tbuckley/cabot-search huggingface dataset:
Neuroendocrine tumours: a hope and a prayer
Authors: A. Grossman
Journal: Gut (2009)

Neuroendocrine tumours (NETs) include a large and protean group of tumours which have certain characteristics in common, and arise from a variety of endocrine cell types.1–3 Classically, they would exclude the pituitary and parathyroid tumours, but include tumours arising from neuroendocrine cells in the gastrointestinal and bronchial tracts, formerly known as carcinoids (a term invented by Siegried Oberndorfer in 1907), the pancreatic islet cells and in some classifications also the parafollicular C cells of the thyroid (medullary thyroid carcinoma) and tumours arising from the sympatho-adrenomedullary system, phaeochromocytomas and paragangliomas. Apart from early surgical intervention, there is essentially no curative modality of treatment. These tumours are not in general very sensitive to conventional chemotherapy or radiotherapy; they also differ from some other malignancies in that surgical intervention has a place even in the presence of metastatic disease, including debulking of primary tumours, metastatectomy, and also other palliative ablative techniques such as radionuclide therapy with [131I]MIBG and [90Y/177Lu]octreotide/octreotate, radiofrequency ablation, hepatic embolisation and chemoembolisation, all of which …
An Apple a Day May Be Safer Than Vitamins
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2008)

any cancer patients and healthy individuals regularly take vitamin and mineral supplements, often with their physician's blessing.Although many doctors may not believe that supplements prevent disease, most think that they can't hurt.But a growing body of research indicates that, at least in some cases, vitamin and mineral supplements may not be entirely benign.Several new reports, including a commentary in this issue of the Journal (p.773-778), are raising concerns about the safety and effi cacy of vitamin and mineral supplements in healthy individuals and cancer patients and survivors.Some experts see a need for further studies, whereas others say that there are suffi cient negative data to stop vitamin trials altogether."A good place for research to start would be food and lifestyle intervention trials," instead of vitamin studies, said Tim Byers, M.D., professor of epidemiology and community health at the University of Colorado School of Medicine in Denver.Recently, an expert panel, which included Byers, issued strong recommendations to cancer patients and survivors against taking any nutritional supplements.Entitled Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective , the extensive report, released in November 2007 by the American Institute for Cancer Research (AICR) and its international affi liate, the World Cancer Research Fund, analyzed more than 440 studies on cancer risk, foods, and vitamin and mineral supplements conducted during the past 20 years.The expert panel warned that certain nutritional supplements appear to be harmful for cancer patients and survivors, countering the conventional wisdom
A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs.
Authors: Reut Shalgi, Michal Lapidot, Ron Shamir, Yitzhak Pilpel
Journal: Genome biology (2005)

In recent years, intensive computational efforts have been directed towards the discovery of promoter motifs that correlate with mRNA expression profiles. Nevertheless, it is still not always possible to predict steady-state mRNA expression levels based on promoter signals alone, suggesting that other factors may be involved. Other genic regions, in particular 3' UTRs, which are known to exert regulatory effects especially through controlling RNA stability and localization, were less comprehensively investigated, and deciphering regulatory motifs within them is thus crucial.By analyzing 3' UTR sequences and mRNA decay profiles of Saccharomyces cerevisiae genes, we derived a catalog of 53 sequence motifs that may be implicated in stabilization or destabilization of mRNAs. Some of the motifs correspond to known RNA-binding protein sites, and one of them may act in destabilization of ribosome biogenesis genes during stress response. In addition, we present for the first time a catalog of 23 motifs associated with subcellular localization. A significant proportion of the 3' UTR motifs is highly conserved in orthologous yeast genes, and some of the motifs are strikingly similar to recently published mammalian 3' UTR motifs. We classified all genes into those regulated only at transcription initiation level, only at degradation level, and those regulated by a combination of both. Interestingly, different biological functionalities and expression patterns correspond to such classification.The present motif catalogs are a first step towards the understanding of the regulation of mRNA degradation and subcellular localization, two important processes which--together with transcription regulation--determine the cell transcriptome.
Knowledge systems in health in sub-Saharan Africa: results of a questionnaire-based survey
Authors: Chris Zielinski, Derege Kebede, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

To describe the mechanisms and systems of knowledge acquisition, creation, diffusion, application and improvement of knowledge in two layers of the health system: health policy formulation and the provision of clinical services.A questionnaire-based survey.Health research institutions in 46 countries of the World Health Organization (WHO) African Region.Key informants in ministries of health and health care institutions in 39 countries of the Region.Existence of knowledge management infrastructure or components of infrastructure in the countries of the Region.Central national bodies are always cited as having a major role in policy-setting. Non-national bodies most frequently provide advice and act in monitoring and evaluation, while decentralised entities are strongly involved in dissemination, implementation, and monitoring and evaluation. In general, ministries tend not to have an explicit knowledge management framework and do not map knowledge sources and flows for policy-making. The main sources of evidence are guidelines or recommendations from international or national agencies, although systematic reviews are rarely used. Routine monitoring and evaluation of quality and effectiveness of the process of policy development and its implementation was reported in 19 of the 39 respondent countries. In most respondent countries, electronic medical records were rarely used.As systematic reviews are rarely utilised as a source of evidence in policy development and few mechanisms exist to assess the performance of the policies, there are significant opportunities for improving policy development.
Analysis of the chronic lymphocytic leukemia coding genome: role of <i>NOTCH1</i> mutational activation
Authors: Giulia Fabbri, Silvia Rasi, Davide Rossi, Vladimir Trifonov, Hossein Khiabanian, Jing Ma, Adina Grunn, Marco Fangazio, Daniela Capello, Sara Monti, Stefania Cresta, Ernesto Gargiulo, Francesco Forconi, Anna Guarini, Luca Arcaini, Marco Paulli, Luca Laurenti, Luigi M. Larocca, Roberto Marasca, Valter Gattei, David Oscier, Francesco Bertoni, Charles G. Mullighan, Robin Foá, Laura Pasqualucci, Raul Rabadan, Riccardo Dalla-Favera, Gianluca Gaidano
Journal: The Journal of Experimental Medicine (2011)

The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown. The full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains &amp;lt;20 clonally represented gene alterations/case, including predominantly nonsilent mutations, and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. Although most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%), as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.
Ventricular arrhythmias associated with coronary artery occlusion and reperfusion in the isolated perfused rat heart: a model for assessment of antifibrillatory action of antiarrhythmic agents
Authors: W. F. LUBBE, P. S. DARIES, L. H. OPIE
Journal: Cardiovascular Research (1978)

Journal Article Ventricular arrhythmias associated with coronary artery occlusion and reperfusion in the isolated perfused rat heart: a model for assessment of antifibrillatory action of antiarrhythmic agents Get access W. F. LUBBE, W. F. LUBBE 1 From the Medical Research Council Ischaemic Heart Disease Research Unit, Department of Medicine, University of Cape Town, and Groote Schuur Hospital, Observatory, 7925, Republic of South Africa 1Requests for reprints and correspondence may be addressed to W. F. Lubbe. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. S. DARIES, P. S. DARIES From the Medical Research Council Ischaemic Heart Disease Research Unit, Department of Medicine, University of Cape Town, and Groote Schuur Hospital, Observatory, 7925, Republic of South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar L. H. OPIE L. H. OPIE From the Medical Research Council Ischaemic Heart Disease Research Unit, Department of Medicine, University of Cape Town, and Groote Schuur Hospital, Observatory, 7925, Republic of South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 12, Issue 4, April 1978, Pages 212–220, https://doi.org/10.1093/cvr/12.4.212 Published: 01 April 1978
LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia
Authors: Stephan Emmrich, Alexandra Streltsov, Franziska Schmidt, Veera Raghavan Thangapandi, Dirk Reinhardt, Jan-Henning Klusmann
Journal: Molecular Cancer (2014)

Long non-coding RNAs (lncRNAs) are recognized as pivotal players during developmental ontogenesis and pathogenesis of cancer. The intronic microRNA (miRNA) clusters miR-99a ~ 125b-2 and miR-100 ~ 125b-1 promote progression of acute megakaryoblastic leukemia (AMKL), an aggressive form of hematologic cancers. The function of the lncRNA hostgenes MIR99AHG (alias MONC) and MIR100HG within this ncRNA ensemble remained elusive.Here we report that lncRNAs MONC and MIR100HG are highly expressed in AMKL blasts. The transcripts were mainly localized in the nucleus and their expression correlated with the corresponding miRNA clusters. Knockdown of MONC or MIR100HG impeded leukemic growth of AMKL cell lines and primary patient samples. The development of a lentiviral lncRNA vector to ectopically express lncRNAs without perturbing their secondary structure due to improper termination of the viral transcript, allowed us to study the function of MONC independent of the miRNAs in cord blood hematopoietic stem and progenitor cells (HSPCs). We could show that MONC interfered with hematopoietic lineage decisions and enhanced the proliferation of immature erythroid progenitor cells.Our study reveals an unprecedented function of lncRNAs MONC and MIR100HG as regulators of hematopoiesis and oncogenes in the development of myeloid leukemia.
Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor
Authors: Erik-Oliver Glocker, Daniel Kotlarz, Kaan Boztug, E. Michael Gertz, Alejandro A. Schäffer, Fatih Noyan, Mario Perro, Jana Diestelhorst, Anna Allroth, Dhaarini Murugan, Nadine Hätscher, Dietmar Pfeifer, Karl-Walter Sykora, Martin Sauer, Hans Kreipe, Martin Lacher, Rainer Nustede, Cristina Woellner, Ulrich Baumann, Ulrich Salzer, Sibylle Koletzko, Neil Shah, Anthony W. Segal, Axel Sauerbrey, Stephan Buderus, Scott B. Snapper, Bodo Grimbacher, Christoph Klein
Journal: New England Journal of Medicine (2009)

We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient.
IgA Anti-transglutaminase Autoantibodies at Type 1 Diabetes Onset Are Less Frequent in Adult Patients and Are Associated With a General Celiac-Specific Lower Immune Response in Comparison With Nondiabetic Celiac Patients at Diagnosis
Authors: Claudio Tiberti, Francesca Panimolle, Margherita Bonamico, Blegina Shashaj, Tiziana Filardi, Federica Lucantoni, Raffaella Nenna, Francesco Costantino, Andrea Lenzi, Susanna Morano
Journal: Diabetes Care (2012)

To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis.IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb(+) DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis.A total of 12.8% DM1 sera were IgA-tTGAb(+), with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb(+) DM1 compared with nondiabetic CD patients.Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis.
Using THz Spectroscopy, Evolutionary Network Analysis Methods, and MD Simulation to Map the Evolution of Allosteric Communication Pathways in c-Type Lysozymes
Authors: Kristina N. Woods, Juergen Pfeffer
Journal: Molecular Biology and Evolution (2015)

It is now widely accepted that protein function is intimately tied with the navigation of energy landscapes. In this framework, a protein sequence is not described by a distinct structure but rather by an ensemble of conformations. And it is through this ensemble that evolution is able to modify a protein’s function by altering its landscape. Hence, the evolution of protein functions involves selective pressures that adjust the sampling of the conformational states. In this work, we focus on elucidating the evolutionary pathway that shaped the function of individual proteins that make-up the mammalian c-type lysozyme subfamily. Using both experimental and computational methods, we map out specific intermolecular interactions that direct the sampling of conformational states and accordingly, also underlie shifts in the landscape that are directly connected with the formation of novel protein functions. By contrasting three representative proteins in the family we identify molecular mechanisms that are associated with the selectivity of enhanced antimicrobial properties and consequently, divergent protein function. Namely, we link the extent of localized fluctuations involving the loop separating helices A and B with shifts in the equilibrium of the ensemble of conformational states that mediate interdomain coupling and concurrently moderate substrate binding affinity. This work reveals unique insights into the molecular level mechanisms that promote the progression of interactions that connect the immune response to infection with the nutritional properties of lactation, while also providing a deeper understanding about how evolving energy landscapes may define present-day protein function.
Rapid Evolution and the Importance of Recombination to the Gastroenteric Pathogen Campylobacter jejuni
Authors: D. J. Wilson, E. Gabriel, A. J.H. Leatherbarrow, J. Cheesbrough, S. Gee, E. Bolton, A. Fox, C. A. Hart, P. J. Diggle, P. Fearnhead
Journal: Molecular Biology and Evolution (2008)

Responsible for the majority of bacterial gastroenteritis in the developed world, Campylobacter jejuni is a pervasive pathogen of humans and animals, but its evolution is obscure. In this paper, we exploit contemporary genetic diversity and empirical evidence to piece together the evolutionary history of C. jejuni and quantify its evolutionary potential. Our combined population genetics–phylogenetics approach reveals a surprising picture. Campylobacter jejuni is a rapidly evolving species, subject to intense purifying selection that purges 60% of novel variation, but possessing a massive evolutionary potential. The low mutation rate is offset by a large effective population size so that a mutation at any site can occur somewhere in the population within the space of a week. Recombination has a fundamental role, generating diversity at twice the rate of de novo mutation, and facilitating gene flow between C. jejuni and its sister species Campylobacter coli. We attempt to calibrate the rate of molecular evolution in C. jejuni based solely on within-species variation. The rates we obtain are up to 1,000 times faster than conventional estimates, placing the C. jejuni–C. coli split at the time of the Neolithic revolution. We weigh the plausibility of such recent bacterial evolution against alternative explanations and discuss the evidence required to settle the issue.
Hantavirus Evolution in Relation to Its Rodent and Insectivore Hosts: No Evidence for Codivergence
Authors: C. Ramsden, E. C. Holmes, M. A. Charleston
Journal: Molecular Biology and Evolution (2008)

Hantaviruses are considered one of the best examples of a long-term association between RNA viruses and their hosts. Based on the appearance of strong host specificity, it has been suggested that hantaviruses cospeciated with the rodents and insectivores they infect since these mammals last shared a common ancestor, approximately 100 million years ago. We tested this hypothesis of host–virus codivergence in two ways: 1) we used cophylogenetic reconciliation analysis to assess the fit of the virus tree onto that of the host and 2) we estimated the evolutionary rates and divergence times for the Hantavirus genus using a Bayesian Markov Chain Monte Carlo method and similarly compared these with those of their hosts. Our reconciliation analysis provided no evidence for a history of codivergence between hantaviruses and their hosts. Further, the divergence times for the Hantavirus genus were many orders of magnitude too recent to correspond with the timescale of their hosts' speciation. We therefore propose that apparent similarities between the phylogenies of hantaviruses and their mammalian hosts are the result of a more recent history of preferential host switching and local adaptation. Based on the presence of clade-defining amino acids in all genomic segments, we propose that the patterns of amino acid replacement in these viruses are also compatible with a history of host-specific adaptation.
The immune privilege by trail expression in hepatocellular carcinoma cells
Authors: Takenari Yamanaka, Katsuya Shiraki, Hidekazu Inoue, Hiroshi Okano, Masatoshi Deguchi, Takahisa Sakai, Shigeru Ohmori, Katsuhiko Fujikawa, Takeshi Nakano
Journal: Journal of Hepatology (2002)
Anterior cingulate engagement in a foraging context reflects choice difficulty, not foraging value
Authors: Amitai Shenhav, Mark A Straccia, Jonathan D Cohen, Matthew M Botvinick
Journal: Nature Neuroscience (2014)

While changes in dACC activity have traditionally been associated with variability in decision difficulty, a recent high-profile study has suggested that dACC instead encodes the value of foraging. In this study, the authors challenge this previous finding by showing that, when foraging value and decision difficulty are effectively dissociated, dACC activity corresponds to changes in choice difficulty. Previous theories predict that human dorsal anterior cingulate (dACC) should respond to decision difficulty. An alternative theory has been recently advanced that proposes that dACC evolved to represent the value of 'non-default', foraging behavior, calling into question its role in choice difficulty. However, this new theory does not take into account that choosing whether or not to pursue foraging-like behavior can also be more difficult than simply resorting to a default. The results of two neuroimaging experiments show that dACC is only associated with foraging value when foraging value is confounded with choice difficulty; when the two are dissociated, dACC engagement is only explained by choice difficulty, and not the value of foraging. In addition to refuting this new theory, our studies help to formalize a fundamental connection between choice difficulty and foraging-like decisions, while also prescribing a solution for a common pitfall in studies of reward-based decision making.
Health Research and the HIPAA Privacy Rule—Reply
Authors: Robert J. Levine
Journal: JAMA (2008)

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Chief medical officer outlines how more data collection can make surgery safer
Authors: A. O'Dowd
Journal: BMJ (2008)

New ways to make surgery safer in England by monitoring and measuring performance have been proposed by the chief medical officer. In his annual report, published this week, Liam Donaldson said that errors in surgery had to be reduced, alongside a culture change. Professor Donaldson made several major announcements in the report, including: