tbuckley/cabot-search huggingface dataset:
A phase II study of bevacizumab with nab-paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma.
Authors: T. D. Tillmanns, M. P. Lowe, L. S. Schwartzberg, M. S. Walker, E. J. Stepanski
Journal: Journal of Clinical Oncology (2010)

5009 Background: Ovarian cancer (OC) has the highest mortality of all cancers involving the female genital tract. Platinum-based therapy is standard primary treatment. Treatments to extend survival, while preserving quality of life, are needed for platinum-resistant patients where current treatment options yield < 4 months progression free survival (PFS) and < 10 months overall survival (OS). This study evaluates the combination of nab-paclitaxel (Abraxane) with bevacizumab in platinum-resistant patients. Methods: 48 patients who had recurrent platinum-resistant OC (93.7%) or primary peritoneal carcinoma with measurable disease (by CT/MRI) were enrolled. 19 (40%) patients had one prior regimen, 27 (56%) had two prior regimens, and 2 (4%) patients had more than two prior regimens. All patients received nab-paclitaxel 100 mg/m2 IV on days 1, 8, 15 with bevacizumab 10 mg/kg IV given on days 1 and 15 every 28 days, and were treated until progression. Results: Mean age was 61 (range 38-87 years) and patients were ECOG 0 (45.8%) or 1 (54.2%) at the time of enrollment. The median PFS, with 37 of 48 patients having experienced disease progression or death, was 8.3 months. Median OS was 16.5 months. Best overall response for the 39 patients who have completed the study to date: partial response: 18 (46.1%); stable disease: 12 (30.8%), progressive disease: 8 (20.5%), and not evaluable: 1 (2.6%). The rate of adverse events was low with 10% of the events reported as grade 3 or 4 toxicities. The most common hematological toxicities were neutropenia (2.6%) and anemia (2.4 %). The most common non-hematological toxicities were nausea (3.8%), nosebleed (3.8%), neuropathy (2.8%) and infection (1.6%). Bowel obstruction occurred in 3.8% of patients. Conclusions: nab-Paclitaxel 100 mg/m2 IV on days 1, 8, 15 in combination with bevacizumab 10 mg/kg IV on days 1 and 15 every 28 days appears to be highly active with impressive PFS and OS combined with low G3/G4 toxicity. Further prospective trials should be explored in this population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience, Genentech
IL-10–producing forkhead box protein 3–negative regulatory T cells inhibit B-cell responses and are involved in systemic lupus erythematosus
Authors: Federica Facciotti, Nicola Gagliani, Barbara Häringer, Johanna Sophie Alfen, Alessandra Penatti, Stefano Maglie, Moira Paroni, Andrea Iseppon, Monica Moro, Maria Cristina Crosti, Katharina Stölzel, Chiara Romagnani, Gabriella Moroni, Francesca Ingegnoli, Sara Torretta, Lorenzo Pignataro, Andrea Annoni, Fabio Russo, Massimiliano Pagani, Sergio Abrignani, Pierluigi Meroni, Richard Flavell, Jens Geginat
Journal: Journal of Allergy and Clinical Immunology (2015)
PR1 peptide vaccination for patients with myeloid leukemias
Authors: M. H. Qazilbash, P. F. Thall, X. Wang, E. Wieder, R. Rios, S. Kant, E. H. Estey, J. E. Cortes, K. Komanduri, R. E. Champlin, J. J. Molldrem
Journal: Journal of Clinical Oncology (2007)

7017 Background: PR1 is a nanomeric HLA-A2-restricted peptide derived from the myeloid leukemia-associated antigens proteinase 3 and neutrophil elastase. Methods: Sixty-six HLA-A2+ patients with acute myeloid leukemia (42), chronic myeloid leukemia (13) or myelodysplastic syndrome (11) were treated with PR1 peptide vaccine. The first 54 patient received three vaccinations, and the last 12 patients were given six vaccinations. The vaccine was injected subcutaneously, at 3 week intervals at one of three dose levels: 0.25, 0.5 or 1.0 mg per vaccination. Immune response to the vaccine was defined as a ≥ 2-fold increase in PR1-specific cytotoxic T lymphocytes. Results: Fifty-three patients had measurable disease (MD) and 13 were in complete remission. The vaccine was well tolerated, with toxicity limited to grade I and II injection site reactions. Forty-four of the 53 patients with MD were evaluable for both immune and clinical responses. PR1-specific immune response was observed in 35/44 (57%) of the evaluable patients. Clinical responses were observed in 10 of the 25 immune responders versus 2 of the 19 immune non-responders (p=0.04). PR1 vaccine-induced immune response was associated with a longer event-free survival, 8.7 months vs. 4.1 months in immune non-responders (p = 0.17). Older age and high blast count were associated with short event-free survival (p=0.01 and &lt;0.001). Conclusion: PR1 peptide vaccine-induced immune response is associated with a superior overall clinical response and a trend towards longer event-free survival in patients with persistent myeloid leukemia. [Table: see text]
Act requires officials to review how US dietary guidelines are formulated
Authors: Michael McCarthy
Journal: BMJ (2015)

A rider attached to the appropriations bill signed into law by President Barack Obama on 18 December requires US officials to conduct a thorough review into how dietary guidelines for the United States are drawn up.

The provision was inserted into the 2200 page Omnibus Appropriations Act in response to charges that the expert advisory panel that helped draw up the new edition of the 2015 US dietary guidelines had ignored research that contradicted its conclusions and had overstepped its brief by commenting on tax and environmental policy.

The legislation denies funding for the next edition of the US Dietary Guidelines for Americans, slated for 2020, unless the secretary of agriculture and the secretary of health and human services ensure that revisions of any dietary or nutritional information are “based on significant scientific agreement” and are “limited in scope to nutritional and dietary information.”

The legislation also requires that the secretary of agriculture engage the National Academy of Medicine to conduct a “comprehensive study of the entire process” used to establish the advisory panel, the Dietary Guidelines Advisory Committee.

The Department of Health and Human Services and the Department of Agriculture are mandated by Congress to publish the Dietary Guidelines for Americans at least every five years. The final guidelines …
Rejection of rejection: a novel approach to overcoming barriers to publication
Authors: Cath Chapman, Tim Slade
Journal: BMJ (2015)

Tired of rejections? Cath Chapman and Tim Slade offer a simple way to fight back

All academics aim to publish in high impact journals. However, many leading scientific and medical journals reject more than 80% of the manuscripts they receive, making rejection the biggest barrier to publication in high quality journals. We propose a novel solution to this problem. It involves very little extra work by submitting authors, is applicable to a wide range of circumstances (such as flawed study, lack of broad interest to the field, or highly critical assessors), and is scaleable to meet the needs of academics from various disciplines. To …
Intermittent hypoxia-induced adipocyte derived secretory products cause inflammatory responses in endothelial cells in vitro
Authors: Mary Y.K. Lee, Judith C.W. Mak, Mary S.M. Ip
Journal: European Respiratory Journal (2014)

Obstructive sleep apnea is characterized by repetitive episodes of intermittent hypoxia (IH) which causes metabolic dysregulation in adipose tissues. The highly vascularized structure of adipose tissues enables the intercellular communication to the vascular endothelium. Activation of endothelium underlies the pathophysiology of endothelial dysfunction and initiates atherosclerosis. It is aimed to investigate the effect of IH on activation of human adipocytes, endothelial EA.hy926 cells (EA) and their interaction  in vitro . Briefly, cultured adipocyte-subcutaneous and EA cells were exposed to IH (O 2 : 1% for 10 minutes alternating with 21% for 5 minutes) for 64 cycles. Some EA cells were incubated with conditioned medium derived from IH-treated adipocytes-subcutaneous (ADIPO). Levels of adiponectin, MCP-1 and IL6, catalase activity and proteins of interests were measured. IH caused significant release of inflammatory cytokines in adipocytes (MCP-1 and IL6) and EA cells (MCP-1) while adiponectin was downregulated in EA cells. Expression of endothelial nitric oxide synthase (eNOS) and catalase activity were reduced while cyclooxygenase-2, inducible NOS, p-Akt (ser473), p-Erk1/2 and p-p38 were increased in EA cells after exposure to IH. ADIPO-treated cells increased phosphorylation of p-Akt (ser473), p-Erk1/2 and p-NF-kB p65. IH induces inflammatory responses in adipocytes as well as endothelial cells with reduced catalase activity and eNOS  in vitro . Comparable activation of inflammatory signalling pathways by IH and ADIPO is observed suggesting a regulatory role of adipocyte-derived secretory products after IH on endothelial functions.
Not just about working hours
Authors: Jonathan R Benger
Journal: BMJ (2008)

Cappuccio and Lockley are over-simplifying a complex situation.1 Since the European Working Time Directive (EWTD) was introduced, consistent concerns have been raised regarding the reduced time that is available for training junior doctors, and the effect that this will have on both clinical experience and quality of care.2 Of particular note, the 2007 National Confidential Enquiry …
Immune surveillance is thwarted by tumor-cell intrinsic beta-catenin signaling
Authors: Stefani Spranger, Brendan Horton, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Growing evidence has emerged that subgroups of cancer patients have a spontaneous T cell-centered immune response reflected by infiltration of antigen-specific CD8+ T cells into the tumor microenvironment. However, another major subgroup of patients completely lacks T cell
Acquired tracheoesophageal fistula - A rare cause of chronic episodic cough
Authors: Amitesh Gupta, Saurabh Kansal, A.P. Kansal, Bidhi Chand
Journal: European Respiratory Journal (2012)

INTRODUCTION- Acquired tracheoesophageal fistula(TOF) is a rare entity and occurs as a result of trauma, malignancy, granulomatous infection, any previous surgery of trachea and oesophagous. Symptoms include uncontrolled coughing after swallowing. The majority of acquired fistulas occur at cervico-thoracic junction.

CASE REPORT -We report a case of 55 yr female who presented to us with cough and regurgitation particularly after intake of liquids since two mths. There was no history of tuberculosis or malignancy. Patient was on antihypertensive agent for four mths but not on ACE inhibitors. On routine investigations TLC and ESR were raised but chest xray was normal.

Sputum was negative for AFB. Patient was managed on lines of Gastro Esophageal Reflux Disease with no improvement. CECT chest showed consolidative changes. Nothing significant found in upper GI endoscopy. Barium swallow revealed the passing of contrast into trachea and in bronchi, showing the presence of tiny fistula at C3-C4 vertebral level. Due to higher position of fistula, patient was advised to undergo surgery.

DISCUSSION- An acquired TOF bypasses the laryngeal protection and leads to repeated aspiration. We are reporting a rare case of acquired TOF possibly of infective etiology which is a rare occrence at such a age. It was also the cause of chronic episodic cough in this patient which was not relieved with various treatments. Malignant and traumatic causes have now superseded infection. Barium swallow will demonstrate the defect in 70% of lesions. The management of acquired TOF inolves minimizing further aspiration to prevent pulmonary infections. Definitive management involves stenting or surgical repair with treatment of underlying cause.
FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver
Authors: Stephanie von Holstein-Rathlou, Lucas D. BonDurant, Lila Peltekian, Meghan C. Naber, Terry C. Yin, Kristin E. Claflin, Adriana Ibarra Urizar, Andreas N. Madsen, Cecilia Ratner, Birgitte Holst, Kristian Karstoft, Aurelie Vandenbeuch, Catherine B. Anderson, Martin D. Cassell, Anthony P. Thompson, Thomas P. Solomon, Kamal Rahmouni, Sue C. Kinnamon, Andrew A. Pieper, Matthew P. Gillum, Matthew J. Potthoff
Journal: Cell Metabolism (2015)
Rheumatic Complaints in Urban and Rural Populations in Osaka
Authors: Kanji Shichikawa, Akira Mayeda, Yoshio Komatsubara, Tadashi Yamamoto, Osamu Akabori, Ichiro Hongo, Toyoji Kosugi, Toshihiko Miyauchi, Masami Orihara, Akira Taniguchi
Journal: Annals of the Rheumatic Diseases (1966)

This survey was made to obtain reliable data for the prevalence of rheumatic complaints in Toyonaka and in Tojo, Tondabayashi.The population sample was examined at home by physicians experienced in the diagnosis of rheumatic diseases.Inquiry was made into all rheumatic complaints especially rheu- matoid arthritis in both urban and rural areas..
A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: Results of NSABP Protocol C-07
Authors: N. Wolmark, S. Wieand, J. P. Kuebler, L. Colangelo, R. E. Smith
Journal: Journal of Clinical Oncology (2005)

LBA3500 Background: The primary aim of this two-arm randomized prospective study was to determine whether FULV + oxaliplatin (FLOX) would prolong 3-year disease-free survival when compared to FULV. Methods: Between February 2000 and November 2002, 2,492 patients (1245 and 1247 in each arm) with stage II and III carcinoma of the colon were randomized to receive either FULV (5-FU, 500 mg/m2 iv bolus weekly x 6; LV, 500 mg/m2 iv weekly x 6, each 8 week cycle x 3) or FLOX (same FULV regimen with oxaliplatin 85 mg/m2 iv administered on weeks 1, 3 and 5 of each 8 week cycle x 3). Results: Three year disease-free survival and toxicity results will be presented using an analysis file with data received by December 31, 2004. We expect to observe approximately 600 events (first recurrence, second primary cancer, or death) with a median follow-up among patients without an event of approximately 33 months. Conclusions: To follow No significant financial relationships to disclose.
Abstract 15423: Plasma Heme oxygenase-1 Predicts Mortality and Neurological Outcome after Out-of-Hospital Ventricular Fibrillation
Authors: Juuso Siren, Jukka Vaahersalo, Ville Pettilä, Ilkka Tikkanen, Päivi Lakkisto
Journal: Circulation (2014)

Introduction:  Heme oxygenase-1 (HO-1) is a stress inducible enzyme implicated in both neuroprotection and cardioprotection. Plasma HO-1 has been shown to increase in critically ill patients and associate with organ dysfunction, but the role of HO-1 in cardiac arrest patients is not known.   Hypothesis:  We investigated the association of HO-1 plasma levels with the outcome of out-of-hospital cardiac arrest (OHCA) patients.   Methods:  A 12-month prospective observational multicenter study in 21 Finnish intensive care units (ICU’s) (the Finnresusci study) in 2010-2011. A subgroup of OHCA patients with initial shockable rhythm was included in this study. Plasma HO-1 was measured at admission and 24 h after ICU admission (day 1) using HO-1 enzyme-linked immunoassay (HO-1 EIA kit, Enzo Life Sciences). The association of plasma HO-1 with time to return of spontaneous circulation (ROSC), APACHE, SAPSII and SOFA scores, ICU mortality, hospital mortality, 90 day mortality and 12-month Cerebral Performance Category (CPC) were analyzed. The primary outcomes were 90-day mortality and 12-month neurological outcome.   Results:  A total of 143 OCHA patients resuscitated from ventricular fibrillation were included in the study. Higher admission and day 1 plasma HO-1 correlated with prolonged time to ROSC (admission, p=0.002, 0.256; day 1, p=0.003, 0.246). Plasma HO-1 also correlated significantly with APACHE (admission, p=0.011, 0.212; day 1, p=0.003, 0.249) and SAPSII (day 1, p=0.022, 0.191) scores. No correlation between HO-1 concentrations and SOFA score was found. The total mortality was 47 out of 143 patients (33%). Greater 90-day and hospital mortalities were associated with higher HO-1 concentrations at admission (90-day mortality, p=0.017; hospital mortality, p=0.039) and day 1 (90-day mortality, p=0.026; hospital mortality, p=0.048). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (p=0.024). The area under the curve for prediction of poor neurological outcome was 0.611.   Conclusions:  We show here for the first time that HO-1 plasma concentrations are associated with ROSC, mortality and long-term neurological outcome in OHCA patients. Plasma HO-1 may aid early prediction of outcome after OHCA.
A new measure of chemotherapy convenience and satisfaction
Authors: K. Yost, E. Hahn, D. Cella
Journal: Journal of Clinical Oncology (2005)

6043 Background: Available measures of patient (pt)-reported outcomes do not capture the burden of i.v. vs. oral administration of chemotherapy. We assessed the reliability and validity of a new Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) in pts receiving treatment in a large phase III trial of oral capecitabine plus i.v. oxaliplatin vs. bolus 5-FU/LV as adjuvant therapy for stage III colon cancer. Methods: CCSQ development involved standard methodology, including content input from experts and pts who identified 10 items measuring chemotherapy convenience and 4 items measuring overall satisfaction with chemotherapy. Convenience items were worded to capture pts’ expectations of chemotherapy at baseline. Satisfaction items were not evaluated at baseline. Factor analysis, reliability, and Rasch analysis were used to assess the measurement properties of the CCSQ. Criterion validity was assessed using clinical variables (adverse events and medical care utilization) to determine the ability to differentiate clinically distinct groups. Responsiveness to change was assessed in an exploratory longitudinal analysis. Results: CCSQ data were available at baseline and after the first study assessment in 208 English-speaking pts. In addition to the satisfaction subscale, factor and Rasch analyses of the 10 convenience items identified 2 factors: concerns (side effects, stress) and convenience. Reliability coefficients for all subscales were high (0.80–0.86). Criterion validity for concerns and satisfaction subscales was good as shown by statistically significant correlations with quality of life, number of days in hospital, and adverse events. These subscales were able to distinguish clinically distinct groups. The concerns subscale demonstrated responsiveness to change. Criterion validity analysis of the convenience subscale is ongoing. Conclusions: The CCSQ is a brief, reliable measure of concerns, convenience and satisfaction in pts receiving chemotherapy. It is a valid measure of concerns and satisfaction, and available evidence suggests that it is also a valid measure of convenience. The CCSQ is currently being used to measure secondary outcomes (perceived treatment convenience and satisfaction) in 3 phase III trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
The relationship between epidermal growth factor receptor(EGFR) mutations and clinico-pathological features in non-small cell lung cancers
Authors: Masaki Tokumo, Shinichi Toyooka, Katsuyuki Kiura, Hisayuki Shigematsu, Kunitoshi Tomii, Motoi Aoe, Kouichi Ichimura, Toshihide Tsuda, Masaaki Yano, Kazunori Tsukuda, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto, Hiroshi Date, Adi F. Gazdar, Nobuyoshi Shimizu
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1669 

Purpose: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor ( EGFR ) gene in non-small cell lung cancers (NSCLCs). Here, we investigated the relationship between EGFR mutation and clinico-pathological features. Experimental Design: EGFR mutational status of 131 NSCLCs was determined mainly in EGFR exons 18-21 by direct sequence and correlated with clinico-pathological parameters. Results: EGFR mutations were present in 41 cases (31%) and the majority of mutations were in-frame deletions of exon 19 (21 cases) and a missense mutation in exon 21 (19 cases). EGFR mutations were frequently associated with adenocarcinoma ( P < 0.0001), never smoker ( P < 0.0001), and female gender ( P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation ( P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Twenty-three cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib-responsiveness ( P = 0.0007). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage, however, the difference was not significant. Conclusions: We demonstrate that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib-responsiveness in NSCLC.
A light-reflecting balloon catheter for atraumatic tissue defect repair
Authors: Ellen T. Roche, Assunta Fabozzo, Yuhan Lee, Panagiotis Polygerinos, Ingeborg Friehs, Lucia Schuster, William Whyte, Alejandra Maria Casar Berazaluce, Alejandra Bueno, Nora Lang, Maria J. N. Pereira, Eric Feins, Steven Wasserman, Eoin D. O’Cearbhaill, Nikolay V. Vasilyev, David J. Mooney, Jeffrey M. Karp, Pedro J. del Nido, Conor J. Walsh
Journal: Science Translational Medicine (2015)

A catheter-based technology reflects light to activate a photocurable adhesive for minimally invasive, atraumatic tissue defect closure.
Ten Years of Grid Cells
Authors: David C. Rowland, Yasser Roudi, May-Britt Moser, Edvard I. Moser
Journal: Annual Review of Neuroscience (2016)

The medial entorhinal cortex (MEC) creates a neural representation of space through a set of functionally dedicated cell types: grid cells, border cells, head direction cells, and speed cells. Grid cells, the most abundant functional cell type in the MEC, have hexagonally arranged firing fields that tile the surface of the environment. These cells were discovered only in 2005, but after 10 years of investigation, we are beginning to understand how they are organized in the MEC network, how their periodic firing fields might be generated, how they are shaped by properties of the environment, and how they interact with the rest of the MEC network. The aim of this review is to summarize what we know about grid cells and point out where our knowledge is still incomplete.
Immune system activation through immunogenic cell death and tumor recruitment of dendritic cells is required for anti-tumor activity of a plant-derived polyphenol rich fraction
Authors: Alejandra Gomez-Cadena, Amaia Martinez-Usatorre, Claudia Urueña, Karol Prieto, Alfonso Barreto, Pedro Romero, Susana Fiorentino
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Chemotherapy faces the problem of chemo-resistance in large part of tumors, leading to the appearance of metastasis difficult to eliminate. Over the past decade an improved understanding of the effect of immunogenic chemotherapy on tumor-host interactions has led to the concept of