tbuckley/cabot-search huggingface dataset:
Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy
Authors: Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Lukasz J. Ochyl, Yao Xu, Alireza Hassani Najafabadi, Lindsay Scheetz, Min-Zhi Yu, Ishina Balwani, Anna Schwendeman, James J. Moon
Journal: Journal of Controlled Release (2018)

Recent studies have shown that certain combinations of Toll-like receptor (TLR) agonists can induce synergistic immune activation. However, it remains challenging to achieve such robust responses in vivo in a manner that is effective, facile, and amenable for clinical translation. Here, we show that MPLA, a TLR4 agonist, and CpG, a TLR9 agonist, can be efficiently co-loaded into synthetic high-density lipoprotein nanodiscs, forming a potent adjuvant system (ND-MPLA/CpG) that can be readily combined with a variety of subunit antigens, including proteins and peptides. ND-MPLA/CpG significantly enhanced activation of dendritic cells, compared with free dual adjuvants or nanodiscs delivering a single TLR agonist. Importantly, mice immunized with physical mixtures of protein antigens ND-MPLA/CpG generated strong humoral responses, including induction of IgG responses against protein convertase subtilisin/kexin 9 (PCSK9), leading to 17–30% reduction of the total plasma cholesterol levels. Moreover, ND-MPLA/CpG exerted strong anti-tumor efficacy in multiple murine tumor models. Compared with free adjuvants, ND-MPLA/CpG admixed with ovalbumin markedly improved antigen-specific CD8+ T cell responses by 8-fold and promoted regression of B16F10-OVA melanoma (P < 0.0001). Furthermore, ND-MPLA/CpG admixed with E7 peptide antigen elicited ~20% E7-specific CD8+ T cell responses and achieved complete regression of established TC-1 tumors in all treated animals. Taken together, our work highlights the simplicity, versatility, and potency of dual TLR agonist nanodiscs for applications in vaccines and cancer immunotherapy.
Impact of Changes in Inflammation on Estimated Ten‐Year Cardiovascular Risk in Rheumatoid Arthritis
Authors: Zhi Yu, Nicole Yang, Brendan M. Everett, Michelle Frits, Christine Iannaccone, Jonathan Coblyn, Michael Weinblatt, Nancy Shadick, Daniel H. Solomon, Katherine P. Liao
Journal: Arthritis & Rheumatology (2018)

Objective Current validated cardiovascular ( CV ) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis ( RA ) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population‐based risk calculators. Methods Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C‐reactive protein ( CRP ) level at 2 consecutive time points 1 year apart ( CRP decrease group and CRP increase group, respectively) were included in this study. We estimated 10‐year CV risk using the following calculators: Framingham Risk Score, 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score, Reynolds Risk Score ( RRS ), and QRISK 2. Of these calculators, only the RRS includes a variable addressing the CRP level. Paired t ‐tests were performed to compare risk scores at baseline and 1‐year follow‐up. We calculated the correlations between the changes in risk scores and changes in pro–B‐type natriuretic peptide (pro BNP ), a surrogate marker of CV risk. Results One hundred eighty RA patients were included in the study (mean age 57.8 years, 84% female, 80% seropositive). Of the calculators studied, only the RRS was sensitive to changes in inflammation; an increase in inflammation was associated with increased estimated CV risk ( P &lt; 0.0001), and only the RRS was correlated with changes in pro BNP (r = 0.17, P = 0.03). Conclusion Our data showed no significant change in CV risk estimated using validated general population CV risk calculators except for the RRS . These findings suggest that CV risk may be modulated by changes in inflammation in RA , which is not typically considered when using existing CV risk calculators.
Universal access to DAA therapy paves the way for HCV control and elimination among people living with HIV in Australia
Authors: M. Martinello, S. Bartlett, G. Dore, R. Bopage, R. Finlayson, D. Baker, M. Bloch, J. Doyle, D. Shaw, K. Hajkowicz, P. Read, E. Filep, L. Lin, J. Yee, T. Applegate, M. Hellard, G. Matthews
Journal: Journal of Hepatology (2018)
A functional metagenomics investigation of cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy
Authors: V.D.I. Gregorio, V. Iebba, F. Guerrieri, M. Levrero, A. Gagliardi, F. Santangelo, A.P. Sobolev, S. Circi, V. Giannelli, L. Mannina, S. Schippa, M. Merli
Journal: Journal of Hepatology (2018)
Abstract 17996: Broad Suppression of NADPH Oxidase Activity Exacerbates Ischemia/reperfusion Injury Via Disturbance of Cell Metabolism
Authors: Shoji Matsushima, Junya Kuroda, Tetsuro Ago, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation (2012)

NADPH oxidases (Noxs), including Nox2 and Nox4, are major sources of reactive oxidative species (ROS), which play a critical role in mediating myocardial injury in response to ischemia/reperfusion (I/R). The goal of this study was to elucidate the specific functions of Nox2 and Nox4 during I/R using loss of function mouse models. Systemic (s) Nox2 KO, sNox4 KO, and cardiac-specific (c) Nox4 KO mice were subjected to I/R (30min/24h). Both myocardial infarct size/area at risk (MI/AAR), evaluated with TTC staining (32 ± 3*,29 ± 4*, 28 ± 6*, 42 ± 4%,  * p 2  -  production, evaluated with lucigenin assays (433 ± 52*,521 ± 88*, 580 ± 106*, 1250 ± 236 RLU), were significantly smaller in sNox2 KO, sNox4 KO, and cNox4 KO than in wild type (WT) mice, suggesting that both Nox2 and Nox4 play an essential role in mediating oxidative stress and myocardial injury in response to I/R. Unexpectedly, however, the MI/AAR was significantly greater in sNox2 KO+cNox4 KO (DKO) mice and transgenic mice (Tg-DN-Nox) with cardiac specific expression of dominant negative Nox, which suppresses both Nox2 and Nox4, than in WT or single KO mice (58±6 * , 65±9 * %), despite significantly lower O 2  -  production in DKO and Tg-DN-Nox4 hearts (257 ± 42 # , 232±12 # , RLU,  # p
A Case of Recurrent Unilateral Periorbital Edema Associated With Subcutaneous Cysticercosis
Authors: Muhammed Razmi T, Satyaswarup Tripathy, Dipankar De, Amanjit Bal, Archana Sundaram, Sanjeev Handa
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Genotype 3 Infection in HIV/HCV co-infected subjects in the DAA era: Real life data from the ICONA/HepaICONA Foundation cohorts
Authors: R. Rossotti, P. Lorenzini, M. Merli, A. Castagna, A. De Luca, A. Antinori, M. Chiamenti, I. Mastrorosa, G. Verucchi, F. Maggiolo, A.D. Monforte, M. Puoti
Journal: Journal of Hepatology (2018)
Adherence to EASL antibiotic treatment recommendations improves the outcomes of patients with cirrhosis and bacterial infections. Results from the ICA Global Study
Authors: S. Piano, V. Singh, P. Caraceni, R. Maiwall, C. Alessandria, J. Fernandez, E. Soares, D.J. Kim, S.E. Kim, M. Marino, J. Vorobioff, R. de Cassia Ribeiro Barea, M. Merli, L. Elkrief, V.M.V. Blasco, A. Krag, S. Singh, L.A. Lesmana, C. Toledo, S. Marciano, V. Xavier, F. Wong, N. Intagliata, L. Rabinowich, L.A. Colombato, S.G. Kim, A. Gerbes, F. Durand, J.P. Roblero, K. Bhamidimarri, T.D. Boyer, M. Maevskaya, E.L. Fassio, H.S. Kim, J.-S. Hwang, A. Gadano, S.K. Sarin, P. Angeli
Journal: Journal of Hepatology (2018)
Towards optimal intraoperative conditions in esophageal surgery: A review of literature for the prevention of esophageal anastomotic leakage
Authors: Boukje Titia Bootsma, Daitlin Esmee Huisman, Victor Dirk Plat, Linda Jeanne Schoonmade, Jurre Stens, Guy Hubens, Donald Leonard van der Peet, Freek Daams
Journal: International Journal of Surgery (2018)
Excipients for the lyoprotection of MAPKAP kinase 2 inhibitory peptide nano-polyplexes
Authors: Alvin J. Mukalel, Brian C. Evans, Kameron V. Kilchrist, Eric A. Dailing, Benjamin Burdette, Joyce Cheung-Flynn, Colleen M. Brophy, Craig L. Duvall
Journal: Journal of Controlled Release (2018)
Clonal interference of signaling mutations worsens prognosis in core-binding factor acute myeloid leukemia
Authors: Raphael Itzykson, Nicolas Duployez, Annette Fasan, Gauthier Decool, Alice Marceau-Renaut, Manja Meggendorfer, Eric Jourdan, Arnaud Petit, Hélène Lapillonne, Jean-Baptiste Micol, Pascale Cornillet-Lefebvre, Norbert Ifrah, Guy Leverger, Hervé Dombret, Nicolas Boissel, Torsten Haferlach, Claude Preudhomme
Journal: Blood (2018)
Long-term outcomes and significance of HBeAg Seroclearance in Chronic Hepatitis B: Novel Predictive Scores for HCC and HBsAg seroclearance
Authors: Y.Y.J. Fung, K.-S. Cheung, D. Wong, L.-Y. Mak, W.P. To, W.-K. Seto, C.L. Lai, M.-F. Yuen
Journal: Journal of Hepatology (2018)
Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?
Authors: Winifred Broekman, Padmini P S J Khedoe, Koen Schepers, Helene Roelofs, Jan Stolk, Pieter S Hiemstra
Journal: Thorax (2018)

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.
Safety and efficacy of Daclatasvir at doses other than 60 mg daily in HIV/HCV co-infected subjects: Data from the ICONA/HepaICONA Foundation cohorts
Authors: R. Rossotti, A. Tavelli, S. Bonora, A. Cingolani, S.L. Caputo, A. Saracino, G. Lapadula, L. Marinaro, C. Uberti-Foppa, C. Mussini, M. Puoti, A.D. Monforte
Journal: Journal of Hepatology (2018)
Age, gender, and performance status effects on efficacy of 3 versus 6 months of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for stage III colon cancer: Phase III ACHIEVE trial as part of the IDEA collaboration.
Authors: Takeshi Kato, Takayuki Yoshino, Takeharu Yamanaka, Masahito Kotaka, Dai Manaka, Tetsuya Eto, Junichi Hasegawa, Akinori Takagane, Masato Nakamura, Yoshinori Munemoto, Fumitaka Nakamura, Hiroyuki Bando, Hiroki Taniguchi, Makio Gamoh, Manabu Shiozawa, Shigetoyo Saji, Yoshihiko Maehara, Tsunekazu Mizushima, Atsushi Ohtsu, Masaki Mori
Journal: Journal of Clinical Oncology (2018)

731 Background: ACHIEVE, a part of the IDEA collaboration, was a multicenter trial randomizing patients with stage III resected colon cancer to either 3 versus 6 months of mFOLFOX6/CAPOX. The primary endpoint was disease-free survival (DFS). We previously reported that the hazard ratios (HRs) of 3 versus 6 months duration in this study according to risk stage (low-risk [T1-3 and N1] or high-risk [T4 or N2]) and regimen (mFOLFOX6 or CAPOX) as well as in overall population were consistent with those observed in the whole IDEA. Methods: ACHIEVE enrolled 1313 patients in Japan between August 2012 and June 2014, out of whom 1291 pts were analyzed for efficacy analysis. As of June 2017, 291 DFS events were observed with a median follow-up time of 39 months. The HR of DFS in the overall population was 0.95 (0.76—1.20) with a 3-year DFS of 80% in 3 months arm and 78% in 6 months arm. In the current study, we investigated subgroup analyses for DFS including age, gender, and ECOG performance status (PS). Results: Outcomes of subgroup analyses are summarized in the Table. With regard to HRs and upper bound on the confidence intervals, the trend of 3 months arm being slightly inferior to 6 months arm in patients with an age of ≥70, female gender, and an ECOG PS of 1; however, there was no evidence of significant interaction across treatment duration and the subgroups. Conclusions: The treatment duration effect did not depend on age, gender, and ECOG PS. Further results according to risk stage and regimen will be presented. Clinical trial information: UMIN 000008543. [Table: see text]
Annals Graphic Medicine - Finding the Funny: Diagnosis/Surgery
Authors: Jade R. Blue
Journal: Annals of Internal Medicine (2018)

Web Exclusives1 May 2018Annals Graphic Medicine - Finding the Funny: Diagnosis/SurgeryFREEJade R. Blue, BA(Hons)Jade R. Blue, BA(Hons)From Ceredigion, Wales, United Kingdom. (J.R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G17-0015 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Ceredigion, Wales, United Kingdom. (J.R.B.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G17-0015.Author/Illustrator Information: Jade Blue is an English-language teacher and trainer based in the United Kingdom, Germany, and Japan. She also works as a research consultant and editor for Cambridge University Press and writes a reflective blog (http://jadeblueefl.wordpress.com). Her research interests focus on drawing in the classroom and learner autonomy. Jade is passionate about doodling and drawing comics and writes a blog about her work (http://jadesdoodles.wordpress.com).Author Contributions: Conception and design: J.R. Blue.Drafting of the article: J.R. Blue.Final approval of the article: J.R. Blue.Administrative, technical, or logistic support: J.R. Blue. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 2018Volume 168, Issue 9Page: W21-W23KeywordsConflicts of interestDisclosure ePublished: 1 May 2018 Issue Published: 1 May 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Review: In cryptogenic stroke with PFO, adding PFO closure to medical therapy reduces recurrence
Authors: Nabeel M. Syed, Wieslaw Oczkowski
Journal: Annals of Internal Medicine (2018)

Source Citation De Rosa S, Sievert H, Sabatino J, et al. Percutaneous closure versus medical treatment in stroke patients with patent foramen ovale: a systematic review and meta-analysis. Ann Intern Med. 2018;168:343-50. 29310133
Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive
Authors: V. Craig Jordan
Journal: Clinical Cancer Research (2018)

Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral selective estrogen receptor degraders (SERD) are required. A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistance to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase I studies. Clin Cancer Res; 24(15); 3480-2. ©2018 AACRSee related articles by Gong et al., p. 3681 and Hamilton et al., p. 3510.
<i>Haldi</i> Ceremony—Historical Use of Turmeric
Authors: Susruthi Rajanala, Neelam A. Vashi
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Corrigendum to “Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine” [Genomics Proteomics Bioinformatics 14 (5) (2016) 298–313]
Authors: Shabbir Ahmed, Zhan Zhou, Jie Zhou, Shu-Qing Chen
Journal: Genomics Proteomics & Bioinformatics (2018)

for any inconvenience caused.
False-positive results with select HIV-1 NAT methods following lentivirus-based tisagenlecleucel therapy
Authors: Theodore W. Laetsch, Shannon L. Maude, Michael C. Milone, Kara L. Davis, Joerg Krueger, Ana Maria Cardenas, Lamis K. Eldjerou, Christopher H. Keir, Patricia A. Wood, Stephan A. Grupp
Journal: Blood (2018)
Urinary epidermal growth factor predicts renal prognosis in antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Liang Wu, Xiao-Qian Li, Tanvi Goyal, Sean Eddy, Matthias Kretzler, Wen-Jun Ju, Min Chen, Ming-Hui Zhao
Journal: Annals of the Rheumatic Diseases (2018)

Introduction The current study aimed to investigate the association between urinary epidermal growth factor (uEGF) and renal disease severity and outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods Intrarenal EGF mRNA expression was extracted from transcriptomic data of microdissected tubulointerstitial compartments of kidney biopsies of patients with AAV. uEGF was measured in 173 patients with AAV in active stage and 143 in remission, and normalised to urine creatinine excretion (uEGF/Cr). The association between uEGF/Cr (or EGF mRNA) and clinical–pathological parameters was tested using linear regression analysis. The ability of uEGF/Cr to predict renal outcomes was analysed using Cox’s regression analysis. Results In patients with AAV, intrarenal EGF mRNA expression was significantly associated with estimated glomerular filtration rate (eGFR)(log 2 ) at time of biopsy (β=0.63, p&lt;0.001). The level of uEGF/Cr was significantly higher in patients in remission than in patients with active disease, both when looking at patients with sequential measurements (2.75±1.03vs 2.08±0.98, p&lt;0.001) and in cross-sectional comparison. uEGF/Cr level was positively associated with eGFR(log 2 ) at time of sampling in both active and remission stage (β=0.60, p&lt;0.001; β=0.74, p&lt;0.001, respectively). Patients with resistant renal disease had significantly lower uEGF/Cr levels than responders (1.65±1.22vs 2.16±1.26, p=0.04). Moreover, after adjusting for other potential predictors, uEGF/Cr was independently associated with composite endpoint of end-stage renal disease or 30% reduction of eGFR (HR 0.61, 95% CI 0.45 to 0.83, p=0.001). Conclusion Lower uEGF/Cr levels are associated with more severe renal disease, renal resistance to treatment and higher risk of progression to composite outcome in patients with AAV.
Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer
Authors: Heba M. Hesham, Deena S. Lasheen, Khaled A.M. Abouzid
Journal: Medicinal Research Reviews (2018)

Abstract Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug‐resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.
Dr Giacomo Rossitto interviews Professor Rhian Touyz, on the translational applications of vascular smooth muscle cell biology in cardiovascular disease
Authors: Giacomo Rossitto, Rhian Touyz
Journal: Cardiovascular Research (2018)

Professor Touyz discusses her passion for translational research and the amazing plasticity of the vascular smooth muscle cell, recently covered in the Cardiovascular Research Spotlight Issues ‘Novel concepts for the role of smooth muscle cells in vascular disease’.
Shedding Light on <i>IDH1</i> Mutation in Gliomas
Authors: Todd C. Hollon, Daniel A. Orringer
Journal: Clinical Cancer Research (2018)

IDH mutation is of central importance in the diagnosis and treatment of gliomas. Fourier-transform infrared spectroscopy, in combination with a supervised machine-learning approach, can be used to detect metabolic alterations induced by IDH1 mutations in a fraction of the time of conventional techniques. Clin Cancer Res; 24(11); 2467-9. ©2018 AACRSee related article by Uckermann et al., p. 2530.