tbuckley/cabot-search huggingface dataset:
The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy.
Authors: K L Griem, I C Henderson, R Gelman, D Ascoli, B Silver, A Recht, R L Goodman, S Hellman, J R Harris
Journal: Journal of Clinical Oncology (1987)

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
5-Fluorouracil + folinic acid with cisplatinum and bleomyein in the treatment of advanced head and neck squamous cell carcinoma
Authors: M. Guaraldi, A. Martoni, A. Tononi, L. Occhiuzzi, U. Caliceti, D. Dall’Olio, P. Laudadio, F. Pannuti
Journal: Annals of Oncology (1991)
Physical activity and exercise lower blood pressure in individuals with hypertension: narrative review of 27 RCTs
Authors: Mats Börjesson, Aron Onerup, Stefan Lundqvist, Björn Dahlöf
Journal: British Journal of Sports Medicine (2016)

Regular physical activity (PA) reduces the blood pressure (BP) of individuals with hypertension. The present review analysed the scientific evidence for the BP lowering effect of aerobic PA in 27 randomised controlled studies on individuals with hypertension, and shows that regular medium-to-high-intensity aerobic activity reduces the BP by a mean of 11/5 mm Hg (level of evidence, 3+). In addition, three randomised controlled trials (RCTs) on isometric (static) activity showed a BP reduction of similar magnitude in hypertensives; dynamic resistance training may show less effect, as shown in five available RCTs (level of evidence 2+). As both the prevalence of hypertension and physical inactivity are high and increasing in today's society, PA has a great role to play as a single (when indicated) or additive treatment for hypertension. Furthermore, as competitive athletes are getting older, it can be expected that more athletes at different competitive levels will have hypertension. Certain considerations must be applied regarding evaluation and treatment of hypertension in athletes. Eligibility for competitive sports may be affected if target organ damage (TOD) is present; however, an athlete with well-controlled BP, having no additional risk factors or TOD, is eligible for all sports.
Predictors of Mortality Poorly Predict Common Measures of Disease Progression in Idiopathic Pulmonary Fibrosis
Authors: Brett Ley, Williamson Z. Bradford, Eric Vittinghoff, Derek Weycker, Roland M. du Bois, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Mortality prediction is well studied in idiopathic pulmonary fibrosis (IPF), but little is known about predictors of premortality disease progression. Identification of patients at risk for disease progression would be useful for clinical decision-making and designing clinical trials.Objectives: To develop prediction models for disease progression in IPF.Methods: In a large clinical trial cohort of patients with IPF (n = 1,113), we comprehensively screened multivariate models of candidate baseline and past-change predictors for disease progression defined by 48-week worsening of FVC, dyspnea (University of California, San Diego Shortness of Breath Questionnaire [UCSD SOBQ]), 6-minute-walk distance (6MWD), and occurrence of respiratory hospitalization, or death. Progression outcomes were modeled as appropriate, by slope change using linear regression models and time to binary outcomes using Cox proportional hazards models.Measurements and Main Results: The overall cohort experienced considerable disease progression. Top-performing prediction models did not meaningfully predict most measures of disease progression. For example, prediction modeling explained less than or equal to 1% of the observed variation in 48-week slope change in FVC, UCSD SOBQ, and 6MWD. Models performed better for binary measures of time to disease progression but were still largely inaccurate (cross-validated C statistic ≤0.63 for ≥10% decline in FVC or death, ≤0.68 for ≥20-U increase in UCSD SOBQ or death, ≤0.70 for ≥100 m decline in 6MWD or death). Models for time to respiratory hospitalization or death (C statistic ≤0.77) or death alone (C statistic ≤0.81) demonstrated acceptable discriminative performance.Conclusions: Clinical prediction models poorly predicted physiologic and functional disease progression in IPF. This is in contrast to respiratory hospitalization and mortality prediction.
Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic <i>RAG</i> defects
Authors: Rosita Rigoni, Elena Fontana, Simone Guglielmetti, Bruno Fosso, Anna Maria D’Erchia, Virginia Maina, Valentina Taverniti, Maria Carmina Castiello, Stefano Mantero, Giovanni Pacchiana, Silvia Musio, Rosetta Pedotti, Carlo Selmi, J. Rodrigo Mora, Graziano Pesole, Paolo Vezzoni, Pietro Luigi Poliani, Fabio Grassi, Anna Villa, Barbara Cassani
Journal: The Journal of Experimental Medicine (2016)

Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated. Here, we show that Rag2R229Q knock-in mice developed an inflammatory bowel disease affecting both the small bowel and colon. Lymphocytes were sufficient for disease induction, as intestinal CD4 T cells with a Th1/Th17 phenotype reproduced the pathological picture when transplanted into immunocompromised hosts. Moreover, oral tolerance was impaired in Rag2R229Q mice, and transfer of wild-type (WT) regulatory T cells ameliorated bowel inflammation. Mucosal immunoglobulin A (IgA) deficiency in the gut resulted in enhanced absorption of microbial products and altered composition of commensal communities. The Rag2R229Q microbiota further contributed to the immunopathology because its transplant into WT recipients promoted Th1/Th17 immune response. Consistently, long-term dosing of broad-spectrum antibiotics (ABXs) in Rag2R229Q mice ameliorated intestinal and systemic autoimmunity by diminishing the frequency of mucosal and circulating gut-tropic CCR9+ Th1 and Th17 T cells. Remarkably, serum hyper-IgE, a hallmark of the disease, was also normalized by ABX treatment. These results indicate that intestinal microbes may play a critical role in the distinctive immune dysregulation of OS.
PET as a biomarker of the antitumor effects of the CDK2 inhibitor BMS-387032
Authors: A. Fischman, S. Letrent, A. Bonab, E. Livni, E. Carter, R. Rubin, D. Mauro, C. Tarby, S. Galbraith, T. Griffin
Journal: Journal of Clinical Oncology (2004)

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Virus-Specific Markers and Virus-Like Particles in Cell Lines of Tumors Produced by CELO Virus in Syrian Golden Hamsters2
Authors: Bonnie B. Asch, Kenneth J. McCormick, Wayne A. Stenback, John J. Trentin
Journal: JNCI Journal of the National Cancer Institute (1978)

Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma tine (RCT) until they had undergone more than 34 passages in vitro. Although 5–10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines.
Elastofibroma: An Electron Microscopic Study
Authors: William G. Banfield, Carolyn K. Lee
Journal: JNCI Journal of the National Cancer Institute (1968)

An electron microscopic study was made of a benign connective tissue tumor, elastofibroma, characterized in light microscopy by “fibers, globes, and irregular masses” which take the elastic tissue stains. These masses were found by electron microscopy to consist of degenerating fibrils, often surrounding an elastic fiber core which was removed by elastase digestion. A matrix material surrounding the degenerating fibrils was also removed by elastase digestion. This material may have represented an elastic staining component of the fibrillar masses and could account for the disappearance of elastic staining from elastase-digested paraffin sections in light microscopy.
Abstract 11155: Impact of Serum Calcium Levels on Mortality of Patients With Heart Failure and Chronic Kidney Disease
Authors: Shunsuke Miura, Akiomi Yoshihisa, Minoru Nodera, Akihiko Sato, Mai Takiguchi, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Takashi Owada, Satoshi Abe, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2014)

Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with vascular calcification and abnormal electrolyte that lead to cardiovascular disease and mortality. CKD-MBD are identified by imbalances in serum calcium (Ca), phosphate, and parathyroid hormone (PTH). Although, the relation of phosphate and PTH to prognosis of HF patients has been reported, prognostic impact of Ca on patients with heart failure (HF) and CKD remains unclear. Methods and Results: Consecutive 191 patients admitted for HF and CKD (estimated GFR &lt; 60 ml/min/1.73 m 2 ) were divided into 3 groups based on levels of corrected Ca: low Ca (Ca &lt; 8.4 mg/dl, n = 32), normal Ca (8.4 ≤ Ca &lt;10.0, n = 149), and high Ca (10.0 ≤ Ca, n = 10) groups. We compared echocardiographic findings and levels of hemoglobin, BNP, troponin T, CRP, estimated GFR, intact PTH, phosphate, zinc (Zn), and magnesium (Mg) among the three groups. Furthermore, we prospectively followed cardiac, non-cardiac, and all-cause mortality. The low Ca group, as compared to normal and high Ca groups, had lower levels of hemoglobin and Zn (hemoglobin: 11.2 vs. 12.4, 13.0 g/dl, P &lt; 0.001; Zn: 58.1 vs. 70.1, 71.0 mg/dl, P = 0.003). Age, body mass index, BNP, troponin T, CRP, estimated GFR, intact PTH, phosphate, Mg, and left ventricular ejection fraction were similar among the three groups. Importantly, cardiac mortality (log-rank P = 0.003) and all-cause mortality (P &lt; 0.001), but not non-cardiac mortality, were higher in low Ca group than in normal and high Ca groups in HF and CKD patients. In the multivariate Cox proportional hazard analyses, hypocalcemia was an independent predictor of cardiac (HR 2.34, P = 0.007) and all-cause mortality (HR 1.89, P = 0.027) in HF and CKD patients. Conclusions: Hypocalcemia was an independent predictor of cardiac and all-cause mortality in HF and CKD patients. Thus, taking appropriate management to control CKD-MBD balance may improve the prognosis of patients with HF and CKD.
Reasons for Patients (Pts) Discontinuing Study Treatment (Tx) in the Phase 3 Alsympca Trial of Radium-223 Dichloride (Ra-223) in Castration-Resistant Prostate Cancer (Crpc) with Bone Metastases (Mets)
Authors: J. Logue, S. Wedel, A. Chodacki, O. Sartor, S. Nilsson, R.E. Coleman, N. James, A. Aksnes, M. Wahba, C. Parker
Journal: Annals of Oncology (2014)
Pilot study of veliparib (ABT-888) with temozolomide (TMZ) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Maha Hussain, Michael Anthony Carducci, Susan F. Slovin, Jeremy Paul Cetnar, Jiang Qian, Evelyn Mary McKeegan, Elizabeth Litvinovich, Brenda Chyla, Robert Hetman, Bhardwaj Desai, Vincent L. Giranda, Joshi J. Alumkal
Journal: Journal of Clinical Oncology (2012)

224 Background: Castration-resistant PC tumors exhibit increased PARP activity (critical enzymes for DNA damage repair). Veliparib is a novel, oral, potent inhibitor of PARP-1 and PARP-2. Preclinically, resistance to oral TMZ treatment in the PC3-Luc prostate cancer mouse model was reversed when mice were treated with veliparib. Based on the synergistic interaction, we evaluated the efficacy and safety of veliparib + TMZ in mCRPC pts. Methods: Eligible pts had mCRPC, PSA&gt;2 ng/mL, progressed on at least one docetaxel based therapy and adequate organ function. Pts received veliparib 40 mg BID Days (D) 1-7 and TMZ D1-5 in 28D cycle (C) until disease progression (PD) or unacceptable toxicities. Tumor response was assessed every 8 weeks. Primary objective: Efficacy based on rate of PSA decline of 30% or greater. Secondary objectives: safety, RECIST objective response rate, progression-free survival (PFS), overall survival (OS) and biomarker analyses. A sample size of 25 pts provided 76% power to differentiate between PSA response rates of 5 and 20% at 1-sided type I error rate of 0.1. Results: 26 pts were enrolled; median age 67 years [55, 81]; median baseline PSA 107 ng/ml (6.9, 4584.4); 7/26 (27%) had 2 prior therapies. Median Cs of veliparib + TMZ received were 2 (range 1–9). Most frequent treatment related adverse events (AE) were fatigue (50%), nausea (38%) and constipation (23%). Grade 3/4 AEs in &gt;10% of pts was thrombocytopenia (15%). All pts are off therapy. 25 pts were PSA response evaluable; 2 pts had a confirmed PSA response; 1 pt had a 37% decrease in PSA while the other pt had a 96% decrease in PSA and a 40% reduction in tumor size. 4/25 pts had stable disease for a minimum of 4 months (m). Median PFS was 2.1 m [95% CI: 1.8, 3.9]; 11/26 pts have died with median OS of 9.1 m [95% CI: 5.5, 11.7]. There was a negative correlation between change from baseline in circulating tumor cells and PFS. Conclusions: Veliparib + TMZ were well tolerated with evidence of some activity. Due to lack of activity of TMZ in CRPC,veliparib-induced potentiation of TMZ may not be clinically significant. Other combinations will be explored with higher doses of veliparib. Biomarker data will be presented.
Complex lifestyle differences make study on potato consumption and risk of gestational diabetes difficult to interpret
Authors: Christopher J Weatherburn
Journal: BMJ (2016)

Bao and colleagues’ interesting study uses data from a questionnaire that was sent every two years to nurses in the US and had a completion rate of over 90%.1 Because the 1991 questionnaire was the first to have dietary questions, effectively the minimum age for inclusion was 26 years or more, which reduces its generalisability to all women of child bearing age. The article details a policy for handling incomplete questionnaires and unrealistic responses, although it did not quantify how many women were excluded for these reasons. It also seems sensible to exclude women who have had previous gestational diabetes mellitus (GDM), not only because they may have changed their lifestyle but because they are more susceptible than the general population to developing GDM in future pregnancies.

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Zika Virus Associated with Microcephaly
Authors: Jernej Mlakar, Misa Korva, Nataša Tul, Mara Popović, Mateja Poljšak-Prijatelj, Jerica Mraz, Marko Kolenc, Katarina Resman Rus, Tina Vesnaver Vipotnik, Vesna Fabjan Vodušek, Alenka Vizjak, Jože Pižem, Miroslav Petrovec, Tatjana Avšič Županc
Journal: New England Journal of Medicine (2016)

A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
Abstract 195: RhoA Controls Myofibroblast Characteristics
Authors: Aline Jatho, Naim Kittana, Kerstin Schenk, Beate Ramba, Wolfram-Hubertus Zimmermann, Susanne Lutz
Journal: Circulation Research (2014)

Purpose: RhoA has been shown to be beneficial in cardiac disease models when overexpressed in cardiomyocytes whereas its role in cardiac fibroblasts (CF) is still poorly understood. During cardiac remodeling CF undergo a transition towards a myofibroblastic phenotype showing an increased proliferation and migration rate. Both processes involve the remodeling of the cytoskeleton, a process known to be strongly regulated by RhoA. Methods: To investigate the role of RhoA in neonatal rat cardiac fibroblasts we used a lentivirus-based knockdown (RhoA-KD-CF). In addition, wild type (wt) CF were treated with 10 μM Fasudil for ROCK inhibition or 5 μg/mL Tubastatin A (Tub A) for tubulin-specific deacetylase HDAC6 inhibition. Cytoskeletal proteins were analyzed by immunoblot and immunofluorescence. Adhesion velocity and migration was determined by microscopy and the serum-driven proliferation rate by nuclei counting. Results: Compared to control cells (shControl) RhoA-KD-CF develop an epithelial-like morphology lacking stress fibers and higher order actin structures like geodesic domes. The orientation of focal adhesions sites along the cell stress axis was also impaired. This phenotype could be mimicked by the treatment of CF with Fasudil. Furthermore, in RhoA-KD-CF cytoskeletal proteins were found to be unchanged except for a decrease in the myofibroblast marker smooth muscle actin by 43% and an increase in acetylated tubulin by 57% without a change in the expression of HDAC6. In order to analyze the impact of both changes we investigated the migration and proliferation rate of CF. First, the reduction of RhoA accelerated the adhesion but decelerated migration (shControl 4043±316 nm/h versus shRhoA 3021±153 nm/h) and second, the serum-driven proliferation rate of RhoA-KD-CF was reduced by 50%. Interestingly, treatment of wt-CF with Fasudil significantly decreased migration velocity by 62% but had no effect on the proliferation rate, whereas Tub A only slightly decreased migration velocity but reduced proliferation rate by 60%. Conclusion: RhoA influences the two main myofibroblast characteristics, migration and proliferation, by interfering with the actin and tubulin cytoskeleton via ROCK and HDAC6, respectively.
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial
Authors: Jonathan E Rosenberg, Jean Hoffman-Censits, Tom Powles, Michiel S van der Heijden, Arjun V Balar, Andrea Necchi, Nancy Dawson, Peter H O'Donnell, Ani Balmanoukian, Yohann Loriot, Sandy Srinivas, Margitta M Retz, Petros Grivas, Richard W Joseph, Matthew D Galsky, Mark T Fleming, Daniel P Petrylak, Jose Luis Perez-Gracia, Howard A Burris, Daniel Castellano, Christina Canil, Joaquim Bellmunt, Dean Bajorin, Dorothee Nickles, Richard Bourgon, Garrett M Frampton, Na Cui, Sanjeev Mariathasan, Oyewale Abidoye, Gregg D Fine, Robert Dreicer
Journal: The Lancet (2016)