tbuckley/cabot-search huggingface dataset:
Abstract 12919: Co-aligned and Inherently Co-registered Intravascular Ultrasound and Optical Coherence Tomography in a Hybrid Imaging Catheter is Feasible for Characterizing Coronary Artery Disease
Authors: Brian H Li, Mark Harduar, Kuljit Virdi, Jonathan Toma, Natasha Alves, Brian K Courtney
Journal: Circulation (2016)

Introduction: Combined use of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) demonstrates synergistic benefits, which may improve the characterization and therapeutics of coronary artery disease. However, sequential use of stand-alone catheters is impractical. Hypothesis: IVUS and OCT can be implemented in a dual-modality catheter with co-alignment of imaging beams, allowing simultaneous imaging of coronary lesions that are inherently co-registered. Methods: A 3-French rotational custom hybrid IVUS-OCT imaging catheter was built using a 40 MHz ultrasound transducer with embedded OCT imaging fiber optics, as well as co-alignment of the IVUS and OCT imaging centers. Ex-vivo intraluminal IVUS and OCT images of 70 coronary artery segments from 5 cadaveric autopsies were acquired simultaneously at 25 frames/sec with 5 mm/sec pull back. Imaging at 100 frames/sec was also briefly conducted. Thirty segments had potential pathological findings and underwent histologic slicing and hematoxylin-eosin staining at 250μm intervals. Morphological features were identified based on standard criteria for IVUS and OCT, then compared to corresponding histology findings. Results: IVUS and OCT were well co-registered based on fiduciary markings. A number of vascular pathologies were identified, including normal, fibrous, lipid-rich, calcified, and thrombus tissues. These findings were confirmed on corresponding histology. Complementary features of IVUS and OCT were also qualitatively apparent. IVUS showed deeper image depth to allow assessment of plaque size and vascular remodeling. OCT showed superior near field imaging, resolution and tissue contrast. Conclusions: We demonstrated feasibility of co-aligning IVUS and OCT, providing co-registered hybrid images that highlight the complementary advantages of both modalities. Quantitative comparison and validation of this technology is on-going.
Effect of HPV vaccination and cervical cancer screening in England by ethnicity: a modelling study
Authors: Helen C Johnson, Erin I Lafferty, Rosalind M Eggo, Karly Louie, Kate Soldan, Jo Waller, W John Edmunds
Journal: The Lancet Public Health (2017)

Health equality is increasingly being considered alongside overall health gain when assessing public health interventions. However, the trade-off between the direct effects of vaccination and herd immunity could lead to unintuitive consequences for the distribution of disease burden within a population. We used a transmission dynamic model of human papillomavirus (HPV) to investigate the effect of ethnic disparities in vaccine and cervical screening uptake on inequality in disease incidence in England.
Resolving the dark side of therapy-driven cancer cell death
Authors: Eduardo Bonavita, Victoria S. Pelly, Santiago Zelenay
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Sulciner et al. (https://doi.org/10.1084/jem.20170681) provide evidence that therapy-induced cancer cell death can, paradoxically, stimulate and accelerate the growth of surviving malignant cells by fueling tumor-promoting inflammation. Resolvins, a class of lipid mediators, counteract this effect, representing an attractive target for therapeutic intervention.
Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma
Authors: B. de Unamuno Bustos, R. Murria Estal, G. Pérez Simó, J. Simarro Farinos, C. Pujol Marco, M. Navarro Mira, V. Alegre de Miquel, R. Ballester Sánchez, V. Sabater Marco, M. Llavador Ros, S. Palanca Suela, R. Botella Estrada
Journal: British Journal of Dermatology (2017)

Promoter methylation of tumour suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival. DNA methylation was analysed using methylation‐specific multiplex ligation‐dependent probe amplification in a series of 170 melanoma formalin‐fixed paraffin‐embedded tumour samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease‐free survival (DFS) and overall survival (OS) were displayed by the Kaplan–Meier method. In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, presence of mitosis and ulceration, fast‐growing melanomas, advancing stage and TERT mutations). Furthermore, Kaplan–Meier survival analysis showed a correlation of methylation and poorer DFS and OS. Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.
Calcium‐binding protein 39 promotes hepatocellular carcinoma growth and metastasis by activating extracellular signal‐regulated kinase signaling pathway
Authors: Lingxi Jiang, Qian Yan, Shuo Fang, Ming Liu, Yan Li, Yun‐Fei Yuan, Yan Li, Yinghui Zhu, Jiali Qi, Xiaodong Yang, Dora Lai Wan Kwong, Xin‐Yuan Guan
Journal: Hepatology (2017)

Calcium-binding protein (CAB39) is a key regulator of a group of sterile 20 kinases. Here, we report that CAB39 was frequently up-regulated in hepatocellular carcinoma (HCC), which was significantly associated with tumor metastasis (P = 0.000), poorer disease-free survival rate (P = 0.027), and poor prognosis (P = 0.000). Ectopic expression of CAB39 in immortalized human liver cell line LO2 and HCC cell lines QGY-7703 and BEL-7402 could increase foci formation, colony formation in soft agar, tumor formation in nude mice, and cell motility. Silencing CAB39 expression in two HCC cell lines, Huh7 and MHCC97H, with short hairpin RNA could effectively abolish its oncogenic function. Further study found that CAB39 contributed to extracellular signal-regulated kinase (ERK) pathway activation, and mutations of the key sites of CAB39 markedly decrease the level of phosphorylated ERK. In addition, CAB39 could promote epithelial-mesenchymal transition by up-regulating N-cadherin and Fibronectin and down-regulating E-cadherin and α-E-catenin. As a result, β-catenin nuclear translocation was increased and its downstream target gene, matrix metalloproteinase-9, was up-regulated.Taken together, our findings suggested that CAB39 played very important oncogenic roles in HCC pathogenesis and progression by activating the ERK signaling pathway. Better understanding of CAB39 may lead to its clinical application as a biomarker for a prognosis predictor and a novel therapeutic target. (Hepatology 2017;66:1529-1545).
Nanocarrier‐Mediated Photochemotherapy and Photoradiotherapy
Authors: Antonia G. Denkova, Robine M. de Kruijff, Pablo Serra‐Crespo
Journal: Advanced Healthcare Materials (2017)

Abstract Photothermal therapy (PTT) and photodynamic therapy (PDT) both utilize light to induce a therapeutic effect. These therapies are rapidly gaining importance due to the noninvasiveness of light and the limited adverse effect associated with these treatments. However, most preclinical studies show that complete elimination of tumors is rarely observed. Combining PDT and PTT with chemotherapy or radiotherapy can improve the therapeutic outcome and simultaneously decrease side effects of these conventional treatments. Nanocarriers can help to facilitate such a combined treatment. Here, the most recent advancements in the field of photochemotherapy and photoradiotherapy, in which nanocarriers are employed, are reviewed.
Dasatinib increases endothelial permeability leading to pleural effusion
Authors: Carole Phan, Etienne-Marie Jutant, Ly Tu, Raphaël Thuillet, Andrei Seferian, David Montani, Alice Huertas, Jan van Bezu, Fabian Breijer, Anton Vonk Noordegraaf, Marc Humbert, Jurjan Aman, Christophe Guignabert
Journal: European Respiratory Journal (2018)

Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion. To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg −1 ·day −1 for 8 weeks). Pleural ultrasonography revealed that rats chronically treated with dasatinib developed pleural effusion after 5 weeks. Consistent with these in vivo observations, dasatinib led to a rapid and reversible increase in paracellular permeability of human pulmonary endothelial cell monolayers as reflected by increased macromolecule passage, loss of vascular endothelial cadherin and zonula occludens-1 from cell–cell junctions, and the development of actin stress fibres. These results were replicated using human umbilical vein endothelial cells and confirmed by decreased endothelial resistance. Interestingly, we demonstrated that this increased endothelial permeability is a reactive oxygen species (ROS)-dependent mechanism in vitro and in vivo using a cotreatment with an antioxidant agent, N -acetylcysteine. This study shows that dasatinib alters pulmonary endothelial permeability in a ROS-dependent manner in vitro and in vivo leading to pleural effusion.
Trends in Self-reported and Biochemically Tested Marijuana Use Among Pregnant Females in California From 2009-2016
Authors: Kelly C. Young-Wolff, Lue-Yen Tucker, Stacey Alexeeff, Mary Anne Armstrong, Amy Conway, Constance Weisner, Nancy Goler
Journal: JAMA (2017)

Trends in Self-reported and Biochemically Tested Marijuana Use Among Pregnant Females in California From 2009-2016Marijuana is the most commonly used illicit drug during pregnancy, and its use is increasing.From 2002 to 2014, the prevalence of self-reported, past-month marijuana use among US adult pregnant women increased from 2.4% to 3.9%. 1 In aggregated 2002-2012 data, 14.6% of US pregnant adolescents reported past-month use. 2 However, studies are limited to self-reported surveys and likely underestimate use due to social desirability bias and underreporting, leaving the scope of the problem unclear.We investigated trends of prenatal marijuana use from 2009-2016 using data from a large California health care system with universal screening via self-report and urine toxicology.Methods | The Kaiser Permanente Northern California (KPNC) institutional review board approved and waived consent for this study.KPNC is an integrated health care system serving approximately 4 million patients representative of the geographic area.The sample comprised KPNC pregnant females 12 years or older who completed a self-administered questionnaire on marijuana use since pregnancy and a cannabis toxicology test (58% occurred at the same visit as the questionnaire, 87% occurred within 2 weeks of completing the questionnaire) during standard prenatal care (at approximately 8 weeks' gestation) from 2009 through 2016.We estimated the adjusted prevalence of prenatal marijuana use via self-report or toxicology annually using Poisson regression with a log link function, controlling for age, race/ ethnicity, and median neighborhood household income using SAS (SAS Institute), version 9.3.Adjusted prevalence estimates used the average covariate distributions across the study period.We tested for linear trends and differences in trends by age.Two-sided P values less than .05were considered statistically significant.
Erratum: Germline mutations predisposing to diffuse large B-cell lymphoma
Authors: O C Leeksma, N F de Miranda, H Veelken
Journal: Blood Cancer Journal (2017)

Correction to: Blood Cancer Journal (2017) 7, e532; doi:/doifinder/10.1038/bcj.2017.15; published online 17 February 2017 Following the online publication of this article, the author noticed an error in Table 1. Reference 3030 should be 29 as both LIG4 mutations originate from the same source.
Hepatocellular carcinoma due to a baffle obstruction after the mustard operation: A case report
Authors: Takeo Yoshihara, Ryotaro Sakamori, Kunimaro Furuta, Minoru Shigekawa, Ryoko Yamada, Takahiro Kodama, Hayato Hikita, Takayuki Yakushijin, Tomohide Tatsumi, Yasushi Sakata, Hidetoshi Eguchi, Yoshiki Sawa, Tetsuo Takehara
Journal: Hepatology (2017)

Yoshihara, Takeo; Sakamori, Ryotaro; Furuta, Kunimaro; Shigekawa, Minoru; Yamada, Ryoko; Kodama, Takahiro; Hikita, Hayato; Yakushijin, Takayuki; Tatsumi, Tomohide; Sakata, Yasushi; Eguchi, Hidetoshi; Sawa, Yoshiki; Takehara, Tetsuo Author Information
Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport Syndrome
Authors: Steven D. Funk, Raymond H. Bayer, Andrew F. Malone, Karen K. McKee, Peter D. Yurchenco, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2017)

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β 2 ( LAMB2 ), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3 −/− mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5 +/− females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α 3 α 4 α 5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.
Abstract P340: The Role of Osteoclast-like Cells in Abdominal Aortic Aneurysm
Authors: Dai Yamanouchi, Colin Stair, Stephanie Morgan, K C Kent
Journal: Circulation Research (2011)

Increasing evidence suggests that arterial calcification is the result of highly organized processes resembling those seen in bone which relies upon a delicate balance between mineral deposition and resorption by osteoblasts and osteoclasts, respectively. Osteoclast-like cells (OLCs) are derived from the monocyte/macrophage lineage and share osteoclast features such as the ability to dissolve extracellular matrix. Although osteoclastogenesis, the development of OLCs, has been reported to occur in calcified arteries, its potential role in the development of abdominal aortic aneurysm (AAA) has yet to be explored. Firstly, we obtained aortic tissues from patients undergoing surgical repair for AAA (N = 5) and aortic occlusive disease (N = 5). Alizarin-Red staining showed calcification in both aneurysmal and occlusive aorta. In contrast, OLCs, recognized as multi-nucleated cells positive for enzymatic TRAP staining, were identified only in aneurysmal aorta (100%, 5 of 5). A time course experiment in mouse calcium chloride-induced AAA (CaCl 2 AAA) showed similarities in both spatial and temporal patterns of calcium deposition and monocyte/macrophage accumulation starting 48 hours followed by OLCs formation peaked at 7 days after CaCl 2 injury. Secondly, we administered bisphosphonate (pamidronate disodium, 1.25 mg/kg, weekly), an inhibitor of osteoclasts, or normal saline as a control, intravenously to mice after CaCl 2 injury (N = 5). Bisphosphonate-treated mice showed a significant reduction in aortic dilation compared to control mice after 7 and 42 days with mean fold change of 1.16 ± 0.04 (vs. 1.65 ± 0.05, P &lt; 0.01) and 1.37 ± 0.12 (vs. 2.17 ± 0.08, P&lt;0.01) respectively. We also studied the effect of bisphosphonate on “developed aneurysm” by delaying the injection of bisphosphonate until one week after the injury to allow the aneurysm to develop prior to injection (N = 5). The mice with delayed bisphosphonate injection also showed significant inhibition compared to the saline control at 42 days (1.56 ± 0.13 vs. 2.42 ± 0.06, P &lt; 0.01). In conclusion, we have demonstrated the existence of OLCs in AAA. We also have demonstrated the inhibitory effect of bisphosphonate on aneurysm. These results indicate a novel approach for the pathogenesis and therapy of AAA.
Stevens-Johnson Syndrome During Pregnancy
Authors: Charles Velter, Claire Hotz, S. Ingen-Housz-Oro, Pierre Wolkenstein, Laurence Fardet
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
SWOG S1221: A phase 1 dose escalation study co-targeting MAPK-dependent and MAPK-independent BRAF inhibitor resistance in BRAF mutant advanced solid tumors with dabrafenib, trametinib, and GSK2141795 (ClinicalTrials.gov NCT01902173).
Authors: Alain Patrick Algazi, James Moon, Bartosz Chmielowski, Roger Lo, Kari Lynn Kendra, Christopher D. Lao, Karl D. Lewis, Rene Gonzalez, Kevin Kim, John E. Godwin, Brendan D. Curti, Megan Othus, Antoni Ribas
Journal: Journal of Clinical Oncology (2017)

2578 Background: Aberrant PI3K/AKT signaling in BRAF mutant cancers contributes to resistance to MAPK pathway blockade. We conducted parallel phase 1 dose escalation studies of the doublet of the BRAFi dabrafenib with the AKT inhibitor GSK2141795 and of the triplet of dabrafenib, the MEKi trametinib, and GSK2141795. Methods: Patients (pts) with BRAF-V600E/K mutant advanced solid tumors with adequate end-organ function were eligible regardless of prior BRAFi and MEKi exposure. All pts received dabrafenib at 150 mg twice daily (bid), in the doublet cohorts together with dose escalation (3 + 3 scheme) of GSK2141795 started at 50 mg daily (qd), and in the triplet cohorts with dose escalation of both trametinib starting at 1.5 mg qd and GSK2141795 starting at 25 mg qd. DLTs included significant grade 3 and 4 adverse events (CTCAE v4) within the first 56 days of treatment. Radiographic responses were assessed at 8-week intervals. Results: No DLTs were observed in the doublet cohorts (N = 8) up to dabrafenib 150 mg bid and GSK2141795 75 mg qd. In the triplet cohorts (N = 11), no DLTs were observed at doses of up to trametinib 1.5 mg daily with GSK2141795 75 mg daily. At the highest triplet dose with dabrafenib 150 mg bid, trametinib 2 mg qd with GSK2141795 75 mg qd, 1 of 2 evaluable pts had a DLT of grade 3 febrile neutropenia and grade 3 maculo-papular rash. 2/2 treatment-naïve in the doublet cohorts had PRs (1 melanoma and 1 thyroid) the latter lasting over 1 year. 1/6 BRAF inhibitor-refractory (melanoma) pts also had an objective response. In the triplet cohorts, 3 of 6 treatment-naïve pts had a PR (1 melanoma, 2 lung). One lung pt remains in PR at 2 months and the otherhas an uPR at 1.2 months. Conclusions: Inhibition of both MAPK and PI3K/AKT pathways was well tolerated, leading to durable objective responses in pts with metastatic melanoma, thyroid cancer, and lung cancer. Further study of dual pathway inhibition is warranted. Funding: Supported in part by NIH/NCI grants CA180888, CA180819; and in part by Novartis Pharmaceuticals Corporation and GlaxoSmithKline, LLC. Clinical trial information: NCT01902173.
Prognostic Model for Resected Squamous Cell Lung Cancer: External Multicenter Validation and Propensity Score Analysis exploring the Impact of Adjuvant and Neoadjuvant Treatment
Authors: Sara Pilotto, Isabella Sperduti, Giovanni Leuzzi, Marco Chiappetta, Felice Mucilli, Giovanni Battista Ratto, Filippo Lococo, Pier Lugigi Filosso, Lorenzo Spaggiari, Silvia Novello, Michele Milella, Antonio Santo, Aldo Scarpa, Maurizio Infante, Giampaolo Tortora, Francesco Facciolo, Emilio Bria
Journal: Journal of Thoracic Oncology (2017)
Determinants of Failure in Hepatic Transplant
Authors: Jorge D. Reyes
Journal: JAMA Surgery (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 Surgery 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 Surgery journal