tbuckley/cabot-search huggingface dataset:
PredSL: A Tool for the N-Terminal Sequence-Based Prediction of Protein Subcellular Localization
Authors: Evangelia I. Petsalaki, Pantelis G. Bagos, Zoi I. Litou, Stavros J. Hamodrakas
Journal: Genomics Proteomics & Bioinformatics (2006)

The ability to predict the subcellular localization of a protein from its sequence is of great importance, as it provides information about the protein's function. We present a computational tool, PredSL, which utilizes neural networks, Markov chains, profile hidden Markov models, and scoring matrices for the prediction of the subcellular localization of proteins in eukaryotic cells from the N-terminal amino acid sequence. It aims to classify proteins into five groups: chloroplast, thylakoid, mitochondrion, secretory pathway, and "other". When tested in a five-fold cross-validation procedure, PredSL demonstrates 86.7% and 87.1% overall accuracy for the plant and non-plant datasets, respectively. Compared with TargetP, which is the most widely used method to date, and LumenP, the results of PredSL are comparable in most cases. When tested on the experimentally verified proteins of the Saccharomyces cerevisiae genome, PredSL performs comparably if not better than any available algorithm for the same task. Furthermore, PredSL is the only method capable for the prediction of these subcellular localizations that is available as a stand-alone application through the URL:http://bioinformatics.biol.uoa.gr/PredSL/.
Natural history of sensitization, symptoms and occupational diseases in apprentices exposed to laboratory animals
Authors: D. Gautrin, H. Ghezzo, C. Infante-Rivard, J-L. Malo
Journal: European Respiratory Journal (2001)

The natural history of the development of sensitization and disease due to high-molecular-weight allergens is not well characterized. This study describes the time-course of the incidence of work-related symptoms, skin reactivity and occupational rhinoconjunctivitis (RC) and asthma (OA); and assesses the predictive value of skin testing and RC symptoms in apprentices exposed to laboratory animals, in a 3–4-yr programme. Four-hundred and seventeen apprentices at five institutions were assessed prospectively with questionnaire, skin-testing with animal-derived allergens, spirometry and airway responsiveness (n=373). Depending on the school, students were seen 8 (n=136), 20 (n=345), 32 (n=355) and 44 (n=98) months after starting the programme. At all visits, the incidence was greater for work-related RC symptoms followed in order by skin reactivity, occupational RC, and, almost equally, OA and work-related respiratory symptoms. The incidence-density figures were comparable for each follow-up period and for most indices up to 32 months after entry into the study and then tended to decrease. The positive predictive values (PPVs) of skin reactivity to work-related allergens for the development of work-related RC and respiratory symptoms were 30% and 9.0%, respectively, while the PPVs of work-related RC for the development of OA was 11.4%. Sensitization, symptoms and diseases occur maximally in the first 2–3 yrs after starting exposure to laboratory animals. Skin reactivity to work-related allergens and rhinoconjuctivitis symptoms have low positive predictive values.
Long-term risk of colorectal cancer after adenoma removal: a population-based cohort study
Authors: Vanessa Cottet, Valérie Jooste, Isabelle Fournel, Anne-Marie Bouvier, Jean Faivre, Claire Bonithon-Kopp
Journal: Gut (2011)

<h3>Background</h3> Previous studies examining the incidence of colorectal cancer after polypectomy have provided discordant findings. The aim of this study was to compare the risk of colorectal cancer after adenoma removal in routine clinical practice with the risk in the general population. <h3>Design</h3> Cohort study based on detailed data from a population-based registry that has collected all cases of both colorectal cancers and adenomas diagnosed in a clearly-defined population since 1976. <h3>Setting</h3> French administrative area of Côte-d9Or (Burgundy). <h3>Methods</h3> Residents of the area diagnosed for the first time with colorectal adenoma between 1990 and 1999 were included (n=5779). Initial and follow-up data until December 2003 were used to calculate the colorectal cancer standardised incidence ratio (SIR) and cumulative probabilities after adenoma removal. <h3>Results</h3> After a median follow-up of 7.7 years, 87 invasive colorectal cancers were diagnosed whereas 69 cases were expected. Compared with the general population, the overall SIR was 1.26 (95% CI 1.01 to 1.56). The risk of colorectal cancer depended on the characteristics of the initial adenoma (SIR 2.23 (95% CI 1.67 to 2.92) for advanced adenomas and 0.68 (95% CI 0.44 to 0.99) for non-advanced adenomas). In cases of advanced adenomas, the SIR was 1.10 (95% CI 0.62 to 1.82) in patients with colonoscopic follow-up and 4.26 (95% CI 2.89 to 6.04) in those without. The 10-year cumulative probabilities of colorectal cancer were, respectively, 2.05% (95% CI 1.14% to 3.64%) and 6.22% (95% CI 4.26% to 9.02%). <h3>Conclusions</h3> In routine practice, the risk of colorectal cancer after adenoma removal remains high and depends both on initial adenoma features and on colonoscopy surveillance practices. Gastroenterologists should encourage patients to comply with long-term colonoscopic surveillance.
G Protein Regulation of Potassium Ion Channels
Authors: Mitsuhiko Yamada, Atsushi Inanobe, Yoshihisa Kurachi
Journal: Pharmacological Reviews (1998)

Upon stimulation of vagal nerves, acetylcholine (ACh)c is released from axonal terminals and decelerates the heart beat. This historic discovery by Otto Loewi in the 1920s established the concept of chemical synaptic transmission ([Loewi, 1921][1]; [Loewi and Navaratil, 1926][2]). Since then, many
Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?
Authors: E Ryan, V Byrnes, B Coughlan, A-M Flanagan, S Barrett, J C O'Keane, J Crowe
Journal: Gut (2002)

<b>Background:</b> The majority of hereditary haemochromatosis (HH) patients are homozygous for the C282Y mutation in the HFE gene. We have demonstrated a homozygote frequency of 1 in 83 for the C282Y mutation in a retrospective analysis of Irish neonates. However, a fully developed phenotype is not observed at the same frequency clinically, suggesting that a large proportion of Irish HH patients may remain undiagnosed. <b>Aims:</b> To determine whether underdiagnosis of HH results from the non-specific nature of early symptoms or incomplete penetrance of the C282Y mutation. <b>Methods:</b> Seventy nine C282Y homozygous individuals identified from family screening for HH and 30 HH probands were investigated. Non-specific symptoms (fatigue, arthropathy, and impotence) and their association with iron indices (transferrin saturation and serum ferritin) and hepatic iron deposition were analysed. <b>Results:</b> We found that 78% of men (mean age 42 years) and 36% of women (mean age 39 years) who were identified as C282Y homozygotes following family screening had iron overload, as defined by a transferrin saturation ≥52% combined with a serum ferritin ≥300 μg/l for men and ≥200 μg/l for women. The frequency of reports of non-specific symptoms in those individuals with iron overload was not significantly different from those who did not have iron overload. <b>Conclusions:</b> Our findings indicate that underdiagnosis of HH may be due to the non-specific nature of early symptoms and less frequently to the incomplete penetrance of the C282Y mutation.
Advance directives on admission. Clinical implications and analysis of the Patient Self-Determination Act of 1990
Authors: J. La Puma
Journal: JAMA (1991)

DESPITE widespread acknowledgment of  need for individuals to draft living wills, durable powers of attorney, or other advance directives, few Americans have done so. To encourage patients to complete advance directives, Congress enacted  Patient Self-Determination Act (hereafter the Act) last October. The Act takes effect on December 1,1991, and requires hospitals, nursing homes, and hospices to advise patients on admission of their right to accept or refuse medical care and to execute an advance directive. Managed care organizations and home health care agencies must provide  same information to each of their members on members' enrollment. Provider organizations will also be required to (1) document whether patients have advance directives, (2) implement advance directive policies, and (3) educate their staffs and communities about advance directives. Compliance with  Act is a condition for Medicare and Medicaid reimbursement and is tied to institutional
Macrophage activation, chronic inflammation and gastrointestinal disease.
Authors: A R Tanner, M J Arthur, R Wright
Journal: Gut (1984)

Progress reportMacrophage activation, chronic inflammation and gastrointestinal diseaseThe involvement of macrophages in chronic inflammatory conditions has been the subject of considerable experimental investigation in recent years.Macrophages are able to secrete a wide range of biologically active compounds.They are important in the control of infection and, through their immunological and non-immunological receptors, macrophages interact with other cell types and a wide variety of proteins.Monocyte proliferation is apparent in a number of disorders, including collagen diseases, many infectious diseases, neo-plastic conditions and chronic inflammatory gastrointestinal diseases.'Generalised proliferation of mature macrophages is present in chronic granulomatous conditions such as tuberculosis, brucellosis and other infections by obligate intracellular parasites as well as in berylliosis and sarcoidosis.Other examples of macrophage proliferation include storage diseases -for example, Gaucher's disease, neoplastic macrophage proliferation and monocyte-macrophage dysfunction syndromes.The latter syndromes include chronic granulomatous disease2 and various lymphoproliferative disorders.3Macrophage dysfunction may also result from adrenocorticosteroid administration or exposure to ionising radiation.'Macrophage cell function has been extensively investigated in disorders such as lepromatous leprosy, miliary tuberculosis, disseminated fungal infections and in Hodgkin's disease.Intrinsic or acquired functional defects, however, have not been convincingly proved in these conditions.4Recent information on the tissue damaging potential of compounds released from activated macrophages has focused interest on a wide variety of chronic inflammatory conditions where macrophages may potentiate tissue damage in a non-specific manner.5Early work in this area concentrated on rheumatic diseases where the results strongly supported the concept of macrophage protease involvement in the promotion of inflammation.6These ideas have been more recently extended to various alimentary conditions,7-' including acute or chronic liver disease and inflammatory bowel disease.The purpose of this review is to highlight recent advances concerning macrophage function, kinetics, activation, and heterogeneity and to consider how far macrophages may be involved in the promotion of inflammation in a variety of gastrointestinal diseases.General information will be presented, followed by a detailed review of the literature relevant to alimentary disease.
Leukaemia inhibitory factor retards the progression of atherosclerosis
Authors: B ROLFE, S STAMATIOU, C WORLD, L BROWN, A THOMAS, J BINGLEY, N WORTH, J CAMPBELL
Journal: Cardiovascular Research (2003)

Objective: Our previous studies showed that the pleiotropic cytokine leukaemia inhibitory factor (LIF) inhibits the de novo formation of experimental atherosclerotic lesions. The present study examined whether LIF also inhibits progression of pre-existing atheroma. Methods: Balloon angioplasty was performed on the right carotid arteries of 18 rabbits immediately before placing animals on a cholesterol-enriched diet. After 4 weeks, at which time the intima:media ratio (I:M) was 0.99±0.12 (n = 6), osmotic minipumps containing LIF (n = 6) or saline control (n = 6) were inserted into the peritoneal cavity of each of the remaining rabbits for a further 4 weeks. Arteries were then harvested for analysis. Results: Continuous administration of LIF for the final 4 weeks of an 8-week cholesterol-enriched diet completely inhibited lesion progression in injured carotid arteries (I:M 1.05±0.16) compared with the saline-treated group at 8 weeks (1.62±0.13; P<0.05). Similarly in contralateral uninjured carotid arteries, LIF treatment prevented an increase in I:M from a baseline of 0.11±0.01 at 4 weeks to 0.15±0.02 at 8 weeks compared with 0.40±0.04 for the saline-treated group at 8 weeks (P<0.05). LIF reduced the number of macrophages in the neointima of uninjured arteries, but had no effect on the cellular composition of injured arteries. LIF treatment normalised smooth muscle-dependent vasoreactivity to phenylephrine and sodium nitroprusside in both injured and uninjured arteries. Expression and activity of inducible nitric oxide synthase (iNOS) were up-regulated in response to hypercholesterolemia with levels further increased following endothelial denudation. With LIF treatment, iNOS expression was increased in uninjured arteries but marginally reduced in injured arteries. LIF receptors were expressed in both uninjured and injured arteries, with LIF treatment having no significant effect on expression levels. Conclusion: LIF prevents progression of pre-formed atherosclerotic plaques, affecting lesion size and vascular reactivity. LIF treatment has differential effects within the artery wall, depending on the presence or absence of de-endothelialisation injury.
Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections
Authors: Bart Ferwerda, Gerben Ferwerda, Theo S. Plantinga, Janet A. Willment, Annemiek B. van Spriel, Hanka Venselaar, Clara C. Elbers, Melissa D. Johnson, Alessandra Cambi, Cristal Huysamen, Liesbeth Jacobs, Trees Jansen, Karlijn Verheijen, Laury Masthoff, Servaas A. Morré, Gert Vriend, David L. Williams, John R. Perfect, Leo A.B. Joosten, Cisca Wijmenga, Jos W.M. van der Meer, Gosse J. Adema, Bart Jan Kullberg, Gordon D. Brown, Mihai G. Netea
Journal: New England Journal of Medicine (2009)

Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with beta-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.
Transgenerational developmental programming
Authors: Catherine E. Aiken, Susan E. Ozanne
Journal: Human Reproduction Update (2013)

The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations.The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models.Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects.The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations beyond F2 as a consequence of development in a suboptimally developed intrauterine tract and not necessarily though directly transmitted epigenetic mechanisms.
Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury
Authors: Phing-How Lou, Liyan Zhang, Eliana Lucchinetti, Markus Heck, Andreas Affolter, Manoj Gandhi, Petra C. Kienesberger, Martin Hersberger, Alexander S. Clanachan, Michael Zaugg
Journal: Cardiovascular Research (2012)

AimsInfarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium.
Revolver Wound of the Brain; Lodgment of the Bullet; Recovery
Authors: P. B. Smith
Journal: BMJ (1892)

BULLET WOUND OF BRAIN. [TxLBJOURAL 627 alternate in arrangement with the other three, which contain respectively a red, a green, and a blue glass.A standard candle is enclosed in a lantern having a circular aperture 25 mm. in diameter on thie side nearest the screen, and this is filled with ground glass.The lantern can be moved to and fro along a horizontal scale graduated in centi- metres from the screen backwards, and its position is indicated by a little pointer which projects from the base of the lantern.A small aperture in the side of the lantern just above this indicator allows the candlelight to illuminate the ,scale just where it is necessary to read it.During the exami- nation daylight is to be so far excluded from the room " as to Tender recognition only possible at close quarters."Donders gave the following formula:It is only necessary to add to the explanation previously -given that A=the distance of the candle behind the screen registered by the normal eye-that is, in practice the eye of the examining surgeon-in order to recognise the colour of the light coming through a 1 millimetre aperture at 5 metres distance; a=the distance of the candle behind the screen registered by the person who is being examined.This factor A is of great importance.It varies with different colours.Donders estimated that with the standard candle and ground ?glass employed by him: A=1.75 metres in the case of the plain ground glass.A=0.65 ,, ,, red glass.A=0.2a ,.green glass.
Practical approach to problems of the parturient diabetic in developing countries.
Authors: C Sutton
Journal: BMJ (1977)

Improved management of diabetic pregnancies at Lautoka Hospital, Fiji, in 1976 resulted in a neonatal survival rate of 100%. Management included attempts to control the maternal blood glucose concentrations with insulin and delaying delivery until there was enough surfactant in the liquor to ensure a viable infant. The techniques are simple to use and require only minimal technological facilities.
Management of nausea and vomiting in pregnancy
Authors: S. Jarvis, C. Nelson-Piercy
Journal: BMJ (2011)

#### Summary points

Nausea and vomiting are the most common symptoms of pregnancy. As a result many medical practitioners will encounter this problem and should be familiar with the appropriate investigations and current treatment options. Nausea and vomiting affect 50-90% of pregnant women, and in about 35% of these women symptoms are of clinical relevance, with both physical and psychosocial sequelae. Although colloquially referred to as “morning sickness,” for many women symptoms persist over the whole day, with a broad spectrum of severity ranging from occasional nausea to fulminant and intractable vomiting. Nausea and vomiting begin in the first trimester, at about six to eight weeks’ gestation, typically peaking at about nine weeks’ gestation and settling by about 12 weeks. Only a minority of women have symptoms after 20 weeks of gestation. Adequate oral hydration and avoidance of dietary triggers are often sufficient, but a proportion of women with severe and protracted nausea and vomiting will need antiemetic drugs.

#### Sources and selection criteria

We performed a PubMed search to identify peer reviewed original articles, meta-analyses, and reviews. Cochrane Collaboration and clinical evidence databases were reviewed as well. We considered only papers written in English and mainly included …
Empirical Assessment of RAD Sequencing for Interspecific Phylogeny
Authors: Astrid Cruaud, Mathieu Gautier, Maxime Galan, Julien Foucaud, Laure Sauné, Gwenaëlle Genson, Emeric Dubois, Sabine Nidelet, Thierry Deuve, Jean-Yves Rasplus
Journal: Molecular Biology and Evolution (2014)

Next-generation sequencing opened up new possibilities in phylogenetics; however, choosing an appropriate method of sample preparation remains challenging. Here, we demonstrate that restriction-site-associated DNA sequencing (RAD-seq) generates useful data for phylogenomics. Analysis of our RAD library using current bioinformatic and phylogenetic tools produced 400× more sites than our Sanger approach (2,262,825 nt/species), fully resolving relationships between 18 species of ground beetles (divergences up to 17 My). This suggests that RAD-seq is promising to infer phylogeny of eukaryotic species, though potential biases need to be evaluated and new methodologies developed to take full advantage of such data.
Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection
Authors: Robert S. Welner, Rosana Pelayo, Yoshinori Nagai, Karla P. Garrett, Todd R. Wuest, Daniel J. Carr, Lisa A. Borghesi, Michael A. Farrar, Paul W. Kincade
Journal: Blood (2008)