tbuckley/cabot-search huggingface dataset:
Abstract P5-06-03: A solution to the APOBEC mutation paradox in breast cancer
Authors: RS Harris, GJ Starrett, JL McCann, MA Carpenter
Journal: Cancer Research (2017)

Abstract Breast cancer has a major genetic component, and individual tumors can have thousands to tens-of-thousands of mutations. Large proportions are cytosine mutations in TCA and TCT trinucleotide motifs. A variety of studies have attributed this mutation signature to the APOBEC family of DNA cytosine deaminases, with previous literature favoring APOBEC3B as the most likely enzyme to bee responsible (from a total of nine active family members). However, breast tumor genomic DNA sequences from patients with a naturally occurring germline deletion of the entire APOBEC3B gene still show an intact APOBEC mutation signature. To resolve this paradox, we tested the hypothesis that the only other functionally dimorphic APOBEC family member, APOBEC3H, may be responsible. First, we performed an unbiased genetic analysis of TCGA data sets and showed that APOBEC3B-null tumors with this mutational bias have at least one copy of the haplotype-I variant of APOBEC3H, despite weak genetic linkage between these two genes (n=14/14). Remarkably, breast tumors without APOBEC3B and APOBEC3H haplotype-I showed no evidence for an APOBEC mutation signature (n=3/3). The proportion of APOBEC signature mutations between the cohort with and the cohort without APOBEC3H haplotype-I was highly significant (p&amp;lt;0.00001 and lower), indicating that these two enzymes alone may be fully responsible (and casting serious doubt on the potential role of APOBEC3A). Second, although deemed inactive in prior studies, we discovered that APOBEC3H haplotype-I has robust activity in biochemical assays with mutation of TCA-containing single-stranded DNA and in cellular assays with hypermutation of HIV-1 cDNA and mutation of a genomic DNA eGFP reporter gene. Third, the subcellular localization APOBEC3H haplotype-I and other expressed variants of this enzyme differed with only the latter showing significant nuclear localization in a panel of cell lines. The genomic mutagenicity and localization of APOBEC3H haplotype-I is attributable to a glycine at position 105, whereas other variants of this enzyme that have an arginine at this position, suggesting a general molecular mechanism. These studies combine to offer a parsimonious solution to the APOBEC mutation paradox with APOBEC3B and APOBEC3H haplotype-I, together, accounting for the strong “APOBEC mutation signature” observed in many breast cancers. Citation Format: Harris RS, Starrett GJ, McCann JL, Carpenter MA. A solution to the APOBEC mutation paradox in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-06-03.
Abstract PR10: Significant improvements in therapeutic index for conjugated payloads using a nanoparticle-drug conjugate (NDC) platform to provide sustained drug release and potentially improved anticancer effects
Authors: Chester Metcalf, Derek van der Poll, Liang Zhao, Tiffany Halo, Doug Lazarus, Adam Stockmann, Christian Peters, Donna Brown, Roy Case, Ellen Rohde, Lata Jayaraman, Hongwei Wang, Tiffany Crowell, Adrian Senderowicz, Scott Eliasof
Journal: Cancer Research (2017)

Abstract Cerulean Pharma Inc.'s Dynamic Tumor Targeting™ Platform creates nanoparticle-drug conjugates (NDCs) designed to significantly mitigate a payload's limitations by providing sustained drug delivery to the tumor and superior therapeutic index through controlled release kinetics. By conjugating drug payloads to our novel β-cyclodextrin-PEG copolymer through linker strategies that allow modulation of release and pharmacokinetics (PK), we provide advantages over entrapped nanoparticle strategies, e.g., polymeric nanoparticles and liposomes. Cerulean has two NDCs in the clinic, CRLX101 and CRLX301, evidencing the translatability of our technology. CRLX101 has been dosed in over 350 patients and CRLX301 is in an ongoing Phase 1/2a trial. Our Dynamic Tumor Targeting Platform is applicable to a diverse range of drug payload possibilities, including small molecules with a host of physiochemical properties, i.e., hydrophobic and hydrophilic payloads, and functional groups with chemical handles for conjugation. To illustrate the capabilities of our platform we will present the biological impact of a series of cabazitaxel-containing NDCs with linkers encompassing a diversity of in vitro release rates. In vivo PK studies showed high and sustained levels of released drug in tumor tissues (&amp;gt;168 hrs), and in vivo mouse tumor model studies demonstrated vastly improved efficacy, i.e., tumor regression and significant tumor growth delay, and survival over separately dosed cabazitaxel including efficacy in a taxane-resistant tumor model. Cerulean continues to expand its platform through the development of new and emerging capabilities to treat patients living with cancer. In this regard, we also will address the future evolution of NDCs, including the conjugation of multiple payloads to a single NDC and the development of antibody-conjugated NDCs. This abstract is also being presented as Poster B43. Citation Format: Chester Metcalf, III, Derek van der Poll, Liang Zhao, Tiffany Halo, Doug Lazarus, Adam Stockmann, Christian Peters, Donna Brown, Roy Case, Ellen Rohde, Lata Jayaraman, Hongwei Wang, Tiffany Crowell, Adrian Senderowicz, Scott Eliasof. Significant improvements in therapeutic index for conjugated payloads using a nanoparticle-drug conjugate (NDC) platform to provide sustained drug release and potentially improved anticancer effects. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr PR10.
ALFA-9000 Trial - An Analysis of Cytogenetic Subsets: Significant Long-Term Benefit of Early Induction Reinforcement Is Observed in CBF-AML Only.
Authors: Claude Gardin, Sylvie Chevret, Christiane Charrin, Xavier Thomas, Christian Bastard, Jean-Luc Lai, Odile Maarek, Stephane de Botton, Dominique Bordessoule, Herve Tilly, Thierry de Revel, Christine Terre, Claude Preudhomme, Francis Bauters, Mauricette Michallet, Denis Fiere, Sylvie Castaigne, Pierre Fenaux, Herve Dombret
Journal: Blood (2005)
Biallelic mutations in human DCC cause developmental split-brain syndrome
Authors: Saumya S Jamuar, Klaus Schmitz-Abe, Alissa M D'Gama, Marie Drottar, Wai-Man Chan, Maya Peeva, Sarah Servattalab, Anh-Thu N Lam, Mauricio R Delgado, Nancy J Clegg, Zayed Al Zayed, Mohammad Asif Dogar, Ibrahim A Alorainy, Abdullah Abu Jamea, Khaled Abu-Amero, May Griebel, Wendy Ward, Ed S Lein, Kyriacos Markianos, A James Barkovich, Caroline D Robson, P Ellen Grant, Thomas M Bosley, Elizabeth C Engle, Christopher A Walsh, Timothy W Yu
Journal: Nature Genetics (2017)
Results of a Multicenter Phase II Trial for Older Patients with c-Kit Positive Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS) Using Low-Dose Ara-C (LDAC) and Imatinib.
Authors: F. Heidel, J. Cortes, F. Ruecker, M. Kaufmann, W. Aulitzky, L. Letvak, T. Kindler, C. Huber, H. Dohner, H. Kantarjian, T. Fischer
Journal: Blood (2005)
More airway smooth muscle in preschool children increases risk of future asthma
Authors: Ruth O'Reilly, Tim Oates, Jie Zhu, Peter Jeffery, Andrew Bush, Sejal Saglani
Journal: European Respiratory Journal (2011)

Introduction:  Accurate prediction of future asthma in preschool wheezers is not possible. Reticular basement membrane (RBM) thickness and airway smooth muscle (ASM) are increased in school-aged asthmatic children [Regamey AJRCCM 2008], but nothing is known about ASM changes in preschool wheezers, or the relationship of early airway pathology to future asthma.   Aims:  1)To measure RBM thickness and ASM in severe preschool wheezers and age-matched controls; 2)To relate preschool RBM thickness and ASM to school age asthma   Methods:  Endobronchial biopsies (EBx) were obtained from preschool wheezers (n=47, median age 26 months) and non-wheezers (n=21, median age 15 months) undergoing clinically indicated bronchoscopy between 2002-2005 [Saglani AJRCCM 2007]. 5μm sections were stained with haematoxylin & eosin. ASM was expressed as a proportion of the subepithelial area. ASM and RBM thickness were quantified using computer analysis. Children were followed up age 6-11 years to determine asthma status.   Results:  At preschool age, RBM thickness was increased in wheezers (n=37, median 4.3μm) compared to controls (n=16, median 3.6μm), p=0.01. ASM was similar between preschool wheezers (n=28, median 0.08) and controls (n=14, median 0.077), p=0.97. 51/68 (75%) children were followed up at school age. School age children with and without asthma had similar RBM thickness in their preschool EBx, p=0.23. However, children with asthma (n=8, median age 9.1 years) had increased preschool ASM (median 0.12) compared to those without asthma (n=24, median age 7.3 years, median ASM 0.066), p=0.007.   Conclusion:  Preschool children whose EBx had a higher proportion (>10%) of ASM had a 10 fold increased risk of asthma at school age.
Sex and Gender Reporting in Research—Reply
Authors: Janine Austin Clayton, Cara Tannenbaum
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
The effect of trainee research collaboratives in the UK
Authors: Dmitri Nepogodiev, Stephen J Chapman, Angelos G Kolias, J Edward Fitzgerald, Matthew Lee, Natalie S Blencowe, Aswin Chari, Aimun Jamjoom, Angelos G Kolias, Veeru Kasivisvanathan, Marta D'Auria, Gael R Nana, Tanvir Sian, Neil Sharma, Aneel Bhangu, J Edward Fitzgerald, James Haddow, Nicholas RA Symons, Sarantos Kaptanis, Pete Coe, Nicholas A Heywood, Deena Harji, Fadlo Shaban, Gijs van Boxel, Jennifer Isherwood, George Murphy, Katie Young, George Ramsay, Nicholas T Ventham, Natalie S Blencowe, Matthew Lee, Alex Ward, Thomas M Drake, James Glasbey, Chetan Khatri, Dmitri Nepogodiev, Joseph Shalhoub, Rhiannon L Harries, Amy Stimpson, David Bartlett, Ewen Griffiths, Paul J Marriott, Thomas D Pinkney, Pritam Singh, Ravinder S Vohra, Richard Wilkin, Stephen J Chapman
Journal: The Lancet. Gastroenterology & hepatology (2017)
Impaired exercise ventilatory efficiency in smokers with low transfer factor but normal spirometry
Authors: Gisele Walter Barbosa, J. Alberto Neder, Karina Utida, Denis E. O'Donnell, Paulo de Tarso Müller
Journal: European Respiratory Journal (2017)

It has long been established that severe decrements in transfer factor for carbon monoxide ( T LCO) are associated with negative outcomes in patients with chronic obstructive pulmonary disease (COPD), including exertional hypoxaemia and poor exercise tolerance [1]. More recently, exercise capacity has been found to be diminished in smokers both with and without airflow limitation, with mild-to-moderate decrements in T LCO [2–4]. The mechanisms that link reduced T LCO to low exercise capacity in smokers without COPD, even in the absence of increased hypoxic drive or overtly abnormal lung mechanics remain unknown. Ventilatory inefficiency in non-COPD smokers is associated with lower exercise capacity <http://ow.ly/Mf7n308Qm5M>
A Role for SCL in Developing Bone? the SCL +19 Core Enhancer Targets Expression to Cells of Developing Bone, Osteocytes, Chondrocytes and Bone Lining Cells.
Authors: Lev Silberstein, John E. Pimanda, Sandie Piltz, Liz Delaney, Scott Oldham, Asha Kallianpur, Massimo Dominici, Stephen Brandt, Berthold Gottgens, Anthony Green
Journal: Blood (2004)
Frequency and predictors of hospitalization during chemotherapy: a systematic review.
Authors: Rebecca M. Prince, Monika K. Krzyzanowska, Eshetu G. Atenafu
Journal: Journal of Clinical Oncology (2015)

6583 Background: Hospitalization during chemotherapy is a significant event from both the patient and healthcare system perspectives but little is known about how often it occurs and in which settings. We conducted a systematic review to define the frequency of and factors associated with treatment-related hospitalization among cancer patients (pts) undergoing chemotherapy. Methods: A systematic search of Medline and EMBASE databases, from 1946 to September 2013, was undertaken to identify articles reporting rates of hospitalization in pts with cancer undergoing chemotherapy. Observational studies and clinical trials were eligible but results were analysed separately for each group. Summary statistics were used to describe the results and the Chi-square test was used to compare the groups. Results: Sixty articles met inclusion criteria: 44 observational studies comprising 189,342 pts and 16 randomized controlled trials comprising 13,086 pts. The majority of articles (80%) focused on chemotherapy given with palliative intent most commonly in breast, lung and colorectal cancers. The proportion of pts hospitalized at least once was significantly higher in observational studies at 32% (range 27-38%) compared with 21% (range 15-27%) in randomized trials (OR 2.13, 95%CI 2.03-2.23, p < 0.0001). A significant difference was seen in both the adjuvant and palliative settings between real life and trial pts with 42 vs 16% (OR 2.94, 95%CI 2.72-3.18, p < 0.0001) of adjuvant and 33 vs 23% (OR 3.24, 95%CI 3.03-3.48, p < 0.0001) of palliative pts being hospitalized, respectively. Factors associated with hospitalization in observational studies included higher comorbidity, type of chemotherapy and geographic location, while performance status and type of chemotherapy were significant predictors in clinical trials. Age was not a risk factor in either population. A number of methodological issues regarding reporting of hospitalization parameters were identified such as poor definitions of the at-risk period and attribution of hospitalization as treatment-related. Conclusions: Hospitalization during chemotherapy is common especially in unselected patient populations. However, few articles report this and often do so poorly.
Annals Story Slam - Just Listen
Authors: Lawrence I. Kaplan
Journal: Annals of Internal Medicine (2017)

Web Exclusives7 March 2017Annals On Being a Doctor Story Slam - Just ListenFREELawrence I. Kaplan, MDLawrence I. Kaplan, MDFrom Temple University, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0029 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Just Listen "Just Listen," by Dr. Lawrence I. Kaplan (Duration 6:17)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Temple University, Philadelphia, Pennsylvania.Current Author Address: Lawrence I. Kaplan, MD; e-mail, [email protected]temple.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 March 2017Volume 166, Issue 5Page: SS1 ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Extracellular matrix remodeling in vivo for enhancing tumor-targeting efficiency of nanoparticle drug carriers using the pulsed high intensity focused ultrasound
Authors: Sangmin Lee, Hyounkoo Han, Heebeom Koo, Jin Hee Na, Hong Yeol Yoon, Kyung Eun Lee, Hyukjin Lee, Hyuncheol Kim, Ick Chan Kwon, Kwangmeyung Kim
Journal: Journal of Controlled Release (2017)
Measuring dyspnoea: new multidimensional instruments to match our 21st century understanding
Authors: Robert B. Banzett, Shakeeb H. Moosavi
Journal: European Respiratory Journal (2017)

Science and medicine are always limited by our measurement instruments, and the study of dyspnoea is no different, being limited by the tools we use to measure what patients feel. Whether researching neurophysiological mechanisms in the MRI scanner or trying to understand an individual patient, we need the best tool for the job. We have advanced from measuring dyspnoea as a yes/no item, to the realisation that patients can scale the sensation, to the understanding that we can measure more than a single aspect of this complex experience. In this issue, Williams et al . [1] have tested two new instruments that attempt to encompass the multidimensional nature of the dyspnoea experience. Developers of the D-12 and MDP add context to M.T. Williams and co-workers' evaluation of these instruments <http://ow.ly/VUqA308ZC7Y>
One-Year Follow-up of the European Ambulance Acute Coronary Syndrome Angiography Trial
Authors: Ajay J. Kirtane, Robert A. Harrington
Journal: JAMA Cardiology (2017)

Enrico Fabris, MD; Sinem Kilic, MD; Arnoud W. J. van’t Hof, MD, PhD; Jurrien ten Berg, MD, PhD; Ana Ayesta, MD, PhD; Uwe Zeymer, MD; Martial Hamon, MD; Louis Soulat, MD; Debra Bernstein, PhD; Prodromos Anthopoulos, MD; Efthymios N. Deliargyris, MD; Philippe Gabriel Steg, MD
Abstract A31: Early signaling dynamics of the epidermal growth factor receptor
Authors: Raven J. Reddy
Journal: Cancer Research (2017)

Abstract Despite extensive study of the EGF receptor (EGFR) signaling network, the immediate posttranslational changes that occur in response to growth factor stimulation remain poorly characterized; as a result, the biological mechanisms underlying signaling initiation remain obscured. To address this deficiency, we have used a mass spectrometry-based approach to measure system-wide phosphorylation changes throughout the network with 10-s resolution in the 80 s after stimulation in response to a range of eight growth factor concentrations. Significant changes were observed on proteins far downstream in the network as early as 10 s after stimulation, indicating a system capable of transmitting information quickly. Meanwhile, canonical members of the EGFR signaling network fall into clusters with distinct activation patterns. Src homology 2 domain containing transforming protein (Shc) and phosphoinositol 3-kinase (PI3K) phosphorylation levels increase rapidly, but equilibrate within 20 s, whereas proteins such as Grb2-associated binder-1 (Gab1) and SH2-containing tyrosine phosphatase (SHP2) show slower, sustained increases. Proximity ligation assays reveal that Shc and Gab1 phosphorylation patterns are representative of separate timescales for physical association with the receptor. Inhibition of phosphatases with vanadate reveals site-specific regulatory mechanisms and also uncovers primed activating components in the network, including Src family kinases, whose inhibition affects only a subset of proteins within the network. The results presented highlight the complexity of signaling initiation and provide a window into exploring mechanistic hypotheses about receptor tyrosine kinase (RTK) biology. Note: This abstract was not presented at the conference. Citation Format: Raven J. Reddy. Early signaling dynamics of the epidermal growth factor receptor. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A31.
Multimorbidity and healthcare utilization among home care clients with dementia in Ontario, Canada: A retrospective analysis of a population-based cohort
Authors: Luke Mondor, Colleen J. Maxwell, David B. Hogan, Susan E. Bronskill, Andrea Gruneir, Natasha E. Lane, Walter P. Wodchis
Journal: PLoS Medicine (2017)

For community-dwelling older persons with dementia, the presence of multimorbidity can create complex clinical challenges for both individuals and their physicians, and can contribute to poor outcomes. We quantified the associations between level of multimorbidity (chronic disease burden) and risk of hospitalization and risk of emergency department (ED) visit in a home care cohort with dementia and explored the role of continuity of physician care (COC) in modifying these relationships.A retrospective cohort study using linked administrative and clinical data from Ontario, Canada, was conducted among 30,112 long-stay home care clients (mean age 83.0 ± 7.7 y) with dementia in 2012. Multivariable Fine-Gray regression models were used to determine associations between level of multimorbidity and 1-y risk of hospitalization and 1-y risk of ED visit, accounting for multiple competing risks (death and long-term care placement). Interaction terms were used to assess potential effect modification by COC. Multimorbidity was highly prevalent, with 35% (n = 10,568) of the cohort having five or more chronic conditions. In multivariable analyses, risk of hospitalization and risk of ED visit increased monotonically with level of multimorbidity: sub-hazards were 88% greater (sub-hazard ratio [sHR] = 1.88, 95% CI: 1.72-2.05, p < 0.001) and 63% greater (sHR = 1.63; 95% CI: 1.51-1.77, p < 0.001), respectively, among those with five or more conditions, relative to those with dementia alone or with dementia and one other condition. Low (versus high) COC was associated with an increased risk of both hospitalization and ED visit in age- and sex-adjusted analyses only (sHR = 1.11, 95% CI: 1.07-1.16, p < 0.001, for hospitalization; sHR = 1.07, 95% CI: 1.03-1.11, p = 0.001, for ED visit) but did not modify associations between multimorbidity and outcomes (Wald test for interaction, p = 0.566 for hospitalization and p = 0.637 for ED visit). The main limitations of this study include use of fixed (versus time-varying) covariates and focus on all-cause rather than cause-specific hospitalizations and ED visits, which could potentially inform interventions.Older adults with dementia and multimorbidity pose a particular challenge for health systems. Findings from this study highlight the need to reshape models of care for this complex population, and to further investigate health system and other factors that may modify patients' risk of health outcomes.
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Myeloid Leukemia (AML): A Donor Versus No Donor Comparison.
Authors: Mohamad Mohty, Hugues de Lavallade, Patrick Ladaique, Catherine Faucher, Norbert Vey, Diane Coso, Anne-Marie Stoppa, Jean-Albert Gastaut, Didier Blaise
Journal: Blood (2005)
The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE
Authors: Jung Hee Kim, Dong Hyun Sinn, Sung Wook Shin, Sung Ki Cho, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Moon Seok Choi
Journal: Clinical and Molecular Hepatology (2017)

See the commentary-article "Is scheduled second chemoembolization necessary for early stage hepatocellular carcinoma showing complete response after first chemoembolization?" on page 31.