tbuckley/cabot-search huggingface dataset:
Sensitivity, Reproducibility and Clinical Utility Of Next-Generation Sequencing (NGS) for BCR-ABL1 Kinase Domain Mutation Screening: Results From The CML Work Package Of The Iron-II (Interlaboratory RObustness Of Next-Generation Sequencing) International Study
Authors: Simona Soverini, Thomas Ernst, Alexander Kohlmann, Caterina De Benedittis, Mary Alikian, Letizia Foroni, Katerina Machova Polakova, Adela Brouckova, Yucel Erbilgin, Ozden Hatirnaz, Ugur Ozbek, Cristina Robledo, Jesus Maria Hernandez, Milena Musilova, Santiago Barrio, Joaquin Martinez-Lopez, Renate Kastner, Thomas Lion, Torsten Haferlach, Andreas Hochhaus, Giovanni Martinelli
Journal: Blood (2013)
Abstract 11585: Lipid Nanoparticle Encapsulated SiRNA Against CCR2 Ameliorates Autoimmune Myocarditis and Impacts Myeloid Progenitor Trafficking
Authors: Florian Leuschner, Gabriel Courties, Rostic Gorbatov, Brena Sena, Tatiana Novobrantseva, Yoshiko Iwamoto, Mikael Pittet, Filip Swirski, Victor Koteliansky, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation (2012)

Background: Myocarditis is characterized by the infiltration of inflammatory cells which damage cardiac myocytes. Monocytes are the most prominent population of accumulating leukocytes. Here we inv...
Abstract 12951: Human C-Type Natriuretic Peptide-53: A Distinct Molecular Form With in vitro and in vivo Biological Actions Through cGMP Generation
Authors: S. J Sangaralingham, Brenda K Huntley, Tomoko Ichiki, Sharon M Sandberg, John C Burnett
Journal: Circulation (2014)

Introduction: ANP and BNP are cardiac hormones that have a natriuretic and diuretic role in heart failure (HF) through guanylyl cyclase receptor A (GC-A) and cGMP generation. C-type natriuretic peptide (CNP) is part of this hormone family and is produced in the heart and endothelium. The biologically active form, CNP-22, is known to have potent anti-remodeling properties through the activation of GC-B and cGMP, but lacks natriuretic actions. Recently we have identified that another larger CNP form, CNP-53, is elevated in the plasma of acute decompensated HF patients, however it unclear if CNP-53 possesses biological actions. Hypothesis: We hypothesized that CNP-53 would be biologically active in vivo and in vitro, and would stimulate GC-B specific cGMP production. Methods: HEK 293 cells over-expressing GC-A and GC-B and human cardiac fibroblasts (hCFs), in which GC-B are in abundance, were stimulated with CNP-53 for 10 minutes at a dose of (10-8M). Two groups of anesthetized rats (n=8) received a 75-minute infusion of normal saline vehicle (V) or CNP-53 (1 ug/kg/min) and then mean arterial pressure (MAP), sodium excretion and urinary and plasma cGMP were assessed. Results: CNP-53 significantly activated cGMP in GC-B HEK cells (75±9 vs. 0.4±0.1 pmol/well, p&lt;0.05) and in hCFs (0.17±0.03 vs. 0.00±0.00 pmol/well, p&lt;0.05) compared to no treatment. In contrast CNP-53 failed to generate cGMP in GC-A HEK cells. In vivo, CNP-53 decreased MAP compared to vehicle (V: 101±2, CNP-53: 94±2 mmHg, p&lt;0.05). CNP-53 had a greater natriuretic effect compared vehicle (V: 0.86±0.11, CNP-53: 1.39±0.21 uEq/min, p&lt;0.05). Urinary cGMP excretion (V: 33±6, CNP-53: 177±28 pmol/min, p&lt;0.05) and plasma cGMP generation was also significantly higher with CNP-53 compared to vehicle (V: 9±2, CNP-53: 91±3 pmol/ml, p&lt;0.05). Conclusions: CNP-53, a higher molecular form of CNP that was reported to be increased human HF plasma, is bioactive with GC-B specific cGMP generation in vitro. Moreover, infusion of CNP-53 generates significant urinary and plasma cGMP and has natriuretic actions with minimal hypotensive effects in vivo. This study advances our understanding of CNP biology and provides new insights into potential CNP therapeutic opportunities targeting the progression of HF.
Abstract 11735: The Hyperglycemic Exacerbation of Myocardial Infarct Size in Mice is Mediated by Splenocytes
Authors: Yikui Tian, Lanlin Chen, Irving L Kron, Brent A French, Zequan Yang
Journal: Circulation (2014)

Background: Acute hyperglycemia (HG) potentiates systemic inflammatory responses and exacerbates myocardial infarct (MI) size in both pre-clinical and clinical studies. As an important immune organ, accumulating evidence now shows that the spleen plays critical roles during myocardial infarction and subsequent healing. The current study was designed to determine whether splenocytes mediate the detrimental myocardial infarct exacerbation of ischemia/reperfusion injury caused by HG.

Methods and Results: C57BL6 (B6) mice underwent 30 min of LAD occlusion followed by 60 min of reperfusion. Acute HG was induced by injection of 20% Dextrose (2 g/kg, ip) 30 min before LAD occlusion. MI size (IF) and risk region (RR) were determined by TTC and Phthalo blue staining, respectively. HG significantly increased MI size by 41% in mice (p<0.01). Splenectomy (SPLX) performed 30 min before ischemia abolished the infarct exacerbating effect of HG. Acute adoptive transfer of splenocytes (SPAT) from B6 mice performed 25 min before ischemia effectively restored the effects of HG on MI in SPLX mice. ATL146e, an adenosine A2A receptor (A2AR) agonist, injected 5 min before reperfusion at 10μg/kg (iv) significantly reduced MI size in both HG (p<0.01) and SPLX+SPAT(B6)+HG groups (p<0.01). Interestingly, ATL146e failed to protect splenectomized HG mice after the adoptive transfer of splenocytes from A2AR knock-out mice (the SPLX+SPAT(A2AR KO)+HG group).

Conclusions: Splenocytes mediate the infarct exacerbating effect of acute HG. Adenosine2A receptors on splenocytes are responsible for mediating the vast majority of the cardioprotection afforded by A2AR agonists under HG conditions. These results may have implications for glycemic control during revascularization procedures and cardiac transplantation. Further studies are warranted to investigate the precise mechanisms of how HG activates splenocytes and which cell types are involved in this phenomenon.

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Rofecoxib associated with weekly irinotecan and infusional 5-fluorouracil as second-line treatment for metastatic colorectal cancer
Authors: G. Gasparini, D. Gattuso, A. Morabito, G. Carillio, S. Vitale, M. Fanelli, F. Torino, P. Bonginelli, M. A. Castellana, L. De Sio
Journal: Journal of Clinical Oncology (2004)

3686 Background:We performed this Phase I –II study to determine the feasibility and activity of a "methronomic" schedule of chemotherapy with weekly irinotecan (CPT 11) and 5-fluorouracil (5-FU) by continuos infusion associated with a selective inhibitor of cyclooxygenase-2 (COX-2) as second-line therapy for advanced colorectal cancer. Methods:The patients (pts) had metastatic disease progressing after an oxaliplatin-based chemotherapy, age ≥ 18 to ≤ 75 years, good performance status and measurable lesions. A cycle of treatment consisted of two phases: induction (weeks 1 to 5), with rofecoxib at the oral dose of 50 mg/day combined with intravenous weekly CPT-11 on days 1–8-15–22 and infusional 5-FU at the dose of 200 mg/m2/day for 5 weeks, and maintenance (weeks 6 to 8) with rofecoxib alone. The starting dose of CPT-11 was of 87.5 mg/m2, further dose escalations were by increments of 12.5 mg/m2 per level up to 125 mg/m2. Results: Fifteen pts have been enrolled in the Phase I study. The dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) were defined by conventional criteria. At the fourth dose level (125 mg/m2) a pt out of the 6 enrolled presented grade 3 reversible diarrhea as one DLT. During the 35 cycles administered, side-effects were moderate, only 7 being complicated by grade 3–4 toxicities. Therefore the dose of the irinotecan of 125 mg/m2 was closen for the Phase II study. Seven of the 15 assessable pts obtained a partial response (46.7%; 95% exact confidence limits: 21 to 71%) with a median duration of 5 months. Thirty-two pts have been enrolled up to now into the Phase II and 26 are evaluable for toxicity and response. No complete response was observed: 11 pts had partial response (42.3 % ) and 10 stable disease (38,5 %). To date, grade 3 diarrhea in 6 pts, grade 3–4 neutropenia in 5 pts, and grade 3 peripheral neuropathy in 1 pt were observed. Conclusions: Rofecoxib associated with weekly irinotecan and infusional 5-fluorouracil is a safe and active second line treatment for metastatic colorectal cancer. The recruitment is ongoing. No significant financial relationships to disclose.
Abstract 15471: Prognostic Value of Cytotoxic T Lymphocytes in Endomyocardial Biopsies of Patients with Dilated Inflammatory Cardiomyopathy
Authors: Felicitas Escher, Uwe Kúhl, Dirk Lassner, Dirk Westermann, Wolfgang Poller, Carsten Tschöpe, Heinz-Peter Schultheiss
Journal: Circulation (2012)

Objective: to analyse the prognostic value of cytotoxic T-lymphocytes (CTLs: Perforin) in a large cohort of patients with dilated inflammatory cardiomyopathy (DCMi). Background: Intramyocardial inf...
Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism
Authors: Annelies Quaegebeur, Inmaculada Segura, Roberta Schmieder, Dries Verdegem, Ilaria Decimo, Francesco Bifari, Tom Dresselaers, Guy Eelen, Debapriva Ghosh, Shawn M. Davidson, Sandra Schoors, Dorien Broekaert, Bert Cruys, Kristof Govaerts, Carla De Legher, Ann Bouché, Luc Schoonjans, Matt S. Ramer, Gene Hung, Goele Bossaert, Don W. Cleveland, Uwe Himmelreich, Thomas Voets, Robin Lemmens, C. Frank Bennett, Wim Robberecht, Katrien De Bock, Mieke Dewerchin, Bart Ghesquière, Sarah-Maria Fendt, Peter Carmeliet
Journal: Cell Metabolism (2016)
Abstract MP95: Prevalence of General and Abdominal Obesity in Adults with Chronic Kidney Disease: Results from NHANES 2007-2012
Authors: Alex R Chang, Lawrence J Appel, Morgan E Grams
Journal: Circulation (2015)

Background: Obesity is associated with increased risk for chronic kidney disease (CKD), and may be a modifiable risk factor for its progression. Prevalence of general and abdominal obesity has not been well-described in a nationally-representative sample of adults with CKD.

Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012 to estimate prevalence of obesity [body mass index (BMI) ≥30 kg/m2], severe obesity (BMI ≥35 kg/m2), and elevated waist circumference (World Health Organization guidelines: women ≥ 88 cm; men ≥ 102 cm) in adults ≥ 20 years for individuals with CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or albumin/creatinine ratio (ACR) ≥ 30mg/g] overall, and in categories of eGFR and ACR. Correlations between BMI and waist circumference were examined and compared between persons with and without CKD. Continuous relationships between eGFR, log-transformed ACR and obesity were examined using logistic regression, adjusted for age, race, and sex.

Results: Prevalence of obesity, severe obesity, and elevated waist circumference was 43.2%, 20.7%, and 67.4% in adults with CKD compared to 33.5%, 13.7%, and 52.6% in adults without CKD (p<0.001 for all comparisons). Overall, the prevalence of obesity and elevated waist circumference tended to increase with more severe category of eGFR and ACR (Figure). BMI and waist circumference were strongly correlated for both adults with CKD (r=0.89) and without CKD (r=0.9). However, 44.2% of non-obese persons with CKD had elevated waist circumference compared to 30.9% of non-obese persons without CKD (p<0.001). In continuous analyses, obesity was associated with higher ACR, particularly among persons with higher eGFR (p for interaction = 0.1); obesity and eGFR were not independently associated.

Conclusion: Obesity, particularly in a central distribution, is common among individuals with CKD. Clinical trials are needed to determine whether reducing weight can prevent or slow progression of CKD.

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HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc
Authors: Yinghui Li, Zhen Wang, Hui Shi, Hang Li, Leilei Li, Runping Fang, Xiaoli Cai, Bowen Liu, Xiaodong Zhang, Lihong Ye
Journal: Cancer Research (2016)

Abstract c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc–mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc–enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis. Cancer Res; 76(2); 293–304. ©2015 AACR.
Solutions for Archiving Data in Long-Term Studies: A Reply to Whitlock et al.
Authors: James A. Mills, Céline Teplitsky, Beatriz Arroyo, Anne Charmantier, Peter. H. Becker, Tim R. Birkhead, Pierre Bize, Daniel T. Blumstein, Christophe Bonenfant, Stan Boutin, Andrey Bushuev, Emmanuelle Cam, Andrew Cockburn, Steeve D. Côté, John C. Coulson, Francis Daunt, Niels J. Dingemanse, Blandine Doligez, Hugh Drummond, Richard H.M. Espie, Marco Festa-Bianchet, Francesca D. Frentiu, John W. Fitzpatrick, Robert W. Furness, Gilles Gauthier, Peter R. Grant, Michael Griesser, Lars Gustafsson, Bengt Hansson, Michael P. Harris, Frédéric Jiguet, Petter Kjellander, Erkki Korpimäki, Charles J. Krebs, Luc Lens, John D.C. Linnell, Matthew Low, Andrew McAdam, Antoni Margalida, Juha Merilä, Anders P. Møller, Shinichi Nakagawa, Jan-Åke Nilsson, Ian C.T. Nisbet, Arie J. van Noordwijk, Daniel Oro, Tomas Pärt, Fanie Pelletier, Jaime Potti, Benoit Pujol, Denis Réale, Robert F. Rockwell, Yan Ropert-Coudert, Alexandre Roulin, Christophe Thébaud, James S. Sedinger, Jon E. Swenson, Marcel E. Visser, Sarah Wanless, David F. Westneat, Alastair J. Wilson, Andreas Zedrosser
Journal: Trends in Ecology & Evolution (2016)
Not a typical case of bilateral knee osteoarthritis
Authors: Morteza Khodaee, Jonathan Seyfert
Journal: BMJ (2016)

A 64 year old woman presented to our clinic with intermittent bilateral knee pain for several years. She described her pain as mild, diffuse, both improved and worsened with walking, and occasionally associated with a sensation of instability. Although she had no history of trauma, mechanical symptoms such as locking, interference with daily activities, or pain in other joints, she did have osteoarthritis of the knee and osteoporosis. Several years earlier she had received a corticosteroid injection in her left knee but had never undergone imaging of her knees. Recently, she had been using paracetamol (acetaminophen) and naproxen as needed for the pain. 

Physical examination showed bilateral genu valgum with bilateral diffuse tenderness to palpation along her joint lines and patellar facets. Bilateral patellar movement caused considerable crepitus and discomfort. She had a small joint effusion in her left knee but not on the right. She had decreased flexion of the knees—110o on the left and 100o on the right. Her gait was mildly antalgic bilaterally. Plain radiography was performed (fig 1⇓).



Fig 1 Anterioposterior plain radiograph of bilateral knees





### 1. What do the radiographs show?

#### Short answer

Multiple calcified bodies of various sizes distributed throughout the knee joint and severe bilateral tricompartmental knee osteoarthritis.

#### Discussion

The multiple calcified bodies of various sizes probably developed at different times. These …
Prognostic Impact of Extranodal Diffuse Large B-Cell Lymphoma in the Era of Immunochemotherapy and PET/CT Staging
Authors: Tarec Christoffer El-Galaly, Diego Villa, Musa Alzahrani, Jakob Werner Hansen, Laurie H. Sehn, Don Wilson, Peter de Nully Brown, Annika Loft, Victor Iyer, Hans Erik Johnsen, Kerry J. Savage, Joseph M. Connors, Martin Hutchings
Journal: Blood (2014)
Octreotide Lar Suitable Treatment for G1-G2 Thoracic Neuroendocrine Tumors (T-Net): Single Center Experience
Authors: R. Marconcini, I. Petrini, L. Galli, E. Vasile, A. Antonuzzo, A. Farnesi, L. Derosa, E. Bracco, R. Viglialoro, A. Falcone, S. Ricci
Journal: Annals of Oncology (2014)
Shining a Light on the Dark Side
Authors: Alvaro F. Vargas Pelaez
Journal: Annals of Internal Medicine (2016)

Letters5 January 2016Shining a Light on the Dark SideAlvaro F. Vargas Pelaez, BSAlvaro F. Vargas Pelaez, BSFrom Penn State College of Medicine, Hershey, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As a third-year medical student rotating in labor and delivery, I agree with a recent commentary (1) and urge everybody to consider his point about Laine and colleagues' editorial (2). As a field, we do need to talk about the good, the bad, and the ugly. However, featuring 2 of these ugly stories about obstetrics and gynecology in an internal medicine journal without input from our colleagues in this field could be counterproductive. If we are ready to talk about the dark side, making a conscious effort to avoid targeting and to start sharing the secrets of ...References1. Jaspan DM. Annals essays portray ob.gyns. unfairly. Ob. Gyn. News. 18 August 2015. Accessed at www.obgynnews.com/views/commentaries/single-article/annals-essays-portray-obgyns-unfairly/bf7bd2bb4b14cf81f43cf1d92c955b99.html on 26 August 2015. Google Scholar2. Laine C, Taichman DB, LaCombe MA. On being a doctor: shining a light on the dark side [Editorial]. Ann Intern Med. 2015;163:320. [PMID: 26280419]. doi:10.7326/M15-1144 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Penn State College of Medicine, Hershey, Pennsylvania.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0514. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOn Being a Doctor: Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Shafik Dharamsi Shining a Light on the Dark Side Linda Ray Shining a Light on the Dark Side Gaetan Sgro , Mark T. Gladwin , Alexander Teng , Akshata Moghe , and Shanta M. Zimmer Shining a Light on the Dark Side Jordan Cohen and Richard I. Levin Shining a Light on the Dark Side Elizabeth Allemann Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Metrics 5 January 2016Volume 164, Issue 1Page: 68KeywordsConflicts of interestDisclosureLabor and deliveryObstetrics and gynecology ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Usefulness of serum cortisol in assessment for the severity of community-acquired pneumonia
Authors: Min-Su Kim
Journal: European Respiratory Journal (2011)

Background: High cortisol levels are frequently observed in patients with severe infections and are of prognostic value in sepsis. The aim of this study was to evaluate the clinical usefulness of serum cortisol in assessment for the severity of community-acquired pneumonia (CAP).

Materials and methods: This study analyzed the results of 52 CAP subjects admitted in Changwon Fatima Hospital between July 2008 to May 2010. Total serum cortisol, infection markers such as C-reactive protein (CRP), procalcitonin (PCT) and CURB (Confusion, Uremia, Respiratory rate, Blood pressure)-65 were examined retrospectively.

Results: In clinically unstable subjects on admission day 4, baseline serum cortisol, CURB-65, and CRP were elevated significantly compared to those of stable subjects.

View this table:

Laboratory parameters and severity scores of the patients according to outcome





Area under curve (AUC) of cortisol, CRP, and CURB-65 from ROC curves were 0.847, 0.783, and 0.724 respectively. In the subjects with serum cortisol ≥22.82 μg/dL, CRP, PCT, CURB-65 score, and mortality were significantly elevated.

Conclusion: These findings suggest that measurement of serum cortisol in early stage may provide helpful information in the assessment of CAP severity.
JARID1D Is a Suppressor and Prognostic Marker of Prostate Cancer Invasion and Metastasis
Authors: Na Li, Shilpa S. Dhar, Tsai-Yu Chen, Pu-Yeh Kan, Yongkun Wei, Jae-Hwan Kim, Chia-Hsin Chan, Hui-Kuan Lin, Mien-Chie Hung, Min Gyu Lee
Journal: Cancer Research (2016)

Abstract Entire or partial deletions of the male-specific Y chromosome are associated with tumorigenesis, but whether any male-specific genes located on this chromosome play a tumor-suppressive role is unknown. Here, we report that the histone H3 lysine 4 (H3K4) demethylase JARID1D (also called KDM5D and SMCY), a male-specific protein, represses gene expression programs associated with cell invasiveness and suppresses the invasion of prostate cancer cells in vitro and in vivo. We found that JARID1D specifically repressed the invasion-associated genes MMP1, MMP2, MMP3, MMP7, and Slug by demethylating trimethyl H3K4, a gene-activating mark, at their promoters. Our additional results demonstrated that JARID1D levels were highly downregulated in metastatic prostate tumors compared with normal prostate tissues and primary prostate tumors. Furthermore, the JARID1D gene was frequently deleted in metastatic prostate tumors, and low JARID1D levels were associated with poor prognosis in prostate cancer patients. Taken together, these findings provide the first evidence that an epigenetic modifier expressed on the Y chromosome functions as an anti-invasion factor to suppress the progression of prostate cancer. Our results also highlight a preclinical rationale for using JARID1D as a prognostic marker in advanced prostate cancer. Cancer Res; 76(4); 831–43. ©2016 AACR.