tbuckley/cabot-search huggingface dataset:
Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction
Authors: Michele L. Esposito, Yali Zhang, Xiaoying Qiao, Lara Reyelt, Vikram Paruchuri, Gavin R. Schnitzler, Kevin J. Morine, Shiva K. Annamalai, Courtney Bogins, Peter S. Natov, Robert Pedicini, Catalina Breton, Andrew Mullin, Emily E. Mackey, Ayan Patel, Ethan Rowin, Iris Z. Jaffe, Richard H. Karas, Navin K. Kapur
Journal: Journal of the American College of Cardiology (2018)
The potential role of pNF-H, a biomarker of white matter damage in central nervous system, as a predictive marker of chemotherapy-induced cognitive impairments.
Authors: Akina Natori, Toru Ogata, Masahiko Sumitani, Takamichi Kogure, Teruo Yamauchi, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2014)

9581 Background: Chemotherapy-induced cognitive impairments (CICI) have been recognized as a clinically-significant issue for cancer survivors, it is urgently required to elucidate the mechanism of CICI and develop diagnostic and therapeutic measures. Previous studies using magnetic resonance imaging showed more decreased white matter integrity in CICI patients than healthy controls. Increased level of the circulating phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), which is one of the major structural proteins in axon, has been reported to be elevated in central nervous system (CNS) disorders. We hypothesize CICI is caused by demyelination in CNS. We examined neuropsychological tests and serum pNF-H level in breast cancer patients receiving adjuvant chemotherapy in a cross-sectional manner. Methods: Early breast cancer patients in various phase of treatment (5 were naïve to chemotherapy, 20 were after 1 cycle of chemotherapy, 20 were after 3 cycles of chemotherapy, 20 were after 7 cycles of chemotherapy, 12 were past chemotherapy patients) were assessed by neuropsycological tests (EuroQOL-5 Dimension, Hospital Anxiety and Depression Scale, State Trait Anxiety Inventory, PainDetect, Epworth Sleepiness Scale, Colored Progressive Matrices, and Cognition Fail Question) and pNF-H at one point. Patients with pNF-H >70.5 μg/ml were considered pNF-H positive. The Chi-square test and the Mann-Whitney test were used to compare data. Results: Increased level of pNF-H was observed in 28.8% of patients who underwent chemotherapy. The rate of pNF-H positive patients of each group significantly increased in proportion to the number of chemotherapy (1 cycle:9.1%, 3 cycle:27.8%, 7 cycle: 61.1%; p<0.05), but none of past chemotherapy patients and chemotherapy-naive patients were pNF-H positive. No differences were observed in neuropsycological tests between each group. Conclusions: Serum pNF-H level in breast cancer patients on chemotherapy was increased in cumulative dose-dependent manner, suggesting its potential application as a biomarker to survey neural damage after chemotherapy.
Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice
Authors: ShoujiMatsushima, TomomiIde, MayumiYamato, HidenoriMatsusaka, FumiyukiHattori, MasakiIkeuchi, ToruKubota, KenjiSunagawa, YasuhiroHasegawa, TatsuyaKurihara, ShinzoOikawa, ShintaroKinugawa, HiroyukiTsutsui
Journal: Circulation (2006)

Background— Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. Methods and Results— We created MI in 12- to 16-week-old, male Prx-3–transgenic mice (TG+MI, n=37) and nontransgenic wild-type mice (WT+MI, n=39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid–reactive substances in the mitochondria were significantly lower in TG+MI than in WT+MI mice (mean±SEM, 1.5±0.2 vs 2.2±0.2 nmol/mg protein; n=8 each, P<0.05). LV cavity dilatation and dysfunction were attenuated in TG+MI compared with WT+MI mice, with no significant differences in infarct size (56±1% vs 55±1%; n=6 each, P=NS) an...
Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31
Authors: Naihan Chen, Charles J. Kroger, Roland M. Tisch, Eric M. Bachelder, Kristy M. Ainslie
Journal: Advanced Healthcare Materials (2018)

Abstract Type 1 diabetes (T1D) is a common autoimmune disease with no cure. T1D subjects are dependent on daily exogenous insulin administration, due to the loss of functional insulin‐producing β cells. Needed are immunotherapies that prevent and/or treat T1D. One approach of immunotherapy is to administer an autoantigen to selectively tolerize diabetogenic effector T cells without global immunosuppression. To date, however, strategies of antigen‐specific immunotherapy are largely ineffective in the clinic. Using an antigen‐specific approach, a biodegradable polymeric delivery vehicle, acetalated dextran microparticles (Ace‐DEX MPs), is applied and T1D development is prevented through coadministration of the immunosuppressant rapamycin and the diabetogenic peptide P31 (Rapa/P31/MPs), via alterations of both innate and adaptive immunity. Ex vivo, adoptively transferred CD4 + T cells exhibit reduced proliferation and an increased ratio of FoxP3 + to IFNγ + T cells. In vitro analysis indicates dendritic cells exhibit a less mature phenotype following coculture with Rapa/P31/MPs, which results in reduced CD4 + T cell proliferation and proinflammatory cytokine production (IFNγ and IL‐2), but promotes PD‐1 expression. Together these results demonstrate Ace‐DEX MP‐based antigen‐specific therapy effectively tolerizes diabetogenic CD4 + T cells to prevent T1D, thereby demonstrating one of the first successful attempts of T1D prevention using a single‐formulation particulate delivery platform.
Intracranial Carotid Artery Calcification From Infancy to Old Age
Authors: Remko Kockelkoren, Jill B. De Vis, Pim A. de Jong, Meike W. Vernooij, Willem P.Th.M. Mali, Jeroen Hendrikse, Thomas Schiestl, Karlijn Pellikaan, Aad van der Lugt, Daniel Bos
Journal: Journal of the American College of Cardiology (2018)
Clonal immunoglobulin λ light‐chain gene rearrangements detected by next generation sequencing in POEMS syndrome
Authors: Chika Kawajiri‐Manako, Naoya Mimura, Masaki Fukuyo, Hiroe Namba, Bahityar Rahmutulla, Yuhei Nagao, Emi Togasaki, Ryoh Shimizu, Nagisa Oshima‐Hasegawa, Shokichi Tsukamoto, Shio Mitsukawa, Yusuke Takeda, Chikako Ohwada, Masahiro Takeuchi, Tohru Iseki, Sonoko Misawa, Koutaro Yokote, Makoto Tsuiji, Satoshi Kuwabara, Emiko Sakaida, Atsushi Kaneda, Chiaki Nakaseko
Journal: American Journal of Hematology (2018)

Polyneuropathy, organomegaly, endocrinopathy, M‐protein, and skin changes (POEMS) syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, extravascular fluid overload, M protein, and a myriad of skin changes. The pathogenesis is poorly understood, but monoclonal plasma cells are λ‐restricted and these immunoglobulin λ light chain variable (IGLV) region genes are derived from only two germlines, either IGLV1‐44 or 1‐40 . Here we analyzed the clonal IGLV gene rearrangements of genomic DNA samples of bone marrow mononuclear cells using next‐generation sequencing (NGS) to understand the clonal composition of IGLV genes in patients with POEMS syndrome (n = 30). The dominant IGLV gene rearrangement of POEMS syndrome‐specific germline sequences were significantly increased in 11 POEMS patients (36.7%; IGLV1‐44 : n = 9, IGLV1‐40 : n = 2). In some cases, IGLV gene rearrangement clone was not detected as significant increase but was detected using cDNA samples by heteroduplex (HD) analysis and Sanger sequencing, suggesting that the quite small number of monoclonal plasma cells may produce large quantity of mRNA of monoclonal proteins. However, significant increase of dominant clone sizes was not directly linked to the initial disease status. On the other hand, in cases with significantly increased dominant clones, they decreased and increased accompanying with disease remission and relapse. These data demonstrate that monoclonal plasma cells are related to the pathogenesis of POEMS syndrome.
DNA methylation-based classification of ependymomas in adulthood: implications for diagnosis and treatment
Authors: Hendrik Witt, Dorothee Gramatzki, Bettina Hentschel, Kristian W Pajtler, Jörg Felsberg, Gabriele Schackert, Markus Löffler, David Capper, Felix Sahm, Martin Sill, Andreas von Deimling, Marcel Kool, Ulrich Herrlinger, Manfred Westphal, Torsten Pietsch, Guido Reifenberger, Stefan M Pfister, Jörg C Tonn, Michael Weller
Journal: Neuro-Oncology (2018)

Ependymal tumors are glial tumors that commonly manifest in children and young adults. Their classification has remained entirely morphological until recently, and surgery and radiotherapy are the main treatment options, especially in adults. Here we sought to correlate DNA methylation profiles with clinical and pathological characteristics in the prospective cohort of the German Glioma Network. Tumors from 122 adult patients with myxopapillary ependymoma, ependymoma, anaplastic ependymoma, subependymoma, or RELA fusion-positive ependymoma classified according to the World Health Organization (WHO) 2016 were subjected to DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform. Molecular data were correlated with histologic features and clinical characteristics. At a median follow-up of 86.7 months, only 22 patients experienced progression (18.0%) and 13 patients (10.7%) died. Each tumor could be assigned to one of the previously defined molecular ependymoma subgroups. All histologic subependymomas corresponded to subependymoma (SE) DNA methylation subgroups, but the reverse was not true: 19 histologic ependymomas (WHO grade II) were allocated to molecular SE groups. Similarly, all histological myxopapillary ependymomas were assigned to the molecularly defined spinal myxopapillary ependymoma (SP-MPE) class, but this molecular subgroup additionally included 15 WHO grade II ependymomas by histology. Overall, WHO grade II ependymomas distributed into 7 molecular subgroups. Most adult patients with ependymoma show a favorable prognosis. Molecular classification may provide diagnostic and prognostic information beyond histology and facilitate patient stratification in future clinical trials. The prognostic significance of a subependymoma or myxopapillary ependymoma DNA methylation phenotype without corresponding histology requires further study. 1. Ependymoma diagnosed in adult patients most often shows a good prognosis. 2. Molecular classification can support diagnostic and prognostic information beyond histology.
Failure to Respond after Reinstatement of Antidepressant Medication: A Systematic Review
Authors: Renske C. Bosman, Ruth C. Waumans, Gabriel E. Jacobs, Richard C. Oude Voshaar, Anna D.T. Muntingh, Neeltje M. Batelaan, Anton J.L.M. van Balkom
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Following remission of an anxiety disorder or a depressive disorder, antidepressants are frequently discontinued and in the case of symptom occurrence reinstated. Reinstatement of antidepressants seems less effective in some patients, but an overview is lacking. This systematic review aimed to provide insight into the magnitude and risk factors of response failure after reinstatement of antidepressants in patients with anxiety disorders, depressive disorders, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD). &lt;b&gt;&lt;i&gt;Method:&lt;/i&gt;&lt;/b&gt; PubMed, Embase, and trial registers were systematically searched for studies in which patients: (1) had an anxiety disorder, a depressive disorder, OCD, or PTSD and (2) experienced failure to respond after reinstatement of a previously effective antidepressant. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Ten studies reported failure to respond following antidepressant reinstatement. The phenomenon was observed in 16.5% of patients with a depressive disorder, OCD, and social phobia and occurred in all common classes of antidepressants. The range of response failure was broad, varying between 3.8 and 42.9% across studies. No risk factors for failure to respond were investigated. The overall study quality was limited. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Research investigating response failure is scarce and the study quality limited. Response failure occurred in a substantial minority of patients. Contributors to the relevance of this phenomenon are the prevalence of the investigated disorders, the number of patients being treated with antidepressants, and the occurrence of response failure for all common classes of antidepressants. This systematic review highlights the need for studies systematically investigating this phenomenon and associated risk factors.
Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis
Authors: Ian D van Koeverden, Marie de Bakker, Saskia Haitjema, Sander W van der Laan, Jean-Paul P M de Vries, Imo E Hoefer, Gert J de Borst, Gerard Pasterkamp, Hester M den Ruijter
Journal: Cardiovascular Research (2018)

The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance. Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome. Testosterone and oestradiol concentrations were determined in blood samples of 611 male carotid endarterectomy patients included in the Athero-Express Biobank Study. T/E2 ratio was associated with baseline characteristics, atherosclerotic plaque specimens, inflammatory biomarkers, and 3 year follow-up information. Patients with low T/E2 ratio had more unfavourable inflammatory profiles compared with patients with high T/E2 as observed by higher levels of C-reactive protein [2.81 μg/mL vs. 1.22 μg/mL (P < 0.001)] and higher leucocyte counts [8.98*109/L vs. 7.75*109/L (P = 0.001)] in blood. In atherosclerotic plaques, a negative association between T/E2 ratio and number of neutrophils [B = −0.366 (P = 0.012)], plaque calcifications [OR: 0.816 (P = 0.044)], interleukin-6 (IL-6) [B = −0.15 (P = 0.009)], and IL-6 receptor [B = −0.13 (P = 0.024)] was found. Furthermore, in multivariate Cox regression analysis, low T/E2 ratio was independently associated with an increased risk for major cardiovascular events (MACE) during 3 year follow-up [hazard ratio 1.67 (95% confidence interval 1.02–2.76), P = 0.043]. In men with elevated body mass index (BMI), these effects were strongest. In male patients with manifest atherosclerotic disease, low T/E2 ratio was associated with increased systemic inflammation, increased inflammatory plaque proteins, and an increased risk of future MACE as compared to men with normal T/E2 ratio. These effects are strongest in men with elevated BMI and are expected to be affected by aromatase activity in white fat tissues. Normalization of T/E2 ratio may be considered as target for the secondary prevention of CVD in men.
Abstract 17096: Enhanced Coronary Arteriolar Reactivity to Vasopressin in Diabetic Patients After Cardiac Surgery
Authors: Nicholas Sellke, Isabella Lawandy, Afshin Ehsan, Yuhong Liu, Frank W Sellke, Jun Feng
Journal: Circulation (2016)

Introduction: Cardioplegic arrest and cardiopulmonary bypass (CP/CPB) are associated with vasomotor dysfunction of coronary arterioles in diabetic patients undergoing cardiac surgery. Hypothesis: D...
Reply to Vincenzo Di Nunno, Matteo Santoni, Alessia Cimadamore, Nicola Battelli, and Francesco Massari's Letter to the Editor re: Gladell P. Paner, Walter M. Stadler, Donna E. Hansel, et al. Updates in the Eight Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. Eur Urol 2018;73:560–9
Authors: Gladell P. Paner, Mahul B. Amin
Journal: European Urology (2018)
Mismatch Repair Protein Defects and Microsatellite Instability in Malignant Pleural Mesothelioma
Authors: Surein Arulananda, Bibhusal Thapa, Marzena Walkiewicz, Giada V. Zapparoli, David S. Williams, Alexander Dobrovic, Thomas John
Journal: Journal of Thoracic Oncology (2018)
Osimertinib Depletes EGFR T790M in the Spinal Fluid of Patients with Carcinomatous Meningitis of Lung Adenocarcinoma Harboring De Novo EGFR T790M
Authors: Satoru Senoo, Kadoaki Ohashi, Kazuya Nishii, Naofumi Hara, Hirohisa Kano, Kiichiro Ninomiya, Yoshinobu Maeda, Katsuyuki Kiura
Journal: Journal of Thoracic Oncology (2018)
Abstract 255: Laminar Shear Stress Enhances the Activity and Localization of RNA Polymerase II on the eNOS Gene
Authors: Martina Weber, Jeffrey P Moore, Charles D Searles
Journal: Circulation (2007)

We have previously found that laminar shear enhances eNOS mRNA stability and translation by altering endothelial NO synthase (eNOS) mRNA 3′ polyadenylation. Transcription is tightly coupled to pre-mRNA processing, and is coordinated by RNA polymerase (RNAP) II. We assessed whether laminar shear stress alters the activity and localization of RNAP II on the eNOS gene. We found that endothelial cells exposed to laminar shear stress had a 2-fold (n=3, p &lt; 0.05) increase in total RNAP II protein levels compared to control; this effect was dose-dependent (0–15 dynes/cm2). Since three different RNAP II phosphoisoforms are associated with different stages of mRNA synthesis, we examined whether shear stress affected protein expression of these particular phosphoisoforms. We found that cells exposed to laminar shear had a 3-fold increase (p&lt;0.05) in expression of RNAP II phosphorylated at serine 2, which is associated with transcription elongation and 3′ polyadenylation. In contrast, shear stress did not alter expression of the other phosphoisoforms. We performed chromatin immunoprecipitation (ChIP) analysis to examine shear-induced changes in RNAP II localization on the eNOS gene. Using antibody against total RNAP II, eNOS sequences along the entire gene were amplified. Using the phosphoserine 2 specific RNAP II antibody, we found active RNAP II predominantly bound to the 3′UTR (exon 26) and downstream sequence of eNOS in sheared cells. These findings were confirmed by quantitative ChIP (3 fold increase, n = 8, p = 0.0378). This suggests that shear-induced changes in RNAP II phosphorylation enhance its ability to polyadenylate eNOS mRNA. Serine 2 phosphorylation is dependent on cyclin-dependent kinase 9 (CDK 9), and shear-induced recruitment of CDK 9 to the eNOS gene was examined. We found that endothelial cells exposed to laminar shear had enhanced localization of CDK 9 to the eNOS promoter and exons 8 and 22, and diminished localizationto exon 26 and in the downstream sequence. This indicates that shear recruits CDK 9 while RNAP II is bound to the promoter and early exons to activate RNAP by phosphorylating serine 2. In conclusion, laminar shear stress enhances eNOS mRNA processing and increases gene expression through recruitment of CDK 9 and activation of RNAP II.
Impact of allergic disorders and anaphylaxis in mastocytosis: Preliminary data from a study of the European Competence Network on Mastocytosis (ECNM) registry
Authors: M. Niedoszytko, A. Gorska, B. Nedoszytko, A. Rabenhorst, W. Sperr, Oude J. Elberink, M. Lange, K. Gleixner, Brazzelli, E. Fontana, B. Vos, A. Reiter, J. Schwaab, R. Zanotti, P. Bonadonna, M. Triggiani, J. Gotlib, M. Doubek, T. Jakob, D. Fuchs, Sabato, A. Zink, A. Bretterklieber, N. Jäkel, K. Sotlar, H. Horny, Belloni A. Fortina, S. Merante, H. Kluin-Nelemans, P. Valent, K. Hartmann
Journal: Allergy (2017)
Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial
Authors: Regina Katzenschlager, Werner Poewe, Olivier Rascol, Claudia Trenkwalder, Günther Deuschl, K Ray Chaudhuri, Tove Henriksen, Teus van Laar, Kevin Spivey, Senthil Vel, Harry Staines, Andrew Lees
Journal: The Lancet Neurology (2018)
Unusual Case of Metastatic Intracranial Hemangiopericytoma and Emphasis on Role of 68Ga-PSMA PET in Imaging
Authors: Kanhu Charan Patro, Madhuri Palla, Raghava Kashyap
Journal: Clinical Nuclear Medicine (2018)

We present a 53 year old woman initially diagnosed as hemangiopericytoma in the posterior fossa on the right side post excision with immunohistochemistry staining for CD34 being positive. Presently, the patient had difficulty in walking due to back pain and pain in left arm. Imaging with F-FDG PET showed low glucose avidity in disease sites but Ga-PSMA PET unequivocally demonstrated multiple skeletal and liver metastases with intense PSMA avidity. Patient received palliative radiotherapy to bone metastasis and was planned for chemotherapy. This report adds to the list of applications of Ga PSMA PET and a possible theranostic target.
Effects of Transendocardial Delivery of Bone Marrow–Derived CD133 <sup>+</sup> Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina
Authors: Wojciech Wojakowski, Tomasz Jadczyk, Aleksandra Michalewska-Włudarczyk, Zofia Parma, Mirosław Markiewicz, Wojciech Rychlik, Magdalena Kostkiewicz, Katarzyna Gruszczyńska, Anna Błach, Monika Dzier˙zak-Mietła, Wojciech Wańha, Joanna Ciosek, Beata Ochała, Łukasz Rzeszutko, Wiesław Cybulski, Łukasz Partyka, Wojciech Zasada, Witold Włudarczyk, Sebastian Dworowy, Wacław Kuczmik, Grzegorz Smolka, Tomasz Pawłowski, Andrzej Ochała, Michał Tendera
Journal: Circulation Research (2016)

New therapies for refractory angina are needed.Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina.Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], P=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months.Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.