tbuckley/cabot-search huggingface dataset:
皮膚遺伝子治療に対する高分岐ポリ(β‐アミノエステル)
Authors: Zhou Dezhong, Gao Yongsheng, Aied Ahmed, Cutlar Lara, Igoucheva Olga, Newland Ben, Alexeeve Vitali, Greiser Udo, Uitto Jouni, Wang Wenxin
Journal: Journal of Controlled Release (2016)
SP0033 The eular campaign “dont delay connect today” and how organisations can get involved
Authors: J Church
Journal: Annals of the Rheumatic Diseases (2017)

Arthritis is a chronic disease with multiple co-morbidities. With the development of powerful biologic drugs, improvements in care pathways for patients and very effective self-management interventions, early diagnosis and intervention can lead to significant improvements in liefstyle, physical movement, incerased well-being and work force participation. Despite its significant impact on the population and the cost to the economy, Arthritis still remains an underfunded subspecialty within the health systems and one that is shrouded in public myth. The EULAR campaign "Done Delay, Connect Today", aims to promote early intervention by encouraging those with typical symptoms to take action and consult their doctor at the earliest possible opportunity. The campaign which will be adopted and executted across all PARE members also aims to dispel the myths and educate the public about the seriosness of arthritis and the need to taek action. <h3>Disclosure of Interest</h3> None declared
Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
Authors: Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T. Fanta, Kimberly C. Banks, In Sil Choi, David E. Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B. Lanman, Lyudmila Bazhenova, Razelle Kurzrock
Journal: Cancer Research (2017)

Abstract Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419–27. ©2017 AACR.
Validation of kinetic modeling of progesterone release from polymeric membranes
Authors: Analia Irma Romero, Mercedes Villegas, Alicia Graciela Cid, Mónica Liliana Parentis, Elio Emilio Gonzo, José María Bermúdez
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Mathematical modeling in drug release systems is fundamental in development and optimization of these systems, since it allows to predict drug release rates and to elucidate the physical transport mechanisms involved. In this paper we validate a novel mathematical model that describes progesterone (Prg) controlled release from poly-3-hydroxybutyric acid (PHB) membranes. A statistical analysis was conducted to compare the fitting of our model with six different models and the Akaike information criterion (AIC) was used to find the equation with best-fit. A simple relation between mass and drug released rate was found, which allows predicting the effect of Prg loads on the release behavior. Our proposed model was the one with minimum AIC value, and therefore it was the one that statistically fitted better the experimental data obtained for all the Prg loads tested. Furthermore, the initial release rate was calculated and therefore, the interface mass transfer coefficient estimated and the equilibrium distribution constant of Prg between the PHB and the release medium was also determined. The results lead us to conclude that our proposed model is the one which best fits the experimental data and can be successfully used to describe Prg drug release in PHB membranes.
Heme Induces NLRP3 Inflammasome Formation in Primary Human Macrophages and May Propagate Hemolytic Inflammatory Processes By Inducing S100A8 Expression
Authors: Angelica A. Silveira, Clare Cunningham, Emma Corr, Wilson Alves Ferreira, Fernando F. Costa, Camila B. Almeida, Nicola Conran, Aisling Dunne
Journal: Blood (2016)
Changes in magnetic resonance imaging scores and ventilation inhomogeneity in children with cystic fibrosis pulmonary exacerbations
Authors: Hartmut Grasemann, Pierluigi Ciet, Reshma Amin, Nancy McDonald, Michelle Klingel, Harm A.W.M. Tiddens, Felix Ratjen, Lars Grosse-Wortmann
Journal: European Respiratory Journal (2017)

Acute pulmonary exacerbations (aPEs) in patients with cystic fibrosis (CF) often result in incomplete recovery of lung function despite treatment, and are associated with lung function decline over time [1, 2]. Monitoring is therefore important to detect aPEs early and to track treatment responses. Recent studies testing pulmonary function with multiple breath washout (MBW) have shown that the lung clearance index (LCI), the main outcome measure of MBW, is a sensitive tool to measure early changes in the CF lung [3, 4]. However, the potential role of MBW and LCI in more advanced CF lung disease is currently unclear. In fact, a recent study demonstrated heterogeneous responses in LCI, with a significant proportion of patients with CF showing worsening of LCI with treatment for aPEs [5]. Resolution of mucus plugging, resulting in recruitment of poorly ventilated areas of the lung to MBW, would potentially explain the discordant changes in pulmonary function testing by spirometry and LCI with treatment. Resolution of mucus plugging may explain worsening LCI during pulmonary exacerbation treatment in children with CF <http://ow.ly/LTLm30dp6hS>
Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management
Authors: Delan Devakumar, Alasdair Bamford, Marcelo U Ferreira, Jonathan Broad, Richard E Rosch, Nora Groce, Judith Breuer, Marly A Cardoso, Andrew J Copp, Paula Alexandre, Laura C Rodrigues, Ibrahim Abubakar
Journal: The Lancet Infectious Diseases (2017)
Human Pluripotent Stem Cell–Derived <i>TSC2</i>-Haploinsufficient Smooth Muscle Cells Recapitulate Features of Lymphangioleiomyomatosis
Authors: Lisa M. Julian, Sean P. Delaney, Ying Wang, Alexander A. Goldberg, Carole Doré, Julien Yockell-Lelièvre, Roger Y. Tam, Krinio Giannikou, Fiona McMurray, Molly S. Shoichet, Mary-Ellen Harper, Elizabeth P. Henske, David J. Kwiatkowski, Thomas N. Darling, Joel Moss, Arnold S. Kristof, William L. Stanford
Journal: Cancer Research (2017)

Lymphangioleiomyomatosis (LAM) is a progressive destructive neoplasm of the lung associated with inactivating mutations in the TSC1 or TSC2 tumor suppressor genes. Cell or animal models that accurately reflect the pathology of LAM have been challenging to develop. Here, we generated a robust human cell model of LAM by reprogramming TSC2 mutation-bearing fibroblasts from a patient with both tuberous sclerosis complex (TSC) and LAM (TSC-LAM) into induced pluripotent stem cells (iPSC), followed by selection of cells that resemble those found in LAM tumors by unbiased in vivo differentiation. We established expandable cell lines under smooth muscle cell (SMC) growth conditions that retained a patient-specific genomic TSC2+/- mutation and recapitulated the molecular and functional characteristics of pulmonary LAM cells. These include multiple indicators of hyperactive mTORC1 signaling, presence of specific neural crest and SMC markers, expression of VEGF-D and female sex hormone receptors, reduced autophagy, and metabolic reprogramming. Intriguingly, the LAM-like features of these cells suggest that haploinsufficiency at the TSC2 locus contributes to LAM pathology, and demonstrated that iPSC reprogramming and SMC lineage differentiation of somatic patient cells with germline mutations was a viable approach to generate LAM-like cells. The patient-derived SMC lines we have developed thus represent a novel cellular model of LAM that can advance our understanding of disease pathogenesis and develop therapeutic strategies against LAM. Cancer Res; 77(20); 5491-502. ©2017 AACR.
Chess Study Revives Debate Over Cognition-Enhancing Drugs
Authors: Jeff Lyon
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
Efficacy of lenalidomide maintenance (LEN) therapy versus placebo, after melphalan, prednisone, bortezomib (MPV) induction therapy in patients (pts) with newly diagnosed multiple myeloma (NDMM): The ARUMM (MM-026) trial.
Authors: Cyrille Hulin, Christian Jacques, Amine Bensmaine, Honeylet Wortman-Vayn, Wei Sun, Anjan Thakurta, Thierry Facon
Journal: Journal of Clinical Oncology (2014)

TPS8629 Background: Improved progression-free survival (PFS) benefits have been reported in several large phase 3 trials with LEN therapy (Attal NEJM 2012, Facon ASH 2013, McCathy NEJM 2012, Palumbo NEJM 2012, Palumbo ASCO 2013), overall survival (OS) advantage has also been observed in some of them. Treatment with LEN therapy has also been well tolerated. Effective continuous maintenance therapy is of great importance to prolong response duration and consequently improved disease outcomes (PFS, OS). Methods: ARUMM is a phase 3b, double-blind, 2-arm study which will compare efficacy and safety of continuous maintenance therapy with LEN vs. placebo until progressive disease (PD) in NDMM pts. Inclusion criteria are: pts ≥ 65 yrs or < 65 yrs not candidates for stem cell transplantation, and who achieved ≥ partial response (PR) as best overall response after 6 to 9 cycles of MPV induction therapy. Exclusion criteria include: prior treatment (Tx) with other anti-myeloma therapies than MPV, and pts who did not reach ≥ PR after MPV induction Tx. Eligible pts will be randomized either to LEN (10 mg/day days 1–21/28-day cycle) or placebo (days 1–21/28-day cycle) until PD. Pts will be stratified according to disease stage (ISS) and prognostic factors at initial diagnosis, and response to MPV induction therapy. PFS is the primary study endpoint and defined as the time from randomization to PD based on IMWG criteria and reviewed by an independent physician or death from any cause, whichever occurs first; secondary endpoints will include overall response rate, OS, quality of life, cytogenetics and tolerability. Safety will include adverse events (AEs), laboratory abnormalities, serious AEs, and second primary malignancies. Exploratory endpoints will include the assessment of minimal residual disease. Approximately 351 pts will be enrolled. The trial has been powered at 80% with a hazard ratio of 0.66 (LEN vs. placebo) for PFS between the 2 arms (29 vs. 19 months) at the 2-sided significance level of 0.05. EudraCT Number: 2013-001729-26 Clinical trial information: 2013-001729-26.
顆粒球形成:SWI/SNFクロマチンリモデリング複合体のSMARCD2サブユニットはCEBPε依存的な機構により顆粒球形成を仲介する
Authors: Priam Pierre, Krasteva Veneta, Rousseau Philippe, Gaboury Louis, Sauvageau Guy, Lessard Julie A, D’Angelo Giovanni
Journal: Nature Genetics (2017)
Synergistic antitumor effect mediated by a paclitaxel-conjugated polymeric micelle-coated oncolytic adenovirus
Authors: Dayananda Kasala, Soo-Hwan Lee, Jin Woo Hong, Joung-Woo Choi, Kihoon Nam, Yoon Ho Chung, Sung Wan Kim, Chae-Ok Yun
Journal: Biomaterials (2017)
Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth
Authors: Shannon Lange, Charlotte Probst, Gerrit Gmel, Jürgen Rehm, Larry Burd, Svetlana Popova
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Prevalence estimates are essential to effectively prioritize, plan, and deliver health care to high-needs populations such as children and youth with fetal alcohol spectrum disorder (FASD). However, most countries do not have population-level prevalence data for FASD. <h3>Objective</h3> To obtain prevalence estimates of FASD among children and youth in the general population by country, by World Health Organization (WHO) region, and globally. <h3>Data Sources</h3> MEDLINE, MEDLINE in process, EMBASE, Education Resource Information Center, Cumulative Index to Nursing and Allied Health Literature, Web of Science, PsychINFO, and Scopus were systematically searched for studies published from November 1, 1973, through June 30, 2015, without geographic or language restrictions. <h3>Study Selection</h3> Original quantitative studies that reported the prevalence of FASD among children and youth in the general population, used active case ascertainment or clinic-based methods, and specified the diagnostic guideline or case definition used were included. <h3>Data Extraction and Synthesis</h3> Individual study characteristics and prevalence of FASD were extracted. Country-specific random-effects meta-analyses were conducted. For countries with 1 or no empirical study on the prevalence of FASD, this indicator was estimated based on the proportion of women who consumed alcohol during pregnancy per 1 case of FASD. Finally, WHO regional and global mean prevalence of FASD weighted by the number of live births in each country was estimated. <h3>Main Outcomes and Measures</h3> Prevalence of FASD. <h3>Results</h3> A total of 24 unique studies including 1416 unique children and youth diagnosed with FASD (age range, 0-16.4 years) were retained for data extraction. The global prevalence of FASD among children and youth in the general population was estimated to be 7.7 per 1000 population (95% CI, 4.9-11.7 per 1000 population). The WHO European Region had the highest prevalence (19.8 per 1000 population; 95% CI, 14.1-28.0 per 1000 population), and the WHO Eastern Mediterranean Region had the lowest (0.1 per 1000 population; 95% CI, 0.1-0.5 per 1000 population). Of 187 countries, South Africa was estimated to have the highest prevalence of FASD at 111.1 per 1000 population (95% CI, 71.1-158.4 per 1000 population), followed by Croatia at 53.3 per 1000 population (95% CI, 30.9-81.2 per 1000 population) and Ireland at 47.5 per 1000 population (95% CI, 28.0-73.6 per 1000 population). <h3>Conclusions and Relevance</h3> Globally, FASD is a prevalent alcohol-related developmental disability that is largely preventable. The findings highlight the need to establish a universal public health message about the potential harm of prenatal alcohol exposure and a routine screening protocol. Brief interventions should be provided, where appropriate.
in vivo ROS応答標的腫瘍治療のための両親媒性ミセルの光増感剤増強分解【Powered by NICT】
Authors: Dai Liangliang, Yu Yonglin, Luo Zhong, Li Menghuan, Chen Weizhen, Shen Xinkun, Chen Feng, Sun Qiang, Zhang Qingfeng, Gu Hao, Cai Kaiyong
Journal: Biomaterials (2016)
Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association
Authors: Brian Feingold, William T. Mahle, Scott Auerbach, Paula Clemens, Andrea A. Domenighetti, John L. Jefferies, Daniel P. Judge, Ashwin K. Lal, Larry W. Markham, W. James Parks, Takeshi Tsuda, Paul J. Wang, Shi-Joon Yoo
Journal: Circulation (2017)

For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes.
慢性社会的ストレスとテロメア長の間の関係の系統的レビュー:ライフコースの展望【Powered by NICT】
Authors: Oliveira Bruna Silva, Zunzunegui Maria Victoria, Quinlan Jacklyn, Fahmi Hassan, Tu Mai Thanh, Guerra Ricardo Oliveira
Journal: Ageing Research Reviews (2016)
Issues with European guidelines for phenylketonuria
Authors: Peter Burgard, Kurt Ullrich, Diana Ballhausen, Julia B Hennermann, Carla E M Hollak, Mirjam Langeveld, Daniela Karall, Vassiliki Konstantopoulou, Esther M Maier, Frauke Lang, Robin Lachmann, Elaine Murphy, Sven Garbade, Georg F Hoffmann, Stefan Kölker, Martin Lindner, Johannes Zschocke
Journal: The Lancet Diabetes & Endocrinology (2017)
Abstract #LB-9: Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation
Authors: Yong Liao, Yongkun Wei, Xiaoyan Zhou, Jer-Yen Yang, Chun Dai, Yun-Ju Chen, Nitin Agarwal, Dos Sarbassov, Daren Shi, Dihua Yu, Mien-Chie Hung
Journal: Cancer Research (2009)

The serine/threonine protein kinase B (PKB, also known as Akt) plays a pivotal role in diverse cellular functions. Activation of Akt requires phosphorylation of Akt at two critical sites: one within the activation loop (T308 for Akt1) and the other with the C-terminus (S473 for Akt1). Elevated expression of activated Akt has been detected in a wide variety of human cancers, yet the mechanism of Akt protein stability regulation remains unclear. In the current study, we showed a strong correlation between the expression levels of an oncogenic peptidyl-prolyl cis/trans isomerase Pin1 and levels of Akt phosphorylation at S473 in multiple cancer types (P    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-9.
The neoepitope landscape in pediatric cancers
Authors: Ti-Cheng Chang, Robert A. Carter, Yongjin Li, Yuxin Li, Hong Wang, Michael N. Edmonson, Xiang Chen, Paula Arnold, Terrence L. Geiger, Gang Wu, Junmin Peng, Michael Dyer, James R. Downing, Douglas R. Green, Paul G. Thomas, Jinghui Zhang
Journal: Genome Medicine (2017)

Neoepitopes derived from tumor-specific somatic mutations are promising targets for immunotherapy in childhood cancers. However, the potential for such therapies in targeting these epitopes remains uncertain due to a lack of knowledge of the neoepitope landscape in childhood cancer. Studies to date have focused primarily on missense mutations without exploring gene fusions, which are a major class of oncogenic drivers in pediatric cancer.We developed an analytical workflow for identification of putative neoepitopes based on somatic missense mutations and gene fusions using whole-genome sequencing data. Transcriptome sequencing data were incorporated to interrogate the expression status of the neoepitopes.We present the neoepitope landscape of somatic alterations including missense mutations and oncogenic gene fusions identified in 540 childhood cancer genomes and transcriptomes representing 23 cancer subtypes. We found that 88% of leukemias, 78% of central nervous system tumors, and 90% of solid tumors had at least one predicted neoepitope. Mutation hotspots in KRAS and histone H3 genes encode potential epitopes in multiple patients. Additionally, the ETV6-RUNX1 fusion was found to encode putative neoepitopes in a high proportion (69.6%) of the pediatric leukemia harboring this fusion.Our study presents a comprehensive repertoire of potential neoepitopes in childhood cancers, and will facilitate the development of immunotherapeutic approaches designed to exploit them. The source code of the workflow is available at GitHub ( https://github.com/zhanglabstjude/neoepitope ).
Genomic Evolution of Breast Cancer Metastasis and Relapse
Authors: Lucy R. Yates, Stian Knappskog, David Wedge, James H.R. Farmery, Santiago Gonzalez, Inigo Martincorena, Ludmil B. Alexandrov, Peter Van Loo, Hans Kristian Haugland, Peer Kaare Lilleng, Gunes Gundem, Moritz Gerstung, Elli Pappaemmanuil, Patrycja Gazinska, Shriram G. Bhosle, David Jones, Keiran Raine, Laura Mudie, Calli Latimer, Elinor Sawyer, Christine Desmedt, Christos Sotiriou, Michael R. Stratton, Anieta M. Sieuwerts, Andy G. Lynch, John W. Martens, Andrea L. Richardson, Andrew Tutt, Per Eystein Lønning, Peter J. Campbell
Journal: Cancer Cell (2017)

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.