tbuckley/cabot-search huggingface dataset:
Urinary acetylated polyamines in ovarian cancer.
Authors: Johanna Unelma Maenpaa, Riikka Niemi, Antti Roine, Merja Hakkinen, Pekka Kumpulainen, Tuomo Keinanen, Jouko Vepsalainen, Terho Lehtimaki, Niku Oksala
Journal: Journal of Clinical Oncology (2015)

5543 Background: Diacetylated polyamines have been detected in the urine of patients with malignant tumors since 1960s but methodological problems have hindered research. We have recently developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a simultaneous analysis of 14 polyamines in free, mono- and diacetylated forms in human urine, without any derivatization. The present study was undertaken to explore urinary polyamine profiles in the differential diagnostics of ovarian tumors in postmenopausal women. Methods: Forty-five postmenopausal women presenting with an abnormal adnexal mass, and as controls, 21 women with genital prolapse scheduled for surgery, were included prospectively. A morning urine sample was obtained before surgery. The urinary concentrations of 14 polyamines were analyzed simultaneously with LC-MS/MS. Preoperative serum CA12-5 concentrations were also determined, and the risk of malignancy indexes (RMI) calculated in the research arm. The statistical analysis was performed by Wilcoxon rank sum test. Results: There were 22 benign and 23 malignant ovarian tumors (16 low malignant potential and 7 high grade tumors). Of the urinary polyamines, N1,N12-diacetylspermine (DiAcSpm) was the best one to make the distinction between the benign and malignant tumors. The urinary levels of DiAcSpm were similar in controls and in women with benign tumors. However, DiAcSpm was elevated in malignant vs. benign tumors (p = 0.0002), in high grade vs. low grade cancers (p = 0.0003), and in Stage III-IV vs. Stage I-II cancers (p = 0.0007), respectively. Also the difference between benign tumors and early-stage cancer (Stage I-II) was statistically significant (p = 0.006). DiAcSpm had similar specificity (Sp) (65%) and better sensitivity (Se) (91%) (AUC 0.82) as CA12-5 (Sp 65% /Se 68 %, with a CA12-5 cut-off value 35, respectively) (AUC 0.75) and as RMI (Sp 70%/Se 68% with a RMI cut-off value 200, respectively) (AUC 0.72). Conclusions: DiAcSpm was elevated in the urine of patients with ovarian cancer as compared to women with benign tumors and to women with genital prolapse. It seems to be able to detect even early-stage cancer, and its performance seems to be at least comparable to CA12-5 and RMI.
AB0879 An internet trial of cherry extract vs. diet modification: patient characteristics, gout severity and diet characteristics
Authors: J Singh, G Mcgwin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is often treated with life-long pharmacological therapies. Patients are interested in non-pharmacological interventions as adjunct to these therapies. To our knowledge, non-pharmacological have not been studied in detail. <h3>Objectives</h3> To describe the baseline characteristics of patients with gout enrolled in an Internet pilot study comparing the benefits and harms of diet modification to cherry extract intake. <h3>Methods</h3> Patients were enrolled over an 8-month period using the Internet. Diagnosis of gout was confirmed by contacting their health care provider. We describe the baseline characteristics of patients with physician-confirmed gout, who were randomized in the Internet gout study. <h3>Results</h3> We randomized 83 participants in an Internet gout pilot study, randomized to diet modification (n=43) or cherry extract (n=40); 3 patients withdrew before receiving intervention. The mean age of study participants was 56 years, (SD, 16), mean body mass index was 33 kg/m<sup>2</sup> (SD, 10), 73% were male; 67% were white Americans, 25% were African Americans and 7% other/mixed race/ethnicity. Participants took a median of 35 minutes to complete study assessment. Almost half of the participants were taking medications for the treatment of gout: allopurinol, 42%; febuxostat, 1%, probenecid, 0%; colchicine, 29%. Forty-five percent participant were taking none of these medications. 41% smoked ever, 27% were using a special diet and participants had alcohol use an average of 2 days in the last week. Average number of gout flares were four in the last year. Dietary assessments showed that average daily intakes were as follows: calories, 2005; carbohydrate, 221 gm; fat, 82 gm; fiber, 19 gm; caffeine, 197 ml. The HEI2010 score of 64 was comparable to what was observed with NHANES for people in the average age range of this study. <h3>Conclusions</h3> Patients recruited in an Internet gout study, successfully responded to assessments, and had patient characteristics similar to gout populations described previously. The dietary assessments in this provide may provide a unique insight to design interventions to improve diet to improve gout outcomes. <h3>References</h3> Singh JA, Bharat A, Edwards NL. An internet survey of common treatments used by patients with gout including cherry extract and juice and other dietary supplements. J Clin Rheumatol. 2015;21(4):225–226. doi:10.1097/RHU.0000000000000246. PubMed PMID: 26010189. <h3>Acknowledgements</h3> This work was supported by a grant from UAB COERE nad UAB MHRC centers. <h3>Disclosure of Interest</h3> J. Singh Grant/research support from: Savient, Takeda, Consultant for: Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, G. MCGWIN: None declared
Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma
Authors: Elizabeth A. Kelly, Stephane Esnault, Lin Ying Liu, Michael D. Evans, Mats W. Johansson, Sameer Mathur, Deane F. Mosher, Loren C. Denlinger, Nizar N. Jarjour
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Mepolizumab, an IL-5-blocking antibody, reduces exacerbations in patients with severe eosinophilic asthma. Mepolizumab arrests eosinophil maturation; however, the functional phenotype of eosinophils that persist in the blood and airway after administration of IL-5 neutralizing antibodies has not been reported.To determine the effect of anti-IL-5 antibody on the numbers and phenotypes of allergen-induced circulating and airway eosinophils.Airway inflammation was elicited in participants with mild allergic asthma by segmental allergen challenge before and 1 month after a single intravenous 750-mg dose of mepolizumab. Eosinophils were examined in blood, bronchoalveolar lavage, and endobronchial biopsies 48 hours after challenge.Segmental challenge without mepolizumab induced a rise in circulating eosinophils, bronchoalveolar lavage eosinophilia, and eosinophil peroxidase deposition in bronchial mucosa. IL-5 neutralization before allergen challenge abolished the allergen-induced rise in circulating eosinophils and expression of IL-3 receptors, whereas airway eosinophilia and eosinophil peroxidase deposition were blunted but not eliminated. Before mepolizumab treatment, bronchoalveolar lavage eosinophils had more surface IL-3 and granulocyte-monocyte colony-stimulating factor receptors, CD69, CD44, and CD23 and decreased IL-5 and eotaxin receptors than blood eosinophils. This activation phenotype indicated by bronchoalveolar lavage eosinophil surface markers, as well as the release of eosinophil peroxidase by eosinophils in the bronchial mucosa, was maintained after mepolizumab.Mepolizumab reduced airway eosinophil numbers but had a limited effect on airway eosinophil activation markers, suggesting that these cells retain functionality. This observation may explain why IL-5 neutralization reduces but does not completely eradicate asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00802438).
Mutation burden and microsatellite instability in colorectal cancer in Japan and US.
Authors: Masayuki Nagahashi, Toshifumi Wakai, Yoshifumi Shimada, Hiroshi Ichikawa, Hitoshi Kameyama, Takashi Kobayashi, Masato Nakajima, Yusuke Muneoka, Kohei Akazawa, Kazuki Moro, Junko Tsuchida, Daiki Soma, Kizuki Yuza, Takuya Ando, Hiroshi Izutsu, Julie Tse, Shujiro Okuda, Kazuaki Takabe, Alexei Protopopov, Stephen Lyle
Journal: Journal of Clinical Oncology (2016)

e15103 Background: It has been previously documented that high somatic mutational rates in cancer as determined by whole genome sequencing correlates with high microsatellite instability (MSI-H) and mutations in the DNA mismatch repair (MMR) pathway quantified by electrophoretic mobility shift with five mononucleotide repeat markers and immunohistochemical staining. Here we demonstrate that the CancerPlex large-scale genomic sequencing platform can accurately and precisely identify patients with high mutational burden and MSI-H. Further, we demonstrate concordance among independent datasets obtained from either Japanese colorectal patients or US colorectal patients as compared with each other and with the publicly available TCGA database. Methods: A retrospective analysis of genomic data obtained from 201 archived FFPE samples from Japanese patients with colorectal cancer (stage I-IV) and 70 US patients with colorectal cancer were analyzed with the CancerPlex platform. Overall mutational burden, mutations present in DNA MMR genes and microsatellite loci were analyzed and compared to the publicly available TCGA database. In some instances, additional histology was performed on sections to stain for the presence or absence of DNA MMR proteins. Whenever possible, histologic lymphocyte scoring was performed on H&E stained slides. Results: CancerPlex identified 17/201 Japanese cases as hypermutated as determined by mutational burden. This highly correlates with MSI-status and DNA repair defects. These data are similar to those obtained by the TCGA on US patients. These data are also in concordance with CancerPlex data obtained from US clinical cases demonstrating the applicability of a large gene panel to Japanese patients. Conclusions: Given the important differences in treatment strategies for patients with MSI tumors and the emerging utilization of immune checkpoint inhibitors for hypermutated tumors, it is becoming imperative to accurately identify all patients with hypermutated tumors. Large panel genomic profiling offers comprehensive analysis of mutation burden and MSI-status.
Oral delivery of a therapeutic gene encoding glucagon-like peptide 1 to treat high fat diet-induced diabetes
Authors: Md Nurunnabi, Seung-Ah Lee, Vishnu Revuri, Yong Hwa Hwang, Sung Hun Kang, Minhyung Lee, Sungpil Cho, Kwang Jae Cho, Youngro Byun, You Han Bae, Dong Yun Lee, Yong-kyu Lee
Journal: Journal of Controlled Release (2017)
The Evolution of the Use of β-Blockers to Treat Heart Failure
Authors: Finn Waagstein, John D. Rutherford
Journal: Circulation (2017)

Finn Waagstein was born in Copenhagen in 1938. He graduated from Aarhus University Medical School in 1964. He received his cardiology training in the Sahlgrenska University Hospital at the University of Gothenburg, Sweden. He was appointed Associate Professor in 1980, and he assisted in establishing and directing the first Swedish heart transplant program. From 1990 he directed the heart failure and cardiomyopathy research programs. He is currently Professor of Cardiology and senior physician at Wallenberg Laboratory. In 2002, he was awarded the King Faisal International Prize for Medicine.
Genetic analysis of H7N9 highly pathogenic avian influenza virus in Guangdong, China, 2016–2017
Authors: Wen Su, Kit Ling Cheng, Daniel K W Chu, Jie Zhou, Xiaoxiao Mao, Zhifeng Zhong, Yingchao Song, Malik Peiris, Jie Wu, Hui-Ling Yen
Journal: Journal of Infection (2017)
Attempting to Define “Hypoallergenic”
Authors: Matthew J. Zirwas
Journal: JAMA Dermatology (2017)

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
Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
Authors: Wei Zhao, Asif Rasheed, Emmi Tikkanen, Jung-Jin Lee, Adam S Butterworth, Joanna M M Howson, Themistocles L Assimes, Rajiv Chowdhury, Marju Orho-Melander, Scott Damrauer, Aeron Small, Senay Asma, Minako Imamura, Toshimasa Yamauch, John C Chambers, Peng Chen, Bishwa R Sapkota, Nabi Shah, Sehrish Jabeen, Praveen Surendran, Yingchang Lu, Weihua Zhang, Atif Imran, Shahid Abbas, Faisal Majeed, Kevin Trindade, Nadeem Qamar, Nadeem Hayyat Mallick, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Khalid Mehmood, Naveeduddin Ahmed, Irshad Hussain Qureshi, None Tanveer-us-Salam, Wasim Iqbal, Uzma Malik, Narinder Mehra, Jane Z Kuo, Wayne H-H Sheu, Xiuqing Guo, Chao A Hsiung, Jyh-Ming J Juang, Kent D Taylor, Yi-Jen Hung, Wen-Jane Lee, Thomas Quertermous, I-Te Lee, Chih-Cheng Hsu, Erwin P Bottinger, Sarju Ralhan, Yik Ying Teo, Tzung-Dau Wang, Dewan S Alam, Emanuele Di Angelantonio, Steve Epstein, Sune F Nielsen, Børge G Nordestgaard, Anne Tybjaerg-Hansen, Robin Young, Marianne Benn, Ruth Frikke-Schmidt, Pia R Kamstrup, J Wouter Jukema, Naveed Sattar, Roelof Smit, Ren-Hua Chung, Kae-Woei Liang, Sonia Anand, Dharambir K Sanghera, Samuli Ripatti, Ruth J F Loos, Jaspal S Kooner, E Shyong Tai, Jerome I Rotter, Yii-Der Ida Chen, Philippe Frossard, Shiro Maeda, Takashi Kadowaki, Muredach Reilly, Guillaume Pare, Olle Melander, Veikko Salomaa, Daniel J Rader, John Danesh, Benjamin F Voight, Danish Saleheen
Journal: Nature Genetics (2017)
Abstract 16726: High Fat Diet Upregulates Il-6 in the Heart Through Pparα
Authors: Shinichi Oka, Akihiro Shirakabe, Santosh Bhat, Peiyong Zhai, Bonaventure Magrys, Michinari Nakamura, Junichi Sadoshima
Journal: Circulation (2016)

Obesity is a risk factor for diastolic heart failure, but the molecular mechanism by which obesity promotes diastolic dysfunction is not well understood. Obesity induces cardiac remodeling through ...
Access to psychiatrists varies widely across UK, royal college says
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Numbers of consultant psychiatrists vary widely across the UK, the Royal College of Psychiatrists reports as it launches a new campaign to promote the specialty.

People living in Scotland had the best access to specialist psychiatric care, with 10 consultant psychiatrists for every 100 000 people on average, while those in Wales had the poorest access, with six per 100 000. England and …
Using Outreach to Improve Colorectal Cancer Screening
Authors: Michael Pignone, David P. Miller
Journal: JAMA (2017)

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
Janus磁気標的化肝癌化学療法のための「ナノ弾丸」【Powered by NICT】
Authors: Shao Dan, Li Jing, Zheng Xiao, Pan Yue, Wang Zheng, Zhang Ming, Chen Qi-Xian, Dong Wen-Fei, Chen Li
Journal: Biomaterials (2016)
Estrogen Receptor α (ERα) phosphorylated protein expression at serines 104/106, 118 and 167 in tissue microarrays (TMAs) of ERα positive invasive ductal breast tumors
Authors: George Skliris, Brian Rowan, Mariam Al-Dhaheri, Peter Watson, Leigh Murphy
Journal: Cancer Research (2008)

1578   It is well known that  ERα activity is regulated by phosphorylation and important phosphorylation sites are Serines 104, 106, 118 and 167. Phosphorylation at serine 118 (P-S118-ERα) and serine 167 (P-S167-ERα) can be regulated by both ligand independent as well as ligand dependent factors, leading to speculation that altered phosphorylation of these sites may play a role in resistance to endocrine therapy for breast cancer.  Development of novel phospho-specific antibodies have provided powerful tools to measure ERα phosphorylation at S104,6, S118 and S167 by immunohistochemistry (IHC), in human breast tumors and determine any associations of ERα phosphorylation with established clinical markers of prognosis and outcome to endocrine therapy. In the largest series of patient samples to date (n=381), P-S118-ERα was significantly associated with a better response to tamoxifen therapy and with markers of good prognosis in 336 primary ERα positive breast biopsies. Patients with P-S118-ERα positive tumors had a longer relapse free survival, compared to those whose tumors were P-S118-ERα negative ( P =0.044). P-S118-ERα was significantly correlated with progesterone receptor (PgR) [ r =0.22, Spearman coefficient,  P  r =- 0.15,  P =0.0064) .  Similar to P-S118-ERα, a trend to better clinical outcome was also observed for P-S167-ERα in 381 breast biopsies. In addition, P-S167-ERα was also positively correlated with PgR LBA ( r =0.17,  P =0.0006), P-S118-ERα ( r =0.29,  P  r =- 0.20,  P  r =0.30,  P  r =0.14,  P =0.025) and inversely with tumor size ( r =- 0.16,  P =0.012). However, no significant association to clinical outcome was found. These data demonstrate for the first time the detection of multiple phosphorylated forms of ERα in breast cancer and suggest that profiles of phosphorylated ERα isoforms might be useful in selecting subgroups of breast cancer patients that would benefit from endocrine therapy.
Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo
Authors: Max Medina-Ramírez, Fernando Garces, Amelia Escolano, Patrick Skog, Steven W. de Taeye, Ivan Del Moral-Sanchez, Andrew T. McGuire, Anila Yasmeen, Anna-Janina Behrens, Gabriel Ozorowski, Tom L.G.M. van den Kerkhof, Natalia T. Freund, Pia Dosenovic, Yuanzi Hua, Alexander D. Gitlin, Albert Cupo, Patricia van der Woude, Michael Golabek, Kwinten Sliepen, Tanya Blane, Neeltje Kootstra, Mariëlle J. van Breemen, Laura K. Pritchard, Robyn L. Stanfield, Max Crispin, Andrew B. Ward, Leonidas Stamatatos, Per Johan Klasse, John P. Moore, David Nemazee, Michel C. Nussenzweig, Ian A. Wilson, Rogier W. Sanders
Journal: The Journal of Experimental Medicine (2017)

Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resulting in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.
Circulating DNA analysis and concordance with tumor section analysis in the detection of KRAS and BRAF point mutations from metastatic colorectal cancer.
Authors: Alain R. Thierry, Florent Mouliere, Safia El Messaoudi, Fanny Rolet, Pierre-Jean Lamy, Evelyne Lopez-Crapez, Caroline Mollevi, Frederic Bibeau, Virginie Loriot, Celine Gongora, Maguy Del rio, Franck Molina, Muriel Mathonnet, Denis Pezet, Marc Ychou
Journal: Journal of Clinical Oncology (2012)

10505 Background: We developed a specific method for circulating cell-free DNA (ctDNA) enabling the detection of point mutations. CtDNA exists at high level in patients with different types of cancer, and presents great potential in regards, in particular, to its low invasiveness, rapid data turnaround and cost effectiveness. We described here the first blinded prospective study on the comparison of KRAS and BRAF mutational status data obtained from the analysis of ctDNA and tumor section. Methods: Intplex is a refined Q-PCR-based method specifically designed to analyze ctDNA. IntPlex allows not only the detection of point mutations, but also the determination of tumor-ctDNA concentration and fragmentation index simultaneously. Intplex sensitivity is 0.01% (mutant to WT ratio) and is unprecedented among Q-PCR-based methods. The study was conducted from a multicenter cohort of 79 metastatic CRC patients not having received chemo- or radio-therapy within the month prior to blood sample collection. Results: Mutational status could not be determined in 9 samples with one of the two methods. CtDNA analysis showed 100% specificity and 87% sensitivity for KRAS detection (only three samples are misclassified) as compared to tumor section analysis with 23/70 (33%) positive samples, the concordance value being 96%. For BRAF mutation, the method exhibited a specificity and a sensibility of 100% with 5/70 (7%) positive samples (concordance of 100%). When combining KRAS and BRAF mutations, 100% specificity, 89% sensibility and 98% concordance were determined. The three discordant samples may be explained by the malignant genotype of primary tumor versus metastasis, or by the sensitivity of our detection method. The mutation load (median, 12.4%) expressed as the proportion of mutant allele in ctDNA is highly variable (0.037% to 69%) among mutated samples showing a very high inter-individual heterogeneity. Conclusions: Our blinded prospective multicenter study clearly showed for the first time that tumor section analysis might be advantageously replaced by ctDNA analysis, enlarging personalized medicine power for cancer patients.