tbuckley/cabot-search huggingface dataset:
Recommendations for epidemiological studies on COPD
Authors: Philip H. Quanjer, Sanja Stanojevic, Maureen P. Swanney, Martin R. Miller
Journal: European Respiratory Journal (2012)

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.
Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival
Authors: A. Italiano, M. Toulmonde, A. Cioffi, N. Penel, N. Isambert, E. Bompas, F. Duffaud, A. Patrikidou, B. Lortal, A. Le Cesne, J.-Y. Blay, R.G. Maki, G.K. Schwartz, C.R. Antonescu, S. Singer, J.-M. Coindre, B. Bui
Journal: Annals of Oncology (2011)
Treatment response in enteropathy associated <scp>T</scp>‐cell lymphoma; survival in a large multicenter cohort
Authors: Petula Nijeboer, Laura R. de Baaij, Otto Visser, Birgit I. Witte, Saskia A.G.M. Cillessen, Chris J. Mulder, Gerd Bouma
Journal: American Journal of Hematology (2015)

Enteropathy‐associated T‐cell lymphoma (EATL) is a T‐cell Non‐Hodgkin Lymphoma which is highly associated with celiac disease. The prognosis of EATL has been considered poor and there are no standardized treatment protocols. Here, we evaluate treatment response and survival of EATL patients in a large multicenter cohort. A total of 61 patients diagnosed with EATL were analyzed. Various treatment regimens were applied in EATL during the past fifteen years including either monotherapy consisting of chemotherapy or resection, or combination therapy with both aforementioned regimens whether or not combined with stem‐cell transplantation (SCT). Overall, 50/61 patients (82%) died after a median of 7.4 months. One‐ and five‐year overall survival was 40 and 11%, respectively. Median follow‐up in the survivors was 26 months. Patients treated with the most aggressive treatment, that is, resection, chemotherapy and autologous SCT, showed the most favourable outcome with complete remission in all patients, the lowest relapse rate and one‐ and five‐year overall survival of 100 and 33%, respectively, although overall survival in this group was not significantly better as compared to patients treated with surgery and chemotherapy. This study indicates that combination treatment is superior compared to monotherapy. Whether or not consolidation therapy with autologous SCT may improve survival needs to be substantiated in a larger randomized international trial. Am. J. Hematol. 90:493–498, 2015. © 2015 Wiley Periodicals, Inc.
REDUCTION OF SICK WASTAGE AFTER ATHLETIC INJURIES
Authors: R. S. Woods
Journal: BMJ (1936)

administer the treatments under the direction and supervision of these qualified specialists.The cost of such treatments will be only one-tenth that of those administered in private practices, and will be often ten times as efficient.It is thus that I forecast the future of electrotherapy.Golding Bird said, " Electricity has been by no means fairly treated," but I am confident that, as we become rmore fully acquainted with Nature's basic principles in health and disease, so we shall tend more and more to utilize her most fundamental, powerful, readily controlled, and most universally called for agent, namely electricity." Naturam expellas furca, tamen usque recurret."Attempts have been made in the past to expel electro- therapy with the pitchforks of prejudice, ignorance, indiffer- ence, or even of ridicule, but nevertheless this form of treatment has always returned with renewed vigour.At the present time it occupies a firmer position in the healing art than ever before in its 200 years of history.Its future, however, rests very largely in the hands of those who direct medical education and research.
Loss of C/EBPα cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage
Authors: Bo T. Porse, David Bryder, Kim Theilgaard-Mönch, Marie S. Hasemann, Kristina Anderson, Inge Damgaard, Sten Eirik W. Jacobsen, Claus Nerlov
Journal: The Journal of Experimental Medicine (2005)

CCAAT/enhancer binding protein (C/EBP)α is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, and is found mutated in 9% of patients who have acute myeloid leukemia (AML). We previously showed that mutations which dissociate the ability of C/EBPα to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation, accumulation of myeloblasts and promyelocytes, and expansion of myeloid progenitor populations—all characteristics of AML. Circulating myeloblasts and hepatic leukocyte infiltration were observed, but thrombocytopenia, anemia, and elevated leukocyte count—normally associated with AML—were absent. These results show that disrupting the cell cycle regulatory function of C/EBPα is sufficient to initiate AML-like transformation of the granulocytic lineage, but only partially the peripheral pathology of AML.
Cellular mechanisms of insulin resistance
Authors: Gerald I. Shulman
Journal: Journal of Clinical Investigation (2000)

It is estimated that by the year 2020 there will be approximately 250 million people affected by type 2 diabetes mellitus worldwide (1). Although the primary factors causing this disease are unknown, it is clear that insulin resistance plays a major role in its development. Evidence for this comes from (a) the presence of insulin resistance 10–20 years before the onset of the disease (2, 3); (b) cross-sectional studies demonstrating that insulin resistance is a consistent finding in patients with type 2 diabetes (3–6); and (c) prospective studies demonstrating that insulin resistance is the best predictor of whether or not an individual will later become diabetic (2, 3). Here, I focus on some recent advances in our understanding of human insulin resistance that have been made using nuclear magnetic resonance spectroscopy (NMR). This technique takes advantage of the spin properties of the nuclei of certain isotopes, such as 1H, 13C, and 31P, which endow the isotopes with a magnetic component that can be used to measure the concentration of intracellular metabolites noninvasively and to assess biochemical differences between normal and diabetic subjects. Drawing on NMR studies from my laboratory and others, I first consider the control of glucose phosphorylation and transport in regulating muscle responses to insulin. I then turn to the effects of fatty acids on insulin responses, showing that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings. Finally, I propose an alternative model that appears to fit these and other available data.
Rate of Negativization of the Basophil Activation Test (BASOTEST) and RAST in Patients with Immediate Allergic Reactions to Amoxicillin
Authors: T.D. Fernandez, M.J. Torres, C. Mayorga, E. Martin, J.L. Rodriguez-Bada, C. Antunez, N. Blanca, J.A. Cornejo-Garcia, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2006)
Development and evaluation of lafutidine solid dispersion via hot melt extrusion: Investigating drug-polymer miscibility with advanced characterisation
Authors: Ritesh Fule, Purnima Amin
Journal: Asian Journal of Pharmaceutical Sciences (2014)

In current study, immediate release solid dispersion (SD) formulation of antiulcer drug lafutidine (LAFT) was developed using hot melt extrusion (HME) technique. Amphiphilic Soluplus® used as a primary solubilizing agent, with different concentrations of selected surfactants like PEG 400, Lutrol F127 (LF127), Lutrol F68 (LF68) were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable. On the contrary, traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC. Atomic Force microscopy (AFM) studies revealed drug- polymer molecular miscibility and surface interaction at micro level. 1H–COSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus®, with chemical shift drifting and line broadening. MD simulation studies using computational modelling showed intermolecular interaction between molecules. Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems. Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD. The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.
Mechanical Bioeffects of Ultrasound
Authors: Diane Dalecki
Journal: Annual Review of Biomedical Engineering (2004)

▪ Abstract Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool. Through both thermal and nonthermal mechanisms, ultrasound can produce a variety of biological effects in tissues in vitro and in vivo. This chapter provides an overview of the fundamentals of key nonthermal mechanisms for the interaction of ultrasound with biological tissues. Several categories of mechanical bioeffects of ultrasound are then reviewed to provide insight on the range of ultrasound bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the potential application of mechanical bioeffects to the design of new therapeutic applications of ultrasound in medicine.
The Impact of rRNA Secondary Structure Consideration in Alignment and Tree Reconstruction: Simulated Data and a Case Study on the Phylogeny of Hexapods
Authors: Harald O. Letsch, Patrick Kück, Roman R. Stocsits, Bernhard Misof
Journal: Molecular Biology and Evolution (2010)

The use of secondary structures has been advocated to improve both the alignment and the tree reconstruction processes of ribosomal RNA (rRNA) data sets. We used simulated and empirical rRNA data to test the impact of secondary structure consideration in both steps of molecular phylogenetic analyses. A simulation approach was used to generate realistic rRNA data sets based on real 16S, 18S, and 28S sequences and structures in combination with different branch length and topologies. Alignment and tree reconstruction performance of four recent structural alignment methods was compared with exclusively sequence-based approaches. As empirical data, we used a hexapod rRNA data set to study the influence of nucleotide interdependencies in sequence alignment and tree reconstruction. Structural alignment methods delivered significantly better sequence alignments compared with pure sequence-based methods. Also, structural alignment methods delivered better trees judged by topological congruence to simulation base trees. However, the advantage of structural alignments was less pronounced and even vanished in several instances. For simulated data, application of mixed RNA/DNA models to stems and loops, respectively, led to significantly shorter branches. The application of mixed RNA/DNA models in the hexapod analyses delivered partly implausible relationships. This can be interpreted as a stronger sensitivity of mixed model setups to nonphylogenetic signal. Secondary structure consideration clearly influenced sequence alignment and tree reconstruction of ribosomal genes. Although sequence alignment quality can considerably be improved by the use of secondary structure information, the application of mixed models in tree reconstructions needs further studies to understand the observed effects.
Anidulafungin versus Fluconazole for Invasive Candidiasis
Authors: Annette C. Reboli, Coleman Rotstein, Peter G. Pappas, Stanley W. Chapman, Daniel H. Kett, Deepali Kumar, Robert Betts, Michele Wible, Beth P. Goldstein, Jennifer Schranz, David S. Krause, Thomas J. Walsh
Journal: New England Journal of Medicine (2007)

Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis.
From an animal's point of view: Motivation, fitness, and animal welfare
Authors: Marian Stamp Dawkins
Journal: Behavioral and Brain Sciences (1990)

Abstract To study animal welfare empirically we need an objective basis for deciding when an animal is suffering. Suffering includes a wide range ofunpleasant emotional states such as fear, boredom, pain, and hunger. Suffering has evolved as a mechanism for avoiding sources ofdanger and threats to fitness. Captive animals often suffer in situations in which they are prevented from doing something that they are highly motivated to do. The “price” an animal is prepared to pay to attain or to escape a situation is an index ofhow the animal “feels” about that situation. Withholding conditions or commodities for which an animal shows “inelastic demand” (i.e., for which it continues to work despite increasing costs) is very likely to cause suffering. In designing environments for animals in zoos, farms, and laboratories, priority should be given to features for which animals show inelastic demand. The care ofanimals can thereby be based on an objective, animal-centered assessment of their needs.
Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups
Authors: Nita A. Limdi, Mia Wadelius, Larisa Cavallari, Niclas Eriksson, Dana C. Crawford, Ming-Ta M. Lee, Chien-Hsiun Chen, Alison Motsinger-Reif, Hersh Sagreiya, Nianjun Liu, Alan H. B. Wu, Brian F. Gage, Andrea Jorgensen, Munir Pirmohamed, Jae-Gook Shin, Guilherme Suarez-Kurtz, Stephen E. Kimmel, Julie A. Johnson, Teri E. Klein, Michael J. Wagner
Journal: Blood (2010)
5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen
Authors: Susan O'Brien, Joseph O. Moore, Thomas E. Boyd, Loree M. Larratt, Aleksander B. Skotnicki, Benjamin Koziner, Asher A. Chanan-Khan, John F. Seymour, John Gribben, Loretta M. Itri, Kanti R. Rai
Journal: Journal of Clinical Oncology (2009)

A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients.Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment.Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004).In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.
Impact of Genetic Architecture on the Relative Rates of X versus Autosomal Adaptive Substitution
Authors: T. Connallon, N. D. Singh, A. G. Clark
Journal: Molecular Biology and Evolution (2012)

Molecular evolutionary theory predicts that the ratio of autosomal to X-linked adaptive substitution (K(A)/K(x)) is primarily determined by the average dominance coefficient of beneficial mutations. Although this theory has profoundly influenced analysis and interpretation of comparative genomic data, its predictions are based upon two unverified assumptions about the genetic basis of adaptation. The theory assumes that 1) the rate of adaptively driven molecular evolution is limited by the availability of beneficial mutations, and 2) the scaling of evolutionary parameters between the X and the autosomes (e.g., the beneficial mutation rate, and the fitness effect distribution of beneficial alleles, per X-linked versus autosomal locus) is constant across molecular evolutionary timescales. Here, we show that the genetic architecture underlying bouts of adaptive substitution can influence both assumptions, and consequently, the theoretical relationship between K(A)/K(x) and mean dominance. Quantitative predictions of prior theory apply when 1) many genomically dispersed genes potentially contribute beneficial substitutions during individual steps of adaptive walks, and 2) the population beneficial mutation rate, summed across the set of potentially contributing genes, is sufficiently small to ensure that adaptive substitutions are drawn from new mutations rather than standing genetic variation. Current research into the genetic basis of adaptation suggests that both assumptions are plausibly violated. We find that the qualitative positive relationship between mean dominance and K(A)/K(x) is relatively robust to the specific conditions underlying adaptive substitution, yet the quantitative relationship between dominance and K(A)/K(x) is quite flexible and context dependent. This flexibility may partially account for the puzzlingly variable X versus autosome substitution patterns reported in the empirical evolutionary genomics literature. The new theory unites the previously separate analysis of adaptation using new mutations versus standing genetic variation and makes several useful predictions about the interaction between genetic architecture, evolutionary genetic constraints, and effective population size in determining the ratio of adaptive substitution between autosomal and X-linked genes.
Transient inhibition by orotic acid does not abolish the in vivo response of rat hepatocytes to a direct mitogen, lead nitrate
Authors: Ezio Laconi, Aroon Yusuf, Ali R. Jahangir, Sergio Laconi, Prema M. Rao, Srinivasan Rajalakshmi, Francesca Sanna, Paolo Pani, Antonio Monni, Dittakavi S.R. Sarma
Journal: Journal of Hepatology (1997)
Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities
Authors: Takashi Igarashi, Jun Inatomi, Takashi Sekine, Seok Ho Cha, Yoshikatsu Kanai, Motoei Kunimi, Kazuhisa Tsukamoto, Hiroaki Satoh, Mitsunobu Shimadzu, Fumiko Tozawa, Tetsuo Mori, Masaaki Shiobara, George Seki, Hitoshi Endou
Journal: Nature Genetics (1999)
Sequence Dependence of Administration of Human Recombinant Tumor Necrosis Factor and Interleukin-2 in Murine Tumor Therapy
Authors: R. J. Zimmerman, S. Gauny, A. Chan, P. Landre, J. L. Winkelhake
Journal: JNCI Journal of the National Cancer Institute (1989)

Simultaneous administration of recombinant human tumor necrosis factor (rhTNF) and interleukin-2 (rhIL-2) has been shown to block tumor take in murine models. We investigated the effects of sequence and schedule of administration as a function of tumor burden with two tumor models (B16 and Meth A). rhTNF followed by rhIL-2 had extraordinary antitumor efficacy, but rhIL-2 followed by rhTNF was much less effective. Sequential rhTNF/rhIL-2 therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in only reduced growth rate. Experiments with genetically immunodeficient mice suggested that T cell factors may be required for synergistic antitumor activity.
Twitterati and Paperati: evidence versus popular opinion in science communication
Authors: Áine MacNamara, Dave Collins
Journal: British Journal of Sports Medicine (2015)

Science communication has traditionally been the remit of peer-reviewed journals with information being shared, almost exclusively, within the academic community. For those working at the coalface the limited scope of this traditional discourse in terms of access and consumption by key stakeholders (eg, coaches, National Governing Bodies of sport, sport scientists) is of concern. In fact, traditional peer-reviewed publication does not seem to be the most effective mechanism for scientists to engage with the public and to disseminate knowledge.

Reflecting these concerns is the trend to use social media to communicate science—tools such as Twitter are an increasingly important part of the scholarly ecology1 ,2 and a powerful influence on professional environments. However, the extent to which the information transmitted by social media is evidence-based rather than opinion-based is questionable. Of course, these concerns are not to say that the academic world should be the only gatekeepers of knowledge, but in a Web 2.0 world where knowledge is made available at a …