tbuckley/cabot-search huggingface dataset:
S135 Can your mobile phone improve your asthma?
Authors: D. Ryan, H. Pinnock, L. Tarassenko, A. Lee, A. Sheikh, D. Price
Journal: Thorax (2010)

<h3>Background</h3> It is recognised that some 45% of the population exhibit poor asthma control. Over 90% of the population possess a mobile phone (&gt;70% over 60 years of age). Mobile technology potentially addresses the barriers of low expectations and poor concordance which are factors in poor asthma control. <h3>Hypothesis</h3> Using mobile phone recording of symptoms, lung function and medication use with instant feedback of asthma control, would improve control compared to using paper diaries. <h3>Trial design</h3> A 6-month researcher-blinded randomised controlled trial <h3>Setting</h3> UK primary care <h3>Method</h3> Using central randomisation, we allocated patients ≥12 years of age with poorly controlled asthma (ACQ&gt;1.5) to either mobile phone or paper-based monitoring. Clinical care was provided by practice asthma nurses in accordance with SIGN/BTS guidelines. Patients were reviewed monthly until control was achieved. A researcher, blinded to allocation assessed outcomes at 3 m and 6 m. Primary outcome measure: change in Asthma Control Questionnaire score between baseline and 6 months. <h3>Results</h3> We randomised 288 patients from 32 practices (209 completed). Baseline characteristics of both groups were similar. Intention to treat analysis, before breaking the randomisation code, showed that control in both groups improved significantly and to a similar extent. ACQ: Group 1 (n=110) Baseline 2.17, 6m 1.25: Group 2 (n=99) Baseline 2.33, 6m 1.17. Mean (95% CI) improvement in ACQ: Group 1 (n=110) 0.84 (0.67, 1.02), Group 2 (n=99) 0.94 (0.77, 1.11) both p&lt;0.001. Between group p=0.434 ns. Approximately 70% in each group improved by ≥0.5 (minimal clinically important difference). <h3>Conclusion</h3> Both groups demonstrated significant improvement in asthma control from baseline. Use of mobile phone technology provided no additional benefit over paper diaries.
Omega-3 Fatty Acids and Mood Disorders
Authors: Gordon Parker, Neville A Gibson, Heather Brotchie, Gabriella Heruc, Anne-Marie Rees, Dusan Hadzi-Pavlovic
Journal: American Journal of Psychiatry (2006)

Objective: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy. Method: Relevant published studies are detailed and considered. Results: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Conclusions: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.
Transendothelial Neutrophil Migration
Authors: Gediminas Cepinskas, Ron Noseworthy, Peter R. Kvietys
Journal: Circulation Research (1997)

Abstract During an acute inflammatory response polymorphonuclear leukocytes (PMNs) adhere to and emigrate across the venular microvasculature. There is general agreement on the mechanisms involved in PMN adhesive interactions. However, the mechanisms by which PMNs migrate across the endothelial lining remain controversial, particularly with respect to the role of elastase. In the present study, we used human umbilical vein endothelial cells (HUVECs) and PMNs to test the hypothesis that the relative role of PMN-derived elastase may be dependent on the degree of HUVEC retraction within monolayers. A high (10 −7 mol/L), but not a low (10 −10 mol/L), concentration of platelet-activating factor (PAF) caused HUVEC retraction of sufficient magnitude to increase transendothelial protein movement. Elastase inhibitors prevented PMN transendothelial migration in response to the low, but not the high, concentration of PAF. These findings suggest that PMN migration across confluent endothelial cells is elastase dependent, whereas PMN migration across retracted endothelial cells is elastase independent. However, under the latter condition (high concentration of PAF), the two endogenous proteases, α 2 -macroglobulin and α 1 -antitrypsin, could interfere with PAF-induced PMN transendothelial migration. Thus, as the concentration of PAF is increased, migrating PMNs use other proteases, in addition to elastase. We also noted that transendothelial protein movement is closely coupled to PMN migration.
Infectious diseases as a trigger in thrombotic microangiopathies in intensive care unit (ICU) patients?
Authors: Paul Coppo, Christophe Adrie, Elie Azoulay, Ghislaine Leleu, Eric Oksenhendler, Lionel Galicier, Jean Roger Le Gall, Annette Bussel, Benoît Schlemmer
Journal: Intensive Care Medicine (2003)
Brain-Derived Neurotrophic Factor Signaling and Subgenual Anterior Cingulate Cortex Dysfunction in Major Depressive Disorder
Authors: Adam Tripp, Hyunjung Oh, Jean-Philippe Guilloux, Keri Martinowich, David A. Lewis, Etienne Sibille
Journal: American Journal of Psychiatry (2012)

Objective The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Method Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf+/−] mice and BDNF exon-IV knockout [BdnfKIV] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Results Based on the results in Bdnf+/− and BdnfKIV mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. Conclusions These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features.
Re: Macrophage Role in the Anti-Prostate Cancer Response to One Class of Antiangiogenic Agents
Authors: A. Dabrowska, J. Golab, A. Giermasz, M. Marczak, M. Jakobisiak
Journal: JNCI Journal of the National Cancer Institute (1999)

As reported in a recent article in the Journal, Joseph and Isaacs (1) tried to combine Linomide® with other antiangiogenic agents known to inhibit tumorassociated macrophages (TAMs) to evaluate their joint antitumor effects. Unfortunately, the combination of Linomide with other antiangiogenic agents did not result in potentiation of therapeutic efficacy. Instead, one of these agents, pentoxifylline, inhibited the an-
Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle<sup>4</sup>-<scp>d</scp>-Phe<sup>7</sup>]-α-MSH
Authors: A.K. Haylett, Z. Nie, M. Brownrigg, R. Taylor, L.E. Rhodes
Journal: British Journal of Dermatology (2010)

Solar urticaria is a rare photosensitivity disorder demonstrating a range of action spectra, which can inflict a very large impact on life quality despite available treatments. Melanin broadly reduces skin penetration by ultraviolet-visible wavelengths, thus increased melanization may protect in solar urticaria.To examine quantitatively for impact of the potent α-melanocyte stimulating hormone analogue afamelanotide ([Nle(4)-D-Phe(7)]-α-MSH, Scenesse(®); Clinuvel Pharmaceuticals Ltd, Melbourne, Vic., Australia) on the solar urticaria response and skin melanization.Five patients with solar urticaria received a single dose of 16 mg subcutaneous afamelanotide implant in winter time. Melanin density was assessed spectrophotometrically from day 0 to day 60. Detailed monochromated light testing to geometric dose series (increment ) of wavelengths 300-600 nm was performed at 0, 30 and 60 days, with assessment of weal and flare area and minimum urticarial dose (MUD). Data were analysed by repeated-measures anova.Mean melanin density increased by day 7, peaked at day 15 and remained elevated at day 60 (P=0·03, 0·01, 0·02 vs. baseline, respectively). Baseline phototesting revealed action spectra of 320-400 (n=1), 320-500 (n=2), 300-600 (n=1) and 370-500 nm (n=1), and on afamelanotide mean rises in MUD of 1-12 and 1-3 dose increments were seen at the individual wavelengths tested, at 30 and 60 days, respectively. A significant fall in weal area occurred across responding wavelengths from 300 to 600 nm at 60 days postimplant (P=0·049 vs. baseline), accompanied by greater than twofold overall increase in MUD (P=0·058 vs. baseline).Melanization following afamelanotide is accompanied by reduction in solar urticaria response across a broad spectrum of wavelengths. Further study is warranted to assess clinical benefit under ambient conditions in summer.
Lymph Node Metastasis in Breast Cancer Xenografts Is Associated with Increased Regions of Extravascular Drain, Lymphatic Vessel Area, and Invasive Phenotype
Authors: Arvind P. Pathak, Dmitri Artemov, Michal Neeman, Zaver M. Bhujwalla
Journal: Cancer Research (2006)

Abstract Interactions between the tumor stromal compartment and cancer cells play an important role in the spread of cancer. In this study, we have used noninvasive in vivo magnetic resonance imaging (MRI) of two human breast cancer models with significantly different invasiveness, to quantify and understand the role of interstitial fluid transport, lymphatic-convective drain, and vascularization in the regional spread of breast cancer to the axillary lymph nodes. Quantitative fluorescence microscopy was done to morphometrically characterize lymphatic vessels in these tumors. Significant differences in vascular and extravascular transport variables as well as in lymphatic vessel morphology were detected between the two breast cancer models, which also exhibited significant differences in lymph node and lung metastasis. These data are consistent with a role of lymphatic drain in lymph node metastasis and suggest that increased lymph node metastasis may occur due to a combination of increased invasiveness, and reduced extracellular matrix integrity allowing increased pathways of least resistance for the transport of extravascular fluid, as well as tumor cells. It is also possible that lymph node metastasis occurred via the cancer cell–bearing tumoral lymphatic vessels. The congestion of these tumoral lymphatics with cancer cells may have restricted the entry and transport of macromolecules. (Cancer Res 2006; 66(10): 5151-8)
Effect of oxygen on breath markers of oxidative stress
Authors: M. Phillips, R.N. Cataneo, J. Greenberg, R. Grodman, R. Gunawardena, A. Naidu
Journal: European Respiratory Journal (2002)

Supplemental oxygen is often administered to induce hyperoxia in nonhypoxic patients for indications such as chest pain, despite lack of evidence of clinical benefit. Induced hyperoxia is potentially toxic, since it may increase oxidative stress and peroxidative damage to deoxyribonucleic acid, lipids and proteins. The aim of this study was to establish whether supplemental oxygen induces oxidative stress in nonhypoxic subjects. Breath markers of oxidative stress were measured in 31 healthy subjects before and after breathing 28% oxygen at 2.0 L x min(-1) via nasal prongs for 30 min while resting. The criterion standard of oxidative stress was the breath methylated alkane contour (BMAC), a three-dimensional plot of the alveolar gradients of C4-C20 alkanes and monomethylated alkanes produced by lipid peroxidation. Volatile organic compounds (VOCs) in breath were assayed by gas chromatography and mass spectroscopy, and the BMACs before and after oxygenation were compared. Following oxygenation, there was a significant increase in mean volume under the curve of the BMAC and in alveolar gradients of three VOCs: 3-methyltridecane, 3-methylundecane and 5-methylnonane. Breath markers of oxidative stress were significantly increased in normal volunteers breathing supplemental oxygen for 30 min.
PTEN Deficiency in Endometrioid Endometrial Adenocarcinomas Predicts Sensitivity to PARP Inhibitors
Authors: Konstantin J. Dedes, Daniel Wetterskog, Ana M. Mendes-Pereira, Rachael Natrajan, Maryou B. Lambros, Felipe C. Geyer, Radost Vatcheva, Kay Savage, Alan Mackay, Christopher J. Lord, Alan Ashworth, Jorge S. Reis-Filho
Journal: Science Translational Medicine (2010)

Endometrioid endometrial cancer cell lines harboring PTEN loss of function have impaired homologous recombination response to DNA double-strand breaks and show an exquisite sensitivity to PARP inhibition.
Controversies in treatment: Should a sexual offender be allowed castration?
Authors: M Alexander, J Gunn, D A Cook, P J Taylor, J Finch
Journal: BMJ (1993)

Should a sexual offender be allowed castration?A 59year old man with a persistent history ofsexual abuse ofchildren has requested castration to stop himselffrom reoffending.Dr Malcolm Alexanderpresents the man's case and highlights some ofthe ethical issues, and three psychiatrists and a lawyer comment on the request.
Unusual Physical Signs in Strangulated Inguinal Hernia
Authors: C. P. Sames
Journal: BMJ (1949)

not known.The incidence of 62% of Staph.pyogenes in the nasopharynx and its relative predominance is not unexpected in view of the findings of others (Kneeland, 1930; Torrey and Reese, 1945).The high incidence of 50% in the faeces is much greater than has been recorded heretofore (Todd, 1922; Crowley, Downie, Fulton, and Wilson, 1941), owing largely, it is believed, to the selective mnedium employed.It is a relevant point in considering the staphylococcus as a. possible aetiological agent in enteritis.The high incidence of penicillin-resistant strains in both nasopharynx and bowel probably reflects the strains cir- culating in a hospital environment.It is of interest that a similar incidence was found by Barber and Rozwadowska-Dowzenko (1948) from strains from infections, also in hos- pital.The figures obtained from this series of infants, taken in conjunction with time and place, may be regarded as a contribution to the further study of penicillin resistance of staphylococci in the community.SummaryAn investigation into the incidence of staphylococci in the nasopharynx and faeces of 130 normal healthy breast-fed infants aged 0-7 days born in the Maternity Department of St. Mary's Hospital, Manchester, is recorded.From the nasopharynx Staph.pyogenes was isolated in 62% of the infants and from the faeces in 50%.
Cooperative Relationship Between Pharmaceutical Companies, Academia, and Media Explains Sharp Decrease in Frequency of Pulmonary Complications After Bortezomib in Japan
Authors: Hiroto Narimatsu, Akiko Hori, Tomoko Matsumura, Yuko Kodama, Morihito Takita, Yukiko Kishi, Tamae Hamaki, Koichiro Yuji, Yuji Tanaka, Tsunehiko Komatsu, Masahiro Kami
Journal: Journal of Clinical Oncology (2008)
Protein kinase Cε: an oncogene and emerging tumor biomarker
Authors: Michael A Gorin, Quintin Pan
Journal: Molecular Cancer (2009)

Members of the protein kinase C (PKC) family have long been studied for their contributions to oncogenesis. Among the ten different isoforms of this family of serine/threonine kinases, protein kinase Cε (PKCε) is one of the best understood for its role as a transforming oncogene. In vitro, overexpression of PKCε has been demonstrated to increase proliferation, motility, and invasion of fibroblasts or immortalized epithelial cells. In addition, xenograft and transgenic animal models have clearly shown that overexpression of PKCε is tumorigenic resulting in metastatic disease. Perhaps most important in implicating the epsilon isoform in oncogenesis, PKCε has been found to be overexpressed in tumor-derived cell lines and histopathological tumor specimens from various organ sites. Combined, this body of work provides substantial evidence implicating PKCε as a transforming oncogene that plays a crucial role in establishing an aggressive metastatic phenotype. Reviewed here is the literature that has led to the current understanding of PKCε as an oncogene. Moreover, this review focuses on the PKCε-mediated signaling network for cell motility and explores the interaction of PKCε with three major PKCε signaling nodes: RhoA/C, Stat3 and Akt. Lastly, the emerging role of PKCε as a tumor biomarker is discussed.
Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells
Authors: Annick Mühlethaler-Mottet, Roland Meier, Marjorie Flahaut, Katia Balmas Bourloud, Katya Nardou, Jean-Marc Joseph, Nicole Gross
Journal: Molecular Cancer (2008)

Abstract Background Histone deacetylase inhibitors (HDACi) are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB) is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. Results We show here that the HDACi Sodium Butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA) strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and Bim EL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-x L , RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. Conclusion HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.
Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction
Authors: Hester M Den Ruijter, Sanne A E Peters, Todd J Anderson, Annie R Britton, Jacqueline M Dekker, Marinus J Eijkemans, Gunnar Engström, Gregory W Evans, Jacqueline de Graaf, Diederick E Grobbee, Bo Hedblad, Albert Hofman, Suzanne Holewijn, Ai Ikeda, Maryam Kavousi, Kazuo Kitagawa, Akihiko Kitamura, Hendrik Koffijberg, Eva M Lonn, Matthias W Lorenz, Ellisiv B Mathiesen, Giel Nijpels, Shuhei Okazaki, Daniel H O'Leary, Joseph F Polak, Jackie F Price, Christine Robertson, Christopher M Rembold, Maria Rosvall, Tatjana Rundek, Jukka T Salonen, Matthias Sitzer, Coen D A Stehouwer, Jacqueline C Witteman, Karel G Moons, Michiel L Bots
Journal: JAMA (2012)

The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent.To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score.Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion.Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke.Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease.We included 14 population-based cohorts contributing data for 45,828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women.The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism
Authors: David A Koolen, Lisenka E L M Vissers, Rolph Pfundt, Nicole de Leeuw, Samantha JL Knight, Regina Regan, R Frank Kooy, Edwin Reyniers, Corrado Romano, Marco Fichera, Albert Schinzel, Alessandra Baumer, Britt-Marie Anderlid, Jacqueline Schoumans, Nine V Knoers, Ad Geurts van Kessel, Erik A Sistermans, Joris A Veltman, Han G Brunner, Bert B A de Vries
Journal: Nature Genetics (2006)
A method to assess compositional bias in biological sequences and its application to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes
Authors: Paul M Harrison, Mark Gerstein
Journal: Genome biology (2003)

We have derived a novel method to assess compositional biases in biological sequences, which is based on finding the lowest-probability subsequences for a given residue-type set. As a case study, the distribution of prion-like glutamine/asparagine-rich ((Q+N)-rich) domains (which are linked to amyloidogenesis) was assessed for budding and fission yeasts and four other eukaryotes. We find more than 170 prion-like (Q+N)-rich regions in budding yeast, and, strikingly, many fewer in fission yeast. Also, some residues, such as tryptophan or isoleucine, are unlikely to form biased regions in any eukaryotic proteome.