tbuckley/cabot-search huggingface dataset:
Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage
Authors: Lauren C Peres, Kara L Cushing-Haugen, Martin Köbel, Holly R Harris, Andrew Berchuck, Mary Anne Rossing, Joellen M Schildkraut, Jennifer A Doherty
Journal: JNCI Journal of the National Cancer Institute (2018)

The understanding of ovarian cancer pathogenesis has recently shifted to recognize distinct changes in how ovarian cancer histotypes are defined. Using the 2014 World Health Organization (WHO) diagnostic guidelines, we classified ovarian cancer histotypes in Surveillance, Epidemiology, and End Results (SEER) cancer registry data and examined survival patterns by histotype and disease stage. We extracted data on 28 118 incident epithelial ovarian cancer cases diagnosed in 2004–2014 from SEER and defined histotype using the 2014 WHO guidelines (high-grade serous, low-grade serous, endometrioid, clear cell, mucinous, carcinosarcoma, and malignant Brenner tumors). By histotype and disease stage, we estimated Kaplan-Meier survival curves and calculated age-adjusted overall and cause-specific survival estimates. Cox proportional hazards regression models were used to estimate histotype-specific hazard ratios (HRs) and 95% confidence intervals (CIs) by disease stage while adjusting for age at diagnosis, region, race/ethnicity, and receipt of surgery. Within two years after diagnosis, localized/regional-stage carcinosarcoma and distant-stage mucinous, clear cell, and carcinosarcoma had a higher risk of mortality compared with high-grade serous, with the most pronounced association for localized/regional carcinosarcoma (>1–2-year time period: HR = 3.81, 95% CI = 2.74 to 5.30) and distant-stage mucinous (0–1-year time period: HR = 3.87, 95% CI = 3.45 to 4.34). In the time period more than four to 10 years after diagnosis, hazard ratios for all histotypes relative to high-grade serous, irrespective of disease stage, were less than 1.00. Cumulatively, both localized/regional and distant-stage low-grade serous and endometrioid carcinomas had the most favorable outcomes. Our large study, which is representative of the United States population and incorporates the most current knowledge of ovarian cancer pathogenesis, highlights the need to recognize ovarian cancer as a set of distinct diseases and not a single entity. Only then will we be able to effectively target the unique features of each histotype to reduce ovarian cancer mortality.
P322Notch signaling pathway is attenuated in aortic endothelial cells of patients with aortic pathologies associated with bicuspid aortic valve
Authors: A Kostina, A Kiselev, H Bjorck, O Irtyuga, A Sergushichev, Y Baranov, P Eriksson, A Kostareva, A Malashicheva
Journal: Cardiovascular Research (2018)
Abstract 13935: Ca2+ Signaling is Required for Cardiomyocyte Hypertrophy During Chamber Development Independent of Contraction or Blood Flow
Authors: Nicholas D Andersen, Kapil Ramachandran, Michelle M Bao, Bijoy Thattaliyath, Geoffrey S Pitt, Margaret L Kirby, Mary R Hutson
Journal: Circulation (2013)

OBJECTIVES: In utero interventions aimed at restoring left ventricular hemodynamic forces in fetuses with prenatally diagnosed hypoplastic left heart syndrome (HLHS) failed to rescue left ventricul...
Identification of Epigenetic Regulators of DUX4-fl for Targeted Therapy of Facioscapulohumeral Muscular Dystrophy
Authors: Charis L. Himeda, Takako I. Jones, Ching-Man Virbasius, Lihua Julie Zhu, Michael R. Green, Peter L. Jones
Journal: Molecular Therapy (2018)

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes. We confirmed several of the strongest and most specific candidates (ASH1L, BRD2, KDM4C, and SMARCA5) in skeletal myocytes from two other unrelated FSHD1 patients, and we showed that knockdown led to reduced levels of DUX4-fl and DUX4-FL target genes, as well as altered chromatin at the D4Z4 locus. As a second mode of validation, targeting the CRISPR/dCas9-KRAB transcriptional repressor to the promoters of several candidates also led to reduced levels of DUX4-fl. Furthermore, these candidates can be repressed by different methods in skeletal myocytes without major effects on certain critical muscle genes. Our results demonstrate that expression of DUX4-fl is regulated by multiple epigenetic pathways, and they indicate viable, druggable candidates for therapeutic target development.
Pharmacological inhibition of myeloperoxidase attenuates nonalcoholic steatohepatitis-induced liver fibrosis in mice
Authors: A. Koop, N. Thiele, D. Steins, T. Diedrich, E. Michaëlsson, J.S.Z. Wiesch, A.W. Lohse, J. Heeren, J. Kluwe
Journal: Journal of Hepatology (2018)
Improving Emergency Insulin Administration
Authors: Robert J. Rushakoff, Heidemarie W. Macmaster
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Concerns About the Approval of Nusinersen Sodium by the US Food and Drug Administration
Authors: Martha S. Gerrity, Vinay Prasad, Adam J. Obley
Journal: JAMA Internal Medicine (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 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
Closing the Loop: From Motor Neuroscience to Neurorehabilitation
Authors: Ryan T. Roemmich, Amy J. Bastian
Journal: Annual Review of Neuroscience (2018)

The fields of human motor control, motor learning, and neurorehabilitation have long been linked by the intuition that understanding how we move (and learn to move) leads to better rehabilitation. In reality, these fields have remained largely separate. Our knowledge of the neural control of movement has expanded, but principles that can directly impact rehabilitation efficacy remain somewhat sparse. This raises two important questions: What can basic studies of motor learning really tell us about rehabilitation, and are we asking the right questions to improve the lives of patients? This review aims to contextualize recent advances in computational and behavioral studies of human motor learning within the framework of neurorehabilitation. We also discuss our views of the current challenges facing rehabilitation and outline potential clinical applications from recent theoretical and basic studies of motor learning and control.
Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia
Authors: Carsten Hjorthøj, Nikolai Albert, Merete Nordentoft
Journal: JAMA Psychiatry (2018)

Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.Information on substance use disorders combined from 5 different registers.Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.
Age, risk and outcomes in idiopathic pulmonary arterial hypertension
Authors: Marius M. Hoeper, Athénaïs Boucly, Olivier Sitbon
Journal: European Respiratory Journal (2018)

The current European pulmonary hypertension (PH) guidelines recommend a risk-based therapeutic approach to patients with idiopathic pulmonary arterial hypertension (IPAH) [1, 2]. The goal is reaching and maintaining a low risk profile. Recent studies from the French PH registry and from the European PH registry COMPERA have confirmed that IPAH patients who meet 3–4 distinct low risk criteria with targeted therapies have 5-year survival rates of 95% or higher [3, 4]. Unfortunately, this was accomplished only in 19% of the patients in the French series and 9% of the patients in COMPERA [4, 5]. The reasons why the majority of patients fail to reach a low risk profile with targeted therapies have not been fully explored. Older patients with IPAH often present with distinct phenotypes and show less improvements with targeted therapy than younger patients <http://ow.ly/vsCb30jqOB3>
The Value in an Ambulatory Blood-Pressure Registry
Authors: Raymond R. Townsend
Journal: New England Journal of Medicine (2018)

Ambulatory blood-pressure monitoring provides the best confirmation of the presence of hypertension detected in the office setting. A systematic review sponsored by the Agency for Healthcare Research and Quality concluded that "evidence supports ambulatory blood-pressure monitoring as the reference standard for confirming elevated office blood pressure … to avoid misdiagnosis and overtreatment," particularly for persons who have elevated blood pressure as measured in the office but normal ambulatory pressure ("white-coat" hypertension).1 In 2011, the United Kingdom's National Institute for Health and Care Excellence recommended that providers obtain ambulatory blood-pressure data to confirm the diagnosis of hypertension (clinical guideline 127). Other medical . . .
Association of Prehospital Advanced Life Support by Physician With Survival After Out-of-Hospital Cardiac Arrest With Blunt Trauma Following Traffic Collisions
Authors: Tatsuma Fukuda, Naoko Ohashi-Fukuda, Yutaka Kondo, Kei Hayashida, Ichiro Kukita
Journal: JAMA Surgery (2018)

Controversy remains as to whether advanced life support (ALS) or basic life support (BLS) is superior for critically ill and injured patients, including out-of-hospital cardiac arrest (OHCA) and major trauma, in the prehospital setting.To assess whether prehospital ALS should be provided for traumatic OHCA and who should perform it.Japanese government-managed nationwide population-based registry data of patients with OHCA transported to an emergency hospital were analyzed. Patients who experienced traumatic OHCA following a traffic collision from 2013 to 2014 were included. Patients provided prehospital ALS by a physician were compared with both patients provided ALS by emergency medical service (EMS) personnel and patients with only BLS. The data were analyzed on May 1, 2017.Advanced life support by physician, ALS by EMS personnel, or BLS only.The primary outcome was 1-month survival. The secondary outcomes were prehospital return of spontaneous circulation and favorable neurologic outcomes with the Glasgow-Pittsburgh cerebral performance category score of 1 or 2.A total of 4382 patients were included (mean [SD] age, 57.5 [22.2] years; 67.9% male); 828 (18.9%) received prehospital ALS by physician, 1591 (36.3%) received prehospital ALS by EMS personnel, and 1963 (44.8%) received BLS only. Among these patients, 96 (2.2%) survived 1 month after OHCA, including 26 of 828 (3.1%) for ALS by physician, 25 of 1591 (1.6%) for ALS by EMS personnel, and 45 of 1963 (2.3%) for BLS. After adjusting for potential confounders using multivariable logistic regression, ALS by physician was significantly associated with higher odds for 1-month survival compared with both ALS by EMS personnel and BLS (adjusted OR, 2.13; 95% CI, 1.20-3.78; and adjusted OR, 1.94; 95% CI, 1.14-3.25; respectively), whereas there was no significant difference between ALS by EMS personnel and BLS (adjusted OR, 0.91; 95% CI, 0.54-1.51). A propensity score-matched analysis in the ALS cohort showed that ALS by physician was associated with increased chance of 1-month survival compared with ALS by EMS personnel (risk ratio, 2.00; 95% CI, 1.01-3.97; P = .04). This association was consistent across a variety of sensitivity analyses.In traumatic OHCA, ALS by physician was associated with increased chance of 1-month survival compared with both ALS by EMS personnel and BLS.
Nonequilibrium Neutral Theory for Hitchhikers
Authors: Yoko Satta, Naoko T Fujito, Naoyuki Takahata
Journal: Molecular Biology and Evolution (2018)

Selective sweep is a phenomenon of reduced variation at presumably neutrally evolving sites (hitchhikers) in the genome that is caused by the spread of a selected allele at a linked focal site, and is widely used to test for action of positive selection. Nonetheless, selective sweep may also provide an unprecedented opportunity for studying nonequilibrium properties of the neutral variation itself. We have demonstrated this possibility in relation to ancient selective sweep for modern human-specific changes and ongoing selective sweep for local population-specific changes.
Tyrosines in the MUC1 cytoplasmic tail modulate oncogenic signaling pathways
Authors: Eric J. Thompson, Kandavel Shanmugam, Kari L. Kotlarczyk, Christine L. Hattrup, Albert Gutierrez, Judy M. Bradley, Pinku Mukherjee, Sandra J. Gendler
Journal: Cancer Research (2005)

946  MUC1 is an oncogene and tumor marker, which is overexpressed in numerous adenocarcinomas. Structurally, it is a transmembrane heterodimer with an extracellular domain composed primarily of heavily glycosylated twenty amino acid tandem repeats and a 72 amino acid cytoplasmic tail (CT). Several protein-protein interaction motifs have been identified in the CT that contain tyrosines, phosphorylation of which leads to the recruitment of receptor and non-receptor tyrosine kinases. The impact of subsequent signaling events is poorly understood. We have developed a cell line based model system to study the significance of tyrosine based signaling of the MUC1 CT within the context of full-length MUC1. COS-7 cells, a MUC1 non-expresser, were utilized to prevent the effects of signaling due to endogenous expression. Critical function(s) of the MUC1 CT tyrosines was addressed by direct comparison of cells expressing wildtype MUC1 (MUC1WT) and MUC1 lacking tyrosines in the CT (MUC1Y0). The broad implications of signaling via the MUC1 CT were determined by studying pathways commonly dysregulated in cancers. To this end, we first addressed the impact of MUC1-dependent signals on proliferative index (PI). Surprisingly, the presence of MUC1WT did not alter the PI, although MUC1Y0 resulted in an approximately 30-fold increase in PI as measured by 3H-thymidine incorporation, which correlated with a robust increase in Erk1/2 phosphorylation. A downstream effector of Erk1/2 activity is AP-1, which was assayed using a luciferase reporter. Cells expressing MUC1Y0 exhibited 2.5 and 5-fold increases in AP-1 activity compared to cells expressing MUC1WT and the neo control, respectively. Secondly, we examined the invasive potential of the cells expressing MUC1WT or MUC1Y0 and found that MUC1Y0 confers a 2-3-fold increase in invasion. In line with these results, we observed a 40% decrease in basal cell death and 33% increased sensitivity to Taxol-induced cell death in the MUC1Y0 cells as compared to MUC1WT or neo control. The relevance of MUC1 CT tyrosine-mediated interactions in modulating cell death via transcriptional regulation of NF-κB complexes was analyzed using a luciferase reporter, which showed 2-fold increased activity for MUC1WT compared to the neo control, while the MUC1Y0 displayed a fifth of the neo control activity. This study demonstrates the importance of the CT tyrosines, the lack of which induced substantial changes in various signaling pathways, and demonstrates for the first time that MUC1 signals can modulate the transcriptional activity of AP-1 and NF-κB. Experiments that delineate this effect of the MUC1 CT via other interactions, which impinge on both cytoplasmic signaling and modulation of transcription of various complexes, are underway. Supported by NIH CA94389 & ACS PF-04-256-01-M601
Uncoupling Diagnosis and Treatment of Incidentally Imaged Renal Masses—Reply
Authors: H. Gilbert Welch, Florian R. Schroeck
Journal: JAMA Internal Medicine (2018)

In Reply We appreciate both responses to our Original Investigation,1 as well as the fact that they are from urological surgeons in Canada and the United Kingdom. We hope all surgeons will agree with the need for more conservative, risk-based strategies for small renal masses.
A Randomized Trial of Early Endovenous Ablation in Venous Ulceration
Authors: Manjit S. Gohel, Francine Heatley, Xinxue Liu, Andrew Bradbury, Richard Bulbulia, Nicky Cullum, David M. Epstein, Isaac Nyamekye, Keith R. Poskitt, Sophie Renton, Jane Warwick, Alun H. Davies
Journal: New England Journal of Medicine (2018)

Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear.
Abstract 12021: Ambulatory Blood Pressure Correlates With Chronic Renal Tubulointerstitial Injury in Patients With IgA Nephropathy
Authors: Kotaro Haruhara, Nobuo Tsuboi, Kentaro Koike, Go Kanzaki, Yusuke Okabayashi, Yoichi Miyazaki, Tetsuya Kawamura, Makoto Ogura, Takashi Yokoo
Journal: Circulation (2015)

Introduction: Hypertension is a major prognostic factor in IgA nephropathy (IgAN), the most common form of primary glomerulonephritis and a major cause of ESRD worldwide. However, there are few studies that assessed the ambulatory blood pressure (ABP) in IgAN patients, which could detect the abnormality in circadian BP and predict long-term renal or cardiovascular outcomes. Hypothesis: Renal histopathological changes established by chronic exposure to injuries may have effects on the abnormal regulation of circadian BP in IgAN patients. Methods: This cross-sectional study included biopsy-proven IgAN patients, in whom both renal biopsy and ABP monitoring were performed during the same hospitalization. The histopathological findings were assessed and analyzed in relation to ABP. Results: A total of 111 IgAN patients were included. The score for interstitial fibrosis and tubular atrophy (IF/TA) was significantly associated with the both values of daytime and nighttime ABP. In contrast, the score for global and segmental glomerulosclerosis, arterial, and arteriole lesions did not show significant associations with these ABP values. These results were almost similar in the subgroup analyses of patients without apparent renal function decline (eGFR&gt;30mL/min/1.73m2) or those without antihypertensive medications. In the multiple linear regression analyses, the severity of IF/TA was associated with the both values of daytime and nighttime ABP, independent of age, gender, renal function, severity of proteinuria, and use of antihypertensive medications. On the other hand, the severity of glomerular lesions was not associated with these ABP values after adjustment (Table). The night to day ratio of mean ABP did not display significant trends according to any renal histopathological lesions. Conclusions: These results suggest that IF/TA is the most relevant renal histopathological finding associated with abnormal regulation of circadian BP in IgAN patients.
P141Raf kinase inhibitor protein mediates myocardial fibrosis in pressure overload through the regulation of the nuclear expression of nuclear factor erythroid 2-related factor 2
Authors: A Kazakov, R A Hall, C Werner, T Meier, A Trouvain, S Rodionycheva, F Lammert, C Maack, M Bohm, U Laufs
Journal: Cardiovascular Research (2018)
A virological response to PEG-IFNa treatment of hepatitis delta is associated with an improved clinical long-term outcome: 10 years follow-up of the HIDIT-1 study
Authors: A. Wranke, C. Yurdaydin, B. Heidrich, Z. Kalliopi, K. Yalcin, T. Fehmi, U. Akarca, F. Lammert, D. Häussinger, T. Müller, M. Wöbse, M.P. Manns, H. Wedemeyer, S. Hardtke
Journal: Journal of Hepatology (2018)