tbuckley/cabot-search huggingface dataset:
The rs2294918 E434K variant modulates patatin‐like phospholipase domain‐containing 3 expression and liver damage
Authors: Benedetta Donati, Benedetta Maria Motta, Piero Pingitore, Marica Meroni, Alessandro Pietrelli, Anna Alisi, Salvatore Petta, Chao Xing, Paola Dongiovanni, Benedetta del Menico, Raffaela Rametta, Rosellina Margherita Mancina, Sara Badiali, Anna Ludovica Fracanzani, Antonio Craxì, Silvia Fargion, Valerio Nobili, Stefano Romeo, Luca Valenti
Journal: Hepatology (2015)

The patatin‐like phosholipase domain‐containing 3 ( PNPLA3 ) rs738409 polymorphism (I148M) is a major determinant of hepatic fat and predisposes to the full spectrum of liver damage in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, first in individuals with contrasting phenotypes (with early‐onset NAFLD vs. very low aminotransferases) and then in a large validation cohort. Rare PNPLA3 variants were not detected by sequencing coding regions and intron‐exon boundaries either in 142 patients with early‐onset NAFLD nor in 100 healthy individuals with alanine aminotransferase &lt;22/20 IU/mL. Besides rs738409 I148M, the rs2294918 G&gt;A polymorphism (E434K sequence variant) was over‐represented in NAFLD (adjusted P = 0.01). In 1,447 subjects with and without NAFLD, the 148M‐434E ( P &lt; 0.0001), but not the 148M‐434K, haplotype ( P &gt; 0.9), was associated with histological NAFLD and steatohepatitis. Both the I148M ( P = 0.0002) and E434K variants ( P = 0.044) were associated with serum ALT levels, by interacting with each other, in that the 434K hampered the association with liver damage of the 148M allele ( P = 0.006). The E434K variant did not affect PNPLA3 enzymatic activity, but carriers of the rs2294918 A allele (434K) displayed lower hepatic PNPLA3 messenger RNA and protein levels ( P &lt; 0.05). Conclusions: Rare loss‐of‐function PNPLA3 variants were not detected in early‐onset NAFLD. However, PNPLA3 rs2294918 E434K decreased PNPLA3 expression, lessening the effect of the I148M variant on the predisposition to steatosis and liver damage. This suggests that the PNPLA3 I148M variant has a codominant negative effect on triglycerides mobilization from lipid droplets, mediated by inhibition of other lipases. (H epatology 2016;63:787–798)
Book: Presidential Disability
Authors: J. Bunker
Journal: BMJ (2001)

The BMJ Bookshop will endeavour to obtain any books reviewed here. To order contact the BMJ Bookshop, BMA House, Tavistock Square, London WC1H 9JR. Tel: 0171 383 6244, Fax: 0171 383 6455 email: moc.pohskoobjmb@sredro Online: www.bmjbookshop.com (Prices and availability subject to change by publishers.)
Preoperative level of VEGF and IL-6 are associated with lymph node invasion and stage in gastric cancer
Authors: S. OH, H. Kwon, H. Yoo, S. Lee, S. Kim, S. Kim, J. Jang, M. Kim, J. Jeong, K. Kim, H. Kim
Journal: Journal of Clinical Oncology (2007)

4626 Introduction: Angiogenesis plays an important role in growth, progression, and metastasis of tumors, and various cytokines are associated with the spread of cancer cell. In this study, we evaluate the role of VEGF and IL-6 in predicting the spread of gastric cancer. Methods: Preoperative one hundred twenty seven gastric cancer patients and 88 healthy subjects’ specimens were examined. The association of VEGF and IL-6 level with clinical and pathological findings was evaluated Results: Serum VEGF and IL-6 level in gastric cancer patients were higher than those in control (P&lt;0.001, P=0.006, respectively). VEGF and IL-6 level were associated with presence of LN metastasis (P=0.003, P=0.041, respectively). IL-6 level was correlated with stage (P=0.012) and depth of invasion (P=0.018). VEGF level was correlated with invasion of lympho-vascular structure (P=0.021). VEGF and IL-6 level was not related to differentiation, size or CEA level. Conclusions: Serum VEGF and IL-6 levels in gastric cancer patients are higher than those in control. Preoperative VEGF and IL-6 levels could be a predictive marker of tumor invasion and LN metastasis. No significant financial relationships to disclose.
By not publishing good qualitative research<i>The BMJ</i>is not fulfilling its values
Authors: Hiba Zafran
Journal: BMJ (2016)

In an era of person centred care, Sackett and colleagues’ definition of evidence based practice (EBP) becomes even more important.1 While quantitative research may currently have the spotlight in generating “best research evidence,” qualitative research has allowed us to rigorously explore and understand the dynamics and complexity of “clinical expertise” and “patient …
The Association of Coronary Artery Calcium With Noncardiovascular Disease
Authors: Catherine E. Handy, Chintan S. Desai, Zeina A. Dardari, Mouaz H. Al-Mallah, Michael D. Miedema, Pamela Ouyang, Matthew J. Budoff, Roger S. Blumenthal, Khurram Nasir, Michael J. Blaha
Journal: JACC. Cardiovascular imaging (2016)
Ciliary neurotrophic factor upregulates follistatin and Pak1, causes overexpression of muscle differentiation related genes and downregulation of established atrophy mediators in skeletal muscle
Authors: Alexandros Tsompanidis, Elizabeth Vafiadaki, Susann Blüher, Georgia Kalozoumi, Despina Sanoudou, Christos S. Mantzoros
Journal: Metabolism (2016)
Phase II trial of DJ-927 as a second-line treatment for colorectal cancer demonstrates objective responses
Authors: J. M. Rhee, F. C. Lee, M. W. Saif, B. Ardalan, R. Wolff, C. Eng, K. R. Bogaard, P. Cheverton, M. Kimura, M. Danna, P. M. Hoff
Journal: Journal of Clinical Oncology (2005)

3654 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center phase II trial to assess the efficacy of DJ-927 administered as second-line therapy in patients with progressive advanced colorectal adenocarcinoma, who have failed irinotecan or oxaliplatin based chemotherapy. DJ-927 is given as a single oral dose on day 1 of a 21-day cycle. The starting dose initially was 27 mg/m2; after treatment of the first 6 patients resulted in < 2 dose limiting toxicities (DLT), the amount per dose was escalated to 35 mg/m2. Since there were <2 DLT for the first 6 patients, this dose was kept for all subsequent patients. A total of 62 patients are planned to be included in the trial. Results: Thus far 15 patients have been enrolled, with 8 having completed two cycles and thus are evaluable for response. The median age is 59 years (range: 36–80) and the median ECOG PS is 0 (range: 0–2). Ten patients had received prior irinotecan and 5 had received oxaliplatin. 37 cycles have been administered. All patients are assessable for toxicity. Two of the first 8 evaluable patients (25%), had a partial response with 3/8 (37.5%) exhibiting stable disease. The main toxicity encountered so far has been neutropenia, Gr 3 and 4 in 7/15 (47%). No Gr. 3 or 4 peripheral neuropathy has been seen. No patient had to discontinue treatment due to toxicity. Conclusions: The preliminary results of this trial indicate that DJ-927 has some activity as second line treatment for advanced colorectal cancer in patients who have failed oxaliplatin- or irinotecan-based therapy. Accrual continues as planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Daiichi
Abstract 14146: The Risk of New-Onset Diabetes Associated With Pravastatin and Relationship Between Pravastatin and Diet Adherence
Authors: Kyoichi Mizuno, Haruo Nakamura, Yasuo Ohashi
Journal: Circulation (2010)

Background and aims: In February 2010, a meta-analysis of 13 statin trials with more than 90,000 individuals, including the MEGA Study, reported that statin treatment significantly increased the ri...
Retrospective screening of solid organ donors in Italy, 2009, reveals unpredicted circulation of West Nile virus
Authors: M R Capobianchi, V Sambri, C Castilletti, A M Pierro, G Rossini, P Gaibani, F Cavrini, M Selleri, S Meschi, D Lapa, A Di Caro, P Grossi, C De Cillia, S Venettoni, M P Landini, G Ippolito, A Nanni Costa, Collective on behalf of the Italian Transplant Network
Journal: Eurosurveillance (2010)

Since the occurrence of West Nile virus (WNV) infection in humans in 2008 in Italy, concerns have been raised about the potential risks associated with solid organ transplantation (SOT). A nationwide retrospective survey showed that 1.2% of SOT donors in 2009 were WNV-seropositive and demonstrated that human WNV infection is distributed throughout several Italian regions. Transmission of WNV or other arboviruses through SOT is a possibility and risk assessment should be carried out before SOT to avoid infection through transplantation.
Comprehensive mutational profiling of core binding factor acute myeloid leukemia
Authors: Nicolas Duployez, Alice Marceau-Renaut, Nicolas Boissel, Arnaud Petit, Maxime Bucci, Sandrine Geffroy, Hélène Lapillonne, Aline Renneville, Christine Ragu, Martin Figeac, Karine Celli-Lebras, Catherine Lacombe, Jean-Baptiste Micol, Omar Abdel-Wahab, Pascale Cornillet, Norbert Ifrah, Hervé Dombret, Guy Leverger, Eric Jourdan, Claude Preudhomme
Journal: Blood (2016)
Growth Inhibition of Estrogen-Sensitive Rat Mammary Tumors. Effect of an Alpha-Fetoprotein-Secreting Hepatoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C Sonnenschein, A A Ucci, A M Soto
Journal: JNCI Journal of the National Cancer Institute (1980)

The growth and regression patterns of estrogen (E)-sensitive mammary tumors (SNMU) and autonomous mammary tumors (ANMU) were studied in normal, castrated, and alpha-fetoprotein (AFP)-secreting and nonsecreting hepatoma-bearing female BUF rats. Both SNMU and ANMU tumors had comparable amounts of E receptor. SNMU tumors grew faster in female hosts than in male hosts. The latency period of SNMU tumors was lengthened when the tumor was inoculated into newborn hosts. These E-sensitive tumors regressed after castration of the adult hosts. Tumor regression was also observed in SNMU-bearing rats inoculated with AFP-secreting hepatomas. The growth pattern of the ANMU tumor was not affected by the sex or age of the host. Castration and inoculation of hepatomas to ANMU tumor-bearing rats did not result in regression of the ANMU tumors. We suggest that AFP inhibited the growth of E-sensitive cells in newborn and hepatoma 7777-bearing hosts. This inhibitory effect of AFP could not be attributed to a "functional castration" resulting from the trapping of 17 beta-estradiol (E2) by AFP, because the plasma levels of E2 in these animals affect levels of gonadotropins. Moreover, castration of hepatoma 7777-bearing rats resulted in increased plasma follicle-stimulating hormone and luteinizing hormones levels. The results strongly suggested that a) the malignant properties of E2-sensitive cells in adult hosts can be controlled by AFP, and b) the mechanism by which AFP inhibits the growth of E2-sensitive cells is independent of the E2 "trapping" phenomenon. An ontogenetic approach to the mechanism of action of estrogens may account for available results.
Cardiovascular risk and sub-clinical atherosclerosis in prostate cancer: patient with and without androgen ablation
Authors: M. Overman, C. Wang, R. Detrano, M. Douglas-Escobar, E. Ipp, B. Hara, E. Layos, R. Swerdloff, N. Berman, R. Chlebowski
Journal: Journal of Clinical Oncology (2004)

4605 Background: Low testosterone levels have been associated with increased cardiovascular disease risk in some reports while androgen ablation is increasingly being used in early stage prostate cancer (PCA). To address this potential co-morbidity of androgen ablation, cardiovascular risk factors and sub-clinical atherosclerosis were assessed in PCA patients with and without androgen ablation.Methods: Using a cross-sectional study design, 52 men with PCA with a PSA < 2.5 and no symptoms, aged 50–80 years, were studied between ≥ 6 months and < 5 years after diagnosis in two groups. The control group had no prior androgen ablative therapy. The androgen ablation group either had prior orchiectomy or were receiving androgen ablative therapy continuously ≥ for 6 months. The study endpoint was composite measure of cardiovascular disease risk comparing ablation and control PCA groups. Evaluations included: testosterone level, lipid profile, urine microalbumin, oral glucose tolerance testing, ankle-brachial index (ABI) for peripheral arterial disease estimate and coronary calcium score by electron beam computed tomography for coronary heart disease estimate. Results: Subclinical diabetes and/or impaired glucose tolerance (IGT) by two hour post tolerance glucose was substantial in both PCA groups (52% in androgen ablation and 45% in controls). Testosterone levels were low to normal (430 ± 142 mg/dl, mean ± SD) in controls (n=31) and very low (19 ± 13 mg/dl) in androgen ablated (n=21) patients. Body weight, total body fat (kg) and body mass index were higher and hemoglobin was lower in the ablation group (all p<0.05). The coronary calcium score (control 240 ± 76, mean SEM versus ablation 162 ± 45) and percent abnormal ABI (control 16% abnormal versus ablation 10% abnormal) were similar in the two groups.Conclusions: Androgen ablation in PCA patients is not associated with measures of increased cardiovascular disease risk. These results add weight to predictions of cardiovascular safety for androgen ablation used for early stage PCA management. The high incidence of subclinical diabetes and IGT in men with PCA warrants further attention. No significant financial relationships to disclose.
Human cases of West Nile Virus Infection in north-eastern Italy, 15 June to 15 November 2010
Authors: L Barzon, M Pacenti, R Cusinato, M Cattai, E Franchin, S Pagni, T Martello, S Bressan, L Squarzon, A M Cattelan, G Pellizzer, P Scotton, A Beltrame, F Gobbi, Z Bisoffi, F Russo, G Palù
Journal: Eurosurveillance (2011)

In 2010, for the third consecutive year, human cases of West Nile virus (WNV) infection, including three confirmed cases of neuroinvasive disease and three confirmed cases of West Nile fever, were identified in north-eastern Italy. While in 2008 and 2009 all human cases of WNV disease were recorded in the south of the Veneto region, cases of WNV disease in 2010 additionally occurred in two relatively small northern areas of Veneto, located outside those with WNV circulation in the previous years. WNV IgG antibody prevalence in blood donors resident in Veneto was estimated as ranging from 3.2 per 1,000 in areas not affected by cases of WNV disease to 33.3 per 1,000 in a highly affected area of the Rovigo province. No further autochthonous human cases of WNV disease were notified in Italy in 2010. The recurrence of human cases of WNV infection for the third consecutive year strongly suggests WNV has become endemic in north-eastern Italy.
Possible role of engraftment syndrome in myelodysplastic syndrome after autologous transplants
Authors: Y. Keung, M. W. Beaty, M. Pettenati, D. Levitan, I. Molnar, M. Thakuri, J. Cruz, D. D. Hurd
Journal: Journal of Clinical Oncology (2008)

18016 Background: Autologous graft versus host disease (GVHD) and engraftment syndrome (ES) are recognized complications after autologous transplantation, probably resulted from dysfunctional host immunity during hematopoietic recovery. Since impaired immunity has been associated with myelodysplastic syndrome, we explore the possible role of GVHD or ES in post-transplant myelodysplastic syndrome/acute myeloid leukemia (MDS). Methods: Consecutive patients with lymphoma (n = 414) undergoing autologous transplantation at our institution from 1/1993 to 6/2006. There were 253 males and 161 females; median age 50 years. There were 72 patients with Hodgkin's (HL) and 342 non-Hodgkin's lymphoma (NHL). 259 received TBI-based regimens and 155 non-TBI-based; 69 patients received transplantation of bone marrow (BM), 336 peripheral blood stem cells (PBSC) and 9 both. Results: Eleven patients had a second autologous transplant for progressive disease and three patients had a second allogeneic transplant for MDS. Ten patients developed severe engraftment syndrome (high fever, skin rash ± pulmonary infiltrate requiring systemic steroid); 33 patients had skin and 2 patients had gastrointestinal biopsies consistent with GVHD. The median follow-up of the patients is 6.0 years and median overall survival is 5.4 years. Twenty-three patients (5.6%) developed MDS with median time of onset of 4.3 years (range 8 months-8.9 years). Additional 5 patients developed clonal karyotypic abnormalities in the bone marrow without clinical MDS. Actuarial probabilities of developing MDS at 5 and 8 years after transplant are 6.9% and 17%, respectively. The development of MDS is independent of the diagnosis, stem cells or the conditioning regimens. Univariate analysis using logrank tests demonstrates that older age, advanced stage, the presence of ES, and longer intervals between the initial diagnoses to transplant as risk factors of developing MDS. Conclusions: Although overall incidence of MDS is only 5.6%, the actuarial risk at 8 years is up to 17% and is probably higher in selected patients. The association of engraftment syndrome to MDS is intriguing. While it may be just a chance association, it is conceivable that perturbation to the host immunity may play a role in the onset of MDS after transplant. No significant financial relationships to disclose.
Algorithm to predict radiological erosions in early rheumatoid arthritis
Authors: P. Emery, A. Gough, J. Devlin, M. Green
Journal: BMJ (1996)

alcohol on young people.We, like Mary-Ann McKibben, believe that a voluntary code is an inadequate means of regulating a multimillion pound industry with multiple producers.In addition to tighter controls on alcohol producers there needs to be stricter enforcement of existing laws on the sale of alcohol to young people.Increasing taxation on particular products may offer a further way of influencing young people's alcohol buying behaviour.Such a move should not be confined to the alcopops but should include white ciders, fruit wines, and vodka, which our report showed to be the drinks of choice of many schoolchildren.
Smart Search and Analysis of ASCO Abstracts: The 2003 ASCO Pilot Breast Cancer Information Exchange (BCIE) project
Authors: A. T. Rappaport, D. R. Adamson, L. Shih, R. G. Smith, J. M. Tenenbaum, B. Khoo, S. Cho, A. C. Wolff, R. W. Carlson, D. A. Whippen
Journal: Journal of Clinical Oncology (2004)

6066 Background: ASCO abstracts are a leading source of cancer research information. The ASCO Breast Cancer Information Exchange (BCIE) project was developed to better organize and access abstracts in breast cancer for a faster, more precise, and targeted search. Methods: Traditional web search engines allow simple keyword-based queries. Improvements in precision and ease of use require software that “knows” the domain. We developed XML/Java models of breast cancer clinical studies, from molecular diagnostics to disease stages. From these models, we developed a study characterization form, included as a voluntary author step in the 2003 Annual Meeting abstract submission process, to capture the study clinical parameters. We also developed a corresponding user search form, publicly available onhttp://webapp.asco.org/bcie. Results: Almost 95% of breast cancer abstract first authors (352) participated, completing the web-based form to characterize their studies from a uniform descriptive variable set. Since 8/02, www.asco.org visitors have used the BCIE search tool to formulate queries. Analysis of a subset of queries (N=691) revealed that 90% selected form-based search variables exclusively or combined with traditional open keyword search terms. On average, 7 search variables were entered per search. The three most selected search variables were study phase, patient sex, and chemotherapeutic agent. In addition, the repository of characterized studies created a detailed index of author-selected consistent-variable descriptors, offering potential for examination of abstract trends within one disease-type, including study types, prognostic factors, therapies, diagnostics, and biomarkers. Heretofore, such analysis has been time consuming, performed manually, and not reflective of authors direct involvement. Conclusions: The BCIE project demonstrates the feasibility of a new technology and process for uniform XML-Java indexing, search, and analysis of published material. The project continues in 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medstory Medstory
Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study
Authors: N. Aldoori, K. Dobson, C.R. Holden, A.J. McDonagh, M. Harries, A.G. Messenger
Journal: British Journal of Dermatology (2016)

Since its first description in 1994, frontal fibrosing alopecia (FFA) has become increasingly common, suggesting that environmental factors are involved in the aetiology. To identify possible causative environmental factors in FFA. A questionnaire enquiring about exposure to a wide range of lifestyle, social and medical factors was completed by 105 women with FFA and 100 age‐ and sex‐matched control subjects. A subcohort of women with FFA was patch tested to an extended British standard series of allergens. The use of sunscreens was significantly greater in the FFA group compared with controls. Subjects with FFA also showed a trend towards more frequent use of facial moisturizers and foundations but, compared with controls, the difference in frequencies just failed to reach statistical significance. The frequency of hair shampooing, oral contraceptive use, hair colouring and facial hair removal were significantly lower in the FFA group than in controls. Thyroid disease was more common in subjects with FFA than controls and there was a high frequency of positive patch tests in women with FFA, mainly to fragrances. Our findings suggest an association between FFA and the use of facial skin care products. The high frequency of sunscreen use in patients with FFA, and the fact that many facial skin care products now contain sunscreens, raises the possibility of a causative role for sunscreen chemicals. The high frequency of positive patch tests in women with FFA and the association with thyroid disease may indicate a predisposition to immune‐mediated disease.
Optimal Proliferation of a Hematopoietic Progenitor Cell Line Requires Either Costimulation With Stem Cell Factor or Increase of Receptor Expression That Can Be Replaced by Overexpression of Bcl-2
Authors: Huei-Mei Huang, Jian-Chiuan Li, Yueh-Chun Hsieh, Hsin-Fang Yang-Yen, Jeffrey Jong-Young Yen
Journal: Blood (1999)
Cancer Stem cells and their cellular origins in primary liver and biliary tract cancers
Authors: Tsunekazu Oikawa
Journal: Hepatology (2016)

Liver and biliary tract cancers are highly aggressive, are heterogeneous in their phenotypic traits, and result in clinical outcomes that are difficult to manage. Cancers have subpopulations of cells termed “cancer stem cells” (CSCs) that share common intrinsic signaling pathways for self‐renewal and differentiation with normal stem cells. These CSCs likely have the potential to evolve over time and to give rise to new genetically and functionally diverse subclones by accumulating genetic mutations. Extrinsic signaling from the tumor microenvironment, including the CSC niche, has been implicated in tumor initiation/progression and heterogeneity through dynamic crosstalk. CSCs have become recognized as pivotal sources of tumor initiation/progression, relapse/metastasis, and chemoresistance. Conclusion : The origins of CSCs are hypothesized to derive from the transformation of normal stem/progenitors and/or from the reprogramming of adult cells that converts them to stem/progenitor traits; however, the precise mechanisms have not yet been fully elucidated. (H epatology 2016;64:645‐651)