tbuckley/cabot-search huggingface dataset:
Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery.
Authors: Javier A. Cienfuegos, Fernando Rotellar, Jorge Baixauli, Carmen Beorlegui, Iosu Sola, Leire Arbea, Carlos Pastor, Jorge Arredondo, Jose Luis Hernandez-Lizoain
Journal: Journal of Clinical Oncology (2015)

695 Background: The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. Methods: A total of 324 patients with LARC treated with CRT were operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification, and the presence of PLVI was studied histologically. Results: At a median follow-up of 79.0 months (range 3–250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2% and 74.9% respectively. The 5- and 10-year disease-free survival (DFS) was 75.1% and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p&lt;0.001). The 10-year OS and DFS was 32.7% and 31.8% for grade 1; 63.8% and 58.6% for grade 2; 75.0% and 70.4% for grade 3; 90.4% and 88.4% for grade 3+, and 96.0% and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, TRG was an independent prognostic factor for OS and DFS. Conclusions: The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.
Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells
Authors: R. Vassena, B. Heindryckx, R. Peco, G. Pennings, A. Raya, K. Sermon, A. Veiga
Journal: Human Reproduction Update (2016)

BACKGROUNDWith the recent development of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 genome editing technology, the possibility to genetically manipulate the human germline (gametes and embryos) has become a distinct technical possibility. Although many technical challenges still need to be overcome in order to achieve adequate efficiency and precision of the technology in human embryos, the path leading to genome editing has never been simpler, more affordable, and widespread.
Trends in Metastatic Breast and Prostate Cancer — Lessons in Cancer Dynamics
Authors: H. Gilbert Welch, David H. Gorski, Peter C. Albertsen
Journal: New England Journal of Medicine (2015)

Interview with Dr. H. Gilbert Welch on trends in the incidence of metastatic cancers and their implications for both screening and our understanding of cancer. (06:57)Download Discordant trends in the incidence of metastatic breast and prostate cancer since the widespread implementation of early-detection efforts may reflect distinct disease dynamics or may result from the different screening strategies used.
Neuropsychological deficits in alcoholic men in their mid thirties
Authors: M J Eckardt, R S Ryback, C P Pautler
Journal: American Journal of Psychiatry (1980)

The authors examined performances on 24 commonly used clinical neuropsychological tests for drug-free alcoholic men in their mid to late 30s either within 2--6 days of their last drink (N = 59) or between 14 and 31 days after their last drink (N = 20). Although mean scores were indicative of impairment on approximately half of the tests, no statistically significant overall difference in performance between individuals tested at these two time periods was observed. Recent and chronic alcohol consumption variables were found to interact with each other and with age and education in a nonlinear fashion in predicting neuropsychological performance. Increased consumption predicted decreased performance even on tests whose mean scores were in the normal range.
ELF3 amplification at 1q32.1 promotes SMAD4-independent tumorigenesis
Authors: Katey S.S. Enfield, Christine Anderson, Erin Marshall, Kevin W. Ng, Brenda de Carvalho Minatel, David A. Rowbotham, Raj Chari, Megan Fuller, Katy Milne, Daiana D. Becker-Santos, Calum MacAulay, Aly Karsan, Stephen Lam, Wan L. Lam
Journal: Journal of Thoracic Oncology (2016)
Correction to "Adipose tissue explants and MDCK cells reciprocally regulate their morphogenesis in coculture"
Authors: Kazuma Udo, Shigehisa Aoki, Kazuyoshi Uchihashi, Maki Kawasaki, Aki Matsunobu, Yuji Tokuda, Akifumi Ootani, Shuji Toda, Jiro Uozumi
Journal: Kidney International (2011)
THU0302 Proposed Disease Activity Category Thresholds for Behcet's Syndrome Activity Scale (BSAS) Scores for a Potential “Treat to Target” Approach to Behcet's Syndrome
Authors: Y. Yazici, H. Bernstein, C. Swearingen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Behcet9s Syndrome Activity Scale (BSAS), a patient reported outcome measure for Behcet9s syndrome, has been validated for routine clincial care and have been shown to differentiate active treatment from placebo in clinical trials. Currently, there are no identified thresholds for disease activity levels for BSAS. <h3>Objectives</h3> To determine resmission, low, moderate and high disease activity level threshold scores for BSAS. <h3>Methods</h3> Behcet9s patients seen at the NYU Behcet9s Center had their demographic, clinical features and outcomes data abstracted. Confirmed Behcet9s diagnosis was determined if ISG criteria were met at any time during the course of observation. Concordance correlation was estimated between the BSAS and the RAPID3; both outcomes were scaled to [0-100]. Proposed BSAS severity categories are as: Near-Remission = [0-10), Low = [10-30), Moderate=[30-60), and High = [60-100]. Weighted Kappa statistics were estimated between BSAS and RAPID3 severity categories. RAPID3 categories were based upon published<sup>1</sup> as well as matching the proposed BSAS severity categories. <h3>Results</h3> First observation data on 832 subjects were abstracted for this analysis. 504 (63%) met ISG criteria for Behcet9s, 616 (74%) were female with an average age of 35 years (±13.8). Concordance between BSAS and RAPID3 was moderate (CCC =0.518). BSAS severity categories classified 7% Near-Remission, 24% Low, 48% Moderate, and 21% of the study population as High disease severity (Table). Published RAPID3 categories classified 44% of subjects as High, while matching RAPID3 categories only classified 20%. Agreement between categories was moderate for both RAPID3 classifications. <h3>Conclusions</h3> BSAS, a patient reported outcome measure for Behcet9s syndrome, correlates well with other composite indices of disease activity. Proposed cut off points for near-remission, low, moderate and high activity for BSAS may be used in clinical care for a "treat-to-target" approach to Behcet9s treatment. <h3>References</h3> Pincus T, Swearingen CJ, Bergman M, Yazici Y. J Rheumatol 2008 Nov;35(11):2136-47. <h3>Disclosure of Interest</h3> Y. Yazici Grant/research support from: BMS, Celgene, Genentech, Consultant for: BMS, Celgene, H. Bernstein: None declared, C. Swearingen: None declared
Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma.
Authors: C Dittrich, E Dittrich, P Sevelda, M Hudec, H Salzer, T Grunt, J Eliason
Journal: Journal of Clinical Oncology (1991)

A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow. Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test). A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population. Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors. Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).
Experts berate government for lack of action on childhood obesity
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The government has done nothing concrete to deal with childhood obesity despite asking for advice and recommendations from health experts, MPs have been told.

Health experts severely criticised the lack of real action taken to reduce childhood obesity when they appeared before the parliamentary health select committee for an evidence session of its inquiry into a childhood obesity strategy, held on 13 October.

The Department of Health is due to publish its “plans for action” on the matter in the next few months. It has asked Public Health England to prepare evidence on cutting sugar consumption to help with the strategy.

MPs asked witnesses why they supported the idea of introducing a 20% tax on sugar sweetened drinks.

Graham MacGregor, chair of the campaign group Action on Sugar, giving evidence, said, “This is part of a package. A sugar tax itself will not prevent obesity. It will play a major role in reducing consumption of sweetened soft drinks.

“Tax for cigarettes and alcohol works. We …
Thymus Lymphocytes in Rats During Induction of Bladder Tumors and Effects of Thymosin Fraction 5 In Vitro
Authors: S Wada, Y Ozaki, S Nishio, M Maekawa, S Kimura, Y Kinoshita
Journal: JNCI Journal of the National Cancer Institute (1985)

Bladder tumors were induced in Wistar rats by oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6], after which changes in bladder mucous membranes and in the response of thymus lymphocytes to concanavalin A (Con A) were studied. The response of thymus lymphocytes to Con A began to decrease from the 8th week after BBN administration, with changes such as hypertrophy or vascular formation in the bladder membrane. The response decreased markedly from the 15th week, when the tumors became visible. At about the 20th week, approximately 95% of the rats had bladder tumors. When thymus lymphocytes were pretreated with thymosin fraction 5 extracted from calf thymus, the response to Con A improved between the 8th and 20th weeks. When the thymus small-lymphocyte population was separated into lighter, intermediate, and heavier subpopulations by discontinuous density gradient centrifugation and an adhesion column, the effect of thymosin fraction 5 was much greater in the lighter subpopulation.
Approaches To Enhance Proliferation of Human Epidermal Keratinocytes in Mass Culture
Authors: F M Price, W G Taylor, R F Camalier, K K Sanford
Journal: JNCI Journal of the National Cancer Institute (1983)

Because of interest in mechanisms of carcinogenesis in human epithelial cells, quantitative procedures were developed for the mass culture of human epidermal keratinocytes in the absence of feeder cells. Several approaches were used to enhance proliferation since target cells are considered most susceptible to transformation if they are treated with carcinogenic agents during DNA synthesis. Mass cultures of enzymatically dispersed human foreskin were initiated in collagen-coated flasks containing medium NCTC 168 with 10% Chelex 100-treated horse serum. Under these conditions, human keratinocytes required a higher calcium ion concentration ([Ca2+]) than that reported for suspensions plated at low cell density. Neither the cohesiveness of the epidermal sheet nor continued proliferation was maintained by 0.15 mM Ca2+; 0.3 mM Ca2+ maintained these properties in primary culture only. A concentration of 1.0 mM Ca2+ provided the highest cell yield for prolonged growth as determined by the enumeration of cell nuclei isolated by citric acid. Reproducibility of successful initiation was achieved by inoculation of cells into a medium designed for clonal growth followed by culture in medium NCTC 168. Thus the balance of nutrients and electrolytes must be adjusted to satisfy the requirements of a dynamically expanding keratinocyte population.
Hazel Patricia Galvin
Authors: Clifford Bailey
Journal: BMJ (2015)

<h3>Abstract</h3> The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomical evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we carried out monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of <i>ex vivo</i> electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (~ four-to eight-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.
Thalidomide in the Treatment of Plasma Cell Malignancies
Authors: S. Vincent Rajkumar, Robert A. Kyle
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.16.3593 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11504740 Thalidomide in the Treatment of Plasma Cell Malignancies S. Vincent RajkumarxS. Vincent RajkumarSearch for articles by this author , Robert A. KylexRobert A. KyleSearch for articles by this author Show More Mayo Clinic and Mayo Foundation, Rochester, MN https://doi.org/10.1200/JCO.2001.19.16.3593 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: A Phase II trial
Authors: A J Lacave, F J Barón, L M Antón, E Estrada, L M De Sande, I Palacio, E Esteban, J M Gracia, J M Buesa, O A Fernández
Journal: Annals of Oncology (1991)
Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two‐Year Followup in the Treatment of Early Aggressive Rheumatoid Arthritis Trial
Authors: Christina Charles‐Schoeman, Xiaoyan Wang, Yuen Yin Lee, Ani Shahbazian, Iris Navarro‐Millán, Shuo Yang, Lang Chen, Stacey S. Cofield, Larry W. Moreland, James O'Dell, Joan M. Bathon, Harold Paulus, S. Louis Bridges, Jeffrey R. Curtis
Journal: Arthritis & Rheumatology (2015)

Objective To evaluate long‐term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Methods Levels of total cholesterol, low‐density lipoprotein (LDL) cholesterol, and high‐density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated‐measures analysis with mixed‐effect linear models to model within‐subject covariance over time. Results Mixed‐effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28‐joint Disease Activity Score, the C‐reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups ( P &lt; 0.001–0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol ( P &lt; 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2‐year followup. Conclusion Decreases in RA disease activity over long‐term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer
Authors: Frank C. Detterbeck, Wilbur A. Franklin, Andrew G. Nicholson, Nicolas Girard, Douglas A. Arenberg, William D. Travis, Peter J. Mazzone, Edith M. Marom, Jessica S. Donington, Lynn T. Tanoue, Valerie W. Rusch, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David G. Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Jeremy Erasmus, Douglas Flieder, Myrna Godoy, Jin Mo Goo, Lawrence R. Goodman, Jim Jett, Paul de Leyn, Alberto Marchevsky, Heber MacMahon, David Naidich, Morohito Okada, Marina Perlman, Charles Powell, Paul van Schil, Ming S. Tsao, Arne Warth
Journal: Journal of Thoracic Oncology (2016)
Study on potato consumption will increase confusion regarding food and the risk of gestational diabetes
Authors: Patrick Mullie, Mathieu Boniol, Philippe Autier
Journal: BMJ (2016)

Using data from the Nurses' Health Study II, Bao and colleagues found a higher prevalence of gestational diabetes mellitus (GDM) with increasing potato consumption. 1 The authors stated that the high glycaemic index of potatoes, which causes a sharp postprandial rise in blood glucose concentrations and a risk of associated pancreatic β cells exhaustion, could explain this association.
Biomarker Analysis of a Phase 1 Study of Mm-111, a Bispecific Her2/Her3 Antibody Fusion Protein, in Combination with Multiple Treatment Regimens in Patients with Advanced Her2 Positive Solid Tumors
Authors: A. Kudla, B. Adiwijaya, V. Paragas, D. Richards, F. Braiteh, A.A. Garcia, C.S. Denlinger, P. Conkling, W.J. Edenfield, S. Anthony, B. Hellerstedt, R. Raju, C. Becerra, W. Harb, D. Smith, K. Kawash, S. Frye, C.F. McDonagh, V. Moyo
Journal: Annals of Oncology (2014)
Abstract P229: Nongenomic Cardioprotective Effect of Dehydroepiandrosterone on Cardiac Hypertrophy: Comparison with 17β-Estradiol-Induced Cardioprotection
Authors: Hideaki Tagashira, Md Shenuarin Bhuiyan, Norifumi Shioda, Kohji Fukunaga
Journal: Circulation Research (2011)

Objective: We recently reported a decreased σ 1 receptor expression in heart following abdominal aortic stenosis in bilateral ovariectomized (OVX) rats. Here, we demonstrated non-genemic cardioprotective effects of dehydroepiandrosterone (DHEA) though σ1 receptor in pressure overload (PO)-induced cardiac dysfunction. Methods: Bilateral ovariectomy was performed in female rats. Two weeks after the sham operation or ovariectomy, pressure-overload was initiated by abdominal aortic banding. 17β-estradiol (E2: 0.1 mg/kg) and DHEA (30 mg/kg) were administered to rats subcutaneously and orally, respectively, for 14 days starting 2 weeks after aortic banding. Hemodynamic parameters and cardiac hypertrophy were measured after 2 weeks of drug treatment. After dissection out of left ventricular, gene expression and hypertrophic signaling were analyzed by real-time RT-PCR and western blot, respectively. Results: Both E2 and DHEA treatments significantly inhibited pressure overload-induced increases both in heart weight/body weight (HW/BW) ratio and lung weight/body weight (LW/BW) ratios. Both E2 and DHEA treatments also ameliorated hypertrophy-induced impairment of left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), left ventricular contraction and relaxation (±dp/dt) rates, heart rate (HR) and mean arterial blood pressure (MABP). Notably, DHEA but not E2 administration rescued PO-induced σ 1 receptor downregulation in left ventricular. Co-administration with NE-100, a σ 1 receptor selective antagonist, inhibited DHEA-induced amelioration of heart dysfunction without effects on E2-induced cardioprotection. Mechanistically, both E2 and DHEA treatments significantly restored PO-induced decreases in Akt phosphorylation and Akt-mediated eNOS phosphorylation (Ser1179). NE-100 treatment totally abolished DHEA-induced Akt and eNOS phosphorylation without effects on E2-induced Akt/eNOS activation. Conclusions: Taken together, based on these results with OVX rat heart, DHEA but not E2 elicits cardioprotective action through σ 1 receptor activation. DHEA-induced Akt/eNOS activation through σ 1 receptors likely mediates the cardioprotective activity.