tbuckley/cabot-search huggingface dataset:
Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer
Authors: Johanna C. Bendell, Michael S. Gordon, Herbert I. Hurwitz, Suzanne F. Jones, David S. Mendelson, Gerard C. Blobe, Neeraj Agarwal, Carolyn H. Condon, Dawn Wilson, Amelia E. Pearsall, Yijun Yang, Ty McClure, Kenneth M. Attie, Matthew L. Sherman, Sunil Sharma
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The angiogenesis inhibitor dalantercept (formerly ACE-041) is a soluble form of activin receptor–like kinase-1 (ALK1) that prevents activation of endogenous ALK1 by bone morphogenetic protein-9 (BMP9) and BMP10 and exhibits antitumor activity in preclinical models. This first-in-human study of dalantercept evaluated its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in adults with advanced solid tumors. Experimental Design: Patients in dose-escalating cohorts received dalantercept subcutaneously at one of seven dose levels (0.1–4.8 mg/kg) every 3 weeks until disease progression. Patients in an expansion cohort received dalantercept at 0.8 or 1.6 mg/kg every 3 weeks until disease progression. Results: In 37 patients receiving dalantercept, the most common treatment-related adverse events were peripheral edema, fatigue, and anemia. Edema and fluid retention were dose-limiting toxicities and responded to diuretic therapy. No clinically significant, treatment-related hypertension, proteinuria, gross hemorrhage, or gastrointestinal perforations were observed. One patient with refractory squamous cell cancer of the head and neck had a partial response, and 13 patients had stable disease according to RECISTv1.1, eight of whom had prolonged periods (≥12 weeks) of stable disease. Correlative pharmacodynamic markers included tumor metabolic activity and tumor blood flow, which decreased from baseline in 63% and 82% of evaluable patients, respectively, and telangiectasia in eight patients. Conclusion: Dalantercept was well-tolerated at doses up to 1.6 mg/kg, with a safety profile distinct from inhibitors of the VEGF pathway. Dalantercept displayed promising antitumor activity in patients with advanced refractory cancer, and multiple phase II studies are underway. Clin Cancer Res; 20(2); 480–9. ©2013 AACR.
β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome
Authors: Çetin Ağar, Gwendolyn M. A. van Os, Matthias Mörgelin, Richard R. Sprenger, J. Arnoud Marquart, Rolf T. Urbanus, Ronald H. W. M. Derksen, Joost C. M. Meijers, Philip G. de Groot
Journal: Blood (2010)
Impaired extracellular matrix degradation in aortic vessels of cirrhotic rats
Authors: Guillermo Fernández-Varo, Manuel Morales-Ruiz, Josefa Ros, Sònia Tugues, Javier Muñoz-Luque, Gregori Casals, Vicente Arroyo, Juan Rodés, Wladimiro Jiménez
Journal: Journal of Hepatology (2006)
Associations of Mortality and Diabetes Complications in Patients With Type 1 and Type 2 Diabetes
Authors: Michael Cusick, Annal D. Meleth, Elvira Agrón, Marion R. Fisher, George F. Reed, Genell L. Knatterud, Franca B. Barton, Matthew D. Davis, Frederick L. Ferris, Emily Y. Chew
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS—We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS—The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06–12.54]) and poor visual acuity (1.74 [1.10–2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS—Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.
Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy
Authors: Sanjit S. Jolly, John A. Cairns, Salim Yusuf, Brandi Meeks, Janice Pogue, Michael J. Rokoss, Sasko Kedev, Lehana Thabane, Goran Stankovic, Raul Moreno, Anthony Gershlick, Saqib Chowdhary, Shahar Lavi, Kari Niemelä, Philippe Gabriel Steg, Ivo Bernat, Yawei Xu, Warren J. Cantor, Christopher B. Overgaard, Christoph K. Naber, Asim N. Cheema, Robert C. Welsh, Olivier F. Bertrand, Alvaro Avezum, Ravinay Bhindi, Samir Pancholy, Sunil V. Rao, Madhu K. Natarajan, Jurriën M. ten Berg, Olga Shestakovska, Peggy Gao, Petr Widimsky, Vladimír Džavík
Journal: New England Journal of Medicine (2015)

During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results.We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days.The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02).In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).
Cell kinetics and tumour formation: Cell turnover in the lungs of mice with hereditary lung tumours
Authors: M. B. Divertie, R. G. Shorter, J. L. Titus
Journal: Thorax (1968)

Cell turnover time varies from one tissue to another but is reproducible as a hereditary characteristic for a given cell line. The present study indicates that it is prolonged in the lungs of mice congenitally predisposed to developing primary lung tumours. Primary malignant tumours occur more frequently in areas of relatively slow cell replacement in the human gastrointestinal tract than in those where cell turnover is rapid. On the basis of these observations it is suggested that postmaturity of a cell may be a significant factor in the development of neoplastic change.
The Relationship of Treatment Adherence to the Risk of Death After Myocardial Infarction in Women
Authors: E J Gallagher, C M Viscoli, R I Horwitz
Journal: JAMA (1993)

To examine the relationship between adherence to a medical regimen and mortality following a myocardial infarction in women.Analysis of the female cohort entered into a randomized double-blind multicenter trial.National Heart, Lung, and Blood Institute beta-Blocker Heart Attack Trial.The 602 women, aged 30 to 69 years, enrolled in the beta-Blocker Heart Attack Trial.Random assignment to propranolol hydrochloride or placebo 5 to 21 days following a myocardial infarction.Adherence for each patient was calculated as the mean of all quarterly adherence estimates during the course of the trial (median follow-up, 26 months). Adherence was classified as good (taking > or = 75% of medication) or poor (taking < 75% of medication). The end point was death from all causes occurring at any time during the trial, adjusted for treatment category and other clinical and sociodemographic features.Adherence data were available on 505 women, of whom 32 (6.3%) died. Death occurred in 13.6% of poor adherers compared with 5.6% of good adherers (relative risk, 2.4; 95% confidence interval, 1.1 to 5.6). The effect of adherence on mortality remained undiminished after adjustment for treatment category (propranolol or placebo), age, severity of myocardial infarction, congestive heart failure, smoking history, marital status, educational level, and race (adjusted relative risk of death for poor adherers, 2.5 to 3.0; P < or = .02).The independent effect of adherence on mortality following a myocardial infarction in women is clinically substantial, statistically significant, and similar in magnitude to that reported earlier for men.
RELATION BETWEEN ORGAN WEIGHTS AND OBSCURE LESIONS IN APPARENTLY NORMAL RABBITS
Authors: Wade H. Brown, Louise Pearce, Chester M. Van Allen
Journal: The Journal of Experimental Medicine (1926)

A study of organ weights was made on a group of 295 normal rabbits for the purpose of determining whether any relation could be detected between the weights of organs and the extent and activity of the lesions found post mortem. The results obtained seemed to indicate that disease, even in its mildest form, is capable of affecting the weights of organs that are not directly involved by the disease process and that the effect produced bears a relation to both the extent and the activity of the lesions present. There was also some evidence that the converse might be true; namely, that the occurrence and subsequent course of disease may be influenced in some measure by the state of organ balance and the ability of the animal organism to adjust itself to meet the demands of disease-producing agencies.
Breastfeeding Is Associated with Infant Gut Microbial Composition
Authors: Kyra J. Jones, Alexandra R. Sitarik, Kei Fujimura, Christine Cole Johnson, Suzanne Havstad, Haejin Kim, Andrea Cassidy-Bushrow, Kevin Bobbitt, Nicholas W. Lukacs, Kimberley J. Woodcroft, Edward M. Zoratti, Albert M. Levin, Ganesa R. Wegienka, Susan V. Lynch, Homer A. Boushey, Dennis R. Ownby
Journal: Journal of Allergy and Clinical Immunology (2015)
PTU-018 Automatic Detection Of ‘suspicious’ Capsule Endoscopy Video Segments
Authors: A Koulaouzidis, S Tsevas, DK Iakovidis
Journal: Gut (2014)

<h3>Introduction</h3> Manual review and annotation of a capsule endoscopy (CE) video requires a considerable amount of reviewing time. The diagnostic accuracy of this process may decrease over time due to reviewer tiredness. Recent studies showed an average detection rate – for the clinically significant findings – as low as 40%.<sup>1</sup> We present a generic computational framework for automatic detection of abnormalities in CE videos. <h3>Methods</h3> A CE video (MiroCam<sup>®</sup>, InrtoMedic Co Ltd, Seoul, Korea), depicting inflammatory changes (aphthae, mucosal breaks, ulcers, erythema) was reviewed and manually annotated by experienced CE reviewer. A total of 1984 frames, containing any pathology, were thumbnailed. The proposed framework considers video frames as members of a vector space represented by their colour information. An unsupervised data reduction algorithm,<sup>2</sup> which does not require any prior knowledge about the data, was then applied on each segment. This algorithm clusters together frames that exhibit similar characteristics e.g., colour distributions. Its output is a subset of video frames extracted from each cluster by applying a threshold to the clustering result. The extracted frames are characteristic of the particular video segment and as a result representative of possible lesions. <h3>Results</h3> The evaluation of the proposed framework aimed to determine its accuracy, in terms of the ratio of the neighbourhoods represented by at least one frame in the system's output and the neighbourhoods that were manually annotated as suspicious for containing lesions. The parameters considered include clustering from 2 to 6 clusters and thresholds<sup>2</sup> varying from 0.004 to 0.6. The obtained accuracy ranged between 76% to 98% depending on the desired sensitivity level of the algorithm, controlled by the threshold. Furthermore, the automatic selection of the representative CE video segments performed by the proposed approach, the number of video frames to be thoroughly examined can be reduced from 30% to 60% of the original video, depending on the clustering and threshold settings. <h3>Conclusion</h3> The application of the proposed framework to the evaluation of CE videos may reduce the rate of false negative evaluations by attracting the attention of the reviewer to automatically identified video segments (or single frames) of interest which are likely to contain lesions. <h3>References</h3> Zheng Y, Hawkins L, Wolff J, Goloubeva O, Goldberg E. Detection of lesions during capsule endoscopy: physician performance is disappointing.<i> Am J Gastroenterol</i>. 2012;107:554–60 Iakovidis DK, Tsevas S, Polydorou A. Reduction of capsule endoscopy reading times by unsupervised image mining. <i>Comput. Med. imaging Graph. Off. J. Comput. Med. Imaging Soc</i>. 2010;34(6):471–478 <h3>Disclosure of Interest</h3> None Declared.
Myocardial Steatosis and Biventricular Strain and Strain Rate Imaging in Patients With Type 2 Diabetes Mellitus
Authors: Arnold C.T. Ng, Victoria Delgado, Matteo Bertini, Rutger W. van der Meer, Luuk J. Rijzewijk, See Hooi Ewe, Hans-Marc Siebelink, Johannes W.A. Smit, Michaela Diamant, Johannes A. Romijn, Albert de Roos, Dominic Y. Leung, Hildo J. Lamb, Jeroen J. Bax
Journal: Circulation (2010)

Magnetic resonance spectroscopy can quantify myocardial triglyceride content in type 2 diabetic patients. Its relation to alterations in left (LV) and right (RV) ventricular myocardial functions is unknown.A total of 42 men with type 2 diabetes mellitus were recruited. Exclusion criteria included hemoglobin A(1c) >8.5, known cardiovascular disease, diabetes-related complications, or blood pressure >150/85 mm Hg. Myocardial ischemia was excluded by a negative dobutamine stress test. LV and RV volumes and ejection fraction were quantified by magnetic resonance imaging. LV global longitudinal and RV free wall longitudinal strain, systolic strain rate, and diastolic strain rate were quantified by echocardiographic speckle tracking analyses. Myocardial triglyceride content was quantified by magnetic resonance spectroscopy and dichotomized on the basis of the median value of 0.76. The median age was 59 years (25th and 75th percentiles, 54 and 62 years). Median diabetes diagnosis duration was 4 years, and median glycohemoglobin level was 6.2 (25th and 75th percentiles, 5.9 and 6.8). There were no differences in LV and RV end-diastolic and end-systolic volume indexes and ejection fraction between patients with high (≥0.76) and those with low (<0.76) myocardial triglyceride content. However, patients with high myocardial triglyceride content had greater impairment of LV and RV myocardial strain and strain rate. The myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate.High myocardial triglyceride content is associated with more pronounced impairment of LV and RV functions in men with uncomplicated type 2 diabetes mellitus.
Classification of severe asthma exacerbations: a proposal
Authors: C Picado
Journal: European Respiratory Journal (1996)

The intensity of asthma exacerbations may vary from mild to severe. Many studies have demonstrated that the speed at which severe asthma exacerbation (SAE) develops varies among patients. In some asthmatics, the exacerbation comes on very quickly, whereas in others there is a progressive deterioration of clinical, functional and blood gas parameters. Sudden SAE are characterised by their explosive presentation and quick recovery. This evolution contrasts with that of patients with a slow onset SAE, who often need prolonged hospitalization. Absence of secretions suctioned from the airways during mechanical ventilation has been reported in sudden SAE, whereas large amounts of viscid mucus are found in patients with the slow onset SAE. The lungs of patients who died during a sudden onset SAE often show empty airways and a predominant neutrophilic infiltration in the bronchial epithelium, in contrast to the presence of abundant eosinophils in patients who died during a slow onset SAE. Sudden onset SAE may occur as sporadic cases or in outbreaks. Sporadic cases may result from the ingestion of nonsteroidal anti-inflammatory drugs (NSAID) in patients with intolerance to these products, massive exposure to common allergens and ingestion of foods containing sulphites. Asthma outbreaks have been described in many cities. In contrast to sudden onset SAE, slow onset SAE is characterized by a progressive deterioration, accompanied by an increase in the use of bronchodilators. Lack of appropriate monitoring of function by peak expiratory flow (PEF) recording, failure of patients to recognize worsening symptoms and underusage of inhaled and oral steroid treatment have been repeatedly identified as factors which are likely to be associated with slow onset SAE. The contribution of psychosocial problems, depression, denial of asthma severity and nonadherence with the treatment should not be overlooked in patients with slow onset SAE. Classification of severe asthma exacerbations into two types (sudden onset and slow onset) could help to reveal the aetiology of the attack and may also be relevant to the management of the patient.
Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenotype.
Authors: E S Raveche, E A Novotny, C T Hansen, J H Tjio, A D Steinberg
Journal: The Journal of Experimental Medicine (1981)

The genetic basis for autoimmunity in NZB mice has been investigated through analysis of recombinant inbred lines produced by mating NZB mice with two different non-autoimmune strains. Several genes (at least six) were found to be necessary for the production of eight traits characteristic of the NZB mice that were studied. No fundamental genetic defect (an "autoimmunity gene") was identified that could give rise to the various autoimmune traits studied. This study strongly suggests that NZB disease results from the actions of several separate genes that together result in the characteristic manifestations of autoimmunity.
Assessment of Four Stakeholder Groups’ Preferences Concerning Outpatient Commitment for Persons With Schizophrenia
Authors: Marvin S. Swartz, Jeffrey W. Swanson, H. Ryan Wagner, Michael J. Hannon, Barbara J. Burns, Martha Shumway
Journal: American Journal of Psychiatry (2003)

Study findings indicating that involuntary outpatient commitment can improve treatment outcomes among persons with severe mental illness remain controversial. Opponents of outpatient commitment argue that its coerciveness is unacceptable even given its arguable benefits. However, it is unclear to what extent the public debate surrounding outpatient commitment represents the preferences of persons with a stake in the benefit or harm resulting from outpatient commitment. This study examines and compares views of outpatient commitment among four stakeholder groups: 1) persons in treatment for schizophrenia and related disorders, 2) family members of persons with these disorders, 3) clinicians treating persons with these disorders, and 4) members of the general public.Subjects from the Piedmont region of North Carolina who were members of the four stakeholder groups were presented with short vignettes that depicted potential outcomes that were associated alternatively with outpatient commitment and with voluntary treatment. Subjects rated each vignette according to how positively or negatively they viewed the overall situation for the individual described. Multivariate regression techniques were used to estimate preference weights for each stakeholder group.With some exceptions, each group gave the highest preference to avoiding involuntary hospitalization, followed by avoiding interpersonal violence and maintaining good interpersonal relationships. No group gave appreciable importance to outpatient commitment, which suggests that avoiding its coerciveness is a lesser concern compared to other outcomes.The findings suggest that these stakeholders are willing to accept the coerciveness of outpatient commitment to gain improved outcomes for certain persons with schizophrenia and related disorders.
Diaspirin Cross-Linked Hemoglobin (DCLHb) in the Treatment of Severe Traumatic Hemorrhagic Shock&lt;SUBTITLE&gt;A Randomized Controlled Efficacy Trial&lt;/SUBTITLE&gt;
Authors: Edward P. Sloan, Max Koenigsberg, David Gens, Mark Cipolle, Jeffrey Runge, Mary Nan Mallory, George Rodman
Journal: JAMA (1999)

ContextSevere, uncompensated, traumatic hemorrhagic shock causes significant morbidity and mortality, but resuscitation with an oxygen-carrying fluid might improve patient outcomes.ObjectiveTo determine if the infusion of up to 1000 mL of diaspirin cross-linked hemoglobin (DCLHb) during the initial hospital resuscitation could reduce 28-day mortality in traumatic hemorrhagic shock patients.Design and SettingMulticenter, randomized, controlled, single-blinded efficacy trial conducted between February 1997 and January 1998 at 18 US trauma centers selected for their high volume of critically injured trauma patients, but 1 did not enroll patients.PatientsA total of 112 patients with traumatic hemorrhagic shock and unstable vital signs or a critical base deficit, who had a mean (SD) patient age of 39 (20) years. Of the infused patients, 79% were male and 56% were white. An exception to informed consent was used when necessary.InterventionAll patients were to be infused with 500 mL of DCLHb or saline solution. Critically ill patients who still met entry criteria could have received up to an additional 500 mL during the 1-hour infusion period.Main Outcome MeasuresTwenty-eight day mortality, 28-day morbidity, 48-hour mortality, and 24-hour lactate levels.ResultsOf the 112 patients, 98 (88%) were infused with DCLHb or saline solution. At 28 days, 24 (46%) of the 52 patients infused with DCLHb died, and 8 (17%) of the 46 patients infused with the saline solution died (P = .003). At 48 hours, 20 (38%) of the 52 patients infused with DCLHb died and 7 (15%) of the 46 patients infused with the saline solution died (P = .01). The 28-day morbidity rate, as measured by the multiple organ dysfunction score, was 72% higher in the DCLHb group (P = .03). There was no difference in adverse event rates or the 24-hour lactate levels.ConclusionsMortality was higher for patients treated with DCLHb. Although further analysis should investigate whether the mortality difference was solely due to a direct treatment effect or to other factors, DCLHb does not appear to be an effective resuscitation fluid.