tbuckley/cabot-search huggingface dataset:
Factors predicting the development of and survival from brain metastasis in transitional cell carcinoma of the bladder
Authors: C. T. Tran, J. George, G. Miranda, O. Hamid, J. P. Stein, D. I. Quinn
Journal: Journal of Clinical Oncology (2007)

15541 Background: To date there are no substantial series reported evaluating brain mets in TCC of the bladder. This makes therapeutic evidence-based decision making in this setting extremely difficult. Methods: We followed 1898 pts with TCC of the bladder treated with cystectomy from 1972–2004. Cohort analysis was undertaken for factors predisposing to and of factors that predict survival after brain mets. Results: With median follow-up of 3.6 yrs for this cohort, 545/1898 (28.7%) recurred, 30 (1.6%) with brain mets. Median time to brain mets development was 1.14 yrs, range 0.0710.92 yrs. Median time to first TCC recurrence in brain met pts was 0.86 yrs vs. 1.03 yrs for whole cohort (p=0.25). Median OS from cystectomy 1.36 yrs vs. 3.49 yrs for whole cohort (p&lt;0.0001). Median time from brain mets to death, 3.3 mths range 0–143 mths, skewed by 2 outliers surviving 18 and 143 mths. The following factors were associated with risk of brain mets: younger age (60.2 vs. 66.3 yrs, p=0.01) and LN status at cystectomy (p=0.02) while gender, smoking status, T stage, margin status were not; tumor grade showed a nonsignificant trend to association with brain mets (p=0.14). Pathological parameters did not correlate with duration to development of brain mets. In predicting OS after brain mets, diagnosis age, duration to first recurrence, duration to brain met, original T and N stage and development of multiple vs. brain alone recurrence did not impact overall survival. Patients having any therapy (19/30): surgery (6), radiation (11) or chemotherapy (10) or combination had a better survival that those not treated (p=0.0002). Each modality was associated with at least a trend to better OS: surgery (p=0.03), RT (p=0.09), CT (p=0.08). Conclusions: These results need to be interpreted in the context of selection bias for active treatment, however, selected patients with brain mets from TCC bladder do appear to benefit from active therapy. More work in this area will hopefully lead to more rational therapy and better outcomes. No significant financial relationships to disclose.
Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial
Authors: Dinesh Khanna, Christopher P Denton, Angelika Jahreis, Jacob M van Laar, Tracy M Frech, Marina E Anderson, Murray Baron, Lorinda Chung, Gerhard Fierlbeck, Santhanam Lakshminarayanan, Yannick Allanore, Janet E Pope, Gabriela Riemekasten, Virginia Steen, Ulf Müller-Ladner, Robert Lafyatis, Giuseppina Stifano, Helen Spotswood, Haiyin Chen-Harris, Sebastian Dziadek, Alyssa Morimoto, Thierry Sornasse, Jeffrey Siegel, Daniel E Furst
Journal: The Lancet (2016)
Financing U.S. Graduate Medical Education: A Policy Position Paper of the Alliance for Academic Internal Medicine and the American College of Physicians
Authors: Renee Butkus, Susan Lane, Alwin F. Steinmann, Kelly J. Caverzagie, Thomas G. Tape, Susan T. Hingle, Darilyn V. Moyer
Journal: Annals of Internal Medicine (2016)

In this position paper, the Alliance for Academic Internal Medicine and the American College of Physicians examine the state of graduate medical education (GME) financing in the United States and recent proposals to reform GME funding. They make a series of recommendations to reform the current funding system to better align GME with the needs of the nation's health care workforce. These recommendations include using Medicare GME funds to meet policy goals and to ensure an adequate supply of physicians, a proper specialty mix, and appropriate training sites; spreading the costs of financing GME across the health care system; evaluating the true cost of training a resident and establishing a single per-resident amount; increasing transparency and innovation; and ensuring that primary care residents receive training in well-functioning ambulatory settings that are financially supported for their training roles.
Initial results from ARIES, a multi-indication bevacizumab (BV) observational cohort study (OCS): Characteristics of metastatic colorectal cancer (mCRC) patients (pts) receiving BV and chemotherapy (CT) in 2<sup>nd</sup> line
Authors: T. S. Bekaii-Saab, J. C. Bendell, A. L. Cohn, M. F. Kozloff, N. Roach, D. J. Sargent, H. Tezcan, A. Grothey, D. M. Purdie, M. M. Sugrue
Journal: Journal of Clinical Oncology (2008)

15002 Background: Bevacizumab (BV) prolongs survival when added to CT in treating 1st or 2nd line mCRC and 1st line non-small cell lung cancer (NSCLC). ARIES, a multi-indication BV OCS, aims to further delineate the clinical effectiveness of BV in a general population of pts with 1st and 2nd line mCRC and 1st line NSCLC receiving BV-containing treatment (tx). This report focuses on 2nd line mCRC pts in ARIES, which includes both BV-naive and BV- exposed pts. Methods: Pts receiving BV as part of 1st or 2nd line tx for locally advanced and unresectable or mCRC participated with a target accrual of 2000. Investigators made all tx and assessment decisions. Data were collected prospectively via an EDC system at baseline (BL) and quarterly until death, consent withdrawal, loss to follow-up, or study closure. Results: As of Sept 5, 2007, 973 1st line and 241 2nd line pts from 248 US sites have enrolled with median follow up 4.9 mo. Most (73%) pts had BL data and ≥1 quarterly update. Select BL characteristics and BV-associated safety events for 1st line and 2nd line mCRC pts are shown (Table). Of 241 2nd line pts, 66% had not received 1st line BV (BV-naïve 2nd line). More BV-naïve pts were ≥75 yrs, black, female, and had history of VTE or GI bleeding than BV-exposed pts. Conclusions: Preliminary data from ARIES suggest there is no increase in the relative number of serious BV-associated safety events in 2nd line mCRC pts who were exposed to BV in 1st line compared to BV-naïve 2nd line pts or 1st line pts. Complete BL data and updated safety for the fully enrolled mCRC cohort will be presented. 1st line mCRC (n=973) 2nd-line mCRC, BV-naïve (n=159) 2nd line mCRC, BV- exposed in 1st line (n= 82) Median age (range) 62 (18–92) 64 (27–86) 64 (25–84) >75 y (%) 15 21 15 ECOG PS, 0/1/≥2 (%) 48/39/7 42/47/6 45/40/11 M/F (%) 57/43 48/52 57/43 White/Black/Other (%) 81/14/5 84/11/5 90/6/4 History of VTE/DVT (%) 6.5 13.4 8.7 History of GI bleeding (%) 12.7 11.3 6.1 Safety (# events) GIP SAE 3 0 1 ATE SAE 8 0 0 Gr 3–4 Bleeding SAE 3 0 0 Other BV-related SAE 3 1 0 New or increased HTN requiring medication 40 1 3 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration C3: Colorectal Cancer Coalition, Genentech, Inc. Amgen, Genentech, Inc., Pfizer, Roche, sanofi-aventis Genentech, Inc. Amgen, Bristol-Myers Squibb, Bristol-Myers Squibb, Genentech, Inc., ImClone Systems Incorporated, Pfizer, Roche, sanofi-aventis Bristol-Myers Squibb, Genentech, Inc., ImClone Systems Incorporated, Pfizer, Roche, sanofi-aventis
An evaluation of methods correcting for cell-type heterogeneity in DNA methylation studies
Authors: Kevin McGregor, Sasha Bernatsky, Ines Colmegna, Marie Hudson, Tomi Pastinen, Aurélie Labbe, Celia M.T. Greenwood
Journal: Genome biology (2016)

Many different methods exist to adjust for variability in cell-type mixture proportions when analyzing DNA methylation studies. Here we present the result of an extensive simulation study, built on cell-separated DNA methylation profiles from Illumina Infinium 450K methylation data, to compare the performance of eight methods including the most commonly used approaches.
Proinflammatory cytokine response toward fungi but not bacteria in chronic granulomatous disease
Authors: Roel P. Gazendam, Annemarie van de Geer, John L. van Hamme, Leanne Helgers, Jan Rohr, Maya Chrabieh, Capucine Picard, Dirk Roos, J. Merlijn van den Berg, T.K. van den Berg, Taco W. Kuijpers
Journal: Journal of Allergy and Clinical Immunology (2016)
Use of Dieselized Farm Equipment and Incident Lung Cancer: Findings from the Agricultural Health Study Cohort
Authors: Séverine Tual, Debra T. Silverman, Stella Koutros, Aaron Blair, Dale P. Sandler, Pierre Lebailly, Gabriella Andreotti, Jane A. Hoppin, Laura E. Beane Freeman
Journal: Environmental Health Perspectives (2015)

Background:Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer.Objectives:We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993–1997) to 2010–2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA.Methods:Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure.Results:Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05).Conclusions:This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted.Citation:Tual S, Silverman DT, Koutros S, Blair A, Sandler DP, Lebailly P, Andreotti G, Hoppin JA, Beane Freeman LE. 2016. Use of dieselized farm equipment and incident lung cancer: findings from the Agricultural Health Study Cohort. Environ Health Perspect 124:611–618; http://dx.doi.org/10.1289/ehp.1409238
PDT: What's Past Is Prologue
Authors: Keith A. Cengel, Charles B. Simone, Eli Glatstein
Journal: Cancer Research (2016)

Abstract Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497–9. ©2016 AACR. See related article by Dougherty et al., Cancer Res 1978;38:2628–35. Visit the Cancer Research 75th Anniversary timeline.
SP0117 Doing it Differently? New Approaches to Student Education and Improving Health Outcomes
Authors: M.D. Iversen
Journal: Annals of the Rheumatic Diseases (2015)

Educators aim to transform students9 knowledge, behaviors, and skills learned in the classroom to relevant situations in the real world. The rapid increasing of technology in healthcare provides a fertile ground for the implementation and evaluation of technology-based and competency driven curricula in the health professions. The technologies available to faculty are vast. These technologies include: web-based learning platforms, student response technologies, learning object creation tools, lecture capture software, e-portfolios, google glasses and computer-based simulation. This presentation will review the latest in technology-based education, provide practical guidance on the use of these technologies in learning and highlight key research in the field of simulated learning and competency assessment. <h3>Disclosure of Interest</h3> None declared
A comprehensive survey of the mutagenic impact of common cancer cytotoxics
Authors: Bernadett Szikriszt, Ádám Póti, Orsolya Pipek, Marcin Krzystanek, Nnennaya Kanu, János Molnár, Dezső Ribli, Zoltán Szeltner, Gábor E. Tusnády, István Csabai, Zoltan Szallasi, Charles Swanton, Dávid Szüts
Journal: Genome biology (2016)

Genomic mutations caused by cytotoxic agents used in cancer chemotherapy may cause secondary malignancies as well as contribute to the evolution of treatment-resistant tumour cells. The stable diploid genome of the chicken DT40 lymphoblast cell line, an established DNA repair model system, is well suited to accurately assay genomic mutations.
Phase II study of induction chemotherapy and concomitant chemoradiotherapy with cisplatin and continuous infusion 5-fluorouracil (PF) for anal carcinoma
Authors: J. G. Freire, M. C. Trindade, A. M. Barata, J. Venâncio, I. Claro, A. H. Fernandes
Journal: Journal of Clinical Oncology (2007)

15148 Background: Chemoradiotherapy is the primary treatment for anal squamous cell carcinoma (ASCC). The aim of this trial was to assess activity and toxicity of induction chemotherapy and concomitant chemoradiotherapy with cisplatin (CDDP) and 5-fluorouracil (5- FU). Methods: Inclusion criteria: invasive, non-metastatic ASCC, age &lt; 70 years, WHO performance status 0 - 2, adequate bone marrow and renal function and written informed consent. Treatment: Five courses of chemotherapy with PF: two induction courses (CDDP 100mg/m2 D1, 5-FU 1000mg/m2 D1–5 Q 21d); two concomitant (CDDP 20mg/m2 D1–4 and D28–31, 5-FU 225mg/m2 continuous infusion D1–31) with the first sequence of radiotherapy (45Gy in 25 fractions of 1.8Gy) and, after a five week gap, one concomitant (CDDP 20mg/m2 D1–4, 5-FU 800mg/m2 D1–4) with the radiation boost (15Gy in 6 fractions of 2.5Gy). The primary endpoints were response rate and toxicity. Results: 26 patients (pts) were included from March 2002 to August 2006 [21 women, 5 men; median age 53 years (29–69)]. Tumor location: anal canal 24 pts, anal margin 2 pts. Histology: squamous cell carcinoma 24 pts, basaloid carcinoma 2 pts. Stage: 35% tumors were T3–4 and 58% were N1–3. Nineteen pts (73%) completed the treatment. Failure to complete treatment were disease progression (1 pt), catheter related complications (2 pts), hematological toxicity (1pt), traumatic bone fracture (1pt); two pts died (one metastatic disease; one pulmonary thromboembolism). Twenty three pts were evaluable for response (1 pt too early). Nineteen pts (76%) had a complete remission (CR); four pts (16%) had local disease persistence. Grade 3 toxicities of 30, 22, 19, 16 and 5% were observed for stomatitis, radiation dermatitis, emesis, hematological toxicity and diarrhea. Grade 4 toxicity was 8% (3 pts: hematological, diarrhea, infection). Sixteen pts (62%) had a treatment delay or dose reduction. At a median follow up of 28 months, the overall survival was 73%. Six pts died, 5 of disease progression. Four pts required a colostomy. Conclusions: The results of this small single institution phase II trial, in line with those of RTOG 98–11, suggest that there is no role for CDDP/5-FU chemoradiotherapy for ASCC. No significant financial relationships to disclose.
The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis
Authors: Björn Löppenberg, Deepansh Dalela, Patrick Karabon, Akshay Sood, Jesse D. Sammon, Christian P. Meyer, Maxine Sun, Joachim Noldus, James O. Peabody, Quoc-Dien Trinh, Mani Menon, Firas Abdollah
Journal: European Urology (2016)
Integrin Ligands with α/β‐Hybrid Peptide Structure: Design, Bioactivity, and Conformational Aspects
Authors: Rossella De Marco, Alessandra Tolomelli, Eusebio Juaristi, Luca Gentilucci
Journal: Medicinal Research Reviews (2016)

Abstract Integrins are cell surface receptors for proteins of the extracellular matrix and plasma‐borne adhesive proteins. Their involvement in diverse pathologies prompted medicinal chemists to develop small‐molecule antagonists, and very often such molecules are peptidomimetics designed on the basis of the short native ligand‐integrin recognition motifs. This review deals with peptidomimetic integrin ligands composed of α‐ and β‐amino acids. The roles exerted by the β‐amino acid components are discussed in terms of biological activity, bioavailability, and selectivity. Special attention is paid to the synthetic accessibility and efficiency of conformationally constrained heterocyclic scaffolds incorporating α/β‐amino acid span.
A Monoclonal IgM Antibody With Specificity To Heat Shock Protein GRP78/BIP Shows Anti- Myeloma Activity In Vitro and In Vivo, Synergy In Combination With Lenalidomide and Safety In a Pilot Phase I Study
Authors: Leo Rasche, Stephanie Braendlein, Johannes Duell, Stefan Knop, Valentina Dubljevic, Andreas Rosenwald, Hermann Einsele, Max S. Topp
Journal: Blood (2013)
Precision medicine to improve survival without increasing costs in advanced cancer patients.
Authors: Lincoln Nadauld, S. Burke Van Norman, Gail Fulde, Justin G. McDermott, David Newman, Allison M. Butler, Brian P. Tudor, Heather Gilbert, Karen Yin Lin, Gary Stone, James M. Ford, Derrick S. Haslem
Journal: Journal of Clinical Oncology (2015)

e17641 Background: The advent of Next-Generation Sequencing (NGS), and other diagnostic technologies, has enabled the use of genomic information to guide targeted treatment in cancer patients. The outcomes and costs associated with the implementation of precision cancer medicine have been difficult to generate. Leveraging the advantages of an integrated healthcare system, we have implemented a clinical cancer genomics program to personalize targeted treatment for advanced cancer patients in a community setting. We report a retrospective analysis of the clinical outcomes associated with precision cancer medicine. Methods: We conducted a matched cohort study of 72 patients from July 2013 to December 2014, with metastatic cancer of diverse subtypes. The outcomes of 36 patients treated with precision cancer medicine were compared to 36 historical control patients who received standard chemotherapy. Study and control patients were matched according to age, gender, histological diagnosis, and number of previous treatment lines. PFS was compared between the two groups using a Cox Proportional Hazard model for survival and accounting for potential confounders. Costs includes ED visits, hospitalizations, NGS costs and costs for targeted or standard therapy. Results: Progression free survival was 22.9 weeks for the treatment group and 12.0 weeks for the historical control group (p = 0.002). Patients receiving precision cancer medicine compared to conventional treatment patients had a hazard ratio of 0.47 (95% confidence interval of 0.29-0.75) when adjusting for age, gender, histological diagnosis and previous treatment lines. Costs per week were $3204 in the targeted group and $3501 in the control cohort (p = 0.385). Conclusions: Precision cancer medicine appears to significantly improve survival for patients with advanced cancer when compared to control patients who received conventional chemotherapy. The additional survival is not associated with increased costs. While the results of this study warrant further investigation in the setting of a prospective randomized control trial, this genomics-based approach appears to be a viable, and perhaps superior, option for patients with advanced or metastatic cancer.
Abstract 290: Proliferation of Cardiac Fibroblasts Defines Early Stages of Genetic Dilated Cardiomyopathy and Precedes Myocardial Metabolic Derangement
Authors: Michael A Burke, Stephen Chang, Danos C Christodoulou, Joshua M Gorham, Hiroko Wakimoto, Christine E Seidman, Jonathan G Seidman
Journal: Circulation Research (2014)

The complex molecular networks underpinning DCM remain poorly understood. To study distinct pathways and networks in the longitudinal development of DCM we performed RNAseq on LV tissue from mice carrying a human DCM mutation in phospholamban (PLN R9C/+ ) before phenotype onset (pre-DCM), with DCM, and during overt heart failure (HF), and also on isolated myocytes and non-myocytes from DCM hearts. PLN R9C/+ mice show progressive fibrosis (20% vs. 1% control, p=6x10 −33 ; n=3) associated with proliferation of cardiac non-myocytes (33% increase over control, p=6x10 −4 ; n=3). Consistent with this, cardiac non-myocytes have upregulated gene expression and pathways, while these are generally downregulated in myocytes. Non-myocytes were enriched in fibrosis, inflammation, and cell remodeling pathways, from pre-DCM to HF. In contrast, myocytes were enriched for metabolic pathways only with overt DCM and HF. Myocytes showed profound derangement of oxidative phosphorylation with DCM (p=2.5x10 −41 ; 44% (53/120) of pathway genes downregulated), suggesting mitochondrial dysfunction. Additionally, we detected probable inhibition of peroxisome proliferator-activated receptor (PPAR) signaling by diminished expression of pathway genes (Figure). DCM and hypertrophic remodeling was compared using RNAseq of a mouse model of HCM; similar patterns of fibrosis with myocyte metabolic dysregulation were evident despite unique differential gene expression patterns between models. DCM caused by PLN R9C/+ is associated with early non-myocyte proliferation and later myocyte metabolic derangement possibly governed by altered PPAR signaling, and is common to DCM and HCM.