tbuckley/cabot-search huggingface dataset:
Abstract B49: Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas
Authors: Clovis Fonseca
Journal: Clinical Cancer Research (2018)

Abstract Gliomas display a high degree of intratumor heterogeneity, including changes in physiologic parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH) have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport dynamics. We therefore hypothesized that glioma cells may display enhanced sensitivity to POH-induced apoptosis due to plasma membrane alterations, while in nontransformed cells, POH may be expelled through thermal agitation. Interactions between POH and the plasma membrane was studied using molecular dynamics simulations. In this phase I/II trial, we set up to evaluate the clinical effectiveness of long-term (up to 5 years) daily intranasal administration of POH in a cohort of 19 patients with low-grade glioma (LGG). Importantly, in a series of clinical studies previously published by our group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort of patients with LGG halted disease progression with virtually no toxicity. Altogether, the results suggest that POH-induced alterations of the plasma membrane might be contributing to its therapeutic efficacy in preventing LGG progression. Citation Format: Clovis Fonseca. Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B49.
THU-427-A community-based fast-track seek-test-treat program to enhance diagnosis and linkage to care for hepatitis C infection among people who inject drugs in Athens, Greece (ARISTOTLE HCV-HIV program)
Authors: Vana Sypsa, Georgios Kalamitsis, Dimitrios Paraskevis, Mina Psichogiou, Sotiris Roussos, Georgios Daikos, George Papatheodoridis, Angelos Hatzakis
Journal: Journal of Hepatology (2019)
FRI-290-The role of bile acids profile and insulin reistance for the prediction of gallstone disease in a prospective cohort of blood donors
Authors: Francesco Azzaroli, Patrizia Simoni, Rosario Arena, Elton Dajti, Federico Ravaioli, Rocco Maurizio Zagari, Alberto Porro, Cecilia Camborata, Annarita Belardinelli, Silvia Spinozzi, Marco Montagnani, Franco Bazzoli, Davide Festi, Franco Placido, Aldo Roda, Giuseppe Mazzella
Journal: Journal of Hepatology (2019)
SAT-492-Associating spleen volume and liver stiffness measurements improves prediction of persistent post-hepatectomy decompensation after resection of hepatocellular carcinoma
Authors: Ramiro Fernandez, Audrey Coilly, Luis Cano, Daniel Cherqui, nicolas golse, Marc-Antoine Allard, Antonio Sa Cunha, René Adam, Cyrille Feray, Didier SAMUEL, Eric Vibert
Journal: Journal of Hepatology (2019)
THU-206-HBV DNA relapse after stopping nucleoside analogue therapy in patients with HBsAg loss: Detectable pre-genomic HBV RNA is a better predictor of relapse than ultra-sensitive HBsAg-‘implications for HBV cure’
Authors: Ivana Carey, Jeffrey Gersch, Christiana Moigboi, Matthew Bruce, Mary Kuhns, Gavin Cloherty, Geoffrey Dusheiko, Kosh Agarwal
Journal: Journal of Hepatology (2019)
FRI-312-Increased levels of bile acid in feces plays an important role in pathophysiology of non-alcoholic steatohepatitis
Authors: Takaomi Kessoku, Takashi Kobayashi, Kento Imajo, Yasushi Honda, Yuji Ogawa, Takuma Higurashi, Shingo Kato, Masato Yoneda, Yousuke Oikawa, Yoshiki Tanaka, Shunji Nakajima, Haruki Usuda, Koichiro Wada, Satoru Saito, Atsushi Nakajima
Journal: Journal of Hepatology (2019)
THU-002-Macrophage activation marker neopterin predicts liver transplantation-free survival in primary sclerosing cholangitis
Authors: Amandeep K Dhillon, Christian Rupp, Mette Vesterhus, Robert Voitl, Marius Trøseid, Øyvind Midttun, Per Ueland, Tom Hemming Karlsen, Martin Kummen, Johannes R. Hov
Journal: Journal of Hepatology (2019)
RASA1 loss in a BRAF-mutated Langerhans cell sarcoma: a mechanism of resistance to BRAF inhibitor
Authors: F. Jouenne, C. Reger de Moura, G. Lorillon, V. Meignin, N. Dumaz, C. Lebbe, S. Mourah, A. Tazi
Journal: Annals of Oncology (2019)
PS-038-A humanized bile acid pool induced by somatic CRISPR/Cas9-mediated deletion of Cyp2c70 modulates effects of pharmacological FXR activation in mice
Authors: Jan Freark de Boer, Esther Verkade, Niels L. Mulder, Hilde D. de Vries, Nicolette Huijkman, Martijn Koehorst, Theo Boer, Justina C. Wolters, Vincent W. Bloks, Bart van de Sluis, Folkert Kuipers
Journal: Journal of Hepatology (2019)
Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors
Authors: Marta Guasch-Ferré, Ambika Satija, Stacy A. Blondin, Marie Janiszewski, Ester Emlen, Lauren E. O’Connor, Wayne W. Campbell, Frank B. Hu, Walter C. Willett, Meir J. Stampfer
Journal: Circulation (2019)

Background: Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial. Methods: We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets. Results: Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference [WMD], 0.065 mmol/L; 95% CI, 0.000–0.129; P for heterogeneity &lt;0.01). When analyzed by specific comparison diets, relative to high-quality plant protein sources, red meat yielded lesser decreases in total cholesterol (WMD, 0.264 mmol/L; 95% CI, 0.144–0.383; P &lt;0.001) and low-density lipoprotein (WMD, 0.198 mmol/L; 95% CI, 0.065–0.330; P =0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, –0.173 mmol/L; 95% CI, –0.260 to –0.086; P &lt;0.001) and high-density lipoprotein (WMD, –0.065 mmol/L; 95% CI, –0.109 to –0.020; P =0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, –0.181 mmol/L; 95% CI, –0.349 to –0.013). Conclusions: Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins.
Decontamination Strategies for Critically Ill Patients
Authors: Chien-Ming Chao, Chih-Cheng Lai
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts
Authors: Yao Sun, Mingxiang Cai, Jiayong Zhong, Li Yang, Jia Xiao, Fujun Jin, Hui Xue, Xiangning Liu, Huisheng Liu, Yongbiao Zhang, Dong Jiang, An Hong, Xunming Ji, Zuolin Wang, Gong Zhang, Xiaogang Wang
Journal: Nature Metabolism (2019)
VULCAN integrates ChIP-seq with patient-derived co-expression networks to identify GRHL2 as a key co-regulator of ERa at enhancers in breast cancer
Authors: Andrew N. Holding, Federico M. Giorgi, Amanda Donnelly, Amy E. Cullen, Sankari Nagarajan, Luke A. Selth, Florian Markowetz
Journal: Genome biology (2019)

VirtUaL ChIP-seq Analysis through Networks (VULCAN) infers regulatory interactions of transcription factors by overlaying networks generated from publicly available tumor expression data onto ChIP-seq data. We apply our method to dissect the regulation of estrogen receptor-alpha activation in breast cancer to identify potential co-regulators of the estrogen receptor's transcriptional response. VULCAN analysis of estrogen receptor activation in breast cancer highlights the key components of the estrogen receptor complex alongside a novel interaction with GRHL2. We demonstrate that GRHL2 is recruited to a subset of estrogen receptor binding sites and regulates transcriptional output, as evidenced by changes in estrogen receptor-associated eRNA expression and stronger estrogen receptor binding at active enhancers after GRHL2 knockdown. Our findings provide new insight into the role of GRHL2 in regulating eRNA transcription as part of estrogen receptor signaling. These results demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.
Abstract 12971: A Novel Combination Therapy with Anti-CD3 Antibody and IL-2 Complexes Against Atherosclerosis Targeting Effector T Cells and Regulatory T Cells
Authors: Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
Journal: Circulation (2013)

Background: Accumulating evidence suggests that a balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for the control of atherosclerotic disease. We hypothesized that combination therapy with anti-CD3 antibody (CD3-Ab) and IL-2/anti-IL-2 monoclonal antibody complexes (IL-2 complexes) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. Methods and results: We treated eight-week old apolipoprotein E-deficient mice fed a high fat diet with vehicle (untreated) (n=10), CD3-Ab (50μg/day) (n=11), IL-2 complexes (1 μg recombinant IL-2 plus 5 μg anti-IL-2 mAb per day) (n=12) and their combination (CD3-Ab + IL-2 complexes) (n=11). Flow cytometric analysis of immune cells was performed at 10 weeks of age and atherosclerosis was assessed at 16 weeks old. CD3-Ab monotherapy moderately reduced atherosclerotic lesion formation (aortic sinus mean plaque area: 62.0±2.8х104 to 53.8±2.3х104 μm2, p≤0.05) compared with untreated con...
Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis
Authors: Simone Herp, Sandrine Brugiroux, Debora Garzetti, Diana Ring, Lara M. Jochum, Markus Beutler, Claudia Eberl, Saib Hussain, Steffi Walter, Roman G. Gerlach, Hans J. Ruscheweyh, Daniel Huson, Mikael E. Sellin, Emma Slack, Buck Hanson, Alexander Loy, John F. Baines, Philipp Rausch, Marijana Basic, André Bleich, David Berry, Bärbel Stecher
Journal: Cell Host & Microbe (2019)
HDAC8 Regulates a Stress Response Pathway in Melanoma to Mediate Escape from BRAF Inhibitor Therapy
Authors: Michael F. Emmons, Fernanda Faião-Flores, Ritin Sharma, Ram Thapa, Jane L. Messina, Jurgen C. Becker, Dirk Schadendorf, Edward Seto, Vernon K. Sondak, John M. Koomen, Yian A. Chen, Eric K. Lau, Lixin Wan, Jonathan D. Licht, Keiran S.M. Smalley
Journal: Cancer Research (2019)

Melanoma cells have the ability to switch to a dedifferentiated, invasive phenotype in response to multiple stimuli. Here, we show that exposure of melanomas to multiple stresses including BRAF-MEK inhibitor therapy, hypoxia, and UV irradiation leads to an increase in histone deacetylase 8 (HDAC8) activity and the adoption of a drug-resistant phenotype. Mass spectrometry-based phosphoproteomics implicated HDAC8 in the regulation of MAPK and AP-1 signaling. Introduction of HDAC8 into drug-naïve melanoma cells conveyed resistance both in vitro and in vivo. HDAC8-mediated BRAF inhibitor resistance was mediated via receptor tyrosine kinase activation, leading to MAPK signaling. Although HDACs function at the histone level, they also regulate nonhistone substrates, and introduction of HDAC8 decreased the acetylation of c-Jun, increasing its transcriptional activity and enriching for an AP-1 gene signature. Mutation of the putative c-Jun acetylation site at lysine 273 increased transcriptional activation of c-Jun in melanoma cells and conveyed resistance to BRAF inhibition. In vivo xenograft studies confirmed the key role of HDAC8 in therapeutic adaptation, with both nonselective and HDAC8-specific inhibitors enhancing the durability of BRAF inhibitor therapy. Our studies demonstrate that HDAC8-specific inhibitors limit the adaptation of melanoma cells to multiple stresses including BRAF-MEK inhibition. SIGNIFICANCE: This study provides evidence that HDAC8 drives transcriptional plasticity in melanoma cells in response to a range of stresses through direct deacetylation of c-Jun.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/11/2947/F1.large.jpg.
Prognostic value of cytokine profile on survival in non-small cell lung cancer patients treated with radiotherapy.
Authors: Shulian Wang, Jie Chen, Randall K Ten Haken, Paul Stanton, Feng Ming Kong
Journal: Journal of Clinical Oncology (2015)

7525 Background: Immunomodulatory and inflammatory cytokines play an important role in cancer development and progression. This study is to investigate the prognostic value of cytokine profile on overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT). Methods: The pre-RT plasma levels of 30 cytokines were measured by multiplex ELISA in 154 stage I-III NSCLC patients who were enrolled in prospective studies. Cox-regression analysis was performed to evaluate the prognostic values of cytokine levels, clinical factors on OS. Results: With a median follow up time of 21.3 months for patients alive, the 3- and 5-year OS was 38.3% and 18.5%, respectively. In univariate analysis, 6 out of 30 cytokines were identified as prognostic biomarkers for OS. Elevated level of TGFa (p = 0.011), IL-1b (p = 0.000), IL-4 (p = 0.048), IL-15 (p = 0.005), EGF (p = 0.011), sCD40L (p = 0.020) was significantly associated with inferior OS. Male (p = 0.034), older age (p = 0.023), poor ECOG performance status (p = 0.002), weight loss (p = 0.036), fatigue (p = 0.005), non-adenocarcinoma histology (p = 0.004), lower RT dose (p = 0.046) were significantly associated with inferior OS. In multivariate analysis, TGFa (p = 0.041), ECOG performance status (p = 0.006), fatigue (p = 0.018), histology (p = 0.019) were independent prognostic factors for OS. Conclusions: Elevated plasma level of TGFa before radiotherapy may represent an independent adverse biomarker for poor OS of NSCLC treated with RT. This result, if validated, will provide important additions to identify risk group of NSCLC patients and guide the development of new targeted therapies. [KFM1]
Anticholinergic Drug Exposure and the Risk of Dementia
Authors: Carol A. C. Coupland, Trevor Hill, Tom Dening, Richard Morriss, Michael Moore, Julia Hippisley-Cox
Journal: JAMA Internal Medicine (2019)

Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.
SAT-045-Prevalence, type and risk factors of colonization by multidrug-resistant bacteria in a large series of patients with decompensated cirrhosis
Authors: Maria Hernandez-Tejero, Fatima Aziz, Cristina Pitart, Francesc Marco Reverte, Irene Campo, Adrià Carpio, Enric Reverter, Angels Escorsell, Santiago Ortiz, Gabriel Mezzano, Pere Ginès, Alex Soriano, Jordi Vila, Javier Fernandez
Journal: Journal of Hepatology (2019)
Lowering of Amyloid-Beta by β-Secretase Inhibitors — Some Informative Failures
Authors: David S. Knopman
Journal: New England Journal of Medicine (2019)

Some trials fail because the experimental treatment proves to be no different than a control or standard intervention. Others fail because of unacceptable side effects. In this issue of the Journal, an article by Egan et al.1 and a letter to the editor by Henley et al.2 describe a third reason for failure — a treatment worsens the target symptoms. The therapeutic intervention of lowering brain amyloid-beta (Aβ) peptide levels to treat patients with Alzheimer's disease is based on a conceptual model in which accumulation of Aβ is causally related to cognitive decline. The model is rooted in the inseparability . . .
FRI-453-Rapamycin promotes tumoricidal immunity in murine HCC by inducing M1-type macrophages and dentritic cells polarization and enhancement of cytotoxic T-cells
Authors: Misbah Aslam, Muhammad Ashfaq-Khan, Asif Qureshi, Simap Celik, Jan-Timon Werle, Marcel Senkowski, Yong Ook Kim, Leonard KAPS, Detlef Schuppan
Journal: Journal of Hepatology (2019)
Combining Pharmacological and Nonpharmacological Interventions in Network Meta-analysis in Psychiatry
Authors: Cinzia Del Giovane, Samuele Cortese, Andrea Cipriani
Journal: JAMA Psychiatry (2019)

Network meta-analyses (NMAs) assess the comparative associations of 2 or more interventions even if they have not been compared in a randomized clinical trial.1 The validity of NMAs is founded on the assumption of transitivity (ie, that effect modifiers do not substantially differ across the included trials).1 The popularity of NMAs on pharmacological or nonpharmacological interventions is increasing in psychiatry.2 Recent NMAs have combined pharmacological and nonpharmacologic interventions in the same network. Although this may be informative for developing guidelines, it is methodologically challenging and could compromise the validity of NMAs. We aimed to evaluate NMAs that combined pharmacological and nonpharmacological interventions and provide guidance on how to conduct them.
Reconciling patients’ need for compensation with doctors’ need for protection
Authors: Giuseppe Vetrugno, Federica Foti, Angelico Spagnolo, Fabio De-Giorgio
Journal: BMJ (2019)

Three days after Ameratunga and colleagues’ paper about the criminalisation of unintentional errors in healthcare was published1 another Boeing 737 Max crashed. Governments have grounded the Boeings and are studying them to identify corrective actions. No need for criminal justice—just a need to understand.

When unintentional medical errors cause adverse events, however, we question whether they were excusable. Nothing changed after The …