tbuckley/cabot-search huggingface dataset:
Overweight children could become the "new norm" for Europe, WHO says
Authors: R. Coombes
Journal: BMJ (2014)

A new large scale analysis has shown alarming rates of overweight children across Europe. The World Health Organization Regional Office for Europe, which released the figures from the 53 WHO European Region member states, said that being overweight was now so common in children, it risked becoming the “new norm.”

New country profiles1 showed that the prevalence of overweight among 11 year old boys …
Sinoatrial pacemaker shift following atrial stimulation in man.
Authors: G Steinbeck, B Lüderitz
Journal: Circulation (1977)

Indirect evidence of a sinoatrial pacemaker shift after programmed atrial stimulation in man is presented. Following electrically induced beats, time intervals and postextrasystolic morphology of atrial electrogram and P waves were scrutinized in 30 catheterization studies. Applying premature atrial stimulation, a decrease of the interval between the last basic atrial depolarization and the stimulus-produced atrial excitation (curtailed cycle) below a critical interval was followed by a sinoatrial pacemaker shift in three cases. This electrophysiologic event consisted of a concomitant change in shape of high right atrial electrogram and an increase of atrial cycle length. Simultaneous alteration of P waves could be detected in 2/3 patients. Assuming that the pacemaker shift indicates the arrival of ectopic activation in the sinus node, capture of the sinus node by the premature beat could be distinguished from failure to capture. Thus, pacemaker shift can be used for estimating sinoatrial conduction time in addition to present methods using measurement of postextrasystolic atrial intervals. The changes described could be seen both before and after atropine administration. Tracings of a pacemaker shift after cessation of rapid atrial pacing are also presented. In summary, we found a sinoatrial pacemaker shift underlying sinus node response to ectopic atrial activation in man, a phenomenon which contributes to our understanding of indirect assessment of sinoatrial conduction time by the premature stimulation technique.
(18) Lichen aureus
Authors: J.R.S. Rendall, T. Robinson
Journal: British Journal of Dermatology (2006)

Journal Article (18) Lichen aureus Get access J.R.S. Rendall, J.R.S. Rendall University College Hospital, London Search for other works by this author on: Oxford Academic Google Scholar T. Robinson T. Robinson University College Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 45–47, https://doi.org/10.1111/j.1365-2133.1976.tb07908.x Published: 01 December 1976
APOPTOSIS AND DISEASE: Regulation and Clinical Relevance of Programmed Cell Death
Authors: Charles M. Rudin, MD, PhD, Craig B. Thompson, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Regulation of the homeostatic balance between cell proliferation and cell death is essential for development and maintenance of multicellular organisms. Physiologic, or programmed, cell death is dependent on a genetically encoded and evolutionarily conserved pathway that induces a form of cellular suicide known as apoptosis. In the past decade, it has become clear that the regulatory mechanisms controlling programmed cell death are as fundamental, and as complex, as those regulating cell proliferation. Perturbation of the signaling cascades regulating apoptosis, whether by extracellular triggers, acquired or germline genetic mutations, or viral mimicry of signaling molecules, can result in a wide variety of human diseases. Analysis of these regulatory pathways has led to a better understanding of the etiology and pathogenesis of many human diseases, notably cancers, infectious diseases including AIDS, autoimmune diseases, and neurodegenerative/neurodevelopmental diseases. Our understanding of the regulation of programmed cell death in health and disease is far from complete, and the challenge of converting that understanding into new therapeutic modalities has only begun to be approached.
International<scp>Con</scp>sensus on drug allergy
Authors: P. Demoly, N. F. Adkinson, K. Brockow, M. Castells, A. M. Chiriac, P. A. Greenberger, D. A. Khan, D. M. Lang, H.‐S. Park, W. Pichler, M. Sanchez‐Borges, T. Shiohara, B. Y.‐H. Thong
Journal: Allergy (2014)

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
Pharmacokinetics of Novel Erythropoiesis Stimulating Protein Compared with Epoetin Alfa in Dialysis Patients
Authors: IAIN C. MACDOUGALL, STEPHEN J. GRAY, ORLAITH ELSTON, CORMAC BREEN, BARBARA JENKINS, JEFF BROWNE, JOAN EGRIE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration—time curve was significantly greater for NESP (291.0 ± 7.6 ng · h per ml versus 131.9 ± 8.3 ng · h per ml; mean ± SEM; P < 0.0005), and clearance was significantly lower (1.6 ± 0.3 ml/h per kg versus 4.0 ± 0.3 ml/h per kg; mean ± SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 ± 2.0 ml/kg versus 48.7 ± 2.1 ml/kg; mean ± SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.
Randomized Trial of Percutaneous Coronary Intervention for Subacute Infarct-Related Coronary Artery Occlusion to Achieve Long-Term Patency and Improve Ventricular Function
Authors: Vladimír Džavík, Christopher E. Buller, Gervasio A. Lamas, James M. Rankin, G.B. John Mancini, Warren J. Cantor, Ronald J. Carere, John R. Ross, Deborah Atchison, Sandra Forman, Boban Thomas, Pawel Buszman, Carlos Vozzi, Anthony Glanz, Eric A. Cohen, Peter Mečiar, Gerald Devlin, Alice Mascette, George Sopko, Genell L. Knatterud, Judith S. Hochman
Journal: Circulation (2006)

In the present study, we sought to determine whether opening a persistently occluded infarct-related artery (IRA) by percutaneous coronary intervention (PCI) in patients beyond the acute phase of myocardial infarction (MI) improves patency and indices of left ventricular (LV) size and function.
FUBAR: A Fast, Unconstrained Bayesian AppRoximation for Inferring Selection
Authors: B. Murrell, S. Moola, A. Mabona, T. Weighill, D. Sheward, S. L. Kosakovsky Pond, K. Scheffler
Journal: Molecular Biology and Evolution (2013)

Model-based analyses of natural selection often categorize sites into a relatively small number of site classes. Forcing each site to belong to one of these classes places unrealistic constraints on the distribution of selection parameters, which can result in misleading inference due to model misspecification. We present an approximate hierarchical Bayesian method using a Markov chain Monte Carlo (MCMC) routine that ensures robustness against model misspecification by averaging over a large number of predefined site classes. This leaves the distribution of selection parameters essentially unconstrained, and also allows sites experiencing positive and purifying selection to be identified orders of magnitude faster than by existing methods. We demonstrate that popular random effects likelihood methods can produce misleading results when sites assigned to the same site class experience different levels of positive or purifying selection—an unavoidable scenario when using a small number of site classes. Our Fast Unconstrained Bayesian AppRoximation (FUBAR) is unaffected by this problem, while achieving higher power than existing unconstrained (fixed effects likelihood) methods. The speed advantage of FUBAR allows us to analyze larger data sets than other methods: We illustrate this on a large influenza hemagglutinin data set (3,142 sequences). FUBAR is available as a batch file within the latest HyPhy distribution (http://www.hyphy.org), as well as on the Datamonkey web server (http://www.datamonkey.org/).
Detection, monitoring, and management of trastuzumab‐induced left ventricular dysfunction: an actual challenge
Authors: Carlo G. Tocchetti, Gianluca Ragone, Carmela Coppola, Domenica Rea, Giovanna Piscopo, Stefania Scala, Claudia De Lorenzo, Rosario V. Iaffaioli, Claudio Arra, Nicola Maurea
Journal: European Journal of Heart Failure (2012)
Serum-free culture success of glial tumors is related to specific molecular profiles and expression of extracellular matrix–associated gene modules
Authors: Rutger K. Balvers, Anne Kleijn, Jenneke J. Kloezeman, Pim J. French, Andreas Kremer, Martin J. van den Bent, Clemens M. F. Dirven, Sieger Leenstra, Martine L. M. Lamfers
Journal: Neuro-Oncology (2013)

Recent molecular characterization studies have identified clinically relevant molecular subtypes to coexist within the same histological entities of glioma. Comparative studies between serum-supplemented and serum-free (SF) culture conditions have demonstrated that SF conditions select for glioma stem-like cells, which superiorly conserve genomic alterations. However, neither the representation of molecular subtypes within SF culture assays nor the molecular distinctions between successful and nonsuccessful attempts have been elucidated. A cohort of 261 glioma samples from varying histological grades was documented for SF culture success and clinical outcome. Gene expression and single nucleotide polymorphism arrays were interrogated on a panel of tumors for comparative analysis of SF+ (successful cultures) and SF− (unsuccessful cultures). SF culture outcome was correlated with tumor grade, while no relation was found between SF+ and patient overall survival. Copy number–based hierarchical clustering revealed an absolute separation between SF+ and SF− parental tumors. All SF+ cultures are derived from tumors that are isocitrate dehydrogenase 1 (IDH1) wild type, chromosome 7 amplified, and chromosome 10q deleted. SF− cultures derived from IDH1 mutant tumors demonstrated a fade-out of mutated cells during the first passages. SF+ tumors were enriched for The Cancer Genome Atlas Classical subtype and intrinsic glioma subtype-18. Comparative gene ontology analysis between SF+ and SF− tumors demonstrated enrichment for modules associated with extracellular matrix composition, Hox-gene signaling, and inflammation. SF cultures are derived from a subset of parental tumors with a shared molecular background including enrichment for extracellular matrix–associated gene modules. These results provide leads to develop enhanced culture protocols for glioma samples not propagatable under current SF conditions.
Decreased T-Cell Receptor Excision Circles in Cutaneous T-Cell Lymphoma
Authors: Kei-ichi Yamanaka, Nikhil Yawalkar, David A. Jones, Daniel Hurwitz, Katalin Ferenczi, Sara Eapen, Thomas S. Kupper
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naïve T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naïve T cells relative to T cells that have undergone expansion. Experimental Design: We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells. Results: We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells. Conclusions: We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.
Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors
Authors: Anne Y. Lai, Motonari Kondo
Journal: The Journal of Experimental Medicine (2006)

The mechanism of lineage commitment from hematopoietic stem cells (HSCs) is not well understood. Although commitment to either the lymphoid or the myeloid lineage is popularly viewed as the first step of lineage restriction from HSCs, this model of hematopoietic differentiation has recently been challenged. The previous identification of multipotent progenitors (MPPs) that can produce lymphocytes and granulocyte/macrophages (GMs) but lacks erythroid differentiation ability suggests the existence of an alternative HSC differentiation program. Contribution to different hematopoietic lineages by these MPPs under physiological conditions, however, has not been carefully examined. In this study, we performed a refined characterization of MPPs by subfractionating three distinct subsets based on Flt3 and vascular cell adhesion molecule 1 expression. These MPP subsets differ in their ability to give rise to erythroid and GM lineage cells but are equally potent in lymphoid lineage differentiation in vivo. The developmental hierarchy of these MPP subsets demonstrates the sequential loss of erythroid and then GM differentiation potential during early hematopoiesis. Our results suggest that the first step of lineage commitment from HSCs is not simply a selection between the lymphoid and the myeloid lineage.
Safety of Short-Term Discontinuation of Antiplatelet Therapy in Patients With Drug-Eluting Stents
Authors: Mark J. Eisenberg, Pierre R. Richard, Danielle Libersan, Kristian B. Filion
Journal: Circulation (2009)

Antiplatelet therapy is often discontinued in patients with drug-eluting stents who are undergoing surgical procedures. However, discontinuation of antiplatelet therapy is an important risk factor for late stent thrombosis. Our objective was to examine the safety of short-term discontinuation of antiplatelet therapy.We systematically searched Medline for reported cases of late stent thrombosis and very late stent thrombosis published between January 2001 and July 2008. We restricted our search to Academic Research Consortium-defined definite cases. We identified 161 cases of late stent thrombosis or very late stent thrombosis from 84 articles (79 from case reports, 61 from registries, and 21 from randomized clinical trials). Patients had a mean age of 58.4+/-13.4 years, and 88% were male. A total of 19 cases occurred in patients who were receiving dual antiplatelet therapy at the time of the event. If patients stopped both antiplatelet agents simultaneously, the median time to event was 7 days. If patients had previously stopped a thienopyridine with no ill effect and subsequently stopped acetylsalicylic acid, the median time to event was also 7 days from the time of acetylsalicylic acid cessation. If the thienopyridine was stopped but acetylsalicylic acid was maintained, the median time to event was 122 days. Among the 48 patients who stopped both agents, 36 cases (75%) occurred within 10 days. Among the 94 patients who discontinued a thienopyridine but continued acetylsalicylic acid, only 6 cases (6%) occurred within 10 days.If acetylsalicylic acid therapy is maintained, short-term discontinuation of a thienopyridine may be relatively safe in patients with drug-eluting stents.
HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo
Authors: Neal A. Fischbach, Sofia Rozenfeld, Weifang Shen, Stephen Fong, Daniel Chrobak, David Ginzinger, Scott C. Kogan, Archana Radhakrishnan, Michelle M. Le Beau, Corey Largman, H. Jeffrey Lawrence
Journal: Blood (2004)
Regulation of Myelination in the Central Nervous System by Nuclear Lamin B1 and Non-coding RNAs
Authors: Shu-Ting Lin, Mary Y Heng, Louis J Ptáček, Ying-Hui Fu
Journal: Translational Neurodegeneration (2014)

Adult-onset autosomal dominant leukodystrophy (ADLD) is a progressive and fatal hereditary demyelination disorder characterized initially by autonomic dysfunction and loss of myelin in the central nervous system (CNS). Majority of ADLD is caused by a genomic duplication of the nuclear lamin B1 gene (LMNB1) encoding lamin B1 protein, resulting in increased gene dosage in brain tissue. In vitro, excessive lamin B1 at the cellular level reduces transcription of myelin genes, leading to premature arrest of oligodendrocyte differentiation. Murine models of ADLD overexpressing LMNB1 exhibited age-dependent motor deficits and myelin defects, which are associated with reduced occupancy of the Yin Yang 1 transcription factor at the promoter region of the proteolipid protein gene. Lamin B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and suggests lamin B1 as an important regulator of myelin formation and maintenance during aging. Identification of microRNA-23 (miR-23) as a negative regulator of lamin B1 can ameliorate the consequences of excessive lamin B1 at the cellular level. miR-23a-overexpressing mice display enhanced oligodendrocyte differentiation and myelin synthesis. miR-23a targets include a protein coding transcript PTEN (phosphatase and tensin homolog on chromosome 10), and a long noncoding RNA (2700046G09Rik), indicating a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin. Here, we provide a concise review of the current literature on clinical presentations of ADLD and how lamin B1 affects myelination and other developmental processes. Moreover, we address the emerging role of non-coding RNAs (ncRNAs) in modulating gene networks, specifically investigating miR-23 as a potential target for the treatment of ADLD and other demyelinating disorders.
Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma
Authors: D B Marmor
Journal: Thorax (2006)

<h3>Abstract</h3> <h3>Objective</h3> To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. <h3>Design</h3> Randomised, phase III, double blinded international, multicentre clinical trial. <h3>Setting</h3> 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). <h3>Participants</h3> 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. <h3>Intervention</h3> Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. <h3>Main outcome measure</h3> The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). <h3>Results</h3> Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. <h3>Conclusion</h3> Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. <h3>Trial registration</h3> Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
Three-year Oncologic and Renal Functional Outcomes After Robot-assisted Partial Nephrectomy
Authors: Ali Khalifeh, Riccardo Autorino, Remi Eyraud, Dinesh Samarasekera, Humberto Laydner, Kamol Panumatrassamee, Robert J. Stein, Jihad H. Kaouk
Journal: European Urology (2013)