tbuckley/cabot-search huggingface dataset:
Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus
Authors: Efrosini Papadaki, Antonis Fanouriakis, Eleftherios Kavroulakis, Dimitra Karageorgou, Prodromos Sidiropoulos, George Bertsias, Panagiotis Simos, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Cerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion MRI (DSC-MRI), a minimally invasive and widely available method of cerebral perfusion assessment, may assist neuropsychiatric SLE (NPSLE) diagnosis. Methods In total, 76patients with SLE (37 primary NPSLE, 16 secondary NPSLE, 23 non-NPSLE) and 31 healthy controls underwent conventional MRI (cMRI) and DSC-MRI. Attribution of NPSLE to lupus or not was based on multidisciplinary assessment including cMRI results and response to treatment. Cerebral blood volume and flow were estimated in 18 normal-appearing white and deep grey matter areas. Results The most common manifestations were mood disorder, cognitive disorder and headache. Patients with primary NPSLE had lower cerebral blood flow and volume in several normal-appearing white matter areas compared with controls (P&lt;0.0001) and lower cerebral blood flow in the semioval centre bilaterally, compared with non-NPSLE and patients with secondary NPSLE (P&lt;0.001). A cut-off for cerebral blood flow of 0.77 in the left semioval centre discriminated primary NPSLE from non-NPSLE/secondary NPSLE with 80% sensitivity and 67%–69% specificity. Blood flow values in the left semioval centre showed substantially higher sensitivity than cMRI (81% vs 19%–24%) for diagnosing primary NPSLE with the combination of the two modalities yielding 94%–100% specificity in discriminating primary from secondary NPSLE. Conclusion Primary NPSLE is characterised by significant hypoperfusion in cerebral white matter that appears normal on cMRI. The combination of DSC-MRI-measured blood flow in the brain semioval centre with conventional MRI may improve NPSLE diagnosis.
Induction of specific anti-tumor responses by CA9 peptide vaccination in patients with metastatic renal cell carcinoma
Authors: Hirotsugu Uemura, Shigeya Uejima, Motoyoshi Tanaka, Kiyohide Fujimoto, Yoshihiko Hirao, Kyogo Itoh
Journal: Cancer Research (2006)

2882  Background: We have previously developed and characterized 9mer peptide vaccines derived from carbonic anhydrase 9 (CA9), a tumor-associated antigen frequently expressed in renal cell carcinomas. To assess the safety and toxicity of the peptide vaccines (CA9p219, p288, p323), a phase-I clinical trial was carried out for patients with cytokine-refractory metastatic renal cell carcinoma. Methods: Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed renal cell carcinoma were enrolled in this study. Eligibility required progressive disease after standard cytokine therapy with interleukin-2 and/or interferon-alpha. Four weeks after any of prior anti-tumor therapy, patients were vaccinated subcutaneously with each peptide vaccine emulsified with incomplete Freund adjuvant at two weeks intervals. Before the first vaccination and after every three vaccinations, blood samples were taken from the patients for toxicity assessment and immunological study to evaluate the presence of cytotoxic T lymphocytes (CTLs) reactive to each peptide as well as CA9 expressing cancer cells. Clinical responses were investigated every three months. Results: Overall peptide vaccinations were generally tolerated with no major adverse events. The most frequent toxicity was skin redness and swelling at the vaccination site. Most of the patients developed peptide-specific CTLs and antibodies (IgG) after the 6th or 9th vaccination, and serial increase of peptide-specific CTL responses and peptide-reactive serum IgG production was observed thereafter. 51Cr release assay revealed that CA9 peptide vaccinations could induce direct killing against endogenously CA9 expressing cancer cells with HLA-A24 restricted manner. Peptide-specific DTH reactions were observed in six patients. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Stable disease more than 6 months was observed in 6 patients for median duration of 12.2 months. Moreover, the median survival time was 26 months and progression free survival was 6.0 months. Conclusions: These results suggest that HLA-A24 restricted CA9 peptide vaccination therapy is safe and applicable for metastatic RCC patients.
Abstract 11981: Can Preoperative Intensive Carotid And Intracranial Artery Screening Reduce Perioperative Strokes in Cardiovascular Surgery?
Authors: Ken-ichi Imasaka, Eiki Tayama, Yukihiro Tomita
Journal: Circulation (2016)

Introduction: The occurrence of stroke is a concern in patients undergoing cardiac surgery (CS) concomitant with carotid and/or intracranial artery disease (CIAD). Although the 2011 American Heart Association guidelines recommend screening only selected patients referred for elective CS, the clinical utility of CIAD screening is poorly understood. Objectives: To evaluate the effectiveness of CIAD screening for patients undergoing elective CS. Methods: Between February 2004 and December 2014, 1095 of 1134 patients (97%) underwent routine CIAD screening before CS at our institute. CS included coronary artery bypass grafting (CABG) in 378 (34%) patients, CABG + valve surgery in 151 (13%), valve surgery in 480 (42%), aortic surgery without brain protection in 43 (4%), and others in 82 (7%). Patients were divided as follows: those who underwent CS before (n=500) and those after (n=634) the introduction of intensive screening (IS) in January 2009. Preoperative screening had undergone transition in 2009, from the evaluation of carotid atherosclerosis alone to that of carotid and intracranial atherosclerosis. Moreover, patients detected with ≥moderate stenosis on IS underwent single-photon emission computed tomography (SPECT) with acetazolamide (ACZ). CIAD was classified based on the degree of stenosis as mild (0%-49% stenosis: n=836 [before/after: 370/466]), moderate (50%-69%: n=118 [56/62]), or severe (70%-100%: n=141 [36/105]). Results: One of 166 (0.6%) patients with ≥moderate stenosis undergoing SPECT with ACZ was diagnosed with impaired cerebral autoregulation and underwent prophylactic superficial temporal artery to middle cerebral artery anastomosis 1 month before CABG. Subsequently, the patient underwent CABG without experiencing postoperative stroke. The introduction of IS significantly reduced the prevalence of perioperative stroke (2.8% vs. 0.9%, P=0.03) and permanent neurological dysfunction (2.4% vs. 0.5%, P=0.01). Additionally, prevalence of intraoperative stroke decreased significantly after the introduction of IS (1.4% vs. 0.2%, P=0.03). Conclusions: Incidence of perioperative stroke decreased following the introduction of IS. Therefore, IS might help identify patients at risk of perioperative stroke.
The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer
Authors: Martin Widschwendter, Michal Zikan, Benjamin Wahl, Harri Lempiäinen, Tobias Paprotka, Iona Evans, Allison Jones, Shohreh Ghazali, Daniel Reisel, Johannes Eichner, Tamas Rujan, Zhen Yang, Andrew E. Teschendorff, Andy Ryan, David Cibula, Usha Menon, Timo Wittenberger
Journal: Genome Medicine (2017)

Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence. We analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNA-methylation-serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis. The cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3–94.8%) and 41.4% (95% CI = 24.1–60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher's exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0–78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3–94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively). Our data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses.
Cовременные возможности повышения эффективности лечения гастроэзофагеальной рефлюксной болезни
Authors: S.M. Tkach
Journal: GASTROENTEROLOGY (2014)

Статья посвящена лечению одного из наиболее распространенных патологических состояний в гастроэнтерологии — гастроэзофагеальной рефлюксной болезни. Основное внимание уделено применению ингибиторов протонной помпы, а также их комбинации с прокинетиками.
The 4-Celled Tetrabaena socialis Nuclear Genome Reveals the Essential Components for Genetic Control of Cell Number at the Origin of Multicellularity in the Volvocine Lineage
Authors: Jonathan Featherston, Yoko Arakaki, Erik R Hanschen, Patrick J Ferris, Richard E Michod, Bradley J S C Olson, Hisayoshi Nozaki, Pierre M Durand
Journal: Molecular Biology and Evolution (2017)

Multicellularity is the premier example of a major evolutionary transition in individuality and was a foundational event in the evolution of macroscopic biodiversity. The volvocine chlorophyte lineage is well suited for studying this process. Extant members span unicellular, simple colonial, and obligate multicellular taxa with germ-soma differentiation. Here, we report the nuclear genome sequence of one of the most morphologically simple organisms in this lineage-the 4-celled colonial Tetrabaena socialis and compare this to the three other complete volvocine nuclear genomes. Using conservative estimates of gene family expansions a minimal set of expanded gene families was identified that associate with the origin of multicellularity. These families are rich in genes related to developmental processes. A subset of these families is lineage specific, which suggests that at a genomic level the evolution of multicellularity also includes lineage-specific molecular developments. Multiple points of evidence associate modifications to the ubiquitin proteasomal pathway (UPP) with the beginning of coloniality. Genes undergoing positive or accelerating selection in the multicellular volvocines were found to be enriched in components of the UPP and gene families gained at the origin of multicellularity include components of the UPP. A defining feature of colonial/multicellular life cycles is the genetic control of cell number. The genomic data presented here, which includes diversification of cell cycle genes and modifications to the UPP, align the genetic components with the evolution of this trait.
Absolute Quantification of Pre-microRNA-155 Copy Numbers By Digital Droplet PCR Identifies Acute Myeloid Leukemia (AML) Patients with Adverse Outcome
Authors: Marius Bill, Madlen Jentzsch, Julia Schulz, Karoline Schubert, Juliane Grimm, Laura Katharina Schmalbrock, Lynn Baquiran Bonifacio, Stefanie Beinicke, Janine Haentschel, Wolfram Poenisch, Gerhard Behre, Vladan Vucinic, Thoralf Lange, Georg-Nikolaus Franke, Dietger Niederwieser, Sebastian Schwind
Journal: Blood (2016)
Complete Remissions (CRs) with Azacitidine Regimens Compared to Crs with 7+3 Induction Chemotherapy and the Effect on Overall Survival
Authors: Megan Othus, Mikkael A Sekeres, Sucha Nand, Guillermo Garcia-Manero, Frederick R. Appelbaum, Harry P. Erba, Elihu H. Estey
Journal: Blood (2016)
Questioning the Effectiveness of Newer Antiseizure Medications
Authors: W. Allen Hauser
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Initiation of Prophylactic Treatment with Subcutaneous C1-Esterase Inhibitor (C1-INH [SC]) for Prevention of Hereditary Angioedema (HAE) Attacks and Onset of Effect: Findings from the Phase III COMPACT Study
Authors: Huamin Henry Li, Marc A. Riedl, Timothy Craig, Hilary J. Longhurst, Marco Cicardi, Bruce L. Zuraw, Henrike Feuersenger
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 16736: The Long Intergenic Non-coding RNA Landscape in Human Macrophage Activation
Authors: Hanrui Zhang, Chenyi Xue, Ying Wang, Wenjun Li, Sara Nunez, Andrea S Foulkes, Jennie J Lin, Christine C Hinkle, Wenli Yang, Edward E Morrisey, Daniel J Rader, Mingyao Li, Muredach P Reilly
Journal: Circulation (2016)

Introduction:  With remarkable plasticity and wide-ranging states of activation in response to environmental challenges, macrophages play a central role in pathogenesis of cardiometabolic diseases (CMDs). However, the long non-coding RNA landscape that regulates macrophage activation is poorly defined.   Hypothesis:  Comprehensive analysis of long intergenic non-coding RNA (lincRNA) expression profiles reveals novel macrophage lincRNA signature.   Methods:  We used deep RNA sequencing to assemble the lincRNA transcriptome in human macrophages (HMDM, N=6 subjects) at rest and also after stimulation with lipopolysaccharide and interferon-gamma for M1-like inflammatory activation, and interleukin-4 for M2-like anti-inflammatory activation (A).   Results:  Through  de novo  assembly, we identified 2,766 macrophage lincRNAs including 861 previously unannotated novel lincRNAs. The majority (86%) was non-syntenic, or syntenic but not annotated in mouse genomes (B). Many macrophage lincRNAs also demonstrated tissue-enriched transcription patterns (12 %) and enhancer-like chromatin signatures (62 %). Macrophage activation, particularly to the M1 phenotype, markedly altered the lincRNA expression profiles with 96 lincRNAs differentially expressed (fold-change > 2 and FDR    Conclusion:  In summary, high-resolution transcriptomics identified 100s of lincRNAs that form part of the cellular response in macrophage activation as well as specific macrophage lincRNAs associated with human CMDs.
Abstract 19281: CT Molecular Imaging of Perivascular Adipose Tissue and Its Linkage to Vascular Disease
Authors: Zhen W Zhuang, Yan Huang, Xiaoyong Yang, Kathleen A Martin, John Hwa, Michael Simons
Journal: Circulation (2016)

Perivascular adipose tissue (PVAT) surrounds the major arteries and regulates endothelial functioning. Healthy PVAT has the brown adipose tissue (BAT) phenotype histologically, and possesses anti-i...
Novel Targeting of Transcription and Metabolism in Glioblastoma
Authors: Yu-Ting Su, Robert Chen, Herui Wang, Hua Song, Qi Zhang, Li-Yuan Chen, Hallie Lappin, Gabriel Vasconcelos, Adrian Lita, Dragan Maric, Aiguo Li, Orieta Celiku, Wei Zhang, Kristan Meetze, Thomas Estok, Mioara Larion, Mones Abu-Asab, Zhengping Zhuang, Chunzhang Yang, Mark R. Gilbert, Jing Wu
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become an effective therapeutic for GBM patients. Experimental Design: To investigate TG02, an agent with known penetration of the blood–brain barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We used human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02. Mechanistic studies included TG02-induced transcriptional regulation, apoptosis, and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays. Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of antiapoptotic proteins and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue. Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Clin Cancer Res; 24(5); 1124–37. ©2017 AACR.
JAK/STAT Pathway Inhibition Reverts IL7-Induced Glucocorticoid Resistance in a Subset of Human T-Cell Acute Lymphoblastic Leukemia
Authors: Cristina Delgado-Martin, Kristin Shimano, Matthew S Zinter, Justin T. Wahlstrom, Geoffrey A. Smith, Jack Taunton, Stuart S. Winter, Justine E. Roderick, Michelle Kelliher, Terzah M. Horton, Brent L. Wood, David T Teachey, Michelle L. Hermiston
Journal: Blood (2016)
Secular trends in incidence of acute gastroenteritis in general practice, France, 1991 to 2015
Authors: Mathieu Rivière, Noémie Baroux, Vanina Bousquet, Katia Ambert-Balay, Pascal Beaudeau, Nathalie Jourdan-Da Silva, Dieter Van Cauteren, Frédéric Bounoure, Fanny Cahuzac, Thierry Blanchon, Thierry Prazuck, Clément Turbelin, Thomas Hanslik
Journal: Eurosurveillance (2017)

We analysed 25 years of general practitioner (GP) visits for acute gastroenteritis (AG) surveillance in France, by the GP Sentinelles network. We searched for time trends of acute gastroenteritis incidence during winter periods. Data from emergency departments and drug reimbursement were additional data sources. A time-series analysis was performed using a generalised additive model for all data sources for the winter period. Virological data were incorporated and compared with the three data sources. The cumulative incidence of GP visits for winter AG exhibited an increasing trend from 1991 until 2008, when it reached 6,466 per 100,000 inhabitants. It decreased thereafter to 3,918 per 100,000 inhabitants in 2015. This decreasing trend was observed for all age groups and confirmed by the generalised additive model. For emergency department visits a decreasing trend was observed from 2004. Drug reimbursement data analyses demonstrated a decreasing trend from when data began in 2009. The incidence reported by GPs and emergency departments was lower following the emergence of norovirus GII.4 2012 (p < 0.0001). Winter AG incidences seem to follow long-term rising and decreasing trends that are important to monitor through continuous surveillance to evaluate the impact of prevention strategies, such as future immunisation against acute viral gastroenteritis.
Chest physician-reported, work-related, long-latency respiratory disease in Great Britain
Authors: Melanie Carder, Andrew Darnton, Matthew Gittins, S. Jill Stocks, David Ross, Chris M. Barber, Raymond M. Agius
Journal: European Respiratory Journal (2017)

Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent. LLRD incidence and incidence rate ratios by occupation were estimated (1996–2014). Mesothelioma cases by occupation were compared with proportional mortality ratios. Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0–8.2); mesothelioma, 5.4 (4.8–6.0); pneumoconiosis, 1.9 (1.7–2.2); lung cancer, 0.8 (0.6–1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2–0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation. Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.