tbuckley/cabot-search huggingface dataset:
Transcatheter Angioplasty for Acquired Pulmonary Vein Stenosis After Radiofrequency Ablation
Authors: Athar M. Qureshi, Lourdes R. Prieto, Larry A. Latson, Geoffrey K. Lane, C. Igor Mesia, Penelope Radvansky, Richard D. White, Nassir F. Marrouche, Eduardo B. Saad, Dianna L. Bash, Andrea Natale, John F. Rhodes
Journal: Circulation (2003)

Pulmonary vein stenosis has recently been recognized as a complication of radiofrequency ablation for atrial fibrillation. This study evaluates the presentation of affected patients and the role of transcatheter therapy for this patient population.This study used a retrospective review of data from 19 patients (age, 51+/-13 years) with pulmonary vein stenosis who underwent catheterization and angiography between December 2000 and December 2002. Quantitative perfusion and spiral CT scans were performed for initial diagnosis and follow-up. The median duration between radiofrequency ablation and the reported onset of respiratory symptoms for 18 of 19 patients was 7.5 weeks (0.1 to 48). After the onset of symptoms, all but two patients were initially misdiagnosed with a symptoms-to-diagnosis duration of 16 weeks (2-59). At initial catheterization, 17 of 19 patients had angioplasty in 30 veins with stent placement in 5 vessels when a flap occurred. Overall vessel diameter increased from 2.6+/-1.6 to 6.6+/-2.4 mm (P<0.0001). There were 4 procedure-related adverse events but no long-term sequelae. Immediate follow-up showed improved flow to involved lung segments. At a median follow-up of 43 weeks (2-92), although repeat angioplasty for restenosis was necessary in 8 of 17 patients, 15 of 17 patients currently have no or minimal persistent symptoms.Pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation is often misdiagnosed. Although further follow-up is necessary to determine long-term success, our data indicate better pulmonary vein flow and symptomatic improvement in the majority of patients undergoing dilation of postablation pulmonary vein stenosis.
The Allocation of Intensivists’ Rounding Time under Conditions of Intensive Care Unit Capacity Strain
Authors: Sydney E. S. Brown, Michael M. Rey, Dustin Pardo, Scott Weinreb, Sarah J. Ratcliffe, Nicole B. Gabler, Scott D. Halpern
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

With rising demand for critical care, intensivists' time must increasingly be divided among patients (1)(2)(3)(4)(5)(6).Recent studies suggest that increased strain at intensive care unit (ICU) admission leads to higher mortality in closed ICUs (7) and that increased strain at discharge leads to increases in ICU readmissions (8).These relationships between strain and outcomes could be mediated by strain-induced changes in the time intensivists devote to patients during patient care rounds (7-9).We therefore examined how the allocation of intensivists' time during rounds changes at times of low versus high ICU strain and whether intensivists preferentially allocate time away from certain patient groups as strain increases.Some results have been previously reported in the form of an abstract (10). MethodsWe conducted a prospective study of patient care rounds in the 24-bed medical ICU of the Hospital of the University of Pennsylvania in 2012.Time spent performing various rounding activities was recorded in real time by trained data collectors, using a tablet computer.Methods for assessing interrater reliability can be found in the online supplement.Data collection was randomly assigned to one of two intensivist-led medical ICU teams each day and was not performed on weekends.Variables describing patient characteristics, staffing, and ICU strain were obtained from the electronic medical record and as part of a separate clinical trial (11).Our analysis focused on "cognitive rounding time" (time spent on the patient's assessment and plan) and on total rounding time (presentation of events and data, assessment and plan, and teaching related to that patient).Three validated strain variables (5) were considered: team census ("census"), representing the number of patients rounded on by the observed team each day; number of new admissions ("admissions") since the end of rounds the previous day; and average severity of illness ("acuity") of patients on the team, using Acute Physiology and Chronic Health Evaluation III (APACHE III) scores ( 12).We constructed explanatory linear mixed-effects models for cognitive and total rounding time for each patient-day.Patients were treated as random clusters, cumulative days hospitalized in the ICU were included as a random slope and as a linear term, and attending was treated as an indicator variable (13).Patient race Definition of abbreviations: ICU = intensive care unit; IQR = interquartile range.*Within 2 calendar days of ICU discharge.† Within 90 days of hospital admission.
Gnathostome Phylogenomics Utilizing Lungfish EST Sequences
Authors: B. M. Hallstrom, A. Janke
Journal: Molecular Biology and Evolution (2008)

The relationship between the Chondrichthyes (cartilaginous fishes), the Actinopterygii (ray-finned fishes), and the piscine Sarcopterygii (lobe-finned fishes) and how the Tetrapoda (four-limbed terrestrial vertebrates) are related to these has been a contentious issue for more than a century. A general consensus about the relationship of these vertebrate clades has gradually emerged among morphologists, but no molecular study has yet provided conclusive evidence for any specific hypothesis. In order to examine these relationships on the basis of more extensive sequence data, we have produced almost 1,000,000 bp of expressed sequence tags (ESTs) from the African marbled lungfish, Protopterus aethiopicus. This new data set yielded 771 transcribed nuclear sequences that had not been previously described. The lungfish EST sequences were combined with EST data from two cartilaginous fishes and whole genome data from an agnathan, four ray-finned fishes, and four tetrapods. Phylogenomic analysis of these data yielded, for the first time, significant maximum likelihood support for a traditional gnathostome tree with a split between the Chondrichthyes and remaining (bone) gnathostomes. Also, the sister group relationship between Dipnoi (lungfishes) and Tetrapoda received conclusive support. Previously proposed hypotheses, such as the monophyly of fishes, could be rejected significantly. The divergence time between lungfishes and tetrapods was estimated to 382–388 Ma by the current data set and six calibration points.
Targeting Tumor Angiogenesis with Histone Deacetylase Inhibitors: the Hydroxamic Acid Derivative LBH589
Authors: David Z. Qian, Yukihiko Kato, Shabana Shabbeer, Yongfeng Wei, Hendrik M.W. Verheul, Brenda Salumbides, Tolib Sanni, Peter Atadja, Roberto Pili
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Angiogenesis is required for tumor progression and represents a rational target for therapeutic intervention. Histone deacetylase (HDAC) inhibitors have been shown to have activity against various tumor cell types by inhibiting proliferation and inducing apoptosis both in vitro and in vivo. HDAC inhibitors have also been reported to inhibit angiogenesis. The goal of this study was to characterize the antiangiogenic and antitumor activity of a recently developed HDAC inhibitor, the hydroxamic derivative LBH589. Materials and Methods: To evaluate the antiangiogenesis activity of LBH589, we did cell cycle analysis, cell proliferation, tube formation, invasion assays in vitro, and Matrigel plug assay in vivo. To determine the antitumor activity of LBH589, we established human prostate carcinoma cell PC-3 xenografts in vivo. To evaluate the effect of LBH589 on endothelial signaling pathways, gene expression, and protein acetylation, we did Western blots and reverse transcription-PCR in human umbilical vein endothelial cells (HUVEC). Immunohistochemical analysis was done to evaluate new blood vessel formation in vivo. Results: LBH589 induced acetylation of histone H3 and α-tubulin protein in HUVECs. Histone and nonhistone protein acetylation correlated with induction of G2-M cell cycle arrest, inhibition of HUVEC proliferation, and viability. Noncytotoxic concentrations of LBH589 inhibited endothelial tube formation, Matrigel invasion, AKT, extracellular signal-regulated kinase 1/2 phosphorylation, and chemokine receptor CXCR4 expression. In vivo dosing of mice with LBH589 (10 mg/kg/d) reduced angiogenesis and PC-3 tumor growth. Conclusion: This study provides evidence that LBH589 induces a wide range of effects on endothelial cells that lead to inhibition of tumor angiogenesis. These results support the role of HDAC inhibitors as a therapeutic strategy to target both the tumor and endothelial compartment and warrant the clinical development of these agents in combination with angiogenesis inhibitors.
Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children
Authors: L. A. M. Smit, V. Lenters, B. B. Høyer, C. H. Lindh, H. S. Pedersen, I. Liermontova, B. A. G. Jönsson, A. H. Piersma, J. P. Bonde, G. Toft, R. Vermeulen, D. Heederik
Journal: Allergy (2015)

Background Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children. Methods We studied 1024 mother–child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5–9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p′-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models. Results In a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52–0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03–2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41–0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61–0.99) was found. Conclusions We found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.
Death after Eating Raw Rice
Authors: T. O. Ward
Journal: BMJ (1863)

effects of the cause which had been in operation to de- termine the attack, with the very compressible and inter- nmittent pulse, the case was treated by stimulating enemata, diffusable stimulants, antispasinodics, and nour- ishing diet.In fact, it was treated on the same principle as aniy other nervous affection of depressing nature would have been.The utility of the cold douche was
Key role of T cell defects in age-related vulnerability to West Nile virus
Authors: James D. Brien, Jennifer L. Uhrlaub, Alec Hirsch, Clayton A. Wiley, Janko Nikolich-Žugich
Journal: The Journal of Experimental Medicine (2009)

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40–50× more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level of cytokine and lytic granule production, each of which are essential for resistance against WNV, and in the ability to generate multifunctional anti-WNV effector T cells, which are believed to be critical for robust antiviral immunity. In contrast, at the peak of the response, old and adult T cells exhibited superimposable peptide sensitivity. Most importantly, although the adult CD4 or CD8 T cells readily protected immunodeficient mice upon adoptive transfer, old T cells of either subset were unable to provide WNV-specific protection. Consistent with a profound qualitative and quantitative defect in T cell immunity, old brains contained at least 12× fewer total effector CD8 T cells compared with adult mice at the peak of brain infection. These findings identify potential targets for immunomodulation and treatment to combat lethal WNV infection in the elderly.
Present Projections of Physician Production
Authors: C. H. William Ruhe
Journal: JAMA (1966)

In October 1959, the report of the Surgeon General's Consultant Group on Medical Education entitled<i>Physicians for a Growing America</i>was published by the US Public Health Service.<sup>1</sup>The chairman of the consultant group was Frank Bane, and the report has been known since that time as the "Bane Report." The consultant group included many outstanding figures in medicine and in education, among them representatives of the American Medical Association and the Association of American Medical Colleges. The chief of the study staff was William H. Stewart, MD, now surgeon general of the Public Health Service. <h3>Bane Report Conclusions</h3> The surgeon general established the consultant group primarily to answer the question: "How shall the nation be supplied with adequate numbers of well-qualified physicians?" The group concluded that: "An increase in graduates sufficient to maintain the present ratio of physicians to population is a minimum essential to protect the health
Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP).
Authors: I V Weller, M F Bassendine, A Craxi, M J Fowler, J Monjardino, H C Thomas, S Sherlock
Journal: Gut (1982)

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 59-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.
Reactive arthritis following culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon: a population-based study
Authors: J M Townes, A A Deodhar, E S Laine, K Smith, H E Krug, A Barkhuizen, M E Thompson, P R Cieslak, J Sobel
Journal: Annals of the Rheumatic Diseases (2008)

To describe the epidemiology and clinical spectrum of reactive arthritis (ReA) following culture-confirmed infection with bacterial enteric pathogens in a population-based study in the USA.We conducted telephone interviews of persons age>1 year with culture confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella and Yersinia infections reported to FoodNet (http://www.cdc.gov/FoodNet/) in Minnesota, USA and Oregon, USA between 2002 and 2004.with new onset joint pain, joint swelling, back pain, heel pain and morning stiffness lasting >or=3 days within 8 weeks of culture (possible ReA) were invited to complete a detailed questionnaire and physical examination.A total of 6379 culture-confirmed infections were reported; 70% completed screening interviews. Of these, 575 (13%) developed possible ReA; incidence was highest following Campylobacter (2.1/100,000) and Salmonella (1.4/100,000) infections. Risk was greater for females (relative risk (RR) 1.5, 95% CI, 1.3 to 1.7), adults (RR 2.5, 95% CI, 2.0 to 3.1) and subjects with severe acute illness (eg, fever, chills, headache, persistent diarrhoea). Risk was not associated with antibiotic use or human leukocyte antigen (HLA)-B27. A total of 54 (66%) of 82 subjects examined had confirmed ReA. Enthesitis was the most frequent finding; arthritis was less common. The estimated incidence of ReA following culture-confirmed Campylobacter, E coli O157, Salmonella, Shigella and Yersinia infections in Oregon was 0.6-3.1 cases/100,000.This is the first population-based study of ReA following infections due to bacterial enteric pathogens in the USA. These data will help determine the burden of illness due to these pathogens and inform clinicians about potential sequelae of these infections.
Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review
Authors: M. Rebolj, J. Bonde, S. H. Njor, E. Lynge
Journal: BMJ (2011)

<b>Objective</b> To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ≥1 relative light units/cut-off level (rlu/co). <b>Design</b> Systematic review. <b>Data sources</b> PubMed. <b>Study selection</b> Randomised controlled trials in primary cervical screening using hybrid capture 2 testing in the intervention arms. Articles published until August 2010 were included if the numbers of women with positive test results and with cervical intraepithelial neoplasia were stratified by hybrid capture 2 cut-off levels. <b>Participants</b> Women in the baseline screening rounds of the trials. <b>Interventions</b> Hybrid capture 2 screening in the baseline round including the diagnostic follow-up as practised in the randomised controlled trials and as reported by hybrid capture 2 cut-off values. <b>Results</b> Owing to heterogeneity in the trials, meta-analysis was not possible. Including cut-off values up to ≥10 rlu/co, 25 observation points were available for analysis. The relative sensitivity for cervical intraepithelial neoplasia grade III or higher at cut-off levels of ≥2, ≥4 or ≥5, and ≥10 rlu/co compared with a cut-off level of ≥1 rlu/co varied by trial, but at their lowest they were 0.97, 0.92, and 0.91, respectively. A similar pattern was observed for cervical intraepithelial neoplasia grade II or higher. The specificity would increase by at least 1%, 2%, and 3%, respectively, so that up to 24%, 39%, and 53%, of positive hybrid capture 2 test results not associated with high grade neoplasia could be avoided. Only two outliers existed to this general pattern. <b>Conclusions</b> Although the data were derived from the baseline screening rounds only, the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥2 rlu/co and ≥10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening, which require 90% or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥1 rlu/co. The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening; this seems reasonably safe and is significantly less burdensome for women.
Organization of kinases, phosphatases, and receptor signaling complexes
Authors: Robynn V. Schillace, John D. Scott
Journal: Journal of Clinical Investigation (1999)

The role of protein‐protein interaction domains in signal transduction has been a topic of intensive study for the last ten years. Many of these studies have focused on the role of protein‐protein interactions in signaling downstream of receptor and nonreceptor tyrosine kinases. However, recent evidence has pointed to the extensive role of protein-protein interaction domains in the localization and scaffolding of signaling molecules. This Perspective series reviews the role of protein‐protein interactions in localization and downstream signaling. The first Perspective in the series, by Schillace and Scott, provides an overview of targeting in signal transduction by protein kinases and phosphatases. The second in this issue, by Fanning and Anderson, explores PDZ domains, important for receptor targeting and clustering in a variety of cell systems. This series continues in the April 1999, no. 7, issue; two Perspectives discuss the role of protein‐protein interactions in signaling downstream of tyrosine kinases. Clements and Koretzky highlight new insights into signaling by lymphocytes, while Virkamaki, Ueki, and Kahn examine the role of protein‐protein interactions in insulin signaling and insulin resistance.
Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation
Authors: R. Dentin
Journal: Journal of Clinical Investigation (2005)

Dietary polyunsaturated fatty acids (PUFAs) are potent inhibitors of hepatic glycolysis and lipogenesis. Recently, carbohydrate-responsive element-binding protein (ChREBP) was implicated in the regulation by glucose of glycolytic and lipogenic genes, including those encoding L-pyruvate kinase (L-PK) and fatty acid synthase (FAS). The aim of our study was to assess the role of ChREBP in the control of L-PK and FAS gene expression by PUFAs. We demonstrated in mice, both in vivo and in vitro, that PUFAs [linoleate (C18:2), eicosapentanoic acid (C20:5), and docosahexaenoic acid (C22:6)] suppressed ChREBP activity by increasing ChREBP mRNA decay and by altering ChREBP translocation from the cytosol to the nucleus, independently of an activation of the AMP-activated protein kinase, previously shown to regulate ChREBP activity. In contrast, saturated [stearate (C18)] and monounsaturated fatty acids [oleate (C18:1)] had no effect. Since glucose metabolism via the pentose phosphate pathway is determinant for ChREBP nuclear translocation, the decrease in xylulose 5-phosphate concentrations caused by a PUFA diet favors a PUFA-mediated inhibition of ChREBP translocation. In addition, overexpression of a constitutive nuclear ChREBP isoform in cultured hepatocytes significantly reduced the PUFA inhibition of both L-PK and FAS gene expression. Our results demonstrate that the suppressive effect of PUFAs on these genes is primarily caused by an alteration of ChREBP nuclear translocation. In conclusion, we describe a novel mechanism to explain the inhibitory effect of PUFAs on the genes encoding L-PK and FAS and demonstrate that ChREBP is a pivotal transcription factor responsible for coordinating the PUFA suppression of glycolytic and lipogenic genes.