tbuckley/cabot-search huggingface dataset:
Abstract 422: Single-stranded library preparation enables unbiased sequencing of damaged, FFPE-derived DNA for both targeted gene capture and WGS applications
Authors: Anna Vilborg
Journal: Cancer Research (2018)

Abstract Next Generation Sequencing is increasingly used in translational cancer research and as a diagnostic test. Most tumor specimens available for testing are formalin-fixed, paraffin-embedded (FFPE) blocks. FFPE-derived DNA is typically damaged, causing difficulties for standard library preparation methods. Frayed ends prevent blunt-ended double-stranded adapter ligation, used for whole genome sequencing (WGS) and targeted bait hybridization library preparation. Fragmented DNA and modified bases interfere with PCR, which underlies amplification based targeted sequencing. We present a single-stranded library preparation method especially forgiving for low quality FFPE-derived DNA. By excising damaged bases and using single-stranded adapter ligation, we omit repair aimed at generating blunt-ended double-stranded DNA, and eliminate the need for whole genome PCR. After ligation of the first adapter, libraries can either undergo second adapter ligation to generate WGS libraries, or be used as input to oligo-selective sequencing (OS-Seq) target capture. We show that our FFPE-derived PCR-free WGS libraries exhibit coverage depth and uniformity highly similar to double-stranded PCR-free libraries of matched cell line (non-FFPE) materials. Additionally, we present performance of our WGS library preparation on clinical FFEP samples. We further demonstrate reproducible high and uniform coverage for reference standards and clinical FFPE samples in targeted capture. We show a lack of correlation between DNA quality and sequencing metrics such as on-target rate (R2=0.005), uniformity (R2=0.0002), and coverage (R2=0.06), with successful removal of C&amp;gt;T FFPE artifacts comparable to standard repair methods. We demonstrate sensitive copy number alteration detection through analysis of coverage depth, feasible due to the absence of pre-capture PCR. In conclusion, our single-stranded library preparation method is forgiving for sample quality and provides uniform and high coverage as the basis for somatic variant calling. Citation Format: Anna Vilborg. Single-stranded library preparation enables unbiased sequencing of damaged, FFPE-derived DNA for both targeted gene capture and WGS applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 422.
Reply to Tremlett and Kanthimathinathan and to Koopman and Kneyber
Authors: Robinder G. Khemani, Kaushik Parvathaneni, Nadir Yehya, Anoopindar K. Bhalla, Neal J. Thomas, Christopher J. L. Newth
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

We appreciate the interest in our recent article, which found that children with pediatric acute respiratory distress syndrome (PARDS) managed with higher FI O 2 relative to the positive endexpiratory pressure (PEEP) levels recommended by the ARDS Network PEEP/FI O 2 protocol had higher mortality (1).This higher mortality held after extensive multivariable and propensity adjustment.However, given the observational, retrospective nature of our study, causality should not be implied.Although our study has limitations, we believe we have demonstrated the need to look more closely at PEEP management in PARDS.There have been no clinical trials surrounding PEEP management in PARDS.Furthermore, PEEP is generally underused as part of the lung recruitment strategy in many pediatric intensive care units, as observational data have consistently demonstrated that PEEP levels are rarely escalated above 10 cm H 2 O, even in circumstances of severe hypoxemia (2-4).With that in mind, we believe the letters provided by Drs.Koopman and Kneyber and Drs.Tremlett and Kanthimathinathan highlight some important pragmatic points to consider as we move forward with further investigations into PEEP management in PARDS.The first point relates to the potential attributable mortality fraction from ARDS.Indeed, it is likely that many children are dying with PARDS and not necessarily from PARDS.Mortality in ARDS (both adult and pediatric) is multifactorial, and both these letters to the editor, as well as texts by many other authors, have argued that mortality may not be the best outcome for ARDS studies (5).In this manuscript, we did not explore specific cause of death, and although that may provide some insight, the somewhat subjective nature of assessments of cause of death limit conclusions.Drs.Koopman and Kneyber argue that children who have withdrawal of support or withholding of life-sustaining therapies are not dying from PARDS.Withdrawal of support is the most common mode of death (not cause) in most intensive care units (6).The factors that contribute to the decision to withdraw support in these patients may relate to underlying comorbidities, but these decisions are invariably tied to the effects of the acute disease (i.e., ARDS) and how it informs the clinician's proposed prognosis.Decoupling this complexity to limit analysis to certain types of patients who have a prespecified cause of death
Caring for Patients With Neurological Impairment
Authors: Jay G. Berry, Sarah D. Berry
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics 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 Pediatrics journal
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration
Authors: Jan P. Vandenbroucke
Journal: Annals of Internal Medicine (2007)

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to cohort studies, case–control studies, and cross-sectional studies, and 4 are specific to each of the 3 study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors, and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, 1 or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (www.strobe-statement.org) should be helpful resources to improve reporting of observational research.
Taking the pain out of the patellofemoral joint: articulating a bone of contention
Authors: Bill Vicenzino, Liam Maclachlan, Michael Skovdal Rathleff
Journal: British Journal of Sports Medicine (2018)

An interesting observation from recent International Patellofemoral Pain Retreats (IPFR) is the relatively low proportion of submitted abstracts focusing on pain sciences (ie, 6% (3/50; Manchester, UK, 2015)1 and 29% (15/52; Gold Coast, Australia). Coupled with a recent IPFR consensus document strongly linking biomechanical factors to elevated patellofemoral joint load and pain, we are left questioning where our contemporary understanding of pain fits?

Patellofemoral pain research is replete with studies evaluating a range of biomechanical features of the condition. For the most, these studies are disparate, with small samples. Powers et al 2 deserve credit and recognition for completing the huge task of efficiently reviewing and summarising this body of work. While this framework helps make sense of a complex range of physical features, we are compelled to address an issue that will likely impede the framework’s usefulness to guide clinical pracice. When viewed in isolation, the pathomechanical framework posits that patellofemoral pain is a peripherally based nociception. This raises a point of contention, …
Annals Graphic Medicine - Finding the Funny: Everything
Authors: Jade R. Blue
Journal: Annals of Internal Medicine (2018)

Web Exclusives3 July 2018Annals Graphic Medicine - Finding the Funny: EverythingFREEJade R. Blue, BA(Hons)Jade R. Blue, BA(Hons)From Ceredigion, Wales, United Kingdom. (J.R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G17-0019 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Take a break and read more of Jade Blue's comical and poignant descriptions of her journey with breast cancer. Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Ceredigion, Wales, United Kingdom. (J.R.B.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G17-0019.Author/Illustrator Information: Jade Blue is an English-language teacher and trainer based in the United Kingdom, Germany, and Japan. She also works as a research consultant and editor for Cambridge University Press and writes a reflective blog (http://jadeblueefl.wordpress.com). Her research interests focus on drawing in the classroom and learner autonomy. Jade is passionate about doodling and drawing comics and writes a blog about her work (http://jadesdoodles.wordpress.com).Author Contributions: Conception and design: J.R. Blue.Drafting of the article: J.R. Blue.Final approval of the article: J.R. Blue.Administrative, technical, or logistic support: J.R. Blue. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 July 2018Volume 169, Issue 1Page: W1-W5KeywordsBreast cancerConflicts of interestDisclosure ePublished: 3 July 2018 Issue Published: 3 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Using Ultrafast Responsive Phosphorescent Nanoprobe to Visualize Elevated Peroxynitrite In Vitro and In Vivo via Ratiometric and Time‐Resolved Photoluminescence Imaging
Authors: Zejing Chen, Peng Yan, Liang Zou, Menglong Zhao, Jiayang Jiang, Shujuan Liu, Kenneth Yin Zhang, Wei Huang, Qiang Zhao
Journal: Advanced Healthcare Materials (2018)

Abstract Peroxynitrite (ONOO ‐ ), a potent biological oxidant, which has a short half‐life in physiological conditions, is related to many diseases. Accurate peroxynitrite determination with superior selectivity and sensitivity is important for understanding biological roles of peroxynitrite in different health and disease tissues. Autofluorescence is an inevitable interference in luminescence biodetection and bioimaging, which often reduces signal‐to‐noise ratio during detection. In this work, a phosphorescent peroxynitrite nanoprobe ( MSN‐ONOO ) which displays two emission bands is prepared by immobilizing two long‐lived phosphorescent iridium(III) complexes that are peroxynitrite‐activable and ‐inert, respectively, into water‐dispersible mesoporous silica nanoparticles. Owing to the fast response rate, excellent sensitivity and outstanding selectivity of the nanoprobe toward peroxynitrite, it is further used for peroxynitrite determination in vitro and in vivo via ratiometric photoluminescence imaging. More notably, taking advantage of the long‐lived phosphorescence of MSN‐ONOO , in vivo elevated peroxynitrite is imaged with diminished autofluorescence interference and improved signal‐to‐noise ratio via time‐resolved photoluminescence imaging. As far as it is known, this is the first time for endogenous peroxynitrite detection in vivo via the time‐resolved photoluminescence imaging. Furthermore, the production of peroxynitrite in inflamed tissues is visualized.
Abstract 12164: Nectin-like Molecule-5 Regulates Formation of Intimal Thickening in Mouse Carotid Artery and Phenotypic Reversion of Vascular Smooth Muscle Cells
Authors: Fumie Kureha, Seimi Satomi-Kobayashi, Mitsuo Kinugasa, Jun Miyoshi, Yoshimi Takai, Ken-ichi Hirata, Yoshiyuki Rikitake
Journal: Circulation (2012)

Background:  Intimal thickening is a phenomenon that is observed at the very early stage of atherosclerosis. It is considered that this phenomenon involves the phenotypic reversion of medial smooth muscle cells (SMCs) from a differentiated to a dedifferentiated state and their subsequent migration into intima and proliferation. We recently reported that the immunoglobulin-like molecule nectin-like molecule (Necl)-5 enhances migration and proliferation of endothelial cells and angiogenesis. Therefore, we anticipated that Necl-5 is involved in intimal thickening. We examined here the roles of Necl-5 in intimal thickening following carotid artery ligation in mice and in phenotypic reversion, migration, and proliferation of cultured SMCs.   Methods and Results:  In vivo , Necl-5 was upregulated in SMCs of the thickened neointima in wild-type (WT) mice at 4 weeks after carotid artery ligation. Compared with that in WT mice, the intimal thickening was less severe in Necl-5 knockout (KO) mice (Intima/media ratio; WT vs. Necl-5 KO = 1.17±0.22 vs. 0.41±0.14, p=0.013). BrdU incorporation in the thickened intima of ligated carotid arteries was decreased in Necl-5 KO mice compared with WT mice at 2 weeks after carotid artery ligation.  In vitro , compared with mouse aortic SMCs (MASMCs) isolated from WT mice, the expression levels of differentiation marker genes, such as SM α-actin, SM22α, and SM-myosin heavy chain, were higher, whereas that of SMemb, a dedifferentiation marker gene, was lower in MASMCs isolated from Necl-5 KO mice. Migration, proliferation, and extracellular signal-regulated kinase (ERK) activity in response to serum were reduced in Necl-5 KO MASMCs compared with WT MASMCs. In WT MASMCs, inhibition of ERK activity increased the expression levels of differentiation marker genes and decreased migration and proliferation in response to serum.   Conclusions:  These findings indicate that Necl-5 regulates ERK activation, which enhances the phenotypic reversion, migration, and proliferation of SMCs, and promotes the formation of intimal thickening following carotid artery ligation. This study reveals Necl-5 as a candidate target molecule for the prevention of atherosclerosis.
Persistence of NS5B-S282T, a sofosbuvir resistance-associated substitution, in a HIV/HCV-coinfected MSM with risk of onward transmission
Authors: Astrid M. Newsum, Richard Molenkamp, Jan T. van der Meer, Sjoerd P. Rebers, Maria Prins, Marc van der Valk, Janke Schinkel
Journal: Journal of Hepatology (2018)
Abstract 2107: A novel real-time cell imaging assay to quantify macrophage efferocytosis
Authors: Daniel Bravo, Jianyong Wang, Yongchang Shi
Journal: Cancer Research (2018)

Abstract Tumor-associated macrophages (TAMs) are found in the microenvironment of solid tumors, representing one of the most abundant immune cell types within tumor stroma. Studies have demonstrated that the presence of TAMs correlates with tumor progression and poor prognosis. The engulfment of apoptotic tumor cells by TAMs (a phagocytic process known as efferocytosis) results in clearance of neoplastic antigens, which prevents antigen presentation and activation of effector T cells. Additionally, it has been shown that TAMs produce cytokines that create an immunosuppressive environment that facilitates tumor evasion of immune surveillance and promotes tumor growth. Furthermore, TAMs have been reported to be key players in the promotion of tumor angiogenesis and metastasis. Since TAMs play such an important role in cancer progression, inhibition of their function in the tumor microenvironment becomes an attractive approach of cancer immunotherapy. Traditionally, quantifying efferocytosis in vitro has been a technically challenging task. Our lab has established a novel high-throughput assay that can be used to screen drug candidates that inhibit TAM efferocytosis. Our new assay uses the IncuCyte ZOOM real-time imaging platform to visualize macrophage efferocytosis of apoptotic cells that are labeled with a pH-sensitive probe (pHrodo) that only emits fluorescence in acidic enviroments. This technology enables us to quantify phagocytic events of apoptotic cells that have been processed into the phagolysosome. By using this method, we quantitatively characterized the efferocytosis activity of TAM-like macrophages that were differentiated from primary human monocytes. We tested several agents (including small-molecule compounds and antibodies) and quantified their activities in blocking efferocytosis of TAMs via IC50 concentrations and potency. This new high-throughput assay platform yields highly robust and reproducible data (Z'=0.69), is fully automated, noninvasive (no washing, fixing or lifting of cells), and works with low cell numbers. Our results show that our efferocytosis assay facilitates high-throughput functional screening and can be utilized to identify and characterize new cancer drug candidates, as well as enables research of efferocytosis mechanisms and functions of phagocytic cells. Citation Format: Daniel Bravo, Jianyong Wang, Yongchang Shi. A novel real-time cell imaging assay to quantify macrophage efferocytosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2107.
Abstract 2416: CREB orchestrates metabolic reprogramming in PDGFRA-addicted lung squamous cell cancer
Authors: Jun Xu, Nan Jin, Min Huang, Jian Ding, Meiyu Geng
Journal: Cancer Research (2018)

Abstract Aberration of platelet-derived growth factor receptor A (PDGFRA) gene has been increasingly identified in multiple types of human cancers, including hematologic malignancies, gastrointestinal stromal tumor (GIST), medulloblastomas and gliomas. In particular, amplification of 4q12 that contains PDGFRA locus has been reported in 3% to 7% of lung adenocarcinomas and 8% to 10% of lung squamous cell carcinomas. However, it remains unclear how amplified PDGFRA drives malignancy of lung squamous cell cancer. To address this question, we used a lung squamous cell cancer cell line NCI-H1703, which has been previously reported to have 24-fold amplification of the 4q12 region. Either siRNA knockdown or small-molecule inhibition of PDGFRA significantly inhibited cell growth, suggesting that PDGFRA was required for driving cell proliferation. We further showed that both oxidative phosphorylation and aerobic glycolysis were significantly affected followed by interference of PDGFRA, by measuring of oxygen consumption rate (OCR) and extra cellular acidification rate (ECAR). In particular, ATP generation level and maximum respiratory capacity, the key parameters of mitochondrial function, were significantly decreased in mitochondrial pressure testing. These observations suggested that oncogenic PDGFRA drove the metabolic reprogramming and promoted tumor malignancy in lung squamous cell cancer. To further explore the regulatory mechanism of the observed metabolic phenotype, we took the approach of genetic sequencing technology to analyze the transcriptome in PDGFRA-driven NCI-H1703 cells treated with or without PDGFRA inhibitor. It revealed that PDGFRA-driven transcriptional regulation of metabolic genes underpinned the specific metabolic phenotypes of mitochondrial function. In addition, analysis of transcriptome as well as a phosphorylated kinase array revealed that a transcription factor, cAMP response element-binding protein (CREB), regulated the metabolic gene expression in PDGFRA-addicted cells. Knockdown of CREB disrupted metabolic gene expression and the mitochondrial function, consistent with aforementioned findings of PDGFRA, suggesting that transcriptional regulation of metabolic genes was orchestrated by CREB. Together, we herein firstly provide the molecular link between oncogenic PDGFRA and metabolic vulnerability and reveal the important role of CREB in orchestrating metabolic reprogramming in PDGFRA-addicted lung squamous cell cancer. Citation Format: Jun Xu, Nan Jin, Min Huang, Jian Ding, Meiyu Geng. CREB orchestrates metabolic reprogramming in PDGFRA-addicted lung squamous cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2416.
Which patients with heart failure should receive specialist palliative care?
Authors: Ross T. Campbell, Mark C. Petrie, Colette E. Jackson, Pardeep S. Jhund, Ann Wright, Roy S. Gardner, Piotr Sonecki, Andrea Pozzi, Paula McSkimming, Alex McConnachie, Fiona Finlay, Patricia Davidson, Martin A. Denvir, Miriam J. Johnson, Karen J. Hogg, John J.V. McMurray
Journal: European Journal of Heart Failure (2018)

Aims We investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient‐reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC. Methods and results PROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months. SPC need was defined as persistently severe impairment of any PROM without improvement (or severe impairment immediately preceding death). We then tested whether need for SPC, so defined, was reflected in DAOH, a measure which combines length of stay, days of hospital re‐admission, and days lost due to death. Of 272 patients recruited, 74 (27%) met the definition of SPC needs. These patients lived one third fewer DAOH than those without SPC need (and less than a quarter of QoL‐adjusted DAOH). A Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score of &lt;29 identified patients who subsequently had SPC needs (area under receiver operating characteristic curve 0.78). Twenty‐four per cent of patients with SPC needs actually received SPC ( n = 18). Conclusions A quarter of patients hospitalised with HF had a need for SPC and were identified by a low KCCQ score on admission. Those with SPC need spent many fewer DAOH and their DAOH were of significantly worse quality. Very few patients with SPC needs accessed SPC services.