tbuckley/cabot-search huggingface dataset:
Abstract 9258: LDL Phenotype-B is Strongly Associated With CHD Risk Among Individuals With CKD. The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: Julio A Lamprea-Montealegre, Brad C Astor, Robyn McClelland, Morgan Grams, Cristopher T Sibley, Pamela Ouyang, Ian de Boer, Moyses Szklo
Journal: Circulation (2013)

Introduction: LDL phenotype B, characterized by high triglyceride (TG), small dense LDL (sd-LDL), and very low-density lipoprotein (VLDL) levels, and low high-density lipoprotein (HDL) levels, is the hallmark lipid phenotype of chronic kidney disease (CKD). Whether this phenotype is associated with clinical coronary heart disease (CHD) in individuals with CKD is not known. Methods: CKD was defined as an eGFR of 15-59 ml/min/1.63m2 (stage 3-4). Principal component analyses were used to account for the correlations among lipoproteins defining lipid phenotype B. Nuclear magnetic resonance spectroscopy was used to measure lipoprotein sub-fractions. CHD was defined as a new MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Results: A total of 6,814 individuals free of CHD at baseline were followed for a median time of 8.5 years. CHD developed in 303 individuals (5%) with eGFR≥60 and in 72 individuals (12%) with CKD (p for difference&lt;0.001). Principal component 1 captured the lipoprotein abnormalities defining lipid phenotype B: high TG levels (r for correlation with PC1=0.78), VLDL (r=0.73), sd-LDL(r=0.82) and low levels of HDL (r=-0.80). Compared to those without CKD, this phenotype (and its components) was more common (p for difference&lt;0.001), and was more strongly associated with CHD in those with CKD (figure): adjusted hazard ratios and 95% confidence intervals 1.13 (1.00-1.28; p=0.05) and 1.51 (1.17-1.94; p=0.001) in eGFR≥60 and CKD respectively (p for interaction=0.04). Conclusion: LDL phenotype-B is strongly associated with CHD risk in individuals with CKD. Whether a modification of the components of this phenotype leads to a reduction in the cardiovascular disease burden of individuals with CKD should be established in future studies.
Abstract 195: Leukemia Inhibitory Factor Stimulates Cardiac Stem Cell--Derived Cardiomyocyte Renewal After Myocardial Infarction Using a Genetic Fate-Mapping Study
Authors: Masato Kanda, Toshio Nagai, Toshinao Takahashi, Mei Lan Liu, Naomichi Kondou, Atushiko T Naito, Hiroshi Akazawa, Yoshio Kobayashi, Issei Komuro
Journal: Circulation Research (2012)

Cardiac stem cells or precursor cells have the potential to regenerate cardiomyocytes, but their role in the efficacy of cardioprotective drugs remains controversial. Therefore, using a genetic fate-mapping model, we tested the hypothesis that leukemia inhibitory factor (LIF) influences cardiac stem cells and stimulates endogenous cardiomyocyte renewal after myocardial infarction (MI). We generated MerCreMer-LacZ mice in which more than 99.9% of the cardiomyocytes in the left ventricular field showed positive 5-bromo-4-chloro-3-indolyl-β-d-galactoside (Xgal) staining just after tamoxifen injection (5mg/kg/d for 2 weeks). Thus, every Xgal-negative cardiomyocyte was derived from a stem or precursor cell after tamoxifen administration. The number of Xgal-negative cardiomyocytes did not change during normal aging spanning 1 year. However, at 3 months after MI, the MI mice had more Xgal-negative cells than the control mice (57.0 ± 12.0 and 3.0 ± 2.6 cells per section, respectively; P &lt; 0.01). The side population (SP) cell fraction contained label-retaining cells, which differentiated into Xgal-negative cardiomyocytes after MI. Among the cytokines secreted after MI, LIF expression increased to 130 fold in MI mice but rapidly decreased within 1 week. Therefore, we injected the LIF plasmid at the time of MI to keep blood LIF concentrations high and examined its effect on regeneration. At 1 month after MI, the MI + LIF group (118.6 ± 51.5 cells per section) had more Xgal-negative cells than the MI + PBS group (37.0 ± 5.5 cells per section; P &lt; 0.05). Echocardiography showed significant recovery of fractional shortening in the LIF-treated group only. Next, we immunohistochemically analyzed the effect of LIF on SP cells. On BrdU administration at 1 week after MI, the percentages of BrdU-positive SP cells in LIF- and PBS-treated mice were 59%, and 35%, respectively, suggesting that LIF influenced SP cell proliferation. The percentages of Ki67- and phosphorylated histone-3-positive SP cells were also higher in LIF-treated mice. Taken together, LIF may stimulate stem cell-derived cardiomyocyte regeneration in part by activating SP cells. We believe our findings will help provide a novel therapeutic strategy for cardiogenesis.
Political orientations do not cancel out, and politics is not about truth
Authors: Hans-Rüdiger Pfister, Gisela Böhm
Journal: Behavioral and Brain Sciences (2015)

Abstract Duarte et al. propose that divergent political biases cancel each other out such that increasing political diversity will improve scientific validity. We argue that this idea is misguided. Their recommendations for improving political diversity in academia bear the danger of imposing political interests on science. Scientific scrutiny and criticism are the only viable remedies for bad science.
Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR])
Authors: Bruce E. Strober, Robert Bissonnette, David Fiorentino, Alexa B. Kimball, Luigi Naldi, Neil H. Shear, Kavitha Goyal, Steven Fakharzadeh, Stephen Calabro, Wayne Langholff, Yin You, Claudia Galindo, Seina Lee, Mark G. Lebwohl
Journal: Journal of the American Academy of Dermatology (2016)
Pharmaceutical association launches electronic drugs compendium for patients
Authors: Gavin Yamey
Journal: BMJ (2000)

The Association of the British Pharmaceutical Industry last week launched an addition to its electronic version of its medicines compendium that is aimed at patients and their carers.

The electronic medicines compendium (www.emc.vhn.net) has been available to doctors since November 1999. As this version carries drug advertisements, it cannot be accessed by the public. The new …
Correction of Hemoglobin Levels in a Heterozygous Humanized Mouse Model of Thalassemia after Fetal Gene Therapy
Authors: Panicos Shangaris, Stavros P Loukogeorgakis, Sindhu Subramaniam, Mike Blundell, Nahla Bakhamis, Shanrun Liu, Simon Eaton, Durrgah Ramachandra, Panayiotis Maghsoudlou, Luca Urbani, Simon Waddington, Joy Archer, Mike Antoniou, Adrian J Thrasher, Thomas Ryan, Paolo De Coppi, Anna David
Journal: Blood (2014)
Finding the Balance of Less Is More
Authors: Katherine Bydalek, Xiulu Ruan
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Half of complaints about hospitals concern poor communication and attitude
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The main complaints about hospitals in England last year that were escalated to the health service ombudsman concerned poor clinical care and treatment, poor communication, and errors in diagnosis.

In 2014-15 the Parliamentary and Health Service Ombudsman received 8853 inquiries about acute trusts, up from 8178 in 2013-14, says a new report.1 The ombudsman makes final decisions on complaints that have not been resolved locally by the NHS in England.

Last year it completed 1652 investigations about acute trusts, up from 852 in 2013-14, largely because of …
Predictive value of lung function below the normal range and respiratory symptoms for progression of chronic obstructive pulmonary disease
Authors: M Albers, T Schermer, Y Heijdra, J Molema, R Akkermans, C van Weel
Journal: Thorax (2007)

Chronic obstructive pulmonary disease (COPD) is an insidiously starting disease. Early detection has high priority because of the possibility of early implementation of smoking cessation interventions. An evidence based model for case finding of COPD is not yet available.To describe the early development of COPD, and to assess the predictive value of early signs (respiratory symptoms, lung function below the normal range, reversibility).In a prospective study, based in general practice, formerly undiagnosed subjects (n = 464) were assessed at baseline and at 5 years for respiratory symptoms and pulmonary function. Odds ratios for early signs were calculated (adjusted for age, gender, pack-years at baseline and smoking behaviour during follow-up), and defined as possible indicators of disease progression.Over a 5 year period, the percentage of subjects with obstruction increased from 7.5% (n = 35) at baseline to 24.8% (n = 115) at 5 years. The presence of mild early signs and lung function below the normal range at baseline were related to an increased risk of developing mild to moderate COPD (GOLD I: OR 1.87 (95% CI 1.22 to 2.87); GOLD II: OR 2.08 (95% CI 1.29 to 3.37) to 2.54 (95% CI 1.25 to 5.19)) at 5 years.Lung function below the normal range and early respiratory signs predict the development and progression of COPD.
Acute coronary syndromes: what about older patients with frailty and multiple comorbidities?
Authors: Sean G Ninan
Journal: BMJ (2015)

Timmis’s useful article does not refer to the management of older patients with multimorbidity, a common scenario in clinical practice.1 Only 14% of participants in clinical trials are over 75 years,2 yet Myocardial Ischaemia National Audit Project registry data indicate that around 40% of patients with acute coronary …
Diffuse Large B-Cell Lymphomas of the Waldeyer’s Ring Frequently Have a Germinal Center-Like Phenotype: A Clinico-Pathological Study of 209 Patients from the Groupe d’Etude des Lymphomes de L’Adulte (GELA).
Authors: Laurence de Leval, Christophe Bonnet, Christiane Copie-Bergman, Laurence Seidel, Josette Brière, Thierry Molina, Bettina Fabiani, Brunangelo Falini, Christian Gisselbrecht, Hervé Thilly, Adelin Albert, Georges Fillet, Philippe Gaulard
Journal: Blood (2007)
Utilizing mechanistic PK/PD modeling to simultaneously examine free CCL2, total CCL2, and CNTO 888 serum concentration time data.
Authors: G. J. Fetterly, T. A. Puchalski, C. H. Takimoto, D. E. Mager, S. Seetharam, T. McIntosh, J. S. De Bono, A. W. Tolcher, H. M. Davis, H. Zhou
Journal: Journal of Clinical Oncology (2010)

3029 Background: The chemokine (C-C motif) CCL2 promotes angiogenesis, tumor proliferation, migration, and metastasis. CNTO 888 is a human IgG1κ monoclonal antibody with high CCL2 binding affinity. A mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed to simultaneously characterize the time course of CNTO 888, free CCL2, and the CNTO 888-CCL2 complex in the serum. Comprehensive PK/PD modeling of oncology biologics targeting soluble ligands have been rare to date. The goal of the analysis was to predict a dose that will maximally affect CCL2 signaling in the serum and utilize that dose for the clinical development of CNTO 888. Methods: PK and PD data from 21 cancer patients with refractory tumors were examined. CNTO 888 dose levels examined were 0.3, 1, 3, 10 and 15 mg/kg. 3 subjects were treated at each dose level for dose levels < 3 mg/kg and 6 subjects each for the 10 and 15 mg/kg dose levels. All dose levels tested were well tolerated with no dose limiting toxicities. CNTO 888, free CCL2, and CNTO 888-CCL2 complex concentrations in serum were determined following the first and fourth dose. PK/PD modeling was conducted using population-based methods. Results: A mechanistic PK/PD model simultaneously described the temporal relationships among serum concentrations of CNTO 888, free CCL2, and the CNTO 888-CCL2 complex. Dose-dependent increases in total CCL2 concentrations were observed and are consistent with shifting free CCL2, which is rapidly cleared in the absence of CNTO 888 to the form bound to CNTO 888 which is cleared much slower. Free CCL2 declined rapidly after the end of the infusion and returned to baseline concentration within 7 days. Mean predicted half-lives of CNTO 888 and the CCL2-CNTO 888 complex were both 2.4 days and only 1 hour for free CCL2. The mean (%SEM) dissociation constant (KD) was 2.4 nM (72%). Conclusions: A mechanistic PK/PD model was developed that simultaneously describes CNTO 888, free CCL2 and the CNTO 888-CCL2 complex concentration-time data in serum. Model parameter estimates are physiologically plausible. This PK/PD model has the potential to predict clinically relevant changes in free CCL2 and the CNTO 888-CCL2 complex. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Ortho Biotech Centocor Ortho Biotech Centocor Ortho Biotech
P-VEBEC: A new 8-weekly schedule with or without rG-CSF for elderly patients with aggressive non-Hodgkin's lymphoma (NHL)
Authors: M Bertini, R Freilone, U Vitolo, B Botto, M Pizzuti, P Gavarotti, A Levis, E Orlandi, L Orsucci, M Pini
Journal: Annals of Oncology (1994)

Chemotherapy regimens devised for elderly patients with intermediate-high grade NHL are a matter of discussion. The aim is to reduce general toxicity without loosing an antilymphoma effect. The most important limiting factor of chemotherapy is myelotoxicity; for this reason the use of growth factor may be useful in these patients.From November '91 to November '92, 67 pts older than 65 years with intermediate-and high-grade advanced-stage NHL were treated with the P-VEBEC regimen, an original scheme with epirubicin 50 mg/m2, cyclophosphamide 350 mg/m2 and etoposide 100 mg/m2 on weeks 1, 3, 5, 7; vinblastine 5 mg/m2 and bleomycin 5 mg/m2 on weeks 2, 4, 6, 8, prednisone 50 mg/m2/day p. os in the first 2 weeks and thereafter every other day. Twenty-eight pts received r-GSF 5 micrograms/kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Their median age was 71 years (65-80), 31 pts were male and 36 female, histology according W.F. was D 6; E 17; F 16; G 19; H 9. Twenty-five percent of pts had B symptoms, 35% had bulky disease, 41% LDH level > normal, 44% stage IV and 26% had B.M. involvement.C.R. was achieved by 66% of pts. Adverse prognostic factors for CR were E histology, stage IV, bone marrow infiltration and LDH above normal. Severe toxicity was never recorded, no toxic death was observed. With a median follow-up of 24 months OS, DFS and EFS were 55%, 52%, and 33%, respectively. EFS was influenced by stage, BM involvement and level of LDH. The relative dose intensity (RDI) was calculated by the method of Hryniuk and Bush. Patients who received rG-CSF had a significantly higher median RDI (94% vs 79%) and lower myelotoxicity (neutrophil nadir < 500 18% vs 56%). The rate of CR was influenced by RDI > 80% (89% vs 56%). EFS was also better in pts who received a RDI higher than 80% (50% vs 18% p = 0.05).P-VEBEC is a feasible cycle in elderly patients; the use of rG-CSF improves RDI. In patients with adverse prognostic factors (BM involvement, poor performance status) a RDI > 0.80 could play a role in improving the outcome.
Computer algorithm could help GPs predict dementia risk
Authors: Jacqui Wise
Journal: BMJ (2016)

Researchers at University College London have developed a simple computer algorithm using routinely collected health data that could help GPs predict the risk of patients developing dementia.

The dementia risk score needs to be further evaluated but may be particularly useful for ruling out patients at very low risk of conditions such as Alzheimer’s disease, the researchers wrote in the open access journal BMC Medicine .1

The study used randomly selected anonymised data collected …
Induction of Stomach Cancer in Rats and Mice by Halogenated Aliphatic Fumigants
Authors: William A. Olson, Robert T. Habermann, Elizabeth K. Weisburger, Jerrold M. Ward, John H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1973)

Ethylene dibromide and 1,2-dibromo-3-chloropropane (DBCP) were administered to Osborne-Mendel rats and (C57BL × C3H)F1 mice via chronic oral intubation 5 times per week at experimentally predetermined maximally tolerated doses and at half those doses. As early as 10 weeks after initiation of treatment, both compounds induced a high incidence of squamous cell carcinomas of the stomach in both species. In addition, DBCP induced mammary adenocarcinomas in the female rats. Possible environmental hazards of these compounds are discussed.
Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens.
Authors: J P Radich, J E Sanders, C D Buckner, P J Martin, F B Petersen, W Bensinger, G B McDonald, M Mori, G Schoch, J A Hansen
Journal: Journal of Clinical Oncology (1993)

PURPOSE The impact of a second marrow transplant on long-term disease-free survival (DFS) was evaluated for 77 consecutive patients aged 2 to 51 years who relapsed subsequent to allogeneic marrow transplantation after high-dose chemotherapy and total-body irradiation (TBI). PATIENTS AND METHODS Patients received a second transplant for recurrent chronic myelogenous leukemia (CML) (n = 28), acute myelogenous leukemia (AML) (n = 32), and acute lymphoblastic leukemia (ALL) (n = 15) or lymphoma (n = 2) that used the same marrow donor as the initial transplant. High-dose chemotherapy of busulfan (BU) and cyclophosphamide (CY), or CY, carmustine (BCNU), and etoposide (VP-16), was used as a preparative regimen for the second transplant. Graft-versus-host disease (GVHD) prophylaxis consisted of the following: no prophylaxis (n = 8), T-cell depletion (n = 36), methotrexate (MTX) only (n = 21), cyclosporine (CSP) only (n = 1), MTX and CSP (n = 9), or anti-thymocyte globulin (ATG) and prednisone (n = 2). RESULTS Engraftment occurred in the 74 assessable patients. Severe veno-occlusive disease (VOD) was the most frequent cause of grades 3 and 4 regimen-related toxicity (RRT); it occurred in 20 patients. The probability of death before day 100 from nonleukemic causes was 36%. The probability of relapse after second transplant was 70%, and the DFS rate was 14% (median DFS, 36 months; range, 22 to 87). The DFS rates for ALL, AML, and CML were 8%, 10%, and 25%, respectively. Multivariate analysis showed that the risk of relapse was inversely associated with acute GVHD (relative risk [RR] of relapse = 0.2; P = .0009). No other factor was associated with relapse. DFS was associated with the presence of acute GVHD (RR of treatment failure = 0.5; P = .0085), and a reduction of DFS was associated with severe VOD (RR = 10.6; P = .0001) and those patients older than 10 years (RR = 2.5; P = .0337). CONCLUSION These data show that some patients may benefit from a second marrow transplant for recurrent leukemia after an initial marrow transplant. Younger patients and patients with CML especially should be considered as potential candidates for a second transplant.
Abstract 18014: Image-Based Patient-Specific Simulations of Ventricular Electrophysiology for Sudden Arrhythmic Death Risk Stratification
Authors: Fijoy Vadakkumpadan, Hermenegild Arevalo, Alexander Jebb, Katherine C Wu, Natalia Trayanova
Journal: Circulation (2013)

Low left-ventricular ejection fraction (LVEF), the main criterion used in current clinical practice to stratify sudden arrhythmic death (SAD) risk, and select patients for prophylactic implantable cardioverter defibrillator (ICD) treatment, has very low sensitivity and specificity. Arrhythmia inducibility in clinical electrophysiological study (EPS) can improve SAD risk prediction, but it is invasive and expensive. We seek to demonstrate that image-based patient-specific simulations of ventricular electrophysiology can be used as a non-invasive and economical surrogate for clinical EPS in predicting SAD risk. Data from 20 patients with myocardial infarction and low LVEF, who were scanned with late gadolinium enhanced cardiac MRI prior to ICD implantation, and followed for appropriate ICD firing and SAD, were used. Nine patients had events and eleven did not. For each patient, a multiscale, biophysically-accurate ventricular model, including inexcitable scar, electrically remodeled gray zone, and estimated fiber orientations, was built from the image data. A programmed electrical stimulation (PES) protocol with 2 ventricular extrastimuli, similar to that used clinically, was performed in each model from 17 LV endocardial sites corresponding to the 17 AHA regions. An inducibility index was calculated for each patient as the proportion of the PES sites from which sustained ventricular arrhythmia was induced. The mean inducibility index was 0.21±0.14 for patients who had an event vs. 0.09±0.14 for those who did not (p&lt;0.05). The figure shows geometries and simulated activation maps of a patient without event (top row) and with event (bottom row). All patients with events had inducibility stimulated from at least 1 site (range: 1-8). In conclusion, we have developed a new index computed from noninvasive simulations of ventricular electrophysiology, that may be able to stratify SAD risk and guide prophylactic treatment delivery.
ssDNA‐Functionalized Nanoceria: A Redox‐Active Aptaswitch for Biomolecular Recognition
Authors: Gonca Bülbül, Akhtar Hayat, Silvana Andreescu
Journal: Advanced Healthcare Materials (2016)

Quantification of biomolecular binding events is a critical step for the development of biorecognition assays for diagnostics and therapeutic applications. This paper reports the design of redox‐active switches based on aptamer conjugated nanoceria for detection and quantification of biomolecular recognition. It is shown that the conformational transition state of the aptamer on nanoceria, combined with the redox properties of these particles can be used to create surface based structure switchable aptasensing platforms. Changes in the redox properties at the nanoceria surface upon binding of the ssDNA and its target analyte enables rapid and highly sensitive measurement of biomolecular interactions. This concept is demonstrated as a general applicable method to the colorimetric detection of DNA binding events. An example of a nanoceria aptaswitch for the colorimetric sensing of Ochratoxin A (OTA) and applicability to other targets is provided. The system can sensitively and selectivity detect as low as 0.15 × 10 −9 m OTA. This novel assay is simple in design and does not involve oligonucleotide labeling or elaborate nanoparticle modification steps. The proposed mechanism discovered here opens up a new way of designing optical sensing methods based on aptamer recognition. This approach can be broadly applicable to many bimolecular recognition processes and related applications.