tbuckley/cabot-search huggingface dataset:
Tuberculosis—diagnosis, management, prevention, and control: summary of updated NICE guidance
Authors: Lucy Elizabeth Hoppe, Rachel Kettle, Michael Eisenhut, Ibrahim Abubakar
Journal: BMJ (2016)

#### What you need to know

Tuberculosis (TB) incidence in the UK remains high compared with other Western European countries.1 It disproportionately affects underserved groups, including homeless people, people in poor housing or affected by poverty, people with problem drug use, and people born in countries with a high incidence of TB.2 However, many cases are preventable with public health measures, and, when disease does occur, most people can be cured. This article summarises the updated recommendations on diagnosing, managing, and preventing TB from the National Institute for Health and Care Excellence (NICE).1 This guidance updates the 2011 clinical guideline3 and incorporates the public health guidance on the identification and management of TB in under-served groups.4

#### What’s new in this guidance

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of …
Serum p53 antibodies is a postoperative predictive biomarker after curative resection in colorectal cancer patients
Authors: A. Takeda
Journal: Journal of Clinical Oncology (2007)

14567 Background: Because alternations of the p53 tumor suppressor gene are the most commonly observed and can occur early in the carcinogenic process, the accumulation of mutant p53 often leads to the production of p53 antibodies in the sera. The aim of this study is to evaluate the clinical usefullness as early detection marker and as a predictive biomarker of serum p53 antibodies in primary colorectal cancer. Methods: Serum samples are obtained before treatment and from time to time postoperatively and stored - 80 0 C until assay. We employed the newly produced quantitative p53 antibodies ELISA Kit (MESACUP anti-p53 Test, MBL, Japan) to determine the presence of p53 antibodies in 311 patients with colorectal adenocarcinoma compared with the conventional two markers of CEA and CA19–9. Post operative clinical course and the long time survival were evaluated in sero-positive patients after resection. Results: The sensitivities of serum p53 antibodies, CEA and CA19–9 were 32.9%, 36.0% and 23.1%, almost equivalent to CEA and significantly higher than CA19–9. No obvious correlations were evident between the status of serum p53 antibodies and values of two markers, resulting in independent of the other markers. The sensitivity rate of CEA turned up as promotion of pathological stage, but the presence of serum p53 antibodies was more significantly associated with stage 0,I,II. One hundred-nine patients who showed preoperatively sero-positive patients were monitored for at least one year after resection. There was a significant correlation between operative curability and postoperative absence of serum p53 antibodies. Most of repeatedly positive patients treated as curative resection developed recurrence within one year in stageIIandIII. Repeatedly detected patients for serum p53 antibodies have a significantly poor prognosis compared with changed negative patients after curative resection in stageIIandIII. Conclusions: Serum p53 antibodies is easy and convenient, non- invasive, detectable many times and not necessary for surgical specimens for assay. Surveillance of p53 antibodies is rapid and readily facilitated test, which appears to be useful as a new tool for early diagnosis and as a postoperative predictive marker for colorectal cancer patients. No significant financial relationships to disclose.
Abstract 2200: A rational approach for discovery of inhibitors of YAP-TEAD interaction
Authors: Claudia Fromond, Laurent Chene, Anne Soude, Martine Barth, Christian Montalbetti, Pierre Broqua
Journal: Cancer Research (2015)

Abstract The Hippo signalling pathway plays a major role in organ growth regulation and tumorigenesis. By sensing contact inhibition, the central kinase network of the hippo pathway controls nuclear translocation and activity of the YAP transcription factor. Once translocated in the nucleus, YAP interacts with the TEAD family of transcription factors and drives expression of gene involved in cell survival and proliferation. Deregulation of the hippo pathway frequently occurs in cancers and high nuclear expression of YAP has been documented in many tumors including lung, colorectal, ovarian and skin cancers. These data suggest that targeting the hippo pathway is a new therapeutic option for the treatment of a large number of cancers. Several approaches are currently proposed to target the hippo pathway such as inhibition of kinases and GPCRs that are upstream regulators of YAP nuclear translocation. However, because YAP and TEAD are the downstream effectors of the Hippo pathway, we believe that targeting YAP-TEAD interaction is the most promising approach to selectively counteract abnormal activity of the Hippo pathway. We have started a drug discovery program aimed at identifying potent inhibitors of YAP-TEAD interaction, based on a combined FBLD/HTS strategy. Druggability of the TEAD protein was assessed by a fragment screen using NMR and SPR technologies. This approach, conforted by assigned HSQC protein NMR information, provided fragment hits which are used as starting points for the identification of more potent binders. We have also designed a dedicated AlphaScreen assay to validate the ability of our compounds to disrupt the YAP-TEAD interaction. Fifty thousand compounds of the Inventiva's library were screened using the AlphaScreen. Several hits in the micromolar range were identified and further confirmed using SPR. Hits are currently tested for their ability to disrupt YAP-TEAD interaction in a cellular context with a transactivation assay and for their ability to block tumoral cell proliferation. Citation Format: Claudia Fromond, Laurent Chene, Anne Soude, Martine Barth, Christian Montalbetti, Pierre Broqua. A rational approach for discovery of inhibitors of YAP-TEAD interaction. [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 2200. doi:10.1158/1538-7445.AM2015-2200
Neocarzinostatin versus m-AMSA or doxorubicin in hepatocellular carcinoma.
Authors: G Falkson, J M MacIntyre, A J Schutt, B Coetzer, L A Johnson, I W Simson, H O Douglass
Journal: Journal of Clinical Oncology (1984)

Sixty-one of 76 patients entered on a prospective randomized trial of neocarzinostatin ( NCZ ) versus m-AMSA or doxorubicin were eligible for analysis. Among these 61 patients at least one episode of severe toxicity was documented in 39% of patients on NCZ and 58% on m-AMSA. Fifty-one of the 61 patients were previously untreated with chemotherapy. Among these 51 patients objective response was documented in two of 25 patients treated with NCZ , none of 17 treated with m-AMSA, and one of nine treated with doxorubicin. Among previously untreated North American and European (NA/E) patients the median survival times were: NCZ 11 weeks and m-AMSA 12 weeks. The data on South African (SA) patients with similar entrance criteria entered on earlier Eastern Cooperative Oncology Group trials were analyzed with that from the randomized trial and show that for SA patients the median survival times were: NCZ , 11 weeks (31 patients); m-AMSA, 13 weeks (33 patients); and doxorubicin, 15 weeks (29 patients).
Extended lymph node dissection in gastric cancer induces substantial stage migration and increases stage-specific survival without improvement of overall survival.
Authors: D Roukos, A Lazaros, A Kappas, A Encke
Journal: Journal of Clinical Oncology (1996)

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.1996.14.8.2408 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708738 Extended lymph node dissection in gastric cancer induces substantial stage migration and increases stage-specific survival without improvement of overall survival. D RoukosxD RoukosSearch for articles by this author , A LazarosxA LazarosSearch for articles by this author , A KappasxA KappasSearch for articles by this author , A EnckexA EnckeSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2408 First Page PDF © 1996 by American Society of Clinical Oncology
Phase II trial of paclitaxel shows antitumor activity in patients with previously treated germ cell tumors.
Authors: R J Motzer, D F Bajorin, L H Schwartz, H S Hutter, G J Bosl, H I Scher, P Lyn, P Fischer
Journal: Journal of Clinical Oncology (1994)

PURPOSE A trial of paclitaxel was conducted in patients with previously treated germ cell tumors (GCT). As the identification of new agents in GCT may be compromised by restricting entry criteria to heavily pretreated patients, an alternative trial design was used in which eligibility was restricted to patients with limited prior therapy. PATIENTS AND METHODS Patients were eligible if their prior therapy was limited to one cisplatin-based regimen or &lt; or = six cycles of prior cisplatin-based therapy. Paclitaxel 250 mg/m2 was administered by continuous infusion over 24 hours every 21 days. The dose of paclitaxel was modified for each patient based on toxicity. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d was administered during nadir periods. RESULTS Thirty-one patients were treated; eight patients (26%) achieved a partial (n = 5) or a complete (n = 3) response. Responses were achieved in patients who had failed to respond to treatment with cisplatin, ifosfamide, and etoposide, and in patients with poor prognostic features, ie, mediastinal primary tumor site and patients with a best prior response of an incomplete response to cisplatin therapy. One complete responder remains continuously free of disease at 13+ months and one of the five patients who achieved a partial response remains progression-free at 14+ months. CONCLUSION Paclitaxel has antitumor activity in GCT and warrants continued study in combination chemotherapy. Phase I/II trials will address its role in combination with cisplatin and ifosfamide and as a part of dose-intensive therapy. Furthermore, the study showed that a trial design in which eligibility criteria limits prior therapy was feasible, resulted in the identification of antitumor activity in a new agent, and may be considered in future trials for other promising new agents in GCT.
Protease inhibitor monotherapy is effective in controlling human immunodeficiency virus 1 shedding in the male genital tract
Authors: A. Torres-Cornejo, O.J. BenMarzouk-Hidalgo, P. Viciana, B. Sánchez, M.A. López-Ruz, L.F. López-Cortés, A. Gutiérrez-Valencia
Journal: Clinical Microbiology and Infection (2015)

Cross-sectional study comparing seminal human immunodeficiency virus type 1 (HIV-1) shedding in patients receiving boosted protease inhibitor monotherapy (mtPI/rtv) (n = 66) versus triple therapy (TT) (n = 61). Seminal HIV-1 shedding rates in patients with undetectable plasma HIV-RNA were 16.0% on mtPI/rtv compared with 28.6% on TT (p 0.173). Aviraemic status and time on viral suppression were independently associated with lack of seminal HIV-1 shedding. During TT, non PI/rtv-based regimens were associated with a better control of HIV infection in semen despite similar time on viral suppression. The use of mtPI/rtv in well-controlled patients is not associated with increased seminal HIV excretion compared with TT.
Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: a Pediatric Oncology Group study.
Authors: A M Langevin, D T Casto, P J Thomas, S D Weitman, C Kretschmar, H Grier, C Pratt, R Dubowy, M Bernstein, S Blaney, T Vietti
Journal: Journal of Clinical Oncology (1998)

PURPOSE A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. PATIENTS AND METHODS A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 microg/m2 per hour. Pharmacokinetics were to be performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. RESULTS Nineteen patients on four dose levels were assessable for toxicities. At 62 microg/m2 per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. Pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of both lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% +/- 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 +/- 3.8 and 7.1 +/- 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 +/- 13.3 L/m2 and 135.3 +/- 52.5 L/m2, respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. CONCLUSION The recommended phase II dose of 9-AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 microg/m2 per hour. Neutropenia and thrombocytopenia were dose limiting.
Relationship between 5-fluorouracil disposition, toxicity and dihydropyrimidine dehydrogenase activity in cancer patients
Authors: A Di Paolo, R Danesi, A Falcone, L Cionini, F Vannozzi, G Masi, G Allegrini, E Mini, G Bocci, P F Conte, M Del Tacca
Journal: Annals of Oncology (2001)
Evaluation of tuberculosis diagnostic criteria in children
Authors: S. Khalilzadeh, M. Hassanzad, N. Baghaiee, A. A. Velayati
Journal: European Respiratory Journal (2011)

The research was performed to review the diagnostic criteria for tuberculosis (TB) in 198 children with confirmed TB. A cross-sectional descriptive study was conducted on a series of 525 children aged 1 to 15 years. Among 525 patients, 198 were diagnosed with TB. Data were collected from patient records, chest radiographs, and laboratory examinations. Demographic and diagnostic characteristics of patients were reviewed using the currently available criteria. In this study, 38.9% of patients were male and 61.1% were female. Among all patients, 34.8% were Iranian and 65.2% were Afghanis. In total, 82.8% of patients reported close contact with a TB case. Among all patients, 13.1% had extrapulmonary tuberculosis, 72.7% had pulmonary tuberculosis, and 14.1% had both pulmonary and extra pulmonary involvement. The frequency of Tuberculin Skin Test (TST), contact, clinical symptoms, radiograph findings, and bacteriology as diagnostic methods was 79.3, 83.8, 83.8, 85.9, and 58.1%, respectively. In our case, 90.4% of patients fulfilled the criteria. A high diagnostic value was determined for smear and culture of gastric aspirates in children. However, this could not be considered as a gold standard for diagnosis of tuberculosis in children. The results of our current diagnostic criteria showed a significant efficacy and accuracy of the mentioned criteria.
Do All Patients with Iron Deficiency Anaemia Need D2 Biopsies?
Authors: G Cullen, AR Aftab, E Kelly, G Courtney
Journal: Endoscopy (2006)

Aims: Biopsies of the second part of the duodenum (D2) are routinely taken in patients undergoing oesophagogastrodoudenoscopy (OGD) as investigation for iron deficiency anaemia (IDA) and cost approximately (pound))280 per patient. The aim of this study was to identify the need for routine D2 biopsies in patients with IDA.
Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG
Authors: Annett Linge, Steffen Löck, Volker Gudziol, Alexander Nowak, Fabian Lohaus, Cläre von Neubeck, Martin Jütz, Amir Abdollahi, Jürgen Debus, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Melanie Avlar, Anca-Ligia Grosu, Christine Bayer, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, Stefan Welz, Daniel Zips, Frank Buchholz, Daniela E. Aust, Gustavo B. Baretton, Howard D. Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Michael Baumann, Mechthild Krause
Journal: Clinical Cancer Research (2016)

To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 22(11); 2639-49. ©2016 AACR.
US dietary guidelines make no recommendation on sugar tax
Authors: Michael McCarthy
Journal: BMJ (2016)

After months of controversy that sparked a congressional hearing into the politics and science behind its recommendations, on 7 January the US government released the eighth edition of its dietary guidelines.

Unlike previous editions, which emphasized individual food groups and nutrients that should be included in a healthy diet, the 2015-2020 Dietary Guidelines for Americans urges consumers to adopt healthy overall eating patterns that include a variety of vegetables, fruits, whole grains, low fat dairy or soy products, and low fat protein sources, such as fish, lean meats, legumes, and soy products.1

In addition to adopting healthy eating patterns, the new guidelines recommend that Americans limit their consumption of added sugars to less than 10% of daily energy intake, saturated fats to less that 10% of daily energy intake, and sodium to …
The human endogenous retrovirus (HERV) derived kidney Cancer antigen CT-RCC1 induces proliferation of CD8+ antigen-specific T-cells in vitro that kill renal cell carcinoma (RCC) and is up-regulated by inhibiting histone deacetylase
Authors: Sheila Rao, Tawab Abdul, Roger Kurlander, Nanae Harashima, Andreas Lundqvist, Julie Hong, Elizabeth Malinzak, Aleah Smith, Elena Cherkasova, Philip McCoy, David Schrump, Richard Childs
Journal: Cancer Research (2008)

1033  Recently, we identified a genetic sequence (called CT-RCC) derived from a HERV type E that encodes an HLA-A11 restricted 10-mer peptide tumor antigen named CT-RCC1. CT-RCC was found to be expressed in approximately 70% of RCC cells and is not expressed in normal tissues including normal kidney tissue or other non-RCC tumor lines.  To evaluate whether the CT-RCC1 peptide is immunogenic in vitro, PMBCs from healthy, HLA-A11+ donors were stimulated with autologous, CT-RCC1 peptide-loaded (10ug/ml) dendritic cells and B-cells followed by antigen-independent nonspecific rapid expansion. Flow analysis using a CT-RCC1 /HLA-A11+ tetramer showed bulk T-cell cultures contained up to 75% CD8+ /CT-RCC1 peptide binding T-cells. Cytotoxicity assays showed in vitro expanded CT-RCC1 specific T-cells lysed an HLA-A11+ RCC cell line that expressed the CT-RCC1 antigen but did not lyse HLA-A11+ fibroblasts or RCC cells that were either HLA-A11 negative or HLA-A11+ /CT-RCC negative; HLA-A11+ /CT-RCC negative RCC cells that were not killed by in vitro expanded CT-RCC1 specific T-cells were killed when pulsed with 10ug/ml of CT-RCC1 peptide. Quantitative Real time PCR showed expression of CT-RCC was upregulated following a six hour exposure to 25ng/ml of the histone deacetylase inhibitor depsipeptide (DP); DP induced a mean 2.5 fold increase in CT-RCC expression, suggesting histone acetylation is involved in the regulation of this HERV gene. In vitro expanded CT-RCC1 specific T-cells killed HLA-A11+ /CT-RCC+ DP-treated tumor cells at significantly higher levels compared to non-DP treated RCC cells (24% vs 11% lysis at a 7:1 E:T ratio; p=0.04). These data suggest the CT-RCC1 peptide antigen is immunogenic in vitro and appears to be a good potential target for T-cell based immunotherapy directed at RCC.
Abstract P384: Overweight, Obesity and its Correlates among Adolescents: a Comparison of Eleven Countries in the Eastern Mediterranean Region
Authors: Christine S Autenrieth, Regina Guthold, Melanie J Cowan, Laura Kann, Faten Ben Abdelaziz, Leanne M Riley
Journal: Circulation (2012)

Background: Overweight and obesity, physical inactivity, and sedentary behavior are important risk factors for chronic diseases; however, for the youth in countries of the Eastern Mediterranean Region (EMR), comparable prevalence data are lacking. Methods: We used data from nationally representative samples of 34,410 13-15 year old schoolchildren who participated in the Global School-based Student Health Survey (Djibouti, Egypt, Jordan, Lebanon, Libyan Arab Jamahiriya, Morocco, Oman, Pakistan, Tunisia, United Arab Emirates, and Yemen). Data on height, weight, physical activity levels, and sedentary behavior were collected from 2005-2009 in these eleven EMR countries and sex- and country-specific prevalence rates were calculated. Results: The prevalence of overweight and obese youth ranged from 6.5% in Pakistan (boys: 5.1%, girls: 8.7%) to 37.6% in the United Arab Emirates (boys: 39.2%, girls: 36.1%), whereas underweight was highest in Yemen (20.8%; boys: 25.4%, girls: 13.0%) and lowest in Egypt (4.0%; boys: 4.7%, girls: 3.2%). Six of the eleven countries had an overweight and obese rate higher than 20%. The combined risk factors of overweight, insufficient amount of physical activity (&lt; 5 days of at least 60 minutes per week), and sedentary behavior (≥ 3 hours of sitting activities per day) ranged from 0.5% in Pakistan to 12.3% in the United Arab Emirates. Conclusion: These data suggest that prevalence of overweight schoolchildren is high in EMR countries. In addition, physical activity levels were below recommendation guidelines in most of the surveyed countries. Efforts to prevent these unfortunate trends should be taken on regional and national levels.
Peanut and nut allergy
Authors: L. R Lever
Journal: BMJ (1996)

Table 1-Comparison of intemal malignancies between patients with multiple basal cell carcinomas and controls Malignancy Cases Controls Haematological* 5 Ot Breast 3 1 Gastrointestinal tract 1 2 Genitournary tract 4 4 Total 13 7 *Four patients had non-Hodgkin's lymphoma and one had chronic myeloid leukaemia.tP = 0.0625, McNemar's test (StatXact Turbo statistical package).