tbuckley/cabot-search huggingface dataset:
Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure.
Authors: J KGwathmey, LCopelas, RMacKinnon, F JSchoen, M DFeldman, WGrossman, J PMorgan
Journal: Circulation Research (1987)

Intracellular Ca2+ release and reuptake are essential for contraction and relaxation of normal heart muscle. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited 2 distinct components. Muscles from failing hearts showed a diminished capacity to restore low resting Ca2+ levels during diastole. These experiments provide the first direct evidence from actively contracting human myocardium that intracellular Ca2+ handling is abnormal and may cause systolic and diastolic dysfunction in heart failure.
More on Fake News, Disinformation, and Countering These with Science
Authors: Lawrence W. Green, Jonathan E. Fielding, Ross C. Brownson
Journal: Annual Review of Public Health (2021)

The difference in difference (DID) design is a quasi-experimental research design that researchers often use to study causal relationships in public health settings where randomized controlled trials (RCTs) are infeasible or unethical. However, causal ...Read More
Rate-modulated pacing.
Authors: SFurman
Journal: Circulation (1990)

The primary role of cardiac rate in adapting cardiac output to changing physiological needs has been more clearly recognized in recent years. Previously, the rate of cardiac stimulation had been determined either at pacemaker manufacture, by programming a single rate, or by sensing the atrium. More recently, sensing another physiological or nonphysiological function that changes in response to body need has become possible. Exercise changes blood oxygen saturation, central venous pH, central venous temperature, minute ventilation and respiratory rate, stroke volume, circulating catecholamines, QT interval, evoked endocardial response to a stimulus, and the mechanics of myocardial contraction. Some sensors respond to muscle work but not to intellectual effort or emotion. Pacemaker-based sensors of physiological function or activity allow a change in cardiac stimulation rate in response to need. Whichever sensor is used, increases in ventricular rate during exercise regularly produce a cardiac output respon...
A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer
Authors: Michael R. Shafique, Terrence L. Fisher, Elizabeth E. Evans, John E. Leonard, Desa Rae E. Pastore, Crystal L. Mallow, Ernest Smith, Vikas Mishra, Andreas Schröder, Kevin M. Chin, Joseph T. Beck, Megan A. Baumgart, Ramaswamy Govindan, Nashat Y. Gabrail, Alexander I. Spira, Nagashree Seetharamu, Yanyan Lou, Aaron S. Mansfield, Rachel E. Sanborn, Jonathan W. Goldman, Maurice Zauderer
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition. Patients and Methods: This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non–small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity. Results: The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria. Conclusions: The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors.
The response of healthy men to treadmill exercise.
Authors: R AWolthuis, V FFroelicher, JFischer, J HTriebwasser
Journal: Circulation (1977)

Heart rates, blood pressures, and functional responses to submaximal, maximal and postexertional treadmill testing are presented for a group of 704 healthy, asymptomatic aircrewmen referred to the USAF School of Aerospace Medicine. The indicated measurements are individually described by the use of percentiles. These data provide the practicing clinician with an accurate and complete description of the response of healthy men to treadmill exercise.
Using Real-World Historical Controls to Evaluate Radiation Dose Escalation in Esophageal Cancer—Reply
Authors: Dawei Chen, Hari Menon, James Welsh
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Countercurrent diffusion in the renal cortex of the rabbit.
Authors: R MEffros, KTaki, EReid, PSilverman
Journal: Circulation Research (1984)

Evidence was obtained for countercurrent diffusion of 14C-n-butanol in the rabbit renal cortex. After injection into the renal artery of perfused, isolated rabbit kidneys, concentrations of both 14C-butanol and tritiated water in the initial samples collected from the renal venous outflow exceeded those of 125I-albumin when the rate of perfusion was low. When flow was increased, the 125I-albumin curve was shifted to earlier times relative to the other labels. These observations confirm the existence of arteriovenous diffusion of 14C-butanol and tritiated water in the kidney. In a second set of experiments, 14C-butanol and tritiated water were infused for 10 or 60 seconds into the renal arteries of anesthetized rabbits, and the kidneys were then removed and frozen in liquid nitrogen. Cores were cut from the kidney surface and sectioned in a cryostat, and the ratio of 14C-butanol to tritiated water was calculated at increasing depths in the cortex. This ratio rose from 0.54 +/- 0.03 (SEM) at the surface to ...
The challenge of CONTEMPO
Authors: H. S. Myer
Journal: JAMA (1981)

For this, the fourth edition of our annual review issue, CONTEMPO, we challenged our contributors to provide articles of interest both to specialists in the same field and to colleagues in other fields. Our contributors have met the challenge. Now, we challenge our readers—to become aware of the clinical developments, research advances, and philosophies of other fields of medicine. As Drs Harry Jacob and Dale Hammerschmidt will discuss in our July 3 CLINICAL PERSPECTIVES, such awareness can spark ideas for new applications of one's own specialized knowledge. We hope all of our readers will profit from the CONTEMPO articles in other fields as well as their own. If computed tomography was the advance of the decade (see CONTEMPO '80), monoclonal antibodies are the advance of the year. Their promise in cancer detection, disease therapy, and research is cited in this year's articles on "The Drug Year," "Oncology," "Nuclear Medicine," "Immunology,"
Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension.
Authors: D YLeung, SGlagov, M BMathews
Journal: Circulation Research (1977)

Absolute and relative quantities of elastin, collagen, and DNA in anatomically defined segments of rabbit ascending aorta (AA) and pulmonary trunk (PT) were compared at intervals from birth to 2 months of age. Identical in size, weight, and composition at birth, the vessels maintained similar lengths and diameters at each age but diverged markedly in weight and scleroprotein content after 1 week. By 2 months, 3 times as much elastin and 1.7 times as much collagen had accumulated in the AA as compared to the PT. By contrast, the increase in total DNA content was the same for both segments. Differences in total fibrous protein accumulation, total elastin accumulation, and elastin content relative to DNA paralleled differences in estimated total medial tangential tension. Proportions of elastin and collagen relative to dry weight increased markedly only between 4 and 2 weeks of age and not thereafter despite continuing rapid growth, steadily increasing medial tension, and increasing total scleroprotein conte...
Endoscopic Findings In Sars-Cov-2 ICU Patients With Gastro Intestinal Bleeding
Authors: A Taiymi, S Belhorma, E Dedane, K Raiss, N El Moutaouakki, A El Mekkaoui, G Kharrasse, A Zazour, W Khannoussi, Z Ismaili
Journal: Endoscopy (2021)

Aims To identify the endoscopic findings in patients with severe SARS COV2 admitted in ICU and presenting GI bleeding.
Protective effect of early and late treatment with nifedipine during myocardial infarction in the conscious dog.
Authors: J AMelin, L CBecker, G MHutchins
Journal: Circulation (1984)

The effect of early and late nifedipine treatment on collateral blood flow and myocardial infarct size was investigated in 24 previously instrumented conscious dogs. Nifedipine was infused intravenously for 5 hr beginning 15 min (n = 9) and 3 hr (n = 6) after permanent occlusion of the midcircumflex coronary artery and compared with early and delayed vehicle treatment (controls; n = 9). Doses of nifedipine (90 to 168 micrograms/hr) were titrated to reduce mean arterial pressure by 5% to 10%. After animals died or were killed 2 to 7 days later, the anatomic risk region, or occluded coronary bed, was defined by postmortem coronary arteriography. The masses of infarct and risk region were measured by planimetry of weighed transverse sections of the left ventricle. Infarct size was smaller (p less than .05) with early and late nifedipine treatment compared with control, both as percent of left ventricle (15.6% and 14.6% vs 21.6%) and as percent of risk region (46.7% and 41.6% vs 65.7%). Collateral blood flow,...
RE: Serum Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial
Authors: J. Suburu, K. Lim, G. Calviello, Y. Q. Chen
Journal: JNCI Journal of the National Cancer Institute (2014)

In July 2013, Brasky and colleagues published a study that positively associated serum phospholipid omega-3 polyunsaturated fatty acids (PUFAs) with prostate cancer risk (1). We would like to raise some of our concerns about this study.

Many clinical studies have demonstrated cancer suppressive effects of omega-3 PUFA consumption (2–4). These studies are well supported by other preclinical studies of animal and cell culture models that use defined and controlled dietary fatty acid interventions (5–7). Nevertheless, there are inconsistencies in the literature, some of which may be due to methodological differences.

Brasky et al. measured phospholipid fatty acids in serum from patients in the SELECT trial. Serum phospholipid represents only one source of fatty acid present in the blood and excludes other sources such as triacylglycerol fatty acids, free fatty acids, and cell membrane fatty acids. It is unclear whether this measurement truly reflects the dietary consumption of PUFAs. In fact, their data show that each experimental group had an approximately 6:1 ratio of omega-6 fatty acid to omega-3 fatty acid. This low ratio is inconsistent with reports from the literature showing ratios typically greater than 20:1 in Western populations (8). Additionally, because the SELECT trial was designed for the study of selenium and vitamin E in prostate cancer patients, it may not be optimized for fatty acid analysis. Serum fatty acids are heavily influenced by feeding/fasting cycles and may vary substantially between subjects based on their most recently consumed meal. Therefore, a well-designed blood sampling protocol is critical.

In disagreement with the study’s conclusions, we would like to present an alternative possibility for the observed increase in phospholipid omega-3 fatty acids of prostate cancer patients. Fatty acids from phospholipids are subject to enzymatic cleavage by specific phospholipase enzymes. Upon their release, omega-3 PUFAs serve as precursors for a variety of proresolving and anti-inflammatory signalling mediators, such as resolvins, protectins, and maresins (9,10). The increased presence of omega-3 PUFAs in the phospholipid fraction suggests a low bioavailability of resolvins and protectins, and thus, this may increase inflammation, thereby promoting cancer development and progression. In this scenario, consumption of omega-3 PUFAs will be beneficial for prostate cancer patients.

In summary, we have concerns about the experimental design of the study published by Brasky and colleagues (1). We disagree with some of the authors’ conclusions, and we urge readers to interpret the data with caution.
121P RAS precision medicine trans-atlantic partnership: Multicentre analysis of RAS and NF1 co-mutations in advanced NSCLC
Authors: H. Adderley, M. Aldea, J. Aredo, M. Carter, M. Church, F. Blackhall, M. Krebs, H. Wakelee, B. Besse, D. Planchard, D. Vasseur, C. Massard, C. Lindsay
Journal: Journal of Thoracic Oncology (2021)
The protective effect of glucose-insulin-potassium on the response to atrial pacing.
Authors: M AChiong, RWest, J OParker
Journal: Circulation (1976)

The effects of glucose-insulin-potassium infusion (GIK) on atrial pacing-induced angina, ST depression, abnormal left ventricular end-diastolic pressure during pacing interruption (LVEDPi) and lactate metabolism (L), were studied in 18 patients: ten had angina during pacing = Ischemic group, and eight (5 normals and 3 with coronary artery disease) remained asymptomatic = Nonischemic group. The study consisted of 8-10 minute periods of control, pacing and recovery, before and after GIK. No untoward effects were observed. Comparison of the pacing responses (GIK vs pre-GIK states) showed that during GIK, angina occurred in only 4 patients, while significantly less severe changes were observed in ST depression (1.4 +/-0.5 vs 2.4 +/- 0.4 mm) and LVEDPi (16 +/- 3 vs 23 +/- 3 mm Hg). Lactate extraction was also higher (8.1 +/- 10.9 vs -5.2 +/- 11.1%), but not significantly so, although L became normal in 4 subjects and improved in another. These results indicate that GIK infusion was well tolerated and had a ben...
Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer
Authors: Jin Ji, Rui Chen, Lin Zhao, Yalong Xu, Zhi Cao, Huan Xu, Xi Chen, Xiaolei Shi, Yasheng Zhu, Ji Lyu, Junfeng Jiang, Yue Wang, Tie Zhou, Jingyi He, Xuedong Wei, Jason Boyang Wu, Bo Yang, Fubo Wang
Journal: Molecular Cancer (2021)

Abstract The landscape and characteristics of circulating exosomal messenger RNAs (emRNAs) are poorly understood, which hampered the accurate detection of circulating emRNAs. Through comparing RNA sequencing data of circulating exosomes with the corresponding data in tissues, we illustrated the different characteristics of emRNAs compared to tissue mRNAs. We then developed an improved strategy for emRNA detection based on the features of circulating emRNAs. Using the optimized detection strategy, we further validated prostate cancer (PCa) associated emRNAs discovered by emRNA-seq in a large cohort of patients and identified emRNA signatures for PCa screening and diagnosis using logistic regression analysis. The receiver operating characteristic curve (ROC) analysis showed that the circulating emRNA-based screening signature yielded an area under the ROC curve (AUC) of 0.948 in distinguishing PCa patients from healthy controls. The circulating emRNA-based diagnostic signature also showed a great performance in predicting prostate biopsy results (AUC: 0.851). In conclusion, our study developed an optimized emRNA detection strategy and identified novel emRNA signatures for the detection of PCa.
Response
Authors: D. Trichopoulos, C. Bamia, P. Lagiou, V. Fedirko, E. Trepo, M. Jenab, T. Pischon, U. Nothlings, K. Overvad, A. Tjonneland, M. Outzen, F. Clavel-Chapelon, R. Kaaks, A. Lukanova, H. Boeing, K. Aleksandrova, V. Benetou, D. Zylis, D. Palli, V. Pala, S. Panico, R. Tumino, C. Sacerdote, H. B. Bueno-De-Mesquita, H. J. Van Kranen, P. H. M. Peeters, E. Lund, J. R. Quiros, C. A. Gonzalez, M.-J. Sanchez Perez, C. Navarro, M. Dorronsoro, A. Barricarte, B. Lindkvist, S. Regner, M. Werner, G. Hallmans, K.-T. Khaw, N. Wareham, T. Key, I. Romieu, S.-C. Chuang, N. Murphy, P. Boffetta, A. Trichopoulou, E. Riboli
Journal: JNCI Journal of the National Cancer Institute (2012)

Re : Hepatocellular Carcinoma Risk factors and Disease Burden in a European Cohort: A Nested Case-Control Study Response
A lesson from the controversy about heart rate adjustment of ST segment depression.
Authors: MBobbio, RDetrano
Journal: Circulation (1991)

To summarize the literature review, the heart rate adjustment appears to be able to perfectly discriminate patients with different numbers of diseased coronary vessels in one center, to increase the diagnostic accuracy of three-vessel or left main disease in eight centers, and unable to improve accuracy in seven centers. To explain those differences, several methodological and statistical biases have been considered. However, a recent report regarding the application of the method in eight centers and a meticulous literature review could not explain the superior performance in some laboratories.
Lactate transport in mammalian ventricle. General properties and relation to K+ fluxes.
Authors: R CShieh, J IGoldhaber, J SStuart, J NWeiss
Journal: Circulation Research (1994)

Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lactate movement in the heart, isolated guinea pig ventricular myocytes were loaded with the fluorescent H+ or K+ indicators, carboxy SNARF-1 or PBFI, respectively, under whole-cell patch-clamp conditions. With H+ as the only permeable monovalent cation, a rapid increase in extracellular L-lactate concentration ([L-]o) from 0 to 30 mmol/L at constant pHo (7.35) caused an intracellular acidification averaging 0.18 +/- 0.02 pH units in 60 seconds (n = 7), reflecting L-lactate influx in association with H+ influx (or OH- efflux). Under voltage-clamp conditions, no significant electrogenic current was associated with H(+)-coupled L-lactate influx, and membrane potential (-75 to +75 mV) had no effect o...
Automaticity and entrance block induced by focal depolarization of mammalian ventricular tissues.
Authors: G RFerrier, J ERosenthal
Journal: Circulation Research (1980)

Isolated canine interventricular septa were studied with standard microelectrode techniques. Focal automaticity was induced by applying depolarizing current through an extracellular pipet in contact with the right bundle branch (RBB) of the ventricular specialized conducting system. Automaticity appeared with depolarization to transmembrane potentials of -50 mV or less. The spontaneous activity was neither depressed nor accelerated when overdrive suppression was attempted. Activity originating within the focus propagated into fully polarized surrounding tissue. However, entrance block, phasically related to the spontaneous cycle length, was an intrinsic property of these foci. Early premature beats initiated outside the focus failed to enter the focus, but the resulting electrotonus delayed the next automatic beat. Late premature beats captured and thereby accelerated the focus. Thus, the automatic foci could be extrafocal activity. Consequently, continous pacing at various rates precipitated complex rhyt...
Pericardial influences on ventricular filling in the conscious dog. An analysis based on pericardial pressure.
Authors: G STyson, G WMaier, C OOlsen, J WDavis, J SRankin
Journal: Circulation Research (1984)

Twenty-five dogs were chronically instrumented to investigate the effects of the normal pericardium on cardiac function. Pulse-transit ultrasonic transducers were implanted to measure multiple ventricular dimensions. The pericardium was incised transversely at the base of the heart and precisely reapproximated, so as to disturb its characteristics minimally. One week later, the dogs were studied in the conscious state, and left ventricular, right ventricular, pericardial, and pleural pressures were measured with matched micromanometers. Data were recorded before and after blood volume expansion. Absolute end-diastolic pericardial pressure varied directly with pleural pressure during the respiratory cycle. Transpericardial pressure (pericardial-pleural pressure) varied little with respiration and was related directly to ventricular diameter during the cardiac cycle with peak transpericardial pressure uniformly occurring at end-diastole. With volume infusion, normalized end-diastolic minor axis diameter and...