tbuckley/cabot-search huggingface dataset:
AB0731 Treatment algorithms for systemic sclerosis according to experts
Authors: A. Fernández-Codina, K.M. Walker, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treatment for many aspects of systemic sclerosis (SSc) lacks agreement. <h3>Objectives</h3> To generate SSc treatment algorithms endorsed by high percentage of SSc experts. <h3>Methods</h3> Experts from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research group (n=170) were asked whether they agreed with SSc algorithms (from 2012<sup>1</sup>). A further 2 consensus rounds refined agreement; 62 (36%), 54 and 48 experts completed surveys. <h3>Results</h3> For scleroderma renal crisis (SRC), 82% of the experts agreed (1st line ACEi, 2nd and 3rd adding: CCB or ARB). Pulmonary arterial hypertension (PAH) had 81% agreement. For mild PAH, PDE5i, then endothelin receptor antagonists plus PDE5i, then prostanoids; while for severe PAH prostanoids were first-line. Raynauds’ phenomenon (RP) had 78% of agreement [mild (1st CCB, 2nd adding PDE5i, 3rd ARB or switching to another CCB, 4th prostanoids), severe (1st CCB, 2nd adding PDE5i, 3rd ERA, 4th prostanoids)]. Digital ulcer (DU) treatment had 69% agreement (1st CCB, 2nd PDE5i). Interstitial lung disease (ILD) had 65% agreement including induction (Mycophenolate mofetil (MMF) then intravenous cyclophosphamide then rituximab) and maintenance (1st line MMF). Skin involvement had 71% agreement. For a modified Rodnan skin score (mRSS) of 24 1st MTX, 2nd MMF; and for mRSS 32 1st MMF, 2nd MTX, 3rd intravenous cyclophosphamide (CYP), 4th hematopoietic stem cell transplantation. For inflammatory arthritis 79% agreed with 1st MTX, 2nd low dose glucocorticoids, 3rd hydroxychloroquine, 4th rituximab or tocilizumab. Cardiac and gastrointestinal algorithms had ≥75% agreement. The evolution of the agreement rates is shown in table 1: Agreement is the% who agreed to the algorithm. SSc: Systemic Sclerosis; NA: Not applicable; †For modified Rodnan skin scores 10, 24 and 32, respectively <h3>Conclusions</h3> Total agreement for SSc algorithms was considerable. These SSc algorithms may guide treatment. <h3>Reference</h3> [1] Walker KM, Pope J. Treatment of Systemic Sclerosis Complications: What to Use When First-Line Treatment Fails-A Consensus of Systemic Sclerosis Experts. Semin Arthritis Rheum2012;42:42–55. <h3>Disclosure of Interest</h3> A. Fernández-Codina Grant/research support from: Spanish Federation for Internal Medicine; Ontario Scleroderma Association, K. Walker: None declared, J. Pope Grant/research support from: AbbVie, Actelion, Amgen, BMS, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB
MicroRNA based immune response signature identifies poor prognostic subgroup within ER negative breast cancers
Authors: S. Rajarajan, J. Prabhu, A. Korlimarla, M. Nair, A. Alexander, R. Kaluve, H. Ps, U. Raja, R. Ramesh, S. Patil, S. Bs, S. Ts
Journal: Annals of Oncology (2018)
Successful HCV treatment of patients on contraindicated anti-epileptic drugs: Role of drug level monitoring
Authors: Minou van Seyen, Elise J. Smolders, Peter van Wijngaarden, Joost P.H. Drenth, Marjan Wouthuyzen-Bakker, Robert J. de Knegt, Pieter Honkoop, Omar El-Sherif, Angela Colbers, David J. Back, David M. Burger
Journal: Journal of Hepatology (2018)
Re: Marco Moschini, Emanuele Zaffuto, Pierre I. Karakiewicz, et al. External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis. Eur Urol 2019;75:319–28
Authors: Nicholas G. Zaorsky, Daniel E. Spratt, Pierre Blanchard
Journal: European Urology (2018)
Neuropeptide receptors as potential pharmacological targets for obesity
Authors: Beatriz T. Meneguetti, Marlon H. Cardoso, Camila F.A. Ribeiro, Mário R. Felício, Ingrid B. Pinto, Nuno C. Santos, Cristiano M.E. Carvalho, Octávio L. Franco
Journal: Pharmacology & Therapeutics (2018)
Moving the Needle Toward a More Personalized Means of Patient Care
Authors: Hanna K. Gaggin, James L. Januzzi
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Abstract 19026: Prospective Registry of Cardiac Critical Illness in the Modern Cardiac Intensive Care Unit (CICU)
Authors: Ryan A Watson, Erin A Bohula, Thomas C Gilliland, Pablo A Sanchez, David D Berg, Benjamin A Olenchock, David A Morrow
Journal: Circulation (2017)

Introduction: ‘Coronary care units’ were created in the 1960s to rapidly identify and treat patients with arrhythmia after acute myocardial infarction (MI). The landscape of care in the modern Card...
Biological Consequences of MHC-II Expression by Tumor Cells in Cancer
Authors: Margaret L. Axelrod, Rebecca S. Cook, Douglas B. Johnson, Justin M. Balko
Journal: Clinical Cancer Research (2018)

Abstract Immunotherapy has emerged as a key pillar of cancer treatment. To build upon the recent successes of immunotherapy, intense research efforts are aimed at a molecular understanding of antitumor immune responses, identification of biomarkers of immunotherapy response and resistance, and novel strategies to circumvent resistance. These studies are revealing new insight into the intricacies of tumor cell recognition by the immune system, in large part through MHCs. Although tumor cells widely express MHC-I, a subset of tumors originating from a variety of tissues also express MHC-II, an antigen-presenting complex traditionally associated with professional antigen-presenting cells. MHC-II is critical for antigen presentation to CD4+ T lymphocytes, whose role in antitumor immunity is becoming increasingly appreciated. Accumulating evidence demonstrates that tumor-specific MHC-II associates with favorable outcomes in patients with cancer, including those treated with immunotherapies, and with tumor rejection in murine models. Herein, we will review current research regarding tumor-enriched MHC-II expression and regulation in a range of human tumors and murine models, and the possible therapeutic applications of tumor-specific MHC-II.
Hyperplastic/proliferating perilobar nephrogenic rests are molecular genetic precursor lesions of Wilms tumor
Authors: Raisa Vuononvirta, Jorge Reis-Filho, Neil Sebire, Alan Mackay, Kerry Fenwick, Alan Ashworth, Kathy Pritchard-Jones, Gordan Vujanic, Chris Jones
Journal: Cancer Research (2007)

2941  Wilms tumor (nephroblastoma) is one of the most common pediatric solid tumors, affecting approximately 1 in 10,000 children. It is considered an embryonal malignancy as it is thought to arise from metanephric blastemal cells that failed to properly differentiate into the epithelial components of the kidney. Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells that are thought to be precursor lesions of Wilms tumor, as they are encountered in 25-40% of patients with nephroblastoma (up to 100% in bilateral disease), and in less than 1% of infant autopsies. Little is known about the molecular alterations present in these putative WT precursor lesions, although loss of heterozygosity (LOH) at 11p13 (WT1) and loss of imprinting at 11p15 (IGF2, H19) have been reported to be early events in Wilms tumorigenesis. We wished to investigate the molecular genetics of nephrogenic rests in order to identify the earliest changes associated with Wilms tumor development. Forty-six cases of perilobar nephrogenic rests (PLNRs) were microdissected from formalin-fixed, paraffin-embedded tissue and profiled by aCGH profiling on a 5.8K 1Mb-spaced or 32K genome-wide tiling path BAC array platform. The majority of PLNRs showed no copy number alterations. Recurrent genomic abnormalities included gains and/or losses at loci known to be involved in Wilms tumor, such as small deletions at 11p13 and trisomies 8 and 12. PLNRs were classified as proliferating or quiescent according to their proliferation index as determined by Ki-67 immunohistochemistry. Proliferating rests harbored significantly more copy number alterations than quiescent PLNRs, and were genetically most similar to Wilms tumors. Paired comparison of the genomic profiles of matched PLNRs and corresponding Wilms tumors from the same patient revealed the same alterations observed in the rests to be present in the tumors, along with additional changes. Those alterations observed in both PLNRs and tumors are defined as early changes in Wilms tumorigenesis, and included gains at 7q, 8, 12 and 18 and losses at 1p, 7p, 11p and 11q. Changes never observed in rests, and only seen (recurrently) in Wilms tumors included gains at 1q, 6, and 15q, and losses at 16q, and may be defined as late events. Interestingly, these loci are reported to be associated with treatment failure and relapse. These data provide a comprehensive mapping of the genomic events associated with Wilms tumor development. Such analysis will provide a framework for refinement of the multi-step model of Wilms tumorigenesis as well as support the concept of hyperplastic PLNRs as molecular genetic precursor lesions of Wilms tumor.
Risk scores overestimated risk for CVD in newly diagnosed type 2 diabetes
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2018)

Source Citation Read SH, van Diepen M, Colhoun HM, et al; Scottish Diabetes Research Network Epidemiology Group. Performance of cardiovascular disease risk scores in people diagnosed with type 2 diabetes: external validation using data from the National Scottish Diabetes Register. Diabetes Care. 2018;41:2010-18. 30002197
Cancer-associated Fibroblast–promoted LncRNA <i>DNM3OS</i> Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma
Authors: Hongfang Zhang, Yuhui Hua, Zhenzhen Jiang, Jing Yue, Ming Shi, Xiaoli Zhen, Xiaoyan Zhang, Ling Yang, Rongjing Zhou, Shixiu Wu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC). Experimental Design: By use of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and in situ hybridization assay. The association of DNM3OS and tumor radioresistance was investigated in vitro and in vivo. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation. Results: Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance in vitro and in vivo by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFβ/PDGFRβ/FOXO1 signaling pathway–dependent manner. FOXO1, a transcription factor downstream of PDGFβ/PDGFRβ signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter. Conclusions: Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.
An in vitro model of metastatic breast cancer cell extravasation through endothelial cell monolayers
Authors: Janet Price, Irene Newsham
Journal: Cancer Research (2008)

441  Metastasis is the principal cause of death from breast cancer. The extravasation of cancer cells from the circulation is thought to be a critical step in metastasis, and is difficult to model in vitro. We are using Electric Cell Substrate Impedance Sensing (ECIS) as a model of cancer cell extravasation through monolayers of endothelial cells. This assay is based on the measurement of changes in resistance across a 250-um electrode to the flow of small AC currents. When cells are plated onto electrodes in modified culture slides, current flow is impeded proportional to the adhesion and attachment of the cells. Extravasation of cells through an endothelial monolayer plated onto the electrodes is detected by a drop in resistance values, corresponding to the increased flow of current as the endothelial cells retract. The assay was used to compare the extravasation abilities of the human breast cancer cell line MDA-MB-231 and isogenic variants established from metastases in the brain and lungs of nude mice. Compared with the original cell line and the lung metastasis-derived variant, the brain metastasis-derived 231-BR3 variant had greater ability to form experimental brain metastases. The 231-BR3 cells also had greater potential to extravasate through a monolayer of rat brain endothelial cells, indicated by a sharp decline in ECIS resistance values by 6 - 8 h after plating the cancer cells. Scanning electron microscopy of the co-cultures showed the appearance of gaps between endothelial cells as cancer cells penetrated the monolayer. The 231-BR3 cells release more vascular endothelial growth factor (VEGF) than MDA-MB-231 cells. VEGF promotes vascular permeability, disrupts endothelial barrier function, and thus may facilitate the extravasation of metastatic cells. Expression of VEGF in 231-BR3 cells was significantly suppressed using siRNA (control = 1,350 pg /ml vs. siRNA treated = 25 pg/ml, measured by ELISA ). The cells with silenced VEGF showed reduced extravasation in the ECIS assay. Pre-treatment of the endothelial cell monolayers for 1 hr with an inhibitor of VEGF-receptor tyrosine kinases (PTK787) also attenuated the extravasation of 231-BR3 cells. The results suggest that high VEGF expression contributed to the enhanced extravasation ability of 231-BR3 cells.  Conclusions: The ECIS assay can provide novel information about interactions between metastatic cells and endothelial cells, and the molecules involved in the process of extravasation. The assay can be used as a tool to identify the molecular regulators of cancer cell extravasation.  Supported in part by the DOD Breast Cancer Research Program, award # W81XWH-06-2-0033.
A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis
Authors: Andrew Volk, Kaiwei Liang, Praveen Suraneni, Xinyu Li, Jianyun Zhao, Marinka Bulic, Stacy Marshall, Kirthi Pulakanti, Sebastien Malinge, Jeffrey Taub, Yubin Ge, Sridhar Rao, Elizabeth Bartom, Ali Shilatifard, John D. Crispino
Journal: Cancer Cell (2018)
AB1171 Ultrasound assessment of the knee in elderly japanese population
Authors: A. Okahata, H. Ito, M. Furu, S. Kuriyama, S. Nakamura, M. Ishikawa, Y. Morita, M. Azukizawa, Y. Hamamoto, Y. Tanaka, Y. Tabara, F. Matsuda, S. Matsuda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is known as degenerative arthritis. Knee OA is a common disease among aged population and one of the leading causes of disability. Many modalities are used to evaluate bony abnormalities and joint space narrowing for knee OA. Ultrasound is one of the imaging modalities for evaluating knee joint structures such as cartilage, meniscus, osteophyte and synovium. There are few large-scale studies focused on ultrasound findings of the knee of the elderly in general population. <h3>Objectives</h3> The aim of our study is to evaluate relationship between clinical and ultrasound findings of the elder population. <h3>Methods</h3> Two hundred and twenty two participants were recruited from Nagahama residents aged 60 years or older. We evaluated the both knees of participants with ultrasound with a 5MHz transducer. Ultrasound scans were performed and assessed by a standardised protocol of the Outcome Measures in Rheumatoid Arthritis Clinical Trial Guidelines. The symptoms were clinically assessed by using <sup>Knee Society Score 2011</sup> (KSS). We statistically examined whether the KSS(symptom) correlated with other clinical parameters and each ultrasonographical findings. <h3>Results</h3> Participants were 65 men and 137 women with a mean age of 67±5 years old. The mean body mass index (BMI) was 21.8±2.76 kg/m<sup>2</sup>. The symptom subscale of KSS were significantly associated with age, BMI, knee maximum extension and flexion angle, suprapatellar effusion, medial meniscus protorusion, medial recess synovial hypertorophy, and femoral and tibial medial osteophytes. Multiple regression analysis showed that medial osteophytes was most closely related to the symptom subscale of KSS among the ultrasound findings and demographic data evaluated. <h3>Conclusions</h3> The present study showed a strong association between the symptoms of the knee and the medial osteophytes in Japanese elder population. <h3>References</h3> [1] Linaker CH,et al. Clin Rheumatol1999. [2] S. Saarakkala,et al.Osteoarthritis and Cartilage2012. [3] Schmidt WA, et al. Ann Rheum Dis2004. [4] Wakefield RJ, et al. J Rheumatol2005 <h3>Disclosure of Interest</h3> None declared
Baby care: RCOG finds average of seven factors behind each stillbirth, neonatal death, and brain injury
Authors: Jacqui Wise
Journal: BMJ (2018)

Different care might have made a difference to the outcome in almost three quarters of cases of stillbirths, neonatal deaths, and severe brain injuries to babies resulting from labour, concludes the latest report from the Royal College of Obstetricians and Gynaecologists.1

The report says that the main areas of care in which improvements might have changed the outcomes included a failure by health professionals to identify or act on relevant risk factors, issues relating to monitoring fetal wellbeing with cardiotocography and blood sampling, and individual education or training issues.

Each Baby Counts is the college’s national quality improvement initiative, which aims to halve by 2020 the number of babies who die or are left severely disabled …
A tired young man with a dysmorphic thumb
Authors: Grzegorz Nalepa
Journal: BMJ (2018)

A 23 year old man with short stature, congenital malformation of the left thumb and both ears, and a single kidney presented with back pain, shortness of breath, fatigue, and easy bruising that had developed over several months. Physical examination revealed hepatosplenomegaly.

His brother had died in early childhood, more than 20 years ago. The patient’s parents reported that his brother, “had similar but worse congenital malformations, including bad kidney problems.”

Full blood count showed pancytopaenia, which prompted further laboratory investigations (table 1).

View this table:

Table 1 
Initial laboratory investigations



Radiography of the patient’s left hand (fig 1) revealed a single fused phalanx, anomalous carpal bones, and a hypoplastic radial styloid.



Fig 1 
(A) Dysmorphic left thumb. …
A real-world study of osimertinib: ASTRIS 2nd DCO Korean subgroup analysis
Authors: J.-S. Lee, B.C. Cho, D.-W. Kim, K. Park, J.H. Kang, S.S. Yoo, S.Y. Lee, C.H. Kim, S.H. Jang, Y.C. Kim, H.-K. Yoon, S.-W. Kim
Journal: Annals of Oncology (2018)
OP0021 Draft classification criteria for the anca associated vasculitides
Authors: J.C. Robson, P.C. Grayson, C. Ponte, R. Suppiah, A. Craven, S. Khalid, A. Judge, A. Hutchings, D. Gray, J. Rosa, J. Barrett, R.A. Watts, P.A. Merkel, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Classification criteria for the ANCA-associated vasculitides (AAVs) were developed in the 1980s prior to the use of ANCA testing and newer imaging techniques. The Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study is an international project to update classification criteria for the systemic vasculitides. <h3>Objectives</h3> Development of draft classification criteria for Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA). <h3>Methods</h3> Three phases: 1) Expert panel review of cases to identify gold standard set of new cases of small vessel vasculitis; 2) Item reduction of &gt;8000 individual DCVAS items using data-driven and consensus methodology; 3) Lasso logistic regression models within each development set comparing each of the AAV types to other small and medium vessel vasculitides. Final criteria derived through clinical consensus, tested in validation set. The classification project has received financial support from the ACR and EULAR. <h3>Results</h3> The expert review process approved 2072/2871 (72%) of physician diagnosed DCVAS cases, including [724 GPA, 291 MPA, 226 EGPA, 51 polyarteritis nodose (PAN), 220 other small vessel disease (SVV)]. Data driven and expert consensus resulted in 91 items retained. Draft criteria, and sensitivity and specificity in table 1. <h3>Conclusions</h3> Draft classification criteria for GPA, MPA and EGPA have been created which reflect current practice and have good sensitivity and specificity. <h3>Acknowledgements</h3> DCVAS sites and expert panel members <h3>Disclosure of Interest</h3> None declared
VIPER: variability-preserving imputation for accurate gene expression recovery in single-cell RNA sequencing studies
Authors: Mengjie Chen, Xiang Zhou
Journal: Genome biology (2018)

We develop a method, VIPER, to impute the zero values in single-cell RNA sequencing studies to facilitate accurate transcriptome quantification at the single-cell level. VIPER is based on nonnegative sparse regression models and is capable of progressively inferring a sparse set of local neighborhood cells that are most predictive of the expression levels of the cell of interest for imputation. A key feature of our method is its ability to preserve gene expression variability across cells after imputation. We illustrate the advantages of our method through several well-designed real data-based analytical experiments.