tbuckley/cabot-search huggingface dataset:
Association of hypertension (HTN) and clinical outcome in a phase II trial of cisplatin (C), pemetrexed (P), and bevacizumab (B) in patients (pts) with untreated malignant mesothelioma.
Authors: S. M. Radaideh, D. E. Gerber, F. Dunphy, J. Yan, Y. Xie, E. L. Fenske, J. Shouldis, H. L. Kindler, J. Dowell
Journal: Journal of Clinical Oncology (2010)

e18012 Background: B is a monoclonal antibody targeting VEGF with demonstrated efficacy in several solid tumors. HTN is a common toxicity of VEGF-targeted therapies, including B, and is a potential surrogate marker of activity for these agents. Methods: We performed a retrospective review of serial blood pressures (BP) in MM pts enrolled in a multicenter phase II study of C, P, and B. Eligible pts had unresectable, histologically confirmed MM, no prior chemotherapy, and PS 0-1. Pts received C 75 mg/m2, P 500 mg/m2 and B 15 mg/kg Q21d for 6 cycles, then B Q21d until progression. BP was recorded at baseline and on day 1 of each cycle. HTN was classified according to European Society of Hypertension (ESH) guidelines. Univariate and multivariate regression analyses were performed to identify differential outcomes between hypertensive and nonhypertensive pts. Results: 45 pts were enrolled at 4 centers between 3/06 and 10/09. Preliminary efficacy data has been presented (ASCO 2009; abstract 7578). Median PFS and OS were 6.9 (95% CI, 5.3-7.7) and 15.3 (95% CI, 11.3-23.5) months (mo). Median PFS and OS for pts with grades (G) 0, 1, and 2/3 HTN are in the tables below. Maximum increase in systolic BP (Smax) also predicted for improved PFS (HR 0.95, 95% CI 0.92-0.98, p=0.001) and OS (HR 0.96, 95% CI 0.93-0.99, p=0.015). In multivariate analysis including EORTC risk score, primary site, Smax, and ESH G1, 2, or 3 HTN, only ESH G1, 2 or 3 HTN predicted for improved PFS (HR 0.21, CI 0.06-0.70, p = 0.01) and OS (HR 0.21, CI 0.06-0.75, p = 0.02). Conclusions: In this study of C, P, and B in MM, development of HTN is a possible biomarker for B activity and is a significant predictor of outcome. # total Median PFS (95% CI)(mo) HR (95% CI) p value ESH grade 0 10 3.1 (2.7, 4.7) Reference ESH grade 1 16 7.7 (5.2, 10.8) 0.13 (0.05, 0.38) 0.0002 ESH grade 2, 3 19 7.3 (6.9, 15.9) 0.10 (0.04, 0.29) < 0.0001 # total Median OS (95% CI)(mo) HR (95% CI) p value ESH grade 0 10 7.9 (6.5, 9.3) Reference ESH grade 1 16 Not reached (11.3, ****) 0.27 (0.08, 0.87) 0.03 ESH grade 2, 3 19 15.9 (14.8, 31.3) 0.25 (0.1, 0.62) 0.003 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI, Roche Abbott Laboratories, Genentech, Lilly, Novartis
Short-type single-balloon enteroscope-assisted ERCP in postsurgical altered anatomy: potential factors affecting procedural failure
Authors: Kei Yane, Akio Katanuma, Hiroyuki Maguchi, Kuniyuki Takahashi, Toshifumi Kin, Satoshi Ikarashi, Itsuki Sano, Hajime Yamazaki, Koh Kitagawa, Kensuke Yokoyama, Hideaki Koga, Kazumasa Nagai, Masanori Nojima
Journal: Endoscopy (2016)

Background and study aims Short-type single-balloon enteroscope (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is a promising alternative treatment in postsurgical altered anatomy. However, it is technically demanding, and factors affecting its technical difficulty have not yet been clarified. This study aimed to examine the procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure. Patients and methods A total of 117 consecutive patients (203 procedures) with surgically altered anatomy underwent ERCP using prototype short SBEs. The procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure were examined retrospectively. Results The enteroscopy success rate and procedural success rate were 92.6 % (95 % confidence interval [CI] 88.1 % - 95.8 %) and 81.8 % (95 %CI 75.8 % - 86.8 %), respectively. Multivariate analyses indicated that pancreatic indication (odds ratio [OR] 4.35, 95 %CI 1.67 - 11.4), first ERCP attempt (OR 6.03, 95 %CI 2.17 - 16.8), and no transparent hood (OR 4.61, 95 %CI 1.48 - 14.3) were potential risk factors for procedural failure. Conclusions Short SBE-assisted ERCP was effective in postsurgical altered anatomy. This large case series suggested the potential factors affecting procedural failure.
Serum Free Light Chain Is Not a Good Biomarker to Predict Post-Transplant Lymphoprolipherative Disorder Development in Renal Transplanted Patients
Authors: Rodrigo Carlini Fernando, Edgar Gil Rizzatti, Walter Moises Tobias Braga, Melina Gonçalves Santos, Mariana Bleker Oliveira, José Osmar Medina Pestana, Otávio Cesar Carvalho Guimarães Baiocchi, Gisele Wally Braga Colleoni
Journal: Blood (2012)
GW26-e1434 Ginsenoside Rb1 prolongs the lifespan and protect against brain aging in C57BL/6J mice
Authors: Bin Zhou, Shujie Yu, Lin Wu, Zhenda Zheng, Yong Liu, Baoshun Hao, Zhiming Song, Lin Chen, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2015)
What do adjuvant and metastatic breast cancer patients (BC) expect from their doctors? Final results of a german survey in 617 patients:
Authors: G. Oskay-Oezcelik, W. Lehmacher, R. Mirz, H. Christ, M. Kaufmann, M. Bamberg, L. Werner, D. Wallwiener, F. Overkamp, H. J. Hindenburg, J. Sehouli
Journal: Journal of Clinical Oncology (2006)

6085 Background: An increasing number of breast cancer patients in western countries are accessing the Internet for medical information. The following study was condcuted to explore the information needs and preferences with special focus on doctor-patient communication. Methods: A questionnaire was developed and validated in a phase-I study and was than administered to breast cancer patients both via internet (online) or via a print-version consisting of 62 questions. Results: A total of 617 patients were interviewed, 552 by online version (online group) and 65 by printed questionnaire (print group). The median age of the online group was 47 years (21–85), for the print group 53 years (40–92). 65% of the patients were treated with the intention of cure, 35% of the patients had a metastatic disease. The median time of consultation communicating the information “You have breast cancer”, was 15 minutes (0–300). The most effective and “patient-relevant source of information and explanations of treatment options was the consultation with their physician (84%). When asked to suggest areas for improvement, most frequent answers were: more alternative therapies should be offered by physician (54%); physicians should have more time for explanations (51%); cooperation between involved physicians should be optimized (39%). Most relevant questions for patients are: “Do I receive the adequate treatment?” (89%); “How many patients with my disease does my physician treat?” (46%); “Can I be enrolled into a trial?” (46%). An independent second opinion centre was desired by 94% of the patients, but only 20% know such an institution. Conclusions: This study underlines the need to give patients with breast cancer all details on treatment options and cancer managements. No significant financial relationships to disclose.
The Middlesbrough early revascularisation to limit INfarction (MERLIN) trial: A randomised trial of rescue angioplasty versus medical treatment for failed fibrinolyis
Authors: AG Sutton, PG Campbell, R Graham, DJ Price, RH Smith, JM Murphy, J Gray, AA Harcombe, JA Hall, RA Wright, de, Belder, Ma
Journal: Circulation (2003)
Natural Killer Cells with NKDG2D Cytotoxicity but NKp30-Dull Phenotype Predominate in Myelodysplastic Syndrome (MDS).
Authors: Fanqi Bai, Jeffrey S. Painter, Cantor Alan, Zou JianXiang, Sheng Wei, Julie Y. Djeu, Alan F. List, P.K. Epling-Burnette
Journal: Blood (2005)
Quality Assessment of 7 Cardiovascular Drugs in 10 Sub-Saharan Countries
Authors: Marie Antignac, Bara Ibrahima Diop, Bernard Do, Roland N’Guetta, Ibrahim Ali Toure, Patrick Zabsonre, Xavier Jouven
Journal: JAMA Cardiology (2016)

Benin (10 of 325 samples [3.1%]), and Congo-Brazzaville (10 of 150 samples [6.7%]).Discussion | To our knowledge, we have presented the first data on the quality of cardiovascular drugs in countries in sub-Saharan Africa.We found a high prevalence of poor-quality drugs, with a little less than 1 in 6 samples failing to meet standards.The observed variation in quality by country merits consideration.Indeed, in 2013, operation BIYELA was carried out in 23 African countries and resulted in the interception of more than 500 million illicit or falsified drugs, most of which were from Benin, Tanzania, and the Democratic Republic of the Congo. 6 Conclusions | A combination of political apathy and corruption may make the task of improving the quality of drugs especially challenging in the developing world.Increasing public awareness and heightening international scrutiny are necessary to bring about changes.Improving the quality of cardiovascular drugs would be a major achievement for the prevention and control of noncommunicable diseases in sub-Saharan Africa.Improvement in the public's access to effective medications also remains an important goal that will help to achieve the target of the United Nations of a 25% reduction in premature cardiovascular disease mortality by 2025. 7Accessibility to quality drug testing for interested parties is a crucial requirement.
O067 : Hematopoietic overexpression of CYP27A1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr-/- mice via NPC-modulated cholesterol transport
Authors: T. Hendrikx, M.L. Jeurissen, S.M. Walenbergh, T. Houben, P.J. van Gorp, F. Verheyen, M.J. Gijbels, E. Leitersdorf, M. Hofker, D. Lütjohann, R. Shiri-Sverdlov
Journal: Journal of Hepatology (2015)
Inherited and Acquired Thrombophilia in Children and Young Adults with Bcr-Abl Negative Chronic Myeloproliferative Disorders.
Authors: Fiorina Giona, Giovanna Palumbo, Patrizia Pignoloni, Angela Amendola, Antonio Chistolini, Anna Maria Testi, Maria Luisa Moleti, Robert Foa, Maria Gabriella Mazzucconi
Journal: Blood (2005)
Activating genomic mutations in the mTOR pathway to predict responses to everolimus and temsirolimus in patients with metastatic renal cell carcinoma (mRCC): Results from a large multi-institutional cohort.
Authors: Andre Poisl Fay, David J. Kwiatkowski, Kathryn P. Gray, Aaron Thorner, Brian I. Rini, Neeraj Agarwal, Thai Huu Ho, Jiaxi Song, Pablo M Barrios, Laurence Albiges, Eliezer Mendel Van Allen, Katherine Maragaret Krajewski, Camillo Porta, Sumanta Kumar Pal, Joaquim Bellmunt, David F. McDermott, Daniel Yick Chin Heng, Sabina Signoretti, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

4519 Background: Mammalian target of rapamycin (mTOR) inhibitors are approved in mRCC, but only a subset of patients derives clinical benefit. Recently, case reports have suggested that mutations in mTOR pathway genes might be associated with response to everolimus and temsirolimus in several malignancies, including mRCC. Methods: We amassed a large international cohort of mRCC patients with available tumor specimens who received mTOR inhibitors and had distinct clinical outcomes: responders were defined as complete response (CR), partial response (PR) or stable disease with any tumor shrinkage or no tumor growth for at least 6 months (R); non-responders were defined as disease progression within the first 3 months of therapy (NR). Tumor DNA from 94 patients was analyzed using a targeted next-generation sequencing panel covering 504 cancer genes. We performed a blinded analysis to investigate the correlation between mutations in mTOR pathway genes and response status. Results: Samples from 79 of 94 patients were successfully sequenced and were included in the analysis. Mutations are summarized in Table 1. Mutations in MTOR, TSC1 or TSC2 were more common in R (12/43) than NR (4/36) (OR: 3.05; p = 0.06; primary hypothesis). Similarly, mutations in TSC1 or TSC2 were more common in R (9/43) than NR (2/36) (OR: 4.42; p = 0.05; secondary hypothesis). In an exploratory analysis, 5/12 with PR/CR had mutations in MTOR, TSC1 or TSC2 vs 4/35 NR (OR: 5.28; p = 0.04). Conclusions: In this large cohort of mRCC patients, mutations in MTOR, TSC1 or TSC2 were more common in patients with clinical benefit from everolimus or temsirolimus than in NR. Mutations in those 3 genes were associated with PR/CR to mTOR inhibitors. In contrast, neither PTEN nor PIK3CA mutations showed any association with response. These findings suggest that a personalized medicine approach has value for selection of mTOR inhibitors in mRCC. Gene Mutation NR(n = 36) n(%) R(n = 43) n(%) Total(N = 79) n(%) MTOR(activating) 2(6) 3(7) 5(6) PTEN(inactivating) 5(14) 5(12) 10(13) TSC1(inactivating) 2(6) 8(19) 10(13) TSC2(inactivating) 0 1(2) 1(1) PIK3CA(activating) 0 1(2) 1(1)
Import and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study
Authors: Maris S Arcilla, Jarne M van Hattem, Manon R Haverkate, Martin C J Bootsma, Perry J J van Genderen, Abraham Goorhuis, Martin P Grobusch, Astrid M Oude Lashof, Nicky Molhoek, Constance Schultsz, Ellen E Stobberingh, Henri A Verbrugh, Menno D de Jong, Damian C Melles, John Penders
Journal: The Lancet Infectious Diseases (2016)
NHS is pushed to the limit as adult social care system reaches “tipping point,” warns regulator
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The NHS is under extreme pressure as a result of serious problems in adult social care services, which are reaching a “tipping point,” a report from the Care Quality Commission (CQC) has said.

The quality regulator’s State of Care report—its annual assessment of the quality of health and adult social care in England—was published on 13 October and said that 71% of the adult social care services that it had inspected were rated “good” and 1% were “outstanding.” 1 It said that 83% of the general practices inspected were “good” and 4% were “outstanding.”

Far less favourable results were reported for the acute sector, where only 51% of the core services provided by NHS acute hospital trusts were “good” and 5% were “outstanding.” …
The use of biomarkers to describe plasma‐, red cell‐, and blood volume from a simple blood test
Authors: Louisa Margit Lobigs, Pierre‐Edouard Sottas, Pitre Collier Bourdon, Zoran Nikolovski, Mohamed El‐Gingo, Evdokia Varamenti, Peter Peeling, Brian Dawson, Yorck Olaf Schumacher
Journal: American Journal of Hematology (2016)

Plasma volume and red cell mass are key health markers used to monitor numerous disease states, such as heart failure, kidney disease, or sepsis. Nevertheless, there is currently no practically applicable method to easily measure absolute plasma or red cell volumes in a clinical setting. Here, a novel marker for plasma volume and red cell mass was developed through analysis of the observed variability caused by plasma volume shifts in common biochemical measures, selected based on their propensity to present with low variations over time. Once a month for 6 months, serum and whole blood samples were collected from 33 active males. Concurrently, the CO-rebreathing method was applied to determine target levels of hemoglobin mass (HbM) and blood volumes. The variability of 18 common chemistry markers and 27 Full Blood Count variables was investigated and matched to the observed plasma volume variation. After the removal of between-subject variations using a Bayesian model, multivariate analysis identified two sets of 8 and 15 biomarkers explaining 68% and 69% of plasma volume variance, respectively. The final multiparametric model contains a weighting function to allow for isolated abnormalities in single biomarkers. This proof-of-concept investigation describes a novel approach to estimate absolute vascular volumes, with a simple blood test. Despite the physiological instability of critically ill patients, it is hypothesized the model, with its multiparametric approach and weighting function, maintains the capacity to describe vascular volumes. This model has potential to transform volume management in clinical settings. Am. J. Hematol. 92:62-67, 2017. © 2016 Wiley Periodicals, Inc.
Molecular Characterization of Clonotypic VDJ Sequences in Waldenstrom’s Macroglobulinemia Suggests Independent Transformation Events in the Development of Biclonal B Cells.
Authors: Jitra Kriangkum, Brian J. Taylor, Steven P. Treon, Michael J. Mant, Tony Reiman, Andrew R. Belch, Linda M. Pilarski
Journal: Blood (2006)
Erratum. Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990–2010. Diabetes Care 2016;39:1643–1649
Authors: Janet L. Leasher, Rupert R.A. Bourne, Seth R. Flaxman, Jost B. Jonas, Jill Keeffe, Novin Naidoo, Konrad Pesudovs, Holly Price, Richard A. White, Tien Y. Wong, Serge Resnikoff, Hugh R. Taylor
Journal: Diabetes Care (2016)
Euthanasia and Physician-Assisted Suicide
Authors: Daniel P. Sulmasy, E. Wesley Ely, Charles L. Sprung
Journal: JAMA (2016)

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High Throughput Sequencing Following Cross-Linked Immune Precipitation (HITS-CLIP) of Argonaute (AGO) Identifies Mir-193a as a Regulator of Jagged1 In Marrow Stromal Cells.
Authors: Ilango Balakrishnan, Xiaodong Yang, Beverly Torok-Storb, Jay Hesselberth, Manoj Pillai
Journal: Blood (2010)
Prostate cancer: Vaccine Sentinel Immunized Node (SIN) target for adjuvant locoregional chemotherapy in autologous vaccine
Authors: E. M. Lasalvia-Prisco, E. Garcia-Giralt, S. Cucchi, J. Vazquez, M. Brent, D. Walton
Journal: Journal of Clinical Oncology (2007)

13500 Background: In cancer patients, the systemic immune response elicited by Tumor Associated Antigens is started by a locoregional immune response at the microenvironment constituted by the antigen source (the tumor) and the draining sentinel lymph node (SLN). The locoregional immune response is decisional because it starts a systemic immune response configured as the SLN response: tolerogenic or protective (AJ Cochran, Nat Rev Immunol, 2006). Cancer vaccines reproduce this locoregional immune response: the vaccination site as the tumor antigen source and the draining SIN as the SLN (ML Disis, Blood, 1996). In experimental models, several chemotherapy drugs, especially Etoposide, injected in the vaccination site switch the locoregional immune response from tolerogenic to protective (RJ Scheper, Invest New Drugs, 1984). This study explores Etoposide as a locoregional adjuvant of the previously described Autologous Thermostable Hemoderivative-Cancer Vaccine ATH-CV (E Lasalvia-Prisco, ASCO, 2006). Methods: Thirty three M1 prostate cancer patients, hormone and chemotherapy resistant, performance status = 2, and PSA rising level, were included in this prospective, IRB-approved phase I/II trial. Patients were 3-group (G) randomized (11 each), submitted to different treatments: G1, no additional oncology treatment; G2, ATH-CV; G3, ATH-CV plus Etoposide 200 μg at vaccination site days 1–4 after vaccine. Statistic assessment (Student’s t-test) was performed at the 30-day end point: ATH sensitization by Delayed Type Hypersensibility test (DTH) and Lymphocyte Proliferative Assay (LPA); PSA serum level and cells immunophenotyping in biopsies of SIN scintigraphy-localized. Results: Statistical significant (p&lt;0.05): DTH test &gt; 5 mm: G1, 0/11; G2, 4/11 and G3, 8/11. LPA &gt; 2.0: G1, 0/11; G2, 5/11 and G3, 9/11. Immunophenotyping: CD4+ CD25+ (Treg): G1&gt;G2&gt;G3. 30 days PSA increase: G1&gt;G2&gt;G3. No relevant toxicity was evidenced. Conclusions: In advanced prostate cancer, when all other treatments are exhausted, the sensitization and tumor antiprogressive effect of ATH-CV were potentiated by Etoposide as local adjuvant. SIN depletion of tolerogenic cells is suggested as mechanism of action. No significant financial relationships to disclose.
Transcriptome-wide effects of inverted SINEs on gene expression and their impact on RNA polymerase II activity
Authors: Mansoureh Tajaddod, Andrea Tanzer, Konstantin Licht, Michael T. Wolfinger, Stefan Badelt, Florian Huber, Oliver Pusch, Sandy Schopoff, Michael Janisiw, Ivo Hofacker, Michael F. Jantsch
Journal: Genome biology (2016)

Short interspersed elements (SINEs) represent the most abundant group of non-long-terminal repeat transposable elements in mammalian genomes. In primates, Alu elements are the most prominent and homogenous representatives of SINEs. Due to their frequent insertion within or close to coding regions, SINEs have been suggested to play a crucial role during genome evolution. Moreover, Alu elements within mRNAs have also been reported to control gene expression at different levels. Here, we undertake a genome-wide analysis of insertion patterns of human Alus within transcribed portions of the genome. Multiple, nearby insertions of SINEs within one transcript are more abundant in tandem orientation than in inverted orientation. Indeed, analysis of transcriptome-wide expression levels of 15 ENCODE cell lines suggests a cis-repressive effect of inverted Alu elements on gene expression. Using reporter assays, we show that the negative effect of inverted SINEs on gene expression is independent of known sensors of double-stranded RNAs. Instead, transcriptional elongation seems impaired, leading to reduced mRNA levels. Our study suggests that there is a bias against multiple SINE insertions that can promote intramolecular base pairing within a transcript. Moreover, at a genome-wide level, mRNAs harboring inverted SINEs are less expressed than mRNAs harboring single or tandemly arranged SINEs. Finally, we demonstrate a novel mechanism by which inverted SINEs can impact on gene expression by interfering with RNA polymerase II.