tbuckley/cabot-search huggingface dataset:
PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1
Authors: Zufeng Ding, Naga Venkata K Pothineni, Akshay Goel, Thomas F Lüscher, Jawahar L Mehta
Journal: Cardiovascular Research (2019)

PCSK9 degrades low-density lipoprotein cholesterol (LDL) receptors and subsequently increases serum LDL cholesterol. Clinical trials show that inhibition of PCSK9 efficiently lowers LDL cholesterol levels and reduces cardiovascular events. PCSK9 inhibitors also reduce the extent of atherosclerosis. Recent studies show that PCSK9 is secreted by vascular endothelial cells, smooth muscle cells, and macrophages. PCSK9 induces secretion of pro-inflammatory cytokines in macrophages, liver cells, and in a variety of tissues. PCSK9 regulates toll-like receptor 4 expression and NF-κB activation as well as development of apoptosis and autophagy. PCSK9 also interacts with oxidized-LDL receptor-1 (LOX-1) in a mutually facilitative fashion. These observations suggest that PCSK9 is inter-twined with inflammation with implications in atherosclerosis and its major consequence-myocardial ischaemia. This relationship provides a basis for the use of PCSK9 inhibitors in prevention of atherosclerosis and related clinical events.
Imaging and quantifying drug delivery in skin – Part 1: Autoradiography and mass spectrometry imaging
Authors: Sébastien Grégoire, Gustavo S. Luengo, Philippe Hallegot, Ana-Maria Pena, Xueqin Chen, Thomas Bornschlögl, Kin F. Chan, Isaac Pence, Peyman Obeidy, Amin Feizpour, Sinyoung Jeong, Conor L. Evans
Journal: Advanced Drug Delivery Reviews (2019)
Is ‘likely pathogenic’ really 90% likely? Reclassification data in ClinVar
Authors: Steven M. Harrison, Heidi L. Rehm
Journal: Genome Medicine (2019)

Abstract In 2015, professional guidelines defined the term ‘likely pathogenic’ to mean with a 90% chance of pathogenicity. To determine whether current practice reflects this definition, ClinVar classifications were tracked from 2016 to 2019. During that period, between 83.8 and 99.1% of likely pathogenic classifications were reclassified as pathogenic, depending on whether LP to VUS reclassifications are included and on how these classifications are categorized.
Anthony James Frew
Authors: Patrick Frew
Journal: BMJ (2019)

The eldest of three brothers, Anthony James Frew (“Tony”) was predestined to study medicine. Home was the GP surgery in Wickford, Essex, where his father, James, and uncle, Tom, worked with their father, Robert Frew, after whom the practice is still named. Every day the doctors met to smoke and discuss patients around the dining room table, under which the children played.

Top Queen’s Scholar at Westminster School, Tony won a scholarship in mathematics to Peterhouse, Cambridge. At interview he was asked what his best break at snooker was. And would he consider any other subject than maths? He chose medicine.

Tony captained the college football team and earned an oar in the Spring bumps. He fenced for the university at sabre and was in the …
Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement
Authors: Sylvain Beurtheret, Nicole Karam, Noemie Resseguier, Remi Houel, Thomas Modine, Thierry Folliguet, Chekrallah Chamandi, Olivier Com, Richard Gelisse, Jacques Bille, Patrick Joly, Nicolas Barra, Alain Tavildari, Philippe Commeau, Sebastien Armero, Mathieu Pankert, Michel Pansieri, Sabrina Siame, René Koning, Marc Laskar, Yvan Le Dolley, Arnaud Maudiere, Bertrand Villette, Patrick Khanoyan, Julien Seitz, Didier Blanchard, Christian Spaulding, Thierry Lefevre, Eric Van Belle, Martine Gilard, Helene Eltchaninoff, Bernard Iung, Jean Philippe Verhoye, Ramzi Abi-Akar, Paul Achouh, Thomas Cuisset, Pascal Leprince, Eloi Marijon, Hervé Le Breton, Antoine Lafont
Journal: Journal of the American College of Cardiology (2019)

Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access. This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR. Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score−based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers. n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.
Patterns of Care and Clinical Outcomes with 7+3 Induction Chemotherapy for Patients (pts) with Acute Myeloid Leukemia (AML) in the United States (US): A Large Population-Based Study
Authors: Amer M. Zeidan, Nikolai A. Podoltsev, Xiaoyi Wang, Jan Philipp Bewersdorf, Rory M Shallis, Scott F. Huntington, Natalia Neparidze, Smith Giri, Steven D. Gore, Xiaomei Ma, Amy J Davidoff, Rong Wang
Journal: Blood (2019)
Abstract 14135: Wide Complex Tachycardia Differentiation Using Computerized Electrocardiogram Interpretation Software Measurements
Authors: Adam May, DeSimone Christopher, Suraj Kapa, Peter Noseworthy, Peter Brady, Abhishek Deshmukh
Journal: Circulation (2018)

Background: The successful differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) has undeniably important therape...
CRL3–SPOP ubiquitin ligase complex suppresses the growth of diffuse large B-cell lymphoma by negatively regulating the MyD88/NF-κB signaling
Authors: Xiaofeng Jin, Qing Shi, Qian Li, Linyi Zhou, Jian Wang, Lei Jiang, Xiaying Zhao, Kai Feng, Ting Lin, Zihan Lin, Hui Zhuang, Jianye Yang, Chongke Hu, Luyi Zhang, Liliang Shen, Ying Lu, Jie Zhu, Haibiao Wang, Honggang Qi, Xiaodan Meng, Yang Xi, Jinchang Pan, Shuai Fang, Haihua Tian, Chengwei Zhou, Pingzhao Zhang, Kun Gao, Shi-min Zhao, Yao Li, Zhaohui Gong, Chenji Wang
Journal: Leukemia (2019)
Delivery strategies of cancer immunotherapy: recent advances and future perspectives
Authors: Zhongwei Zhao, Liyun Zheng, Weiqian Chen, Wei Weng, Jingjing Song, Jiansong Ji
Journal: Journal of Hematology & Oncology (2019)

Abstract Immunotherapy has become an emerging strategy for the treatment of cancer. Immunotherapeutic drugs have been increasing for clinical treatment. Despite significant advances in immunotherapy, the clinical application of immunotherapy for cancer patients has some challenges associated with safety and efficacy, including autoimmune reactions, cytokine release syndrome, and vascular leak syndrome. Novel strategies, particularly improved delivery strategies, including nanoparticles, scaffolds, and hydrogels, are able to effectively target tumors and/or immune cells of interest, increase the accumulation of immunotherapies within the lesion, and reduce off-target effects. Here, we briefly describe five major types of cancer immunotherapy, including their clinical status, strengths, and weaknesses. Then, we introduce novel delivery strategies, such as nanoparticle-based delivery of immunotherapy, implantable scaffolds, injectable biomaterials for immunotherapy, and matrix-binding molecular conjugates, which can improve the efficacy and safety of immunotherapies. Also, the limitations of novel delivery strategies and challenges of clinical translation are discussed.
DCC is a potential methylation marker in human cancers
Authors: K. Yamashita, H. L. Park, D. Sidransky, M. Watanabe
Journal: Journal of Clinical Oncology (2007)

15054 Background: DCC (deleted in colorectal cancer) is a tumor suppressor gene, and known to be inactivated by mutation in human cancers. In this study, we revealed DCC gene promoter methylation in primary human esophageal and breast cancers and refer to its excellence as a cancer-prone marker. Methods: Quantititative TaqMan real time polymerase chain reaction; 20 esophageal squamous cell carcinoma (ESCC) and the corresponding non-cancerous esophageal mucosal tissues, 58 breast cancer tissues, and ESCC cell lines. Results: (1) In ESCC tissues, DCC hypermethylation is detected in 18/20 cases (sensitivity=90%), while it is detected in only 2/20 normal cases (specificity=90%). (2) In breast cancer tissues, DCC hypermethylation is detected in 29/58 cases (50%), and patients with higher methylation of DCC showed size larger than 6 cm (100%) as compared with those less than 6 cm (45.3%)(p&lt;0.025). (3) DCC is silenced in cancer cell lines, and found to be reactivated by demethylating agent in several cell lines, while still silenced in other cell lines. Conclusions: In ESCC, DCC hypermethylation could be an excellent potential marker. DCC inactivation is partially explained by methylation, however other mechanism could be involved like p53. The accurate mechanism of DCC requires further elucidation, but its potential as a tumor marker in SCC is considered excellent to apply for cancer detection using human body fluid. No significant financial relationships to disclose.
Co-morbilities and survival of patients initially diagnosed with extensive-stage small cell lung cancer: Impact of hypertension, diabetes and chronic hepatitis B viral infection
Authors: W. Xiu, Y. Huang, X. Zhou, L. Zhou, J. Xue, J. Zhu, M. Huang, F. Peng, Y. Liu, Y. Xu, Y. Zhang, M. Yu, Y. Li, Y. Wang, Y. Lu, Y. Gong
Journal: Annals of Oncology (2019)
Myxomatous Mitral-Valve Prolapse
Authors: Faraz A Farooqui, Siddharthan Deepti
Journal: New England Journal of Medicine (2019)

A 22-year-old man presented with palpitations and chest discomfort. Echocardiography revealed an enlarged, thickened mitral-valve leaflet with systolic prolapse of multiple segments (shown in a video), and a diagnosis of myxomatous mitral-valve prolapse was made.
Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)
Authors: Kevin J Monahan, Nicola Bradshaw, Sunil Dolwani, Bianca Desouza, Malcolm G Dunlop, James E East, Mohammad Ilyas, Asha Kaur, Fiona Lalloo, Andrew Latchford, Matthew D Rutter, Ian Tomlinson, Huw J W Thomas, James Hill
Journal: Gut (2019)

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.
Structural variant calling: the long and the short of it
Authors: Medhat Mahmoud, Nastassia Gobet, Diana Ivette Cruz-Dávalos, Ninon Mounier, Christophe Dessimoz, Fritz J. Sedlazeck
Journal: Genome biology (2019)

Abstract Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution—giving rise to the differences within populations and among species. Nevertheless, characterizing SVs and determining the optimal approach for a given experimental design remains a computational and scientific challenge. Multiple approaches have emerged to target various SV classes, zygosities, and size ranges. Here, we review these approaches with respect to their ability to infer SVs across the full spectrum of large, complex variations and present computational methods for each approach.
An evaluation of a throat discomfort visual analogue scale in chronic cough
Authors: James H. Hull, Emil S. Walsted, Matthew J. Pavitt, Bethany Tidmarsh, Julia Selby
Journal: European Respiratory Journal (2019)

<b>Chronic cough (CC) is common. Recognition of laryngeal hypersensitivity (LHS) allows for targeted treatment. A throat visual analogue scale (VAS) allows for a rapid and simple method to detect LHS in CC and identifying targeted intervention.</b>http://bit.ly/32zPFiK
Diagnosis and Management of Hyperparathyroidism—Reply
Authors: Elizabeth A. Alore, David J. Ramsey, Konstantinos I. Makris
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Maternal iron supplementation in pregnancy and asthma in the offspring: follow-up of a randomised trial in Finland
Authors: Seif O. Shaheen, Mika Gissler, Graham Devereux, Maijaliisa Erkkola, Tarja I. Kinnunen, Harry Mcardle, Aziz Sheikh, Elina Hemminki, Bright I. Nwaru
Journal: European Respiratory Journal (2020)

Evidence for the hypothesis that prenatal nutrition may influence the risk of childhood respiratory and atopic disorders has strengthened in recent years. For example, randomised controlled trials (RCTs) have suggested that maternal supplementation with vitamin D or fish oil in pregnancy could prevent early childhood wheezing and asthma in the offspring [1, 2]. Another nutrient of interest is iron. Animal experiments have implicated iron in fetal airway development [3]. In two UK population-based birth cohorts, using different approaches, we have found evidence suggesting that lower maternal iron levels in pregnancy may increase the risk of wheezing, atopy and lower lung function in the offspring [4–7]. However, the possibility that unmeasured or residual confounding might explain these observational findings cannot be ruled out. A study in the USA reported that maternal anaemia was associated with an increased risk of childhood asthma in offspring of mothers with asthma, but not in those whose mothers did not have asthma [8], although we did not confirm such effect modification [5]. Iron supplementation in pregnancy may reduce the risk of asthma in the offspring <http://bit.ly/2UHmfid>
The origin of the coding metaphor in neuroscience
Authors: Justin Garson
Journal: Behavioral and Brain Sciences (2019)

Abstract To assess Brette's proposal to expunge “coding” from the neuroscientist's lexicon, we must consider its origins. The coding metaphor is due largely to British nerve physiologist Edgar Adrian. I suggest two ways that the coding metaphor fueled his research. I conclude that the debate today should not be about the “truth” of the metaphor but about its continuing utility.
Heterogeneity of Molecular Mechanisms Determining Blood Cancer Cell Lines Resistance to Natural Killer Cells in the Context of Tumor-Stromal Interactions: Insights from Studies of Pooled "DNA-Barcoded" Cell Line Panels
Authors: Sara Gandolfi, Michal Sheffer, Olli Dufva, Khalid Saeed, Emily Lowry, Olga Dashevsky, Ryosuke Shirasaki, Ricardo De Matos Simoes, Jennifer Roth, Rizwan Romee, Satu Mustjoki, Constantine S. Mitsiades
Journal: Blood (2019)
Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data
Authors: Fenglin Liu, Yuanyuan Zhang, Lei Zhang, Ziyi Li, Qiao Fang, Ranran Gao, Zemin Zhang
Journal: Genome biology (2019)

Abstract Background Systematic interrogation of single-nucleotide variants (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single-cell level. While SNV detection from abundant single-cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed. Results Here, we perform a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2, and VarScan2, using both simulation and scRNA-seq datasets, and identify multiple elements influencing their performance. While the specificities are generally high, with sensitivities exceeding 90% for most tools when calling homozygous SNVs in high-confident coding regions with sufficient read depths, such sensitivities dramatically decrease when calling SNVs with low read depths, low variant allele frequencies, or in specific genomic contexts. SAMtools shows the highest sensitivity in most cases especially with low supporting reads, despite the relatively low specificity in introns or high-identity regions. Strelka2 shows consistently good performance when sufficient supporting reads are provided, while FreeBayes shows good performance in the cases of high variant allele frequencies. Conclusions We recommend SAMtools, Strelka2, FreeBayes, or CTAT, depending on the specific conditions of usage. Our study provides the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.
Carcinogenicity of some industrial chemical intermediates and solvents
Authors: Ivan Rusyn, Fiorella Belpoggi, Luisa Camacho, Heiko U. Käfferlein, Russell Cattley, Cherie F Estill, Jun Kanno, Frank Le Curieux, Jaroslav Mráz, Georgia K. Roberts, William A. Stubbings, Takashi Umemura, Jelle Vlaanderen, Veronique Bouvard, Yann Grosse, Lamia Benbrahim-Tallaa, Jennifer Girschik, Fatiha El Ghissassi, Elaine G. Rowan, Felicia Chung, Mengmeng Li, Mary K. Schubauer-Berigan, Kathryn Z. Guyton
Journal: The Lancet Oncology (2019)
Molecular Mechanisms Mediating Relapse Following Ivosidenib Monotherapy in Patients with IDH1-Mutant Relapsed or Refractory Acute Myeloid Leukemia
Authors: Sung Choe, Hongfang Wang, Courtney D. DiNardo, Eytan M. Stein, Stephane De Botton, Amir T. Fathi, Martin S. Tallman, Hagop M. Kantarjian, Richard M. Stone, Lynn Quek, Zenon Konteatis, Lenny Dang, Vickie Zhang, Hua Liu, Eyal C. Attar, Bin Wu
Journal: Blood (2019)
Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL
Authors: Sonia Rodriguez, Christina Abundis, Francesco Boccalatte, Purvi Mehrotra, Mark Y. Chiang, Mary A. Yui, Lin Wang, Huajia Zhang, Amy Zollman, Ricardo Bonfim-Silva, Andreas Kloetgen, Joycelynne Palmer, George Sandusky, Mark Wunderlich, Mark H. Kaplan, James C. Mulloy, Guido Marcucci, Iannis Aifantis, Angelo A. Cardoso, Nadia Carlesso
Journal: Leukemia (2019)

Abstract Timed degradation of the cyclin-dependent kinase inhibitor p27 Kip1 by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leukemia models, with little effect on normal tissues. We also demonstrate a novel feed forward feedback loop by which Notch and IL-7 signaling cooperatively converge on SKP2 induction and cell cycle activation. These studies show that the Notch/SKP2/p27 Kip1 pathway plays a unique role in T-ALL development and provide a proof-of-concept for the use of SKP2 as a new therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL).
ILF2 Antisense Oligonucleotide Therapy and a CRISPR/Cas9-Based Screening for DNA Repair Effectors Identify Synthetic Lethal Approaches Enhancing Myeloma Cells Sensitivity to DNA Damage
Authors: Natthakan Thongon, Christopher Jackson, Pamela Lockyer, Jintan Liu, Andrea Santoni, Ashley Rose, Guillermo Garcia-Manero, Simona Colla
Journal: Blood (2019)