tbuckley/cabot-search huggingface dataset:
Funding uplift agreed under GP contract deal
Authors: Gareth Iacobucci
Journal: BMJ (2016)

General practitioners in England will receive a 1% pay uplift next year after the BMA and NHS Employers reached an agreement on contractual arrangements for 2016/17.

The £220m (€281m; $310m) pay uplift is part of an overall funding increase of 3.2% for practices, which includes another 2.2% uplift to cover practice expenses like staffing and higher Care Quality Commission regulatory fees.

The changes—that will start on 1 April 2016—follow the end of annual talks between the BMA’s GP committee and NHS Employers on behalf of the government and NHS England.1

The deal also includes an agreement to end the dementia enhanced service and transfer the attached £42m to GPs’ core funding.

The parties agreed …
Abstract 1166: ASCT2: A novel metabolic target for cancer therapy
Authors: Nabendu Pore, Wanda King, Kristen Lekstrom, Susan Wilson, Robert Hollingsworth, David A. Tice, Emil Michelotti
Journal: Cancer Research (2015)

Abstract Uncontrolled proliferation of cancer cells is often fueled by the deregulation of various cellular signaling pathways. Such deregulation also frequently rewires the metabolism of cancer cells in order to meet their increased need for energy and nutrients required for growth and proliferation. In the process, tumor cells produce high levels of anabolic intermediates required for biosynthesis of macromolecules and redox homeostasis. Many of these building blocks are derived from tri-carboxylic acid cycle (TCA) intermediates that need to be replenished in a process called anapleurosis. Glutaminolysis, the process in which glutamine (Gln) is converted into TCA intermediates by glutaminase is one of the key pathways that feeds anapleurosis in cancers. Many tumor cell lines fail to grow in the absence of glutamine and are therefore addicted to this nutrient. Glutamine is a preferred substrate for ASCT2, a member of ASC family of amino acid transporters, and thus this transporter may play a role in this addiction. We screened a variety of cancer cells for their dependence on Gln and determined that a significant subset of cell lines require this important nutrient. Biochemical experiments indicated that the ASCT2 family of proteins is the main driver of Gln transport. In agreement with these findings, shRNA-mediated knock down of ASCT2 significantly inhibited 14C-Gln uptake and tumor cell proliferation. Expression of an shRNA-resistant ASCT2 gene rescued both the inhibition of cell proliferation and transport of Gln. Furthermore, stable knockdown of ASCT2 induced autophagy and significantly slowed growth in vivo of various tumor types such as colon carcinoma, prostate carcinoma, and in neuroblastoma. The above findings identify ASCT2 as an attractive target for therapeutic intervention. Note: This abstract was not presented at the meeting. Citation Format: Nabendu Pore, Wanda King, Kristen Lekstrom, Susan Wilson, Robert Hollingsworth, David A. Tice, Emil Michelotti. ASCT2: A novel metabolic target for cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1166. doi:10.1158/1538-7445.AM2015-1166
Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain
Authors: Sheena Derry, Philip Wiffen, Andrew Moore
Journal: JAMA (2016)

<h3>Clinical Question</h3> Are topical nonsteroidal anti-inflammatory drugs (NSAIDs) associated with reduced pain intensity in acute musculoskeletal conditions, but without increased adverse events? <h3>Bottom Line</h3> When treating musculoskeletal conditions such as sprains, strains, and contusions, topical NSAIDs are associated with greater pain relief, but are not associated with an increase in adverse events compared with placebo.
Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants
Authors: J. Fareed, D. A. Hoppensteadt, M. Demir, O. Iqbal, W. Jeske, M. Tobu, R. Bick
Journal: Journal of Clinical Oncology (2006)

10573 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.
Correlation of quantitative p95HER2, HER2, and HER3 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant chemotherapy and trastuzumab.
Authors: Jose Caetano Villasboas, Judith Hurley, Jodi Marie Weidler, Agnes Paquet, Carmen Gomez Fernandez, Maureen Cioffi Lavina, Jeff Sperinde, Ahmed Chenna, Mojgan Haddad, Yolanda Lie, John William Winslow, Weidong Huang, Christos J. Petropoulos, Mark D. Pegram
Journal: Journal of Clinical Oncology (2012)

137 Background: Elevated p95HER2 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p95] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data is available on the correlation between p95 and pCR to T in the neoadjuvant (NEO) setting, where p95 was measured by immunohistochemistry. The current study aims to determine whether quantitative p95, HER3 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: pCR data and quantitative HER2 (H2T), p95, and HER3 (H3T) results by HERmark/VeraTag assays were available in 45 patient cases with pre-therapy, formalin-fixed, paraffin-embedded breast tumors. pCR was defined as the absence of invasive disease in the breast. Quantitative biomarker data were correlated with pCR according to previously published or presented biomarker cutoffs. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; p&lt;0.0001) and was significantly associated with higher H2T levels (p=0.02) and lower H3T levels (p=0.04). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups (median H2T=111.5 vs 150.5, respectively; p=0.721). However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group (median H2T=254 vs 37.3; p=0.024). Using multivariate logistic regression, increasing log(H2T) (p = 0.012), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T, particularly in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. Lower H3T was also associated with pCR. A trend towards pCR was seen in tumors with low p95. These data suggest that quantitative H2T, H3T and p95 may provide additional information on response to T-based regimens in breast cancer stratified by ER status. Additional investigation into the relationship between quantitative H2T, p95 and H3T expression and T response in the NEO setting in larger cohorts is warranted.
The runaway center as community mental health center
Authors: J S Gordon
Journal: American Journal of Psychiatry (1978)

The runaway centers that evolved in the late 1960s in response to the needs of troubled young people are fulfilling many of the goals of the community mental health center (CMHC) movement. These centers provide their young clients the five basic CMHC services--inpatient services, outpatient services, emergency services, partial hospitalization, and consultation and education--in an individualized and economical manner. They can serve as a model for a variety of community services, such as drop-in centers for troubled individuals, mediation centers for families, shelters for battered women, and residences for people suffering an acute psychotic break.
Assessment of Minimal Residual Disease in Standard-Risk AML
Authors: Adam Ivey, Robert K. Hills, Michael A. Simpson, Jelena V. Jovanovic, Amanda Gilkes, Angela Grech, Yashma Patel, Neesa Bhudia, Hassan Farah, Joanne Mason, Kerry Wall, Susanna Akiki, Michael Griffiths, Ellen Solomon, Frank McCaughan, David C. Linch, Rosemary E. Gale, Paresh Vyas, Sylvie D. Freeman, Nigel Russell, Alan K. Burnett, David Grimwade
Journal: New England Journal of Medicine (2016)

Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number of molecular genetic markers and morphology-based assessment of remission. Sensitive detection of a leukemia-specific marker (e.g., a mutation in the gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during remission.
From alga to omega; have we reached peak (fish) oil?
Authors: Paul R Clayton, Szabolcs Ladi
Journal: Journal of the Royal Society of Medicine (2015)

Summary While the Inuit diet was highly cardio-protective and consuming oily fish within a Western diet is to a lesser degree, the case for purified fish oil supplements is less convincing. Purification of fish oil removes lipophilic polyphenols which likely contribute to the health benefits of oily fish; leaving the ω3 highly unsaturated fatty acids exposed and prone to conferring oxidative and inflammatory stress. The authors believe that due to such issues as dietary shift, it may now be inadvisable to prescribe or sell purified ω3 highly unsaturated fatty acids supplements, unless the appropriate co-factors are included.
Lessons in comparative oncology.
Authors: P H Sugarbaker
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.7.1099 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2045850 Lessons in comparative oncology. P H SugarbakerxP H SugarbakerSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.7.1099 First Page PDF © 1991 by American Society of Clinical Oncology
Triggers in the pathway from lung cell damage to malignancy: The glycans.
Authors: Anwaar Mohammed Saeed, Ammar Ali Alkhazna, Betty Herndon, Daniel Dim
Journal: Journal of Clinical Oncology (2013)

e22189 Background: It has been reported that carbon nanoparticles (CN) produce mesothelioma as readily as do asbestos fibers. We have studied early CN damage in experimental animals, quantifying toxicity by release from cells of the nuclear chaperone HMGB1. Damage-released HMGB1 binds to receptors (RAGE, CD24) to upregulate cytokines and produce regulatory signals that control cell homeostasis. Further, HMGB1 has recently been shown to form a complex with P53, one of the most commonly mutated genes in human cancers, and HMGB1 is the controlling factor in autophagy, an important new field in translational cancer research. Methods: One HMGB1 receptor, CD24, is the source of a whole-receptor antibody used to determine extent of malignancy during surgery. CD24 is highly glycosylated. We hypothesized that carbohydrate vs protein specificity would show differences in tumor character. Would antibodies to the CD24 carbohydrate moiety reflect a tumor glycan character, and how would this relate to the tumor profile such as metastasis? With cooperation of TMC pathology Dept, blocks (N=15 each) of lung squamous cell, adenocarcinoma, and small cell cancer were sectioned and stained with mouse monoclonals to CD24, IgM –glycan, IgG-protein fraction. Results: Small cell and adenocarcinoma lung tumors showed mostly similar staining by CD24 protein vs CD24 glycan antibodies. Squamous cell CA showed elevated carbohydrate CD24 staining with negative or low protein stain in over half of the cases, and examination of patient records are being studied to determine metastatic character, lung- damage history and tumor chemotherapy response. Conclusions: Squamous cell tumors demonstrate significantly more staining by antibody to the glycan moiety of CD24, p=0.02. There was no relationship between numbers of positive nodes and staining, although other chart information awaits analysis. Research continues into the significance of this glycan CD24 receptor for HMGB1, our marker for nanoparticle lung damage, and its relationship to malignant transformation. [Table: see text]
Towards a de-biased social psychology: The effects of ideological perspective go beyond politics
Authors: David C. Funder
Journal: Behavioral and Brain Sciences (2015)

Abstract Reasonable conservatives are in short supply and will not arrive to save social psychology any time soon. The field needs to save itself through de-biasing. The effects of a liberal worldview permeate and distort discussion of many topics that are not overtly political, including behavioral genetics and evolutionary psychology, the fundamental attribution error, and the remarkably persistent consistency controversy.
Results of phase IV clinical trial of combining endostar with chemotherapy for treatment of advanced non-small cell lung cancer (NSCLC).
Authors: J. Wang, Y. Sun, S. Qin
Journal: Journal of Clinical Oncology (2010)

7598 Background: In order to further explore the efficacy of Endostar in combination with other standard chemotherapy in the management of advanced NSCLC as well as prognostic factors in advanced NSCLC, we conducted a multicentre phase IV clinical trial with combination of Endostar and chemotherapy. Methods: This trial was an open, multi-center clinical trial. All patients were diagnosed clinically and pathologically with advanced NSCLC. After enrollment, patients would be administered with standard chemotherapy and Endostar as treatment. Specific chemotherapy depends on the investigator's decision, but chemotherapy regimens remain standard chemotherapy as recommended by NCCN guideline for advanced NSCLC. Efficacy was evaluated after every 2 cycles of treatment. If there is any objective evidence of disease progression during the trial, the trial for this patient should be terminated immediately. The primary endpoint of this trial is overall survival (OS). In the first 6 months, follow-up was conducted every 2 months, subsequently every 4 months until death. Patients who did not have exact date of death were considered to be censored on the date of last follow-up confirming patients alive. Results: A total of 2,725 subjects were enrolled in this trial, and 1,219 subjects had died up to Oct. 15, 2009. The survival analysis showed that MST was 17.57 months, 1-year survival rate was 63.68%, 2-year survival rate was 39.79%, and median TTP was 7.37 months. Objective response rate (ORR) was 23.93%, and disease control rate (DCR) was 76.07%. There is no significant difference in the survival prognosis among combined regimens of Endostar and different standard chemotherapies. The primary clinical survival prognosis factors of advanced NSCLC are initial and retreatment, with or without distant metastasis, performance status, pathology and gender. Conclusions: Combined Endostar and standard chemotherapy regimens could improve the median survival time and overall survival rate of patients with advanced NSCLC, and there is no significant increase of the adverse effects of chemotherapy. The results of phase III and IV clinical trials were comparable. No significant financial relationships to disclose.
The frequency of methylation of the <i>NT5E</i> gene in metastatic breast cancer.
Authors: C. Lo Nigro, L. Lattanzio, M. Monteverde, N. Syed, A. M. Thompson, O. Garrone, F. Cavicchioli, F. Tonissi, A. Comino, A. McHugh, F. Roncaroli, C. Palmieri, P. Schmid, M. C. Merlano, T. Crook
Journal: Journal of Clinical Oncology (2011)

e11553 Background: Ecto-5-prime-nucleotidase (NT5E; CD73) catalyzes the conversion of purine 5-prime mononucleotides to nucleosides, the preferred substrate being AMP. Deficiency of NT5 occurs in a variety of immunodeficiency diseases and some studies have associated over-expression of NT5E with clinically aggressive neoplastic disease. Here we describe transcriptional down-regulation of the NT5E gene in breast cancer and show that this is associated with aberrant methylation in the CpG island located in its 5' regulatory sequences. Methods: Methylation in the NT5E CpG island was analysed by methylation specific PCR (MSP) and quantitative pyrosequencing in a panel of 10 breast carcinoma cell lines and two independent clinical series of breast carcinomas, comprising 80 and 140 cases respectively and 17 brain metastatic breast cancer lesions. The breast carcinomas were predominantly invasive ductal carcinomas, untreated at the time of surgery and randomly selected from our clinical practice. Expression was assessed by qRT-PCR. Results: NT5E mRNA was down-regulated in 4/10 breast carcinoma cell lines analysed. Down-regulation was associated with aberrant methylation in the CpG island located in the 5' regulatory sequences of the NT5E gene: methylation was present only in cell lines with down-regulation and the CpG island was unmethylated in cell lines which express the gene. Moreover, expression of NT5E was up-regulated by azacytidine. In clinical cases, methylation (assessed by pyrosequencing and/or MSP) was present in 28% and 41% of cases in independent clinical series of primary carcinomas. Methylation was more common in primary cases which ultimately relapsed at distant metastatic sites. Strikingly, methylation was particularly common in 9/16 brain metastatic lesions. Conclusions: In contrast to previous reports, we show that methylation of NT5E is common in metastatic breast cancer, particularly in intra-cranial metastases. Our data implicate transcriptional silencing of NT5E as a common epigenetic event in metastatic breast cancer and imply that detection of methylated DNA may have utility as a prognostic and/or predictive biomarker in breast cancer.
Breast cancer overall survival: Local statistics versus international statistics.
Authors: J. P. Re, M. Blanco Villalba, G. Streich
Journal: Journal of Clinical Oncology (2010)

e12059 Background: In Argentina, the general oncology practice is guided by the international statistics such as overall survival. With such information, which reflects the characteristics of a similar but not equal population, there might be differences. Such potential differences encourage us to try to identify if there are such differences. As a first approach, we compared the overall survival for breast cancer patients as published in National Cancer Institute—Surveillance, Epidemiology, and End Results (SEER) (Table 4.12; Source: http://seer.cancer.gov/csr/1975_2006/results_merged/topic_survival.pdf) to a local database of historical patients. Table 4.12: Cancer of the Female Breast (Invasive); Survival Rates, by Race, Diagnosis Year, Stage and Age. Stage: All Stages 89.1; Localized 98.3; Regional 83.5; Distant 23.3; Unstaged 57.7; In Situ 100.0. Local Database. Stage: All Stages 38% (Total Patients 846); Localized 93% (Total Patients 61); Regional 45% (Total Patients 517); Distant 11% (Total Patients 268). Methods: We compared the previously mentioned table with the results obtained from our local and historical database; we could find the following differences: for all stages, there is a difference of 51.1%. For Localized, data is quite similar. For Regional, there is a difference of 32.5%. For Distant, there is a difference of 12.3%. Results: As per the results of the comparison of both tables, we can confirm there are substantial differences in overall survival for breast cancer patients when compared to international statistics, this should encourages us to find out if the standard of care as stated in the NCCN guidelines, are applicable to our population, or if we should, through further investigation, create our own local standard of care, taking into consideration the outcome of our local population. Conclusions: We should guide our local practice based on local and regional statistics, and compare them to international ones, only as a guideline. If we could achieve this practice, we could Taylor the treatments to best fit our needs. No significant financial relationships to disclose.
Combat neurosis in inner-city schools
Authors: A M Bloch
Journal: American Journal of Psychiatry (1978)

The author studied 253 classroom teachers who were referred for psychiatric evaluation because of varying degrees of psychological stress and physical trauma. These teachers had experienced actual assault or the threat of assault in inner-city schools. The author evaluated these patients' ego functioning, attitudes, current life situations, and the presence of any predisposing factors. On the basis of these evaluations and using guidelines established in studies of combat neurosis, he recommends that individuals who experience severe occupational stress be provided psychological training to prepare them to handle stress, constant support of and access to people in administrative positions, and a mechanism for crisis intervention.