tbuckley/cabot-search huggingface dataset:
Prevention of Colitis and Colitis-Associated Colorectal Cancer by a Novel Polypharmacological Histone Deacetylase Inhibitor
Authors: Tzu-Tang Wei, Yi-Ting Lin, Ruo-Yu Tseng, Chia-Tung Shun, Yu-Chin Lin, Ming-Shiang Wu, Jim-Min Fang, Ching-Chow Chen
Journal: Clinical Cancer Research (2016)

Colorectal cancer is a worldwide cancer with rising annual incidence. Inflammation is a well-known cause of colorectal cancer carcinogenesis. Metabolic inflammation (metaflammation) and altered gut microbiota (dysbiosis) have contributed to colorectal cancer. Chemoprevention is an important strategy to reduce cancer-related mortality. Recently, various polypharmacologic molecules that dually inhibit histone deacetylases (HDAC) and other therapeutic targets have been developed.Prevention for colitis was examined by dextran sodium sulfate (DSS) mouse models. Prevention for colorectal cancer was examined by azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models. Immunohistochemical staining was utilized to analyze the infiltration of macrophages and neutrophils and COX-II expression in mouse tissue specimens. The endotoxin activity was evaluated by Endotoxin Activity Assay Kit.We synthesized a statin hydroxamate that simultaneously inhibited HDAC and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Its preventive effect on colitis and colitis-associated colorectal cancer in mouse models was examined. Oral administration of this statin hydroxamate could prevent acute inflammation in the DSS-induced colitis and AOM/DSS-induced colorectal cancer with superior activity than the combination of lovastatin and SAHA. It also reduced proinflammatory cytokines, chemokines, expression of COX-II, and cyclin D1 in inflammation and tumor tissues, as well as decreasing the infiltration of macrophages and neutrophils in tumor-surrounding regions. Stemness of colorectal cancer and the release of endotoxin in AOM/DSS mouse models were also attenuated by this small molecule.This study demonstrates that the polypharmacological HDAC inhibitor has promising effect on the chemoprevention of colorectal cancer, and serum endotoxin level might serve as a potential biomarker for its chemoprevention. Clin Cancer Res; 22(16); 4158-69. ©2016 AACR.
Extramedullary Disease Is Common In Newly Diagnosed AML But Has No Independent Prognostic Significance, Including CNS Involvement: Analysis Of 3,522 AML Patients Treated On Consecutive ECOG Trials 1980-2008
Authors: Chezi Ganzel, Judith Manola, Dan Douer, Jacob M. Rowe, Hugo F Fernandez, Elisabeth Paietta, Mark R. Litzow, Ju-Whei Lee, Selina M Luger, Hillard M. Lazarus, Larry Cripe, Martin M Oken, Peter A Cassileth, Martin S. Tallman
Journal: Blood (2013)
Systemic therapy for stage IV non-small cell lung cancer: Single-center U.K. practice 2001-2008.
Authors: A. C. Thompson, C. R. Lewanski, S. Dubash, M. Singhera, S. Mahmoud
Journal: Journal of Clinical Oncology (2010)

e18140 Background: The management of stage IV NSCLC involves the use of a variety of systemic therapies. The proportion and outcome of patients receiving multiple lines of systemic therapy is poorly documented in the United Kingdom. A single-center, single-consultant practice in the United Kingdom was reviewed retrospectively September 2001 to December 2008. Methods: Data from 154 patients with stage IV NSCLC with a minimum of 1-year follow up was analyzed. All patients received at least one course of systemic therapy. Survival was calculated from date of first cycle systemic therapy administered. We analyze survival in relation to number of systemic therapy regimens employed and number of cycles received. Systemic therapy includes chemotherapy and tyrosine kinase inhibitors (TKIs). Results: All patients received at least one systemic therapy regimen; second-, third-, and fourth-line systemic therapy was given to 51.3%, 16.2%, and 1.9% of these patients respectively. The Table details the systemic therapy regimes employed for each line of treatment. Median survival of those patients that received only 1 regimen was 5 months. For those that received a total of 2, 3, or 4 regimes median survival was 8, 12.5, and 31 months respectively. For the 153 patients who received 1st line chemotherapy (TKIs excluded) median survival was 4 months if they received ≤2 cycles and 9 months if > 2 cycles. For 2nd line chemotherapy median survival was 7 months (≤2 cycles) and 11 months (>2 cycles) and for 3rd line chemotherapy where all patients (n=8) received >2 cycles chemotherapy, median survival was 22.5 months. Conclusions: Survival from stage IV NSCLC improves with each additional line of systemic therapy in appropriately selected patients. Those that complete more than 2 cycles of each chemotherapy regimen also do better. First line Second line Third line Fourth line Gem/vin and platinum doublet 140 (90.1%) 3 (3.8%) 3 (12%) — Gem/vin single agent 13 (8.4%) 2 (2.5%) 3 (12%) — Docetaxol single agent — 51 (64.6%) 2 (8%) — TKI 1 (0.6%) 23 (29.1%) 17 (68%) 3 (100%) Total 154 79 25 3 Abbreviations: Gem, gemcitabine; Vin, vinorelbine; TKI, tyrosine kinase inhibitor (erlotinib/gefitinib). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, Roche Lilly, Roche
Correlations of mRNA expression levels of genes in the targeted pathways and Kras mutation status in patients with colorectal cancer.
Authors: D. Yang, W. Zhang, T. Winder, P. O. Bohanes, Y. Ning, K. D. Danenberg, A. B. El-Khoueiry, P. M. Wilson, M. J. Labonte, H. Lenz
Journal: Journal of Clinical Oncology (2010)

10641 Background: There are major breakthroughs in treatment for patients with advanced colorectal cancer (CRC) recently. In addition to 5- fluorouracil (5-FU) and its prodrug, capecitabine, 2 chemotherapy drugs: irinotecan and oxaliplatin, 2 EGFR inhibitors: cetuximab and panitumumab, and a VEGF inhibitor: bevacizumab are approved for treatment of CRC. These drugs are involved in the pathways: 5-FU metabolism (TS, DPD), DNA repair (ERCC1), angiogenesis (VEGF and its receptors), and growth factors (EGFR, Kras). We hypothesized that the correlations of intratumoral mRNA levels of genes involved in these pathways may vary by Kras mutation status and show significant interactions which may influence potential treatment selection. Methods: Formalin fixed paraffin-embedded (FFPE) tumor specimens were retrieved from 149 patients with advanced CRC prior to receiving therapies. Intratumoral mRNA levels were assessed using laser capture microdissection and quantitative Real-time PCR. Kras mutation analysis was determined by DNA sequencing after microdisection. Principal components analysis and Pearson's correlation coefficients were performed to estimate the correlations of mRNA expression levels by Kras mutation status in the key pathways. Results: There were 78 men and 71 women with median age of 58 years (range: 29-84). 27 stage II, 56 III and 66 IV CRC. 90% patients had colon. 38% patients harbored mutant Kras. The mRNA levels of the genes were not statistically different by Kras mutation status, except ERCC1. ERCC1 expression level was statistically higher in patients carrying mutant Kras than wildtype Kras (p=0.045). The correlations of expression levels between 4 pathways varied by Kras mutation status. There were significant correlations between EGFR and ERCC1 in patients with wildtype, but not in mutant Kras. Significant correlations were observed in 5-FU metabolism and ERCC1, and EGFR among patients with mutant, but not in wildtype Kras. Conclusions: Gene expression levels in the targeted pathways, drug metabolisms, and DNA repair may be correlated. Their correlations may depend on Kras mutation status. Future prospective studies are needed to confirm our findings. No significant financial relationships to disclose.
Junior doctors announce five days of full strike action
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors in England will take five consecutive days of full strike action in September, the BMA has said.

Junior doctors will stage a full withdrawal of labour for five days, between the hours of 8 am and 5 pm, from Monday 12 September to Friday 16 September, the association said. The action will be followed by further dates that are yet to be confirmed. The action was announced after the plans were approved by BMA Council.

In July, junior doctors and medical students in …
Care for Transgender Persons
Authors: Anne A. Lawrence, Kenneth J. Zucker
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NHS is unlikely to return to high levels of funding until 2049
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The record levels of funding enjoyed by the NHS in 2009 might not return until 2049, a health policy expert has told peers.

Several predictions of how much the UK will spend on health and social care as part of its gross domestic product (GDP) have been studied by John Appleby, chief economist for health think tank the Nuffield Trust.

Appleby appeared before the House of Lords NHS sustainability committee for an evidence session held on 6 September for its inquiry into the long term sustainability of the NHS.

Peers asked about the various projected health and social care funding pressures from different models up to 2030.

Appleby said that he had looked at five models—including one from the Office for Budget Responsibility’s (OBR) …
Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes
Authors: Bingdi Chen, Wenjun Le, Yilong Wang, Zhuoquan Li, Dong Wang, Ling Lin, Shaobin Cui, Jennifer J. Hu, Yihui Hu, Pengyuan Yang, Rodney C. Ewing, Donglu Shi, Zheng Cui
Journal: Theranostics (2016)

A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers.The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes.All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes.The relative surface charges of cancer cells could be quantified by the percentage of cells captured magnetically.The activities of glucose metabolism had a profound impact on the surface charge level of cancer cells.The data indicate that an elevated glycolysis in the cancer cells led to a higher level secretion of lactate.The secreted lactate anions are known to remove the positive ions, leaving behind the negative changes on the cell surfaces.This unique metabolic behavior is responsible for generating negative cancer surface charges in a perpetuating fashion.The metabolically active cancer cells are shown to a unique surface electrostatic pattern that can be used for recovering cancer cells from the circulating blood and other solutions.
Acute, Exercise Dose-Dependent Impairment in Atrial Performance During an Endurance Race
Authors: Maria Sanz-de la Garza, Gonzalo Grazioli, Bart H. Bijnens, Sebastian I. Sarvari, Eduard Guasch, Carolina Pajuelo, Daniel Brotons, Enric Subirats, Ramon Brugada, Emma Roca, Marta Sitges
Journal: JACC. Cardiovascular imaging (2016)
Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle–Invasive Bladder Cancer Patients
Authors: Laurent Derré, Valérie Cesson, Ilaria Lucca, Yannick Cerantola, Massimo Valerio, Urs Fritschi, Yannis Vlamopoulos, Rodolfo Burruni, Anne-Sophie Legris, Florence Dartiguenave, Dalila Gharbi, Virginie Martin, Laurent Vaucher, Daniel E. Speiser, Pedro Romero, Patrice Jichlinski, Denise Nardelli-Haefliger
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Treatments with cancer vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T cells in the bladder and tumor-regression in murine bladder cancer models. Here, we determined whether an adjuvanted cancer vaccine can be safely administered with concomitant standard intravesical Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle–invasive bladder cancer (NMIBC). Experimental Design: In a nonrandomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine injections or BCG instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG instillations. Results: The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T cells were induced in blood, irrespective of BCG treatment. Interestingly, such T cells were only detected in urine upon BCG-induced T-cell infiltration. Conclusions: Cancer vaccines, including strong adjuvants, can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T cells in the bladder upon BCG provides proof-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717–25. ©2016 AACR.
Scientific intuitions about the mind are wrong, misled by consciousness
Authors: Leonid Perlovsky
Journal: Behavioral and Brain Sciences (2016)

Abstract Logic is a fundamental reason why computational accounts of the mind have failed. Combinatorial complexity preventing computational accounts is equivalent to the Gödelian incompleteness of logic. The mind is not logical, but only logical states and processes in the mind are accessible to subjective consciousness. For this reason, intuitions of psychologists, cognitive scientists, and mathematicians modeling the mind are biased toward logic. This is also true about the changes proposed in After Phrenology (Anderson 2014).
LP41 : Liver fibrosis epidemiology revisited using software combined biomarker: Proof of concept using 1,081,658 centralized fibrotest (FT) prescriptions
Authors: T. Poynard, O. Deckmyn, J. Sebastian, M. Munteanu, Y. Ngo, F. Drane, J. Queen, J.M. Castille
Journal: Journal of Hepatology (2015)
Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases
Authors: Mübeccel Akdis, Alar Aab, Can Altunbulakli, Kursat Azkur, Rita A Costa, Reto Crameri, Su Duan, Thomas Eiwegger, Andrzej Eljaszewicz, Ruth Ferstl, Remo Frei, Mattia Garbani, Anna Globinska, Lena Hess, Carly Huitema, Terufumi Kubo, Zsolt Komlosi, Patricia Konieczna, Nora Kovacs, Umut C Kucuksezer, Norbert Meyer, Hideaki Morita, Judith Olzhausen, Liam O'Mahony, Marija Pezer, Moira Prati, Ana Rebane, Claudio Rhyner, Arturo Rinaldi, Milena Sokolowska, Barbara Stanic, Kazunari Sugita, Angela Treis, Willem van de Veen, Kerstin Wanke, Marcin Wawrzyniak, Paulina Wawrzyniak, Oliver F Wirz, Josefina Sierra Zakzuk, Cezmi A Akdis
Journal: Journal of Allergy and Clinical Immunology (2016)
Racial differences in treatment decision-making patterns and decisional regret in patients with localized prostate cancer.
Authors: Daniel J. Kim, Lauren Hurwitz, Jennifer Cullen, Jane Hudak, Maryellen Colston, Judith Travis, Sally Elsamanoudi, Inger L. Rosner
Journal: Journal of Clinical Oncology (2016)

48 Background: Racial disparities in prostate cancer (PCa) incidence, health-related quality of life (HRQoL), treatment outcomes, and decisional regret have been reported. This study evaluated decision-making in African American (AA) and Caucasian (CA) patients with localized PCa to better understand HRQoL domains associated with post-treatment regret. Methods: This is a prospective cohort study evaluating patients with low- and intermediate-risk PCa in a racially diverse, equal access health-care setting who enrolled in a multidisciplinary clinic at Walter Reed National Military Medical Center. Demographic, clinical, and treatment outcomes data were collected. Validated questionnaires were administered, including the Control Preferences scale, Decision Regret scale (DRS), Expanded Prostate Cancer Index Composite (EPIC), and Medical Outcomes Study Short Form (SF36). Questionnaires were given at fixed intervals post-treatment. Results: A total of 297 (37.8%) AA and 489 (62.2%) CA patients were included in this study. AA patients were more likely to elect radiation therapy (RT) and less likely to elect radical prostatectomy (RP) or active surveillance. AA patients preferred more physician involvement in decision-making. Significantly higher regret was observed for AA patients after RP at 6 and 24 months, compared to CA patients. Only 6-month urinary bother was associated with regret in AA patients while, among CA patients, regret was associated with mental health and sexual bother. Among XRT patients, multiple HRQoL domains were associated with regret in AA patients, while only 36-month mental health was associated with regret in CA patients. Conclusions: Several key differences were noted across race in terms of HRQoL domains that were associated with patient regret. This cohort is now being followed for patient satisfaction with medical care. Such data may further help physicians tailor conversations with patients during treatment decision making to optimize HRQoL and minimize regret.
Progressive Brain Atrophy in Super-refractory Status Epilepticus
Authors: Sara Hocker, Elanagan Nagarajan, Alejandro A. Rabinstein, Dennis Hanson, Jeffrey W. Britton
Journal: JAMA Neurology (2016)

Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking.To document and quantify the development of atrophy over time in SRSE.This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015.Change in VBR (ΔVBR) as a percentage of the starting measure.Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was found (Spearman r = 0.54; P = .02).Atrophy developed in all patients with SRSE who underwent serial imaging, despite administration of agents for seizure control. The degree of atrophy appears to be related to the duration of SRSE.
Regulating Firearm Advertisements
Authors: John E. Pipas
Journal: JAMA (1997)

To the Editor.  —As a strong supporter of the Second Amendment and a firm believer in an individual's right to keep and bear arms, I find the article by Dr Vernick and colleagues 1 concerning the regulation of firearm advertisements to be rather novel. Since it is obvious that challenging gun owners directly is not effective, we now have a group trying to limit the advertising of guns.  To the authors of this article, I offer the words of wisdom that my father imparted to me and that I have passed on to my children: A gun is a dangerous item if misused; all guns are loaded; and never point a gun at something that you do not want to shoot. If these simple ideas are instilled into the minds of everyone to whom guns are available, it will ensure that a gun is no more dangerous than many other items found around
The inflammasome as a novel target for the detection and treatment of non-alcoholic steatohepatitis
Authors: Sofie Walenbergh, Tim Hendrikx, Veerle Bieghs, Patrick van Gorp, Mandy M. Steinbusch, Fons Verheyen, Sander Rensen, Wim Buurman, Steven Olde Damink, Jan Willem Greve, Ad A. Masclee, Ger H. Koek, Marten H. Hofker, Ronit Shiri-Sverdlov
Journal: Hepatology (2012)
Suicide crisis among indigenous Australians tests rural services
Authors: Paul Smith
Journal: BMJ (2016)

A psychiatrist working in one of the world’s worst suicide hotspots has said that identifying people at risk is like “capturing lightning in a jar.”

Murray Chapman is clinical director of the Kimberley Mental Health and Drug Service, which is based in Broome in remote northwestern Australia, more than 2000 km from Perth. Indigenous communities in the region are in the grip of a suicide crisis.

In March a 10 year old indigenous girl is believed to have hanged herself, in one of more than 20 recent suspected suicide cases being investigated by the Western Australia state coroner.

Chapman, who is originally from the United Kingdom and has spent the past 14 years in the Kimberley region, said, “We know we [mental health services] can’t stop it on our own. We have a certain role. We save one or two, but we are standing at the bottom of a cliff. Trying to …
Pancreatic Cancer Cell Lysis by Cell-Penetrating Peptide-MAGE-A3–Induced Cytotoxic T Lymphocytes
Authors: Ramesh B. Batchu, Oksana V. Gruzdyn, Aamer M. Qazi, Ebrahem M. Mahmud, Gamal Mostafa, Donald W. Weaver, Scott A. Gruber
Journal: JAMA Surgery (2016)