tbuckley/cabot-search huggingface dataset:
Trisomy 13 and 18—Treatment Decisions in a Stable Gray Zone
Authors: John D. Lantos
Journal: JAMA (2016)

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
Genome-Wide Abnormality Patterns of B-Lineage Acute Lymphoblastic Leukemia in Adults in Comparison with Pediatric Cases
Authors: Bai-Yan Wang, Yuan-Fang Liu, Jing-Yan Tang, Zhao-Hui Gu, Wei-Na Zhang, Zi-Guan Zhang, Qiang Wang, Bing Chen, Sheng-Yue Wang, Yong-Mei Zhu, Jun-Min Li, Jin Wang, Yun Bai, Gang Lu, Min-Jun Yang, Jin-Li Zhang, Jing-Yi Shi, Kan-Kan Wang, Chun-Ming Pan, Jing Lu, Lu Jiang, Yang Li, Chun-Jun Zhao, Jing Chen, Long-Jun Gu, Jian-Qing Mi, Ben-Shang Li, Zhu Chen, Sai-Juan Chen
Journal: Blood (2014)
The Histologic Classifications of Lung Adenocarcinomas Are Discriminable by Unique Lineage Backgrounds
Authors: Haichuan Hu, Zhengliang Sun, Yuan Li, Yiliang Zhang, Hang Li, Yang Zhang, Yunjian Pan, Lei Shen, Rui Wang, Yihua Sun, Haiquan Chen
Journal: Journal of Thoracic Oncology (2016)
Expanding Nilotinib Access in Clinical Trials (ENACT) Study in Adult Patients (Pts) with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) in Blast Crisis (BC), Accelerated Phase (AP), or Chronic Phase (CP): Preliminary Safety Analysis.
Authors: Franck Nicolini, Giuliana Alimena, Haifa-Kathrin Al-Ali, Andrey Zaritskey, Zhixiang Shen, Saengsuree Jootar, Graeme Smith, Yanzhi Hsu, Maria Luisa Veronese, David A. Rizzieri
Journal: Blood (2007)
Abstract 4654: A novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), control hepatocellular carcinoma effectively through inhibiting STAT3
Authors: Rueyshyang Soong
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma(HCC) is one of the most common malignancy, especially in the HBV endemic Asia area. However, there is still lack of effective chemotherapy drug to treat HCC, expect Sorafenib, tyrosine kinase inhibitor, the only FDA approved chemotherapy drug to treat HCC. In this study, we explore the chemotherapeutic properties of a novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), and its ability to manipulate the tumor microenvironment. Unlike the marketed proteasome inhibitor Bortezomib, a chemotherapeutic drug used to treat relapsed multiple myeloma, which inhibits the 20S catalytic core of the 26S proteasome, RA190 irreversibly binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory cap of the 26S proteasome. RA190 inhibits proteasome function and triggers accumulation of polyubiquinated proteins, and has been shown to induce endoplasmic reticulum stress-related apoptosis in HepG2 and Hepa3B hepatoma cell lines. We also found RA190 We observed a significant apoptosis of cancer cells after treatment of RA190. These changes in cancer cell lines were caused by reduction of STAT3 activity. We also proved the treatment effect of RA190 in orthotropic HCC animal models. The initial study of this novel proteasome inhibitor demonstrates its potential as an effective HCC therapy. Citation Format: Rueyshyang Soong. A novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), control hepatocellular carcinoma effectively through inhibiting STAT3. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4654.
Effect of the timing of sunitinib administration on the predictive value of biomarkers in renal cell cancer (mRCC).
Authors: John Michael Louis Ebos, Michalis Mastri, John M. Hudson, Christina R. Lee, Amanda Tracz, Kristopher Attwood, Peter N. Burns, Robert S. Kerbel, Georg A. Bjarnason
Journal: Journal of Clinical Oncology (2015)

11096 Background: Angiogenic cytokines influence tumor growth in mRCC patients (pts) and are modulated by diurnal fluctuations. The timing of antiangiogenic tyrosine kinase inhibitor (TKIs) administration may impact efficacy, toxicity and biomarker expression. Methods: 34 mRCC pts, randomized to receive sunitinib at 8 AM or 8 PM on a 28 days (d) on/14 d off schedule, had blood sampling before and during Rx on the first cycle for potential biomarkers including: sunitinib and metabolite blood levels, 18 circulating angiogenic factors (CAFs) and 4 circulating angiogenic cell types including circulating endothelial cells (CECs). Results: Spearman analysis of the 24 biomarkers obtained on d 14 showed significantly better correlations with OS and PFS in PM-treated pts. Three CAFs in PM-treated pts significantly correlated with both OS and PFS. These included Leptin (r = 0.7182, p = 0.0128 and r = 0.8364, p = 0.0022, respectively), IL-8 (r = -0.635, p = 0.0485 and r = -0.5735, p = 0.031, respectively) and PDGF-ββ (r = -0.8455, p = 0.001 and r = -0.6818, p = 0.0251, respectively). Circulating Leptin levels correlated with sunitinib-metabolite levels in both AM and PM-treated patients (r = 0.7832, p = 0.0038 and r = 0.6848, p = 0.0347, respectively). Conclusions: This is the first study to suggest that a consistent sunitinib dosing time may improve the predictive value of some biomarkers for OS and PFS in mRCC pts. A panel of predictive circulating cytokines (Leptin, IL-8, and PDGF-ββ) was identified for pts receiving Rx at night. Furthermore, Leptin may have value as a biomarker of sunitinib-metabolite levels independent of dosing timing. The potential impact of Rx-time on the predictive value of some biomarkers may have hampered the discovery of consistently useful predictive biomarkers for sunitinib efficacy in mRCC patients to date. Clinical trial information: OCT125.
Immune perturbations in HIV-1–infected individuals who make broadly neutralizing antibodies
Authors: M. Anthony Moody, Isabela Pedroza-Pacheco, Nathan A. Vandergrift, Cecilia Chui, Krissey E. Lloyd, Robert Parks, Kelly A. Soderberg, Ane T. Ogbe, Myron S. Cohen, Hua-Xin Liao, Feng Gao, Andrew J. McMichael, David C. Montefiori, Laurent Verkoczy, Garnett Kelsoe, Jinghe Huang, Patrick R. Shea, Mark Connors, Persephone Borrow, Barton F. Haynes
Journal: Science Immunology (2016)

Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1-infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1-infected individuals who made bnAbs and compared them with those who did not do so, and determined immune traits associated with the ability to produce bnAbs. HIV-1-infected individuals with bnAbs had a higher frequency of blood autoantibodies, a lower frequency of regulatory CD4
When hospitals switch to electronic records
Authors: Robert L Wears
Journal: BMJ (2016)

If nothing goes wrong, is everything all right?

In a linked paper, Barnett and colleagues (doi:10.1136/bmj.i3835) studied the consequences of one of the most disruptive events a hospital can experience, short of mass casualty incidents or natural disasters—implementing a new electronic health record (EHR) system.1 Reports of unintended consequences2 and patient harms3 from these events have raised understandable concerns about how well we manage them. The investigators addressed these concerns by estimating changes in a set of outcome measures at several months before and after implementation of a new EHR in 17 US hospitals; they then compared those changes with changes in the same measures in 399 control hospitals over the same regions and dates. They included only “big bang” implementations, in which all clinical functions transition to the new system on a single “go live” date; these are likely more disruptive than gradual roll-outs. The primary outcomes were changes in 30 day mortality and readmissions; …
Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse
Authors: M. Bertolini, M. Pretzlaff, M. Sulk, M. Bähr, J. Gherardini, Y. Uchida, M. Reibelt, M. Kinori, A. Rossi, T. Bíró, R. Paus
Journal: British Journal of Dermatology (2016)

Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA.To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs?Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry.Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP(+) nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed.These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate 'HF-IP guardian' that may be therapeutically exploited to inhibit the progression of AA lesions.
Abstract 38: The clinical significance of GLUT1 expression in gastrointestinal stromal tumor
Authors: Daisuke Kuroda, Junji Kurashige, Masaaki Iwatsuki, Tsugio Eto, Yuka Tamaoki, Mayuko Ohuchi, Kenichi Nakamura, Ryuma Tokunaga, Hironobu Shigaki, Hiromitsu Hayashi, Takatsugu Ishimoto, Yoshifumi Baba, Yasuo Sakamoto, Naoya Yoshida, Hideo Baba
Journal: Cancer Research (2016)

Abstract Background: Gastrointestinal stromal tumor (GIST) is, though it is as rare as its incidence is about 7 to 20 cases per million population per year, one of the most common non-epithelial malignant tumors of the gastrointestinal tract. Recently it was reported that Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is useful in diagnosis and evaluation of malignant grade of GIST. At the same time, expression of glucose transporter 1 (GLUT1), which is a membranous protein facilitates the transport of glucose across the plasma membranes into cells, was reported to be correlated with maximum standardized uptake value (SUVmax) in PET/CT and malignant grade of various kinds of cancers. In this study, the correlation of GLUT1 expression with malignant grade in GIST was investigated. Methods: We evaluated the protein expression of GLUT1 in immunohistochemistry in the surgically resected specimens in 67 GIST cases, and analyzed the correlation of the other clinicopathological factors. Results: The number of cases in which the expression of GLUT1 judged to be confirmed in immunohistochemistry was 45 (73.7%). GLUT1 expression group had significantly higher preoperative SUVmax in PET/CT than GLUT1 non-expression group (p = 0.03), had larger tumors in diameter (p = 0.015), and was more malignant by Fletcher classification (p&amp;lt;0.01). Additionally, tumor rupture rate tended to be higher in GLUT1 expression group, though there is no tendency of the correlation with tumor necrosis. Eventually, relapse free survival, as not significantly, tend to be shorter in GLUT1 expression group. Conclusion: In our study, expression of GLUT1 is correlated with malignant grade in GIST. GLUT1 expression might be a phase of higher metabolic and malignant activity of GIST cells. GLUT1 might be a useful prognostic marker in GIST cases. Citation Format: Daisuke Kuroda, Junji Kurashige, Masaaki Iwatsuki, Tsugio Eto, Yuka Tamaoki, Mayuko Ohuchi, Kenichi Nakamura, Ryuma Tokunaga, Hironobu Shigaki, Hiromitsu Hayashi, Takatsugu Ishimoto, Yoshifumi Baba, Yasuo Sakamoto, Naoya Yoshida, Hideo Baba. The clinical significance of GLUT1 expression in gastrointestinal stromal tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 38.
Chanarin-Dorfman syndrome caused by a novel splice site mutation in ABHD5 (vol 158, pg 1378, 2008)
Authors: S. Badeloe, M. van Geel, Lily Nagtzaam, M. E. Rubio-Gozalbo, R. L. Oei, P. M. Steiljen, M. A. M. van Steensel
Journal: British Journal of Dermatology (2008)
Impact of the national prevention policy and scrum law changes on the incidence of rugby-related catastrophic cervical spine injuries in French Rugby Union
Authors: E Reboursiere, Y Bohu, D Retière, B Sesboüé, V Pineau, J P Colonna, J P Hager, J C Peyrin, J Piscione
Journal: British Journal of Sports Medicine (2016)

Catastrophic cervical spine injuries are rare in rugby union but require close monitoring. The aim of this study was to analyse the incidence of severe cervical spine injuries and determine the impact of a national prevention programme and new scrum rules implemented by the French Rugby Union.A prospective study was performed between 2006 and 2013 including all players affiliated to the French Rugby Union. All cervical spine injuries resulting in death, tetraplegia or a permanent neurological deficit were included. Prevention programmes were implemented from 2007 to 2013 and a change in scrum rules in 2010. To measure the impact of rule changes, results between 2006-2010 and 2010-2013 were compared using a Poisson regression.Altogether, 31 injuries were observed and the mean annual incidence was 1.6 per 100 000 players. There were significantly more injuries in senior players compared to junior players (3.5 vs 0.6 per 100 000 players; CI 95% (2.1 to 4.9) vs (0.1 to 1.0)). Incidence decreased from 1.8 in 2006 to 1.0 per 100 000 players in 2013 (p<0.0001). After 2010, there were significantly fewer injuries during scrums (p=0.02). In contrast, there were significantly more injuries in backs during 2010-2013 compared to 2006-2010 (p=0.003).The incidence of catastrophic cervical spine injuries has declined in French Rugby Union. The implementation of specific prevention programmes and scrum law changes has notably resulted in a decrease in scrum injuries in forwards. This prospective study should be continued to monitor the future progression of injuries and adapt prevention programmes accordingly.
Abstract 4285: Intra-individual variation in circulating miRNA expression levels in human plasma samples
Authors: Jie Wu, Hui Cai, Yong-Bing Xiang, Charles Matthews, Fei Ye, Wei Zheng, Qiuyin Cai, Xiao-Ou Shu
Journal: Cancer Research (2016)

Abstract Circulating miRNAs as possible non-invasive biomarkers for disease risk assessment and cancer early diagnosis has attracted increasing interest. Little information, however, is available regarding the intra-individual variation of circulating miRNA levels. We measured miRNA expression in repeated plasma samples that were collected 6 to 12 months apart from 53 healthy individuals participating in a sub-study nested in the Shanghai Women's and Shanghai Men's Health Studies. Total RNA, including miRNA, was isolated from plasma using Qiagen's miRNeasy Serum/Plasma Kit. Three synthetic spike-in RNA oligos (osa-miR414, cel-miR248, and ath-miR159a) were added to control for variances in the starting material and the efficiency of RNA extraction. NanoString's Human v2 miRNA Expression Assay, which includes CodeSets of probes specific for 800 common human miRNAs, was used for the miRNA assays. The derived miRNA counts were first corrected by subtracting the background counts and then were normalized by using the average count from three spike-in oligos and the top fifty miRNAs that gave most significant hybridization signals. The intra-individual variation was evaluated by an intra-class correlation coefficient (ICC). A total of 185 miRNAs were detected in at least 10% of samples. The detectable rate varied for each miRNA, with 69 and 44 miRNAs being detected in 50% and 75% of samples, respectively. The median ICC was 0.46 for all of the 185 detectable miRNAs. Among them, 41% (75 miRNAs) had an ICC ≥0.5, and 42 miRNAs had an ICC ≥0.6. The ICC is higher for miRNAs with higher expression levels and higher detection rates, when compared to their counterparts with lower expression or detection rates. In summary, we found that 185 miRNAs were expressed in at least 10% of plasma samples, and 69 miRNAs in 50% of samples from healthy Chinese men and women, and that 75 of these miRNAs had an ICC ≥0.5. These results suggest that common circulating miRNAs can serve as reliable biomarkers for epidemiological and clinical research. Citation Format: Jie Wu, Hui Cai, Yong-Bing Xiang, Charles Matthews, Fei Ye, Wei Zheng, Qiuyin Cai, Xiao-Ou Shu. Intra-individual variation in circulating miRNA expression levels in human plasma samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4285.
Abstract 15656: Noninvasive Evaluation of Benign and Malignant Early Repolarization With a New Concept of Late Potentials in the High Resolution Magnetocardiography
Authors: Naotsugu Iwakami, Takeshi Aiba, Shiro Kamakura, Hiroshi Takaki, Kouhei Ishibashi, Ikutaro Nakajima, Yuko Yamada, Kouji Miyamoto, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Kengo Kusano, Wataru Shimizu, Masaru Sugimachi
Journal: Circulation (2013)
Abstract 3760: XCE853 is a promising protein disulfide isomerase (PDI) inhibitor exhibiting a strong inhibitory activity in preclinical tumor models
Authors: Gregoire P. Prevost, Marine Garrido, Maria Serova, Jean François Briand, Mathieu Gutmann, Patrick Ladam, Denis Carniato, Annemilai Tijeras-Raballand, Armand De Grammont, Anne Chauchereau, Marc-Henry Pitty, Paul Foster
Journal: Cancer Research (2016)

Abstract Protein disulfide isomerase (PDI) is a chaperone protein that regulates oxidative protein folding as well as cell viability. Increased PDI levels have been documented in a variety of human cancers, including ovarian, prostate, and lung cancers. Inhibition of PDI activity leads to apoptosis in cancer, suggesting that PDI is a promising druggable target. XCE853 is a synthetic small molecule displaying an excellent docking with the human PDI. XCE853 inhibits in vitro recombinant PDI activity. In addition, the proliferation of a large panel of human tumor cells is blocked by XCE853 with IC50s in the nanomolar range through an irreversible cytolysis. XCE853 is also active on a large panel of drug resistant human cancer cells. XCE853 induced an irreversible cytolysis of human tumor cells after a short in vitro exposure independently of efflux pumps leading to a tumor cell death by autophagy and particles release (vesicles or protein aggregates). In addition, the ex-vivo approach using fresh human tumor explants cultivated in 3 dimensions with low concentrations of XCE853 has shown a strong decrease of the proliferation (KI-67 labeling) in several tumor types. Finally, XCE853 displayed excellent oral bioavailability in mice and was able to block the growth of several human cancers using in vivo xenograft models leading to a complete tumor growth arrest even after the cessation of the treatment. Altogether, these data support further efforts on this drug candidate to initiate the preclinical studies and to define the most relevant human tumor types. Citation Format: Gregoire P. Prevost, Marine Garrido, Maria Serova, Jean François Briand, Mathieu Gutmann, Patrick Ladam, Denis Carniato, Annemilai Tijeras-Raballand, Armand De Grammont, Anne Chauchereau, Marc-Henry Pitty, Paul Foster. XCE853 is a promising protein disulfide isomerase (PDI) inhibitor exhibiting a strong inhibitory activity in preclinical tumor models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3760.
Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?
Authors: Alexandra Fouts, Laura Pyle, Liping Yu, Dongmei Miao, Aaron Michels, Jeffrey Krischer, Jay Sosenko, Peter Gottlieb, Andrea K. Steck
Journal: Diabetes Care (2016)

OBJECTIVE To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. RESULTS Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA1c, and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P &amp;lt; 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P &amp;lt; 0.0001). CONCLUSIONS ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future.