tbuckley/cabot-search huggingface dataset:
A Health System Program To Reduce Work Disability Related to Musculoskeletal Disorders
Authors: Lydia Abásolo, Margarita Blanco, Javier Bachiller, Gloria Candelas, Paz Collado, Cristina Lajas, Marcelino Revenga, Patricia Ricci, Pablo Lázaro, Maria Dolores Aguilar, Emilio Vargas, Benjamín Fernández-Gutiérrez, César Hernández-García, Loreto Carmona, Juan A. Jover
Journal: Annals of Internal Medicine (2005)

Background: Musculoskeletal disorders (MSDs) are a frequent cause of work disability, accounting for productivity losses in industrialized societies equivalent to 1.3% of the U.S. gross national product. Objective: To evaluate whether a population-based clinical program offered to patients with recent-onset work disability caused by MSDs is cost-effective. Design: Randomized, controlled intervention study. The inclusion and follow-up periods each lasted 12 months. Setting: Three health districts in Madrid, Spain. Patients: All patients with MSD-related temporary work disability in 1998 and 1999. Intervention: The control group received standard primary care management, with referral to specialized care if needed. The intervention group received a specific program, administered by rheumatologists, in which care was delivered during regular visits and included 3 main elements: education, protocol-based clinical management, and administrative duties. Measurements: Efficacy variables were 1) days of temporary work disability and 2) number of patients with permanent work disability. All analyses were done on an intention-to-treat basis. Results: 13 077 patients were included in the study, 7805 in the control group and 5272 in the intervention group, generating 16 297 episodes of MSD-related temporary work disability. These episodes were shorter in the intervention group than in the control group (mean, 26 days compared with 41 days; P < 0.001), and the groups had similar numbers of episodes per patient. Fewer patients received long-term disability compensation in the intervention group (n = 38 [0.7%]) than in the control group (n = 99 [1.3%]) (P < 0.005). Direct and indirect costs were lower in the intervention group than in the control group. To save 1 day of temporary work disability, $6.00 had to be invested in the program. Each dollar invested generated a benefit of $11.00. The program's net benefit was in excess of $5 million. Limitations: The study was unblinded. Conclusions: Implementation of the program, offered to the general population, improves short- and long-term work disability outcomes and is cost-effective.
Advances in Cardiac Cellular Electrophysiology: Implications for Automaticity and Therapeutics
Authors: G A Gintant, I S Cohen
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study
Authors: Alison T. Stopeck, Allan Lipton, Jean-Jacques Body, Guenther G. Steger, Katia Tonkin, Richard H. de Boer, Mikhail Lichinitser, Yasuhiro Fujiwara, Denise A. Yardley, María Viniegra, Michelle Fan, Qi Jiang, Roger Dansey, Susie Jun, Ada Braun
Journal: Journal of Clinical Oncology (2010)

This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases.Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression).Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39).Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
Platelet Extracellular Regulated Protein Kinase 5 Is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion
Authors: Scott J. Cameron, Sara K. Ture, Deanne Mickelsen, Enakshi Chakrabarti, Kristina L. Modjeski, Scott McNitt, Michael Seaberry, David J. Field, Nhat-Tu Le, Jun-ichi Abe, Craig N. Morrell
Journal: Circulation (2015)

Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes. In comparison with platelet activation in normal healthy conditions, less attention is given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species-rich environments may not be the same as in normal healthy conditions. Extracellular regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase family member activated in hypoxic, reactive oxygen species-rich environments and in response to receptor-signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells after ischemia. We present evidence that platelets express ERK5 and that platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent reactive oxygen species-mediated mechanisms in ischemic myocardium.Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and that platelet-specific ERK5(-/-) mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5-regulated proteins is reduced in ERK5(-/-) platelets post-MI.ERK5 functions as a platelet activator in ischemic conditions, and platelet ERK5 maintains the expression of some platelet proteins after MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment.
Protracted Suspension of the Moral and Intellectual Consciousness in Epilepsy
Authors: J. S. Thomson
Journal: BMJ (1877)

been doing, but she just laughed at me, and would not believe that it was she who had set the tables for dinner.From the commencement, it might be about half an hour before she fully recovered consciousness.)"This, as I have said, was the most decided attack she has had of this kind.On another occasion, about six months previously, she took one when about to go to an evening entertainment, and, while in it, with a pair of scissors cut out a large part of the side of her dress.And, a few days ago, during a similar seizure, she took a pin and undid the sewing of the hem of an apron, taking great care not to break the thread.After doing so, she began to make a fringe at the edge of the apron with the pin.The attendant now stopped her, and, in about two minutes afterwards, slhe recovered consciousness.As formerly, she was quite unaware of what she had been doing.When not suffering from epilepsy, this woman is intelligent and active, though rather irritable.She occasionally, but not regularly, assists the attendants in arranging the tables for meals.Besides this case, there is another one under my care at present, in which the automatic acts are even more striking in some respects than those above-mentioned, but I do not feel at liberty to describe it in detail.I may state, however, that the patient has been subject to epileptic " absences" during the last eighteen months, and occasionially, while in them, has acted very strangely in the streets and in houses where he was visiting.
Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target
Authors: Bengt Samuelsson, Ralf Morgenstern, Per-Johan Jakobsson
Journal: Pharmacological Reviews (2007)

Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) is the most abundant prostaglandin in the human body. It has a large number of biological actions that it exerts via four types of receptors, EP1–4. PGE<sub>2</sub> is formed from arachidonic acid by cyclooxygenase (COX-1 and COX-2)-catalyzed formation of prostaglandin H<sub>2</sub> (PGH<sub>2</sub>) and further transformation by PGE synthases. The isomerization of the endoperoxide PGH<sub>2</sub> to PGE<sub>2</sub> is catalyzed by three different PGE synthases, viz. cytosolic PGE synthase (cPGES) and two membrane-bound PGE synthases, mPGES-1 and mPGES-2. Of these isomerases, cPGES and mPGES-2 are constitutive enzymes, whereas mPGES-1 is mainly an induced isomerase. cPGES uses PGH<sub>2</sub> produced by COX-1 whereas mPGES-1 uses COX-2-derived endoperoxide. mPGES-2 can use both sources of PGH<sub>2</sub>. mPGES-1 is a member of the membrane associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily. It requires glutathione as an essential cofactor for its activity. mPGES-1 is up-regulated in response to various proinflammatory stimuli with a concomitant increased expression of COX-2. The coordinate increased expression of COX-2 and mPGES-1 is reversed by glucocorticoids. Differences in the kinetics of the expression of the two enzymes suggest distinct regulatory mechanisms for their expression. Studies, mainly from disruption of the <i>mPGES-1</i> gene in mice, indicate key roles of mPGES-1-generated PGE<sub>2</sub> in female reproduction and in pathological conditions such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis. These findings indicate that mPGES-1 is a potential target for the development of therapeutic agents for treatment of several diseases.
Bronchopulmonary Carcinoid: Phenotype and Long-term Outcome in a Single-Institution Series of Italian Patients
Authors: Massimo Rugge, Matteo Fassan, Roberto Clemente, Giovanna Rizzardi, Luciano Giacomelli, Gianmaria Pennelli, Claudia Mescoli, Daniela Segat, Federico Rea
Journal: Clinical Cancer Research (2008)

The histologic distinction between low-grade typical and intermediate-grade atypical bronchopulmonary carcinoids basically lies on cellular differentiation, mitotic activity, and presence of "neoplastic" necrosis; at single patient level, however, none of these features enables a reliable prediction of the clinicopathologic outcome.The long-term postsurgical outcome of a single-institution series of 67 radically treated bronchopulmonary carcinoids was correlated with the tumor phenotype assessed by combining conventional histology with a panel of immunohistochemical markers exploring cell differentiation (chromogranin, NSE, TTF1), cell turnover (Mib1), and apoptosis (Bcl2, Bax).Fifty-eight (86.6%) carcinoids were assessed as low-grade typical and nine (13.4%) were assessed as intermediate-grade atypical. The mean follow-up was of 85.13 months (range, 28-168; median, 82.0). All cases expressed neuroendocrine markers, whereas TTF1 was never expressed. At univariate analysis, tumor recurrence (n = 6) correlated significantly with the carcinoid histotype (P = 0.002) and with each of the following variables: tumor location (P = 0.01), mitotic index (P = 0.003), necrosis (P = 0.002), tumor vascular invasion (P = 0.0001), Mib1 expression (P = 0.005), Bcl2 expression (P = 0.024), and synchronous node metastasis (P = 0.028). The best cutoffs for Mib1 and Bcl2 expression (calculated by receiver operating characteristic curves) discriminating recurrent versus nonrecurrent tumors were 5.4% for Mib1 and 2.0% for Bcl2 (Mib1: sensitivity, 83%; specificity, 97%; area under curve, 0.844 +/- 0.14; Bcl2: sensitivity, 83%; specificity, 65%; area under curve, 0.769 +/- 0.12). By stratifying the patients according to the obtained cutoffs, significant differences emerged in the patients' disease-free survival (log-rank test: Mib1, P = 0.0001; Bcl2, P = 0.01).Mib1 and Bcl2 significantly discriminate between recurrent versus nonrecurrent tumors, producing a biologically plausible, diagnostically suitable immunohistochemical pattern.
Hydration Status Affects Nuclear Distribution of Transcription Factor Tonicity Responsive Enhancer Binding Protein in Rat Kidney
Authors: JUNG H. CHA, SEUNG KYOON WOO, KI H. HAN, YOUNG H. KIM, JOSEPH S. HANDLER, JIN KIM, H. MOO KWON
Journal: Journal of the American Society of Nephrology (2001)

Tonicity responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity responsive expression of proteins that catalyze cellular accumulation of compatible osmolytes. In cultured MDCK cells, hypertonicity stimulates the activity of TonEBP via a combination of increased protein abundance and increased nuclear localization. For investigating regulation of TonEBP in the kidney, rats were subjected to water loading or dehydration. Water loading lowered urine osmolality and mRNA expression of sodium/myo-inositol cotransporter (SMIT), a target gene of TonEBP, in the renal medulla; dehydration doubled the urine osmolality and increased SMIT mRNA expression. In contrast, overall abundance of TonEBP and its mRNA measured by immunoblot and ribonuclease protection assay, respectively, was not affected. Immunohistochemical analysis, however, revealed that nuclear distribution of TonEBP is generally increased throughout the medulla in dehydrated animals compared with water loaded animals. Increased nuclear localization was particularly dramatic in thin limbs. Notable exceptions were the middle to terminal portions of the inner medullary collecting ducts and blood vessels, where a change in TonEBP distribution was not evident. Immunohistochemical detection of SMIT mRNA revealed that the changes in nuclear distribution of TonEBP correlate with expression of SMIT. It is concluded that under physiologic conditions, nucleocytoplasmic distribution is the dominant mode of regulation of TonEBP in the renal medulla.
CD4<sup>+</sup>CD25<sup>+</sup>Regulatory T Cells and Their Therapeutic Potential
Authors: David A. Randolph, C. Garrison Fathman
Journal: Annual Review of Medicine (2005)

The human immune system mounts specific responses to a vast array of antigens. Although this is clearly beneficial in fighting off harmful infections and cancerous cells, the system must be carefully controlled to ensure that normal self-antigens are not targeted. A recently characterized subset of T cells, identified by their cell surface expression of CD4 and CD25, is critical in regulating the function of other immune cells and preventing potentially harmful autoimmune responses. This article reviews what is currently known about these so-called regulatory T cells and discusses the therapeutic potential of these cells to modulate human immune-based diseases.
Effects of Moderate Exercise Training on Thallium Uptake and Contractile Response to Low-Dose Dobutamine of Dysfunctional Myocardium in Patients With Ischemic Cardiomyopathy
Authors: Romualdo Belardinelli, Demetrios Georgiou, Leonard Ginzton, Giovanni Cianci, Augusto Purcaro
Journal: Circulation (1998)

Background —There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans. However, the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular (LV) systolic dysfunction. Methods and Results —To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium, 46 patients (42 men, 4 women; mean age, 57±9 years) with chronic coronary artery disease and impaired LV systolic function (ejection fraction &lt;40%) were randomly assigned to two groups. The exercise group (n=26) underwent exercise training at 60% of peak oxygen uptake for 8 weeks. The control group (n=20) was not exercised. At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine (5 to 10 μg/kg per minute) followed by thallium myocardial scintigraphy. Coronary angiography was performed in 23 patients at baseline and after 8 weeks. After 8 weeks, peak oxygen uptake increased significantly only in trained patients (24%). Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients (28% and 31%, respectively; trained versus control: P &lt;.001 for both). In a subgroup of trained patients, both improvements were correlated with an increase in the coronary collateral score ( P &lt;.005 and P &lt;.001, respectively). Conclusions —Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy. The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy.
Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection
Authors: Giovanni Nigro, Stuart P. Adler, Renato La Torre, Al M. Best
Journal: New England Journal of Medicine (2005)

Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy.We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously).In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, -infinity to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects.Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.
CVTree3 Web Server for Whole-Genome-Based and Alignment-Free Prokaryotic Phylogeny and Taxonomy
Authors: Guanghong Zuo, Bailin Hao
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.
Accountability and Public Health Policies Impacting Proper Ebola Response: Time for a Bioethics Oversight Board
Authors: Ramin Asgary
Journal: The American Journal of Bioethics (2015)

In November, 2014, at the time of the American Society of Tropical Medicine and Hygiene (ASTMH) and the American Public Health Association (APHA) annual conferences in New Orleans, LA, the Louisian...
c-Myc Alterations Confer Therapeutic Response and Acquired Resistance to c-Met Inhibitors in MET-Addicted Cancers
Authors: Aijun Shen, Lu Wang, Min Huang, Jingya Sun, Yi Chen, Yan-Yan Shen, Xinying Yang, Xin Wang, Jian Ding, Meiyu Geng
Journal: Cancer Research (2015)

Use of kinase inhibitors in cancer therapy leads invariably to acquired resistance stemming from kinase reprogramming. To overcome the dynamic nature of kinase adaptation, we asked whether a signal-integrating downstream effector might exist that provides a more applicable therapeutic target. In this study, we reported that the transcriptional factor c-Myc functions as a downstream effector to dictate the therapeutic response to c-Met inhibitors in c-Met-addicted cancer and derived resistance. Dissociation of c-Myc from c-Met control, likely overtaken by a variety of reprogrammed kinases, led to acquisition of drug resistance. Notably, c-Myc blockade by RNA interference or pharmacologic inhibition circumvented the acquired resistance to c-Met inhibition. Combining c-Myc blockade and c-Met inhibition in MET-amplified patient-derived xenograft mouse models heightened therapeutic activity. Our findings offer a preclinical proof of concept for the application of c-Myc-blocking agents as a tactic to thwart resistance to kinase inhibitors.