh
Journal: Blood (2014)
Abstract 244: Ethnic Differences among Middle Eastern Arabs and South Asians with In-Hospital Cardiac Arrest: A 20-Year Experience From a Middle-Eastern Country (1991-2010)
Authors: Amar M Salam, Hajar AlBinali, Rajvir Singh, Awad Al-Qahtani, Jassim Al Suwaidi
Journal: Circulation (2013)

Objectives: Most of the published research on in-hospital cardiac arrest (IHCA) is limited to studies in the developed world and included mainly Caucasian and African-American patients. The world literature on the clinical epidemiology of IHCA in other ethnic groups is very scarce. The aim of this study was to compare the clinical characteristics, risk profiles and outcome of Middle Eastern Arabs compared to South Asians patients with IHCA using a 20-year national cardiology registry in a Middle-Eastern Country. Methods: Retrospective analysis of all patients that developed IHCA in Qatar from 1991 through 2010 was made. Patients were compared according to ethnicity. Clinical characteristics, management and outcomes were analyzed. Results: During the 20-years period 41,436 patients were hospitalized to the cardiology service in Qatar from 1991 to end of 2010. Of these 22755 were Arabs and 13905 South Asians. The remaining patients were from many other ethnicities and were excluded for the purpose of this study. Of the 2 study groups 1529 patients developed IHCA during hospitalization; 1079 Arabs (4.7%) and 450 South Asians (3.2%), p = 0.001. Arabs with IHCA were 13 years older and had a higher body mass index compared to Asians. Arabs had significantly higher prevalence of hypertension, diabetes mellitus, chronic renal impairment and prior myocardial infarction while current smoking status and acute coronary syndromes were significantly more common in Asians. The in-hospital mortality rate was significantly higher in Arabs with IHCA compared to Asians (82.8% versus 78%; p=003) [table]. Conclusions: Our study demonstrates that Arabs have a higher incidence of IHCA compared to South Asians and that this is associated with a lower in-hospital survival rates and a higher cardiovascular risk profiles in Arabs. The current study underscores the need to study IHCA among various ethnicities around the world.
Expression and Prognostic Significance of Mesothelin in Her-2-Positive and Triple-Negative Breast Cancer Patients
Authors: I.V. Bayoglu, B. Kucukzeybek, Y. Küçükzeybek, I. Yildiz, M. Akyol, U. Varol, A. Alacacioglu, L. Demir, A. Dirican, Y. Yildiz, M.O. Tarhan
Journal: Annals of Oncology (2014)
Ovarian metastases in stage Ib to IIb carcinoma of the uterine cervix
Authors: M. Shimada, J. Kigawa, S. Yamaguchi, R. Nishimura, T. Nakanishi, K. Kuzuya, M. Suzuki, T. Kita, Y. Kikuchi, N. Terakawa
Journal: Journal of Clinical Oncology (2004)

5061 Background: Recently, uterine cervical cancer has increased in young women. The management of ovaries is important in patients with cervical cancer. In the previous studies, the number of patients with cervical cancer was too small to draw conclusion about the impact of various clinicopathologic features in ovarian metastases. We conducted the present review to determine clinicopathological features in over 3,000 patients with cervical cancer who underwent radical hysterectomy included bilateral salpingo-oophorectomy. The present study involved the largest series of patients with ovarian metastases. Methods: A total of 3,352 patients with stage Ib to IIb cervical cancer underwent radical hysterectomy included bilateral salpingo-oophorectomy between 1980 and 2002 in our 5 institutes. All patients were identified by the medical records. Of 3,352 patients with cervical cancer, 42 (1.3%) had ovarian metastases. The clinicopathological features in those patients were examined. Results: The mean age of patients with ovarian metastases was 52.5 years (range: 29–73 years). Out of 42 cases, there were 12 in stage Ib, 5 in stage IIa, and 25 in stage IIb. No patients with stage Ib1 squamous cell carcinoma had ovarian metastases. The incidence of ovarian metastases was shown in Table. Ovarian metastases were more frequently in adenocarcinoma than that in squamous cell carcinoma (3.91% vs. 0.76%). The 5-year survival rate was 40.1% for stage Ib, 66.7%, for stage IIa, and 23.6% for stage IIb in patients with ovarian metastases. The side of ovarian metastases did not correlate with the side of lymphnode involvement or paracolpium invasion. Conclusions: The present study indicates that ovaries in stage Ib-IIa patients with squamous cell carcinoma can be preserved. In contrast, patients with cervical adenocarcinoma are recommended to remove ovaries. No significant financial relationships to disclose.
Stopping vs. Continuing Aspirin before Coronary Artery Surgery
Authors: Paul S. Myles, Julian A. Smith, Andrew Forbes, Brendan Silbert, Mohandas Jayarajah, Thomas Painter, D. James Cooper, Silvana Marasco, John McNeil, Jean S. Bussières, Sophie Wallace
Journal: New England Journal of Medicine (2016)

Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery.
Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma
Authors: Hayley E. Bullen, Yonggen Jia, Yoshiki Yamaryo-Botté, Hugo Bisio, Ou Zhang, Natacha Klages Jemelin, Jean-Baptiste Marq, Vern Carruthers, Cyrille Y. Botté, Dominique Soldati-Favre
Journal: Cell Host & Microbe (2016)
Association between psoriasis and inflammatory bowel disease: a Danish nationwide cohort study
Authors: A. Egeberg, L. Mallbris, R.B. Warren, H. Bachelez, G.H. Gislason, P.R. Hansen, L. Skov
Journal: British Journal of Dermatology (2016)

Psoriasis, Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders with overlapping genetic architecture. However, data on the frequency and risk of CD and UC in psoriasis are scarce and poorly understood.To investigate the association between CD and UC in patients with psoriasis.All Danish individuals aged ≥ 18 years between 1 January 1997 and 31 December 2012 were linked in nationwide registers. Psoriasis severity was defined in two models: hospital visits and medication. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios (IRRs) were estimated by Poisson regression.In the total cohort (n = 5 554 100) there were 75 209 incident cases of psoriasis, 11 309 incident cases of CD and 30 310 incident cases of UC, during follow-up. The adjusted IRRs (95% confidence intervals) of CD were 1·28 (1·03-1·59), 2·56 (1·87-3·50), 2·85 (1·72-4·73) and 3·42 (2·36-4·95) in patients with mild psoriasis, severe psoriasis (hospital), severe psoriasis (medication) and psoriatic arthritis, respectively. Similarly, the adjusted IRRs of UC were 1·49 (1·32-1·68), 1·56 (1·22-2·00), 1·96 (1·36-2·83) and 2·43 (1·86-3·17), respectively. The 10-year incidence of CD was 2-5 per 1000 patients and of UC 7-11 per 1000 patients, depending on psoriasis severity and the presence of psoriatic arthritis. Additionally, an increased risk of incident psoriasis was found following CD or UC.We observed a psoriasis-associated increased risk of CD and UC, which was higher in severe psoriasis, and an increased risk of psoriasis in patients with inflammatory bowel disease. Increased focus on gastrointestinal symptoms in patients with psoriasis may be warranted.
“Real-life” Frontline Dasatinib Treatment in Unselected Elderly Patients with Chronic Myeloid Leukemia
Authors: Roberto Latagliata, Fabio Stagno, Mario Annunziata, Elisabetta Abruzzese, Alessandra Iurlo, Nicola Sgherza, Carmen Fava, Antonella Gozzini, Gianfranco Giglio, Federica Sorà, Sabrina Leonetti Crescenzi, Monica Bocchia, Monica Crugnola, Gabriele Gugliotta, Isabella Capodanno, Sara Galimberti, Costanzo Feo, Raffaele Porrini, Patrizia Pregno, Massimo Breccia, Paolo G Vigneri, Malgorzata Monika Trawinska, Attilio Guarini, Giuliana Alimena
Journal: Blood (2014)
Self-control, cultural animals, and Big Gods
Authors: Tania Reynolds, Roy F. Baumeister
Journal: Behavioral and Brain Sciences (2016)

Abstract As Norenzayan et al. cogently argue, religions that proliferated most successfully did so because they facilitated prosociality and cooperation in large-scale, anonymous groups. One important way that religion promotes cooperation may be through improving self-control. In this comment, we cover some potential obstacles to implementing self-control and how religion can overcome them.
Performance of cognitively impaired oncology patients and normal controls on functional MRI tasks
Authors: L. I. Wagner, J. J. Sweet, D. Cella, K. A. Havlin, S. Forrestal, T. Parrish, D. R. Gitelman
Journal: Journal of Clinical Oncology (2004)

8023 Background: Cancer patients undergoing chemotherapy have demonstrated cognitive deficits on neuropsychological evaluation and patient-reported measures. Preliminary functional neuroimaging studies have begun to identify correlates of this cognitive decline. Methods: To further examine these neurocognitive changes, 8 right-handed oncology patients (mean 54.6 years, 7/8 female) with cognitive deficits (≥1 SD below age-adjusted mean ≥3 domains on a neuropsychological battery) completed a functional MRI (fMRI). Impaired domains included cognitive efficiency (8/8), working memory (6/8), visuospatial skills (6/8), and delayed memory (5/8). Twelve right-handed cognitively normal age- and gender-matched healthy controls (mean 53.1 years, 11/12 female) completed the same fMRI procedures. The task was a non-verbal, visual n-back task, consisting of fractal stimuli with presentations organized in block design (Ragland et al., 2002). Subjects were cued to the specific task (0, 1, or 2-back) before each block. fMRI was performed on a 3 Tesla scanner and both anatomic (MPRAGE) and functional (echo planar images sensitive to BOLD contrast) images were acquired. Data were analyzed using SPM2. Images underwent standard preprocessing steps and a random effects analysis. Results: Both patients and controls were able to perform all conditions with a high degree of accuracy. A conjunction analysis for the 2-back versus 0-back conditions showed significant common areas of activation for the oncology and control groups in right frontal regions (insula, inferior and middle frontal gyri, frontal eye field, dorsolateral prefrontal cortex, and orbitofrontal cortex), midline supplementary motor cortex, and bilateral parietal cortex. Conclusions: Established patterns of brain activation associated with fMRI tasks (Ragland et al., 2002) were replicated among patients and controls. Oncology patients completed the difficult working memory task and showed apparently normal brain activations, despite cognitive impairments. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Ortho Biotech
Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer.
Authors: S M Swain, M E Lippman, E F Egan, J C Drake, S M Steinberg, C J Allegra
Journal: Journal of Clinical Oncology (1989)

The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment.