tbuckley/cabot-search huggingface dataset:
Abstract 1033: Simultaneous Clot-targeted Factor Xa Inhibition And Selective Blockade Of Activated GPIIb/IIIa On Platelets Results In Delayed But Potent Antithrombotic Effects Without Bleeding Time Prolongation.
Authors: Christoph E Hagemeyer, Steffen U Eisenhardt, Nicole Bassler, Patrick Stoll, Meike Schwarz, Yung C Chen, Ingo Ahrens, Christoph Bode, Karlheinz Peter
Journal: Circulation (2007)

Background: We generated phage-display-derived anti-GPIIb/IIIa single-chain antibodies (e.g. scFv SCE5) that specifically bind to the activated GPIIb/IIIa only and thus specifically block activated platelets only. ScFv SCE5 demonstrates strong antithrombotic potency, comparable to the conformation-unspecific blockers tirofiban and eptifibatide. In contrast bleeding times were not prolonged with scFv SCE5. Here we now use the possibility to add effector molecules using molecular biology methods. The highly potent anticoagulant TAP (tick anticoagulant peptide), which is a direct factor Xa (fXa) inhibitor, was used as an effector molecule. Methods and Results: We genetically fused the activation-specific scFv with TAP, expressed the constructs in E.coli and purified the 39 kDa protein via its Histag binding to Nickel beads. Specific binding of the fusion molecules MA2/SCE5-TAP and strong inhibition of fibrinogen binding was proven in flow cytometry; anti-fXa activity was demonstrated in chromogenic assays. In vivo anticoagulative efficiency was determined by Doppler-flow in a ferric chloride-induced carotid artery thrombosis model in mice. Prolongation in occlusion time with SCE5-TAP was significantly stronger compared to SCE5 alone, recombinant TAP, non-binding mut-scFv-TAP as well as the clinical used drugs enoxaparine and eptifibatide. In contrast to the other anticoagulants tested, bleeding time was not prolonged by SCE5-TAP. Flow experiments studying platelet adhesion on collagen revealed a possible mechanism for the unique finding of a fully normal bleeding time: LIBS exposure on adhering platelets and as such the anticoagulative targeting potency of SCE5-TAP was delayed until considerable layers of platelets were deposited. Conclusions: The combination of activation-specific GPIIb/IIIa blockade and fXa inhibition in one clot-targeted molecule further improves in-vivo antithrombotic efficiency without causing any bleeding time prolongation. The delay of the observed targeting effect may allow a sealing of injuries with platelet layers but may be in time for the prevention of occlusive platelet aggregates. The described blockers represent a new type of highly selective drugs that warrant further clinical development.
Abstract 2315: Elderly Patients Experience an Equal Clinical Efficacy With No Observed Increase in Complications From More Aggressive Left Atrial Ablation
Authors: Tobin Lim, John D Day, Brian G Crandall, Tami L Bair, Heidi T May, Jeffrey S Osborn, Jeffrey L Anderson, Donald L Lappe, Jennifer Nelson, Thomas J Bunch
Journal: Circulation (2009)

Background: An aging population coupled with more patients living longer with cardiovascular disease have resulted in a dramatic increasing prevalence of elderly patients with atrial fibrillation (...
Abstract 1185: Role Of Sphingosine-1-Phosphate (S1P) In Insulin Signaling.
Authors: Suzanne M Nicholl, Elisa Roztocil, Mark G Davies
Journal: Circulation (2007)

A failure to increase glucose disposal into peripheral tissues in response to insulin leads to impaired insulin signaling and an inability to uptake glucose leading to the onset of insulin resistance, a major contributing factor to diabetes. We examined the role of sphingosine-1-phosphate (S1P) in insulin signaling and its ability to regulate glucose uptake in skeletal muscle cells. S1P, a sphingolipid found in abundance in the circulation, has been implicated in not only mediating crosstalk with other signaling pathways but has also been implicated in insulin resistance. We hypothesize that S1P interacts with post-receptor insulin signaling to increase glucose disposal in an in vitro model of insulin resistance using differentiated mouse skeletal C2C12 myotubes. Our data demonstrates that S1P (10μM) increases basal glucose levels similar to that observed in response to insulin (100nM) under conditions of low glucose (** p &lt; 0.005: n = 3). Conversely, high glucose conditions completely inhibit both insulin and S1P stimulated glucose uptake (*p &lt; 0.01:n = 3). Pre-incubation with S1P does not augment insulin-induced glucose uptake (***p &lt; 0.001:n = 3), suggesting that S1P does not act via a separate signaling pathway. This is confirmed by our data demonstrating that S1P-induced glucose uptake is abrogated by Cytochalasin B (*p &lt; 0.001:n = 3). In addition, the PI3-K inhibitors, LY294002 and Wortmannin, the Akt inhibitor, AKT2 and the p38MAPK inhibitor, SB203580 significantly inhibited glucose uptake in response to S1P, demonstrating their importance in S1P-induced glucose uptake (*p &lt; 0.05:n = 3). S1P2 and S1P3 receptor expression were upregulated in response to insulin (~2-fold over basal) under low glucose conditions suggesting that insulin may regulate S1P signaling via one or both of these receptors. S1P increased serine phosphorylation of IRS1, both at serine 307 and serines 636/639 maximally after 15 minutes of stimulation. This data has important clinical implications in patients with metabolic syndrome who have impaired skeletal muscle glucose disposal due to insulin resistance and will help guide present and future therapy for patients who have this rapidly growing disease.
Abstract 2002: Comparison of Image Characteristics of Plaques in Culprit Coronary Arteries by 64 Slice CT and Intravascular Ultrasound in Acute Coronary Syndrome
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Iwao Ishibashi, Yoshiya Miyazaki, Yoshiaki Sakai, Koki Matsuno, Susumu Namikawa, Masanori Sano, Tomoki Yamaoka, Kenichiro Kubo, Masae Uehara, Issei Komuro
Journal: Circulation (2008)
Neuroscience and psychiatry: marriage or coexistence?
Authors: H Pardes
Journal: American Journal of Psychiatry (1986)

Psychiatry, which has experienced the influence of many thrusts in its history, is currently experiencing the impact of neuroscience. Clinicians view the impact with excitement and with apprehension. The author reviews examples of the excitement of scientific developments related to psychiatry. He traces the coexisting evolution of a more differentiated clinical psychiatry and deals with questions of reconciling neuroscience and behavioral approaches. The author's contention is that neuroscience will strengthen psychiatry and that biological and psychological integration will thus be enhanced.
Abstract 5471: NAD(P)H Oxidase Nox4 in Vascular Endothelial and Smooth Muscle Cells May Be Involved in the Regulation of Basal Blood Pressure
Authors: Junya Kuroda, Tetsuro Ago, Junichi Sadoshima
Journal: Circulation (2009)

Reactive oxygen species (ROS) play an important role in mediating changes in blood pressure, vascular remodeling, and arteriosclerosis. All vascular cell types including vascular endothelial cells (ECs) and smooth muscle cells (SMCs) produce ROS, primarily through NAD(P)H oxidase (Nox) family enzymes, including Nox1, Nox2 and Nox4. Nox4 is predominantly expressed in ECs and SMCs and its expression in the vasculature is upregulated by aging. In order to elucidate the function of Nox4 in blood vessels, we established transgenic mice with EC- and SMC-specific overexpression of wild-type Nox4 (EC-Nox4, SMC-Nox4) and dominant negative Nox4 (EC-DN-Nox4, SMC-DN-Nox4). EC- and SMC-specific overexpression was achieved with SM22 α and Tie2 promoters, respectively. Enhanced expression of Nox4 or DN-Nox4 in ECs or SMCs was confirmed by immunostaining of blood vessels with a specific anti-Nox4 antibody. Superoxide producing activity in blood vessels was enhanced in EC-Nox4 (129.5±15.2%) and SMC-Nox4 (142.2±12.9%), and attenuated in EC-DN-Nox4 (30.6±4.9%) and SMC-DN-Nox4 (49.4±10.2%) compared to non-transgenic controls, as evaluated by dihydroethidium staining. At 3 months of age, EC-Nox4 exhibited significantly lower systolic blood pressure than WT (96.3±5.5 vs. 110.3±5.0 mmHg, p &lt; 0.05) as determined by the tail-cuff method. Conversely, SMC-Nox4 exhibited significantly higher systolic blood pressure than WT (122.7±3.2 vs. 107.3±3.9 mmHg, p &lt; 0.05). Blood pressure in EC-DN-Nox4 or SMC-DN-Nox4 was not statistically different from WT. At 3 months of age, none of the transgenic mouse lines exhibited obvious histopathological changes in vasculature, including aortas and arterioles in hearts and kidneys. Elevation of blood pressure induced by continuous infusion of angiotensin II (Ang II) (0.6 ng/g/min) in EC-Nox4 or SMC-Nox4 was not significantly different from WT at day 3, 7 and 14. Taken together, these results suggest that upregulation of Nox4 in SMCs and ECs increases superoxide production, thereby increasing or decreasing, respectively, blood pressure at baseline, without affecting Ang II-induced elevation in blood pressure.
Abstract 151: Obesity and Cooling Time to Target Temperature in Patients Undergoing Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest
Authors: Jason Schauer, Douglas Kupas
Journal: Circulation (2012)

Introduction: Therapeutic hypothermia (TH) is an important treatment to improve neurologic outcome in victims of out-of-hospital cardiac arrest (OHCA). It has been shown that shorter times to targe...
Size of Extranodal Extension on Sentinel Lymph Node Dissection in the American College of Surgeons Oncology Group Z0011 Trial Era
Authors: Audrey H. Choi, Summer Blount, Mia N. Perez, Carlos E. Chavez de Paz, Samuel A. Rodriguez, Matthew Surrusco, Carlos A. Garberoglio, Sharon S. Lum, Maheswari Senthil
Journal: JAMA Surgery (2015)

Based on the American College of Surgeons Oncology Group Z0011 trial exclusion criteria, patients with T1N0 or T2N0 breast cancer with 1 or 2 positive sentinel lymph nodes (SLNs) are recommended to undergo axillary lymph node dissection if extranodal extension (ENE) is present.OBJECTIVE To determine the effect of ENE size on residual axillary nodal burden, disease recurrence, and survival in patients meeting Z0011 criteria. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort study between January 1, 2000, and December 31, 2012, at a single tertiary cancer center.Patients had T1 or T2 breast cancer with 1 or 2 positive SLNs.The ENE was classified as 2 mm or smaller or as larger than 2 mm. MAIN OUTCOMES AND MEASURESNodal burden, disease recurrence, and overall survival. RESULTSOf 208 patients, 149 (71.6%) had no ENE, 21 (10.1%) had ENE 2 mm or smaller, and 38 (18.3%) had ENE larger than 2 mm on SLN dissection.The median follow-up time was 60 months (range, 1-158 months).The mean (SD) total number of positive lymph nodes differed significantly for the group with no ENE (1.72 [1.39]) vs the group with ENE 2 mm or smaller (3.22 [2.09]; P < .001)and vs the group with ENE larger than 2 mm (4.26 [5.01]; P < .001).Similar patterns were observed for mean (SD) nonsentinel lymph node metastases: 0.48 (1.30) for no ENE vs 1.91 (2.07) with ENE 2 mm or smaller (P = .02)and vs 2.95 (4.95) with ENE larger than 2 mm (P < .001).For the group without ENE vs the group with ENE 2 mm or smaller, there were no significant differences in recurrence (distant recurrence, 4 patients [2.7%] vs 1 patient [4.8%], respectively; P = .62)or in mortality (18 patients [12.1%] vs 4 patients [19.1%], respectively; P = .48).For the group without ENE vs the group with ENE larger than 2 mm, there were no significant differences in recurrence (distant recurrence, 4 patients [2.7%] vs 4 patients [10.5%], respectively; P = .19)or in mortality (18 patients [12.1%] vs 9 patients [23.7%], respectively; P = .07).CONCLUSIONS AND RELEVANCE Presence of ENE on SLN dissection is associated with N2 disease.Despite increased nodal burden, patients with 1 or 2 positive SLNs and ENE 2 mm or smaller demonstrated recurrence and survival rates similar to those of patients without ENE.Reporting of ENE size should be standardized and required.
Abstract 14545: Glucagon-Like Peptide-1 Receptor Activation With Liraglutide During Acute Myocardial Infarction Improves Myocardial Salvage and Systolic Left Ventricular Function
Authors: Torsten P Vahl, Carlos G Santos-Gallego, Teresa Arias, Kiyotake Ishikawa, Armando U Cuesta, Javier Sanz, Martin E Goldman, Roger J Hajjar, Valentin Fuster, Juan J Badimon
Journal: Circulation (2013)

Introduction: Glucagon-like Peptide-1 (GLP-1) is an intestinal hormone that plays an important role for normal glucose tolerance. Recent studies suggest that GLP-1 has anti-apoptotic and cytoprotec...
Abstract 14217: Enhanced LV Stiffening Assessed by Diastolic Wall Strain is Associated with Poor Prognosis in Patients with Heart Failure and Moderately Reduced Ejection Fraction
Authors: Yukitoshi Ikeya, Yasushi Sakata, Ohtani Tomohito, Yasuharu Takeda, Shunsuke Tamaki, Yousuke Omori, Yasumasa Tsukamoto, Atsushi Hirayama, Kazuhiro Yamamoto, Toshiaki Mano, Issei Komuro
Journal: Circulation (2012)

Objectives: Diastolic wall strain (DWS), an index based on the linear elastic theory and a simple calculation, has been proven to reflect LV stiffening in an animal model and to predict worse outco...
Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients
Authors: M Berger, J Vollmann, F Hohagen, A König, H Lohner, U Voderholzer, D Riemann
Journal: American Journal of Psychiatry (1997)

The authors' goal was to test the hypothesis that the antidepressant effect of total sleep deprivation can be maintained by initially avoiding sleep during a supposedly "critical" time period in the early morning.They studied 33 inpatients with major depression, melancholic type, all of whom responded positively to total sleep deprivation. Twelve of the patients were men and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00 midnight, which then was shifted back by 1 hour each day until a sleep time of 11:00 p.m. to 6:00 a.m. was reached.Twenty (61%) of the 33 patients who responded to total sleep deprivation with an improved state of mood maintained this improvement during sleep phase advance therapy. Drug-free and medicated patients did not differ from each other.The rapid amelioration of mood observed with total sleep deprivation can be preserved with a succeeding phase shift of the sleep period.
Proteolytic regulation of β-catenin by calpain and potential role in cancer
Authors: Jonathan Rios-Doria, Arul M. Chinnaiyan, Mark A. Rubin, Mark L. Day
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1442 

Mutations in the regulatory domain of β-catenin have been implicated in cancer. These mutations cause stabilization of β-catenin and increased TCF-dependent transcriptional activity. The cysteine protease calpain has been implicated in human tumorigenesis and is a potential target for therapy. We found that β-catenin is proteolytically cleaved by calpain, resulting in the removal of the N-terminal regulatory domain. Treatment of MCF-7 cells with ionomycin activated calpain and resulted in the generation of a 75-kDa β-catenin fragment. Calpain activation was confirmed by Western analysis of spectrin, a known substrate of calpain. Pre-treatment of cells with calpain inhibitors blocked β-catenin cleavage, implicating calpain in this process. The β-catenin75 fragment was also generated by calpain in vitro . β-catenin cleavage resulted in an increase in TCF-dependent transcriptional activity, and this activity was blocked by pre-treatment of cells with calpain inhibitors. β-catenin75 accumulated in the nucleus, supporting a role for β-catenin75 in enhanced TCF-dependent transcriptional activity. Expression analysis of m-calpain cDNA levels in a prostate cancer microarray demonstrated increased m-calpain levels in 49 localized and 19 metastatic prostate cancer samples compared to 26 normal prostate samples. These data demonstrate that calpain can proteolytically cleave β-catenin resulting in a stable and transcriptionally active 75-kDa fragment. Given the low frequency of β-catenin mutation in some cancers, β-catenin cleavage by calpain might represent a novel mechanism by which β-catenin is activated during tumorigenesis.
Abstract 3958: Understanding "Functional" Tricuspid Regurgitation Accompanying Mitral Valve Disease
Authors: Lina Vargas, Sarinya Puwanant, Edward R Nowicki, Jeevanantham Rajeswaran, Allan L Klein, Eugene H Blackstone, Gosta B Pettersson
Journal: Circulation (2009)

Objective: To understand the relation of degree of tricuspid regurgitation (TR) accompanying mitral valve disease (so-called “functional” TR) to both right heart (RH) dilatation (remodeling) and ri...
Report on Cancer Risks Associated with the Ingestion of Asbestos
Authors: R. Lemen, T. Meinhardt, G. Becking, K. Cantor, J. Cherner
Journal: Environmental Health Perspectives (1987)

Cancer risks associated with ingestion of asbestos are discussed. Asbestos contamination of drinking water is considered. At least 66.5% of the United States water systems are capable of eroding asbestos cement pipes. The ability of water to leach asbestos from asbestos cement pipes can be modified by coatings applied to the inside pipe surface. Asbestos contamination in foods or pharmaceuticals is discussed. Asbestos fibers at concentrations of 1.1 to 172.7 million fibers per liter have been found in beverages. To date, studies supported by the Food and Drug Administration (FDA) have provided no evidence that ingesting asbestos results in an increased cancer risk. The FDA has determined that no prohibition on using asbestos filters in processing food, beverages, and non-parenteral drugs is needed. Toxicological studies on asbestos ingestion and carcinogenicity are reviewed. Epidemiological evaluations of the association between drinking-water supplies containing asbestos and cancer mortality are discussed. It is concluded that the available information is insufficient for assessing the risk of cancer associated with ingesting asbestos.
The diagnosis of malignancy following a venous thromboembolic event - how high is the risk?
Authors: Emma Crawford, Harmesh Moudgil, Thirumalairengarajan Naicker, Nawaid Ahmad, Koottalai Srinivasan
Journal: European Respiratory Journal (2014)

UK guidance on the treatment of venous thromboembolism (VTE) recommends that patients with a first, unprovoked VTE should be screened for malignancy. This is based on two historical population-based studies which suggest that between 7.5 and 11% of patients diagnosed with an unprovoked VTE will develop cancer in the following two years. (Murchison, J.T. et al. Br J Cancer 2004;91(1):92-95. Baron, J.A. et al. Lancet 1998; 351(9109):1077-1080.) We wanted to compare local figures with this historical data in order to aid local guideline development.  A retrospective case note review identified 417 patients within our institution diagnosed with VTE between January 2010 and January 2011.  Ten of these patients (2%) developed cancer in the two years following diagnosis.  In 2 out of 10 of these patients, tests performed as part of the routine work-up for VTE identified abnormalities that ultimately led to a diagnosis of cancer. None of the patients had extensive malignancy screening as advocated by current UK guidance.  Within our local population, the risk of developing cancer in the two years following an unprovoked VTE appears to be significantly less than figures quoted in the literature. UK guidelines may not reflect current medical practice, which could be identifying cancer earlier, nor does it take into account the possibility of regional and national variations of disease. A cautious approach should be taken when counselling patients regarding future cancer risk and when considering further investigations for malignancy.
Effectiveness of community-based screening for depression
Authors: S F Greenfield, J M Reizes, K M Magruder, L R Muenz, B Kopans, D G Jacobs
Journal: American Journal of Psychiatry (1997)

The effectiveness of a voluntary depression screening program was assessed by determining 1) whether participants in the 1994 National Depression Screening Day went for recommended follow-up examinations and 2) the characteristics that differentiated those who did and did not return.Randomly selected participants (N = 1,169) from 99 facilities completed a follow-up telephone survey.Of 805 people for whom follow-up was recommended, 56.5% (N = 455) went for an appointment. The severity of depressive symptoms in these subjects ranged from severe (33.4%, N = 152) and marked (41.3%, N = 188) to minimal (17.1%, N = 78) and normal (8.1%, N = 37). Subjects with marked or severe depression were more likely to respond to the screening recommendation than were those with minimal depressive symptoms. However, at each level of symptom severity, subjects who had received previous treatment were more likely to adhere to the screening recommendation than were those with no previous treatment. Of those who returned for a recommended follow-up, 72.1% were diagnosed with depression. Of those who did not return, 29.5% cited lack of insurance, under insurance, or inadequate finances, and 38.0% felt they could "handle" depression on their own.Voluntary screening for depression is an effective way to bring certain untreated depressed individuals to treatment. Inadequate insurance and the belief that individuals can manage depression on their own continue to be barriers to seeking treatment among some depressed individuals who attend a depression screening program.
Protecting children from armed conflict
Authors: D. Southall, K. Abbasi
Journal: BMJ (1998)

Once wars and other conflicts begin, children suffer abuse—physical, sexual, and emotional. This is despite international laws to protect them.1 Recent studies on the psychological consequences of armed conflict have shown that the resultant unhappiness and mental disturbance is so great in children that it can rarely be repaired.2 4 The answer therefore has to be prevention, and, if that fails, the international community needs to act rapidly to protect vulnerable children.

In conflicts over the past 10 years 90% of casualties have been civilians. Two million children have been killed and 4–5 million seriously injured (usually without analgesia, anaesthesia, or surgical facilities to treat them). Twelve million children have been made homeless, over one million orphaned, and countless psychologically traumatised. Three quarters of deaths from antipersonnel mines are among children.

#### United Nations Convention on the Rights of the Child (International Law in 1990)

In accordance with their obligations under International Humanitarian laws in armed conflicts, States Parties shall take all feasible measures to ensure protection and care of children who are affected by an armed conflict.—Article 38, pt 4

Inequalities in health care, and the poverty in which a …
The Radiation Recovery Factor: Preservation by the Polge-Smith-Parkes Technique
Authors: David W. H. Barnes, John F. Loutit
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article The Radiation Recovery Factor: Preservation by the Polge-Smith-Parkes Technique Get access David W. H. Barnes, David W. H. Barnes Medical Research Council's Radiobiological Research Unit, Atomic Energy Research Establishment, Harwell, Berks, England Search for other works by this author on: Oxford Academic PubMed Google Scholar John F. Loutit John F. Loutit Medical Research Council's Radiobiological Research Unit, Atomic Energy Research Establishment, Harwell, Berks, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 901–905, https://doi.org/10.1093/jnci/15.4.901 Published: 01 February 1955 Article history Received: 11 October 1954 Published: 01 February 1955