tbuckley/cabot-search huggingface dataset:
Cardiac infarction injury score: an electrocardiographic coding scheme for ischemic heart disease.
Authors: P MRautaharju, J WWarren, UJain, H KWolf, C LNielsen
Journal: Circulation (1981)

A multivariate decision-theoretic electrocardiogram (ECG) classification scheme called Cardiac Infarction Injury Score (CIIS) was developed using ECGs of 387 patients with myocardial infarction (MI) and 320 subjects without infarction. The most accurate and stable classification was achieved by using a combination of eight binary (single threshold), three ternary (two thresholds), and four ECG features measured on a continuous scale. For practical visual coding of ECGs, the CIIS coding procedure uses a checklist containing 12 items measured from the conventional 12-lead ECG. The CIIS test results indicate that, in comparison with conventional ECG criteria for MI used in clinical trials, the diagnostic accuracy can be considerably improved by optimizing feature and threshold selection and by multivariate analysis. The CIIS detected MI with a sensitivity of 85% and a specificity of 95%. Using a higher severity level, a specificity of 99% was achieved, with a sensitivity of 71%. One of the primary uses of th...
Improving Adherence to Endoscopy Guidelines for Triage and Surveillance In a Single Endoscopy Unit
Authors: J Cudmore, S Stewart, H Kerr, P MacMathuna, J Leyden, C Lahiff, B Kelleher, J Muslow, G Bennett
Journal: Endoscopy (2021)

Aims Encouraging adherence to agreed triage guidelines is a critical facet of endoscopy waiting list management, particularly in the current climate of COVID-19. Unfortunately, few such guidelines exist and there is considerable variability in their application.
Next-Generation Sequencing of 487 Esophageal Adenocarcinomas Reveals Independently Prognostic Genomic Driver Alterations and Pathways
Authors: Smita Sihag, Samuel C. Nussenzweig, Henry S. Walch, Meier Hsu, Kay See Tan, Francisco Sanchez-Vega, Walid K. Chatila, Sergio A. De La Torre, Assem Patel, Yelena Y. Janjigian, Steven Maron, Geoffrey Y. Ku, Laura H. Tang, Jaclyn Hechtman, Pari M. Shah, Abraham J. Wu, David R. Jones, Daniela Molena, David B. Solit, Nikolaus Schultz, Michael F. Berger
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To delineate recurrent oncogenic driver alterations and dysregulated pathways in esophageal adenocarcinoma and to assess their prognostic value. Experimental Design: We analyzed a large cohort of patients with lower esophageal and junctional adenocarcinoma, prospectively sequenced by MSK-IMPACT with high-quality clinical annotation. Patients were subdivided according to treatment intent, curative versus palliative, which closely mirrored clinical staging. Genomic features, alterations, and pathways were examined for association with overall survival using Cox proportional hazard models, adjusted for relevant clinicopathologic factors knowable at the time of diagnosis. Results: Analysis of 487 patients revealed 16 oncogenic driver alterations, mostly amplifications, present in ≥5% of patients. Patients in the palliative-intent cohort, compared with those in the curative-intent cohort, were more likely to have metastatic disease, ERBB2 amplifications, Cell-cycle and RTK–RAS pathway alterations, as well as a higher fraction of genome altered and rate of whole-genome doubling. In multivariable analyses, CDKN2A alterations, SMAD4 alterations, KRAS amplifications, Cell-cycle and TGFβ pathways, and overall number of oncogenic drivers were independently associated with worse overall survival. ERBB2 amplification was associated with improved survival, presumably due to trastuzumab therapy. Conclusions: Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, CDKN2A, KRAS, and SMAD4 represent prognostic biomarkers, given their strong association with poor survival.
The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents
Authors: Pauline Dürr, Katja Schlichtig, Carolin Kelz, Birgit Deutsch, Renke Maas, Michael J. Eckart, Jochen Wilke, Harald Wagner, Kerstin Wolff, Caroline Preuß, Valeska Brückl, Norbert Meidenbauer, Christian Staerk, Andreas Mayr, Rainer Fietkau, Peter J. Goebell, Frank Kunath, Matthias W. Beckmann, Andreas Mackensen, Markus F. Neurath, Marianne Pavel, Frank Dörje, Martin F. Fromm
Journal: Journal of Clinical Oncology (2021)

Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking.Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience.Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group.Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
Abstract 17065: Performance of Cardiovascular Disease Risk Scores to Identify Coronary Artery Calcium Burden in Retired National Football League Players
Authors: Genevieve E Smith, Jonathan A Drezner, Camilo Fernandez, Gregory W Stewart
Journal: Circulation (2020)

Introduction: Coronary artery calcium (CAC) is a robust predictor of coronary events in asymptomatic individuals with latent atherosclerotic cardiovascular disease (CVD). While evidence suggests CAC scoring may augment traditional CVD risk scores in clinical decision making, evidence is limited on the compared ability of CVD risk scores to identify the degree of coronary atherosclerosis as quantified by absolute CAC, particularly in former elite athlete populations. We investigated this in a cohort of retired National Football League (NFL) players. Methods: We analyzed data on 752 retired NFL players (aged 55.2 ± 9.0 years, 53.7% African-American] that underwent health screening and CAC scoring with the NFL Player Care Foundation. Three 10-year CVD risk scores were compared: Framingham Coronary Heart Disease (FCHD), Framingham CVD (FCVD), and Atherosclerotic CVD Risk Pooled Cohort Equations (PCE). Receiver operating characteristic curves were fitted in 3 models: FCHD (Model 1), FCVD (Model 2), and PCE (Model 3, used as reference based on 2013 AHA guidelines). Contrast analyses identified the model with highest discriminative ability (c statistic) versus CAC = 0 for each CAC score category: &gt;0 and &lt;100, 100-400, and &gt;400. Results: Compared to PCE , FCVD exhibited the highest discriminative ability for CAC &gt; 0 and &lt; 100 ( c statistic 0.7071 vs 0.6706, p&lt;0.0001), while FCHD had the lowest for both CAC 100-400 ( c statistic 0.7198 vs 0.7664, p=0.0165) and CAC &gt;400 ( c statistic 0.7728 vs 0.8460, p&lt;0.0001). No additional differences were identified (Figure 1). Conclusion: Traditional CVD risk scores differ in performance to predict absolute CAC among retired NFL players, underscoring a need for refinement of coronary event risk prediction models to enhance the ability of such models to identify, specifically, low CAC, as even low CAC burden confers increased risk compared to CAC absence. This may include accounting for elite athlete-specific characteristics.
Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.
Authors: NTakahashi, MIto, SIshida, TFujino, TSaikawa, MArita
Journal: Circulation (1992)

BACKGROUNDPrevious evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs).METHODS AND RESULTSWe assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the tak...
Computational Assessment of Protein–protein Binding Affinity by Reversely Engineering the Energetics in Protein Complexes
Authors: Bo Wang, Zhaoqian Su, Yinghao Wu
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The cellular functions of proteins are maintained by forming diverse complexes. The stability of these complexes is quantified by the measurement of binding affinity, and mutations that alter the binding affinity can cause various diseases such as cancer and diabetes. As a result, accurate estimation of the binding stability and the effects of mutations on changes of binding affinity is a crucial step to understanding the biological functions of proteins and their dysfunctional consequences. It has been hypothesized that the stability of a protein complex is dependent not only on the residues at its binding interface by pairwise interactions but also on all other remaining residues that do not appear at the binding interface. Here, we computationally reconstruct the binding affinity by decomposing it into the contributions of interfacial residues and other non-interfacial residues in a protein complex. We further assume that the contributions of both interfacial and non-interfacial residues to the binding affinity depend on their local structural environments such as solvent-accessible surfaces and secondary structural types. The weights of all corresponding parameters are optimized by Monte-Carlo simulations. After cross-validation against a large-scale dataset, we show that the model not only shows a strong correlation between the absolute values of the experimental and calculated binding affinities, but can also be an effective approach to predict the relative changes of binding affinity from mutations. Moreover, we have found that the optimized weights of many parameters can capture the first-principle chemical and physical features of molecular recognition, therefore reversely engineering the energetics of protein complexes. These results suggest that our method can serve as a useful addition to current computational approaches for predicting binding affinity and understanding the molecular mechanism of protein–protein interactions.
Involvement of endothelin in the regulation of human vascular tonus. Potent vasoconstrictor effect and existence in endothelial cells.
Authors: TMiyauchi, YTomobe, RShiba, TIshikawa, MYanagisawa, SKimura, YSugishita, IIto, KGoto, TMasaki
Journal: Circulation (1990)

Endothelin, a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various vessels of experimental animals. To study the involvement of endothelin in the regulation of vascular tonus in humans, isolated human mesenteric arteries were investigated by both pharmacological and immunohistochemical methods. The vasoconstrictor action of endothelin-1 was examined on ring segments of human mesenteric arteries. Endothelin-1 induced a slowly developing and sustained contraction, with an EC50 value (half-maximal effective concentration) of 2.9 x 10(-9) M, two orders of magnitude smaller than that of norepinephrine (EC50 of 3.9 x 10(-7) M), indicating that the vasoconstrictor action of endothelin-1 is about 100 times more potent than that of norepinephrine. The contractile effect of endothelin-1 was affected neither by adrenergic, cholinergic, histaminergic, nor serotonergic antagonists, nor by inhibitors of arachidonic acid metabolism. The vasoconstrictor response...
Home monitoring reduced short stay admissions in suspected COVID-19 patients: COVID-box project
Authors: Ebru Dirikgil, Rick Roos, Geert H. Groeneveld, Christian Heringhaus, Anna V. Silven, Annelieke H.J. Petrus, Maria Villalobos-Quesada, Roula Tsonaka, Paul J.M. van der Boog, Ton J. Rabelink, Willem Jan W. Bos, Niels H. Chavannes, Douwe E. Atsma, Y.K. Onno Teng
Journal: European Respiratory Journal (2021)

<b>Tele-monitoring during the COVID-19 pandemic is recognised as a safe strategy to monitor patients at home. This is the first controlled study that demonstrates the effectiveness of home monitoring to reduce hospital admissions during a 28-day follow-up.</b>https://bit.ly/39vvngH
Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis.
Authors: M RBennett, G IEvan, A CNewby
Journal: Circulation Research (1994)

We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inactive in cotransformation and autosuppression assays (VSM-D106-143 myc cells). Clones of transfected VSM-myc cells were isolated that constitutively expressed a range of levels of c-Myc protein from that observed in normal proliferating VSMCs to approximately seven times normal. The growth rates of these clones and their responses to growth inhibitors were then assessed. VSM-myc clones possessed a shorter mean intermitotic time than normal cells, which was inversely correlated (P < .05) with the level of c-Myc protein expressed. VSM-myc cells also expressed lower levels of alpha-smooth muscle actin mRNA and protein and exhibited an altered morphology. The proliferation of normal VSMCs and VSM-D...
Vasectomy and Increased Risk of Prostate Cancer
Authors: Abraham Morgentaler
Journal: JAMA (1993)

To the Editor.  —In a recent issue ofJAMA, Giovannucci et al1,2report in two studies an association between vasectomy and prostate cancer, concluding in both that their work supports a causal relationship. However, a major study flaw invalidates any possible conclusion regarding causality. Namely, Giovannucci et al failed to obtain reliable information on the incidence of prostate cancer in their study population in a systematic manner and have therefore identified only a fraction of the clinically detectable cases of prostate cancers in their study population. Index cases were identified entirely on the basis of self-reports or spousal reports, a particularly insensitive assay for the presence of a disease such as prostate cancer, which may be asymptomatic even at advanced stages. As an illustration, Labrie and coworkers3identified 57 cases of prostate cancer among 1002 men selected from electoral rolls, for a detection rate of 5.7%, whereas Giovannucci
Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure.
Authors: R JCody, F BMüller, S HKubo, HRutman, DLeonard
Journal: Circulation (1986)

We developed an isolated limb preparation to evaluate the direct vasoactive properties of cardioactive drugs on the forearm vasculature in patients with congestive heart failure. Using this model, we infused milrinone in subsystemic doses (1, 10, and 20 micrograms/min per 100 ml forearm volume [FAV] ) into the brachial artery of 13 patients with moderate-to-severe congestive heart failure. We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery. This preparation enabled us to assess the direct forearm vascular response to milrinone. Compared with baseline forearm blood flow (2.46 +/- 1.37 ml/min/100 ml FAV), the three doses of milrinone resulted in increases in forearm blood flow to 2.66 +/- 1.43, 4.21 +/- 1.79, and 6.73 +/- 3.69 ml/min/100 ml FAV. This was associated with a reduction of forearm vascular resistance from the baseline value of 52 +/- 38 U to 47 +/- 36, 25 +/- 13, and 17 +/- 10 U. The p value for ...
Review of lipid-lowering clinical trials in relation to observational epidemiologic studies.
Authors: H ATyroler
Journal: Circulation (1987)

A review of the experimental clinical trials and observational cohort evidence relating serum cholesterol level and its reduction to risks of coronary heart disease (CHD) discloses strong similarities among the quantitative and qualitative relationships found in these studies. Not only are the risk functions similar, but the percent reduction observed is the same as that predicted from the population experience and is proportional to the degree of cholesterol lowering. Furthermore, the risk function is continuous from the highest to the lowest serum cholesterol levels studied. These findings confirm the lipid hypothesis and indicate that lowering serum cholesterol reduces CHD risk. The understanding and control of CHD requires a dual approach: (1) identification and treatment of high-risk individuals, and (2) modification of environmental and behavioral determinants to achieve more favorable distributions of serum cholesterol in populations.
Expression and insulin-like growth factor-dependent proteolysis of insulin-like growth factor-binding protein-4 are regulated by cell confluence in vascular smooth muscle cells.
Authors: AKamyar, C JPirola, H MWang, BSharifi, SMohan, J SForrester, J AFagin
Journal: Circulation Research (1994)

Insulin-like growth factor (IGF)-I is markedly induced after balloon injury in the rat aorta, where it may serve to mediate vascular repair. Because the bioavailability of IGF-I is modulated by IGF-binding proteins (IGFBPs), we examined the regulation of IGFBPs by IGFs in primary cultures of rat aortic smooth muscle cells (SMCs). Serum-deprived SMC-conditioned medium contains IGFBPs of 38 to 45 kD (only in confluent cultures), 30 kD (possibly IGFBP-2), 28 kD, and 24 kD (IGFBP-4), the latter being the most abundant. IGF-I and IGF-II but not insulin evoked a marked decrease of IGFBP-4 as early as 4 hours after treatment. IGFBP-4 mRNA abundance, however, was entirely unaffected by IGF-I for up to 48 hours. IGF-I analogues with high affinity for the IGF-I receptor and weak affinity for IGFBP paradoxically evoked a small increase in IGFBP-4, probably through a general increase in protein synthesis. IGF-I only minimally decreased IGFBP-4 content in medium of sparse cultures, whereas it completely abolished IGFB...
Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques?
Authors: M DRekhter, DGordon
Journal: Circulation Research (1994)

Previous studies have indicated the focal presence of growth factors and focal low levels of cell proliferation in human atherosclerotic plaques. Using human carotid plaques and an antibody to platelet-derived growth factor (PDGF)-A chain, we have begun to assess growth factor significance by spatially correlating growth factor gene expression with actual cell proliferation. Since PDGF is a mitogen for smooth muscle and related cells and since inflammatory cells (eg, macrophages) can also proliferate in these lesions, it was important to exclude inflammatory cell proliferation from this consideration. Therefore, we have used a triple immunolabeling approach, combining the above anti-PDGF-A chain antibody with an inflammatory cell cocktail (CD68+CD45 for monocyte/macrophages and lymphocytes) and adding an anti-proliferating cell nuclear antigen (PCNA) antibody to mark proliferating cells. In the carotid atherosclerotic plaques, PDGF immunostaining was distributed focally, preferentially in the fibrous cap ...
Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium.
Authors: C MBoulanger, F CTanner, M LBéa, A WHahn, AWerner, T FLüscher
Journal: Circulation Research (1992)

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endotheli...
Prediction of successful outcome in 130 patients undergoing percutaneous balloon mitral valvotomy.
Authors: V MAbascal, G TWilkins, J PO'Shea, C YChoong, I FPalacios, J DThomas, ERosas, J BNewell, P CBlock, A EWeyman
Journal: Circulation (1990)

We studied 130 patients undergoing percutaneous balloon mitral valvotomy. The relation between valvular morphology according to a previously described echocardiographic scoring system and hemodynamic outcome expressed as qualitative (good and suboptimal) and as absolute change in valve area was analyzed. The relative importance of the individual components of this echocardiographic score (valvular thickening, mobility, calcification, and subvalvular disease) to the change in valve area after valvotomy was also examined. Mean transmitral pressure gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001), and mitral valve area increased from 0.9 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.0001). Results in individual patients were variable. Eighty-four percent (61 of 73) of patients with an echocardiographic score of 8 or less had a good outcome (final valve area greater than or equal to 1.5 cm2 and an increase in valve area of greater than or equal to 25%), whereas 58% (33 of 57) of patients...