tbuckley/cabot-search huggingface dataset:
Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial
Authors: M. Rabaglio, Z. Sun, K.N. Price, M. Castiglione-Gertsch, H. Hawle, B. Thürlimann, H. Mouridsen, M. Campone, J.F. Forbes, R.J. Paridaens, M. Colleoni, T. Pienkowski, J.-M. Nogaret, I. Láng, I. Smith, R.D. Gelber, A. Goldhirsch, A.S. Coates
Journal: Annals of Oncology (2009)
Nocturnal periodic breathing and the development of acute high altitude illness.
Authors: U Eichenberger, E Weiss, D Riemann, O Oelz, P Bärtsch
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We tested the hypothesis that periodic breathing (PB) at high altitude is more frequent and arterial oxygen desaturation more severe during sleep in subjects developing high altitude pulmonary edema (HAPE) or acute mountain sickness (AMS) compared with subjects remaining healthy. We registered thoraco-abdominal movement, electro-encephalogram and oxygen saturation by pulse oximeter (pSao2) in 21 subjects during the first night spent at the altitude of 4,559 m. During the subsequent stay at 4,559 m, eight subjects remained well (controls), five subjects developed AMS and eight subjects developed HAPE. PB was found in all sleep stages and the percentage PB in any sleep stage was not significantly different between groups. There was a trend towards more PB in the HAPE vs. AMS and control group lasting 80 +/- 5 (mean +/- SE), 58 +/- 7, 57 +/- 9% of analyzable time, respectively (p = 0.09). The mean nocturnal decrease of pSao2 for these groups was 8.7 +/- 1.9, 5.4 +/- 2.1, 4.8 +/- 1.2%; (p = 0.36) and the median nocturnal pSao2 was 49 +/- 3, 63 +/- 3, and 63 +/- 4% (p = 0.02). Arterial blood gas analysis before and after sleep recordings indicate that the significantly lower Sao2 in the HAPE group is secondary to gas exchange rather than ventilation. The nocturnal decrease of pSao2 did not correlate with the time of PB nor the number of desaturation events > or = 4%. These findings suggest that more frequent PB in the HAPE group is a consequence of lower Sao2 due to impairment of gas exchange.
Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer
Authors: C. Liedtke, K. Broglio, S. Moulder, L. Hsu, S.-W. Kau, W.F. Symmans, C. Albarracin, F. Meric-Bernstam, W. Woodward, R.L. Theriault, L. Kiesel, G.N. Hortobagyi, L. Pusztai, A.M. Gonzalez-Angulo
Journal: Annals of Oncology (2009)
Severely Impaired Cardiac Autonomic Nervous Activity After the Fontan Operation
Authors: Hideo Ohuchi, Satoshi Hasegawa, Kenji Yasuda, Osamu Yamada, Yasuo Ono, Shigeyuki Echigo
Journal: Circulation (2001)

Background Elevated neurohumoral activity and an abnormal cardiopulmonary response to exercise are well-established characteristics in patients after the Fontan operation. However, there have been few studies addressing cardiac autonomic nervous activity (CANA) in these patients. Methods and Results We evaluated CANA in 63 post-Fontan patients and 44 controls. Cardiac parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) changes after cholinergic blockade, HR variability, and arterial baroreflex sensitivity. Cardiac sympathetic nervous activity was estimated by the heart to mediastinum [ 123 I]metaiodobenzylguanidine activity ratio (H/M) and the HR increase (ΔHR) after isoproterenol infusion (β). ΔHR and peak oxygen uptake (V̇ o 2 ) were measured by exercise test. There was no difference in β between the Fontan group and controls. PSNA and H/M were markedly lower than in controls ( P &lt;0.001). PSNA and β were related to ΔHR ( P &lt;0.05); however, peak V̇ o 2 was not correlated with ΔHR. Neither PSNA nor H/M was associated with clinical features, including hemodynamics, type of repair, number of surgical procedures, age at Fontan operation, or follow-up period, and administration of an angiotensin-converting enzyme inhibitor did not improve the impaired CANA in these patients. Conclusions After the Fontan procedure, postsynaptic β-sensitivity is maintained and is important in ΔHR during exercise as is PSNA, although ΔHR does not determine exercise capacity. The lack of a relationship between CANA and clinical features implies that, in addition to surgical damage, the Fontan circulation per se may impair CANA. Angiotensin-converting enzyme inhibitor administration does not change this abnormality.
Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes
Authors: Akash Kumar, Evan A Boyle, Mari Tokita, Andrei M Mikheev, Michelle C Sanger, Emily Girard, John R Silber, Luis F Gonzalez-Cuyar, Joseph B Hiatt, Andrew Adey, Choli Lee, Jacob O Kitzman, Donald E Born, Daniel L Silbergeld, James M Olson, Robert C Rostomily, Jay Shendure
Journal: Genome biology (2014)

Abstract Background The extent of intratumoral mutational heterogeneity remains unclear in gliomas, the most common primary brain tumors, especially with respect to point mutation. To address this, we applied single molecule molecular inversion probes targeting 33 cancer genes to assay both point mutations and gene amplifications within spatially distinct regions of 14 glial tumors. Results We find evidence of regional mutational heterogeneity in multiple tumors, including mutations in TP53 and RB1 in an anaplastic oligodendroglioma and amplifications in PDGFRA and KIT in two glioblastomas (GBMs). Immunohistochemistry confirms heterogeneity of TP53 mutation and PDGFRA amplification. In all, 3 out of 14 glial tumors surveyed have evidence for heterogeneity for clinically relevant mutations. Conclusions Our results underscore the need to sample multiple regions in GBM and other glial tumors when devising personalized treatments based on genomic information, and furthermore demonstrate the importance of measuring both point mutation and copy number alteration while investigating genetic heterogeneity within cancer samples.
Non-selective β-blockers are associated with improved survival in patients with ascites listed for liver transplantation
Authors: Joanna A Leithead, Neil Rajoriya, Nadeem Tehami, James Hodson, Bridget K Gunson, Dhiraj Tripathi, James W Ferguson
Journal: Gut (2014)

Recent data have suggested that non-selective β-blockers (NSBB) are associated with increased mortality in patients with cirrhosis and refractory ascites. However, other evidence implies that NSBB may be beneficial in this setting by reducing bacterial translocation. Our aim was to determine whether NSBB use was a risk factor for mortality in patients with end-stage chronic liver disease and ascites awaiting liver transplantation.This was a single-centre retrospective study of 322 patients with ascites listed January 2007 to July 2011.NSBB patients (n=159) and non-NSBB patients (n=163) were comparable with regards to listing model for end-stage liver disease score (p=0.168), frequency of hepatocellular carcinoma (p=0.193) and refractory ascites (35.2% vs. 37.4%, p=0.681). 82 patients died, 221 patients were transplanted and 19 patients were removed from the list during a median follow-up duration of 72 days; the median time to death was 150 and 54 days in the NSBB and non-NSBB groups, respectively. In a multivariate competing risk Cox model, patients on NSBB had reduced mortality compared with propensity risk score-matched non-NSBB patients (HR 0.55; 95% CI 0.32 to 0.95, p=0.032). Similarly, in the subgroup of patients with refractory ascites (n=117), NSBB remained independently associated with less waitlist death (adjusted HR 0.35; 95% CI 0.14 to 0.86, p=0.022).NSBB in patients with ascites and refractory ascites listed for liver transplantation are not detrimental, and instead are associated with reduced waitlist death. Our findings argue that NSBB are safe and may confer benefit in patients with ascites complicating end-stage liver disease.
Palliative radiotherapy and chemotherapy instead of surgery in symptomatic rectal cancer with synchronous unresectable metastases: a phase II study
Authors: D. Tyc-Szczepaniak, L. Wyrwicz, L. Kepka, W. Michalski, M. Olszyna-Serementa, J. Palucki, L. Pietrzak, A. Rutkowski, K. Bujko
Journal: Annals of Oncology (2013)
PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects
Authors: Karoline V. Gleixner, Matthias Mayerhofer, Karl J. Aichberger, Sophia Derdak, Karoline Sonneck, Alexandra Böhm, Alexander Gruze, Puchit Samorapoompichit, Paul W. Manley, Doriano Fabbro, Winfried F. Pickl, Christian Sillaber, Peter Valent
Journal: Blood (2005)
Effects of a drug overdose in a television drama on presentations to hospital for self poisoning: time series and questionnaire study
Authors: K. Hawton, S. Simkin, J. J Deeks, S. O'Connor, A. Keen, D. G Altman, G. Philo, C. Bulstrode
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives</b>: To determine whether a serious paracetamol overdose in the medical television drama <i>Casualty</i> altered the incidence and nature of general hospital presentations for deliberate self poisoning. <b>Design</b>: Interrupted time series analysis of presentations for self poisoning at accident and emergency departments during three week periods before and after the broadcast. Questionnaire responses collected from self poisoning patients during the same periods. <b>Setting</b>: 49 accident and emergency departments and psychiatric services in United Kingdom collected incidence data; 25 services collected questionnaire data. <b>Subjects</b>: 4403 self poisoning patients; questionnaires completed for 1047. <b>Main outcome measures</b>: Change in presentation rates for self poisoning in the three weeks after the broadcast compared with the three weeks before, use of paracetamol and other drugs for self poisoning, and the nature of overdoses in viewers of the broadcast compared with non-viewers. <b>Results</b>: Presentations for self poisoning increased by 17% (95% confidence interval 7% to 28%) in the week after the broadcast and by 9% (0 to 19%) in the second week. Increases in paracetamol overdoses were more marked than increases in non-paracetamol overdoses. Thirty two patients who presented in the week after the broadcast and were interviewed had seen the episode—20%said that it had influenced their decision to take an overdose, and 17% said it had influenced their choice of drug. The use of paracetamol for overdose doubled among viewers of <i>Casualty</i>after the episode (rise of 106%; 28% to 232%). <b>Conclusions</b>: Broadcast of popular television dramas depicting self poisoning may have a short term influence in terms of increases in hospital presentation for overdose and changes in the choice of drug taken. This raises serious questions about the advisability of the media portraying suicidal behaviour.
Hyperoxia Increases Phosphodiesterase 5 Expression and Activity in Ovine Fetal Pulmonary Artery Smooth Muscle Cells
Authors: Kathryn N. Farrow, Beezly S. Groh, Paul T. Schumacker, Satyan Lakshminrusimha, Lyubov Czech, Sylvia F. Gugino, James A. Russell, Robin H. Steinhorn
Journal: Circulation Research (2007)

In the pulmonary vasculature, cGMP concentrations are regulated in part by a cGMP-dependent phosphodiesterase (PDE), PDE5. Infants with persistent pulmonary hypertension of the newborn (PPHN) are often mechanically ventilated with high oxygen concentrations. The effects of hyperoxia on the developing pulmonary vasculature and PDE5 are largely unknown. Here, we demonstrate that exposure of fetal pulmonary artery smooth muscle cells (FPASMCs) to high levels of oxygen for 24 hours leads to decreased responsiveness to exogenous NO, as determined by a decreased intracellular cGMP response, increased PDE5 mRNA and protein expression, as well as increased PDE5 cGMP hydrolytic activity. We demonstrate that inhibition of PDE5 activity with sildenafil partially rescues cGMP responsiveness to exogenous NO. In FPASMCs, hyperoxia leads to increased oxidative stress without increasing cell death. Treatment of normoxic FPASMCs with H 2 O 2 is sufficient to induce PDE5 expression and activity, suggesting that reactive oxygen species mediate the effects of hyperoxia in FPASMCs. In support of this mechanism, a chemical antioxidant, N -acetyl-cysteine, is sufficient to block the hyperoxia-mediated increase in PDE5 expression and activity and rescue cGMP responsiveness to exogenous NO. Finally, ventilation of healthy neonatal sheep with 100% O 2 for 24 hours leads to increased PDE5 protein expression in the resistance pulmonary arteries and increased PDE5 activity in whole lung extracts. These data suggest that PDE5 expression and activity play a critical role in modulating neonatal pulmonary vascular tone in response to common clinical treatments for PPHN, such as oxygen and inhaled NO.
Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969–2002
Authors: Knut Stokkeland, Lena Brandt, Anders Ekbom, Rolf Hultcrantz
Journal: Hepatology (2006)

Liver cirrhosis may be complicated by the development of esophageal varices. The treatment of esophageal varices has changed radically during the last 30 years. Our aim was to study whether the prognosis for patients with esophageal varices had improved in Sweden between 1969 and 2002. We linked register data from the Hospital Discharge Register and from the Causes of Death Register at The National Board of Health in Sweden between 1969 and 2002 to identify and follow-up all patients with esophageal varices according to International Classification of Diseases-8, -9, and -10. There were 12,281 patients hospitalized with esophageal varices, and for all patients there was an increase in the 5-year survival in the years between 1969 and 1979 as opposed to the years between 1990 and 2002. Better survival occurred for women compared with men, for younger patients compared with older, and for patients hospitalized in the latest decade compared with the earlier decades. We found a significant decrease in the mortality caused by esophageal varices during the years studied but no decrease attributable to other causes. In conclusion, mortality for patients hospitalized with esophageal varices in Sweden decreased between 1969 and 2002. The decrease is seen for both 1- and 5-year mortality, and this suggests that the use of new treatment strategies both for acute variceal hemorrhage and secondary prophylaxis has had an impact on prognosis.
Colour Vision and Tests for Colour Blindness
Authors: C. D. Marshall
Journal: BMJ (1914)

THiERSE is scarcely any stubject in the domain medicine and surgery wlhichl lhas been more misrepresented tlhan that of the facts of coloutr blindness, nor is there in wlhiclh such lack of discrimination has been shown with regard to the selectioni of appropriate detection.Many of us iknowv from experience how tlhe metlhods advocated by Edriclge-Greenlhave won all along the line, and that those wlho hiave not been so blinded by prejtudice as to reftuse to examiiine the facts have been overwhelming weight of evidence to admit that explains the facts, and that hiis methods are efficient reliable for the detection of errors of the colour Lately, however, it has been freely stated that not most, s'cientific menl have failed to be convinced lhave rejected" hiis ideas as untenable.Such statements have beenmade withotut a shiadow of proof that such is the case, and in or(ler to shlow how far it is from tlhe truth I wish to review briefly wlhat somne of the miiost eminent menihave said regarding his work.I slhouild point out that whlat follow s represents olily a very fractioni of simiiilar ev,idenice, but I have tions froni-i the writings of those whlose niames are well known in science tlhat aniy statement they make cannot but carry weight, and must be respeected those wlho are in any way conversant with the ppsition they occuIpy in the scienltific worldl.It is also hoped that tllis miiay serve to stop the disseminatioii of reports wlichl are so freelybanlded abouit an-idlwhich.aree so foreign to the facts of the 'case.
Mitochondrial DNA Phylogeny in Eastern and Western Slavs
Authors: B. Malyarchuk, T. Grzybowski, M. Derenko, M. Perkova, T. Vanecek, J. Lazur, P. Gomolcak, I. Tsybovsky
Journal: Molecular Biology and Evolution (2008)

To resolve the phylogeny of certain mitochondrial DNA (mtDNA) haplogroups in eastern Europe and estimate their evolutionary age, a total of 73 samples representing mitochondrial haplogroups U4, HV*, and R1 were selected for complete mitochondrial genome sequencing from a collection of about 2,000 control region sequences sampled in eastern (Russians, Belorussians, and Ukrainians) and western (Poles, Czechs, and Slovaks) Slavs. On the basis of whole-genome resolution, we fully characterized a number of haplogroups (HV3, HV4, U4a1, U4a2, U4a3, U4b, U4c, U4d, and R1a) that were previously described only partially. Our findings demonstrate that haplogroups HV3, HV4, and U4a1 could be traced back to the pre-Neolithic times (∼12,000–19,000 years before present [YBP]) in eastern Europe. In addition, an ancient connection between the Caucasus/Europe and India has been revealed by analysis of haplogroup R1 diversity, with a split between the Indian and Caucasus/European R1a lineages occurring about 16,500 years ago. Meanwhile, some mtDNA subgroups detected in Slavs (such as U4a2a, U4a2*, HV3a, and R1a1) are definitely younger being dated between 6,400 and 8,200 YBP. However, robust age estimations appear to be problematic due to the high ratios of nonsynonymous to synonymous substitutions found in young mtDNA subclusters.
Chlamydia pneumoniae induces neointima formation in coronary arteries of normal pigs
Authors: S Pislaru
Journal: Cardiovascular Research (2003)

Objectives: We evaluated the role of intracoronary, intrapulmonary and macrophage-mediated delivery of C. pneumoniae (Cp) on coronary lesion formation. Methods: Pigs were allocated to one of three coronary protocols (intracoronary, macrophage or control groups) or to a fourth—a pulmonary group. In the intracoronary group Cp was injected into the wall of the left anterior descending (LAD) and right coronary arteries (RCA) and vehicle into the circumflex (CX). In the macrophage group autologous macrophages preincubated with Cp or not were injected into the LAD and CX wall, respectively. Animals in the control group received vehicle in LAD and CX. In the pulmonary group aerosolised Cp was given intrabronchially, after a single injection of vehicle into the LAD wall. Delivery into the coronary artery wall was performed with a balloon catheter with low-profile injector ports. Results: Seroconversion occurred in the following proportions: 5/6 (intracoronary group), 4/5 (macrophage group), 0/6 (control group), and 1/6 (intrapulmonary group). Significantly higher maximal intimal thickness (MIT) was observed in LADs of intracoronary and pulmonary groups when compared to corresponding CXs. The presence of Cp antigen was associated with higher MIT (r=0.73; P<0.0001). Injection of macrophages into the coronary artery wall did not induce proliferation. Arteries without coronary interventions were morphologically normal. Conclusions: Intracoronary and intrapulmonary but not macrophage-mediated Cp inoculation were associated with moderate intimal proliferation in the absence of a lipid-rich diet. Pre-existing coronary lesions seem a prerequisite for Cp-induced proliferation.
Hypnotic treatment of smoking: the single-treatment method revisited
Authors: B Berkowitz, A Ross-Townsend, R Kohberger
Journal: American Journal of Psychiatry (1979)

The authors replicated Spiegel's single-treatment method by treating 40 self-referred patients in a one-hour hypnosis session for smoking. Their results, a 6-month total abstinence rate of about 25%, were comparable with Spiegel's experience. They recommend future studies that include nontreatment control groups to validate the effects of the hypnotic treatment method of smoking.
Human respiratory syncytial virus viroporin SH: a viral recognition pathway used by the host to signal inflammasome activation
Authors: Kathy Triantafilou, Satwik Kar, Emmanouil Vakakis, Sailesh Kotecha, Martha Triantafilou
Journal: Thorax (2012)

<h3>Background</h3> Respiratory syncytial virus (RSV) remains the leading cause of serious viral bronchiolitis and pneumonia in infants and young children throughout the world. The burden of disease is significant, with 70% of all infants being infected with RSV within the first year of their life. 40% of those children discharged from hospital have recurrent, repeated respiratory symptoms and wheezing for at least 10 years. The infection is also an important illness in the elderly and immunocompromised individuals. Ongoing symptoms relate to continued lung inflammation. One cytokine that is associated with RSV infection is IL-1β, but the mechanism of activation remain unclear. <h3>Objectives</h3> In the current study, we set out to decipher the molecular mechanisms of RSV-induced inflammasome activation. <h3>Methods and results</h3> Using deletion mutants of the virus and measuring IL-1β secretion, as well as caspase 1 expression via western blotting, we demonstrate that the NLRP3 inflammasome is activated through the small hydrophobic (SH) RSV viroporin which induces membrane permeability to ions or small molecules. Confocal microscopy revealed that during virus infection, SH seems to accumulate within lipid rafts in the Golgi compartments. <h3>Conclusions</h3> Upon RSV infection, SH gets localised in the cell membranes and intracellular organelle membranes, and then induces permeability by disrupting membrane architecture, thus leading us to believe that formation of viral ion channels in lipid bilayers of cells is a viral recognition pathway used by the host to signal inflammasome activation.
Allogeneic induction of the human T cell-instructed monocyte procoagulant response is rapid and is elicited by HLA-DR.
Authors: H Helin, T S Edgington
Journal: The Journal of Experimental Medicine (1983)

The recognition of alloantigens by human lymphoid cells initiates a collaborative cellular pathway that rather rapidly induces in adherent cells (monocytes) the synthesis and expression of cell surface tissue factor, the initiating cofactor of the extrinsic coagulation pathway. This response was vigorous, generating tissue factor to a level nearly comparable to the response to endotoxin. However, it was temporally discordant with characterized lymphoid procoagulant responses to endotoxin, virus, and immune complexes in that it reached a maxima at 48 h, well after these other responses but clearly much faster than the well recognized proliferative responses to allogeneic stimulation. Using the Daudi lymphoblastoid B cell line, the allogeneic response could be fully elicited in a dose-dependent fashion within 18 h. The induction of monocyte tissue factor required collaboration with T lymphocytes, in accord with previously described T cell-instructed monocyte responses. HLA-DR was implicated as the allogeneic signal by the ability of two monoclonal antibodies to completely block, in a dose-dependent fashion, the induction of this pathway. Notably, the allogeneic procoagulant response was quantitatively discordant with respect to the allogeneic proliferative response, suggesting differences in specificity. This relatively rapid response may be applicable to typing of determinants in the major histocompatibility complex that are not equivalently identified by alternative analyses, and may be significant in tissue transplantation. The cellular pathway, linking allogeneic recognition with induction of a monocyte response that initiates the coagulation pathway, represents a further example of the linkage between these biologic systems, and is consistent with a pathogenetic role in allograft rejection by the promotion of vascular thrombosis and interstitial fibrin accumulation.