tbuckley/cabot-search huggingface dataset:
Stepwise Screening of Atrial Fibrillation in a 75-Year-Old Population
Authors: JohanEngdahl, LisbethAndersson, MariaMirskaya, MårtenRosenqvist
Journal: Circulation (2013)

Background—Atrial fibrillation (AF) is a frequent source of cardiac emboli in patients with ischemic stroke. AF may be asymptomatic and therefore undiagnosed. Screening for silent AF seems suitable in risk populations, however little is known on the yield and cost-effectiveness of such screening. Methods and Results—All inhabitants in the municipality of Halmstad, Sweden aged 75 to 76 years were invited to a stepwise screening program for AF. As a first step, participants recorded a 12-lead ECG and reported their relevant medical history. Those with sinus rhythm on 12-lead ECG, no history of AF, and ≥2 risk factors according to CHADS2 were invited to a 2-week recording period using a hand-held ECG and asked to record 20 or 30 seconds twice daily and if palpitations occurred. One thousand, three hundred thirty inhabitants were invited, of whom 848 (64%) participated. Previously undiagnosed silent AF was found in 10 (1%) among 848 individuals who recorded 12-lead ECG. Among 81 patients with known AF, 35 (43...
Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase
Authors: AndreasFriebe, DorisKoesling
Journal: Circulation Research (2003)

In this review, we outline the current knowledge on the regulation of nitric oxide (NO)-sensitive guanylyl cyclase (GC). Besides NO, the physiological activator that binds to the prosthetic heme group of the enzyme, two novel classes of GC activators have been identified that may have broad pharmacological implications. YC-1 and YC-1-like substances act as NO sensitizers, whereas the substance BAY 58-2667 stimulates NO-sensitive GC NO-independently and preferentially activates the heme-free form of the enzyme. Sensitization and desensitization of NO/cGMP signaling have been reported to occur on the level of NO-sensitive GC; in the present study, an alternative mechanism is introduced explaining the adaptation of the NO-induced cGMP response by a long-term activation of the cGMP-degrading phosphodiesterase 5 (PDE5). Finally, regulation of GC expression and a possible modulation of GC activity by other factors are discussed.
Abstract 17895: Complementary Prognostic Value of Cardiac Metaiodobenzylguanidine Imaging and Diastolic Wall Strain in Patients With Preserved Left Ventricular Ejection Fraction Admitted for Acute Decompensated Heart Failure
Authors: ShunsukeTamaki, TakahisaYamada, TakashiMorita, YoshioFurukawa, YusukeIwasaki, MasatoKawasaki, AtsushiKikuchi, TakumiKondo, MasashiIshimi, HideyukiHakui, TatsuhisaOzaki, YoshihiroSato, MasahiroSeo, IyoIkeda, EijiFukuhara, MasatakeFukunami
Journal: Circulation (2015)

Introduction: Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging has been reported to provide prognostic information in patients with heart failure with preserved ejection fraction (HFpEF). On the other hand, diastolic wall strain (DWS) has been recently introduced as a simple and feasible echocardiographic index in assessing left ventricular (LV) diastolic stiffness, and has been shown to be associated with poor outcome in patients with HFpEF. Hypothesis: We assessed the hypothesis that cardiac MIBG imaging and DWS might have a complementary prognostic value in HFpEF patients admitted for acute decompensated heart failure (ADHF). Methods: We studied 70 consecutive patients admitted for ADHF and discharged with survival whose LV ejection fraction measured by echocardiography was ≧40% (age: 77±12 years, male: 49%, NYHA class at discharge: 2.2±0.8). Cardiac MIBG imaging and echocardiography were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate were c...
Recurrent acute pancreatitis due to pancreatic duct ascariasis in a young man
Authors: Radhika Chavan, Mohan Ramchandani, Zaheer Nabi, Sundeep Lakhtakia, Jahangeer Basha, D. Reddy
Journal: Endoscopy (2018)

A 26-year-old man presented with abdominal pain and vomiting for 7 days. He had had similar complaints a few months previously. His laboratory evaluation showed a raised serum amylase (878 IU/dL) and a bulky pancreas on ultrasonography of the abdomen. Other etiological work-up for acute pancreatitis was normal. Contrast-enhanced computed tomography (CT) scanning revealed a normal pancreas with a linear hypodense structure in the second part of the duodenum ([Fig. 1]).
What are the risk factors for injuries and injury prevention strategies for skiers and snowboarders in terrain parks and half-pipes? A systematic review
Authors: Olivier Audet, Brent E Hagel, Albertro Nettel-Aguirre, Tatum Mitra, Carolyn A Emery, Alison Macpherson, Marie Denise Lavoie, Claude Goulet
Journal: British Journal of Sports Medicine (2018)

Objective To synthesise the current evidence regarding the risk factors, the injury prevention strategies and the profile of injured skiers and snowboarders in terrain parks (TPs) and half-pipes (HPs). Design Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Data sources Literature searches from six electronic databases and manual searches were performed. Eligibility criteria for selecting studies Inclusion criteria were: (1) publication based on original data; (2) injuries sustained in TPs or HPs; (3) recreational skiing or snowboarding injuries; (4) observational or experimental study design with a comparison group. Results No study explored the risk factors in HPs or the prevention strategies in TPs or HPs. From the literature retrieved, there is strong evidence that skiing or snowboarding in a TP is a risk factor for head, neck, back and severe injuries. Two papers assessed the risk factors for injuries in TPs, mainly demonstrating that features promoting aerial manoeuvres or a large drop to the ground were associated with higher feature-specific injury rates. The profile of injured skiers and snowboarders in TPs described in the literature suggested some evidence of associations between factors including activity, sex, skill level, helmet use, age and TP injuries. Summary/conclusions This systematic review demonstrates the need for studies identifying the risk factors for injuries to skiers and snowboarders and on interventions to reduce the risk of injury in TPs and HPs. Studies addressing the issue of TP design should be considered. PROSPERO registration number CRD42016045206.
Abstract 1539: In vivo study of natural killer cell cytotoxicity against cholangiocarcinoma in a nude mouse model
Authors: Inhye Jung, DoHee Kim, Yong Yoon Chung, Seung Woo Park, Da Kyung Yoo
Journal: Cancer Research (2018)

Abstract NK cell is one of the lymphocytes clinically used for various cancer types. Cytotoxicity of NK cell to cholangiocarcinoma (CC), however, has not been studied yet, nor has NK cell therapy against CC been clinically applied. In this study, relevance of NK cell therapy for antitumor efficacy against CC was preclinically investigated. Human HuCCT-1 cells, an intrahepatic CC cell line, were xenografted into nude mice. The HuCCT-1 tumor-bearing nude mice then received multiple infusions of ex vivo expanded human NK cell (SMT01) and were evaluated for in vivo cytotoxic activity of the NK cells. Dosage-dependent safety and toxicity of SMT01 was evaluated at three different dose levels. The mice well tolerated the maximum dose of SMT01. All of the three dosage groups did not show any significant adverse event. To evaluate in vivo activity of SMT01 against CC, we administered 5 infusions of SMT01 into the HuCCT-1 tumor-bearing nude mice. A standard chemotherapy as a positive control was also included. The result showed that SMT01 infusions resulted in significant inhibition of the CC tumor growth compared to the negative control (normal saline infusion), suggesting that NK cell contains in vivo cytolytic activity against cholangiocarcinoma. When body weights of the nude mice were measured, however, the body weight of the nude mice administered with chemotherapy was found to be maintained as lowest among all treatment groups while all the NK cell infusion groups well maintained the body weight during the treatment, suggesting beneficial effect of NK cell therapy in relevance of quality of life. IHC experiments and TUNEL assay using the tumor tissue sections clearly supported the cytotoxicity results of SMT01 against CC. We found that a robust infiltration of the infused NK cells was located along the loose tissue where feeding vessels entered. TUNEL-positive tumor cells were mainly localized at the vicinity of populated NK cells. In conclusion, our in vivo study demonstrates that NK cell also contains cytolytic activity against cholangiocarcinoma. Further investigation of the NK cell-based immunotherapy can be useful to determine cancer therapeutics for the specific tumor. Citation Format: Inhye Jung, DoHee Kim, Yong Yoon Chung, Seung Woo Park, Da Kyung Yoo. In vivo study of natural killer cell cytotoxicity against cholangiocarcinoma in a nude mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1539.
Abstract 3672: The three-dimensional (3D) spatial lamin A/C organization in normal lymphocytes, and in Hodgkin and Reed-Sternberg cells
Authors: Fabio Contu, Aleksander Szczurek, Roberta Vanni, Hans Knecht, Sabine Mai
Journal: Cancer Research (2018)

Abstract Classical Hodgkin Lymphoma (HL) is a B-Cell lymphoma comprising mononucleated Hodgkin cells (H) and diagnostic bi- to multi-nucleated Reed Sternberg cells (RS). Genomic instability in HL is characterized by telomere dysfunction caused by critically short telomeres and telomere uncapping. Super resolution microscopy showed significant increases in the amount of DNA-poor nuclear spaces in HL compared to normal primary lymphocytes. A direct 3D interaction between telomeres and shelterin protein TRF2 is progressively disrupted from H to RS cells by either massive upregulation or downregulation of TRF2. TRF2 interacts with nuclear matrix protein lamin A/C in the maintenance of the 3D genome organization, which is disturbed in H and RS cells. Therefore we hypothesized that the TRF2- telomere-lamin A/C interaction is also disturbed in H and RS cells and leads to organizational alterations of the genome in HL. To this end, we analyzed lamin A/C expression levels of lymphocytes, H and RS cells and found that lamin A/C is upregulated in cancer cells compared to both activated and resting lymphocytes. The regular homogeneous and round shaped pattern found in lymphocytes was replaced in H and RS cells by a more irregular one, characterized by the presence of lamin A/C invaginations and septa that subdivide the nuclei into multiple smaller compartments. Our data show no co-localization between telomeres and lamin A/C in the DNA-poor spaces. Lamin A/C bordered the DNA-poor spaces but was never found inside them or in association with inner telomere fragments. 3D TRF-2 staining showed upregulation of the protein compared to normal lymphocytes, in correlation with the observation made in EBV-negative patients with clinically aggressive disease. The analysis of pre-treatment Hodgkin's patients' samples will allow to determine whether the TRF2-telomere-lamin A/C binding is different in patients with recurrent versus non-recurrent disease. Citation Format: Fabio Contu, Aleksander Szczurek, Roberta Vanni, Hans Knecht, Sabine Mai. The three-dimensional (3D) spatial lamin A/C organization in normal lymphocytes, and in Hodgkin and Reed-Sternberg cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3672.
Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial
Authors: Ganesh Raghu, Carlos A Pellegrini, Eric Yow, Kevin R Flaherty, Keith Meyer, Imre Noth, Mary Beth Scholand, John Cello, Lawrence A Ho, Sudhakar Pipavath, Joyce S Lee, Jules Lin, James Maloney, Fernando J Martinez, Ellen Morrow, Marco G Patti, Stan Rogers, Paul J Wolters, Robert Yates, Kevin J Anstrom, Harold R Collard
Journal: The Lancet Respiratory Medicine (2018)
Abstract 20455: Comparing the Efficacy of Contractile and Pre-Contractile Cardiomyocytes in Restoring the Function of the Injured Myocardium
Authors: RahulThakker, AtsushiTachibana, YukaMatsuura, MouerWang, EricRulifson, PhillipYang
Journal: Circulation (2014)

BACKGROUND: Cell therapy has shown to promote the repair of injured cardiac muscle post-myocardial infarction (MI). However, transplantation of human embryonic stem cell (hESC)-derived cardiomyocytes (hCMs) has not demonstrated consistent functional restoration of the injured myocardium. This may be explained by their reduced plasticity and engraftment potential due to their developmentally differentiated state. HYPOTHESIS: Pre-contractile hCMs (pre-hCMs) will provide significant and sustained restoration of the injured myocardium compared to the contractile hCMs. METHODS & RESULTS: H7 hESCs were differentiated through small molecule manipulation of the Wnt signaling pathway in cardiac development. Cells were cultured for 2 days with 6 uM CHIR99021, a Wnt activator, followed by another 2 days with 5 uM IWR-1, a Wnt inhibitor. Spontaneous contractility was typically observed around 10 days after initial exposure. For the purpose of analysis, hCMs were harvested at day 35 and pre-hCMs were harvested at day ...
Genomic Profiling in Patients With Malignant Peripheral Nerve Sheath Tumors Reveals Multiple Pathways With Targetable Mutations
Authors: Henry G. Kaplan, Steven Rostad, Jeffrey S. Ross, Siraj M. Ali, Sherri Z. Millis
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: The aim of this study was to determine the frequency of alterations in BRAF and other RAS/RAF genes, as well as other targetable pathways in malignant peripheral nerve sheath tumors (MPNSTs). Patients and Methods: Pathology specimens were available for 2 cohorts: (1) patients with MPNST at Swedish Cancer Institute (n=17) from 2004 through 2016, and (2) patients with MPNST evaluated for >300 genomic alterations at Foundation Medicine from 2014 through 2016 (n=186; including 2 Swedish patients with BRAF-mutated MPNST). Results: Of 201 MPNSTs, 13 (6.5%) demonstrated BRAF alterations. In the Foundation Medicine cohort, 10 of 84 tumors (11.9%) with no NF1 alterations had BRAF mutations (5 were V600E, 5 other), as did 3 of 102 (2.9%) tumors with NF1 alterations (1 V600E, 2 other). In the Foundation Medicine cohort, 47% of patients had an alteration in at least one other gene in the RAS/RAF pathway (not including NF1 or BRAF); 46% had alterations in the PI3 pathway, with 70% having alterations in at least 1 of the 2 pathways; 57% had a CDKN2A alteration (80% in BRAF-mutated and 71% in NF1-altered patients); and 70% had an alteration in DNA repair genes. MPNST, both NF1 wild-type and NF1-mutated, often harbor alterations in the RAS/RAF pathway as well as changes related to DNA repair and CDKN2A/B. V600E and other mutations occur in BRAF, suggesting the need for second-generation activating BRAF inhibitors. The concurrence of BRAF and/or NF1 alterations with CDKN2A/B mutations, in particular, may be significant in the transformation of neurologic tumors from benign to malignant. Conclusions: All MPNSTs would benefit from a comprehensive genomic analysis. Treatments targeted to RAS/RAF, DNA repair, and CDKN2A/B pathways should be used and/or developed to treat this uncommon tumor.
Efficacy of Olyset Duo, a bednet containing pyriproxyfen and permethrin, versus a permethrin-only net against clinical malaria in an area with highly pyrethroid-resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial
Authors: Alfred B Tiono, Alphonse Ouédraogo, Daouda Ouattara, Edith C Bougouma, Sam Coulibaly, Amidou Diarra, Brian Faragher, Moussa W Guelbeogo, Nelson Grisales, Issa N Ouédraogo, Zininwindé Amidou Ouédraogo, Margaret Pinder, Souleymane Sanon, Tom Smith, Fiona Vanobberghen, N'Fale Sagnon, Hilary Ranson, Steve W Lindsay
Journal: The Lancet (2018)
Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1
Authors: Brinda Emu, Jeffrey Fessel, Shannon Schrader, Princy Kumar, Gary Richmond, Sandra Win, Steven Weinheimer, Christian Marsolais, Stanley Lewis
Journal: New England Journal of Medicine (2018)

Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4.In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later. Through week 25 of the study, patients received 800 mg of ibalizumab every 14 days, combined with an individually optimized background regimen including at least one fully active agent. The primary end point was the proportion of patients with a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (day 7) to day 14.A total of 31 patients completed the study. The mean baseline viral load was 4.5 log10 copies per milliliter, and the mean CD4 count was 150 per microliter. Of the 40 patients in the intention-to-treat population, 33 (83%) had a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (P<0.001 for the comparison with the control period). The mean viral-load decrease was 1.1 log10 copies per milliliter. During the control period, 1 patient, who received the optimized background regimen prematurely, had a decrease in viral load of 0.5 log10 copies per milliliter. At week 25, patients who had received ibalizumab plus an optimized background regimen had a mean decrease of 1.6 log10 copies per milliliter from baseline; 43% of the patients had a viral load of less than 50 copies per milliliter, and 50% had a viral load of less than 200 copies per milliliter. Among 10 patients who had virologic failure or rebound, in vitro testing identified 9 who had a lower degree of susceptibility to ibalizumab than at baseline. The most common adverse event was diarrhea (in 20% of patients). Four patients died from causes related to underlying illnesses; 1 had a serious adverse event (the immune reconstitution inflammatory syndrome) that was deemed to be related to ibalizumab therapy.In patients with MDR HIV-1 infection who had advanced disease and limited treatment options, ibalizumab had significant antiviral activity during a 25-week study. Evidence of the emergence of diminished ibalizumab susceptibility was observed in vitro in patients who had virologic failure. (Funded by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed Biologics; TMB-301 ClinicalTrials.gov number, NCT02475629 .).
Abstract 12503: Synchrotron Radiation Coronary Microangiography for Evaluating Changes in the Caliber of the in vivo Rat Coronary Artery After Endothelin Administration
Authors: HiroakiSakamoto, ShonosukeMatsushita, KazuyukiHyodo, ChihoTokunaga, FujioSato, YujiHiramatsu
Journal: Circulation (2014)

Background: Conventional coronary angiography can visualize vessels of 300 μm in diameter, but not those of smaller diameter, such as the proliferating collateral arteries of ischemic heart disease and the new blood vessels formed in regenerative medicine. We have developed a system of synchrotron radiation coronary microangiography (SRCA) in the in vivo rat. The purpose of this study was to define the minimum detectable caliber change in the coronary arteries of the in vivo rat by inducing vasoconstriction with endothelin during SRCA. Method: SRCA was performed at the Photon Factory of the High Energy Accelerator Research Organization (Tsukuba, Japan). The advantages of synchrotron radiation derived X-rays are high spatial resolution (5 μm/pixel) due to increased photon density and straightness of beam. High density resolution is obtained with a high-gain avalanche rushing amorphous photoconductor camera using a fiber-optic plate. Rats were anesthetized. The polyethylene tube for angiography was inserted...
Prevalence of Disabilities and Health Care Access by Disability Status and Type Among Adults — United States, 2016
Authors: Catherine A. Okoro, NaTasha D. Hollis, Alissa C. Cyrus, Shannon Griffin-Blake
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Persons with disabilities face greater barriers to health care than do those without disabilities (1). To identify characteristics of noninstitutionalized adults with six specific disability types (hearing, vision, cognition, mobility, self-care, and independent living),* and to assess disability-specific disparities in health care access, CDC analyzed 2016 Behavioral Risk Factor Surveillance System (BRFSS) data. The prevalences of disability overall and by disability type, and access to health care by disability type, were estimated. Analyses were stratified by three age groups: 18-44 years (young adults), 45-64 years (middle-aged adults), and ≥65 years (older adults). Among young adults, cognitive disability (10.6%) was the most prevalent type. Mobility disability was most prevalent among middle-aged (18.1%) and older adults (26.9%). Generally, disability prevalences were higher among women, American Indians/Alaska Natives (AI/AN), adults with income below the federal poverty level (FPL), and persons in the South U.S. Census region. Disability-specific disparities in health care access were prevalent, particularly among young and middle-aged adults. These data might inform public health programs of the sociodemographic characteristics and disparities in health care access associated with age and specific disability types and guide efforts to improve access to care for persons with disabilities.
Mechanism of Hydrocortisone Potentiation of Responses to Epinephrine and Norepinephrine in Rabbit Aorta
Authors: Stanleykalsner
Journal: Circulation Research (1969)

Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing e...